The effect of age and sex on brain metabolites: from childhood to adulthood

Ortuño, María; Fortea, Adriana; Valli, Isabel; Muñoz-Moreno, Emma; Borràs, Roger; Martínez-Serrano, Irene; Masias Bruns, Mireia; Camprodon-Boadas, Patricia; Vilajosana, Enric; Fortea, Lydia; Raduà, Joaquim; Serna, Elena de la; Baeza, Inmaculada; Castro-Fornieles, Josefina; Sugranyes, Gisela

doi:http://dx.doi.org/10.1016/j.neuroimage.2025.121353

The effect of age and sex on brain metabolites: from childhood to adulthood

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Ortuño M, Fortea A, Valli I, Muñoz-Moreno E, Borràs R, Martínez-Serrano I, et al. The effect of age and sex on brain metabolites: from childhood to adulthood. Neuroimage. 2025 Aug 15;317:121353. DOI: 10.1016/j.neuroimage.2025.121353

Abstract

Abnormalities in the concentration of brain metabolites have been found across neuropsychiatric conditions. This cross-sectional study set out to examine the relationship between levels of neurometabolites and age and sex —key modulators of brain function and structure—, continuously from childhood to early adulthood, in areas relevant to the study of psychiatric disorders. Magnetic resonance spectroscopy (¹H MRS) data was acquired in the dorsomedial prefrontal region (dmPF) and the medial temporal lobe (mTL) in 128 healthy individuals aged 7 to 34 years, 68.5 % females (ndmPF = 124; nmTL = 75). Absolute concentrations of glutamate (Glu), glutamate and glutamine (Glx), myo-inositol (mIns), N-acetyl-aspartate and N-acetyl-aspartyl-glutamate (tNAA), glycerophosphocholine and phosphocholine (tCho), and creatine and phosphocreatine (tCr) were determined, and tested for the effects of age, sex and their interaction. In the dmPF, there were linear, age-related decreases in Glu and Glx. The association between levels of both tNAA and tCr and age adjusted to a quadratic model, consisting of a positive association until ages 20.79 and 22.82, respectively, and a negative relationship thereafter. There was a significant effect of sex in the mTL, whereby concentrations of Glu, Glx and mIns were lower in females than in males. No age by sex interactions were detected. These findings highlight the importance of accounting for both linear and non-linear age-related effects and for the potential effect of sex when interpreting disease-related differences in ¹H MRS-quantified metabolites from childhood through to adulthood.