Science of depression

Question 1

What is the accepted understanding of depression at the moment?

Answer 1

Stress vulnerability model

Question 2

What effects does depression have on the HPA axis?

Answer 2

• Increased CRH
• Enlarged adrenals and pituitary
• Impaired/reduced negative feedback
• Reduced glucocorticoid receptors expression in brain

Question 3

What can cause ACTH increase in response to stress? regardless of whether they have a diagnosed major depressive disorder?

Answer 3

History of childhood trauma

Question 4

Steroids (cortisol) is increased in depression and these are thought to be…

Answer 4

neurotoxic
cause neuro-vulnerability
affect dendrite formation
reduce neurogenesis
particularly affect hippocampus

Question 5

Where has depression been found to cause volume loss within the brain?

Answer 5

the frontal lobes and hippocampus

Question 6

What does the medial prefrontal cortex within the frontal lobe do?

Answer 6

Evaluates emotional state and involved in social cognition

Question 7

What does the dorsolateral prefrontal cortex do?

Answer 7

Involved with problem solving and working memory

Question 8

which bit of the frontal lobe has the most volume loss in depression?

Answer 8

dorsolateral prefrontal cortex (then medial)

Question 9

How much is the hippocampus reduced in size in depression?

Answer 9

up to 20% reduction in size, which is mostly irreversible. It has a dose -related effect, meaning the more severe the depression, the greater the reduction in hippocampus size

Question 10

What effect does stress have on dendrites and how is it mediated?

Answer 10

Stress reduces dendrites, this is mediated by the reduction in neurotrophins e.g. BDNF (stress reduces BDNF, and this is also seen in depression). This results in less synaptic connections between neurons.

Question 11

Why do antidepressants take a long time to work? ( start to see effects after 3-6 weeks)

Answer 11

as they effect the gene expression

Question 12

what is the mechanism of action for antidepressants?

Answer 12

• Increase glucocorticoid receptor expression, so the HPA axis is improved
• Increases neurotrophin BDNF
• Increases neurogenesis
• And so therefore increases connectivity and plasticity within the brain

Question 13

How is depression as a disease defined?

Answer 13

Depression is a disease of reduced plasticity and reduced connectivity at a cellular level.
Depression is a disease of increased self-referential thinking.