Depression - Neurochemistry

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Early research into biological factors in depression centered upon monoaminergic theories with particular focus first on norepinephrine and later serotonin.

This work followed a number of pharmacological observations following the use of various compounds eg:

Reserpine, an early antihypertensive, caused depression in some patients and depleted monoamine stores in rat brain;
Iproniazid, a drug studied as an antitubercular agent, elevated depressed mood and inhibited monoamine degradation by the enzyme, monoamine oxidase;
Imipramine, a tricyclic compound originally studied as an antipsychotic,had marked antidepressant effects and blocked the reuptake of norepinephrine (and to some extent serotonin) into presynaptic neurons.

These observations led researchers to argue that norepinephrine activity was decreased in depressive disorders and elevated in manic or excited states. This was idea was further developed by Schildkraut’s catecholamine hypothesis of depression

Other researchers proceeded by comparing groups of normal and depressed people and identified a number of differences in depressives.

Elevated corticotropin-releasing hormone (CRH);
Elevated acetylcholine activity;
Increased Gamma-aminobutyric acid (GABA) levels;
Excessive glucocorticoid activity in psychotic major depression;
Hippocampal volume loss,perhaps reflecting the effects of excessive glucocorticoids onneurogenesis .