Neurobiology of mental illnesses Flashcards
Aetiology of schizophrenia
- Stress factors
- Genetics
Stress factors
- Utero insults: such as hypoxia
- Perinatal injury/ trauma
- Migration
- Cannabis use
Genetics
- Genes: COMT, dysbindin 1, NRG1
- Polygenic with partial penetrance.
Dopamine
- Function
- Receptor
- Amino acid derivative
Function
- Motor control
- Executive function
- Motivation and reward
- Lactation
Receptor
- G-protein
Derived from tyrosine
Dopaminergic pathways: projections and function
- Mesolimbic
- Nigrostriatal
- Mesocortical
- Tuberoinfundibular
Mesolimbic
- From VTA to ventral striatum (nucleus accumbens, olfactory tubercle).
- Involved in reward, aversion
Nigrostriatal
- From substantial nigra to basal ganglia (caudate, putamen)
- Motor function
Mesocortical
- VTA to pre-frontal cortex
- Executive function
Tuberoinfundibular
- Hypothalamus (arcuate nucleus) to pituitary
- Involved in lactation/ prolactin release
Evidence of non-dopaminergic involvement of schizophrenia
Iicit drugs that increase glutamate mimic psychosis
- PCP
- ketamine
Too little glutamate in PFC mirrors psychosis
NMDA receptor autoimmune encephalitis
- Causes psychosis
Glutamate-dopamine hypothesis of schizophrenia
Hypoactivity of PFC
- Less glutamate causes less stimulation of PFC via mesocortical pathway
- Causes negative symptoms
Overactivity of the mesolimbic system
- Less stimulation of VTA from PFC, causes less disinhibition of mesolimbic pathway (GABA)
- Increases positive symptoms
Serotonin and evidence of link to psychosis
Illicit drug
- LSD is a 5HT2a agonist= powerful hallucinogen
Antipsychotic drugs work on 5HT2a
- Clozapine
- Quetiapine
- Risperidone
Action of typical antipsychotic
Blocks postsynaptic D2 receptors
- Reduces positive symptoms by blocking mesolimbic pathway
HOWEVER
- Can worsen negative symptoms by blocking mesocortical pathway
- Causes extrapyramidal side effects by blocking nigrostriatal neurones
- Causes hyperprolactinaemia by blocking tuberoinfundibular pathway.
Neuroanatomical changes in schizophrenia
Enlarged ventricles
Reduced grey matter volumes
Decreased gyrification
Loss of asymmetry in planum temporale (audio processing regions)
Organic causes of psychosis
NMDA receptor autoimmune encephalitis
Huntington’s chorea
Temporal lobe epilepsy
Wilson’s disease
Parkinson’s
NMDA Receptor autoimmune encephalitis
- Pathophysiology
- Presentation
- Association
- Treatment
Autoimmune condition where Ab are formed against NR1 and NR2 subunits of NMDA
- Blocks the effect of glutamate
Presentation
- Flu-like illness
- Encephalitis
- Psychosis
Associated with teratomas
- Ovarian and testicular cancers
Treatment
- Steroids
Huntington’s
- Pathophysiology + psychosis
Autosomal dominant disease
- CAG repeats >28= glutamate toxicity
- Dopamine overload causes psychotic symptoms
Wilson’s disease
- Pathophysiology + psychosis
Autosomal recessive disease
- Copper deposits in basal ganglia
- Mimics psychosis, dementia and depression
Stress- diathesis model
Combination of genetic vulnerability/ polygenic partial penetrance and environmental stressors causes certain psychological disease
- Depression
- Schizophrenia
Neurophysiology of bipolar
- System affected
- PFC
Dysregulation of the limbic system
- which is important for emotional regulation.
Limbic system has executive function over certain brain areas to control emotional states
- In bipolar there is decreased PFC and progressive hypoactivity
Amygdala
- Increased volume, becomes overactive (possibly due to glutamate activity)
Risk factors for depression
Female
Family history
Stressors
- Divorce
- Bereavement
- Job loss/ unemployment
Monoamine hypothesis of depression
- Evidence
Depletion Monoamines causes symptoms
- Serotonin
- NA
- Dopamine
Serotonin
- Dietary depletion in tryptophan causes relapse of depression if there is FH or had previous episode
- Reserpine causes depressive symptoms (blocks uptake and postsynaptic receptors)
- SSRIs have anti-depressive effects
NA
- SNRI cause remission in depression when SSRIs don’t work
- Some depressed patients show decreased NA receptor density
Noradrenaline
- Precursor
- Projections
Precursor
- Tyrosine
Projects from locus corelus into the limbic and frontal lobe
Serotonin
- Precursor
- Projections
Made from tryptophan
Projection from raphe nucleus
Role of amygdala in anxiety
Amygdala receives input from PFC and thalamus
- Initiates physiological response to perceived danger
- Overactive HPA (due to chronic release of cortisol, dysregulates negative feedback)
PFC
- Processes danger from sensory input before outputing into amygdala
Thalamus
- Output into amygdala is unconscious pathway
PTSD pathophysiology
Shrunken hippocampus
- Processes and stores memories
- Recalls memory in fragments
Limbic dysfunction
- Hippocampus stimulates amygdala to relive memory and feeds it into PFC
PFC
- Does not rationalise the situation= avoidance/ escape
