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. 2019 Dec;24(12):1856-1867.
doi: 10.1038/s41380-018-0273-4. Epub 2018 Oct 19.

Clinical, Cortical Thickness and Neural Activity Predictors of Future Affective Lability in Youth at Risk for Bipolar Disorder: Initial Discovery and Independent Sample Replication

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Clinical, Cortical Thickness and Neural Activity Predictors of Future Affective Lability in Youth at Risk for Bipolar Disorder: Initial Discovery and Independent Sample Replication

Michele A Bertocci et al. Mol Psychiatry. .
Free PMC article


We aimed to identify markers of future affective lability in youth at bipolar disorder risk from the Pittsburgh Bipolar Offspring Study (BIOS) (n = 41, age = 14, SD = 2.30), and validate these predictors in an independent sample from the Longitudinal Assessment of Manic Symptoms study (LAMS) (n = 55, age = 13.7, SD = 1.9). We included factors of mixed/mania, irritability, and anxiety/depression (29 months post MRI scan) in regularized regression models. Clinical and demographic variables, along with neural activity during reward and emotion processing and gray matter structure in all cortical regions at baseline, were used to predict future affective lability factor scores, using regularized regression. Future affective lability factor scores were predicted in both samples by unique combinations of baseline neural structure, function, and clinical characteristics. Lower bilateral parietal cortical thickness, greater left ventrolateral prefrontal cortex thickness, lower right transverse temporal cortex thickness, greater self-reported depression, mania severity, and age at scan predicted greater future mixed/mania factor score. Lower bilateral parietal cortical thickness, greater right entorhinal cortical thickness, greater right fusiform gyral activity during emotional face processing, diagnosis of major depressive disorder, and greater self-reported depression severity predicted greater irritability factor score. Greater self-reported depression severity predicted greater anxiety/depression factor score. Elucidating unique clinical and neural predictors of future-specific affective lability factors is a step toward identifying objective markers of bipolar disorder risk, to provide neural targets to better guide and monitor early interventions in bipolar disorder at-risk youth.


Participants guessed whether a card (value,1–9) was higher/lower than 5, participants then viewed the number, possible outcome (win, green arrow; loss, red arrow),and fixation cross. In control trials, participants pressed a button marked “X,” then viewed an asterisk, circle, and fixation cross. The paradigm included 9 blocks: 3 win (80% win, 20% loss trials), 3 loss (80% loss, 20% win trials) and 3 control (constant in earnings) blocks. Control blocks had six control trials, whereas guessing blocks (Win and Loss) had five trials in an oddball format. Emotion processing task: Representation of an emotional face (angry condition) and a shape (control condition) trials of the emotional dynamic faces task. There were 3 blocks for each of the 4 emotional trials with 12 stimuli per block. There were 12 control blocks with 6 stimuli per block. During this task, participants viewed a face changing from a neutral to a happy, sad, angry (depicted here), or fearful emotional expression during a 1000-ms trial. During the control condition, participants viewed a dark grey oval increasing in size during the trial. Participants were required to identify the color of an oval superimposed over both the face and the shape the color was presented between 200 and 650ms of a trial.
CALS-P relationships. A. Representation of left precuneus and left vlPFC, regions differentially associated with mixed/mania or irritability factor scores. B. Comparison of TIME1:CALS-P normative and higher scores. C. Graphs of left vlPFC thickness -future mixed/mania factor score. Circles = participants with TIME1:CALS-P score of 9 or below; Diamonds = participants with TIME1:CALS-P score above 9. Abbreviations: CALS-P = parent report of Child Affective Lability Scale.

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