Affect disorders. 

Affect disorders. Сlinic, types of motion

Classification of psychotropic drugs, indications, complications and methods of correction.

Schizophrenia, schizotypical and delusional disorders.

 

Bipolar disorder is characterized by the occurrence of at least one manic or mixed-manic episode during the patient’s lifetime. Most its also, at other times, have one or more depressive episodes, intervals between these episodes, most patients return to ir normal state of well-being. Thus bipolar disorder is a “cyclic” f periodic” illness, with patients cycling “up” into a manic or d-manic episode, then returning to normal, and cycling n” into a depressive episode from which they likewise eventually or less recover. Bipolar disorder is probably equally common among men and women and has a lifetime prevalence of from 1.3 to 1.6%.

 

Bipolar disorder in the past has been referred to as “manic depressive illness, circular type.” As noted in the introduction to the chapter on major depression, the term “manic depressive illness,” at least in the United States, has more and more come to be used as equivalent to bipolar disorder. As this convention, however, is not worldwide, the term “bipolar” may be better, as it clearly indicates that the patient has an illness characterized by “swings” to the manic “pole” and generally also to the depressive “pole.”

 

ONSET

 

 Bipolar disorder may present with either a depressive or a manic episode, and the peak age of onset for the first episode, whether depressive or manic, lies in the teens and early twenties. Earlier onsets may occur; indeed some patients may have their first episode at 10 years of age or younger. After the twenties the incidence of first episodes gradually decreases, with well over 90% of patients having had their first episode before the age of 50. Onsets as late as the seventies or eighties have, though very rare, been seen.

 

Premorbidly, these patients may either be normal or display mild symptoms for a variable period of time before the first episode of illness.

 

CLINICAL  FEATURES

The discussion of signs and symptoms proceeds in three parts: first, a discussion of a manic episode; second, a discussion of a depressive episode; and, third, a discussion of a mixed-manic episode.

 

Manic Episode

 

The nosology of the various stages of a manic episode has changed over the decades. In current DSM-IV nomenclature, hypomanic episodes are separated from the more severe full manic episodes, which in turn are characterized as either mild, moderate, severe, or severe with psychotic features. Kraepelin, however, divided the “manic states” into four forms—hypomania, acute mania, delusional mania, and delirious mania—and noted that his observation revealed “the occurrence of gradual transitions between all the various states.” In a similar vein, Carlson and Goodwin, in their elegant paper of 1973, divided a manic episode into “three stages”: hypomania, or stage I; acute mania, or stage II; and delirious mania, or stage III. As this “staging” of a manic episode is very useful from a descriptive and differential diagnostic point of view, it is used in this chapter. Thus, when the term “manic episode” is used it may refer to any one of the three stages of mania: hypomania, acute mania, or delirious mania.

 

Manic episodes are often preceded by a prodrome, lasting from a few days to a few months, of mild and often transitory and indistinct manic symptoms. At times, however, no prodromal warning signs may occur, and the episode starts quite abruptly. When this occurs, patients often unaccountably wake up during the night full of energy and vigor—the so-called “manic alert.”

 The cardinal symptoms of mania are the following: heightened mood (either euphoric or irritable); flight of ideas and pressure of speech; and increased energy, decreased need for sleep, and hyper-activity. These cardinal symptoms are most plainly evident in hypomania. In acute mania they exacerbate and may be joined by delusions and some fragmentation of behavior, and in delirious mania only tattered scraps of the cardinal symptoms may be present, otherwise being obscured by florid and often bizarre psychotic symptoms. Although all patients experience a hypomanic stage, and almost all progress to at least a touch of acute mania, only a minority finally are propelled into delirious mania. The rapidity with which patients pass from hypomania through acute mania and on to delirious mania varies from a week to a few days to as little as a few hours. Indeed, in such hyperacute onsets, the patient may have already passed through the hypomanic stage and the  acute manic stage before he is brought to medical attention. The duration of an entire manic episode varies from the extremes of as little as a few days or less to many years, and rarely even to a decade or more. On the average, however, most first episodes of mania last from several weeks up to 3 months. In the natural course of events, symptoms tend to gradually subside; after they fade many patients feel guilty over what they did and perhaps are full of self-reproach. Most patients are able to recall what happened during hypomania and acute mania; however, memory is often spotty for the events of delirious mania. With this brief general description of a manic episode in mind, what follows now is a more thorough discussion of each of the three stages of mania.

 Hypomania. In hypomania the mood is heightened and elevated. Most often these patients are euphoric, full of jollity and cheerfulness. Though at times selfish and pompous, their mood nevertheless is often quite “infectious.” They joke, make wisecracks and delightful insinuations, and those around them often get quite caught up in the spirit, always laughing with the patient, and not at him. Indeed, when physicians find themselves unable to suppress their own laughter when interviewing a patient, the diagnosis of hypomania is very likely. Self-esteem and self-confidence are greatly increased. Inflated with their own grandiosity, patients may boast of fabulous achievements and lay out plans for even grander conquests in the future. In a minority of patients, however, irri­tability may be the dominant mood. Patients become demanding, inconsiderate, and intemperate. They are constantly dissatisfied and intolerant of others, and brook no opposition. Trifling slights may enrage the patient, and violent outbursts are not uncommon. At times, pronounced lability of mood may be evident; otherwise supremely contented patients may suddenly turn dark, churlish, and irritable.

 In flight of ideas the patient’s train of thought is characterized by rapid leaps from one topic to another. When flight of ideas is mild, the connections between the patient’s successive ideas, though perhaps tenuous, may nonetheless be “understandable” to the listener. In somewhat higher grades of flight of ideas, however, the connections may seem to be illogical and come to depend more on puns and word plays. This flight of ideas is often accompanied by pressure of thought. Patients may report that their thoughts race, that they have too many thoughts, that they run on pell-mell. Typically, patients also display pressure of speech. Here the listener is deluged with a torrent of words. Speech may become imperious, incredibly rapid, and almost unstoppable. Occasionally, after great urging and with great effort, patients may be able to keep silent and withhold their speech, but not for long, and soon the dam bursts once again.

 Energy is greatly, even immensely, increased, and patients feel less and less the need for sleep. They are on the go, busy and involved throughout the day. They wish to be a part of life and to be involved more and more in the lives of those around them. They are strangers to fatigue and are still hyperactive and ready to go when others must go to bed. Eventually, the patients themselves may finally go to sleep, but within a very brief period of time they then awaken, wide-eyed, and, finding no one else up, they may seek someone to wake up, or perhaps take a whistling stroll of the darkened neighborhood, or, if alone, they may spend the hours before daybreak cleaning out closets or drawers, catching up on old correspondence, or even paying bills.

 In addition to these cardinal symptoms, hypomanic patients are often extremely distractible. Other conversations and events, though peripheral to the patients’ present purposes, are as if glittering jewels that they must attend to, to take as their own, or simply to  admire. In listening to patients, one may find that a fragment of another conversation has suddenly been interpolated into their flight of ideas, or they may stop suddenly and declare their unbounded admiration for the physician’s clothing, only then again to become one with the preceding rush of speech.

 Hypomanic patients rarely recognize that anything is wrong with them, and though their judgment is obviously impaired they have no insight into that condition. Indeed, as far as hypo-manic patients are concerned, the rest of the world is sick and impaired; if only the rest of the world could feel as they do and see as clearly as they do, then the rest of the world would be sure to join them. These patients often enter into business arrangements with unbounded and completely uncritical enthusiasm. Ventures are begun, stocks are bought on a hunch, money is loaned out without collateral, and when the family fortune is spent, the patient, undaunted, after perhaps a brief pause, may seek to borrow more money for yet another prospect. Spending sprees are also typical. Clothes, furniture, and cars may be bought; the credit card is pushed to the limit and checks, without any і foundation in the bank, may be written with the utmost alacrity. Excessive jewelry and flamboyant clothing are especially popular. The overinvolvement of patients with other people typically leads і the most injudicious and at times unwelcome entanglements, ssionate encounters are the rule, and hypersexuality is not ncommon. Many a female hypomanic has become pregnant dur-; such escapades. If confronted with the consequences of their ehavior, hypomanic patients typically take offense, turn perhaps bdignantly self-righteous, or are quick with numerous, more or plausible excuses. When hypomanic patients are primarily able rather then euphoric, their demanding, intrusive, and [judicious behavior often brings them into conflict with others I with the law.

 Acute Mania.   The transition from hypomania to acute mania irked by a severe exacerbation of the symptoms seen in hypo-ilia, and the appearance of delusions. Typically, the delusions grandiose: millions of dollars are held in trust for them; sby stop and wait in deferential awe as they pass by; the Ident will  announce their elevation to cabinet rank. Religious sions are very common. The patients are prophets, elected by a magnificent, yet hidden, purpose. They are enthroned; I God has made way for them. Sometimes these grandiose iions are held constantly; however, in other cases patients may ily boldly announce their belief, then toss it aside with :r, only to announce yet another one. Persecutory delusions > appear and are quite common in those who are of a pre-fiantly irritable mood. The patients’ failures are not their own : results of the treachery of colleagues or family. They are uted by those jealous of their grandeur; they are pilloried, I by the enemy. Terrorists have set a watch on their houses : to destroy them before they can ascend to their thrones. Uy, along with delusions, patients may have isolated ations. Grandiose patients hear a chorus of angels singing [raises; the persecuted patients hear the resentful muttering rious crowd.

 Hyperactivity becomes more pronounced, and the patient’s behavior may begin to fragment. Impulses come at cross purposes, and patients, though increasingly active, may be unable to complete anything. Fragments of activity abound: patients may run, hop in place, roll about the floor, leap from bed to bed, race this way and then that, or repeatedly change their clothes at a furious pace.

 Occasionally, patients in acute mania may evidence a passing fragment of insight: they may suddenly leap to the tops of tables and proclaim that they are “mad,” then laugh, lose the thought, and jump back into their pursuits of a moment ago. Some may devote themselves to writing, flooding reams of paper with an extravagant handwriting, leaving behind an almost unintelligible, tangential flight of written ideas. Patients may dress themselves in the most fantastic ways. Women may decorate themselves with garlands of flowers and wear the most seductive of dresses. Men may be festooned with ribbons and jewelry. Unrestrainable sexuality may come to the fore. Patients may openly and shamelessly proposition complete strangers; some may openly and exultantly masturbate. Strength may be greatly increased, and sensitivity to pain may be lost.

 Delirious Mania. The transition to delirious mania is marked by the appearance of confusion, more hallucinations, and a marked intensification of the symptoms seen in acute mania. A dreamlike clouding of consciousness may occur. Patients may mistake where they are and with whom. They cry out that they are in heaven or in hell, in a palace or in a prison; those around them have all changed—the physician is an executioner; fellow patients are secret slaves. Hallucinations, more commonly auditory than visual, appear momentarily and then are gone, perhaps only to be replaced by another. The thunderous voice of God sounds; angels whisper secret encouragements; the devil boasts at having the patient now; the patient’s children cry out in despair. Creatures and faces may appear; lights flash and lightning cracks through the room. Grandiose and persecutory delusions intensify, especially the persecutory ones. Bizarre delusions may occur, including Schneiderian delusions. Electrical currents from the nurses’ station control the patient; the patient remains in a telepathic communication with the physician or with the other patients.

 Mood is extremely dysphoric and labile. Though some patients still are occasionally enthusiastic and jolly, irritability is generally quite pronounced. There may be cursing, and swearing; violent threats are made, and if patients are restrained they may spit on those around them. Sudden despair and wretched crying may grip the patient, only to give way in moments to unrestrained laughter.

 Flight of ideas becomes extremely intense and fragmented. Sentences are rarely completed, and speech often consists of words or short phrases having only the most tenuous connection with the other. Pressure of speech likewise increases, and in extreme cases the patient’s speech may become an incoherent and rapidly changing jumble. Yet even in the highest grades of incoherence, where asso­ciations become markedly loosened, these patients remain in lively contact with the world about them. Fragments of nearby conversa­tions are interpolated into their speech, or they may make a sudden reference to the physician’s clothing or to a disturbance somewhere else on the ward.

 Hyperactivity is extreme, and behavior disintegrates into numerous and disparate fragments of purposeful activity. Patients may agitatedly pace from one wall to the other, jump to a table top, beat their chest and scream, assault anyone nearby, pound on the windows, tear the bed sheets, prance, twitter, or throw off their clothes. Impulsivity may be extreme, and the patient may unexpectedly commit suicide by leaping from a window.

 Self-control is absolutely lost, and the patient has no insight and no capacity for it. Attempting to reason with the patient in deliri­ous mania is fruitless, even assuming that the patient stays still enough for one to try. The frenzy of these patients is remarkable to behold and rarely forgotten. Yet in the height of delirious mania, one may be surprised by the appearance of a sudden calm. Instantly, the patient may become mute and immobile, and such a catatonic stupor may persist from minutes to hours only to give way again to a storm of activity. Other catatonic signs, such as echolalia and echopraxia and even waxy flexibility, may also be seen.

 As noted earlier not all manic patients pass through all three stages; indeed some may not progress past a hypomanic state. Regardless, however, of whether the peak of severity of the individual patient’s episode is found in hypomania, in acute mania, or in delirious mania, once that peak has been reached, a more or less gradual and orderly subsidence of symptoms occurs, which to a greater or lesser degree retraces the same symptoms seen in the earlier escalation. Finally, once the last vestiges of hypomanic symptoms have faded, the patient is often found full of self-reproach and shame over what he has done. Some may be reluctant to leave the hospital for fear of reproach by those they harmed and offended while they were in the manic episode.

 In current nomenclature, those patients whose manic episodes never pass beyond the stage of hypomania are said to have “Bipolar II” disorder, in contrast with “Bipolar I” disorder wherein the mania does escalate beyond the hypomanic stage. Recent data indicate that bipolar II disorder may be more common than bipolar I disorder; however, should a patient with bipolar II disorder ever have a manic episode wherein stage II or III symptoms occurred, then the diagnosis would have to be revised to bipolar I.

 Occasionally the age of the patient may influence the presentation of mania. Adolescents and children, for example, seem particularly prone to the very rapid development of delirious mania. On the other extreme, in the elderly, one may see little or no hyperactivity. Some elderly manic patients may sit in the same chair all day long, chattering away in an explosive flight of ideas. Mental retardation may also influence the presentation of mania. Here in the absence of speech one may see only increased, seemingly purposeless, activity.

 

Depressive Episodes

 

The depressive episodes seen in bipolar disorder, in contrast to those typically seen in a major depression, tend to come on fairly acutely, over perhaps a few weeks, and often occur without any significant precipitating factors. They tend to be characterized by psychomotor retardation, hyperphagia, and hypersomnolence and are not uncommonly accompanied by delusions or hallucinations. On the average, untreated, these bipolar depressions tend to last about a half year.

 Mood is depressed and often irritable. The patients are discontented and fault-finding and may even come to loathe not only themselves but also everyone around them.

 Energy is lacking; patients may feel apathetic or at times weighted down.

Thought becomes sluggish and slow. Patients cannot concentrate to read and cannot remember what they do read. Comprehending alternatives and bringing themselves to decisions may be impossible.

 Patients may lose interest in life; things appear dull and heavy and have no attraction.

 Many patients feel a greatly increased need for sleep. Some may succumb and sleep 10, 14, or 18 hours a day. Yet no matter how much sleep they get, they awake exhausted, as if they had not slept at all. Appetite may also be increased and weight gain may occur, occasionally to an amazing degree. Conversely, some patients may experience insomnia or loss of appetite.

 Psychomotor retardation is the rule, although some patients may show agitation. In psychomotor retardation the patient may lie in bed or sit in the chair for hours, perhaps all day, profoundly apathetic and scarcely moving at all. Speech is rare; if a sentence is begun, it may die in the speaking of it, as if the patient had not the energy to bring it to conclusion. At times the facial expression may become tense and pained, as if the patient were under some great inner constraint.

 Pessimism and bleak despair permeate these patients’ outlooks. Guilt abounds, and on surveying their lives patients find themselves the worst of failures, the greatest of sinners. Effort appears futile, and enterprises begun in the past may be abandoned. They may have recurrent thoughts of suicide, and impulsive suicide attempts may occur.

 Delusions of guilt and of well-deserved punishment and persecution are common. Patients may believe that they have let children starve, murdered their spouses, poisoned the wells. Unspeakable punishments are carried out: their eyes are gouged out; they are slowly hung from the gallows; they have contracted syphilis or AIDS, and these are a just punishment for their sins.

 Hallucinations may also appear and may be quite fantastic. Heads float through the air; the soup boils black with blood. Auditory hallucinations are more common, and patients may hear the heavenly court pronounce judgment. Foul odors may be smelled, and poison may be tasted in the food.

 

In general a depressive episode in bipolar disorder subsides gradually. Occasionally, however, it may come to an abrupt termi­nation. A patient may arise one morning, after months of suffering, and announce a complete return to fitness and vitality. In such cases, a manic episode is likely to soon follow.

 

Mixed-Manic Episode

 

Mixed-manic episodes are not as common as manic episodes or depressive episodes, but tend to last longer. Here one sees various admixtures of manic and depressive symptoms, sometimes in sequence, sometimes simultaneously. Euphoric patients, hyperactive and pressured in speech, may suddenly plunge into despair and collapse weeping into chairs, only to rise again within hours to their former elated state. Even more extraordinary, patients may be weeping uncontrollably, with a look of unutterable despair on their faces, yet say that they are elated, that they never felt so well in their lives, and then go on to execute a lively dance, all the while with tears still streaming down their faces. Or a depressed and psy-chomotorically retarded patient may consistently dress in the brightest of clothes, showing a fixed smile on an otherwise expressionless face. These mixed-manic episodes must be distinguished from the transitional periods that may appear in patients who “cycle” directly from a manic into a depressive episode, or vice versa, without any intervening euthymic interval. These transitional periods are often marked by an admixture of both manic , and depressive symptoms; however, they do not “stand alone , as episodes of illness unto themselves, but are always both immediately preceded and followed by a more typical episode of  homogenous manic or homogenous depressive symptoms. In contrast the mixed-manic episode “stands alone.” It starts with mixed symptoms, endures with them, and finishes with them, and is neither immediately preceded nor immediately followed by an episode of mania or by an episode of depression.

 At this point, before proceeding to a consideration of course, two other disorders that are strongly associated with bipolar disorder should be mentioned, namely alcoholism and cocaine addiction. During manic episodes, patients with these addictions are especially likely to take cocaine or drink even more heavily, and the effects of these substances may cloud the clinical picture.

 

COURSE

 

Bipolar disorder is an episodic or, as noted earlier, “cyclical” illness, being characterized in most patients by the intermittent lifelong appearance of episodes of illness, in between which most patients experience a “euthymic” interval during which they more or less return to their normal state of health.

 The pattern and sequencing of successive episodes is quite variable among patients. The duration of the euthymic interval varies from as little as a few weeks or days to as long as years, or ; even decades. In contrast, however, to the extreme variability of the і euthymic intervals among patients, finding a certain regular  pattern in the history of any given patient is not unusual. Indeed in ome patients the euthymic interval is so regular that patients can predict sometimes to the month when the next episode will occur, he postpartum period is a time of increased risk. Occasionally, jjne may also see a “seasonal” pattern, with manic episodes more :ly in the spring or early summer and depressive ones in the fall r winter.

 Early on in the overall course of the illness the cycle length, or ne from the onset of one episode to the onset of the next, tends shorten. Specifically, whereas the duration of the episodes nselves tends to be stable, the euthymic interval shortens, so des come progressively closer together. With time, however, ; duration of the euthymic interval stabilizes. Patients who have four or more episodes of illness in any one • are customarily referred to as “rapid cyclers.” Although only  10% of all patients with bipolar disorder display such a jiern of rapid cycling, these patients are nevertheless clinically : important as they tend to be relatively “resistant” to many ntly available treatments. On the other extreme, the euthymic 1 may be so long, lasting many decades, that the patient dies jpre the second episode is “due,” thereby having only one episode ness during an entire lifespan.

 he sequence of episodes is also quite variable among patients, ply would one find a patient whose course is characterized by rly alternating manic and depressive episodes; most patients ‘ a preponderance of either depressive episodes or of manic For example, in an extreme case a patient may have through-life perhaps six depressive episodes and only one manic one. fie other extreme, another patient might have up to a dozen des of mania and only one depressive one. Indeed one may nter a patient who has only manic episodes and never any ■sive ones. Such “unipolar manic” patients are very rare. In . a depressive preponderance is more common in females, f inanic one in males.

 Noted earlier, for most patients the interval between episodes nic and free of symptoms. In at least a quarter of all cases, ‘, the interval may be “colored” by very mild symptoms, and tion of this “coloring,” or its “polarity,” correlates with the preponderance of episodes. For example, a patient with very mild subhypomanic symptoms during the interval is likely to have more manic episodes than depressive ones, and the converse holds true for the patients whose interval is clouded with mild depression or fatigue. In general, among women the preponderance of episodes are depressive; among men, manic.

 In perhaps a quarter of all cases, the course exhibits “coupling.” Here a manic episode may invariably and immediately be followed by a depressive one, or vice versa. In such cases the transition from one episode to the next may be marked by a mixture of symptoms, as if the various symptoms of the preceding episode trailed off at different rates, while the various symptoms of the following episode appeared also at varying rates, such that the two coupled episodes in a sense overlapped and interdigitated with each other, with this interdigitation presenting as the mixture of symptoms. Such “overlap” or transitional experiences must, as noted earlier, be distinguished from mixed-manic episodes proper, which stand on their own.

 Occasionally, one may find bipolar patients in whom certain conditions, pharmacologic and otherwise, can more or less reliably precipitate a manic episode. These include serotoninergic agents such as tryptophan or 5-hydroxytryptophan; noradrenergic agents, such as cocaine, stimulants, or sympathomimetics, or situations in which noradrenergic tone is increased as in alcohol or sedative-hypnotic withdrawal or in the abrupt discontinuation of long-term treatment with clonidine; dopaminergic agents such as L-dopa or bromocriptine; and treatment with exogenous steroids, such as prednisone. Older antidepressants, such as the MAOIs and tricydics, are particularly notorious for precipitating manic episodes in bipolar patients, and some evidence suggests that these antidepressants, in addition to being capable of precipitating a manic episode, may also alter the fundamental course of bipolar disorder and increase the frequency with which future episodes occur: newer antidepressants, such as SSRIs, bupropion and venlafaxine, do not appear as likely to precipitate mania. Phototherapy may also induce manic episodes in those patients whose course exhibits a “seasonal pattern.”

 

 COMPLICATIONS

 

In mania, spending sprees and ill-advised business ventures may land patients in serious debt, or even bankruptcy. Hypersexuality may lead to unplanned and unwanted pregnancies or ill-considered marriages. A reckless exuberance may carry the patient past all speed limits and into conflict with the law; accidents are common. Irritable manics are likewise often in conflict with the law and may pick fights and create disputes with whomever they come in contact. Friendships may be broken, and divorce may occur.

 

Suicide occurs in from 10 to 20% of patients with bipolar disorder and appears to be more common in those who have only hypomanic episodes (i.e., those with bipolar II disorder) than in those whose manic episodes progress beyond the first stage (i.e., those with bipolar I disorder). Although most suicides appear to occur during episodes of depression, patients in a mixed-manic episode may be at an even higher risk.

 

The complications of a depressive episode are as outlined in the chapter on major depression.

 

 

 

ETYOLOGY

 Genetic factors almost certainly play a role in bipolar disorder. A higher prevalence of bipolar disorder exists among the first-degree relatives of patients with bipolar disorder than among the relatives of controls or the relatives of patients with major depression, and the concordance rate among monozygotic twins is significantly higher than that among dizygotic twins. Similarly and most tellingly, adoption studies have demonstrated that the prevalence of bipolar disorder is several-fold higher among the biologic parents of bipolar patients than among the biologic parents of control adoptees.

 Genetic studies in bipolar disorder have been plagued by failures of replication. In all likelihood, multiple genes on multiple different chromosomes are involved, each conferring a susceptibility to the disease.

 Autopsy studies, likewise, have often yielded inconsistent results. Perhaps the most promising finding is of a reduced neuronal number in the locus ceruleus and median raphe nucleus.

 Endocrinologic studies have yielded robust findings, similar to those found in major depression, including non-suppression on the dexamethasone suppression test and a blunted TSH response to TRH infusion.

 Other robust findings include a shortened latency to REM sleep upon infusion of arecoline and the remarkable ability of intra­venous physostigmine to not only bring patients out of mania but also to cast them down past their baseline and into a depression.

 Taken together, these findings are consistent with the notion that bipolar disorder is, in large part, an inherited disorder charac­terized by episodic perturbations in endocrinologic, noradrenergic, serotoninergic and cholinergic function, with these in turn possibly being related to subtle microanatomic changes in relevant brainstem structures.

 

DIFFERENTIAL DIAGNOSIS

 In distinguishing bipolar disorder from other disorders, the single most useful differential feature is the course of the illness. Essentially no other disorder left untreated presents with recurrent episodes of mood disturbance at least one of which is a manic episode, with more or less full restitution to normal functioning between episodes. Thus if the patient in question has had previous episodes and if the available history is complete, then one can generally state with certainty whether the patient has bipolar disorder. However, these are two big “ifs,” and in clinical practice history may either be absent or unobtainable, and herein arises diagnostic difficulty.

 

Occasionally a patient in a manic episode is brought to the emergency room by police with no other history except that he was arrested for disturbing the peace. If the patient is in the stage of acute mania with perhaps irritability and delusions of persecution, one might wonder if the patient is currently in the midst of the onset of paranoid schizophrenia or of its exacerbation. Here the behavior of the patient when left undisturbed is helpful: left to themselves, patients with paranoid schizophrenia often sit quietly, patiently waiting for the next assault, whereas patients with acute mania continue to display their hyperactivity and pressured speech. If the patient is in the stage of delirious mania, the differential would include an acute exacerbation of catatonic schizophrenia and also a delirium from some other cause. The quality of the hyperactivity seen in the excited subtype of catatonic schizophrenia is different from that seen in mania. The catatonic schizophrenic, no matter how frenzied, remains self-involved and has little contact with those around him. By contrast, manic patients, no matter how fragmented their behavior, show a desire and a compelling interest to be involved with others. In the highest grade of delirious mania, the patient, as noted earlier, may lapse  into a confusional stupor. At this point, the differential becomes very wide, as discussed in the chapter on delirium. At times, a “cross-sectional” view of the patient, say in the emergency room, may allow an accurate diagnosis; however, a “longitudinal” view is always more helpful. As noted earlier, all patients in delirious mania or acute mania have already passed from relatively normal functioning through the distinctive stage of mania. Obtaining a history of this progression from normal through and past stage I hypomania allows for a more certain diagnosis.

 The distinction between secondary mania and a manic episode of bipolar disorder is discussed in that chapter.

 At times patients with schizoaffective disorder, bipolar type, may be very difficult to distinguish from those with bipolar disorder. Here a precise interval history is absolutely necessary. In schizoaffective disorder psychotic symptoms, such as delusions, hallucinations, or incoherence, persist between the episodes, in contrast to the “free” intervals seen in bipolar disorder. The interval psychotic symptoms seen in schizoaffective disorder may be very mild indeed, and thus close and repeated observation over extended periods of time may be required to ascertain their presence.

 Cyclothymia may at times present diagnostic difficulty, for it also presents a history of discrete individual episodes. The difference is that in cyclothymia the manic symptoms are very mild. The possibility also exists, however, that the apparently cyclothymic patient is presenting, in fact, with a very long prodrome to bipolar disorder. Thus continued observation over many years may necessitate a diagnostic revision if a manic episode should ever occur.

 The differential between a postpartum psychosis and a bipolar disorder that has become “entrained” to the postpartum period is discussed in that chapter.

 The persistence of very mild affective symptoms between episodes might suggest, depending on the polarity of the symptoms, a diagnosis of dysthymia or of hyperthymia. Here, however, temporal continuity of these symptoms with a full episode of illness betrays their true nature, that of either a prodrome or of a condition of only partial remission of a prior episode.

 The distinction between a depressive episode occurring as part of a major depression and one occurring as part of bipolar disorder is considered in the chapter on major depression.

 The overall treatment of bipolar disorder is conveniently approached by considering, in turn, the treatment of the manic or mixed-manic episode first, then the treatment of the depressive episode, in each instance considering three phases of treatment: acute, continuation, and preventive. As will be seen, of all the medications useful in bipolar disorder, lithium is probably the best choice as it is the only one which has been shown to be effective for all three phases of treatment for both manic and depressive episodes.

 

Manic or Mixed-Manic Episodes

 

Acute Treatment. The acute treatment of a manic or mixed-manic episode almost always involves the administration of either a mood stabilizer (i.e., lithium, valproate or carbamazepine) or an antipsychotic (i.e., olanzapine, risperidone, aripiprazole, quetiap-ine or ziprasidone), or most commonly, a combination of a mood stabilizer and an antipsychotic. Although there are no hard and fast rules for choosing among these agents, some general guidelines may be offered. Certainly, if the patient has a history of an excellent response to a particular agent, then it should be seriously considered. Lacking such a history, and assuming there are no significant contraindications, the first choice among the mood stabilizers is probably lithium, as it has the longest track record. Divalproex is a close second, and, in the case of episodes with a significant depressive component, and certainly in the case of a mixed-manic episode, is actually superior to lithium. Another advantage of divalproex is the rapidity with which it becomes effective when a “loading” strategy is used, with patients often responding in a matter of days, in contrast with the week or two required with lithium. Carbamazepine is probably a little less effective than lithium, and, in general, is not as well-tolerated. Among the antipsychotics, the first choice is probably olanzapine in that it has the longest track record among these second generation agents in this regard and has also, in contrast with the other second generation agents, been shown to be effective in preventive treatment.

 When symptoms are relatively mild, that is to say of hypomanic intensity, utilization of a mood stabilizer alone may be sufficient. However, when the mania has escalated into stage II or III, a mood stabilizer alone is generally not capable of controlling the clinical storm quickly enough, and in such cases it is common practice to initiate treatment with a combination of a mood stabilizer and one of the second-generation antipsychotics. In emergent situations, one may also employ one of the protocols outlined in the chapter on rapid pharmacologic treatment of agitation. Consideration should also be given to ЕСТ: bilateral ЕСТ is effective for mania and is indicated when the foregoing treatments are not successful or in life-threatening situations where urgent improvement is absolutely required. Should ЕСТ be utilized, lithium should not be administered concurrently, as it may enhance ECT-induced confusion.

 Many manic patients require admission to a locked unit. Stimulation, including visitors, mail, and phone calls, should be kept to an absolute minimum, as it routinely exacerbates manic symptoms. Indeed, occasional patients in acute mania, still possessed of a few tattered shreds of insight, may demand to be put in seclusion. Isolated from all stimuli, they gradually improve, although their symptoms only partially abate. A calm, patient, and nonconfrontive manner is generally best; sometimes sharing the patient’s jokes may be calming and helpful in enlisting cooperation. At times, however, a “show of force” may be necessary; indeed violent, irritable, and very agitated patients, though completely unfazed by routine measures, may calm down immediately upon the appearance of several formidable male orderlies, who, though calm, clearly “mean business.” Restraints, however, may be required.

 Continuation Treatment.   Once acute treatment has been successful in bringing the manic symptoms under control, continuation treatment is begun. As noted earlier the average duration of ;the first manic episode is about 3 months, and that of a mixed-manic episode a little longer. The purpose of continuation treatment і to prevent a breakthrough of symptoms until such time as the episode itself has run its course. Generally this is accomplished by JMitinuing the regimen that was effective during the acute phase. . Lithium is used it may be necessary during the continuation  to reduce the dose. In many patients even though the dose of dum is held constant, the blood level rises when the manic symptoms eventually come under complete control. The unexpected appearance of side effects to lithium may indicate this and should y°mPt a blood level determination. If ЕСТ were used, a mood stabilizer should be started after treatment is terminated.

 If the patient decides not to enter into a preventive phase of treatment, one must estimate when the patient’s current episode, in all likelihood, will go into a spontaneous remission. A prior history of manic episodes may provide some guidance here; if that is lacking, one is guided by the duration of an average episode, mentioned earlier. Clearly, if the patient is having breakthrough manic symptoms, no matter how mild, treatment should continue. Furthermore, even when the estimated date of remission has passed, one should continue treatment if the patient’s life is unstable, and wait until a period of relative stability has occurred before exposing the patient to the risk, however small, of relapse. If lithium was utilized, it is important to taper the dose over a few weeks time, as it appears that abrupt discontinuation of lithium predisposes to a recurrence of mania. Although the need for tapering has not been demonstrated for the other agents, prudence dictates the use of a gradual taper here also.

 Preventive Treatment. The decision to embark on preventive treatment is based on several factors including the following: frequency of episodes, severity of episodes, rapidity with which episodes develop, and side effects of the agent used. Frequent episodes, perhaps occurring more than once every 2 years, usually constitute an indication for preventive treatment; a frequency of one every 5 or 10 years, however, may be such that the risk to the patient of another episode is outweighed by the trouble of taking medicine and any attendant side effects. Severe episodes, however, no matter how infrequent, may warrant prevention. Whereas the patient’s employer and family may be able to tolerate a manic episode limited to a hypomanic stage, a mania that enters a delirious stage is usually so destructive that it should be guarded against. Patients whose episodes tend to develop very slowly, over perhaps weeks or a month, may be able to “catch” themselves before their insight and judgment are lost. By making timely application for treatment, they may be able to bring the episode under control on an outpatient basis. Those whose episodes come on acutely over a few days or even hours, however, are defenseless and thus more appropriate for preventive treatment.

 

 If preventive treatment is elected, then the patient should be treated with a mood stabilizer (lithium, divalproex or carbamazepine) or olanzapine. Among the mood stabilizers, lithium has the longest track record and is therefore a reasonable first choice. Divalproex and carbamazepine may also be considered; however, the data supporting the use of divalproex as a preventive agent are not that good and carbamazepine is generally not very well tolerated. If lithium is used, it is important to keep the serum level between 0.6 and 1.0 mEq/L. The optimum dose for valproate and for carbamazepine for prophylaxis has not as yet been determined; prudence suggests using a dose similar to that which was effective for continuation treatment. When “breakthrough” symptoms of mania occur it is imperative to determine the patient’s thyroid status: hypothyroidism, even if manifest by only a slight rise in TSH, will blunt the response to any mood stabilizer, and must be corrected. When breakthrough mania occurs despite normal thyroid status and good compliance, consideration may be given to switching to monotherapy with another mood stabilizer or to using a combination of mood stabilizers such as lithium plus divalproex or lithium plus carbamazepine. Given the possibility of such “breakthrough” manias, it is generally prudent, in the case of reliable patients being maintained on a mood stabilizer, to prescribe a supply of adjunc-tive medication (e.g., olanzapine) to take at home in order to abort an episode and obviate the need for admission. In this regard, outpatients should be clearly instructed to call the physician should they even experience a “hint” of manic symptoms.

 Olanzapine has recently been shown to be effective in preventive treatment, and thus may be considered as an alternative to a mood stabilizer. It must be borne in mind, however, that, as compared with the mood stabilizers, especially lithium, the experience with olanzapine is limited; furthermore, emerging data regarding the risks of diabetes and hyperlipidemia with olanzapine may also temper enthusiasm for the long-term use of this agent.

 As noted in the section on course, various pharmacologic conditions, such as the use of sympathomimetics, the abrupt dis­continuation of long-term treatment with donidine, and the like, may precipitate manic episodes, and these conditions should be avoided whenever possible. Furthermore, as noted earlier, insomnia, or simply voluntarily going without sleep, may also precipitate a manic episode, and consequently, good sleep hygiene should be promoted.

 Recently it has been shown that cognitive behavioral therapy may, when used in conjunction with preventive pharmacologic treatment, reduce the frequency of breakthrough episodes. The mechanism here is not dear, and it also must be kept in mind that no form of psychotherapy is effective for either acute or continuation treatment of mania.

 

Depressive Episodes

 

Acute Treatment. When a depressive episode occurs in a patient with bipolar disorder the first step in the acute phase of treatment is to ensure that the patient is taking an antimanic drug, such as lithium, valproate, or carbamazepine, in a dose that would be effective in the acute treatment phase of mania. If the depression is not severe, one may want to wait 2 or 3 weeks to see if the depressive symptoms begin to clear, as this may often happen when one of these three agents is used. When depressive symptoms persist or when they are so severe to begin with that one cannot wait, one may add an antidepressant or consider adding lamotrigine or perhaps topiramate. Traditionally an antidepressant has been used; however, though effective, all the antidepressants entail the risk of precipitating a manic episode; a strategy for choosing and utilizing an antidepressant is discussed in the chapter on major depression. Neither lamotrigine nor topiramate carry a risk of inducing a manic episode, and between the two, the evidence for the effectiveness of lamotrigine is much stronger. In mild cases of depression, one may also consider the use of cognitive-behavioral therapy.

 Continuation Treatment.  Once the depressive symptoms are relieved, treatment should be continued until the patient has been asymptomatic for a significant period of time. If an antidepressant were added to a mood stabilizer, one should probably consider discontinuing the antidepressant after the patient has been asymptomatic for a matter of months. Given the ongoing risk of a “precipitated” mania, it is preferable to discontinue the drug as soon as possible: if depressive symptoms recur, one may always restart it. In the case of topiramate or lamotrigine, the optimum duration of continuation treatment is not clear. Prudence suggests that if one knows, from history, how long the patient’s. Depressive episodes tend to last, that treatment be continued somewhat past the expected date of spontaneous remission of the depression.

 

Preventive Treatment. Lithium, carbamazepine and lamotrigine are all effective in preventing future depressive episodes. Preventive treatment with antidepressants in bipolar disorder is generally not justified, given the ongoing risk of precipitating a manic episode.

 

Other Treatment Considerations

 

Pregnancy. Pregnancy constitutes a special challenge in the treatment of bipolar disorder. None of the mood stabilizers are safe during pregnancy (especially the first trimester). First generation antipsychotics, such as haloperidol, are probably less teratogenic-the teratogenic potential of olanzapine is not as yet clear. If mania does occur during pregnancy, then the risks to the fetus must be carefully weighed against the risks inherent in a manic episode. ЕСТ should be carefully considered given that, with proper anesthetic technique, it is of low risk to the fetus.

 

Bipolar women currently in the preventive phase of treatment may often be safely managed into and through a planned pregnancy. Preventive treatment may be continued up to a few days before conception is attempted. If conception does not occur, preventive treatment is restarted and continued until the couple again wishes to conceive. Once conception does occur, preventive treatment is withheld, to be restarted immediately upon delivery; indeed, barring obstetric complications, it should be restarted within hours. In collaboration with the obstetrician, adjunctive treatment is then made available should manic symptoms appear. In cases where the risk of a relapse of mania is high and outweighs the risk to the fetus, one may consider restarting a mood stabilizer after the first trimester. With regard to breast feeding, no firm advice can be given: although maternal use of lithium, valproate and carbamazepine have all been rarely associated with adverse effects in breast-fed infants, large, controlled studies are lacking. Consequently the decision to breast feed or not should be made in light of the entire clinical picture, including the mother’s illness and response to treatment.

 

Substance Use. As noted earlier, alcohol abuse or alcoholism and cocaine addiction are not infrequently associated with bipolar disorder, and these must also be treated.

Schizophrenia, schizotypical and delusional disorders

 

Schizophrenia (/ˌskɪtsɵˈfrɛniə/ or /ˌskɪtsɵˈfriːniə/) is a mental disorder characterized by a breakdown of thought processes and by a deficit of typical emotional responses. Common symptoms include auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social or occupational dysfunction.

History of schizophrenia

 

The word schizophrenia was coined by Eugen Bleuler in 1908, and was intended to describe the separation of function between personality, thinking, memory, and perception. He formally introduced the term on 24 April 1908 in a lecture given at a psychiatric conference in Berlin and in a publication that same year. Bleuler later expanded his new disease concept into a monograph in 1911, which was finally translated into English in 1950.

The history of ‘schizophrenia’ is complex and not easy to characterize in a linear historical narrative, although attempts continue to be made. According to some, the disease has always existed only to be ‘discovered’ during the early 20th century. The plausibility of this claim depends upon the success of retrospectively diagnosing earlier cases of madness as ‘schizophrenia’. According to others, ‘schizophrenia’ names a culturally determined clustering of mental symptoms. What is known for sure is that by the turn of the 20th century the old concept of insanity had become fragmented into ‘diseases’ (psychoses) such as paranoia, dementia praecox, manic-depressive insanity and epilepsy (Emil Kraepelin’s classification). Dementia praecox was reconstituted as schizophrenia, paranoia was renamed as ‘delusional disorder’ and manic-depressive insanity as ‘bipolar disorder’ (epilepsy was transferred from psychiatry to neurology). It is important to emphasize that the ‘mental symptoms’ included under the concept schizophrenia are real enough, make people suffer, and will always need understanding and treatment. However, whether the historical construct currently called ‘schizophrenia’ is required to achieve this therapeutic goal remains a moot point.

 

Diagnoses in ancient times

 

Accounts of a schizophrenia-like syndrome are thought to be rare in the historical record prior to the 19th century, although reports of irrational, unintelligible, or uncontrolled behavior were common. There has been an interpretation that brief notes in the Ancient Egyptian Ebers papyrus may imply schizophrenia, but other reviews have not suggested any connection. A review of ancient Greek and Roman literature indicated that although psychosis was described, there was no account of a condition meeting the criteria for schizophrenia. A 2012 paper suggested that psychiatric conditions, such as paranoid schizophrenia and others associated with psychotic spectrum symptoms, may be possible explanations for revelatory driven experiences and activities such as those of Abraham, Moses, Jesus and Saint Paul.

Bizarre psychotic beliefs and behaviors similar to some of the symptoms of schizophrenia were reported in Arabic medical and psychological literature during the Middle Ages. In The Canon of Medicine, for example, Avicenna described a condition somewhat resembling the symptoms of schizophrenia which he called Junun Mufrit (severe madness), which he distinguished from other forms of madness (Junun) such as mania, rabies and manic depressive psychosis. However, no condition resembling schizophrenia was reported in Şerafeddin Sabuncuoğlu’s Imperial Surgery, a major Islamic medical textbook of the 15th century. Given limited historical evidence, schizophrenia (as prevalent as it is today) may be a modern phenomenon, or alternatively it may have been obscured in historical writings by related concepts such as melancholia or mania.

 

Influential earlier concepts

 

A detailed case 1809 report by John Haslam concerning James Tilly Matthews, and a separate account by Philippe Pinel also published in 1809, are often regarded as the earliest cases of schizophrenia in the medical and psychiatric literature. The Latinized term dementia praecox entered psychiatry in 1886 in a textbook by asylum physician Heinrich Schüle (1840-1916) of the Illenau asylum in Baden. He used the term to refer to hereditarily predisposed individuals who were “wrecked on the cliffs of puberty” and developed acute dementia, while others developed the chronic condition of hebephrenia. Emil Kraepelin had cited Schüle’s 1886 textbook in the 1887 second edition of his own textbook, Psychiatrie, and hence was familiar with this term at least six years before he himself adopted it. It later appeared in 1891 in a case report by Arnold Pick which argued that hebephrenia should be regarded as a form of dementia praecox. Kraepelin first used the term in 1893. In 1899 Emil Kraepelin introduced a broad new distinction in the classification of mental disorders between dementia praecox and mood disorder (termed manic depression and including both unipolar and bipolar depression). Kraepelin believed that dementia praecox was caused by a life-long, smoldering systemic or “whole body” process of a metabolic nature that would eventually affect the functioning of the brain in a final decisive cascade. Hence, he believed the entire body — all the organs, glands and peripheral nervous system — was implicated in the natural disease process. Although he used the term “dementia,” Kraepelin seemed to use the term synonymously with “mental weakness,” mental defect,” and “mental deterioration,” but distinguished it from other uses of the term dementia, such as in Alzheimer’s disease, which typically occur later in life. In 1853 Bénédict Morel used the term démence précoce (precocious or early dementia) to describe a group of young patients who were suffering from “stupor”.It is sometimes argued that this first use of the term signals the medical discovery of schizophrenia. However, Morel employed the phrase in a purely descriptive sense and he did not intend to delineate a new diagnostic category. Moreover, his traditional conception of dementia differed significantly from that employed in the latter half of the nineteenth-century. Finally, there is no evidence that Morel’s démence précoce had any influence on the later development of the dementia praecox concept by either Arnold Pick or Emil Kraepelin.

Kraepelin’s classification slowly gained acceptance. There were objections to the use of the term “dementia” despite cases of recovery, and some defence of diagnoses it replaced such as adolescent insanity. The concept of adolescent insanity or developmental insanity had been advanced by Scottish psychiatrist Thomas Clouston in 1873, describing a psychotic condition which generally afflicted those aged 18–24 years, particularly males, and in 30% of cases proceeded to ‘a secondary dementia’.

The word schizophrenia—which translates roughly as “splitting of the mind” and comes from the Greek roots schizein (σχίζειν, “to split”) and phrēn, phren- (φρήν, φρεν-, “mind”) was coined by Eugen Bleuler in 1908 and was intended to describe the separation of function between personality, thinking, memory, and perception. Bleuler described the main symptoms as 4 A’s: flattened Affect, Autism, impaired Association of ideas and Ambivalence. Bleuler realized that the illness was not a dementia as some of his patients improved rather than deteriorated and hence proposed the term schizophrenia instead. However, many at the time did not accept that splitting or dissociation was an appropriate description, and the term would later have more significance as a source of confusion and social stigma than scientific meaning.

The term schizophrenia is commonly misunderstood to mean that affected persons have a “split personality”. Although some people diagnosed with schizophrenia may hear voices and may experience the voices as distinct personalities, schizophrenia does not involve a person changing among distinct multiple personalities. The confusion arises in part due to the meaning of Bleuler’s term schizophrenia (literally “split” or “shattered mind”). The first known misuse of the term to mean “split personality” was in an article by the poet T. S. Eliot in 1933.

Scratch-drawings on the wall in St. Elizabeths Hospital made by a patient with “a disturbed case of dementia praecox”.

In the first half of the 20th century schizophrenia was considered to be a hereditary defect, and sufferers were subject to eugenics in many countries. Hundreds of thousands were sterilized, with or without consent—the majority in Nazi Germany, the United States, and Scandinavian countries. Along with other people labeled “mentally unfit”, many diagnosed with schizophrenia were murdered in the Nazi “Action T4” program.

 

Anti-psychiatry

Anti-psychiatry refers to a diverse collection of thoughts and thinkers that challenge the medical concept of schizophrenia. Anti-psychiatry emphasizes the social context of mental illness and re-frames the diagnosis of schizophrenia as a labeling of deviance. Anti-psychiatry represented dissension of psychiatrists themselves about the understanding of schizophrenia in their own field. Prominent psychiatrists in this movement include R. D. Laing, David Cooper. Related criticisms of psychiatry were launched by philosophers such as Michel Foucault, Jacques Lacan, Gilles Deleuze, and Félix Guattari.

Anti-psychiatrists agree that ‘schizophrenia’ represents a problem, and that many human beings have problems living in modern society. But they protest the notion that schizophrenia is a disease, and that people who suffer from it are sick. Instead, they often suggest that schizophrenics appear crazy because they are intelligent and sensitive beings confronted with a mad world. Conversely, anti-psychiatry often describes the institutional world as itself pathological and insane because of the way it subordinates human beings to bureaucracy, protocol, and labels.

 

Controversies over validity in the 1970s

In 1970 psychiatrists Robins and Guze introduced new criteria for deciding on the validity of a diagnostic category and proposed that cases of schizophrenia where people recovered well were not really schizophrenia but a separate condition.

In the early 1970s, the diagnostic criteria for schizophrenia was the subject of a number of controversies which eventually led to the operational criteria used today. It became clear after the 1971 US-UK Diagnostic Study that schizophrenia was diagnosed to a far greater extent in America than in Europe. This was partly due to looser diagnostic criteria in the US, which used the DSM-II manual, contrasting with Europe and its ICD-9. David Rosenhan’s 1972 study, published in the journal Science under the title On being sane in insane places, concluded that the diagnosis of schizophrenia in the US was often subjective and unreliable.

Politicization in the Soviet Union

 

In the Soviet Union the diagnosis of schizophrenia has also been used for political purposes. The prominent Soviet psychiatrist Andrei Snezhnevsky created and promoted an additional sub-classification of sluggishly progressing schizophrenia. This diagnosis was used to discredit and expeditiously imprison political dissidents while dispensing with a potentially embarrassing trial. The practice was exposed to Westerners by a number of Soviet dissidents, and in 1977 the World Psychiatric Association condemned the Soviet practice at the Sixth World Congress of Psychiatry. Rather than defending his claim that a latent form of schizophrenia caused dissidents to oppose the regime, Snezhnevsky broke all contact with the West in 1980 by resigning his honorary positions abroad.

 

DSM III (1980)

 

The 1970s controversies lead to the revisioot only of the diagnosis of schizophrenia, but the revision of the whole DSM manual, resulting in the publication of the DSM-III in 1980. The revision was based on Feighner Criteria and Research Diagnostic Criteria that had in turn developed from Robins’ and Guze’s criteria, and which were intended to make diagnosis more reliable (consistent). Since the 1970s more than 40 diagnostic criteria for schizophrenia have been proposed and evaluated.

 

Schneiderian classification

In the early 20th century, the psychiatrist Kurt Schneider listed the forms of psychotic symptoms that he thought distinguished schizophrenia from other psychotic disorders. These are called first-rank symptoms or Schneider’s first-rank symptoms. They include delusions of being controlled by an external force; the belief that thoughts are being inserted into or withdrawn from one’s conscious mind; the belief that one’s thoughts are being broadcast to other people; and hearing hallucinatory voices that comment on one’s thoughts or actions or that have a conversation with other hallucinated voices. Although they have significantly contributed to the current diagnostic criteria, the specificity of first-rank symptoms has been questioned. A review of the diagnostic studies conducted between 1970 and 2005 found that they allow neither a reconfirmatioor a rejection of Schneider’s claims, and suggested that first-rank symptoms should be de-emphasized in future revisions of diagnostic systems.

 

Causes

 

Genetic

Estimates of heritability vary because of the difficulty in separating the effects of genetics and the environment. The greatest risk for developing schizophrenia is having a first-degree relative with the disease (risk is 6.5%); more than 40% of monozygotic twins of those with schizophrenia are also affected. A child of two parents with schizophrenia has a 46% chance of developing the disorder. It is likely that many genes are involved, each of small effect and unknown transmission and expression. Many possible candidates have been proposed, including specific copy number variations, NOTCH4, and histone protein loci. A number of genome-wide associations such as zinc finger protein 804A have also been linked. There appears to be significant overlap in the genetics of schizophrenia and bipolar disorder.[30] Evidence is emerging that the genetic architecture of schizophrenia involved both common and rare risk variation.

Assuming a hereditary basis, one question from evolutionary psychology is why genes that increase the likelihood of psychosis evolved, assuming the condition would have been maladaptive from an evolutionary point of view. One idea is that genes are involved in the evolution of language and humaature, but to date such ideas remain little more than hypothetical iature.

 

Environment

 

Environmental factors associated with the development of schizophrenia include the living environment, drug use and prenatal stressors. Parenting style seems to have no major effect, although people with supportive parents do better than those with critical or hostile parents. Living in an urban environment during childhood or as an adult has consistently been found to increase the risk of schizophrenia by a factor of two, even after taking into account drug use, ethnic group, and size of social group. Other factors that play an important role include social isolation and immigration related to social adversity, racial discrimination, family dysfunction, unemployment, and poor housing conditions.

 

Drug use

 

Amphetamine, cocaine, and to a lesser extent alcohol, can result in psychosis that presents very similarly to schizophrenia. Although not generally believed to be a cause of the illness, people with schizophrenia use nicotine at much greater rates than the general population. About half of those with schizophrenia use drugs or alcohol excessively. Evidence supports a link between earlier onset of psychotic illness and cannabis use; alcohol use is not associated with an earlier onset of psychosis. Other drugs may be used only as coping mechanisms by individuals who have schizophrenia to deal with depression, anxiety, boredom, and loneliness. There is evidence that alcohol abuse via a kindling mechanism can occasionally cause the development of a chronic substance induced psychotic disorder, i.e. schizophrenia. The more often cannabis is used, the more likely a person is to develop a psychotic illness, with frequent use being correlated with twice the risk of psychosis and schizophrenia. Whether cannabis use is a contributory cause of schizophrenia, rather than a behavior that is simply associated with it, remains controversial.

 

Developmental factors

 

Factors such as hypoxia and infection, or stress and malnutrition in the mother during fetal development, may result in a slight increase in the risk of schizophrenia later in life. People diagnosed with schizophrenia are more likely to have been born in winter or spring (at least in the northern hemisphere), which may be a result of increased rates of viral exposures in utero. This difference is about 5 to 8%.

 

Mechanisms of schizophrenia

 

The underlying mechanisms of schizophrenia, a mental disorder characterized by a disintegration of the processes of thinking and of emotional responsiveness, are complex. A number of theories attempt to explain the link between altered brain function and schizophrenia. One of the most important is the dopamine hypothesis. This attributes psychosis to the faulty distribution, regulation, and function of dopaminergic neurons. Specifically, atypicallity is observed within the D2 subtype, a common target for all antipsychotic drugs. Along with glutamate, dopamine is involved in the advancement and reinforcement of the abnormal thought patterns in schizophrenia. Similarly, dopamine facilitates abnormal long term potentiation within the striatum, basal ganglia, cingulate cortex (specifically the cingulate gyrus), and prefrontal cortex, among other limbic system structures.

Glutaminergic abnormalities may also figure in schizophrenia. Specifically, a deficit in metabotropic glutamate receptors 1 and 5 (the primary post-synaptic receptors) results in a relative excess of the activity of the other 6 presynaptic receptors. In turn, a reduction of cAMP levels in these glutaminergic neurons lowers the activity of the NMDA receptor, a receptor crucial for the phenomena of LTP. This then leads to altered K+, Na+, and Ca2+ levels within the cell. In addition, the protein reelin, a crucial modulator of NMDA function in the hippocampus, is in lowered concentrations in both schizophrenic and psychotic bipolar disorder patients.

This protein enhances LTP activity. That is, the risk for psychotic disorders is associated with alterations in the expression and distribution of a wide variety of G protein coupled receptors. Specifically alterations in the autoreception of metabotropic receptors creates abnormal ligand gated ion channel activity, resulting in maladaptive synaptic plasticity.

A leading hypothesis treats schizophrenia as a neurodevelopmental and neurodegenerative disease, in which “developmental insults as early as late first or early second trimester lead to the activation of pathologic neural circuits during adolescence or young adulthood”, but critics say the neurodevelopmental hypothesis “does not fully account for a number of features of schizophrenia”.

 

Indeed, schizophrenia requires not only genetically induced neurological deficits, but unique psychological stressors as well. It is fundamentally different from other developmental disorders, in that it is “self-induced” to some extent. That is, it results from an otherwise normal process for plasticity that advances to form a “parallel”, isolated circuit, similar to distributed computing, but on a much more integrated way. The causes of schizophrenia remain poorly understood.

In 2010 another hypothesis of schizophrenia was formulated: abnormal immune system development may help explain roles of prenatal hazards, post-pubertal onset, stress, genes, climate, infections, and brain dysfunction. The immune hypotheses is supported by findings of high serum levels of inflammatory markers.

Particular focus has been placed upon the function of dopamine in the mesolimbic pathway of the brain. This focus largely resulted from the accidental finding that a drug group which blocks dopamine function, known as the phenothiazines, could reduce psychotic symptoms. It is also supported by the fact that amphetamines, which trigger the release of dopamine, may exacerbate the psychotic symptoms in schizophrenia.

An influential theory, known as the Dopamine hypothesis of schizophrenia, proposed that excess activation of D2 receptors was the cause of (the positive symptoms of) schizophrenia. Although postulated for about 20 years based on the D2 blockade effect common to all antipsychotics, it was not until the mid-1990s that PET and SPET imaging studies provided supporting evidence. This explanation is now thought to be simplistic, partly because newer antipsychotic medication (called atypical antipsychotic medication) can be equally effective as older medication (called typical antipsychotic medication), but also affects serotonin function and may have slightly less of a dopamine blocking effect.

Interest has also focused on the neurotransmitter glutamate and the reduced function of the NMDA glutamate receptor in schizophrenia. This has largely been suggested by abnormally low levels of glutamate receptors found in postmortem brains of people previously diagnosed with schizophreniaand the discovery that the glutamate blocking drugs such as phencyclidine and ketamine can mimic the symptoms and cognitive problems associated with the condition.

The fact that reduced glutamate function is linked to poor performance on tests requiring frontal lobe and hippocampal function and that glutamate can affect dopamine function, all of which have been implicated in schizophrenia, have suggested an important mediating (and possibly causal) role of glutamate pathways in schizophrenia. Positive symptoms fail however to respond to glutamatergic medication. A commonly known side effect associated with schizo-affective patients known as akathisia (mistaken for schizophrenic symptoms) was found to be associated with increased levels of norepinephrine.

ErbB4 protein abnormalities are also associated with neuropathophysiology of the schizophrenic brain.

Glutamate

 

 

Glutamate is the primary excitatory neurotransmitter in the CNS. As such, it is crucial for the formation of any positive gain circuits within the brain. Of specific interest in this disorder are the presynaptic metabotropic receptors, which act as autoreceptors, regulating glycine and glutamate receptors, also known as NMDA receptors. NMDA receptors are unique in that they are voltage dependent, that is, at 0 or near 0 membrane potential, they are blocked by Mg2+ ions. Only when there is a depolarization do these Ca2+ channels open. This is the primary reason for the phenomena of LTP. While this a crucial component of the plasticity system of the brain, the GABA system, and Monoamine regulatory GPCRs are the primary way this can create long range order.

Interest has focused on these neurotransmitter, given the reduced function of the NMDA glutamate receptor in schizophrenia, and the ability for exogenuos agent to induce specific symptoms of this illness. This is supported by the fact that NMDA antagonists can create some of the negative symptoms of schizophrenia, e.g. catatonia, thought disorder, typical of schizophrenic, psychotic patients. However, dopaminergic drugs like methamphetamine and cocaine can cause some of the psychotic symptoms of schizophrenia, like paranoid delusions, agitation, and others.

The NMDA component has largely been suggested by abnormally low levels of glutamate receptors found in postmortem brains of people previously diagnosed with schizophrenia and the discovery that the glutamate blocking drugs such as phencyclidine and ketamine can mimic the symptoms and cognitive problems associated with the condition, while the dopaminergic part of this illness is suggested by the D2 antagonisms that is a common mechanism of action by all antipsychotic drugs, typical and atypical.

The fact that reduced glutamate function is linked to poor performance on tests requiring frontal lobe and hippocampal function and that glutamate can affect dopamine function, all of which have been implicated in schizophrenia, have suggested an important mediating (and possibly causal) role of glutamate pathways in schizophrenia. Further support of this theory has come from preliminary trials suggesting the efficacy of coagonists at the NMDA receptor complex in reducing some of the positive symptoms of schizophrenia. Note that the specific mechanisms of this are yet to be elucidated, as it involves a complex interplay between 5-HT1A, 5-HT2A, 5-HT1B, 5-HT2C, 5-HT6, and 5-HT7, D2, D1, the endocannabinoid systsem, including CB2, which regulates glial cell NT release.

 

Dopamine

 

Particular focus has been placed upon the function of dopamine in the mesolimbic pathway of the brain. This focus largely resulted from the accidental finding that a drug group which blocks dopamine function, known as the phenothiazines, could reduce psychotic symptoms. An influential theory, known as the “dopamine hypothesis of schizophrenia”, proposes that a malfunction involving dopamine pathways is therefore the cause of (the positive symptoms of) schizophrenia.

Evidence for this theory includes findings that the potency of many antipsychotics is correlated with their affinity to dopamine D2 receptors; and the exacerbatory effects of a dopamine agonist (amphetamine) and a dopamine beta hydroxylase inhibitor (disulfiram) on schizophrenia; and post-mortem studies initially suggested increased density of dopamine D2 receptors in the striatum. Such high levels of D2 receptors intensify brain signals and can exacerbate positive symptoms (i.e. hallucinations and paranoia) in schizophrenia. Impaired glutamate (a neurotransmitter which directs neuron to pass along an impulse) activity appears to be another source of schizophrenia symptoms.

However, there was controversy and conflicting findings over whether postmortem findings resulted from drug tolerance to chronic antipsychotic treatment. Compared to the success of postmortem studies in finding profound changes of dopamine receptors, imaging studies using SPET and PET methods in drug naive patients have generally failed to find any difference in dopamine D2 receptor density compared to controls. Comparable findings in longitudinal studies show: ” Particular emphasis is given to methodological limitations in the existing literature, including lack of reliability data, clinical heterogeneity among studies, and inadequate study designs and statistic,” suggestions are made for improving future longitudinal neuroimaging studies of treatment effects in schizophrenia. A recent review of imaging studies in schizophrenia shows confidence in the techniques, while discussing such operator error. In 2007 one report said, “During the last decade, results of brain imaging studies by use of PET and SPET in schizophrenic patients showed a clear dysregulation of the dopaminergic system.”

Recent findings from meta-analyses suggest that there may be a small elevation in dopamine D2 receptors in drug-free patients with schizophrenia, but the degree of overlap between patients and controls makes it unlikely that this is clinically meaningful. While the review by Laruelle acknowledged more sites were found using methylspiperone, it discussed the theoretical reasons behind such an increase (including the monomer-dimer equilibrium) and called for more work to be done to ‘characterise’ the differences. In addition, newer antipsychotic medication (called atypical antipsychotic medication) can be as potent as older medication (called typical antipsychotic medication) while also affecting serotonin function and having somewhat less of a dopamine blocking effect. In addition, dopamine pathway dysfunction has not been reliably shown to correlate with symptom onset or severity. HVA levels correlate trendwise to symptoms severity. During the application of debrisoquin, this correlation becomes significant.

Giving a more precise explanation of this discrepancy in D2 receptor has been attempted by a significant minority. Radioligand imaging measurements involve the monomer and dimer ratio, and the ‘cooperativity’ model. Cooperativitiy is a chemical function in the study of enzymes. Dopamine receptors interact with their own kind, or other receptors to form higher order receptors such as dimers, via the mechanism of cooperativity. Philip Seeman has said: “In schizophrenia, therefore, the density of methylspiperone sites rises, reflecting an increase in monomers, while the density of raclopride sites remains the same, indicating that the total population of D2 monomers and dimers does not change.” (In another place Seeman has said methylspiperone possibly binds with dimers) With this difference in measurement technique in mind, the above mentioned meta-analysis uses results from 10 different ligands. Exaggerated ligand binding results such as SDZ GLC 756 (as used in the figure) were explained by reference to this monomer-dimer equilibrium.

According to Seeman, “…Numerous postmortem studies have consistently revealed D2 receptors to be elevated in the striata of patients with schizophrenia”.However, the authors were concerned the effect of medication may not have been fully accounted for. The study introduced an experiment by Abi-Dargham et al. in which it was shown medication-free live schizophrenics had more D2 receptors involved in the schizophrenic process and more dopamine. Since then another study has shown such elevated percentages in D2 receptors is brain-wide (using a different ligand, which did not need dopamine depletion). In a 2009 study, Annisa Abi-Dagham et al. confirmed the findings of her previous study regarding increased baseline D2 receptors in schizophrenics and showing a correlation between this magnitude and the result of amphetamine stimulation experiments.

Some animal models of psychosis are similar to those for addiction – displaying increased locomotor activity. For those female animals with previous sexual experience, amphetamine stimulation happens faster than for virgins. There is no study on male equivalent because the studies are meant to explain why females experience addiction earlier than males.

Even in 1986 the effect of antipsychotics on receptor measurement was controversial. An article in Science sought to clarify whether the increase was solely due to medication by using drug-naive schizophrenics: “The finding that D2 dopamine receptors are substantially increased in schizophrenic patients who have never been treated with neuroleptic drugs raises the possibility that dopamine receptors are involved in the schizophrenic disease process itself. Alternatively, the increased D2 receptor number may reflect presynaptic factors such as increased endogenous dopamine levels (16). In either case, our findings support the hypothesis that dopamine receptor abnormalities are present in untreated schizophrenic patients.” (The experiment used 3-N-[11C]methylspiperone – the same as mentioned by Seeman detects D2 monomers and binding was double that of controls.)

It is still thought that dopamine mesolimbic pathways may be hyperactive, resulting in hyperstimulation of D2 receptors and positive symptoms. There is also growing evidence that, conversely, mesocortical pathway dopamine projections to the prefrontal cortex might be hypoactive (underactive), resulting in hypostimulation of D1 receptors, which may be related to negative symptoms and cognitive impairment. The overactivity and underactivity in these different regions may be linked, and may not be due to a primary dysfunction of dopamine systems but to more general neurodevelopmental issues that precede them. Increased dopamine sensitivity may be a common final pathway.

Another finding is a six-fold excess of binding sites insensitive to the testing agent, raclopride; Seeman said this increase was probably due to the increase in D2 monomers. Such an increase in monomers may occur via the cooperativity mechanism which is responsible for D2High and D2Low, the supersensitive and lowsensitivity states of the D2 dopamine receptor. More specifically, “an increase in monomers, may be one basis for dopamine supersensitivity”.

Another one of Seeman’s findings was that the dopamine D2 receptor protein looked abnormal in schizophrenia. Proteins change states by flexing. The activating of the protein by folding could be permanent or fluctuating, just like the course of patients’ illnesses waxes and wanes. Increased folding of a protein leads to increased risk of ‘additional fragments’ forming. The schizophrenic D2 receptor has a unique additional fragment when digested by papain in the test-tube, but none of the controls exhibited the same fragment. The D2 receptors in schizophrenia are thus in a highly active state as found by Seeman et al.

 

Structural findings

 

Studies have tended to show various subtle average differences in the volume of certain areas of brain structure between people with and without diagnoses of schizophrenia, although it has become increasingly clear that there is no single pathological neuropsychological or structural neuroanatomic profile, due partly to heterogeneity within the disorder.

 

 

Neurological mechanisms

 

Those with a diagnosis of schizophrenia have both changes in brain structure and brain chemistry, including dopamine. Studies using neuropsychological tests and brain imaging technologies such as fMRI and PET to examine functional differences in brain activity have shown that differences seem to most commonly occur in the frontal lobes, hippocampus and temporal lobes. Due to the alteration ieural circuits some feel schizophrenia should be viewed as a collection of neurodevelopmental disorders. These differences have been linked to the neurocognitive deficits often associated with schizophrenia.

The past 30 years of brain imaging supports the neurobiological pathologies of psychiatric diseases. The neurobiological abnormalities are so varied that no single abnormality is observed across the entire group of people with DSM-IV–defined schizophrenia. In addition, it remains unclear whether the structural differences are unique to schizophrenia or cut across the traditional diagnostic boundaries between schizophrenia and affective disorders – though perhaps being unique to conditions with psychotic features.

Studies of the rare childhood-onset schizophrenia (before age 13) indicate a greater-than-normal loss of grey matter over several years, progressing from the back of the brain to the front, leveling out in early adulthood. Such a pattern of “pruning” occurs as part of normal brain development but appears to be exaggerated in childhood-onset psychotic diagnoses, particularly schizophrenia. Abnormalities in the volume of the ventricles or frontal lobes have also been found in several studies but not in others. Volume changes are most likely glial and vascular rather than purely neuronal, and reduction in grey matter may primarily reflect a reduction of neuropil rather than a deficit in the total number of neurons. Other studies, especially some computational studies, have shown that a reduction in the number of neurons can cause psychotic symptoms. Studies to date have been based on small numbers of the most severe and treatment-resistant patients taking antipsychotics.

The most consistent volumetric findings are (first-onset patient vs control group averages), slightly less grey matter volume and slightly increased ventricular volume in certain areas of the brain. The two findings are thought to be linked. Although the differences are found in first-episode cases, grey matter volumes are partly a result of life experiences, drugs and malnutrition etc., so the exact role in the disorder is unclear.

In addition, ventricle volumes are amongst the mostly highly variable and environmentally influenced aspects of brain structure, and the percentage difference in group averages in schizophrenia studies has been described as “not a very profound difference in the context of normal variation.” A slightly smaller than average whole-brain volume has also been found, and slightly smaller hippocampal volume in terms of group averages. These differences may be present from birth or develop later, and there is substantial variation between individuals.

 

MRI

 

There have also been findings of differences in the size and structure of certain brain areas in schizophrenia. A 2006 metaanalysis of MRI studies found that whole brain and hippocampal volume are reduced and that ventricular volume is increased in patients with a first psychotic episode relative to healthy controls. The average volumetric changes in these studies are however close to the limit of detection by MRI methods, so it remains to be determined whether schizophrenia is a neurodegenerative process that begins at about the time of symptom onset, or whether it is better characterised as a neurodevelopmental process that produces abnormal brain volumes at an early age. In first episode psychosis typical antipsychotics like haloperidol were associated with significant reductions in gray matter volume, whereas atypical antipsychotics like olanzapine were not. Studies ion-human primates found gray and white matter reductions for both typical and atypical antipsychotics.

Abnormal findings in the prefrontal cortex, temporal cortex and anterior cingulate cortex are found before the first onset of schizophrenia symptoms. These regions are the regions of structural deficits found in schizophrenia and first-episode patients.

Positive symptoms, such as thoughts of being persecuted, were found to be related to the medial prefrontal cortex, amygdala, and hippocampus region. Negative symptoms were found to be related to the ventrolateral prefrontal cortex and ventral striatum.

Ventricular and third ventricle enlargement, abnormal functioning of the amygdala, hippocampus, parahippocampal gyrus, neocortical temporal lobe regions, frontal lobe, prefontal gray matter, orbitofrontal areas, parietal lobs abnormalities and subcortical abnormalities including the cavum septi, pellucidi, basal ganglia, corpus callosum, thalamus and cerebellar abnormalities. Such abnormalities usually present in the form of loss of volume.

Most schizophrenia studies have found average reduced volume of the left medial temporal lobe and left superior temporal gyrus, and half of studies have revealed deficits in certain areas of the frontal gyrus, parahippocampal gyrus and temporal gyrus. However, at variance with some findings in individuals with chronic schizophrenia significant group differences of temporal lobe and amygdala volumes are not shown in first-episode patients on average.

Finally, MRI studies utilizing modern cortical surface reconstruction techniques have shown widespread reduction in cerebral cortical thickness (i.e., “cortical thinning”) in frontal and temporal regionsand somewhat less widespread cortical thinning in occipital and parietal regions in patients with schizophrenia, relative to healthy control subjects. Moreover, one study decomposed cortical volume into its constituent parts, cortical surface area and cortical thickness, and reported widespread cortical volume reduction in schizophrenia, mainly driven by cortical thinning, but also reduced cortical surface area in smaller frontal, temporal, parietal and occipital cortical regions.

 

fMRI

Functional magnetic resonance imaging and other brain imaging technologies allow for the study of differences in brain activity among people diagnosed with schizophrenia

The use of functional MRI (fMRI) with cognitive behavioral science allows scientists to investigate and uncover areas of the brain that are not working appropriately in the schizophrenic brain, leading the behavioral deficits. Through this effort there have been several areas of the brain that are responsible for cognitive processing that have been identified to be malfunctioning in the schizophrenic brain. These studies have demonstrated abnormalities at the early steps of sensory processing. This may influence further errors when it comes to more comprehensive and complex evaluation processing, which compounds the problem.

 

DT-MRI

 

Diffusion tensor MRI (DTI) allows for the investigation of white matter more closely than traditional MRI. A 2009 meta-analysis of diffusion tensor imaging studies identified two consistent locations of reduced fractional anisotropy (roughly the level of organization of neural connections) in schizophrenia. This suggest that two networks of white matter tracts may be affected in schizophrenia, with the potential for “disconnection” of the gray matter regions which they link. Reduced anisotropy levels of white matter integrity and decreased anisotropy in the splenium of the corpus callosum.

 

PET

 

Data from a PET studysuggests that the less the frontal lobes are activated during a working memory task, the greater the increase in abnormal dopamine activity in the striatum, thought to be related to the neurocognitive deficits in schizophrenia.

PET scanning is a useful tool to allow the imaging of brain physiology. PET is useful to elaborate hypothesis of the origins of brain pathology, to relate symptoms to biological variables and to study individuals at increased risk. Studies measuring cerebral metabolic rate for glucose (CMRglc) and cerebral blood flow (CBF) have indicated an indirect measurement of synaptic activity. The ability to detect dysfunction of the communication between glutamatergic neurons and astrocytes may lead to an increased understanding of altered functional brain images.

PET scan findings indicate cerebral blood flow decreases in the left parahippocampal region. PET scans also show a reduced ability to metabolize glucose in the thalamus and frontal cortex. PET scans also show involvement of the medial part of the left temporal lobe and the limbic and frontal systems as suffering from developmental abnormality. PET scans show thought disorders stem from increased flow in the frontal and temporal regions while delusions and hallucinations were associated with reduced flow in the cingulate, left frontal, and temporal areas. PET scans done on patient who were actively having auditory hallucinations revealed increased blood flow in both thalami, left hippocampus, right striatum, parahippocampus, orbitofrontal, and cingulate areas.

 

CT

 

Computed Tomography scans of schizophrenic brains show several pathologies. The brain ventricles are enlarged as compared to normal brains. The ventricles hold cerebrospinal fluid (CSF) and enlarged ventricles indicate a loss of brain volume. Additionally, schizophrenic brains have widened sulci as compared to normal brains, also with increased CSF volumes and reduced brain volume.

 

EEG

 

Electroencephalograms (EEG) measure the electrical impulses on the surface of the brain. EEGs have demonstrated abnormalities of the P300 waveform in cortical event related potentials including nerve voltage conduction in the temporal lobe in both right-handed and left-handed schizophrenics.

Psychological mechanisms

Many psychological mechanisms have been implicated in the development and maintenance of schizophrenia. Cognitive biases have been identified in those with the diagnosis or those at risk, especially when under stress or in confusing situations. Some cognitive features may reflect global neurocognitive deficits such as memory loss, while others may be related to particular issues and experiences.

Despite a demonstrated appearance of blunted affect, recent findings indicate that many individuals diagnosed with schizophrenia are emotionally responsive, particularly to stressful or negative stimuli, and that such sensitivity may cause vulnerability to symptoms or to the disorder. Some evidence suggests that the content of delusional beliefs and psychotic experiences can reflect emotional causes of the disorder, and that how a person interprets such experiences can influence symptomatology. The use of “safety behaviors” to avoid imagined threats may contribute to the chronicity of delusions. Further evidence for the role of psychological mechanisms comes from the effects of psychotherapies on symptoms of schizophrenia.

 

Diagnosis

 

Schizophrenia is diagnosed based on criteria in either the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, version DSM-IV-TR, or the World Health Organization’s International Statistical Classification of Diseases and Related Health Problems, the ICD-10. These criteria use the self-reported experiences of the person and reported abnormalities in behavior, followed by a clinical assessment by a mental health professional. Symptoms associated with schizophrenia occur along a continuum in the population and must reach a certain severity before a diagnosis is made. As of 2009 there is no objective test.

 

Criteria

 

The ICD-10 criteria are typically used in European countries, while the DSM-IV-TR criteria are used in the United States and to varying degrees around the world, and are prevailing in research studies. The ICD-10 criteria put more emphasis on Schneiderian first-rank symptoms. In practice, agreement between the two systems is high.

According to the revised fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), to be diagnosed with schizophrenia, three diagnostic criteria must be met:

Characteristic symptoms: Two or more of the following, each present for much of the time during a one-month period (or less, if symptoms remitted with treatment).

·        Delusions

·        Hallucinations

·        Disorganized speech, which is a manifestation of formal thought disorder

·        Grossly disorganized behavior (e.g. dressing inappropriately, crying frequently) or catatonic behavior

·        Negative symptoms: Blunted affect (lack or decline in emotional response), alogia (lack or decline in speech), or avolition (lack or decline in motivation)

If the delusions are judged to be bizarre, or hallucinations consist of hearing one voice participating in a running commentary of the patient’s actions or of hearing two or more voices conversing with each other, only that symptom is required above. The speech disorganization criterion is only met if it is severe enough to substantially impair communication.

·        Social or occupational dysfunction: For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning such as work, interpersonal relations, or self-care, are markedly below the level achieved prior to the onset.

·        Significant duration: Continuous signs of the disturbance persist for at least six months. This six-month period must include at least one month of symptoms (or less, if symptoms remitted with treatment).

If signs of disturbance are present for more than a month but less than six months, the diagnosis of schizophreniform disorder is applied. Psychotic symptoms lasting less than a month may be diagnosed as brief psychotic disorder, and various conditions may be classed as psychotic disorder not otherwise specified. Schizophrenia cannot be diagnosed if symptoms of mood disorder are substantially present (although schizoaffective disorder could be diagnosed), or if symptoms of pervasive developmental disorder are present unless prominent delusions or hallucinations are also present, or if the symptoms are the direct physiological result of a general medical condition or a substance, such as abuse of a drug or medication.

 

Subtypes

 

The DSM-IV-TR contains five sub-classifications of schizophrenia, although the developers of DSM-5 are recommending they be dropped from the new classification:

 

Paranoid type: Delusions or auditory hallucinations are present, but thought disorder, disorganized behavior, or affective flattening are not. Delusions are persecutory and/or grandiose, but in addition to these, other themes such as jealousy, religiosity, or somatization may also be present. (DSM code 295.3/ICD code F20.0)

 

Disorganized type: Named hebephrenic schizophrenia in the ICD. Where thought disorder and flat affect are present together. (DSM code 295.1/ICD code F20.1)

Catatonic type: The subject may be almost immobile or exhibit agitated, purposeless movement. Symptoms can include catatonic stupor and waxy flexibility. (DSM code 295.2/ICD code F20.2)

 

Undifferentiated type: Psychotic symptoms are present but the criteria for paranoid, disorganized, or catatonic types have not been met. (DSM code 295.9/ICD code F20.3)

 

Residual type: Where positive symptoms are present at a low intensity only. (DSM code 295.6/ICD code F20.5)

 

 

 

The ICD-10 defines two additional subtypes:[69]

Post-schizophrenic depression: A depressive episode arising in the aftermath of a schizophrenic illness where some low-level schizophrenic symptoms may still be present. (ICD code F20.4)

Simple schizophrenia: Insidious and progressive development of prominent negative symptoms with no history of psychotic episodes. (ICD code F20.6)

 

Schizophrenia typically is characterized by perturbations in cognition, affect and behavior, all of which have a bizarre aspect. Delusions, also generally bizarre, and hallucinations, generally auditory in type, also typically occur. The original name for this illness, “dementia praecox,” was coined by Emil Kraepelin, a German psychiatrist in the late nineteenth and early twentieth century, whose description of the illness remains a guiding force for modern investigators.

 Schizophrenia is a relatively common disorder, with a lifetime prevalence of about 1%. Although the overall sex ratio is almost equal, males tend to have an earlier onset than females, a finding accounted for by the later age of onset in those females who lack a family history of the disease.

 

Onset

 

Although most patients fall ill in late teenage or early adult years, the range of age of onset is wide: childhood onset may occur, and in some instances symptoms may not appear until the sixties.

 There may or may not be a prodrome before the actual onset of symptoms. In some cases the “pre-morbid personality” appears completely normal. In others, however, peculiarities may have been apparent for years or even decades before the In cases where the prodrome began in childhood, the itory may reveal introversion and peculiar interests. In cases here the prodrome began later, after the patient’s person-lity was formed, family members may recall a stretch of time herein the patient “changed” and was no longer “the same.” Prior interests and habits may have been abandoned and replaced by a certain irritable seclusiveness, or perhaps fuspiciousness.

 The onset of symptoms may be acute or insidious, cute onsets tend to span a matter of weeks or months and be characterized by confusion or at times by depressive symptoms. Patients may recognize that something is wrong, and may make some desperate attempts to bring some order the fragmenting experience of life.  By contrast, in cases an insidious onset the patient may not be particularly [ibled at all. Over many months or a year or more, evanescent ges may occur: fleeting whispers, vague intimations, or Pge occurrences.

 

Clinical features

 

Although the clinical presentation of schizophrenia varies widely among patients, certain signs and symptoms, though present to different degrees, are consistently present, and these include hallucinations, delusions, disorganized speech and catatonic or bizarre behavior. “Negative” symptoms (e.g., flattening of affect) are often also seen but in some cases are quite mild. Generally, based on the constellation of symptoms present, one may classify any given case of schizophrenia into one of several subtypes, namely the paranoid, catatonic, hebephrenic (“disorganized”) and simple subtypes, with a large proportion of patients, however, failing to clearly fit any subtype and being characterized as having “undiffer-entiated” schizophrenia.

 Hallucinations are very common in schizophrenia. Patients may hear things, often voices, or they may see things; hallucinations of taste, touch, and smell may also occur. But of all these, the hearing of voices is most characteristic of schizophrenia.

 The voices may come from anywhere. They come from the air; God or angels send them. They may come from the television or radio; wiring may emanate the voices. Special devices may be planted in the walls or furniture. Sometimes they are in clothing; often they are localized to certain parts of the body. They come from the bowels, the liver, from “just behind the ear.” They may be male or female; the patient may or may not be able to recognize the identity of the speaker. It is a sibling, or a dead parent. Most often, though, the voices are not recognized as belonging to anyone; they are from strangers. They may be clear and easily understood; sometimes they are deafening and compelling—”everything else is shut out.” At other times they may be soft, “just a mumbling,” indistinct and fading.

 What the voices say is extremely varied: however, certain themes are relatively common. Voices may comment on what the patient is doing. Often two voices argue with one another about the patient. Often the voice echoes or repeats what the patient thought. Thoughts are “audible”; they are “heard out loud”; they are repeated on the television.

 At times “command hallucinations,” or voices that tell the patient what to do, may be heard. At times these are imperious and irre­sistible; at other times they are soft, “suggestive only.” Sometimes they command innocuous things; the patient may be directed to shave again. At other times they may command the patient to commit suicide or to hurt others. Usually the commands can be resisted, but not always. Sometimes they are overwhelmingly compelling—”they must be obeyed.”

 The patients generally hear only short phrases, perhaps single words. Only very rarely do the voices speak at length in a coherent way. Often the patient is tortured by the voices. Patients may hear threats of death, accusations of unspeakable sins, or announcements that the gallows are being erected.

 Rarely patients are encouraged or comforted by the voices. An angel’s voice may proclaim their divinity; seductive voices may whisper enticement; their names may be praised. Unutterable joys are set aside for them. Patients who hear such voices may have a beatific countenance.

 Most patients find the voices as real sounding as the voice of any other person. They may talk back to them out loud or may even argue with them. At times when the voices are unpleasant, the patient may try to drown them out by listening to music or to the television.

 In addition to hearing voices patients may also hear sounds, such as a creaking or a rattling of chains. Footsteps or a tapping on the windows is heard. Hissing and whistling also may be heard. Sometimes a ringing of church bells or an explosion is heard. Hammering means the gallows are being constructed. Very rarely the patient may hear music.

 Visual hallucinations, though common, play a relatively less prominent part in the clinical picture of schizophrenia than do auditory hallucinations. They may be poorly formed, indistinct, seen only “out of the corner of the eye.” They may, however, be vivid and compellingly realistic. Strange people walk the halls; the devil in violent red appears in front of the patient; heads float through the air. Reptilian forms appear in the bath; things crawl in the food; a myriad of insects appear in the bedding. The electric chair is made ready; torturers approach; a chorus of sympathetic angels is seen.

 Hallucinations of smell and taste, though not common, may be particularly compelling to the patient. Poison gas is smelled; it seems to be coming from the heating ducts. The patient smelb putrefied flesh, so the corpses must be buried nearby. At times inexpressibly beautiful perfumes are appreciated, a seduction seems close at hand.

 Tastes, often foul and bitter, may appear on the tongue “from nowhere.” Often, however, something is detected in food or drink. Patients detect something brackish, a poisonous or medicinal taste. Patients may refuse all food and drink and declare that they have had enough poison already.

 Hallucinations of touch, also known as haptic or tactile hallucinations, are relatively common. Something is crawling on them; a pricking is coming from behind. At night all manner of things are felt. Fluids are poured over the body; a caressing is felt, as are lips on all parts. Electrical sensations may be felt at any time. Sometimes patients may feel things inside their bodies. Their intestines shrivel up; the ovaries burst; the brain is pressed upon.

 Delusions are almost universal in schizophrenia. The content of the delusions is extremely varied: patients may feel persecuted; they may have grandiose ideas; all manner of things may refer and pertain to them; thoughts may be broadcast, withdrawn, or inserted into them; they may feel influenced and controlled by outside forces; bizarre, loathsome events may occur. These beliefs may grow in the patient slowly. At first there may be only an inkling, a suspicion; only with time does conviction occur. Conversely, sudden enlightenment may occur; all may be immediately clear. Sometimes patients may have lingering doubts about the truth of these beliefs, but for most they are as self-evident  as any other belief. Occasionally patients may argue with those who disagree, but for the most part they do not press their case on the unbeliever. Most often the delusions are poorly coordinated with each other; typically they are contradictory and poorly elaborated. Occasionally, however, they may be systematized, and this is especially the case in the paranoid subtype.

 Delusions of persecution are particularly common. There is a conspiracy against the patient; the FBI has coordinated its efforts with the local police. Plain-clothes officers follow the patient. At times the surveillance is covert. Satellites are used. Listening devices have been placed in the walls; the telephone is tapped. The patient is followed by cars; headlights blink on and off to indicate that capture is imminent. The food is poisoned. Electrical currents are passed through the body at night; internal organs are horribly manipulated during sleep. Tortures are prepared; escape is not possible. Sometimes patients may stoically endure their persecution, and at other times they may fight back. To the patient, this unprovoked assault may be a justifiable defense. Other patients attempt to flee their persecutors and may move to another state. For a time they may feel less insecure, but eventually they see signs that they have been found and again the persecution begins. Some patients attempt to protect themselves against noxious influences by armoring themselves or their apartments. One patient who believed that persecutors sent electrical charges down through the ceiling at night papered the entire ceiling with aluminum foil and for a time felt protected.

 Grandiose delusions also occur frequently, often in conjugation with delusions of persecution. Patients are attacked by jealous enemies who seek to bar them from the throne. They are to be exalted; the angel of the Lord has visited them. Millions of dollars are kept secretly away from them. They embark for Washington; the President wishes their advice. Commonly most patients do not act on their delusions; rather they seem content to be comforted and sustained by them. Exceptions do occur, of course. One patient announced a plan for world happiness in a full-page newspaper ad; another sent a letter of advice to the Secretary of State.

 Delusions of reference are intimately tied to delusions of persecution or of grandeur. Here patients believe that otherwise chance occurrences or random encounters have special meaning for them. What was done refers to them; it pertains to them. A busboy leaves a particle of food on the table; it is an intentional offense to the patient. The street lights blink on; it is a sign for the persecutors to close in for the final attack. The televisioewscaster speaks in code; the songs on the radio hold special meaning for the patient. There are no more coincidences in life, no accidental happenings. To the grandiose patient the events of creation are exalting; to the persecuted patient, walking the streets can provoke a terrifying self-consciousness. Everything is pregnant with meaning.

 Some patients may develop some peculiarly bizarre beliefs about thinking itself, known as thought broadcasting, thought withdrawal, and thought insertion. In thought broadcasting patients experience thoughts as being broadcast from their heads, as if by electricity. “It is like radio broadcasting,” explained one patient. These thoughts may then be picked up by others. Some patients compare it to telepathy; some feel they can receive others’ thoughts. “There is mind reading going on,” commented one patient. Sometimes the television may broadcast their thoughts back to them. In thought withdrawal the patients’ thoughts are removed, taken from them. The mind is left blank. “There are no thoughts anymore,” complained one patient. Magnetic devices may be used; the thoughts are never returned.

 Patients who experience this symptom of thought withdrawal may concurrently, if they happen to be speaking their thoughts, display the sign known as “thought blocking.” Here, patients in the middle of speaking abruptly cease talking, and this happens precisely because they abruptly find themselves with no thoughts to express. In thought insertion, a phenomenon opposite to that of thought withdrawal occurs. Here patients experienced the insertion of thoughts into their minds. The thoughts are alien, not their own; they were placed there by some other agency. The thoughts are transmitted toward them electrically; they can feel a tingling as they enter their brain. They cannot rid themselves of them.

 Allied to the foregoing three delusions are what are known as delusions of influence, or control. Patients experience their thoughts, emotions, or actions to be directly controlled by some outside force or agency. They are made to experience or do these things; they are like robots or automatons, without any independence of will. The influence may emanate from the television broadcast tower; a spell may be cast on them; a massive computer has merged its workings into them. They are not themselves anymore.

 Other delusions may occur. In fact any imaginable belief may be held, no matter how fantastic. Angels live in the patient’s nose; sulphur is cast on the body during sleep; parents have risen from their graves; all fluids have evaporated from the body. Another delusion is the delusion of doubles, also known as the “Capgras phenomenon,” or the delusion of impostors. Here the patient believes that someone, or something, has occupied the body of another. Although the body looks the same and the voice is the same, indeed, for all intents and purposes, it is the same person, yet the patient knows without doubt that it is an impostor. The patient may see subtle signs of it elsewhere; it is part of the conspiracy. The senses cannot be trusted anymore; appearances must be doubted. Doubles may be used for one’s spouse or children; no one is immune. The patient must be on guard at all times.

 Disorganized speech is the next symptom to consider. Here, we are concerned not so much with the content of the patient’s speech, that is to say with delusions, but rather with the form of speech. This “formal thought disorder” is most often characterized as “loosening of associations”; less frequently it is referred to as incoherence or “derailment.” The patient’s speech becomes illogical; ideas are juxtaposed that have no conceivable connection. Family member may say that the patient “doesn’t make sense.” Its extreme, loosening of associations may present as a veritable ,Jcffrord salad.” An example of loosening of associations follows. «?! patient was asked to report the previous day’s activities; the I’-‘iii nt replied, in part, “The sun bestrides the mouse doctor. In the iing, if you wish. Twenty-five dollars is a lot of money! Large  and eyes. Terrible smells. Rat in the socket. Can there be j’rt ness? Oh, if you only knew!” Here any inner connection Hig the various ideas and concepts is lost; it is as if they came tr’>ndom. Or to put it another way the thoughts are no longer Sjul-directed”; they no longer cohere in pursuit of a common ‘pose. If patients are pressed to explain what they mean, they are Me to offer a satisfactory reply. The question may be responded but only with another incoherent utterance. Interestingly, у these patients seem little concerned about their incoherence, seem oblivious to it and make little if any effort to clarify t they say.

 Wed to loosening of associations are neologisms. These are і that occur in the normal course of the patient’s speech and h patient treats as an integral part of it, but that convey no more meaning to the listener than if they were from a long-dead foreign language. To the patient, however, they have as much meaning and status as any other word, but that meaning is private and inaccessible to the listener. When one patient was offered a cup of coffee, the reply was, “Yes, doctor, thank you. With bufkuf.” When asked the meaning of “bufkuf,” the patient replied “Oh, you know,” and made no further effort to define or explain it.

 Catatonic symptoms include negativism, certain peculiar disturbances of voluntary activity known as catalepsy, posturing, stereotypies and echolalia or echopraxia.

 Negativism is characterized by a mulish, automatic, almost instinctual opposition to any course of action suggested, demanded, or merely expected. In some cases this negativism is passive: if food is placed in front of patients, they do not eat; if their clothes are set out for them, they do not dress; if a question is asked, they do not answer, and a bizarre scowl may mar the facial expression. In more extreme cases the negativism becomes active, and patients may do the exact opposite of what is expected: if shown to their room, they may enter another; if asked to open their mouths, they may clamp shut; if asked to walk from a burning room, they may walk back in. Such active negativism seems neither thought out nor done for a purpose; rather it appears instinctual, as if the patients themselves had no choice but to do the opposite. Remarkably, in some patients one may see the exact opposite of negativism in the symptom known as “automatic obedience.” Here, patients do whatever they are told to do, regardless of what it is. In the nineteenth century, one way to test for this symptom was to tell a patient that you wished him to stick the tongue out so that it might be pierced with a needle. Patients would protrude their tongues and not flinch when pierced by the needle.

 Catalepsy, or, as it is also known, waxy flexibility, is characterized by a state of continual and most unusual muscular tension. If one attempts to bend the patient’s arm, it is as if one were bending a length of thick metal wire, like soldering wire. Definite resistance, though not great enough to hinder movement, is nevertheless present. The remarkable aspect here is that, as in bending the wire, the patient retains whatever position the limb, or for that matter, the body, is placed in. This happens regardless of whether the patient is instructed to maintain the position or not. In this way the most uncomfortable, grotesque, and strenuous positions may be maintained for hours. This symptom, rarely seen in modern times, was common before the advent of antipsychotic medicines in the middle of the twentieth century. The back wards of state hospitals housed many catatonic patients who held their bodies in positions throughout each nursing shift, day in and day out.

 Posturing is said to occur when the patient, for no discernible reason, assumes and maintains a bizarre posture. One may keep the arms cocked; another stood bent at the waist to the side.

 Stereotypies are constituted by bizarre, perseverated behaviors. A patient may march back and forth along the same line for hours; another may repeatedly dress and undress. Other persons may be approached again and again, each time being asked the same ques­tion. The same piece of paper may be folded and unfolded until it disintegrates. Most patients can offer no reason for their senseless activity. When asked, a patient replied, “it must be so.”

 Echolalia and echopraxia are said to occur when the patient’s behavior mirrors that of the other person, and, importantly, when this happens automatically, and in the absence of any request. If asked a question the echolalic patient will simply repeat it, sometimes over and over again. The echopraxic patient may clumsily mirror the gestures and posture of the interviewer and, as in echolalia, may continue to do this long after the other person has left, as if uncontrollably compelled to maintain the same activity. Here it as if the ability to will something independent of the environment has been lost, and the patient is thus left enslaved in a mimicry of whatever is close at hand.

 Bizarre behavior may manifest as mannerisms, bizarre affect or an overall disorganization and deterioration of behavior.

 Mannerisms are bizarre or odd caricatures of gestures, speech, or behavior. In manneristic gesturing patients may offer their hands to shake with the fingers splayed out, or the fingers may writhe in a peculiar, contorted way. In manneristic speech, cadence, modula­tion, or volume are erratic and dysmodulated. One patient may speak in a sing-song voice, another in a telegraphic style, and yet another with pompous accenting of random syllables. Overall behavior may become manneristic. Rather than walking, some patients may march in bizarre, stiff-legged fashion.

 Bizarre affect appears to represent a distortion of the normal connection between felt emotion and affective expression. Often, facial expression appears theatrical, wooden, or under a peculiar constraint. Patients may report feeling joy, yet the rapturous facial expression may appear brittle and tenuous. Conversely patients may report grief, and indeed tears may be present, yet the emotion lacks depth, as if patients were merely wearing a mask of grief that might disappear at any moment. Inappropriate affect may also be seen. Here the connection between the patient’s ideas and affect seems completely severed. A young patient, grief stricken at a parent’s funeral, was seen to snicker; another patient, relating the infernal tortures suffered just the night before, smiled beatifically.

 Another, very important form of bizarre affect is unprovoked and mirthless laughter. For no apparent reason patients may break into bizarre and unrestrainable laughter. Though appearing neither happy nor amused, the laughter continues. Some patients report that they were unable to not laugh, that the laughter moved itself no matter how they felt.

 

 The overall deterioration of behavior in schizophrenia is what often makes these patients “stand out” in public. Patients become untidy and may neglect to bathe or wash their clothes; the fingernails may become very long. Dress and grooming may become bizarre. Several layers of clothing are often worn, even during the summer. Bits of string or cloth may festoon the patient’s hair or garments; makeup may be smeared on. Not uncommonly, paranoid patients shave their heads, and this often reliably predicts an oncoming exacerbation of illness, and also some form of self-mutilation. Patients may pluck out their eyelashes or cut deep gouges in their legs. Some seem to be almost completely analgesic: an eye may be plucked out; pieces of flesh may be bitten off, in extreme cases, self-evisceration may occur, “just to see” what the intestines look like. Although most ofteo purpose seems to drive this bizarre behavior, at times the patient may offer a reason. One patient wallpapered the walls, ceiling, and floors with aluminum foil “to keep the rays out”; another kept cotton in the ears “to keep the voices away.”

 Negative symptoms include flattening of affect, alogia (also commonly known as poverty of speech and thought), and avolition.

 Flattening of affect, also known, when less severe, as “blunting” of affect, is characterized by a lifeless and wooden facial expression accompanied by an absence or diminution of all feelings. This is quite different from a depressed appearance. In depression patients appear drained or weighted down; there is a definite sense of something there. In flattening, however, patients seem to have nothing to express; they are simply devoid of emotion. They appear unmoved, wooden, and almost at times as if they were machines.

  Poverty of speech is said to occur when patients, though perhaps talking a normal amount, seem to “say” very little. There is a dearth of meaningful content to what they say and speech is often composed of stock phrases and repetitions. Poverty of thought is characterized by a far-reaching impoverishment of the entire thinking of the patient. The patient may complain of having “no thoughts,” that “the head is empty,” that there are no “stirrings.” Of its own accord nothing “comes to mind.” If pressed by a question the patient may offer a sparse reply, then fail to say anything else.

 Avolition, referred to by Kraepelin as “annihilation of the will,” is said to be present when patients have lost the capacity to embark on almost any goal-directed activity. Bills are not paid; the house is not cleaned; infants are neither changed nor fed. This is not because patients feel inhibited, lack interest, or suffer from fatigue, but rather because the ability to will an action has become deficient.

 Before leaving this discussion of the individual signs and symptoms of schizophrenia and proceeding to a discussion of subtypes, two other symptoms, neither of which fit neatly into the categories employed above, should be mentioned, namely ambivalence and “double bookkeeping.”

 Ambivalence may render patients incapable of almost any volitional activity. Here, patients experience two opposed courses of action at the same time, and for lack of ability to decide between them, do nothing. One patient stood at the washstand for hours unable to decide whether to shave or to use the toothbrush. This “paralysis of will,” however, may at times be easily removed if another person gives directions. In this case an aide simply told the patient to brush his teeth and then put the toothbrush in the patient’s hand. Immediately and with peculiar alacrity the patient then set to brushing his teeth. This kind of ambivalence found in schizophrenia is to be distinguished from the indecisiveness seen at times in depression and the “normal” ambivalence that anyone may experience. The depressed patient’s inability to embark on decision-making stems more from a lack of energy and initiative; unlike the patient with schizophrenia, the depressed patient generally is not able to act when others make the decision. Iormal circumstances competing desires may leave the patient unable to decide. With time, however, a normal person makes a decision because the capacity to do so is not lost. In schizophrenia, however, it is this very capacity that is no longer present.

 “Double bookkeeping,” a phenomenon first identified by Bleuler, refers to the patient’s ability to, as it were, live in two worlds at the same time. On the one hand is the world of voices, visions, and delusions, and on the other hand, and quite coincident with this psychotic world, is the world as perceived by others. To the patient both worlds seem quite real. For example, a patient may hear a voice as clearly as the voice of the physician and believe it just as real, yet at the same time acknowledge that the physician does not hear it. Or the grandiose patient who fully believed that a coronation was imminent may yet continue to work at a janitor s job and go on doing so, living in two worlds, and feeling little if any conflict between them. A variant of double bookkeeping, known as “double orientation,” or “delusional disorientation,” may at times mislead the interviewer into thinking that the patient is disori­ented. For example, a grandiose patient believed that he was John F. Kennedy, and when asked what year it was replied 1962. Later on, however, when filling out a form, he put down the correct year.

 Subtypes of schizophrenia are characterized by particular constellations of symptoms and include the following: paranoid, catatonic, hebephrenic (or “disorganized”), and simple (which has also been referred to as “simple deteriorative disorder”). Patients whose illness does not fall into any of these subtypes are said to have an “undifferentiated” subtype. Subtype diagnosing is not an academic exercise, for, as discussed under Course, the different subtypes may have different prognoses. Furthermore, knowing the subtype allows one to predict with better confidence how any given patient might react in any specific situation.

 Paranoid schizophrenia, which tends to have a later onset than the other subtypes, is characterized primarily by hallucinations and delusions. Other symptoms, such as loosening of associations, bizarre behavior, or flattened or inappropriate affect, are either absent or relatively minor. The hallucinations are generally auditory and typically hostile or threatening. The delusions are generally persecutory and referential. Voices warn patients that their supervisors plot against them. They begin to suspect that their co-workers talk about them behind their backs and laugh quietly as they pass by. Newspaper headlines pertain to them; the CIA is involved; meal portions at the factory cafeteria are secretly poisoned, and patients may refuse to eat at work. At times these patients may appeal to the police for help, or they may suffer their slights in rigid silence. Their attitude becomes one of intense, constrained anger and suspiciousness. Occasionally they may move away to escape their persecutors, yet eventually they are “followed.” At times they may turn on their supposed attackers, and violent outbursts may be seen.

  In paranoid schizophrenia, more so than in the other subtypes, the delusions may be somewhat systematized, even plausible. In most cases, however, inconsistencies appear, which, however, have no impact on the patients. Often, along with persecutory delusions, one may also see some grandiose delusions. Patients believe themselves persecuted not for a trivial reason; others now know that the patient recently acquired a controlling interest in the company. Rarely, grandiose delusions may be more prominent than persecutory ones and may dominate the entire clinical picture. A patient may believe herself anointed with holy oil; trumpets blared forth: her appearance as a prophet. She has a message that will save the world, and sets about spreading it.

 Catatonic schizophrenia manifests in one of two forms: stuporous a catatonia or excited catatonia. In the stuporous form one sees varying й combinations of immobility, negativism, mutism, posturing, and &waxy flexibility. One patient curled into a rigid ball and lay on the sjbed, unspeaking, for days, moving neither for defecatioor Urination, and catheterization was eventually required. Saliva Spooled from the mouth, and as there was no chewing, food simply Bay in the oral cavity and there was danger of aspiration. Another «Patient stood praying in a corner, mumbling very softly.

 Although some patients with catatonic schizophrenia may display only one of these two forms, in most cases they are seen to alternate in the same patient. In some cases a form may last days, weeks, or longer, before passing through to the other. In other cases, however, a rapid and unpredictable oscillation from one form to another may occur. A stuporous patient suddenly, without warning, jumped from his bed, screamed incoherently, and paced agitatedly from one wall of the room to another. Then, in less than an hour, the patient again rapidly fell into mute immobility.

 Hebephrenic schizophrenia tends to have an earlier onset than the other subtypes and tends to develop very insidiously. Although delusions and hallucinations are present, they are relatively minor, and the clinical picture is dominated by bizarre behavior, loosened associations, and bizarre and inappropriate affect. Overall the behavior of these patients seems at times a caricature of childish silliness. Senselessly they may busy themselves first with this, then with that, generally to no purpose, and often with silly, shallow laughter. At other times they may be withdrawn and inaccessible. Delusions, when they occur, are unsystematized and often hypochondriacal iature. Some may display very marked loosening of associations to the point of a fatuous, almost driveling incoherence.

 Simple schizophrenia has perhaps the earliest age of onset, often first beginning in childhood, and shows very gradual and insidious progression over many years. Delusions, hallucinations, and loosening of associations are sparse, and indeed are for the most part absent. Rather the clinical picture is dominated by the annihilation of the will, impoverishment of thought, and flattening of affect. Gradually over the years these patients fall away from their former goals and often become cold and distant with their former acquaintances. They may appear shiftless, and some are accused of laziness. Few thoughts disturb their days, and they may seem quite content to lie in bed or sit in a darkened room all day. Occasionally some bizarre behavior or a fragmentary delusion may be observed. For the most part, however, these patients do little to attract any attention; some continue to live with aged parents; others pass from one homeless mission to another.

 Undifferentiated schizophrenia is said to be present when the clinical picture of any individual case does not fit well into one of the foregoing subtypes. This is not uncommonly the case, and it also appears that in some instances the clinical picture, which initially did “fit” a subtype description, may gradually change such that it no longer squares with one of the specific subtypes: this appears to be more common with the catatonic and hebephrenic subtypes than with paranoid or simple schizophrenia.

 Before leaving this discussion of subtypes, it is appropriate to briefly discuss another proposal for subdividing schizophrenia, which is said by some to have more predictive and heuristic value than the classical subtyping just discussed. Two subdivisions are proposed: “good prognosis,” “reactive,” or “type I” schizophrenia, and “poor prognosis,” “process,” or “type II” schizophrenia. The contrasting characteristics of these two subdivisions are outlined in Table 67-1. “Positive” symptoms are hallucinations, delusions and disorganization of speech, whereas “negative” symptoms consist of flattening of affect, poverty of thought and avolition.

 Although this “good prognosis”/”poor prognosis” scheme is useful, many patients do not fit neatly into type I or type II but rather evidence a mixture of features of both types. Indeed, whether this typology represents an advance over the old “classical” subtypes is not yet clear. One might, for example, argue that the type I patient has paranoid schizophrenia and the type II patient has simple schizophrenia. Further research is needed.

 

 

 Course

 

Schizophrenia is a chronic disease, and, in most cases, exhibits one of two overall patterns. In one, the course of symptoms is waxing and waning, whereas in the other there is a more or less stable chronicity.

 The waxing and waning course is marked by exacerbations and partial remissions. The pattern of these changes is often quite irregular, as are the durations of the exacerbations and partial remissions, ranging from weeks, to months, or even years. Some patients, during episodes of partial remission of the “positive” symptoms, may develop a sustained and pervasive depressed mood accompanied by typical vegetative symptoms. This condition, often referred to as a “postpsychotic depression,” increases the risk of suicide. Importantly, such a postpsychotic depression should not be confused with the frequent, transient, and isolated depressive symptoms seen during an exacerbation of the other symptoms of the illness.

 At times, exacerbations may be precipitated by life stresses; however, at other times they simply happen. Among the stresses that can precipitate exacerbations, living in a family with high “expressed emotion” is important. Such family members tend to be intrusive, critical, and over-involved, and patients exposed to such an onslaught, even when provided with optimum medical treatment, are likely to relapse. Some patients experience this fluctuating course for their entire lives; in many others, however, after 5 to 20 years, this pattern gives way to one of stable chronicity.

 The stable chronicity seen in some patients may appear in some cases after the initial onslaught of symptoms seen at the onset of the disease has dampened, and in others, as for example those with simple, schizophrenia, it may be apparent from the onset itself. Over long periods of time, patients with this course may show very slow progression until the disease eventually “burns out” leaving them in a deteriorated state.

 The classical subtype diagnosis may allow for some prediction as to course. Those with paranoid or catatonic schizophrenia tend to pursue a fluctuating course, and of the two the eventual outcome appears to be worse for the catatonic subtype. The hebephrenic and simple subtypes tend to pursue either a stable or progressively deteriorating chronicity, and of the two the simple subtype seems to often undergo the greatest deterioration.

 As noted earlier one may also make predictions as to course by subdividing cases into Type I and Type II, with the Type I cases showing a waxing and waning course and the Type II cases undergoing a more or less chronic deterioration.

 Before leaving this discussion of the course of the disease, it is appropriate to consider whether or not schizophrenia, in the natural course of events, and in the absence of antipsychotic treatment, ever undergoes a full and complete remission. Certainly, far-reaching remissions have been documented; indeed, in many cases patients may appear at first glance to be recovered, and if one’s definition of “recovery” or “remission” is broad enough, as is the case in many published studies, one might say that a remission did occur. However, on closer inspection one may generally find lingering residual symptoms in these “recovered” patients, such as fleeting hallucinations, odd thoughts, mannerisms or a certain poverty of thought. Thus, although “social” recoveries in the absence of treat­ment, although rare, do occur, it is very unlikely that, in the natural course of the disease, there is ever a restitutio ad integrum.

 

Complications

 

Academic and business failure are common; most patients are incapable of sustaining intimate relationships. About half attempt suicide, and about 10% succeed. Most suicides occur early in the course of the illness; depressive symptoms, as are seen in postpsychotic depression, male sex and unemployment increase the risk.

 A not uncommon, but often overlooked, complication is hyponatremia. Some patients become “compulsive water drinkers”; however, the hyponatremia appears not to be caused solely by excessive intake of water. The renal tubule cells appear to be hypersensitive to ADH, leading to a urine osmolality that is less than maximally dilute relative to the degree of hyponatremia. Symptoms are as described in the chapter on hyponatremia.

 

Differential diagnosis

 

Given the broad range of symptoms that may occur in schizophrenia, it is not surprising that the differential diagnosis is quite large.

 A manic episode of a bipolar disorder may “cross-sectionally” appear similar to hebephrenia, excited catatonia, or paranoid schizophrenia. If, however, one has an accurate history, the diagnosis is relatively straightforward. In schizophrenia, which is a chronic illness, psychotic symptoms almost always precede the .’ excitation; in mania, which occurs as an episodic illness, however, ji ffective symptoms appear first, and psychotic ones only appear as he patient progresses into the acute stage of mania and on up to lie height of a manic episode, delirious mania. When a history is eking, certain symptomatic differences may allow for a differen-diagnosis. The mood and affect of a patient with mania are pically “infectious” and well developed. By contrast, the mood of і excited hebephrenic is one of silly, shallow hilarity, which, rather і provoking laughter, might leave the interviewer with a sense puzzlement. Furthermore the activity of a manic patient is ingoing and extroverted; this is in striking contrast to an excited Statonic who, though hyperactive, remains withdrawn and may avoid contact with others. Finally, the irritable manic is “on attack,” whereas the agitated patient with paranoid schizophrenia  guard.” Both are dangerous, the manic recklessly so, the schizophrenic only if approached in what appears to the patient to hostile manner.

 Here, however, the psychotic symptoms are preceded by depressive ones and only occur when the depressive symptoms. By contrast, whereas depressive symptoms may occur schizophrenia, no invariable relationship exists between them he psychotic symptoms. In schizophrenia one sees psychotic symptoms both when the patient is depressed and also when free of depressive symptoms. Should this history regarding the course of the depression be unavailable, certain “cross-sectional” features may assist in the differential diagnosis. Delusions, when they appear in a depressive episode, tend to be “mood congruent”; that is, they make sense given the way the patient is feeling. Conversely, in schizophrenia the delusions tend to be bizarre and generally unrelated to the mood.

 The differential diagnosis between a catatonic stupor and a psychomotorically retarded depression may be facilitated if the patient is closely observed for movement over an extended period of time. In stupor one may occasionally see rapid movements as the negativism briefly remits; by contrast, in a psychomotorically retarded depression all movements are always slowed down.

 The differential diagnosis between schizoaffective disorder and schizophrenia rests on a thorough and accurate history of the course of the illness. Both illnesses are characterized by chronic psychotic symptoms, such as hallucinations and delusions; however, in schizoaffective disorder one also sees the occurrence of full and sustained affective episodes (depressive, manic or mixed manic) during which, importantly, one also sees an exacerbation of the pre-existing psychotic symptoms. Although schizophrenia may also be marked by mood disturbances, these tend to be transient and not severe. One exception to this is the post-psychotic depression, described earlier under “Course,” which is sustained and may be quite severe. Here, however, there is not an exacerbation of psychotic symptoms and it is this which distinguishes the depression of post-psychotic depression in schizophrenia from the depression seen in schizoaffective disorder.

 As alcoholism and schizophrenia not uncommonly occur in the same patient, the differential diagnosis between alcohol hallucinosis or alcoholic paranoia and schizophrenia may be difficult. Certainly, if the psychotic symptoms began before the patient started to drink or relatively early on in the drinking career, then the diagnosis of schizophrenia would be favored. When, however, psychotic symptoms begin after many years of alcoholism and repeated episodes of delirium tremens, the differential between paranoid schizophrenia and alcohol hallucinosis or alcoholic paranoia may be difficult. The presence of mannerisms, stereotyp-ies, or loosened associations favor schizophrenia; a remission of symptoms after 6 months or more of abstinence would favor alcohol hallucinosis or alcoholic paranoia.

 Delusional disorder, or paranoia, is distinguished from paranoid schizophrenia by    the systematization and “plausibility” of the delusions in paranoia and by the absence of symptoms typical of schizophrenia, such as loosening of associations, mannerisms, and stereotypies. Hallucinations, though they may appear in paranoia, play only a minor role in contrast with paranoid schizophrenia, where they are often abundant.

 Paranoid personality disorder may be very difficult to distinguish from paranoid schizophrenia. Certainly the presence of delusions or hallucinations would favor a diagnosis of schizophrenia; however, in both disorders patients may be very guarded and secretive, and the interviewer may not be able to reliably determine if psychotic symptoms are present. In such instances the overall demeanor and behavior of the patient may help. The patient with paranoid personality disorder presents a fully integrated and internally consistent behavioral repertoire; indeed one may get the sense of a seamless fabric of anger and resentment. By contrast, the patient with paranoid schizophrenia often displays some fragmentation: affect may be somewhat dysmodulated or inappropriate; associations maybe somewhat loosened; a mannerism may be seen.

 Schizotypal personality disorder is distinguished from most of the subtypes of schizophrenia by the absence of psychotic symptoms. Differentiation from simple schizophrenia may not be possible on the basis of “cross-sectional” data. The course of the illness, how­ever, enables a differential diagnosis: the patient with schizotypal personality disorder presents a stable clinical picture over time, whereas the patient with simple schizophrenia presents a clinical picture marked by progressive deterioration.

 Patients with borderline personality disorder when under great stress may occasionally experience hallucinations and delusions. By contrast, in schizophrenia these symptoms, though exacerbated by stress, are present also in calm times.

 Obsessions and compulsions may occasionally be seen in the prodrome to schizophrenia; the eventual appearance of unrelated psychotic symptoms, however, clarifies their differential import.

 Autism may at times be difficult to distinguish from schizophrenia of childhood onset. Certainly, if symptoms appear before the age of 3 years, autism is the more likely diagnosis, as the earliest noted age of onset of  schizophrenia is 5 years of age. The presence of hallucinations and delusions indicates schizophrenia; their absence, however, does not rule against schizophrenia, as young children may not be able to report such symptoms. Conversely the presence of typical autistic symptoms, such as gaze avoidance or a “flapping” tremor, argues strongly for a diagnosis of autism.

 Mental retardation and schizophrenia are two not uncommon illnesses, and their coincidence in the same patient is not rare. Such “engrafted” schizophrenia may be heralded by a deterioration in a previously stable condition or by the appearance of delusions, hallucinations, or loosening of associations, features that are not seen in straightforward mental retardation. However, in patients with severe or profound mental retardation, such symptoms may not be ascertainable at all. In such instances close examination should be made for signs such as bizarre or flattened affect, echopraxia, and waxy flexibility.

 Intoxication with phencyclidine, stimulants, or cocaine may produce psychotic symptoms; the prior history of substance use, a compatible urine or serum toxicology, and  the remission of symptoms with enforced abstinence make the diagnosis.

 Folie a deux, as described in that chapter, is distinguished by the presence of a “dominant” partner who does have schizophrenia, and by recovery with forced separation of the patient from this dominant partner. Malingering or factitious’ illness may at times cause diagnostic difficulty. Certainly the presence of mannerisms and similar symptoms would argue for schizophrenia because these symptoms are generally not known to the public at large and in any case are very difficult to fake.

 Psychosis may also occur secondary to a large number of neurologic disorders, as discussed in the chapter on Secondary Psychosis. Of these, the most likely to be confused with schizophrenia are the chronic interictal psychosis, Huntington’s disease, Wilson’s disease and metachromatic leukodystrophy.

 Before leaving this section on differential diagnosis, a word is in order regarding the putative entities known as “brief psychotic disorder” and “schizophreniform disorder,” each of which are discussed in more detail in their own chapters. Both these illnesses are characterized by symptoms essentially identical to those which may be seen in schizophrenia: where they differ is in their supposed course. Patients who experience a full and complete remission of their psychosis in less than one month are said to have brief psychotic disorder and those whose psychosis persists past one  month but fully remits before six months are said to have schizophreniform disorder. There is debate as to whether either disorder actually exists. Certainly there are patients with psychosis who remit fully with antipsychotic treatment, but whether there are patients who remit fully and completely, without a lingering trace of psychosis, without treatment, has not been demonstrated conclusively. Although by convention a diagnosis of schizophrenia is withheld until the patient has been ill for at least six months, one should always be prepared to revise the diagnosis of brief psychotic disorder and schizophreniform disorder as the months go by and the patient, as is almost always the case, remains ill.

 

Treatment

 

The treatment of schizophrenia almost always involves the use of an antipsychotic drug. Patients may also be seen in supportive psychotherapy, either on an individual basis or in a group, and in social skills training groups. A “token economy” approach may be required for severely debilitated patients. Families may also be seen, not only for educational purposes, but also to enable them to lessen the kinds of family interactions that tend to be followed by relapse. Assistance may be required to enable the patient to secure housing and employment.

 The antipsychotics may be broadly divided into two groups, namely “first generation,” or “typical” drugs, and “second generation,” or “atypical” drugs. All of these agents are covered in detail in their respective chapters in the Section on Psychopharmacology, and discussion here will be limited to only a few. Commonly used first generation antipsychotics include haloperidol, fluphenazine and chlorproamzine. There is an ever growing number of second generation drugs, which now includes dozapine, olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole. Clozapine, olanzapine and risperidone are probably all therapeutically superior to the first generation agents (especially with regard to negative symptoms), and, in the cases of olanzapine and risperidone, are generally better tolerated. Although quetiapine, ziprasidone and aripiprazole are also in general better tolerated than the first generation agents, it is not as yet clear that they are therapeutically superior.

 

 All other things being equal, it is probably best to begin treatment with a second generation agent, such as olanzapine or risperidone; clozapine, although therapeutically superior to either of these, has such severe side-effects that it is generally held in reserve for treatment-resistant patients, as discussed below.

 

The other second generation agents (quetiapine, ziprasidone and aripiprazole) cannot be as strongly recommended: although they are in general better-tolerated than the first generation drugs, there is not yet good evidence for their therapeutic superiority over the first generation agents. The choice between olanzapine  and risperidone is not easy, as it is not as yet clear whether one is therapeutically superior to the other. In terms of side effects, olanzapine carries the risks of weight  weight gain, diabetes and hyperlipidemia, whereas risperidone is more likely than olanzapine to cause extrapyramidal side effects such as akathisia or parkinsonism. Olanzapine may be used in doses ranging from 10 to 30 mg daily, and in the case of risperidone a dose of 4 mg daily appears optimal.

 In some cases, it may be appropriate to use a first generation agent. Cost is an issue for many patients: the oral preparations of the first generation agents, unlike the second generation ones, are all available in generic form, and the cost differences can be very large. Another issue is a history of a good response: for patients who have done perfectly well on a first generation agent, there may be little reason to change. Finally, there is the availability of two of the first generation agents, haloperidol and fluphenazine, in long-acting injectable decanoate preparations: noncompliance with oral  medications is very common in schizophrenia, and in some cases the use of a long-acting injectable is the only way to maintain the patient in the community. Although a long-acting injectable form of risperidone has been developed, it has not, as of this writing, been released in the United States; if it is released, then this reason for using a first generation agent may well disappear. Choosing among the first generation agents is simplified, as discussed in that chapter, by dividing them into “low potency” drugs, such as chlorpromazine, and “high potency” drugs, such as haloperidol or fluphenazine. Low potency agents tend to cause sedation, hypotension and anticholinergic effects (e.g., dry mouth, blurry vision, constipation, urinary hesitancy), but have a lower tendency to cause extrapyramidal side effects (e.g., parkinsonism, dystonia, akathisia); high potency drugs, by contrast, exhibit a high potential for extrapyramidal side effects, but are relatively benign otherwise. Sometimes the choice between low and high potency drugs may be made on the basis of side effects: for example, a patient with postural dizziness probably should not be given a low potency agent that might exacerbate postural hypotension; on the other hand a patient in traction might not tolerate a dystonia very well at all and might be better served by a low potency agent. In cases where side effects are not a compelling issue, then using either haloperidol or fluphenazine is probably best, as this would facilitate transition to a decanoate form should that become necessary.

 

Once an antipsychotic has been chosen, it should be given at an adequate trial, not only in terms of duration but also dose. In general, presuming the dose is adequate, two weeks is long enough to see an initial response. Adequate doses for risperidone and olanzapine were discussed earlier; doses for the other atypicals are discussed in the respective chapters. Adequate oral doses for haloperidol and fluphenazine are 5 to 15 mg/d, and for chlor­promazine 100-300 mg. Obviously, lower doses are indicated for the elderly and frail and for patients with significant hepatic dysfunction or for those with significant general medical illnesses. In some cases, in particular with agitated or assaultive patients, one may have to use adjunctive treatments at the start, and continue them until the antipsychotic has had a chance to take effect. Divalproex, given in a loading dose of 15 to 20 mg/kg/d for other­ wise healthy patients, is effective, as is use of as needed doses of a benzodiazepine, such as lorazepam at 2 mg orally roughly every four hours. In some cases one may also simply use much higher

‘ doses of the antipsychotic; however, this always incurs the risk of worse side effects.

 

Farmacologic Treatment of Agitation.

 

If the patient gets an initial good response, then the agent may continued as maintenance treatment, as discussed below. If the onse is only partial, but otherwise promising, one may ontinue treatment for an additional four weeks. At that point, if he response is good one may move to maintenance treatment.

If : response is less than adequate, then one should first review the > and make sure the diagnosis is correct. Assuming the diagnosis then one should consider significantly increasing the , and observing the patient for another couple of weeks. If the onse is still inadequate or if side effects are unacceptable, jen one may consider switching to another agent. Certainly, if the it had not been given a trial of risperidone or olanzapine, one ‘ should be considered, and if one of these two had been and found wanting, then the other should be given a trial.

 A good response is followed by maintenance treatment; an inadequate response should prompt consideration of dozapine.

 Clozapine is superior to every other antipsychotic, and may succeed where all the others have failed. Enthusiasm for its use, however, is tempered by its many side effects, most notably the risk of agranulocytosis and the necessity for routine CBCs. Details regarding clozapine are covered in the respective chapter.

 Maintenance treatment is appropriate for almost all patients. Initially, patients should be maintained on a dose similar, if not identical, to that which initially provided relief. Once patients are stable in the community, cautious dose adjustments may be considered once every three or four months. As noted earlier, in many cases the course of schizophrenia is characterized by a waxing and waning of symptoms, and in these cases, it is appropriate to attempt to “titrate” the dose to the underlying severity of the disease. Furthermore, some patients may become so distressed at side effects that they find a mild increase in the symptoms of the disease a reasonable price to pay for a reduction in the intensity of side effects. Should patients become almost symptom free, some psychiatrists may elect to decrease the dose in a step-wise fashion every 3 months until either symptoms reappear or drug discontinuation is achieved, with the patient being left with only mild, residual symptoms. Unfortunately, however, even when patients and family members are instructed regarding the “early warning signs” of relapse, troublesome symptom recurrence is common; therefore, chronic maintenance treatment, albeit with low doses, may be better than intermittently attempting trials at drug discontinuation. In general, over long term follow-up it is appropriate to keep the dose overall as low as possible to reduce the risk of tardive dyskinesia. This side effect, discussed in its own chapter, occurs in a significant minority of patients who take antipsychotics over the long haul, and hence the physician must always be alert to the emergence of any abnormal involuntary movements.

 Should a post-psychotic depression occur, it is appropriate to give an antidepressant, such as an SSRI, and to treat the patient in the same fashion as one would acutely treat a depressive episode that occurred in a major depression, as described in the chapter. One must always be careful, however, to distinguish between a depression and a antipsychotic-induced bradykinesia (or akinesia), as may be seen especially when high potency first generation agents are used. Bradykinesia, as discussed in the chapter on first generatioeuroletics, when occurring in isolation, may appear similar to a psychomotorically-retarded depression. ЕСТ may also be helpful in post-psychotic depression. Interestingly, ЕСТ is also at times effective in catatonic schizophrenia, whether excited or stuporous, regardless of whether depressive symptoms are present.

 Before leaving the subject of antipsychotic treatment, a word is in order regarding akathisia. This extrapyramidal side-effect, also discussed in more detail in the chapter on first generation antipsychotics, may “masquerade” as an exacerbation of psychosis, and if this diagnosis is missed then the clinician, mistakenly believing that the exacerbation of psychotic symptoms is resulting from an exacerbation of the underlying illness, might go ahead and increase the dose of the antipsychotic, thus increasing the akathisia and initiating a downwardly spirally therapeutic misadventure.

 

 After antipsychotics have brought more florid symptoms under control, patients may profit from cognitive-behavioral therapy and, if still in contact with family, family therapy. Insight or psychoanalytically oriented psychotherapy is contraindicated. Not only does it not help, but also indeed some patients may worsen while being thus treated.

Electroconvulsive therapy is not considered a first line treatment but may be prescribed in cases where other treatments have failed. It is more effective where symptoms of catatonia are present, and is recommended for use under NICE guidelines in the UK for catatonia if previously effective, though there is no recommendation for use for schizophrenia otherwise. Psychosurgery has now become a rare procedure and is not a recommended treatment for schizophrenia.

 When families are involved, psychoeducationally oriented multiple-family groups are very helpful. Parents should be clearly told that they did not “cause” the illness and that no connection exists between child-rearing or early childhood events and the appearance of schizophrenia. When family members are critical, intrusive, and over-involved, behavioral family therapy aimed at reducing these behaviors is very helpful and reduces the number of hospital stays required.

 

 

 Hospitalization is required for most patients at some point in their illness, and in some cases, repeated admissions occur. Involuntary admission may be required and may be lifesaving. Partial hospitalization services are available in many areas and have enabled many former “back ward” patients to survive and maintain themselves in the community.

 

Prognosis

 

Schizophrenia has great human and economic costs. It results in a decreased life expectancy of 12–15 years, primarily because of its association with obesity, sedentary lifestyles, and smoking, with an increased rate of suicide playing a lesser role. These differences in life expectancy increased between the 1970s and 1990s, and between the 1990s and first decade of the 21st century did not change substantially in a health system with open access to care (Finland).

Schizophrenia is a major cause of disability, with active psychosis ranked as the third-most-disabling condition after quadriplegia and dementia and ahead of paraplegia and blindness. Approximately three-fourths of people with schizophrenia have ongoing disability with relapses and 16.7 million people globally are deemed to have moderate or severe disability from the condition. Some people do recover completely and others function well in society. Most people with schizophrenia live independently with community support. In people with a first episode of psychosis a good long-term outcome occurs in 42%, an intermediate outcome in 35% and a poor outcome in 27%.Outcomes for schizophrenia appear better in the developing than the developed world. These conclusions, however, have been questioned.

There is a higher than average suicide rate associated with schizophrenia. This has been cited at 10%, but a more recent analysis of studies and statistics revises the estimate to 4.9%, most often occurring in the period following onset or first hospital admission. Several times more (20 to 40%) attempt suicide at least once. There are a variety of risk factors, including male gender, depression, and a high intelligence quotient.

Schizophrenia and smoking have shown a strong association in studies world-wide. Use of cigarettes is especially high in individuals diagnosed with schizophrenia, with estimates ranging from 80% to 90% being regular smokers, as compared to 20% of the general population. Those who smoke tend to smoke heavily, and additionally smoke cigarettes with high nicotine content. Some evidence suggests that paranoid schizophrenia may have a better prospect than other types of schizophrenia for independent living and occupational functioning.

 

Psychosocial

 

Psychotherapy is also widely recommended, though not widely used in the treatment of schizophrenia, due to reimbursement problems or lack of training. As a result, treatment is often confined to psychiatric medication.

Cognitive behavioral therapy (CBT) is used to target specific symptoms and improve related issues such as self-esteem, social functioning, and insight. Although the results of early trials were inconclusive as the therapy advanced from its initial applications in the mid-1990s, more recent reviews clearly show CBT is an effective treatment for the psychotic symptoms of schizophrenia.

Another approach is cognitive remediation therapy, a technique aimed at remediating the neurocognitive deficits sometimes present in schizophrenia. Based on techniques of neuropsychological rehabilitation, early evidence has shown it to be cognitively effective, resulting in the improvement of previous deficits in psychomotor speed, verbal memory, nonverbal memory, and executive function, such improvements being related to measurable changes in brain activation as measured by fMRI.

Metacognitive training: In view of a many empirical findings suggesting deficits of metacognition (thinking about one’s thinking, reflecting upon one’s cognitive process) in patients with schizophrenia, metacognitive training (MCT) is increasingly adopted as a complementary treatment approach. MCT aims at sharpening the awareness of patients for a variety of cognitive biases (e.g. jumping to conclusions, attributional biases, over-confidence in errors), which are implicated in the formation and maintenance of schizophrenia positive symptoms (especially delusions), and to ultimately replace these biases with functional cognitive strategies.

The training consists of 8 modules and can be obtained cost-free from the internet in 15 languages. Studies confirm the feasibility and lend preliminary support to the efficacy of the intervention. Recently, an individualized format has been developed which combines the metacognitive approach with methods derived from cognitive-behavioral therapy.

Family Therapy or Education, which addresses the whole family system of an individual with a diagnosis of schizophrenia, has been consistently found to be beneficial, at least if the duration of intervention is longer-term. Aside from therapy, the impact of schizophrenia on families and the burden on careers has been recognized, with the increasing availability of self-help books on the subject.[35][36] There is also some evidence for benefits from social skills training, although there have also been significant negative findings. Some studies have explored the possible benefits of music therapy and other creative therapies.

The Soteria model is alternative to inpatient hospitalization using full non professional care and a minimal medication approach. Although evidence is limited, a review found the programme equally as effective as treatment with medications but due to the limited evidence did not recommend it as a standard treatment.