Adolescents with bipolar disorder (BD) show altered reward circuit resting state functional connectivity (rsFC) phenotypes in the brain compared with those without BD, which may explain their heightened risk of self-harm, a recent study shows. The study exploring the association was recently published in Psychological Medicine.

Self-harm, both with and without suicide attempt, is the strongest predictor of future suicide attempt among youth and young adults age 10 to 24. BD is also a risk factor for suicide. To better understand why youth and young adults with BD have a higher risk of suicide than those without BD, the researchers analyzed resting-state fMRI images of the brain to explore reward circuit function. Reward circuit dysfunction is associated with both BD and self-harm.

The researchers recruited adolescents and young adults aged 13 to 20 with and without BD. The total population included 71 participants with BD and 70 without BD. Their results showed differences in rsFC in the left amygdala, right orbitofrontal cortex (OFC), and right dorsolateral prefrontal cortex (dlPFC), among other variations.

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“BD youth with and without a history of self-harm had decreased functional connectivity from the left nucleus accumbens seed to the left superior parietal lobule compared to [healthy control] youth,” the researchers reported. “There was no difference between BD youth with and without a history of self-harm, limiting the interpretation that this finding may be related to self-harm.”

The cross-sectional, observational design were both cited as limitations. Longitudinal studies may help determine whether connectivity patterns precede self-harm, the researchers stated. In addition, the study used one analytical approach. Follow-up studies using different methods and measurements may help provide additional useful insights.

“This study provides preliminary inferences regarding the neurobiology of self-harm among adolescents with BD, a group at extraordinarily high risk of suicide,” the researchers concluded. “With continued efforts, this line of research has the potential to yield objective indicators of self-harm risk that might assist with risk stratification and, ultimately, influence the process of selecting, targeting, and monitoring the effects of various preventive and treatment interventions for self-harm. In the interim, present findings may help reduce the blame, bias, and disadvantage faced by adolescents with mood disorders and self-harm.”


Dimick MK, Hird MA, Sultan AA, et al. Resting-state functional connectivity indicators of risk and resilience for self-harm in adolescent bipolar disorder. Psychol Med. Published online March 8, 2022. doi:10.1017/S0033291721005419