Depression and bipolar

Question 1

Groups experiencing higher prevalence

Answer 1

BAME, carers, domestic violence, homeless, disabled, LGBT, refugees, addicts, etc…

Question 2

Neuroanatomy

Answer 2

Prefrontal cortex, amygdala, and hippocampus affected.

structural changes can occur. smaller hippocampus.

Question 3

Early antidepressants and monoamine hypothesis

Answer 3

Dysregulation in monoamine signalling in the brain was assumed to be the cause of depression.

TCAs and MAOIs developed for this reason.

Does not explain why antidepressants take 2-3 weeks to work, and explain the pathophysiology of depression.

Question 4

HPA axis in depression

Answer 4

Depressed individuals display HPA hyperactivation, with increased [cortisol] in saliva, plasma, and urine, and increased [corticotropin releasing hormone] in CSF and brain.

Pituitary and adrenal glands also see increased size.

the negative feedback of cortisol on the hypothalamus and the pituitary gland is also compromised.

Antidepressants enhance the cortisol negative feedback, and reduce the HPA hyperactivity.

Question 5

Neurotrophic (BDNF) hypothesis.

Answer 5

Suggests depression is caused by reduced [BDNF] and that antidepressants work by increasing BDNF

Question 6

NTs in depression

Answer 6

decreased 5-HT seen in many patients.

decreased tyrosine often seen, which leads to decreased DA

Question 7

Non-pharmacological treatments

Answer 7

CBT to stop the cycle of negative thinking that affects the individual

Question 8

TCAs

Answer 8

e.g., amitriptyline inhibits SERT and NAT. also has antihistamine and anticholinergic effects. Cardiovascular effects can be fatal in overdose

Question 9

MAOIs

Answer 9

e.g., phenelzine, selegiline
cheese reaction can occur, whereby tyramine metabolism is impaired, and can replace NA from vesicle storage, leading to compromised neuronal signalling

Question 10

SSRIs

Answer 10

First line option
less toxic in overdose and less side effects

Question 11

SNRIs and NRIs

Answer 11

SNRI: venlafaxine
NRI: reboxetine

Question 12

Mirtazapine

Answer 12

Enhances NA and 5-HT signalling.
5-HT2 antagonist - presynaptic Gai receptor.
also blocks presynaptic alpha2-AR that inhibits NA release

Question 13

Theories for delay in antidepressant efficacy

Answer 13

Neurochemical theory: suggests increased EC [5-HT] activates the auto receptor 5-HT1 to inhibit the presynaptic neurone. after a few weeks, the receptor becomes desensitised.

Another theory (based on BDNF theory) suggests the delay is due to the slow increase in BDNF expression.

Question 14

Bipolar

Answer 14

Cycle between depression (at least two weeks) and mania

first episode before age 30, peak incidence 15-19

Diagnosed by specialist mental health professional - potential for misdiagnosis

Question 15

Bipolar treatments

Answer 15

For mania: antipsychotics e.g., haloperidol, olanzapine, or risperidone (acute), lithium or olanzapine (long-term)
For depression: SSRI with olanzapine, or olanzapine alone.

Question 16

Lithium safety

Answer 16

Lithium has a very small therapeutic window (0.5-1 mol/L), so plasma concentrations must be monitored to ensure dose is effective and safe

Concs above 1 have wide range of severe physical and mental side effects.

Concs above 2 risk convulsions, renal failure, coma, and death