The Trajectory of Prefrontal GABA levels in Initially Antipsychotic-Naïve Patients with Psychosis during Two Years Treatment and associations with Striatal Cerebral Blood Flow and Outcome.

BACKGROUND: Gamma-aminobutyric acid (GABA)-ergic function in the prefrontal cortex seems dysfunctional in first-episode patients with psychosis, but the impact of longer-term treatment and relation to clinical outcomes as well as striatal activity are unknown.

METHODS: Longitudinal study of 39 antipsychotic-naïve and benzodiazepine-free patients with psychosis (22.4 ± 5.4 years, 64% females) and 54 matched healthy controls (HCs) (22.2 ± 4.3 years, 61% females) followed-up after six weeks (28 patients, 51 HCs), six months (17 patients, 47 HCs), and two years (21 patients, 43 HCs). GABA levels in dorsal anterior cingulate cortex (dACC) and striatal resting cerebral blood flow (rCBF) were assessed on a 3T MR scanner at all visits.

RESULTS: GABA levels in dACC were significantly lower in patients at baseline and after six weeks, but not after six months and two years. Analyses of groups separately revealed decreased GABA levels after two years in HCs but stable levels in patients. Treatment increased striatal rCBF after six weeks and six months but not after two years. GABA levels were negatively associated with striatal rCBF in both groups at all visits. Last, lower baseline GABA levels in patients were related to less functional improvement after two years.

CONCLUSIONS: The findings suggest a different trajectory of GABA levels and striatal perfusion in first-episode patients over two years of antipsychotic treatment compared with HCs and indicate a downregulatory role of prefrontal GABAergic function on striatum. Moreover, abnormally low prefrontal GABA level at illness onset may be a marker for a more severe prognosis.