Schizophrenia: Neurobiology and treatment Flashcards
Percentage risk of schizophrenia in monozygotic twins
- Up to 50%
Genetic risk of schizophrenia
- 1% general population
- Partial penetrance(interaction of genes and environment)
- Likely to be polygenic - multiple susceptibility genes
- Presence of these and environmental factors triggers schizophrenia
What does the genetics of schizophrenia overlap with
- Overlaps with the genetics of autism and other neurodevelopmental disorders
Environmental causes of schizophrenia at birth
- Obstetric complications
- Prenatal infection
- Nutritional deficiency
Environmental causes of schizophrenia during adolescence
- Adverse life events
- Substance abuse
(cannabis use - 6x risk)
Structural changes in the brain in schizophrenic patients
• Ventricular enlargement
• Reduced brain volume (less gray matter)
(temporal lobes, frontal lobes, subcortical structures)
Cytoarchitectural differences in cortex and hippocampus
- Gray matter loss: 1. Synaptic pruning + 2. Increased myelination
What is paracingulate sulcus morphology associated with
- Hallucinations
Neurodevelopmental model of schizophrenia
- During adolescence, grey matter is lost(pink), which may speed up in early-onset schizophrenia
Dynamic changes in male and female teenagers with schizophrenia
- A consistent pattern of progressive grey matter loss, in parietal, frontal, and temporal cortices, is observed in independent groups of male and female patients
- A single pattern is observable in both boys and girls, supporting the anatomical specificity of the findings
dIPFC significance in healthy volunteers and schizophrenics
Increase in activity in dIPFC seen in healthy volunteers. Absent in schizophrenics
What is pruning and why is it relevant to schizophrenia
- Pruning is a sort of clean-up job conventionally thought to eliminate weak synapses and leave strong ones
- In schizophrenia, it was suspected, the pruning process hacked away indiscriminately, knocking out strong synapses along with weak ones
Normal neurodevelopmental model of schizophrenia
- Proliferation
- Migration
- Arborization(circuit formation)
- Myelination
Functional changes of the auditory cortex activation during hallucinations
- Auditory cortex activation during hallucinations(fMRI evidence)
What are oscillations in the brain
- Important organisers of brain activity, plasticity and connectivity(maturation)
What is neuronal synchrony
- Well-timed coordination and communication between neural populations
When do high frequency oscillations and synchrony emerge
- Emerge during the transition from adolescence to adulthood
- Differences in neural oscillations and synchrony between controls and patients with schizophrenia
What is hypofrontality
- State of decreased cerebral blood flow in the prefrontal cortex of the brain
- Hypofrontality is symptomatic of several neurological medical conditions such as schizophrenia, ADHD, bipolar disorder and major depressive disorder
Neurophysiology summary in schizophrenics
- Hypofrontality
- Hyper-excitable sensory cortex
- Abnormal neural oscillations
Features of typical antipsychotic(neuroleptic) drugs
- D2 receptor antagonists
- Prevent positive symptoms
Which is a more potent antipsychotic, chlorpromazine or haloperidol
- Haloperidol is more potent than chlorpromazine
Examples of DA agonists
- Cocaine, amphetamine, L-dopa can(in large doses) cause positive symptoms of schizophrenia(eg psychosis)
- These drug-induced psychoses can be treated with the D2 antagonist antipsychotic drugs
Which dopamine receptors are Gs coupled
D1 and D5
Location of D1 receptors
- Caudate putamen NAcc
- Olfactory tubercle
Location of D5 receptors
- Hippocampus
- Hypothalamus
