historical figures in schizophrenia research emil kraepelin –1883: “dementia praecox”...
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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
– AssociationsAssociations– AffectAffect– AmbivalenceAmbivalence– AutismAutism
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
M F Total
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)
(1) delusions
(2) hallucinations
(3) disorganized speech (incoherence-”word salad”)
(4) grossly disorganized or catatonic behavior
(5) 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)
C. 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
Frontal Lobe Issues Functional 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
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 tooSensitive…
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