Send to

Choose Destination
Biol Psychiatry. 2011 Sep 15;70(6):537-44. doi: 10.1016/j.biopsych.2011.04.019.

Rare copy number deletions predict individual variation in human brain metabolite concentrations in individuals with alcohol use disorders.

Author information

Department of Psychology, University of New Mexico, Albuquerque, New Mexico, USA.



Although variations in neurometabolite concentrations occur in diverse neuropsychiatric and neurodegenerative disorders, little is known about the nature of underlying genetic influences. The current study investigated the importance of a specific type of genetic mutation, copy number variation (CNV), for neurometabolite concentrations in a bilateral anterior cingulate voxel.


These neurometabolic signals were quantified using proton magnetic resonance spectroscopy ((1)H-MRS): N-acetylaspartate (NAA), creatine-phosphocreatine (Cre), glutamate/glutamine (Glx), myoinositol (mI), and phosphorylcholine-glycerol phosphorylcholine (Cho). Genetic data were collected using the Illumina 1MDuoBeadChip Array from a sample adults with alcohol use disorders (n = 146).


The number of base pairs lost through rare copy number deletions (occurring in less than 5% of our sample) predicted lower NAA, Cre, mI, and Glx. More total rare deletions also predicted lower NAA, Cre, and Glx. Principal components analyses of the five neurometabolites identified two correlated components, the first comprised of NAA, Glx, and Cre, and the second comprised of Cho, mI, and to a lesser extent, Cre. The number and length of rare deletions were correlated with the first component, capturing approximately 10% of phenotypic variance, but not the second component.


These results suggest that mutation load affects neurometabolite concentrations, potentially increasing risk for neuropsychiatric disorders. The greater effect of CVNs on NAA, Glx, and Cre may reflect a greater sensitivity to the effects of mutations (i.e., reduced canalization) for neurometabolites related to metabolic activity and cellular energetics, due to extensive recent selection pressure on these phenotypes in the human lineage.

[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms


Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center