Age- and alcohol-related differences in adolescent neurometabolite levels

Adolescence is a critical period for neurometabolite maturation as well as the initiation of alcohol use. However, despite its importance for long-term neurodevelopmental outcomes, the impact of alcohol use during adolescence on neurometabolites remains understudied.

We conducted an exploratory study using 3T proton magnetic resonance spectroscopy (1H-MRS) to examine age- and alcohol-related associations with six neurometabolites in the 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) with moderate-to-high alcohol use who completed 1H-MRS scans and self-reported their alcohol use. Alcohol use variables included as follows: estimated lifetime drinking episodes and past 60-day 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. There were no associations with lifetime drinking episodes.

In a sample of moderate-to-heavy drinking adolescents, findings suggest associations between age and neurometabolites in dACC neurometabolites, which potentially reflect ongoing neuronal maturation, myelination, and shifts in excitatory and inhibitory neurotransmission. Lower tNAA among recent heavier drinkers may reflect associations between alcohol exposure and neuronal damage. Broader neurometabolic effects may emerge only with heavier or prolonged alcohol use.