Dataset Information

Altered neural responses to social fairness in bipolar disorder.

ABSTRACT: Bipolar Disorder (BD) has a debilitating impact on psychosocial functioning and social decision-making. Recent evidence using the Ultimatum Game (UG) has shown increased rejection of moderately unfair offers in BD, suggesting impaired processing of ambiguous social information related to fairness. The present study builds upon this finding to investigate the neural substrates of fairness processing in BD. During functional magnetic resonance imaging scanning, euthymic BD patients (n = 41) and matched healthy controls (HC; n = 41) accepted or rejected very unfair, moderately unfair, or fair offers in the UG. Acceptance rates of moderately unfair offers were significantly lower in BD patients. This aberrant behavior co-occurred with abnormal brain responses to moderately unfair offers. Compared to HC, BD patients exhibited hypoactivation of right anterior insula in response to moderately unfair offers suggesting impaired integration of affective and contextual information. BD patients also displayed stronger deactivation of posterior and middle insula in response to moderately unfair offers reflecting impaired processing of the contextual aspects of fairness. The level of impulsivity of BD patients positively correlated with the abnormal deactivation of posterior and middle insula. A separate analysis revealed increased activation of dorsal ACC and left ventrolateral PFC in response to rejected compared to accepted offers in BD patients. Taken together, our findings suggest impaired processing of ambiguous social information in euthymic BD patients which is associated with increased rejection of moderately unfair offers. This impairment may reflect a failure to integrate contextual information and may be related to increased trait impulsivity.

SUBMITTER: Lois G

PROVIDER: S-EPMC7666350 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Altered neural responses to social fairness in bipolar disorder.

Lois Giannis G Schneider Eva E EE Kaurin Aleksandra A Wessa Michèle M

NeuroImage. Clinical 20201103

Bipolar Disorder (BD) has a debilitating impact on psychosocial functioning and social decision-making. Recent evidence using the Ultimatum Game (UG) has shown increased rejection of moderately unfair offers in BD, suggesting impaired processing of ambiguous social information related to fairness. The present study builds upon this finding to investigate the neural substrates of fairness processing in BD. During functional magnetic resonance imaging scanning, euthymic BD patients (n = 41) and ma ...[more]

PMID: 33395978

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Project description:The transition to motherhood involves CNS changes that modify sociability and affective state. However, these changes also put females at risk for postpartum depression and psychosis, which impairs parenting abilities and adversely affects children. Thus, changes in expression and interactions in a core subset of genes may be critical for emergence of a healthy maternal phenotype, but inappropriate changes of the same genes could put women at risk for postpartum disorders. This study evaluated microarray gene expression changes in medial prefrontal cortex (mPFC), a region implicated in both maternal behavior and psychiatric disorders. Postpartum mice were compared to virgin controls housed with females and isolated for identical durations. Using the Modular Single-set Enrichment Test (MSET), we found that the genetic landscape of maternal mPFC bears statistical similarity to gene databases associated with schizophrenia (5 of 5 sets) and bipolar disorder (BPD, 3 of 3 sets). In contrast to previous studies of maternal lateral septum and medial preoptic area, enrichment of autism and depression-linked genes was not significant (2 of 9 sets, 0 of 4 sets). Among genes linked to multiple disorders were fatty acid binding protein 7 (Fabp7), glutamate metabotropic receptor 3 (Grm3), platelet derived growth factor, beta polypeptide (Pdgfrb), and nuclear receptor subfamily 1, group D, member 1 (Nr1d1). RT-qPCR confirmed these gene changes as well as FMS-like tyrosine kinase 1 (Flt1) and proenkephalin (Penk). Systems-level methods revealed involvement of developmental gene networks in establishing the maternal phenotype and indirectly suggested a role for numerous microRNAs and transcription factors in mediating expression changes. Together, this study suggests that a subset of genes involved in shaping the healthy maternal brain may also be dysregulated in mental health disorders and put females at risk for postpartum psychosis with aspects of schizophrenia and BPD. In total, 10 total RNA samples derived from micropunched medial prefrontal cortex were used for microarray analysis: 5 samples from lactating maternal mice (maternal) and 5 samples from age-matched virgin mice (virgin). All samples are biological replicates.

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.

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Altered neural responses to social fairness in bipolar disorder.

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Altered neural responses to social fairness in bipolar disorder.

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