Neurochemistry

Brain concentrations of monoamine neurotransmitters, and/or sensitivity of their receptor sites, appear to be altered in affective disorders. Noradrenaline (NA) and/or 5-hydroxytryptamine (5-HT, serotonin) are implicated in depressive illness; dopamine is implicated in mania. Evidence for neurotransmitter involvement includes the following points:

• Most drugs that are effective in treating depression increase the availability of NA and/or 5-HT in the brain.

Antihypertensive drugs, such as reserpine, that deplete brain monoamine concentrations, can cause depression.

• Antipsychotic drugs, which block dopamine receptors, have a therapeutic effect in mania.

• Plasma concentration of tryptophan, a precursor of 5-HT, and the concentration of 5-HT in platelets are reduced in some depressed patients.

Cerebrospinal fluid (CSF) concentrations of the amine metabolites 5-HIAA (5-hydroxyindole acetic acid), HVA (homovanillic acid), and MHGP (methoxy-hydroxy-phenylethylene glycol), as well as urine concentrations of MHGP, are reduced in some depressed patients.

• Post-mortems on depressed patients who died by suicide show low concentrations of 5-HT and 5-HIAA in the brain itself.

Such studies are difficult because delicate measurements are involved; concentrations of amine metabolites may reflect changes in the rest of the body rather than the brain itself; and findings may be affected by diet, exercise, and diurnal rhythms.

Drugs that affect other neurotransmitters such as NA are as effective as anti-depressants as those that predominantly affect serotonin. Thus, simplistic theories of depression as a chemical imbalance ('your stores of serotonin are running out') are incompatible with the complexity of the various neurotransmitters and various receptors for them, as delineated by psychopharmacologists.

It seems likely that the neurochemical disturbance in depression is the route - or final common pathway - by which the depression is produced, rather than the ultimate origin of it.

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