MRS Shows Regionally Increased Glutamate Levels among Patients with Exhaustion Syndrome Due to Occupational Stress.

Despite the rapid increase of reports of exhaustion syndrome (ES) due to daily occupational stress, the mechanisms underlying ES are unknown. We used voxel-based 1H-MR spectroscopy to examine the potential role of glutamate in this condition. The levels of glutamate were found to be elevated among ES patients (n = 30, 16 females) compared with controls (n = 31, 15 females). Notably, this increase was detected only in the anterior cingulate and mesial prefrontal cortex (ACC/mPFC), and the glutamate levels were linearly correlated with the degree of perceived stress. Furthermore, there was a sex by group interaction, as the glutamate elevation was present only in female patients. Female but not male ES patients also showed an increase in N-acetyl aspartate (NAA) levels in the amygdala. No group differences were detected in glutamine concentration (also measured). These data show the key role of glutamate in stress-related neuronal signaling and the specific roles of the amygdala and ACC/mPFC. The data extend previous reports about the neurochemical basis of stress and identify a potential neural marker and mediator of ES due to occupational stress. The observation of specific sex differences provides a tentative explanation to the well-known female predominance in stress-related psychopathology.