LEC 15: Depression

What is Major Depression Disorder?

a mood disorder where individuals experience persistent feeling of sadness and hopelessness, and lose interest in activities they once enjoyed

Prevalence of depression

• the most common mood disorder, affects 1 in 6 people

• twice as many females diagnosed relative to males

Diagnostic criteria for depression

• persistent feeling of sadness

• loss of interests in activities

• diminished ability to concentrate, or indecisiveness

• excessive inappropriate guilt

How depressive disorders present differently in males and females

• may have psychosocial explanation, such as social discrimination

• Links between estrogen and the HPA axis:

  • estrogen itself seems protective against stress and depression

  • the negative feedback system is more efficient during the follicular phase, when estrogen is high

  • females show lower cortisol levels in response to social stress during the follicular phase

  • mood tends to drop during luteal phase

Etiology of depression

There is extensive evidence for a genetic link to depression but the non-genetic, environmental component is still larger

• example: stressful life events

Monoamine Hypothesis

• it was thought that depression was strictly due to a deficit in monoamine signaling

• monoamine: neurotransmitters that contain one amino group connected to an aromatic ring by a two-carbon chain

Evidence for and against the monoamine hypothesis

Evidence for:

• drugs that are effective in treating depression target these systems:

  • MAO inhibitors are effective antidepressants

  • Selective serotonin reuptake inhibitors (SSRIs) are antidepressants that block the reuptake of serotonin at the synapse

  • Selective noradrenergic reuptake inhibitors (SNRIs) are antidepressants that block the reuptake of noradrenaline at synapses

Evidence against:

• there is little evidence that low levels of these neurotransmitters cause depression

• long lag time between treatment and reduction of symptoms

• SSRIs increase risk of suicide in children and adolescents

The glucocorticoid hypothesis of depression

Suggests that dysfunctional regulation of the HPA axis stress response contributes to depression

HPA axis dysregulation in depression

• hypercortisolemia

  • chronic stress can lead to oversecretion of cortisol, associated with depression in adulthood

• impaired negative feedback of HPA axis

  • people with depression cannot shut down their stress response as easily

Depression and the hippocampus

• there is evidence that the hippocampus is damaged by chronic major depression

• neuroimaging shows reduction in hippocampal volume in patients with depression

• however, antidepressants can help by increasing the rate of neurogenesis in the hippocampus, reversing the damage

Psilocybin

• a compound found in various species of fungi (mushrooms) that may reduce symptoms of depression

• an agonist to several serotonergic receptors and structurally similar to serotonin

SSRIs at the synapse

• following release, excess serotonin is broken down by the enzyme monoamine oxidase (MAO), and is also cleared by serotonin reuptake transporters

• SSRIs work primarily by blocking serotonin reuptake transporters

• this leads to an increase in serotonin in the synapse