Predicting Bipolar Disorder Risk Factors in Distressed Young Adults From Patterns of Brain Activation to Reward: A Machine Learning Approach

BACKGROUND: The aim of this study was to apply multivariate pattern recognition to predict the severity of behavioral traits and symptoms associated with risk for bipolar spectrum disorder from patterns of whole-brain activation during reward expectancy to facilitate the identification of individual-level neural biomarkers of bipolar disorder risk. METHODS: We acquired functional neuroimaging data from two independent samples of transdiagnostically recruited adults (18-25 years of age; n = 56, mean age 21.9 ± 2.2 years, 42 women; n = 36, mean age 21.2 ± 2.2 years, 24 women) during reward expectancy task performance. Pattern recognition model performance in each sample was measured using correlation and mean squared error between actual and whole-brain activation-predicted scores on behavioral traits and symptoms. RESULTS: In the first sample, the model significantly predicted severity of a specific hypo/mania-related symptom, heightened energy, measured by the energy manic subdomain of the Mood Spectrum Structured Interviews (r = .42, p = .001; mean squared error = 9.93, p = .001). The region with the highest contribution to the model was the left ventrolateral prefrontal cortex. Results were confirmed in the second sample (r = .33, p = .01; mean squared error = 8.61, p = .01), in which the severity of this symptom was predicted using a bilateral ventrolateral prefrontal cortical mask (r = .33, p = .009, mean squared error = 9.37, p = .04). CONCLUSIONS: The severity of a specific hypo/mania-related symptom was predicted from patterns of whole-brain activation in two independent samples. Given that emerging manic symptoms predispose to bipolar disorders, these findings could provide neural biomarkers to aid early identification of individual-level bipolar disorder risk in young adults

Elevated serum measures of lipid peroxidation and abnormal prefrontal white matter in euthymic bipolar adults: toward peripheral biomarkers of bipolar disorder

Diffusion tensor imaging (DTI) studies consistently reported abnormalities in fractional anisotropy (FA) and radial diffusivity (RD), measures of the integrity of white matter (WM), in bipolar disorder (BD), that may reflect underlying pathophysiologic processes. There is, however, a pressing need to identify peripheral measures that are related to these WM measures, to help identify easily obtainable peripheral biomarkers of BD. Given the high lipid content of axonal membranes and myelin sheaths, and that elevated serum levels of lipid peroxidation are reported in BD, these serum measures may be promising peripheral biomarkers of underlying WM abnormalities in BD. We used DTI and probabilistic tractography to compare FA and RD in ten prefrontal-centered WM tracts, 8 of which are consistently shown to have abnormal FA (and/or RD) in BD, and also examined serum lipid peroxidation (lipid hydroperoxides, LPH and 4-hydroxy-2-nonenal, 4-HNE), in 24 currently euthymic BD adults (BDE) and 19 age- and gender-matched healthy adults (CONT). There was a significant effect of group upon FA in these a priori WM tracts (BDECONT: F[1,41]=10.3; P=0.003), and a significant between-group difference in LPH (BDE>CONT: t[40]=2.4; P=0.022), but not in 4-HNE. Multivariate multiple regression analyses revealed that LPH variance explained, respectively, 59 and 51% of the variance of FA and RD across all study participants. This is the first study to examine relationships between measures of WM integrity and peripheral measures of lipid peroxidation. Our findings suggest that serum LPH may be useful in the development of a clinically relevant, yet easily obtainable and inexpensive, peripheral biomarkers of BD

Elevated serum measures of lipid peroxidation and abnormal prefrontal white matter in euthymic bipolar adults: toward peripheral biomarkers of bipolar disorder

Diffusion tensor imaging (DTI) studies consistently reported abnormalities in fractional anisotropy (FA) and radial diffusivity (RD), measures of the integrity of white matter (WM), in bipolar disorder (BD), that may reflect underlying pathophysiologic processes. There is, however, a pressing need to identify peripheral measures that are related to these WM measures, to help identify easily obtainable peripheral biomarkers of BD. Given the high lipid content of axonal membranes and myelin sheaths, and that elevated serum levels of lipid peroxidation are reported in BD, these serum measures may be promising peripheral biomarkers of underlying WM abnormalities in BD. We used DTI and probabilistic tractography to compare FA and RD in ten prefrontal-centered WM tracts, 8 of which are consistently shown to have abnormal FA (and/or RD) in BD, and also examined serum lipid peroxidation (lipid hydroperoxides, LPH and 4-hydroxy-2-nonenal, 4-HNE), in 24 currently euthymic BD adults (BDE) and 19 age- and gender-matched healthy adults (CONT). There was a significant effect of group upon FA in these a priori WM tracts (BDECONT: F[1,41]=10.3; P=0.003), and a significant between-group difference in LPH (BDE>CONT: t[40]=2.4; P=0.022), but not in 4-HNE. Multivariate multiple regression analyses revealed that LPH variance explained, respectively, 59 and 51% of the variance of FA and RD across all study participants. This is the first study to examine relationships between measures of WM integrity and peripheral measures of lipid peroxidation. Our findings suggest that serum LPH may be useful in the development of a clinically relevant, yet easily obtainable and inexpensive, peripheral biomarkers of BD