Virtually all
antidepressant and
antipsychotic drugs, including
clozapine,
rimcazole and
lithium ion, are proconvulsants, and convulsive therapy, using
metrazol, a known
GABA-A antagonist, as well as electro-convulsive therapy, can be effective in treating both
schizophrenia and
affective psychoses. Many
antidepressant and
antipsychotic drugs, including
clozapine, as well as some of their metabolites, reverse the inhibitory effect of
GABA on 35S-TBPS binding, a reliable predictor of
GABA-A receptor blockade. A review of relevant literature suggests that 1) "functional"
psychoses constitute a continuum of disorders ranging from
schizophrenia to
affective psychoses with overlap of symptoms, heredity and treatments, 2) a weakening of GABergic inhibitory activity, or potentiation of counterbalancing glutamatergic neurotransmission, in the brain, may be involved in the therapeutic activities of both
antidepressant and
antipsychotic drugs, and 3)
schizophrenia and the
affective psychoses may be different expressions of the same underlying defect: GABergic preponderance/glutamatergic deficit.
Schizophrenia and
affective psychoses share the following: 1) several treatments are effective in both, 2) similar modes of inheritance, 3) congruent seasonal birth excesses, 4) enlarged cerebral ventricles and cerebellar vermian
atrophy, 5)
dexamethasone non-suppression. Both genetic and environmental factors are involved in both
schizophrenia and
affective psychoses, and several lines of evidence suggest that important environmental factors are neurotropic pathogens that selectively destroy glutamatergic neurons. One group of genes associated with
psychoses may increase vulnerability to attack and destruction, by neurotropic pathogens, of excitatory glutamatergic neurons that counterbalance inhibitory GABergic neurons. A second group of genes may encode subunits of overactive
GABA-A receptors, while a third group of genes may encode subunits of hypo-active
glutamate receptors. Improved
antipsychotic drugs may be found among selective blockers of
GABA-A receptor subtypes and/or enhancers of glutamatergic neurotransmission. A mechanism similar to kindling, leading to long-lasting reduction of GABergic inhibition in the brain, may be involved in several treatments of
psychoses.