Finally, evidence for altered glutamate neurotransmission within the previously mentioned brain regions, as well as the anterior cingulate cortex (ACC), has been reported in clinical studies of alcohol-dependent individuals as well.124–131 For example, a proton magnetic resonance spectroscopy (MRS) study examining the role of hippocampal glutamate in major depression and risky alcohol drinking revealed that elevated glutamate levels in the hippocampus were directly associated with both the presence of major depression and self-reported risky drinking.132 These authors noted that the major depression and risky drinking group did not differ from the control group in age-of-first alcohol use, Alcohol Use Disorders Identification Test (AUDIT) survey scores or smoking behavior; but, this group did have significantly more FHP individuals (approximately six-fold) indicating a possible confound. Another recent MRS study provided support for differences in glutamate activity of FHP versus FHN individuals.133 These authors reported that glutamate/glutamine ratios increased significantly between adolescence and emerging adulthood in FHN, but not FHP, individuals. This suggests that having a familial history of AUDs may genetically predispose an individual for abnormal developmental changes in glutamatergic neurotransmission across periadolescence.133
