Stability of plasma GABA at four-year follow-up in patients with primary unipolar depression

The biology of mood disorders involves γ-aminobutyric acid (GABA), a neurotransmitter whose levels in plasma likely reflect brain GABA activity. Previous research has shown that a subset of patients with primary unipolar major depression have low plasma GABA levels, which parallels findings from studies of cerebrospinal fluid. We have completed a 4-year follow-up on 46 male patients with primary unipolar depression. Plasma levels of GABA were stable over this time. For the group, mean plasma GABA levels on follow-up did not change significantly from entry levels. Plasma GABA levels measured on follow-up were significantly (p< .001) correlated with entry levels. Patients with low plasma GABA levels (< 100 pmol/ml) on entry into the study were likely to remain low on follow-up, and patients with plasma GABA levels in the control range (≥ 100 pmol/ml) at entry similarly remained in this category (X2 = 7.23, p = .007). This was true whether or not the patient had recovered from depression on follow-up. Levels of plasma GABA did not significantly correlate with severity of depression at either entry (p = .40) or follow-up (p = .52), nor was there a significant correlation between change in plasma GABA and change in the 17-item Hamilton Depression Rating Scale score from entry to follow-up (p = .89). These data are consistent with the notion that plasma GABA is independent of clinical state in patients with primary unipolar depression. Low plasma GABA may be a trait marker of illness in a subset of patients with mood disorder.