The Stress-Diathesis Hypothesis / Neurogenic

Question 1

What does this believe?

Answer 1

That there are other events which are taking place in the brains of patients with schizophrenia

Question 2

What occurs in the hippocampus?

Answer 2

Reduced hippocampus volume - shrinkage if depressed
Negative correlation with the total hippocampal volume and days left untreated - suggesting that the longer that they wait, the more their hippocampus shrinks

Question 3

What is the HPA axis?

Answer 3

Our central stress response system

Hypothalamus
Anterior pitutary
Adrenal cortex

Question 4

What is responsible for the change in people with depression?

Answer 4

Need to look at depression as a disorder to do with anxiety and stress, which is ongoing

Question 5

What occurs in the HPA axis?

Answer 5

In the hypothalamus, there is a CRF releasing factor which sends a message t the anterior pituitary to release ACTH. Once released, goes down to the adrenal cortex which then releases cortisol

Question 6

What are the parts of the adrenal cortex?

Answer 6

Has a cortex - which releases cortisol

Has a middle part that is related to the flight or fight response

Question 7

What is negative feedback in the HPA?

Answer 7

Amydgala is stimulated from a negative event
Feeds to HPA axis, which releases cortisol
The cortisol goes to the hippocampus, which receives a signal, the job is to deal with it and feedback to the HPA axis to stop releasing the ACTH because everything is okay

Question 8

What is the role of the hippocampus in the HPA axis?

Answer 8

Negative feedback - needs to tell HPA to stop releasing ACTH because everything is okay

Question 9

What happens in situations of chronic stress?

Answer 9

Chronic activation of glucorticoid receptors in the hippocampus: increased Ca entry too neurons, too much Ca entry means that the cells die. The hippocampus can’t feedback to limit cortisol production. So depression could be from: diminished activity in hippocampus and loss of feedback to HPA axis

Question 10

What happens when given artificial cortisol?

Answer 10

People given dexamathasone
Controls: activates GR and the negative feedback system
Decreased levels of ACTH and cortisol in control.
Depressed patients: less sensitive to the cortisol - poor negative feedback and more sensitive to CRH (activation system very sensitive)

Question 11

What are depressed patients according to the stress hypothesis?

Answer 11

Hyperactive HPA axis
High blood levels of cortisol
High brain levels of CRH

Question 12

What happens when you inject CRH into an animal?

Answer 12

Symptoms of depression
Insomnia
Lack of appetite
Lack interest in sex

Question 13

What does this theory believe the only difference is?

Answer 13

The genes to do with the HPA axis

Question 14

Why is the HPA overactive?

Answer 14

Chronic high levels of cortisol
Loss of neurons in the hippocampus because excitotoxity - shrinkage of hippocampus
Loss of GR’s
Decrease in negative feedback from the HPA axis and hippocampus because the hippocampus is shrinking so not working

Question 15

Do antidepressants result in increased neurogenesis in the hippocampus?

Answer 15

They don’t just increase monoamines but they eventually increase neurogenesis
Patients were taking:
MAO-I, SSRI’s or NE reuptake inhibitor for 2-4 weeks
Measured number of new born cells in the hippocampus
All of the drugs increase the neurogenesis in the hippocampus, doesn’t make a difference
Reverse the effect of hippocampus shrinkage

Question 16

What is important for normal development?

Answer 16

Neurotrophins or neurotropic factors

Question 17

What is BDNF?

Answer 17

A neurotropic factor - supports the idea that we need a health environment for existing neurons and new neurons to thrive

Question 18

What does BDNF do?

Answer 18

Injections of BDNF in the rat brain reduces neuronal death and protects neurons that have been treated with toxins
Chronic stress in animals decreases the amount of BDNF and increases cell death
Levels of BDNF are reduced in people with depression - reversed by antidepressants

Question 19

What can increase BDNF?

Answer 19

Exercise - making your brain healthy, a good environment for new neurons to be born in

Question 20

What is the difference between the hippocampus in normal patients, stressed ones and ones on antidepressants?

Answer 20

Normal - survival and growth
Stress - increased cortisol, less BDNF, atrophy and death = increased vulnerability (need environment too?
Antidepressants - increased 5HT and NE and BDNF, increase survival and growth

Question 21

Why are some people more susceptible than others in developing depression?

Answer 21

Because of the 5HT transporter - there is a functional polymorphism in the region of the serotonin transporter, which moderates the influence of stressful life events on depression

Question 22

What did Caspi et al find?

Answer 22

Longitudinal study from aged 3-20, recording stressful life events (abuse during childhood, romantic disasters, illnesses, job crisis). Followed 847 people up for more than 20 years. Found a functional polymorphism in the serotonin transporter gene which moderated the influence of stressful life events
Short short allele - more susceptible to develop depression, but only if coupled with life events - more stressful life events, more depression / suicide attempts
Long long - well protected, but long long is more associated with psychopathology

Question 23

What did Caspi et al provide evidence for?

Answer 23

A gene by environment interaction - individuals response to environmental insults is moderated by his or her genetic make up

Question 24

What are further findings on the serotonin transporter?

Answer 24

Rausch et al - depressed people with two long alleles were more likely to respond to treatment with an antidepressant drug than those who had one or two short alleles - 2 long more likely to respond to placebo too
Lee et al - found that depressed people with two long alleles who were treated with antidepressant drugs had a much better long term outcome (3 years) than did people with one or two short alleles
Neumeister et al - tryptophan depletion was more likely to produce symptoms of depression in people with one or short short alleles