Are there specific abnormalities in activity and functional connectivity in emotion processing and regulation neural circuitries in offspring at risk for bipolar disorder?
In this cross-sectional study, relative to offspring of healthy parents, offspring of parents with bipolar disorder had significantly greater right rostral anterior cingulate cortex activity when regulating attention away from happy faces, which was significantly positively correlated with affective lability symptom severity. Additionally, offspring of parents with bipolar disorder had significantly greater amygdala to left caudal anterior cingulate cortex functional connectivity to fearful faces relative to offspring of parents without bipolar disorder but with other psychiatric disorders.
Greater activity and functional connectivity during emotion regulation tasks in the anterior cingulate cortex may help distinguish youth at risk for bipolar disorder from healthy youth and from youth at risk for other psychiatric disorders.
Bipolar disorder (BD) is difficult to distinguish from other psychiatric disorders. Neuroimaging studies can identify objective markers of BD risk.
To identify neuroimaging measures in emotion processing and regulation neural circuitries and their associations with symptoms specific to youth at risk for BD.
Design, Setting, and Participants
This cross-sectional (August 1, 2011, to July 31, 2017) and longitudinal (February 1, 2013, to November 30, 2017) neuroimaging study performed at the University of Pittsburgh Medical Center compared a sample of 31 offspring of parents with BD (OBP) with 28 offspring of comparison parents with non-BD psychopathologies (OCP) and 21 offspring of healthy parents (OHP); OBP, OCP, and OHP were recruited from the Bipolar Offspring Study and the Longitudinal Assessment of Manic Symptoms Study.
Main Outcomes and Measures
Group differences in activity and functional connectivity during emotional face processing and n-back task performance in amygdala, dorsolateral and ventrolateral prefrontal cortices (PFC), caudal anterior cingulate cortices (cACC), and rostral anterior cingulate cortices (rACC) neuroimaging measures showing between-group differences and symptom severity (anxiety, affective lability, depression, mania). We hypothesized that elevated amygdala activity and/or lower PFC activity and abnormal amygdala to PFC functional connectivity would distinguish OBP from OCP and OHP, and magnitudes of these abnormalities would positively correlate with elevated symptom severity. We explored associations between changes in neuroimaging and symptom measures over follow-up (mean [SD], 2.9 [1.4] years) in a subset of participants (n = 30).
Eighty participants were included (mean [SD] age, 14.2 (2.1) years; 35 female). Twelve neuroimaging measures explained 51% of the variance in the results of neuroimaging measures overall. Of the 12, 9 showed significant main associations of the group; however, after post hoc analyses and Bonferroni corrections, only 7 showed statistically significant associations between groups (corrected P < .05 for all). Of the 7, 2 showed significant relationships with symptoms. Offspring of parents with BD had greater right rACC activity when regulating attention to happy faces vs OCP (mean [SD] difference, 0.744 [0.249]; 95% CI, 0.134-1.354; P = .01), which positively correlated with affective lability severity (ρ = 0.304; uncorrected P = .006). Offspring of parents with BD had greater amygdala to left cACC functional connectivity when regulating attention to fearful faces vs OCP (mean [SD] difference, 0.493 [0.169]; 95% CI, 0.079-0.908; P = .01). Increases in this measure positively correlated with increases in affective lability over follow-up (r = 0.541; P = .003).
Conclusions and Relevance
Greater anterior cingulate cortex activity and functional connectivity during emotion regulation tasks may be specific markers of BD risk. These findings highlight potential neural targets to aid earlier identification of and guide new treatment developments for BD.
Acuff HE, Versace A, Bertocci MA, et al. Association of Neuroimaging Measures of Emotion Processing and Regulation Neural Circuitries With Symptoms of Bipolar Disorder in Offspring at Risk for Bipolar Disorder. JAMA Psychiatry. 2018;75(12):1241–1251. doi:10.1001/jamapsychiatry.2018.2318
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