Neuro 5/6: Neurobiology and neurochemistry in mental health

Question 1

what is the stress diathesis model? (schizophrenia)

Answer 1

stress = in utero insults (hypoxia)
psychological stress cannabis use

diathesis = genes such as COMT, dysbindin1 and NRG1, these are polygenic and partial penetrance.

Question 2

define psychosis

Answer 2

‘break from reality’ defined as 7 days of psychotic sx but they can be on a continuum.

Question 3

what are the sx of schizophrenia

Answer 3

Positive:Voices, delusions, thought insertion/withdrawal/broadcast

Negative: Neglect, isolation, lack of emotional expression, avolition

Cognitive: Reduced concentration and attention, reduced executive functioning (ability to plan complex tasks)

Question 4

what is dopamine and what is its precursor?

Answer 4

Monoamine neurotransmitter
Metabotropic, G-protein coupled receptors
Precursor = Tyrosine

Question 5

what does dopamine do?

Answer 5

Executive functions Motor control Motivation Reward Lactation Nausea

Question 6

describe the different pathways

Answer 6

Mesocortical (VTA-> cortex)
mesolimbic (VTA-> nucleus accumbens)
nigrostriatal (susbtanantia nigra -> caudate nucleus putamen)
tuberoinfundibular (hypothalamus -> pituitary)

Question 7

how does SCZ affect the pathways?

Answer 7

upregulation of DA in mesolimbic -> +ve sx

downregulation in mesocortical -> -ve sx

Question 8

how would a typical antipsychotic work?

Answer 8

blocks DA in both mesocortical and mesolimbic making +ve sx better but -ve sx worse

Question 9

why do antipsychotics cause hyperprolactinaemia

Answer 9

Dopamine has inhibitory effect on prolactin release.
Reduced dopamine by D2 antipsychotics therefore causes
Hyperprolactinaemia

Question 10

why would the dopamine theory not be the correct one?

Answer 10

New atypical antipsychotics work in different ways on non-dopaminergic pathways

Illicit drugs that don’t work on dopamine can mimic psychosis (e.g. magic mushrooms, PCP)

Medical conditions affecting different receptors can cause psychosis

Question 11

how do antipsychotics cause EPSE?

Answer 11

Too little dopamine effect in Nigrostriatum causes Extrapyramidal Side Effects

Question 12

what are some reasons as to why glutamate would be involved in psychosis?

Answer 12

Ketamine and PCP (angel dust) act on NMDA glutamate receptor and are powerful causes of psychosis

Research shows too little glutamate in pre-frontal cortex mirrors psychosis

NMDA receptor autoimmune encephalitis causes psychosis

Question 13

how does Glu lead to psychosis?

Answer 13

Reduction in glutamate release leads to direct loss of dopamine release in PFC via mesocortical pathway

Reduction in glutamate release leads to increased positive symptoms by mesolimbic pathway

Question 14

how does GABA cause psychosis?

Answer 14

GABA is the brain’s main inhibitory neurotransmitter

Reduction in glutamate release leads to reduced GABA inhibition which increases positive symptoms (dopamine hyperactivity in mesolimbic pathway)

Question 15

what is serotonin?

Answer 15

5-HT

Question 16

what are the anatomical changes seen in schizophrenia?

Answer 16

Enlarged ventricles
Reduced grey matter volumes
Decreased gyrification
Loss of asymmetry of planum temporale (associated with auditory processing)

Question 17

what are some organic causes of psychosis?

Answer 17

NMDA receptor autoimmune encephalitis 
Huntingdon’s Chorea
Temporal Lobe Epilepsy
 Wilson’s Disease
Parkinson’s Disease

Question 18

what is NMDA receptor encephalitis?

Answer 18

Antibodies form against NR1 and NR2 subunits of NMDA (glutamate) receptor
Associated with teratomas
Presents with flu like illness or encephalitis or psychotic symptoms
May need ITU due to autonomic instability
Immunosuppression with steroids

Question 19

what is temporal lobe epilepsy and how can it cause psychosis?

Answer 19

Can have no impairment of consciousness during seizure
Depending on part of temporal lobe can have hallucinations in all modalities, extreme fear, amnesia, difficulty maintaining thoughts, dissociation
Can have post-ictal psychosis
Can have inter-ictal (between seizures) psychosis
Require EEG and neurologist input

Question 20

What is wilson’s disease?

Answer 20

Autosomal recessive disease
Faulty ATP7B gene affecting Wilson’s disease protein
Leads to copper deposition in brain and liver
Affects Basal Ganglia
Neuropsychiatric complications include cognitive impairement, depression and psychosis
Don’t forget to look for kayser-Fleischer rings in the eyes

Question 21

what is Hungtington’s Chorea?

Answer 21

Autosomal dominant – CAG triplet repeats in the Huntingtin gene
CAG >28 unstable during replication
28-35 is subthreshold, 35-40 “reduced penetrance”
Every generation increases the instability of the CAG triplets and therefore risks increasing the number of repeats.
This leads to earlier onset and more severe symptoms (particularly if subthreshold parent)
This is called genetic anticipation
Pathophysiology of psychosis unclear, ?dopamine overload following cell death

Question 22

what are the 2 types of Bipolar affective disorder?

Answer 22

Discrete episodes of depression AND mania/hypomania.Bipolar Type 1 = Depression and ManiaBipolar Type 2 = Depression and Hypomania

Question 23

what is the role of the limbic system?

Answer 23

Role of limbic system:
Emotional regulation
Memory formation
Learning

Question 24

how are emotions processed?

Answer 24

There is both communication TO PFC as well as “Top down” regulation FROM the PFC.Oschner 2005
This allows for executive control of emotional states

Question 25

what is the theory of limbic dysregulation in Bipolar disorder?

Answer 25

Underactivation of pre-frontal cortex seen using fMRI Chen et al 2011
AND
PFC volume loss observed as disease progresses
LEADS TO
Reduced “Topdown” regulation
Reduced connectivity between PFC and amygdala

Question 26

what is the role of the amygdala in bipolar disorder?

Answer 26

Overactivity of Amygala on fMRI in response to faces

Decreased volume of amygdala seen in pediatric cases and those with bipolar and first episode psychosis.

Question 27

what are the physical changes in the brain in bipolar?

Answer 27

Loss of prefrontal cortex mass and progressive hypoactivation

Sustained hyperactivity of amygdala and increasing volume size

Question 28

what are the 3 key sx of depression?

Answer 28

Low mood
Anhedonia
Tiredness

Question 29

what are some additional sx seen in depression?

Answer 29

Cognitive (hopelessness, helplessness, worthlessness, guilt, poor concentration, poor attention, lack of motivation)
Somatic (early morning waking, loss of appetite, weight loss, libido)
Motor symptoms (slow motor movements – “Motor Retardation”)

Question 30

What is the stress diathesis model for depression?

Answer 30

stress = Divorce BereavementRelationship Breakup Job Loss

diathesis = Female Gender
genetic vulnerability

Question 31

what is the monoamine theory?

Answer 31

All derived from aromatic acids Receptors act downstream on Adenyl Cyclase or Phospholipase C
All have designated monoamine transporters for transport in/out of cell e.g. Seretonin Transporter, Dopamine transporter etc…All are broken down by Monoamine Oxidase

Question 32

what is evidence for low serotonin in MDD?

Answer 32

Dietary depletion of tryptophan (precursor for serotonin) can cause relapse of depression in patients who have previous diagnosis or family members

Reserpine – An antihypertensive that causes rapid depletion of serotonin in the synaptic cleft classically causes depression

Selective Serotonin Reuptake Inhibitors (SSRIs) work by blocking the reuptake of serotonin in to the pre-synaptic neuron

Question 33

how is NA involved in MDD?

Answer 33

Noradrenaline projects from the Locus Coreleus to innervate the limbic system and frontal lobe

Decreased noradrenergic receptor density seen in some patients with depression

Question 34

what is the difference between an anxiety disorder and fear?

Answer 34

Fear (Imminent danger) vs. Anxiety (anticipation of potential threat)

Question 35

what occurs in the amygdala in anxiety?

Answer 35

The Amygdala differentiates the sensory information sent by the thalamus to identify threat from no threat.

If a threat is perceived through the conscious or unconscious pathways, the Amygdala can initiate a physiological response that we see in stress reactions and anxiety disorders

Question 36

what are the characteristic signs of PTSD?

Answer 36

Post Traumatic Stress Disorder characterised by hypervigilence, flashbacks, nightmares and avoidance.

In PTSD the hippocampus shrinks

Question 37

describe the step by step of how PTSD occurs?

Answer 37

trigger -> hippocampus recalls a small fragment of memory -> amygdala reacts to memory -> PFC unable to rationalise situtation -> unable to recognise person is safe -> person attempts to avoid or escape.