Measurement of GABA and glutamate-glutamine levels with 1 H-magnetic resonance spectroscopy in the neocortex of healthy subjects: the influence of age, sex, and education

INTRODUCTION : The two main neurotransmitters in the human brain are excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA). Measuring their levels in the living brain is an important readout for studies investigating the pathophysiology of psychiatric disorders. However, numerous factors may influence neurotransmitter levels; therefore, it is important to determine their effects. Here, we studied the effects of age, sex, and education level on glutamate and GABA levels. METHODS : A total of 69 healthy subjects, aged 18–49 years were investigated, with a sex ratio of 29 males / 40 females. GABA + and glutamate + glutamine (Glx) levels were measured using a MEGA-PRESS sequence at 3T in the anterior cingulate cortex (ACC). Water- and creatine-referenced GABA + and Glx measurements were performed to compare different referencing and correction approaches and examine the influence of demographic factors. RESULTS : We found a significant influence of sex, age, and education level on neurotransmitter levels. Glx levels were higher in the ACC in men than in women, whereas GABA+ levels were similar between the sexes. Age was positively correlated with GABA+ levels in the ACC in the entire cohort. In contrast, Glx levels were negatively correlated with age in the ACC of the entire cohort and in women only. Education level was negatively correlated with Glx levels in the ACC in men. CONCLUSION : Our data support the notion that both age and sex affect glutamate and GABA levels in the human brain. Furthermore, our results imply that MRS studies should also consider the education level of subjects.