Evidence for the segregation of a major gene for human plasma GABA levels

Gamma-aminobutryic acid (GABA) is a major neurotransmitter in the central n ervous system, and plasma levels of GABA may reflect brain GABA activity. I n 35-40% of patients with mood disorders, plasma GABA levels are low compar ed to psychiatrically normal controls.' Low plasma GABA in this subgroup of patients has characteristics of a biological trait marker for mood disorde rs. Low plasma GABA is also found in a subset of patients with alcohol depe ndence, but not in schizophrenia, anxiety, or eating disorders, suggesting some diagnostic specificity.(2) Previous data from a small study of monozyg otic twins are consistent with the hypothesis that plasma GABA levels are u nder genetic control.(3) To better understand these mechanisms, we conducte d a segregation analysis of plasma GABA levels in a sample of 157 individua ls from 50 nuclear families. Analysis using the Class D regressive model in dicated that the familial transmission of plasma GABA levels is compatible with the segregation of a recessive major gene. Our results suggest that pl asma GABA levels are under single gene control. Future research should addr ess the precise mechanisms which may account for the abnormality in GABA le vels seen in a subset of patients with mood disorders.