Neurometabolic profiles of the ventromedial prefrontal cortex in adolescents with bipolar depression and clinically significant obsessive–compulsive symptoms: a cross-sectional proton magnetic resonance spectroscopy study

This study aimed to compare ventromedial prefrontal cortex (vmPFC) neurometabolites in adolescents with bipolar II disorder (BD-II) with and without clinically significant obsessive-compulsive symptoms (OCS) and examine their clinical associations. A total of 28 adolescents with BD-II depression and clinically significant OCS (BD-II-OCS), 30 adolescents with BD-II depression without OCS (BD-II-non-OCS), and 26 healthy controls (HCs) were recruited. N-acetylaspartate-to-creatine (NAA/Cr), choline-containing compounds-to-creatine (Cho/Cr), myo-inositol-to-creatine (mI/Cr), and glutamate plus glutamine-to-creatine (Glx/Cr) ratios in the vmPFC were measured using single-voxel proton magnetic resonance spectroscopy (¹H-MRS). Compared with the HC group, the NAA/Cr ratio was significantly lower in both BD-II groups, with the lowest value in the BD-II-OCS group; the Glx/Cr ratio was also significantly lower in the BD-II-OCS group than in the other two groups. These group differences remained significant after adjustment for illness duration and other covariates. The BD-II-OCS group had a longer illness duration than the BD-II-non-OCS group, and Glx/Cr was negatively correlated with HDRS-24 scores only within the BD-II-non-OCS group. In exploratory in-sample ROC analysis, NAA/Cr yielded an AUC of 0.870 for discriminating BD-II-OCS from HC and an AUC of 0.733 for discriminating between the two patient groups. Adolescents with BD-II depressive episodes accompanied by clinically significant OCS exhibited lower vmPFC NAA/Cr and Glx/Cr ratios, suggesting possible alterations in neuronal integrity and glutamatergic metabolism. NAA/Cr showed preliminary in-sample discrimination, but independent validation across the full OCS severity range is required.