Cerebral Blood Flow and Core Mood Symptoms in Youth Bipolar Disorder: Evidence for Region-Symptom Specificity.

Abstract

Building on prior findings in adults, this study investigated regional cerebral blood flow (CBF) in relation to DSM-5 criterion A symptoms of depression and mania in youth with bipolar disorder (BD). The study recruited 81 youths with BD and 75 healthy controls 13-20 years old. CBF was ascertained using pseudocontinuous arterial spin labeling magnetic resonance imaging. Region-of-interest analyses examined the amygdala, anterior cingulate cortex (ACC), middle frontal gyrus, and global gray matter CBF. The association of criterion A depression and mania symptoms with CBF was examined dimensionally in youth with BD in regression analyses with continuous symptom severity scores. Age and sex were included as covariates. False discovery rate (FDR) was used to correct for 28 tests (4 regions by 7 symptoms; α< .0017). CBF for BD and healthy control groups was compared to give context for findings. In youth with BD, depressed mood inversely correlated with ACC (β=-0.31, puncorrected= .004, pFDR= .056) and global (β=-0.27, puncorrected= .013, pFDR= .09) CBF. The same pattern was observed for anhedonia (ACC CBF: β=-0.33, puncorrected= .004, pFDR= .056; global CBF: β=-0.29, puncorrected= .008, pFDR= .07). There were no significant findings for manic symptoms or in BD vs healthy control contrasts. The present findings, while not significant after correction for multiple testing, highlight the potential value of focusing on ACC in relation to depressed mood and anhedonia, and demonstrate that CBF is sensitive to depression symptom severity in youth. Lack of findings regarding manic symptoms may relate to the exclusion of fully manic participants in this outpatient sample.