Inhibitory neurotransmission in frontostriatal circuitry: implications for psychomotor and vegetative symptoms in depressive episodes

Background Gamma-aminobutyric acid (GABA) dysfunction has been implicated in depression, although research findings remain inconsistent. This may indicate that distinct biological mechanisms underlie different symptom profiles in depressive episodes. GABA deficiency might be especially relevant in cases characterised by psychomotor retardation and vegetative symptoms, which are prominent in melancholia. This study aimed to investigate if such melancholic features are related to GABA levels or GABA _A -receptor availability. Methods Forty-two patients diagnosed with either bipolar or unipolar depression were assessed both before and after a clinical trial involving repetitive transcranial magnetic stimulation. GABA and glutamate levels in the dorsal anterior cingulate cortex (dACC) were measured using a [ ¹ H] magnetic resonance spectroscopy MEGA-PRESS sequence. A subset of 28 patients underwent [ ¹¹ C]flumazenil positron emission tomography (PET) to evaluate GABA _A -receptor availability in the dACC, basal ganglia, and hypothalamus. Psychomotor retardation was assessed using the expressive subscale of the Clinical Assessment Interview for Negative Symptoms. Sleep disturbances were evaluated using components of the Pittsburgh Sleep Quality Index, while appetite loss was measured using an item from the Montgomery-Åsberg Depression Rating Scale – Self-rated. The scores were standardised and combined to create composite measures for vegetative and somatic symptoms. Additionally, baseline psychomotor activity was measured using accelerometry. Results The findings did not establish that psychomotor or vegetative symptoms were associated with GABA levels or GABA _A -receptor availability in the frontostriatal pathways or hypothalamus. Conclusions To better understand the relationship between GABA dysfunction and melancholic features, future studies should ideally focus on patients exhibiting more pronounced psychomotor and vegetative symptoms. Trial registration: Not applicable.