Major Depressive Disorder (MDD)

Symptoms

- chronic emptiness
- unyielding sadness
- hopelessness
- restlessness
- fatigue
- reduced interest in or pleasure from hobbies/socializing/family/friends (anhedonia)
- suicidal ideations
- changes in eating/sleeping habits
- impaired concentration/speech
- poor grooming
- irritability
- substance use

Treatment

- antidepressants (can take 2-8 weeks to take effect)
- antianxiety drugs (can take 2-8 weeks to take effect)
- antipsychotic drugs
- psychotherapy
- electroconvulsive therapy (ECT) (last resort)

Monoamine Hypothesis of MDD

a decrease in the level of monoamine neurotransmitters (norepinephrine, dopamine, and serotonin) causes the depression

Monoamine Receptor Hypothesis of MDD

the low levels of monoamine NTs cause the brain to produce more receptors (upregulation) for these molecules in order to absorb as many as possibe

Why does the clinical effect of antidepressants take 2-6 (sometimes 8) weeks?

although the levels of monoamine NTs increase rapidly after the introduction of an antidepressant (usually through blocking the reuptake of the NTs by the presynaptic neuron), the levels of monoamine receptors must reduce (longer process) before the clinical effects can be seen (high [NT] + low [NT receptors] = less depression)

Neurotrophic Hypothesis of MDD

- prolonged increased cortisol levels (as seen in depression) inhibit the formation of brain-derived neurotrophic factor (BDNF)
- decreased BDNF causes a decrease in synaptic connections, neuroplasticity, and neurogenesis (overall decrease in brain health/size/activity, specifically the hippocampus)

Neuroendocrine Hypothesis of MDD

- typically cortisol binds to glucocorticoid receptors (GRs) in the hippocampus and pituitary gland to shut off the HPA axis (negative feedback) (see GAD flashcards for info on HPA axis)
- prolonged increased cortisol levels cause the loss of the negative feedback mechanism by decreasing the sensitivity of GRs (cortisol production increases)
- hypercortisolemia in the brain changes the emotion-cognitive circuitry by uncoupling the amygdala from the hippocampus (adaptive learning) and increasing connectivity with the striatum (habitual learning) leading to depressive symptoms

What factors make someone more likely to be predisposed to MDD?

- genetics
- altered brain chemistry (monoamine hypothesis)
- poverty
- social isolation
- adverse life events (child abuse, loss, illness, etc.)
- lack of close, confiding relationships
- female gender