Age- and alcohol-related differences in adolescent neurometabolite levels

Adolescence is a critical period for neurometabolite maturation as well as the onset of alcohol use, yet remains underexplored despite its significance for long-term neurodevelopmental outcomes. We used 3T proton magnetic resonance spectroscopy (MRS) to examine age- and alcohol-related associations with six neurometabolites in dorsal anterior cingulate cortex (dACC) that are involved in key neural functions: glutamate + glutamine (Glx), GABA plus macromolecules (GABA+), total N-acetylaspartate (tNAA), total choline (tCho), total creatine (tCr), and myo-inositol (mI). Participants were 84 adolescents (ages 17 - 22; 67% female) who completed MRS scans and self-reported past-60-day alcohol use via a modified Timeline Followback survey. Alcohol use variables included total drinking days, total binge drinking days, total number of drinks, and drinks per drinking day. Older adolescents had higher levels of GABA+, tNAA, tCho, and mI, and lower levels of Glx and Glx/GABA+; tCr was not associated with age. More alcohol use - specifically more drinking days, binge drinking days, and number of drinks - was associated with lower tNAA levels. Findings suggest age-related variation in dACC neurometabolites, which potentially reflect ongoing neuronal maturation, myelination, and shifts in excitatory and inhibitory neurotransmission. Lower tNAA among heavier drinkers may reflect associations between alcohol exposure and neuronal damage. Broader neurometabolic effects may emerge only with heavier or prolonged alcohol use.