Schizophrenia
Schizophrenia is not an extreme of a normal brain state
loss of contact with reality
disruption of thought, perception, mood, movement
onset during adolescence or early adulthood
Grouped into three clusters
Positive
Negative
Cognitive Impairment
paranoid delusions, hallucinations
reduced expression of emotion (flat)
withdrawal of social interactions
impoverished content of thought and speech
difficulty in initiating goal-directed behavior
impaired working memory and executive function
inability to organize one's life (contributor to long term disability)
seen in healthy relatives of patients with schizophrenia (genetic predisposition)
antipsychotic drugs: diminish positive symptoms
Biological Basis of Schizophrenia
Genetics: schizophrenia has highest heritability of the mental illnesses (50% heritability in identical twins)
Other factors that can convert inherited genetic vulnerability into the disease
new mutations
epigenetics: environment, nutrition, social factors that affect gene expression
environmental factors
drug use
maternal infection during pregnancy
hypoxia during fetal development
The Neurodevelopmental Hypothesis of Schizophrenia
Early life stressors and in utero problems increase risk of schizophrenia
schizophrenics show
reduced brain volume
altered neural circuits
loss of dendrites and dendritic spines
loss of gray matter counterbalanced by enlarged ventricles
loss of gray matter in prefrontal cortex: region critical for working memory
loss of gray matter in temporal lobe, amygdala, hippocampus: regions for cognition and emotion
Dopamine Hypothesis
high doses of amphetamines --> psychotic symptoms (positive signs) identical to schizophrenia
amphetamines (stimulants) ENHANCE release of dopamine
effective treatments for positive symptoms: BLOCK dopamine receptors
HYPOTHESIS: schizophrenia results from TOO MUCH dopamine
Glutamate Hypothesis
schizophrenics have LOW levels of glutamate receptors
PCP and ketamine (NMDA glutamate receptor antagonists) produce schizo-like symptoms
animal models of schizophrenia have diminished activation of NMDA receptors
SCHIZOPHRENIA MAY ARISE from NMDA glutamate receptor deficits
Genes implicated in schizophrenia
metabotropic glutamate receptors
NMDA receptors
Postsynaptic density proteins
Activity-regulated cytoskeletal-associated protein
calcium channels
Treatments: drug therapy and psychosocial support
neuroleptics
antagonist at dopamine receptor subtypes
combat POSITIVE SYMPTOMS
side effects
persistent motor impairments
Parkinson-like symptoms
eventual tardive dyskinesia
dyskinesia - involuntary movements of lips and jaw
Atypical neuroleptics
bind to serotonin and dopamine receptors, possibly GABA
effective against negative AND positive symptoms
3rd generation drugs: Aripiprazole - treat positive symptoms
Newest focus: drugs that increase NMDA responsiveness