The science of depression

Question 1

What are the biological symptoms of depression?

Answer 1

Poor sleep
Poor appetite
Reduced libido
Poor concentration

Question 2

What are the cognitive symptoms of depression?

Answer 2

Worthlessness (poor self esteem)
Guilt
Hopelessness
Suicidal thoughts

Question 3

What is the stress vulnerability model?

Answer 3

Different people have different vulnerabilities to stress
Can be genetic or as a result of early/prenatal experience
Early experience sets the neuroendocrinilogical thermostat - epigenetics

Question 4

How does the HPA axis have a role in depression?

Answer 4

Increased CRH in depression
Enlarged adrenals and pituitary physically
Reduced negative feedback loops
Reduced GR expression in the brain (glucocorticoid resistance)

Question 5

How does early adversity and parenting affect depression?

Answer 5

History of childhood maltreatment (with or without current clinical depression)
Causes increased ACTH release in response to stress (HPA axis)

Question 6

What affects HPA axis function in animal studies?

Answer 6

Offspring of high licking lab rats show high GR expression (higher ACTH suppression), even if swapped at birth or brushed by research assistant
social rank in monkeys - subordinate monkeys have increased cortisol in hair, heavier adrenal glands, reduced dexamethasone suppression

Question 7

How do steroids (according to findings) affect the brain?

Answer 7

Suggest they are neurotoxic
cause neuro-vulnerability
Affect dendrite formation
Reduces neurogenesis
Causes changes to the EEG
Particularly affects the frontal lobes and hippocampus

Question 8

What is the medial PFC? How does depression affect it?
What is the dorsolateral PFC? How does depression affect it?

Answer 8

Evaluating emotional state, involved in social cognition
Has less volume loss

Involved in working memory and problem solving
Large volume loss

Question 9

How does depression affect the hippocampus?

Answer 9

Known to be important for memory
Bilateral lesions - complete anterograde memory loss
Reduced size in MDD, up to 20%

Question 10

Neurogenesis

Question 11

stress and neurogenesis

Question 12

how does stress affect dendrited

Question 13

What is BDNF?

Answer 13

brain derived neurotrophic factor
A neurotrophin, affects neuroplasticity by affecting dendrites

Question 14

How do stress and BDNF interact?

Answer 14

In animals stress causes decreased BDNF
Reversed with antidepressants

Low BDNF in unmedicated depressives, normal to high in medicated
Lowest levels in post-mortems of suicide victims

Question 15

Why do antidepressants take so long to work?

Answer 15

They change gene expression
In turn changes function of the cell
In turn changes dendritic spine formation
Changes circuits and way people think

Question 16

What genes do antidepressants affect?

Answer 16

Increase GR expression (regulating HPA activity)
Increase neurogenesis
Increase BDNF synthesis - so improve connectivity of dendritic spines, inc no synapses

Question 17

What does MDD stand for?

Answer 17

Major depressive disorder

Question 18

What is measured by modern scanning tools? e.g. MRI

Answer 18

Based on oxygen or glucose take up
Functional connectivity - spatially distinct areas of the brain showing similar activity at similar times
Allows the study of networks

Question 19

What is the function of the default mode network?

Answer 19

Reliably lit up when you didn’t ask someone to do a task
What ‘lights up’ when there’s nothing to do (resting state)
Daydreaming, internal ‘flow’ of consciousness
Autobiographical details
Self reference - referring to traits or states, emotional and moral reasoning
Thinking about others - empathy - social judgement/evaluations

Question 20

How is DMN affected in depression?

Answer 20

One network has to be ‘switched off’ for another to properly ‘switch on’
People with depression struggle to ‘switch out’ of the default mode network in response to a task
Excessive rumination

Question 21

What is ego dissolution?

Answer 21

Decrease in sense of self-importance
Lack of sense of self

Question 22

What is the entropic brain hypothesis?

Answer 22

Brain tries to reduce entropy - reduce ‘surprise’
Through top-down processing
Making predictions about the future
High entropy state of the brain - flexible states, high disorder - psychedelic state, REM sleep/dreaming, near death experiences
Low entropy state - low disorder, rigid states - coma, depression, OCD, addiction, narrow thinking, deep sleep

Question 23

Does mindfullness meditation treat depression ?

Answer 23

Reduces activity on the DMN
sorta, yeah

Question 24

How can depression be described by neuroscience? Psychology?

Answer 24

Reduced plasticity
Reduced connectivity at the cellular level

Disease of increased self-referential thinking
Reduced connectivity at the interpersonal level

Question 25

What are the 5 pillars of well being?

Answer 25

Physical activity
Connect with others
Learn something new
Practice mindfullness
Acts of generosity

Question 26

How can modern society be depressogenic?

Answer 26

Over-emphasis on the self and one’s rank
Self-referential ruminations
Fear of social threat
Much more aware of other’s social standing - think of social status monkeys