Transcript Right now over 2 million adult Americans have schizophrenia

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
Major Depression
Panic Disorder
Social Phobia
Schizophrenia
M
12.7
2.0
11.1
1.3
F
21.3
5.0
15.5
0.7
Total
17.1
3.5
13.3
1.0
Prevalence relative to medical disorders
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
Etiology of Schizophrenia
Genetic Influences
Adoption Studies
Implies genetic factors not environmental
Genetics and Family Studies
Etiology of Schizophrenia
Brain Abnormalities
Hippocampus
Due to virus (Flu) 2nd trimester: adhesion molecules causing pathological migration
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
Frontal Lobe Abnormalities - PET image of twins during
WCST
Ventricles Enlarged
MRI – Discordant
(bigger differences in males- ventricle size
Post-Mortem Neuroanatomy
Disturbed connection between thalamus and PFC
Serendipity Strikes Again!!!!
1960 – discovery that striatums (caudate
putamens) depleted of Dopamine
Dopamine Hypotheses of
Schizophrenia
• Dopamine
– Schizophrenia due to over activity
Dopamine of Antagonist
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)
Evidence in Support
•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?