Functional brain abnormalities in adolescents and young adults with bipolar depression with mixed features: Insights from resting-state fMRI

J Psychiatr Res. 2025 Sep 3;190:490-498. doi: 10.1016/j.jpsychires.2025.09.001. Online ahead of print.

ABSTRACT

OBJECTIVE: Bipolar depression with mixed features (BD-MF) is a distinct subtype of bipolar disorder (BD), characterized by emotional instability, impulsivity, and an elevated risk of suicide. However, its neurobiological mechanisms remain poorly understood. This study aims to investigate these mechanisms in BD-MF patients using resting-state fMRI.

METHODS: A total of 208 adolescents and young adults with bipolar depression episodes and 169 healthy controls (HC) were recruited. The final analysis included 78 patients with BD-MF, 110 patients with bipolar depression without mixed features (BD-nMF), and 164 HC. The patients were classified according to DSM-5 criteria. Clinical assessments were conducted using the Hamilton Depression Rating Scale-17 (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), and Young Mania Rating Scale (YMRS). Resting-state fMRI was analyzed using the mean fractional amplitude of low-frequency fluctuations (mfALFF) to identify functional abnormalities, and correlations between mfALFF values and clinical symptoms were examined.

RESULTS: BD-MF patients exhibited significantly increased mfALFF values in the right precuneus, left inferior parietal lobule, and right middle frontal gyrus compared to BD-nMF and HC (P < 0.05, FDR corrected). Hyperactivation of the right precuneus correlated with mixed features (r = 0.364, P < 0.001) and agitation scores (r = 0.275, P < 0.001). Left inferior parietal lobule activity correlated with suicide scores (r = 0.241, P < 0.001), and right middle frontal gyrus hyperactivation correlated with mixed features (r = 0.293, P < 0.001).

CONCLUSIONS: This study identified significant increases in brain activity in the right precuneus, left inferior parietal lobule, and right middle frontal gyrus in BD-MF patients. These regions may serve as potential neuroimaging biomarkers for BD-MF, with their activation patterns correlating with mixed features, agitation, and suicide risk. Future research should explore the temporal dynamics and clinical relevance of these changes to enhance diagnostic and therapeutic strategies.

PMID:40912055 | DOI:10.1016/j.jpsychires.2025.09.001