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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.

On the basis of these differences hypotheses have been developed for the causal role of a number of mechanisms in depression these include:

Chemical imbalance theory of mental health

  • Depression and beta-endorphin
  • Depression and norepinephrine
  • Depression and dopamine
  • Depression and GABA

See also


Key texts – Books

Additional material – Books

Key texts – Papers

  • Schatzberger,AF, Garlow, SJ and Nemeroff,CB, Molecular and cellular mechanisms in depression.Full text]

Additional material - Papers

External links


Neurochemistry of depression: Academic support materials

  • Neurochemistry of depression: Lecture slides
  • Neurochemistry of depression: Lecture notes
  • Neurochemistry of depression: Lecture handouts
  • Neurochemistry of depression: Multimedia materials
  • Neurochemistry of depression: Other academic support materials
  • Neurochemistry of depression: Anonymous fictional case studies for training