Psychosis & Schizophrenia

Question 1

Epidemiology of schizophrenia

Answer 1

Affects 1% of people worldwide

Lifetime prevalence of suicide is 10%

Question 2

Clinical characteristics of schizophrenia

Answer 2

Onset of symptoms usually occurs between the ages of 18-25 and includes:

Positive symptoms: hallucinations (usually auditory), delusions

Negative symptoms: Lack of attention, lack of pleasure, loss of will, flattened affect, disorganized thoughts and speech

Question 3

Diagnostic criteria for schizophrenia

Answer 3

2 of the following present for at least 1 month:

Delusions
Hallucinations
Disorganized speech or behavior
Negative symptoms (i.e. affective flattening)

*Symptoms must cause social/occupational dysfunction and must not be attributable to some other condition

Question 4

What is the concordance rate of schizophrenia amongst identical twins?

Answer 4

70%

Question 5

Gross brain changes in schizophrenia

Answer 5

Enlarged lateral ventricles

Reduced volume of hippocampus, superior temporal gyrus, and dorsolateral prefrontal cortex (DLPFC)

Question 6

Role of dorsolateral prefrontal cortex in schizophrenia

Answer 6

DLPFC exhibits decreased activity as compared to normal controls, but increased activity as compared to executive function task performance-matched controls

i.e. schizophrenic patients exhibit inefficiency of the DLPFC

Question 7

What is the dopamine hypothesis of schizophrenia?

Answer 7

Hyepractivity of the mesolimbic dopaminergic neurons is associated with the positive symptoms of schizophrenia

Hypoactivity of mesocortical dopamine neurons is associated with negative symptoms of schizophrenia

D2 receptor antagonists treat psychosis; drugs that increase dopamine levels (amphetamine) exacerbate psychosis

Question 8

Neuropathological findings of schizophrenia

Answer 8

Decreased size and density of pyramidal neurons in the prefrontal cortex

Reduced GABAergic interneurons in layer III of the DLPFC

Decreased dendritic spines and presynaptic inputs in affected brain regions

Question 9

What is the glutamate model of schizophrenia?

Answer 9

Suggests that schizophrenia may be a result of glutamatergic hypoactivity

Prolonged exposure to NMDA receptor antagonists (PCP, Ketamine) is associated with psychotic illness

Question 10

What is the potential overlap between the dopaminergic and glutamatergic hypothesis of schizophrenia?

Answer 10

Chronic NMDA antagonist administration results in persistent elevation of dopamine release in the NAc (mesolimbic) and decreases dopamine release in the prefrontal cortex (mesocortical)

Question 11

What is the structure of the DLPFC?

Answer 11

Part of the association cortex, which modulates executive function

Comprised of six-layer isocortex:

Layers 2 and 4 contain inhibitory interneurons
Layers 3 and 5 contain excitatory pyramidal cells

Question 12

Environmental risk factors for schizophrenia

Answer 12

Prenatal infection
Prenatal nutrition
Pregnancy and birth complications
Social biology (migration, urbanicity)
Early drug abuse

Question 13

Typical antipsychotics

Answer 13

i.e. Haloperidol

D2 receptor antagonist, effective in 75% of acutely psychotic patients; more effective in treating positive symptoms caused by hyperactive dopamine activity of the mesolimbic system, poorly effective in treating negative symptoms caused by hypoactivity of the mesocortical system

Side effects: Dry mouth, muscle stiffness, muscle cramping, trempors, weight gain, EPS

Question 14

Extra-pyramidal side effects (EPS)

Answer 14

Constellation of side effects caused by blockade of D2 receptors, more commonly seen with 1st generation anti-psychotics:

Akathisia
Parkinsonism
Dystonias

Question 15

Atypical antipsychotics

Answer 15

I.e. Risperidone, Clozapine

Less EPS side effects
Other side effects: weight gain, hypercholesterolemia, diabetes, granulocytosis, diabetes