Depression

Unipolar depression

- Mixed Anxiety and depression

Bipolar Depression

- Bipolar Affective disorder with manic episodes

Brain changes in depression

Nucleus Accumbens: Decrease in volume and bold signal during reward related task

Ventral Tegmental Area: NA

Hippocampus: Decrease in volume during positive word encoding task

Basolateral Amygdala: Decrease in volume and increase in resting state BOLD signal

Medial prefrontal cortex: Decrease in volume and decrease in BOLD signal during reversal learning task

Genetics

• Twin studies
• Concordance rate higher for Bipolar disorder

Learned Helplessness

• Animals show biological features of depression. REM sleep alterations, loss of bodyweight, diminished sexual activity elevated in corticosterone
• Links to cognitive function to biological function
• Brain Noradrenaline levels recover after 48 hours

Neurochemical Hypothesis

• Depression due to depletion of monoamines EXAMPLE: Noradrenaline, serotonin, dopamine originated as drugs that depleted such as reserpine neurotransmitters
• Reserpine depressed due to reduced levels of noradrenaline
• Serotonin involved in pain sensitivity, emotionality and response to negative consequences
• Mutation: Repeat length polymorphism in photometer region

Monoamine Oxidase Inhibitors

• Inhibiting the enzyme monoamine oxidadase MAO that breaks down serotonin
• Blocking the transporter protein for serotonin re-uptake 
• Major mechanism controlling extracellular monoamine dynamics is reuptake
• This is achieved through presynaptic neurons via plasma membrane transporters
• These remove neurotransmitters from outside the cells and recycle back into releasing or neighboruing terminals

Tricyclics

• Inhibit reuptake of noradrenaline and serotonin

SSRIs

• Inhibit reuptake of serotonin

SSNRIs

• Act via inhibition of reuptake of 5HT and NA

• CRF is a major neuropeptide mediator of stress response in the CNS
• It is expressed in the paraventricular nucleus of the hypothalamus and co-ordinates the release of ACTH from the anterior pituitary
• CRF increased in CSF of depressed patients

HPA Axis

• CRF released in response to environmental stressor
• ACTH is then released by the pituitary
• Which in turn releases cortico steroids
• When stressor terminated negative feedback occurs, shut down of the HPA Axis

CRF and Depression

• Elevated corticosteroids good context of stress
• Elevated in times of threat
• Elevated chronically at times of loss of control
• However transient activation does not cause stress, seen following drugs such as amphetamine and novelty
• Excessive long term activation of HPA may induce long term damage
• LEADS to: Enlargement of adrenal glad
• AD lower activity in HPA axis