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Chapter 11.doc

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McGill University
PSYC 311
Jason Scott Ferrell

Ch 11: Schizophrenia  Schizophrenia is a psychotic disorder characterized by major disturbances in thought, emotion, and behaviour: disordered thinking in which ideas are not logically related, faulty perception and attention, flat or inappropriate affect, and bizarre disturbances in motor activity  Patients with schizophrenia withdraw from ppl and reality often into a fantasy life of delusions and hallucinations  Schizophrenia is one of the most severe psychopathologies; however its life time prevalence is generally accepted to be about 1%  Concluded that there may be real variation in schitzo across geographical regions around the world with Asian populations having the lowest prevalence rates  Higher in males than in females (male- female = 1:4)  Although schitzo sometimes begins in childhood it usually appears in late adolescence or early adulthood or early adulthood somewhat earlier for men than for women  Ppl with schitzo typically have a # of acute episodes of their symptoms.  Between episodes they often have less severe but still very deliberating symptoms.  Most ppl with schiotzo are treated in the community however hospitalization is sometimes necessary  Concluded that almost one half (46%) do not require inpatient services. However ppl who were 1 diagnosed while inpatstnts and those residing in rural areas were most likely to require additional inpatient services in the 1 year of treatment  In Canada hospitalization rates are typically much higher among young men relative to young women accounting for 19.9% of separations from general hospitals. Scitzo accounts for 30.9% of separations from psyiatric hospitals  About 10% of ppl with scitzo commit suicide  Many ppl with scitzo remain chronically disabled. The disability can be attributed to symptoms inherent to schitzo as well as the comorbid disorders from which approx 50% of those with shcitzo suffer  In 2004 there were an estimated 234,305 ppl in Canada with schozto. Overall 374 deaths that year were attributed to schizto. The illness total costs were $6.85 billon 70% of which was the cost of lost productivity Schizophrenia and comorbidity  Comorid conditions appear to play a role in the development, severity and course of schito. Comorbid substance abuse is a major problem for patients with schizto occurring in as many as 70% of them  37% of the sample of ppl with schizto showed current evidence of substance us disorders. The relationship was especially common among men and analyses suggested that childhood conduct disorder problems are potent risk factors for substance use disorders in shcizto  about 40% of the participants were depressed at the outset. Over the next three years those diagnosed with shcizto who were also depressed relative to the non depressed group were more likely to use relapse related mental health services to be a safety concern, to have substance related problems and report poorer life satisfaction, quality of life, mental functioning, family relationships and medication adherence.  Comorbid anxiety disorders are also common and can impose an additional burden on ppl with schizo and results in further decline in their perceived quality of life.  Comobidity with obsessive compulsive disorder is also related to a previous history of suicidal ideation and suicide attempts  Post traumatic stress disorder is highly prevalent and under diagnosed among military veterans with shizto  Developing( prodromal) phase of schito. Found that prodomol patients experience a wide variety of comorbid psychiatric syndrome especially major depressive disorder and cannabis dependence CLINICAL SYMPTOMS OF SCHIZOPHRENIA  The symptoms of patients with shcizto involve disturbances in several major areas: thought, perception, and attention; motor beh; affect or emotion; and life functioning  Although only some of these problems may be present at any given time  The duration of the disorder is also imp in diagnosis  Unlike most of the diagnostic categories we have considered no essential symptom must be present for a diagnosis of schizo  Thus patients with schizto can differ from each other more than do patients with other disorders  The key to understanding shcito is to recognize its heterogeneity  The presentation, course and outcome of shcito are variable and diverse  Currently evidence indicates that it is hard to find specific traits or characteristics that are shared by all persons with a diagnosis or schizo Positive symptoms  Comprise excesses or distortions such as disorganized speech, hallucinations and delusions.  They are what define for the most part an acute episode of schiz  Positive symp are the present of too much of a beh that is not apparent in most ppl while the negative symp are the absence of a beh that should be evident in most ppl  Disorganized speech----also known as formal though disorder, disorganized speech refers to problems in organizing ideas and in speaking so that a listener can understand  There’s incoherence found in conversations of indivb with S. although the patient may make repeated references to central ideas or a them the images and fragments of thought are not connected; it is difficult to understand what they’re saying  Disturbances in speech were at one time regarded as the principal clinical symp of s ad they remain one of the criteria for the diagnosis. But evidence indicates that the speech of many patients with s is not disorganized and that the presence of disorganized speech does not discriminate well between s and other psychoses such ass some mood dis. Patients in manic episode exhibit loos associations as much as those with s  Delusions--- beliefs held contrary to reality are common positive symp of s. persecutory delusions like these were found in 65% of a larger cross national sample  Delusions make take several other forms as well:  The patient may be the unwilling recipient of bodily sensations or thoughts imposed by an external agency  Patients may believe that their thoughts are broadcast or transmitted so that others know what they are thinking  Patients may think their thoughts are being stolen from them suddenly and unexpectedly by an external force  Some patients believe that their feelings are controlled by an external force.  Some patients believe that their beh is controlled by an external force  Some patients believe that impulses to behave in certain ways are imposed on them by some external force  Although delusions are found among more than half pf ppl with schizto as with speech disorganization they are also found among patients with other diagnoses—ex: mania and delusional depression. The delusions of patients with s are often more bizarre though than patients in other diagnostic categories. They are also highly implausible Hallucinations and other disorders of perception  Patients with s often report that the world seems somehow diff or even unreal to them. A patient may mention changes in how his or her body feels or the patients body may become so depersonalized  Some ppl report having difficulty in attending to what is happening around them  The most dramatic distortions of perception are hallucinations, sensory experiences in the absence of any stimulation from the environment. They are often more auditory than visual 74% sample had auditory hallucinations  Some hallucinations occur more often in patients with s than in other psychotic patients. They types of hallucinations include the following: some patients with s report hearing their own thought spoken by another voice, or hear voices arguing, or they hear voices commenting on their beh Negative symptoms  Consist of behavioural deficits, such as avolition, alogia, anhedonia, flat affect, and asociliaty  These symptoms tend to endure beyond an acute episode and have profound effects on the lives of patients with s. they are also imp as the presence of many negative symp is a strong predictor of a poor quality of life two years following hospitalization  Some evidence that negative symp are associated with earlier onset brain damage (enlarged ventricles) and progressive loss of cognitive skills (IQ decline)  Ex; flat effect (lack of emotional expressiveness) can be a side effect of antipsychotic medication  Observing patients over extended periods of time negative symp such as flat affect and anhedonia are difficult to distinguish from aspects of depression so specifity becomes an issue Avolition  apathy or avoliytion referred to lack of energy and a seeming absence of interest in or an inability to persist in what are usually routine activities.  Patients may become inattentive to grooming and personal hygiene  They have difficulty persisting at work, school or household chores and may spend much of their time sitting around doing noting Alogia  A negative thought disorder, alogia can take several forms. In poverty of speech, the sheer amount of speech is greaydly reduced.  In poverty of content of speech the amount if discourse is adequate but it conveys little info and tends to be vague and repetitive Anhedonia  An inability to experience pleasure. its manifested as a lack of interest in recreational activities, failure to develop close relationships with other ppl and lack of interest in sex. Patents are aware of this symp and report that normally pleasurable activities are not enjoyable for them Flat affect  Virtually no stimulus can elicit an emotional response. The patient may stare vacantly, the muscles of the face flaccid, the eyes lifeless  When spoken to the patient answers in a flat and toneless voice.  Flat affect was found in 66% of a large sample of patients with s  The concept of flat affect refers only to the outward expression of emotion and not to the patients inner experience which may not be improvishered at all  While the patients were much less facially expressive than were the non patients they reported about the same amount of emotion and were even more physiologically aroused asociality  Some have severely impaired social relationships  They have few friends, poor social skills, and little interest in being with other ppl  Ppl diagnosed with s have lower socialability and greater shyness  Ppl with s also reported more childhood social troubles  These manifestations of s are often the first to appear beginning in childhood before the onset of more psychotic symp  Confirmed that ppl with s did less well on facial affect recognition and facial recognition tasks  These deficits persisted and were evident when the patients were reassessed three moths later even though there were substantial improvements in the # of both positive and negative symp since initial hospitalization Other symptoms  One problem is that the positive and negative symp do not necessarily reflect exclusive subtypes cyz they are dimensions that often coexist within the same patient.  Moreover several other symp of s do not fit neatly into the positive negative scheme. Two important symp in this category are catatonia and inappropriate affect. Many patients also exhibit various forms of bizarre beh. They may talk to themselves in public, hoard food or collect garbage Catatonia  Several motor abnormalities. Some patients gesture repeatedly, using peculiar and sometimes complex sequences of the finger, hand and arm movements that often seem to be purposeful, odd as they may be  Others manifest an unusual increase in their overall level of activity, which might include much excitement wild flailing of the limbs and great expenditure of energy similar to that seen in mania  Catatonic immobility- patients adopt unusual postures and maintain them for very long periods of time. A patient may stand on one leg, with the other tucked up toward the butt and remain in this position all day. They may also have waxy flexibility whereby another person can move the patients limbs into strange positions that they maintain for extended periods Inappropriate affects  Some ppl with s have this. The emotional responses of these indiv are out of context; for ex: the patient may laugh when hear that someone died  These ppl are likely to shift rapidly from one emotional state to another for no discernible reason. This symp is quite rare but its appearance is of considerable diagnostic imp cuz its relatively specific to s  Strongest predictor of this social disability is chronic cognitive impairment. The high substance abuse rates perhaps reflect an attempt to achieve some relief from negative emotions. Suicide rate among plp with s is high HISTORY OF THE CONCEPT OF SCHIZOPREHNIA Early descriptions  Concept of s by kraeplin and blueler. Kreplain= dementia praecox; the early term for s in 1898. he diff btwn manic depressive illness and dementia praecox. Dementia praecox included several diagnostic concepts- dementia paranoids, catatonia and hebephrenia. These disorders were symptomatically diverse bit but Kraeplin believed they shared a common core  Bleuler wanted to define the core of the disorder and move away from K emphasis on age of onset and course in the def of s. Bleuler broke with K on two major points: he believed that the dis did not have an early onset and it did not inevitably progress toward dementia. Therefore he thought the name was no longer good and changed it to s. from Greek work schizein meaning to split and phren meaning mind  But he faced a conceptual problem cuz symptoms could vary w/ each person  The concept B adopted was the “breaking of associative threads”  For b associative threads joined not only words but thoughts. Thus goal oriented efficient thinking and communication were possible only when these hypothetical structures were intact.  Blocking- an apparently total loss of a train or thought – as a complete disruption of the persons associate threads The historical prevalence of schizophrenia  Suggests that rates of s have fallen sharply since the 1960  There was a substantial decrease in inpatient prevalence rates of s between 1986 and 1996 with no corresponding increase in outpatient prevalence rates  At the NY state psychiatric institute 20% of the patients were diagnosed with s in the 1930s. the #s increased through the 1940s and in 1952 peaked at 80%. In contrast the concept of s prevalent in Europe remained narrower. The % of patients diagnosed with s at maudsley hospital in London for ex; stayed relatively constant at 20% for a 40 yr period  The concept of s was further broadened by three additional diagnostic practises:  1) U.S clinicians tended to diagnose s whenever delusions or hallucinations were present. Cuz these symptoms particularly delusions, occur also in mood disorders, may patients with a DSM-II diagnosis of s may actually have had a mood disorder  2) patients whom we could now diagnose as having a personality disorder and were diagnosed as s according to DSM-II criteria.  3) patients with an acute onset of s symptoms and a rapid recovery were diagnosed as having s The DSM-IV-TR Diagnosis  the US concept of s shifted from broad def to a def that narrows the range of patients diagnosed as s in 5 ways:  1) the diagnostic criteria are presented in explicit and considerable detail  2) patients with symptoms of a mood disorder are specifically excluded. Scizoaffective disorder comprises a mixture of symp of s and mood disorders.  3) DSM-IV-TR requires at least 6 months of disturbances for the diagnosis. The 6 month period must include at least one month of the active phase, which is defined by the presence of at least two of the following: delusions, hallucinations, disorganized speech, grossly disorganized or catatonic beh and negative symp  the remaining time required within the minimum six months can be either a prodormal (before the active phase) or a residual (after the active phase) period. Problems during the prodormal and residual phases include social withdrawal, impaired role functioning, blunted or inappropriate affect, lack of initiative, vague and circumstantial speech, impairment in hygiene and grooming, odd beliefs or magical thinking and unusual perceptual experiences. These criteria eliminate patients who have a brief psychotic episode which is often stress related and then recover quickly. The symp of s dis are the same as those of s but last only from one to six months. Brief psychotic dis lasts from one day to one month and is often brought on by extreme stress such as bereavement  4) some of what DSM-II regarded as mild forms of s are now diagnosed as personality dis  5) DSM-IV-TR differentiates between paranoid s and delusional disorder. A person with delusional disorder is troubled by persistent persecutory delusions or by delusional jealousy, which is the unfounded conviction that a spouse or lover is unfaithful. There are also delusions of being followed, somatic delusions and delusions of erotomania (believing that one is loved by some other person, usually a complete stranger with a higher social status).  Unlike person with paranoid s the person with delusional dis does not have disorganized speech or hallucinations. Delusional dis is quite rare and typically begins later on in life than s. in most families it appears to be related to s perhaps genetically Categories of s in DSM-IV-TR  Three types of s included are disorganized (hebephrenic) catatonic and paranoid Disorganized s  K hebephrenic form of s is called disorganized s in dsm-iv-tr.  Speech is disorganized and hard for a listener to follow. Ppl may speak incoherently, stringing together similar sounding words and even inventing new words often accompanied by silliness or laugher.  They may have flat affect or experience constant shifts of emotion, breaking into inexplicable fits of laughter and crying, their beh is generally disorganized and not goal directed  Ppl sometimes deteriate to the point of incontinence, voiding anywhere and at any time and completely neglect their appearance Catatonic s  Ppl typically alternate between catatonic immobility and wild excitement but one of these symp may predominate.  These patients resist instructions and suggestions and often echo (repeat back) the speech of others.  The onset of this may be more sudden than the onset of other forms of s although the person is likely to have previously sown some apathy and withdrawal from reality.  Catatonic s is barley seen today prob cuz of drug therapy and how effective it is on these bizarre motor processes  Lethargica (sleeping sickness) Paranoid s  Assigned to many mental patients  Key to this diagnosis sis presence of prominent delusions. Delusions of persecution are most common but ppl experience grandiose delusions in which they have exaggerated sense of their own imp, power, knowledge and identity  Some ppl are plagued by delusional jealousy the unsubstantiated belief that their sexual partner is unfaithful.  Vivid auditory hallucinations may accompany the delusions.  Ppl with paranoid s often develop ideas of reference – they incorporate unimportant events within a delusional framework and read personal significance into the trivial activities of others  Ppl with paranoid s are agitated, argumentative, angry and sometimes violent. They are also more alert and verbal than are patients with others types of sc. Their languages although filled with references to delusions is not disorganized Evaluation of the subtypes  Overall usefulness of subtypes is often questioned  Diagnostic reliability is reduced  Subtypes have little predictive validity – diagnosis of one over another form of s provides little info that is helpful in treating or in predicting the course of problems. Also considerable overall among the types  The cluster analysis identified 5 subtypes: including 1 group with normative, intact cognition. The other four groups included an “executive subtype” which was distinguished by impairment on the Wisconsin card sorting test; an executive-motor subtype which had deficits only in motor functioning and a dementia subtype which has pervasive and generalized cognitive impairment.  Heinrichs concluded that there is a “primacy of cognition” in s with average effect sizes from studies of memory, attention, language and reasoning being at least twice as large as those obtained in studies that examine s with structural brain MRI and PET scans  Explanations why the link between s and cognition is much stronger 1) there is illness related brain disturbance that could have a pervasive influence on brain systems that are active in information processing. 2) cognitive deficits reflect genetically determined constraints 3) influence on chronic stress and distress on cognition in ppl prone to s  Most patients show mixed symp and that very dew patients fit into the pure positive or pure negative types  Subsequent analyses have revealed three dimensions not two. Show that positive symp should be divided into 2 categories: a positive symp component consisting of delusions and hallucinations and a disorganized component includes bizarre beh and disorganized speech ETIOLOGY OF S The genetic data  S is transmitted genetically Family studies—  risk for s in general population is little less than 1%  Negative symp of s appear to have a stronger genetic component Twin studies  concordance for identical twins 44.3%, although that greater than fraternal twins 12.08% is less than 100%.  Concordance among MZ twins does increase when the proband is more severely ill Adoption studies  overall the control ppl were rated as less disabled than the kids of mothers with s.  31 of the 47 kids of mothers with s buy only 9 of the 50 controls were given a DSM diagnosis. None of the controls was diagnosed as s but 16.6% of the offspring of women with s were diagnosed  study gives imp info on genetic factors in develop of s . kids reared without contact with their so called pathogenic mothers were still more likely to become s than were the control patients  kids of mom with s were also more likely to be diagnosed as mentally defective, psychopathic, and neurotic Molecular genetics  it does not appear that the genetic predisposition to s is transmitted by a single gene; several multi or polygenic models remains viable.  Hunt for s related genes has proven more difficult than expected for several reasons including 1) lack of preciseness in defining the boundaries of the clinical phenotype 2) absence of biological tests that confirm diagnostic categorization 3) clinical heterogeneity and the complex nature of s  Alternative strategies for s vulnerability gene identification were and are needed. S research turned to the endophenotypic strategy . endophentoyupes are characteristics that reflect the actions of genes predisposing an indiv to a disorder even in the absence of a diagnosable pathology.  Imp cuz indiv endophenotypoe are determined by fewer genes than the more complex s phenotype. Thus the complexity of genetic analyses would be reduced  Possible role of many specific genes: serotonin type 2A receptor (5—HT2a) gene, dopamine DS receptor gene, and chromosomal region on chromosome 6,8, 13 and 22. also suggested that G protein signalling 4 a gene localized to chromosome 1q23 plays a role in s susceptibility  Increasing evidence for an overlap in genetic susceptibility including s and bipolar disorder Evaluation of the genetic data  s is not complete due to genetics  S is defined by beh: it is a phenotype and thus reflects the influence of both genetics and enviro  Genetics predispose ppl to it and ten you need stress to bring it out Biochemical factors  best researched factors :dopamine Dopamine activity  excess dopamine leads to s is based on the fact that drugs used to treat s reduce dopamine activity but produce side effects remsnling the symp of Parkinson’s disease  Parkinson’s is known to be caused in part by low levels of dopamine in a particular nerve tract of the brain.  As time went on assumption that excess dopamine led to s was not true cuz the major metabolites of dopamine homovanillic acid (HVA) was not found in greater amounts in patients with s  Research on the antipsychotics mode of action suggest that the dopamine receptors are a more likely locus of disorder than the level of dopamine itself  excess dopamine receptors may not be responsible for all the symp of s; in fact they appear to be related to mainly to positive symp  amphetamines worsen positive symp and lessen negative one. Amtipsyhcotics lessen positive symmp but there effect on negative symp is less clear; some studies show no benefit while others show a reduction in negative symp  prefrontal cortex is thought to be esp relevant to the negative symp of s the under activity in this part of the brain may also be the cause of negative symp in s  antipsychotics do not have major effects on the dopamine neurons in the prefrontal cortex they are ineffective treatments for negative symp evaluation of the dopamine theory  dopamine theory isn’t complete theory of s other neurotransmitters  glutamate a transmitter that is widespread in the human brain may also play a role. Low levels of this have been found in cerebrospinal fluid of ppl with s  street drug PCP can induce psychotics states including both positive and negative sump in normal ppl. Interferes with one of glutamates receptors schizophrenia and the brain: structure and function  search for brain abnormality that causes s began as early as the syndrome was identified. Enlarged ventricles  this implies a loss of sub cortical brain cells. Structural problems in sub cortical temporal limbic areas such as the hippocampus and the basal ganglia and in the prefrontal and temporal cortex  CT and MRI scans reveal that esp males have enlarged ventricles. Research also shows a reduction in cortical grey matter in both the temporal and frontal regions and reduced volume in basal ganglia and limbic structures suggesting deteoritation or atrophy of brain tissue  Large ventricles in ppl with s are correlated with impaired performance on neuropsychological tests, poor adjustment poor adjustment prior to the onset of the dis and poor response to drug treatment  Study found that large ventricles can be detected both in ppl with a 1 episode of s and in patients with chronic s. the ventricles are not progressive. Thus enlarged ventricles do not simply reflect chronic untreated s  Enlarged ventricles are not specific to s as they are also evident in the CT scabs of ppl with other psychoses such as bipolar disorder The prefrontal cortex (very imp)  The prefrontal cortex is known to play a role in beh such as speech, decision making and willed action, all of which are disrupted in s  Lack of illness awareness is related to poorer neuropsychological performance more often in patients with s than in bipolar ppl supporting the hypothesis that lack of awareness is related to defective front lobe functioning  MRI studies have shown reductions in grey matter in the prefrontal cortex  Ppl with s have shown low metabolic rates in the prefrontal cortex  Ppl with s do poorly on the tests and also fail to show activation in the prefrontal region  The frontal hypo activation is less pronounced in the nons twin of discordant MZ pairs  Failure to show frontal activation is related to the severity of negative symp  The normal ppl showed greater prefrontal cortical activation Congenital and developmental considerations  Consequence of damage during gestation or birth  Many studies have shown high rates of delivery complications in ppl with s, such complications could have led to a reduced supply of oxygen to the brain resulting in damage  The risk for s is increased in those who experience complications and have a genetic predisposition  Possible that a virus invades the virus and damages it during fetal develop nd  Ppl ho have been exposed to the virus during the 2 trimester had much higher rates than those who had been exposed in either trimesters  Influenza exposure during early to mid gestation was associated with a 3 fold increase of s and st that 1 trimester exposure confndred a 7 fold increased risk. We know that cortical develop is in a critical stage of growth during the 2 trimester  The brains of ppl with s have shown reduced # of cells in the outer layers of the cortex both in the prefrontal and the temporal areas.  Widespread thinning of the cortex of ppl with s has been reported apparently resulting from loss of dendrites and axons  Neurons in the fontal cortex have been shown to be smaller than normal in patients with s  Although rare the onset of positive symp can occur before the age of 12. kids who exhibit this early onset tend to show clear evidence of general brain deterotitaion.  Ex: childhood onset s kids show an approx 10% relative brain tissues loss at age 12 however this proportion increase to the 20-25% range by age 18  That prenatal exposure to infections including influenza, rubella, and toxoplasmosis and maternal cytokines are associated with increased risk of s  Prefrontal cortex is a brain structure that matures late typically in adolescence. Thus an injury to this area may remain silent until the period of develop when the prefrontal cortex begins to play a large role in beh. Dopamine activity also peaks in adolescence which may set the stage for onset of s symp Recent research  Zakzanis; conclusion tha the specific role of deficits in the temporal lobes has been overstated and that more diffuse dysfunction exists  MRI studies found a subtle 4% but significant bilateral hippocampal volume reduction in ppl with s  Regional volume reductions were esp marked in bilateral medial temporal lobe regions  Reported finding reduced hippocampus volume amog twins with s relative to twins without s  They reported that ppl had smaller medial temporal lobe volumes relative to controls but that the volume diff was not specific for either region or hemisphere  Reduced cerebral blood volume accompanies brain size in s and proposed that chronic cerebral blood volume eventually results in neuronal loss and cognitive impairments  The results suggested that violet ppl with s and a history of anti social and or substance use manifest neural dysfunction affecting basal or orbital pats or the prefrontal cortex Psychological stress and s  Data as show that as with other dis increased in life stress increase the likelihood of a relapse  Ppl who take pare in stress mgt program are less likely to be readmitted to the hospital the year following treatment esp if they had attended treatment session regularly  Two stressed have played an imp role in s: social class and family Social class and s  S are found in central city areas inhibited by ppl in the lowest socio economic class  The rate of s was found to be twice as high in the lowest social class as in the 2 lowest class  Found tat ppl with s are downwardly mobile in occupational status. But an equal # of studies have shown that ppl with s are not downwardly mobile  Found evidence for social selection hypothesis: of 26 patients in the lowest social class only 4 had fathers in the lowest class  The data are more supportive of the social selection theory than of the sociogenic theory  The prevalence of s among Africans from the Caribbean who remain in their native country is much lower than among those who have emigrated to London The family and s  Moms found to be rejecting, overprotective, self sacrificing, impervious to the feelings of others, rigid and
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