Affective disorders: Neurobiology and treatment

Question 1

There are two models used to outline the neurobiology of affective disorders. Outline both

Answer 1

1. Current stress, genetic functions and adverse childhood experience affect HPA Axis function. This leads to elevated cortisol leading to decreased serotonin and noradrenaline function
2. Current stress and genetic functions cause decrease in serotonin and noradrenaline function

MONOAMINE DYSFUNCTION IMPLICATED
**Target for traditional anti-depressant

Question 2

Outline the aetiology of affective disorders

Answer 2

Multifactorial
Incompletely understood
Precipitated by stressful life events

Question 3

Monoamine dysfunction is implicated in affective disorders

What are the individual roles of noradrenaline, serotonin, and dopamine?

What are their combined roles?

Answer 3

NA- Attention
Serotonin- Impulsivity, suicidal ideation
Dopamine- psychomotor activation, euphoria

NA+ 5HT: Anxiety, irritability
NA+ DA: motivation, energy
DA+ 5HT: sleep, appetite, sexual functions, aggressiveness

All: Mood, emotions, cognitive functions

Question 4

Consider the treatment options for affective disorders.

What are considered 1st and 2nd generation antidepressants?

Answer 4

1st generation antidepressants: monoamine oxidase inhibitors, tricyclic antidepressants

2nd generation antidepressants: SSRT, Serotonin-noradrenaline reuptake inhibitors, alpha-2 and serotonin antagonist, dopamine-noradrenaline reuptake inhibitor

Question 5

Explain the Hypothalamus-Pituitary-Adrenal dysfunction in mood disorders

Answer 5

Evidenced to be implicated in depressive/anxiety disorders
-Changes in hormone production

Lack of dexamethasone suppression
Glucocorticoid receptor alterations
Depression in Cushing’s disease

Question 6

How is inflammation implicated in depression?

Answer 6

• Increased plasma cytokine levels (IL-6 and TNF-a) and inflammatory markers
• Increased comorbidity between chronic inflammation and depression- administration of cytokines provokes depressive symptoms
• PET studies show microglial actvation in brain of depressed patients

Question 7

What is the role of specific brain areas in depression?

Answer 7

Increased activity (amygdala, VST, PFC) to negative stimuli - fearful faces

Decreased activity (in VST) to positive emotional stimuli, and during receipt and anticipation of reward

***BIAS of attention towards negative stimuli, and away from positive and reward-related stimuli

Question 8

Which molecules/processes are involved in bipolar disorder?

Answer 8

Stress hormones, glucocorticoids
Inflammation
Neurotrophins
Oxidative stress
Catecholamines

Question 9

CLINICAL APPLICATION

What does short-term treatment for bipolar disorder aim to do?

What does long-term treatment for bipolar disorder aim to do?

Which categories of drugs are available?

Answer 9

• Reduce the severity and shorten duration of acute episodes
• Achieve remission of symptoms
• Prevention of new episodes
• Achieve adequate inter-episode control of residual/chronic mood symptoms

Antipsychotics, lithium, anticonvulsants, antidepressants

Question 10

In bipolar disorder, how are antidepressants to be administered?

Answer 10

Co-prescribed with an anti-manic drugs

Don’t use potent anti-depressant in bipolar e.g. a tricyclic as it causes mania!

Good treatment: mood stabilizers which are effective for depression as well e.g. lithium or anticonvulsants

Question 11

Treatment of acute manic episodes?

Answer 11

• Dopamine antagonist
• Sodium valporate

DISCONTINUE ANTIDEPRESSANT TREATMENT

Question 12

Long-term treatment for bipolar?

Answer 12

Lithium as initial monotherapy

• if ineffective, poorly tolerated, poor adherance:
  
  • Sodium valporate
  • Dopamine antagonists/ partial agonists
  • Carbamazepine

Question 13

Side effects of bipolar drug treatments?

Answer 13

Kidney and thyroid dysfunction (lithium)

Weight gain

Metabolic syndrome

Hyperprolactinaemia (dopamine antagonist)

Tardive dyskinesia (Decreased in newer treatments)

Liver damage (Valporate)