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Historical figures in schizophrenia research. Emil Kraepelin 1883: “Dementia Praecox” separated schizophrenia from bipolar disorder (manic-depressive psychosis) based on the clinical course of the syndromes Eugene Bleuler 1911: “Schizophrenia” – 1909: Genetic
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Historical figures in schizophrenia research • Emil Kraepelin • 1883: “Dementia Praecox” separated schizophrenia from bipolar disorder (manic-depressive psychosis) based on the clinical course of the syndromes • Eugene Bleuler • 1911: “Schizophrenia” – 1909: Genetic splitting of the mind between thought and emotion • Associations • Affect • Ambivalence • Autism
Epidemiology • Prevalence ~1%; male = female Right now over 2 million adult Americans have schizophrenia • Seen in all cultures at similar frequency • Onset usually late adolescence to young adulthood, earlier in males than females (reactive: leaving home, loss of parent, 1st sex experience) • Increased chance of being born in the winter or early spring
Prevalence of Selected DSM-IV Axis I Disorders MFTotal Major Depression 12.7 21.3 17.1 Panic Disorder 2.0 5.0 3.5 Social Phobia 11.1 15.5 13.3 Schizophrenia 1.3 0.7 1.0
Schizophrenics have: • Increased mortality rate from accidents and natural causes: • life span is shortened by about a decade • some under-diagnosis of medical illness is present • ~10-15% suicide; ~50% attempt • early in illness and young age • high premorbid function • depression • the latter two often contributing to demoralization • Illness seems concentrated in urban settings, i.e., it is somewhat correlated with population density in larger cities • Illness seems concentrated in lower socioeconomic classes (1/3 of homeless)
Diagnosis of Schizophrenia A. Characteristic symptoms: > 2 of 5 (active phase symptoms – Criterion A) • delusions • hallucinations • disorganized speech (incoherence-”word salad”) • grossly disorganized or catatonic behavior • negative symptoms, i.e., affective flattening, alogia, or avolition * bizarre delusions or running commentary voices or voices conversing with each other
Diagnosis of Schizophrenia B.Social/occupational dysfunction (50% unemployed) • Duration: at least 6 mo. (include at least 1 month of symptoms from Criterion A) D&E. Mood Disorder, Substance/general medical condition exclusion F. No Pervasive Developmental Disorder: (ex:Autism) (only if prominent delusions or hallucinations are also present for at least a month)
Subtypes • Catatonic • Catatonic behavior dominates (catalepsy-muscle rigidity/agitation) • Less common nowadays • Disorganized (hebephrenic) • Disorganized speech, behavior, and affect (flat or inappropriate) • Paranoid • Delusions and/or auditory hallucinations • Not limited to persecutory themes • Tends to have a later onset and better course
Adoption Studies Implies genetic factors not environmental
Due to virus (Flu) 2nd trimester: adhesion molecules causing pathological migration
Frontal Lobe IssuesFunctional brain imaging (PET, rCBF) • Failure to increase blood flow to the dorsolateral prefrontal cortex while performing the activation task of the Wisconsin Card Sorting Test • Reduced blood flow to the left globus pallidus (an even earlier finding in the course of illness) suggests a problem in the system connecting the basal ganglia to the frontal lobes • Correlation with severity of disease present
Wisconsin Card Sorting Task • Subjects are asked to sort each upcoming card on to one of the four piles (they are not directed but may use shape, color or number). They are told correct/incorrect. Whichever category they choose is correct for a given number of categories then is met with an “incorrect” response. Subjects must “switch sets” to get a correct response. Failure to switch sets is termed “perseveration”. • Schizophrenic subjects perseverate relative to normal controls, Green et al, 1992
Post-Mortem NeuroanatomyDisturbed connection between thalamus and PFC
1960 – discovery that striatums (caudate putamens) depleted of Dopamine
Dopamine Hypotheses of Schizophrenia • Dopamine • Schizophrenia due to over activity
Clorpromazine (Carlsson, 1963) • - expected DA levels to decrease • Metabolite increased • D2 receptor blockers work not • because to much dopamine but • Because to many receptors or too • Sensitive…
Dopamine Hypotheses of Schizophrenia (revised) • Dopamine • Positive symptoms of schizophrenia attributed to hyperdopaminergic function (more receptors or increased sensitivity, etc, D2)
Dopamine hypothesis - weaknesses: • Some atypical antipsychotics such as clozapine are not as well correlated with respect to D2 dopamine receptor binding and clinical potency • Does not account for negative symptoms of schizophrenia
Evidence against DA hypothesis of • Schizophrenia – Glutamate??? • Disorganized thought symptoms of schizophrenia attributed to hypofunctional glutamate system • Glutamate antagonists such as PCP and ketamine mimic disorganized thought, may also cause psychosis and negative symptoms?