Schizophrenia

Question 1

Schizophrenia: DSM-5 criteria

Answer 1

• delusions, hallucinations, disorganized speech, disorganized/catatonic behaviour, and/or negative symptoms for a significant potion of time over a month
• marked impairment in functioning in work, interpersonal relations, self-care, etc.
• disturbance persists for at least 6 months, including 1 month of active-phase symptoms, including residual symptoms where symptoms may be attenuated (weak)
• schizoaffective disorders have been ruled out
• disturbance not attributed to a substance or other medical condition

Question 2

what schizophrenia looks like: symptoms

Answer 2

• Positive symptoms: agitation of behaviour (delusions, hallucinations, paranoia)
• Negative symptoms: blunting of responses (i.e., diminished emotional expression or avolition -> motivation to complete tasks)
• Cognitive symptoms (ie. Disorganized thoughts, memory problems)
• Mood symptoms (anxious, irritable, etc.)
• Unemployment, poverty homelessness common
• What it doesn’t look like: dissociative identity disorder

Question 3

schizophrenia: prevalence

Answer 3

• ~1% of population
• More common in men
• Onset: teens to early 30’s

Question 4

who is at risk for schizophrenia?

Answer 4

• Genetics (much higher risk if twin or parents have it)
• Living in urban environment
• Migration
• Marijuana (could trigger it?)
• Male

Question 5

structural and functional brain changes in schizophrenia

Answer 5

• Structural: widespread decreased gray matter, sometimes abnormal white matter, enlarged ventricles
• Functional: abnormal (often hypoactive) frontal and temporal lobes (including hippocampus), dysfunctional dopamine neurotransmission (pre- and post-synaptic), probably much more
• • Best considered a neurodevelopmental disorder

Question 6

non-pharmacological treatments

Answer 6

• CBT can manage positive and negative symptoms when combined with pharmacological treatments
• Insight therapies and counselling can be useful along with medication

Question 7

pharmacological treatments

Answer 7

• Anti-psychotic drugs/neuroleptics are most common treatments for positive symptoms
• • Discovery of neuroleptics: surgeon noticed the drugs had calming effect and alleviated symptoms of psychosis
• Less luck in treating negative symptoms

Question 8

dopamine theory of schizophrenia

Answer 8

• Theory that schizophrenia is caused by too much activity at receptors for the neurotransmitter dopamine
• Based on several findings:
• • Brains of individuals with Parkinson’s disease have dopamine depletions, and antipsychotic drugs produce symptoms similar to Parkinson’s
• • Drugs known to increase dopamine levels (ie. Amphetamine, cocaine) produce symptoms of schizophrenia
• • Efficacy of an antipsychotic drug is correlated with degree to which is blocks activity at dopamine receptors (ie. You give it at dose that’s most affective for relieving symptoms, which is influenced by how strongly drug binds to dopamine receptors)

Question 9

Problems with dopamine theory of schizophrenia

Answer 9

• Newer “atypical” antipsychotic drugs produce wide variety of changes in brain and were just as good (and just as bad) as traditional antipsychotics)
• It takes 2-3 weeks for antipsychotic drugs to work, yet their effects on dopamine receptor activity are immediate
• Most patients show no significant improvement to the first antipsychotic they are given

Question 10

glutamate hypofunction theory

Answer 10

Dysfunction of glutamate NMDA receptors on the GABAergic interneurons leads to decrease in GABAergic transmission -> decreased inhibition

Question 11

glutamate hypofunction theory: support

Answer 11

• NMDAR co-agonists (ie. Glycine, d-serine) provide small improvement
• CB1 receptor activation causes CB1-NMDAR internalization
• Chronic NMDAR antagonism changes DA transmission

Question 12

glutamate hypofunction theory: problems

Answer 12

Positive symptoms fail to respond to glutamatergic medication

Question 13

schizophrenia

Answer 13

• Best considered neurodevelopmental disorder (markers available early in life)
• Involves changes in macro- and micro-circuitry across the brain
• May lower the bar for signal-to-noise ratio - ie. Lower threshold is perceived as an external signal (mistaking internal noise for external signal)

Question 14

prodomal/CHR syndrome

Answer 14

• emergence of attenuated/weak symptoms like perplexity, unusual beliefs, hearing indistinct noises, etc.
• lasts ~1yr
• semi-structured interviews used to ascertain when people are in a prodomal state
• potent predictor of psychosis (1/4 of cases convert to full psychosis within a year, many others within 2-3 years)

Question 15

results of prospective longitudinal neuroimaging studies of CHR cases

Answer 15

show a steep rate of grey matter thinning in right superior and medial prefrontal cortex before onset of schizophrenia

Question 16

benefits of prospective longitudinal designs in studying schizophrenia

Answer 16

allows researchers to assess temporal precedence and meditational influences among potentially interacting variables (ie. reduces directionality and third variable issues)

Question 17

what role might immune processes play in emergence of psychosis?

Answer 17

• might influence grey matter reduction leading to psychosis

- higher levels of cytokines predict steeper rates of GM reduction

Question 18

source monitoring

Answer 18

• understanding whether items were actually perceived vs. imagined (by yourself or another person)
• networks involving medial PFC (reality monitoring) play a role in source monitoring
• disruptions of source memory may lay groundwork for disruptions of belief evaluation -> underlie earliest prodromal symptoms and eventually lead to more severe symptoms like hearing voices

Question 19

Article: NMDA-glutamate-receptor hypofunction theory

Answer 19

• NMDA receptor hypofunction may contribute to schizophrenia
• increased glutamate levels found in patients during first schizophrenic episode, and in CHR subjects
• NMDA receptors involved in synaptic pruning may drive accelerated grey matter loss
• NMDA signaling my interrupt prediction-error signals that mediate between beliefs and experiences, contributing to delusions

Question 20

article: dopamine theory

Answer 20

• based on fact that antipsychotic drugs block dopamine D2 receptors and drugs that stimulate dopamine produce short psychotic states
• some studies have shown increased dopamine synthesis exists in parts of striatum that project to PFC during prodromal phase -> heightened sense of salience of stimuli, playing a role in paranoia
• however, evidence of increased dopamine receptors in schizophrenics is inconsistent, and no mechanism has been found for dopamine synthesis capacity during progression from prodomal to fully psychotic (may be downstream consequence of NMDA hypofunction)