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Background: It has been suggested that the dorsolateral prefrontal cortex (DLPFC), especially the left DLPFC, has an important role in the pathophysiology and the treatment of major depressive disorder (MDD); furthermore, the contributory and antidepressant role of y-aminobutyric acid (GABA) is increasingly recognized. Given that most female patients with MDD are of reproductive age, we sought to assess in vivo baseline GABA levels in the left DLPFC among unmedicated females of reproductive age with depression. Methods: We compared healthy females and females with MDD. Both groups were of reproductive age. We confirmed absence of current or past psychiatric diagnosis among healthy controls or a current diagnosis of MDD via a structured interview. We measured GABA+ (including homocarnosine and macromolecules), referenced to creatine and phosphocreatine, via magnetic resonance spectroscopy using a 3 Tesla magnet. Results: We included 20 healthy controls and 13 participants with MDD. All participants were unmedicated at the time of the study. All females were scanned during the early follicular phase of the menstrual cycle. Levels of GABA+ in the left DLPFC were significantly lower among participants with MDD (median 0.08) than healthy controls (median 0.10; U = 66.0, p = 0.02, r = 0.41). Limitations: When we adjusted for fit error as a covariate, we lost statistical significance for left DLPFC GABA+. However, when we adjusted for signal-to-noise ratio, statistical significance was maintained. Conclusion: Our results suggest that GABA+ levels in the left DLPFC may vary by depression status and should be examined as a possible treatment target., Introduction It has been suggested that the dorsolateral prefrontal cortex (DLPFC), especially the left DLPFC, has a role in the pathophysiology and the treatment of major depressive disorder (MDD). Positron [...]