Dataset Information

The impact of familial risk and early life adversity on emotion and reward processing networks in youth at-risk for bipolar disorder.

ABSTRACT: A recently developed risk calculator for bipolar disorder (BD) accounts for clinical and parental psychopathology. Yet, it is understood that both familial predisposition and early life adversity contribute to the development of BD. How the interplay between these two factors influence emotion and reward processing networks in youth at risk for BD remains unclear. In this exploratory analysis, offspring of BD parents performed emotion and reward processing tasks while undergoing a fMRI scan. Risk calculator score was used to assess risk for developing BD in the next 5 years. Environmental risk was tabulated using the Stressful Life Events Schedule (SLES). Emotion and reward processing networks were investigated for genetic and/or environment interactions. Interaction effects were found between risk calculator scores, negative SLES score and activity in right amygdala and bilateral fusiform gyri during the emotion processing task, as well as activity in the fronto-, striatal, and parietal regions during the reward processing task. Our findings are preliminary; however, they support the unique and interactive contributions of both familial and environmental risk factors on emotion and reward processing within OBP. They also identify potential neural targets to guide development of interventions for youth at greatest risk for psychiatric disorders.

SUBMITTER: Hanford LC

PROVIDER: S-EPMC6907842 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The impact of familial risk and early life adversity on emotion and reward processing networks in youth at-risk for bipolar disorder.

Hanford Lindsay C LC Eckstrand Kristen K Manelis Anna A Hafeman Danella M DM Merranko John J Ladouceur Cecile D CD Graur Simona S McCaffrey Alicia A Monk Kelly K Bonar Lisa K LK Hickey Mary Beth MB Goldstein Tina R TR Goldstein Benjamin I BI Axelson David D Bebko Genna G Bertocci Michele A MA Gill Mary Kay MK Birmaher Boris B Phillips Mary L ML

PloS one 20191212 12

A recently developed risk calculator for bipolar disorder (BD) accounts for clinical and parental psychopathology. Yet, it is understood that both familial predisposition and early life adversity contribute to the development of BD. How the interplay between these two factors influence emotion and reward processing networks in youth at risk for BD remains unclear. In this exploratory analysis, offspring of BD parents performed emotion and reward processing tasks while undergoing a fMRI scan. Ris ...[more]

PMID: 31830059

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Project description:ObjectiveBipolar disorder (BD) is highly heritable. Neuroimaging studies comparing unaffected youth at high familial risk for BD (i.e., those with a first-degree relative with the disorder; termed "high-risk" [HR]) to "low-risk" (LR) youth (i.e., those without a first-degree relative with BD) and to patients with BD may help identify potential brain-based markers associated with risk (i.e., regions where HR+BD≠LR), resilience (HR≠BD+LR), or illness (BD≠HR+LR).MethodDuring functional magnetic resonance imaging (fMRI), 99 youths (i.e., adolescents and young adults) aged 9.8 to 24.8 years (36 BD, 22 HR, 41 LR) performed a task probing face emotion labeling, previously shown to be impaired behaviorally in youth with BD and HR youth.ResultsWe found three patterns of results. Candidate risk endophenotypes (i.e., where BD and HR shared deficits) included dysfunction in higher-order face processing regions (e.g., middle temporal gyrus, dorsolateral prefrontal cortex). Candidate resilience markers and disorder sequelae (where HR and BD, respectively, show unique alterations relative to the other two groups) included different patterns of neural responses across other regions mediating face processing (e.g., fusiform), executive function (e.g., inferior frontal gyrus), and social cognition (e.g., default network, superior temporal sulcus, temporo-parietal junction).ConclusionIf replicated in longitudinal studies and with additional populations, neural patterns suggesting risk endophenotypes could be used to identify individuals at risk for BD who may benefit from prevention measures. Moreover, information about risk and resilience markers could be used to develop novel treatments that recruit neural markers of resilience and attenuate neural patterns associated with risk. Clinical trial registration information-Studies of Brain Function and Course of Illness in Pediatric Bipolar Disorder and Child and Adolescent Bipolar Disorder Brain Imaging and Treatment Study; http://clinicaltrials.gov/; NCT00025935 and NCT00006177.

Project description:ImportanceBipolar disorder (BD) is difficult to distinguish from other psychiatric disorders. Neuroimaging studies can identify objective markers of BD risk.ObjectiveTo 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 participantsThis 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 measuresGroup 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).ResultsEighty 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 relevanceGreater 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.

Project description:ImportanceEarly identification of individuals at high risk for the onset of bipolar spectrum disorder (BPSD) is key from both a clinical and research perspective. While previous work has identified the presence of a bipolar prodrome, the predictive implications for the individual have not been assessed, to date.ObjectiveTo build a risk calculator to predict the 5-year onset of BPSD in youth at familial risk for BPSD.Design, setting, and participantsThe Pittsburgh Bipolar Offspring Study is an ongoing community-based longitudinal cohort investigation of offspring of parents with bipolar I or II (and community controls), recruited between November 2001 and July 2007, with a median follow-up period of more than 9 years. Recruitment has ended, but follow-up is ongoing. The present analysis included offspring of parents with bipolar I or II (aged 6-17 years) who had not yet developed BPSD at baseline.Main outcomes and measuresThis study tested the degree to which a time-to-event model, including measures of mood and anxiety, general psychosocial functioning, age at mood disorder onset in the bipolar parent, and age at each visit, predicted new-onset BPSD. To fully use longitudinal data, the study assessed each visit separately, clustering within individuals. Discrimination was measured using the time-dependent area under the curve (AUC), predicting 5-year risk; internal validation was performed using 1000 bootstrapped resamples. Calibration was assessed by comparing observed vs predicted probability of new-onset BPSD.ResultsThere were 412 at-risk offspring (202 [49.0%] female), with a mean (SD) visit age of 12.0 (3.5) years and a mean (SD) age at new-onset BPSD of 14.2 (4.5) years. Among them, 54 (13.1%) developed BPSD during follow-up (18 with BD I or II); these participants contributed a total of 1058 visits, 67 (6.3%) of which preceded new-onset BPSD within the next 5 years. Using internal validation to account for overfitting, the model provided good discrimination between converting vs nonconverting visits (AUC, 0.76; bootstrapped 95% CI, 0.71-0.82). Important univariate predictors of outcome (AUC range, 0.66-0.70) were dimensional measures of mania, depression, anxiety, and mood lability; psychosocial functioning; and parental age at mood disorder.Conclusions and relevanceThis risk calculator provides a practical tool for assessing the probability that a youth at familial risk for BPSD will develop new-onset BPSD within the next 5 years. Such a tool may be used by clinicians to inform frequency of monitoring and treatment options and for research studies to better identify potential participants at ultra high risk of conversion.

Dataset Information

The impact of familial risk and early life adversity on emotion and reward processing networks in youth at-risk for bipolar disorder.

Publications

The impact of familial risk and early life adversity on emotion and reward processing networks in youth at-risk for bipolar disorder.

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