Schizophrenia neurobiology and treatment Flashcards Preview

202: Theme 3, Modulatory systems in psychiatry > Schizophrenia neurobiology and treatment > Flashcards

Flashcards in Schizophrenia neurobiology and treatment Deck (18)
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1

Genetics of schizophrenia

Has genetic risk
- Around 50% risk in monozygotic twin

Interaction of genes and environment
- Partial penetrance of genes

Polygenic

2

Genetic and environmental relationship to environment

Genes are susceptible during puberty- when brain is maturing

At birth:
- Obstetric complications
- Prenatal infections
- Nutritional deficiency

All environmental factors that makes genes more susceptible

Adverse life events and substance abuse in adolescence can trigger the disease

3

Neuropathology
- Structural changes

Enlarged ventricles

Reduced brain volume
- Less grey matter in temporal, frontal and subcortex

Cortex and hippocampal cytoarchitectural differences

4

Neuropathology of hallucinations

Paracingulate sulcus morphology
- Shorter length was more present in those with hallucinations

5

Neurodevelopment model of schizophrenia
- Grey matter

During adolescence, grey matter in lost
- Schizophrenic subjects show this is significantly larger

- During pruning, strong synapses were removed along with weak ones
- Chandelier cells are unable to cultivate pyramidal cells during puberty = prefrontal cortex unable to generate synchronised firing

6

Functional changes in schizophrenia
- Hypofrontality

Hypofrontality
- During periods of high cognitive load

Wisconsin card sorting test shows reduced cognitive flexibility
- Does not show increased activity in dorsolateral prefrontal cortex

7

Functional changes
- Hallucinations

Auditory cortex activate occurs during hallucination

8

Neurophysiological changes in schizophrenia [3]

Hypofrontality
- Activity in the dorsolateral prefrontal cortex does not increase during cognition
- Shown with Wisconsin Card sorting test

Hyper-excitable sensory cortex
- Incorrect pruning of synapses
- Causes neurones to fire out of sync

Abnormal neural oscillations
- Lower frequency oscillations and synchrony

9

Diffuse modulatory system affected in schizophrenia

Dopaminergic:
- Nigrostriatal
- Mesolimbic
- Mesocortical

10

Dopamine theory for schizophrenia
- Evidence

Typical antipsychotic drugs prevent positive symptoms
- D2 receptor antagonist

Dopamine agonists [e.g cocaine, amphetamine] can cause positive symptpms

11

D1 receptor family

Gs protein receptors

Includes:
- D1, D5

12

D1 receptor

Part of D1 receptor family
- Gs coupled
Found in
- Caudate
- Putamen
- Nucleus accumbens
- Olfactory tubercule

13

D5 receptor

D1 family of receptors
- Gs protein coupled

Located in:
- Hippocampus
- Hypothalamus

14

Atypical antipsychotics

Specific dopamine antagonist that do not have extrapyramidal effects like typical antipsychotics

E.g
- Clozapine [D4], improves positive and negative symptoms
- Risperidone
- Olanzapine

15

Clozapine side effects [6]

Weight gain

Sedation

Hypersalivation

Tachycardia

Hypotension

Neutropenia

16

Glutamate hypothesis for schizophrenia
- Evidence

PCP [angel dust]: NDMA antagonist
- Causes positive, negative and cognitive symptoms of schizophrenia
- Models schizophrenia in studies

Genetically engineered mice with less NMDA receptors
- Mice show behavioural abnormalities similar to the drug-induced schizophrenia in animals

17

PCP and hypofrontality

PCP is used to model schizophrenia in animal studies

1. PCP antagonises NMDA in the prefrontal cortex
- Less excitatory firing to the GABA neurones in ventral tegmental area

2. GABA neurones in VTA are less inhibited
- Dopaminergic projections from VTA to nucleus accumbens are less inhibited

3. Greater DA release = less activation of dopaminergic neurones projecting from the VTA to PFC
- Less glutamate = hypofrontality

18

Neurocognitive deficits of schizophrenia

Lower IQ

Attentional deficit

Impaired working memory

Planning and information processing deficits