Jensen, J. E. | Search bioRxiv

bioRxiv2022

Anterior cingulate metabolite levels, memory, and inhibitory control in abstinent men and women with Alcohol Use Disorder

AimsAlcohol use disorder (AUD), has been shown to have harmful cognitive and physiological effects, including altered brain chemistry. Further, although men and women may differ in vulnerability to the neurobiological effects of AUD, results of existing studies have been conflicting. Brain metabolite levels and cognitive functions were examined in a cross section of men with AUD (AUDm) and women with AUD (AUDw) to determine degree of abnormalities after extended periods of abstinence (mean, six years), and to evaluate gender differences in cognitive and metabolite measures. MethodsParticipants were 40 abstinent individuals with AUD (22 AUDw, 18 AUDm) and 50 age-equivalent non-AUD comparison participants (26 NCw, 24 NCm). Proton magnetic resonance spectroscopy (MRS) was employed at 3 Tesla to acquire metabolite spectra from the dorsal anterior cingulate cortex (dACC). Brain metabolites N-acetylaspartate (NAA), choline (Cho), myo-Inositol (mI), and glutamate & glutamine (Glx) were examined relative to measures of memory and inhibitory control. ResultsMetabolite levels in the AUD group showed no significant differences from the NC group. Memory and inhibitory-control impairments were observed in the AUD group. There also were significant group-specific associations between metabolite ratios and measures of inhibitory control. There were no Group-by-Gender interactions for the four metabolite ratios. ConclusionsThese findings demonstrate that brain metabolite levels in men and women with AUD, following long-term abstinence, do not differ from individuals without AUD. The data also provide evidence of associations between metabolite levels and measures of inhibitory control, a functional domain important for curtailing harmful drinking.

neuroscience↗

bioRxiv2020

Glutamatergic adaptation to stress in medial prefrontal cortex underlies risk and resilience for pessimistic beliefs

Stress is a major risk factor for the development of mental illness, including major depressive disorder (MDD), yet the underlying biological mechanisms remain unclear. Particular challenges lie in disentangling adaptive versus maladaptive responses to repeated stress exposure. Preclinically, stress-induced changes in glutamatergic function have been frequently observed in the medial prefrontal cortex (mPFC), a key region for mediating adaptive stress responses. Here, we examined stress-induced changes in mPFC glutamate using magnetic resonance spectroscopy (MRS) in four human samples varying in perceived stress exposure. Changes in mPFC glutamate following an acute stressor were reliably moderated by recent perceived stress in healthy controls. This adaptive glutamate response was absent in unmedicated individuals with MDD and was associated with excessively pessimistic beliefs as assessed via ecological momentary assessments over a 1-month follow-up period. Taken together, these data provide novel evidence for glutamatergic adaptation to stress in mPFC that is significantly disrupted in MDD.

neuroscience↗