Neurochemical metabolite characteristics of the ventromedial prefrontal cortex in adolescents with bipolar depression comorbid with obsessive-compulsive symptoms

ObjectiveTo investigate the neuro-metabolic mechanisms underlying obsessive-compulsive symptoms (OCS) in adolescents with bipolar disorder (BD) during depressive episodes, and to analyze the association between ventromedial prefrontal cortex (vmPFC) neurometabolite levels and OCS.MethodsThis retrospective study included 65 adolescents (aged 13-19) with BD depressive episodes. Based on the presence of OCS and scores on the Children’s Yale-Brown obsessive-compulsive scale (CY-BOCS ≥16 or ≤7), participants were divided into an OCS group ( n=31) and a non-OCS group ( n=34). Proton magnetic resonance spectroscopy (¹H-MRS) was used to measure vmPFC metabolite, including N-acetylaspartate (NAA), the glutamic acid and glutamine complex (Glx), and creatine (Cr), and to calculate their ratios (NAA/Cr, Glx/Cr, etc.). Associations with OCS were assessed using binary logistic regression, receiver operating characteristic (ROC) curves, and tertile analysis.ResultsThe OCS group showed lower NAA/Cr (median: 1.64 vs. 1.74, P=0.045) and Glx/Cr (median: 0.76 vs. 0.96, P=0.022) in the vmPFC compared to the non-OCS group; differences remained significant after adjusting for age and sex ( PP>0.05). Reduced NAA/Cr was independently associated with OCS ( OR=0.156, 95% CI: 0.032-0.759, P=0.021). The ROC curve for NAA/Cr yielded an AUC of 0.670 (95% CI: 0.532-0.807, P=0.016), with an optimal cutoff of 1.679, sensitivity of 54.8%, and specificity of 79.4%. Tertile analysis indicated a possible nonlinear relationship between NAA/Cr and OCS: Using the lowest tertile (NAA/Cr valuesOR of 0.217 (95% CI: 0.057-0.824, P=0.025), while the highest tertile (NAA/Cr values>1.803) showed a borderline association ( OR=0.280, 95% CI: 0.078-1.014, P=0.053), with no linear trend ( Ptrend=0.062).ConclusionLower vmPFC NAA/Cr may be related to the neurobiological mechanism of OCS in adolescents with BD depression, but its discriminative ability is limited. Further validation using multimodal indicators is warranted.