High Risk For Bipolar Disorder Research Articles

Towards a neurodevelopmental model of bipolar disorder: a critical review of trait- and state-related functional neuroimaging in adolescents and young adults.

Neurodevelopmental mechanisms are increasingly implicated in bipolar disorder (BD), highlighting the importance of their study in young persons. Neuroimaging studies have demonstrated a central role for frontotemporal corticolimbic brain systems that subserve processing and regulation of emotions, and processing of reward in adults with BD. As adolescence and young adulthood (AYA) is a time when fully syndromal BD often emerges, and when these brain systems undergo dynamic maturational changes, the AYA epoch is implicated as a critical period in the neurodevelopment of BD. Functional magnetic resonance imaging (fMRI) studies can be especially informative in identifying the functional neuroanatomy in adolescents and young adults with BD (BDAYA) and at high risk for BD (HR-BDAYA) that is related to acute mood states and trait vulnerability to the disorder. The identification of early emerging brain differences, trait- and state-based, can contribute to the elucidation of the developmental neuropathophysiology of BD, and to the generation of treatment and prevention targets. In this critical review, fMRI studies of BDAYA and HR-BDAYA are discussed, and a preliminary neurodevelopmental model is presented based on a convergence of literature that suggests early emerging dysfunction in subcortical (e.g., amygdalar, striatal, thalamic) and caudal and ventral cortical regions, especially ventral prefrontal cortex (vPFC) and insula, and connections among them, persisting as trait-related features. More rostral and dorsal cortical alterations, and bilaterality progress later, with lateralization, and direction of functional imaging findings differing by mood state. Altered functioning of these brain regions, and regions they are strongly connected to, are implicated in the range of symptoms seen in BD, such as the insula in interoception, precentral gyrus in motor changes, and prefrontal cortex in cognition. Current limitations, and outlook on the future use of neuroimaging evidence to inform interventions and prevent the onset of mood episodes in BDAYA, are outlined.

A comprehensive assessment of the association between common drugs and psychiatric disorders using Mendelian randomization and real-world pharmacovigilance database

Medications prescribed for chronic diseases can lead to short-term neuropsychiatric symptoms, but their long-term effects on brain structures and psychiatric conditions remain unclear. We comprehensively analyzed the FDA Adverse Event Reporting System database and conducted drug target Mendelian Randomization (MR) studies on six categories of common drugs, 477 brain imaging-derived phenotypes (IDPs) and eight psychiatric disorders. Genetic instruments were extracted from expression quantitative trait loci (eQTLs) in blood, brain, and other target tissues, protein quantitative trait loci (pQTLs) in blood, and genome-wide association studies (GWAS) of hemoglobin and cholesterol. Summary statistics for brain IDPs, psychiatric disorders, and gut microbiome were obtained from the BIG40, Psychiatric Genomics Consortium, and MiBioGen. A two-step MR and mediation analysis were employed to screen possible mediators of drug-IDP effects from 119 gut microbiota genera and identify their mediation proportions. Among 19 drug classes, six drugs were found to be associated with higher risks of psychiatric adverse events, while 11 drugs were associated with higher risks of gastrointestinal adverse events in the FAERS analysis. We identified ten drug-psychiatric disorder associations, 202 drug-IDP associations, 16 drug-microbiota associations, and four drug-microbiota-IDP causal links. For example, PPARG activation mediated HbA1c reduction caused a higher risk of bipolar disorder (BD) II. Genetically proxied GLP-1R agonists were significantly associated with an increase in the volume of the CA3-head of the right hippocampus and the area of the left precuneus cortex, both of which have been shown to correlate with cognition in previous studies. Common drugs may affect brain structure and risk of psychiatric disorder. Oral medications in particular may exert some of these effects by influencing gut microbiota. This study calls for greater attention to be paid to the neuropsychiatric adverse effects of drugs and encourages drug repurposing. National Natural Science Foundation of China (grant No. 82330035, 82130043, 82172685, and 82001223), National Natural Science Foundation of Hunan Province (grant No. 2021SK1010), and the Science Foundation for Distinguished Young Scholars of Changsha (grant No. kq2209006).

The Impact on Anxiety Symptoms of an Immersive Virtual Reality Remediation Program in Bipolar Disorders: A Randomized Clinical Trial.

Background: The objective of this work is to investigate the effectiveness of a cognitive remediation intervention on anxiety symptoms in people with bipolar disorder and the therapeutic effect on people whose anxiety symptoms were above the threshold for a screener and whose comorbidity could be identified as an anxiety disorder. Methods: The experimental intervention included 24 sessions (around 45 min each), two for each week over three months. The entire program was inspired by user-centered rehabilitation principles in a recovery-oriented perspective and an approach to bipolar disorder in an evolutionary and non-discriminating vision. The primary outcomes measure the score of the Zung Self-Rating Anxiety Scale (SAS), hypothesizing a higher decrease in the experimental group than in the control group. The survey has been conducted per the CONSORT guidelines for feasibility studies. Results: We evaluate a decrease in the overall SAS score from T0 to T1 to be higher in the experimental group compared to the control group, indicating an improvement in anxiety symptoms (p < 0.0001). Conclusions: The study suggests that virtual reality could have a role in treating anxiety symptoms and disorders in young adults with bipolar disorders or anxiety symptoms in people with hyperactivity and novelty-seeking behaviorsunder stress and high risk for bipolar disorder.

Moderating effect of shift work on sleep and depression in individuals at high risk of bipolar disorder

BackgroundSocial Zeitgeber Theory posits that disruptions in social rhythms can increase susceptibility to bipolar disorder (BD). Shift work (SW) is one of the external factors that cause instability in social rhythms and the sleep-wake cycle. This study evaluated the moderating influences of SW on the risks of BD and sleep-related parameters and depressive symptoms. Furthermore, we evaluated the specific work schedules including daytime, nighttime, and regular and irregular rotating SW. MethodsAn online survey was administered to 6665 participants, with 3379 (50.7 %) classified as individuals with high scores of Mood Disorder Questionnaire (MDQ). The survey included the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Scale (ISI), Epworth Sleepiness Scale (ESS), and Center for Epidemiologic Studies Depression Scale (CES-D). ResultsA multivariate regression model revealed significant interactive effects of MDQ positivity and SW on PSQI, ISI, and CES-D scores, but not ESS scores. In a secondary analysis of the high MDQ screen group, daytime workers had lower scores in sleep disturbances and depressive symptoms compared to those engaged in other forms of SW. LimitationsOnline surveys were accessible voluntarily, leading to potential selection bias. Cross-sectional data identified associations, not causal relationships. Only a self-reported questionnaire was used. ConclusionsOur findings emphasize the advantages of a daytime work schedule for individuals at high risk of BD. In accordance with the principles of social rhythm interpersonal therapy, sleep interventions for individuals at high risk of BD should include the maintenance of a consistent daytime schedule.

Evaluation of Neurocognitive Functions of Children and Adolescents Diagnosed with Pediatric Bipolar Disorder and Disruptive Mood Dysregulation and at High Risk for Bipolar Disorder

IntroductionPediatric Bipolar Disorder (BPD) is a chronic psychiatric disorder that alters normal and psychological development processes among patients. Although cognitive deficits in BPD have identified in recent studies, little is known about the developmental trajectory of these deficits. DMDD is a newly defined diagnosis included in the DSM-V. Since it added a new dimension to the clinical spectrum but few studies conducted on DMDD, there are some conflicting discussions in the literature about how to distinguish this disorder from other childhood psychiatric disorders and how to treat it.ObjectivesThe aim of this study was to determine the phenomenological and neuropsychological differences between children and adolescents with a diagnosis of BPD (Pediatric Bipolar Disorder), DMDD (Disruptive Mood Dysregulation Disorder), and children and adolescents who are genetically at high risk for Bipolar Disorder (BD), and healthy controls (HCs) who do not have any psychiatric diagnosis, to investigate endophenotypes that may be predictive for BD.MethodsOur study sample consists of four groups, the BPD group (n=30), the Risk group (n=25), the DMDD group (n=36), and the Healthy Control group (n=29). All participants were evaluated by the “Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children—Now and Lifetime Pattern (K-SADS-PL)”. “Young Mania Rating Scale/Parent Form (YMRS-ABF), Conner’s Parent Rating Scale (CPRS-48), Child and Adolescent Behavior Rating Scale (CBCL)” scales were filled by parents, and “Child Depression Inventory (CDI), Youth Self-Report Form for 11-18 Years Olds (YSR)” scales were filled by children and adolescents. Neurocognitive test battery was applied to each participant: Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), Stroop Color and Word Test (SCWT), Trait Making Test A and B sections (TMT-A/B), California Verbal Learning Test-Child version (CVLT-C).ResultsWhile it was determined that the cases in the BPD and DMDD groups performed significantly worse in CPT, SCWT, CVLT-C, TMT A/B tests compared to healthy controls, it was found that the subjects in the Risk group performed worse at the CPT test than healthy controls. In addition, the cases in the BPD, Risk and DMDD groups reported more clinical and behavioral problems than the healthy controls.ConclusionsThere is a significant deterioration in the areas of continuous attention, processing speed, cognitive flexibility, response prevention, verbal memory and working memory in the BPD and DMDD groups, and in the continuous attention area in the Risk group compared to healthy controls. Prospective follow-up and imaging studies using larger samples and a larger neurocognitive test battery in the future will better reveal the neuropsychological characteristics of the BPD, Risk and DMDD groups.Disclosure of InterestNone Declared

Psychiatric Polygenic Risk Scores Across Youth With Bipolar Disorder, Youth at High Risk for Bipolar Disorder, and Controls

There is a pronounced gap in knowledge regarding polygenic underpinnings of youth bipolar disorder (BD). This study aimed to compare polygenic risk scores (PRSs) in youth with BD, youth at high clinical and/or familial risk for BD (HR), and controls. Participants were 344 youths of European ancestry (13-20 years old), including 136 youths with BD, 121 HR youths, and 87 controls. PRSs for BD, schizophrenia), major depressive disorder, and attention-deficit/hyperactivity disorder were constructed using independent genome-wide summary statistics from adult cohorts. Multinomial logistic regression was used to examine the association between each PRS and diagnostic status (BD vs HR vs controls). All genetic analyses controlled for age, sex, and 2 genetic principal components. The BD group showed significantly higher BD-PRS than the control group (odds ratio= 1.54, 95% CI= 1.13-2.10, p= .006), with the HR group numerically intermediate. BD-PRS explained 7.9% of phenotypic variance. PRSs for schizophrenia, major depressive disorder, and attention-deficit/hyperactivity disorder were not significantly different among groups. In the BD group, BD-PRS did not significantly differ in relation to BD subtype, age of onset, psychosis, or family history of BD. BD-PRS derived from adult genome-wide summary statistics is elevated in youth with BD. Absence of significant between-group differences in PRSs for other psychiatric disorders supports the specificity of BD-PRS in youth. These findings add to the biological validation of BD in youth and could have implications for early identification and diagnosis. To enhance clinical utility, future genome-wide association studies that focus specifically on early-onset BD are warranted, as are studies integrating additional genetic and environmental factors. We worked to ensure sex and gender balance in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Association between polymorphisms of TLR2-1-6 and bipolar disorder in a tunisian population.

Bipolar disorder (BD) is a complex neuropsychiatric disease that has been strongly linked to immune dysregulation. In particular, an abnormal inflammatory response mediated by toll-like receptor 2 - 1/6 (TLR2-1/6) was described in BD. Nevertheless, genetic factors' contribution is still unknown. Thus, we suggested that functional polymorphisms of TLR2, 1 and 6 could be involved in BD predisposition. TLR2, 1 and 6 polymorphisms were genotyped by PCR-RFLP in 292 controls and 131 patients from a Tunisian population. Polymorphisms and haplotype associations were explored in BD and binary logistic regression analysis was performed for more powerful associations. In dominant model, we found a significantly higher genotype and minor allele frequencies in healthy females compared to patients for TLR2-196-174Ins/Del (p = 0.04; OR = 0.3, p = 0.04; OR = 0.3, respectively) and for TLR6-S249P only with minor allele (p = 0.03; OR = 0.2). In contrast, TLR2-R677W CT + TT and T allele frequencies were significantly higher in BD (padjusted<10- 4; ORadjusted =46.6, p < 10- 4; OR = 6.3, respectively), specifically in females (CT + TT: 100%). Similarly, TLR1-R80T showed significantly increased GC + CC and C allele frequencies in patients compared to controls (padjusted=0.04; ORadjusted=4, p = 0.009; OR = 4.3, respectively). Moreover, haplotype investigation demonstrated that InsGTCGT (p < 10- 4, OR = 275) and delGCCGT (p = 0.03, OR = 18.5) were significantly overrepresented in BD patients compared to controls. We suggest that TLR2-196-174Ins/Del and TLR6-S249P could be protective factors of females against BD. However, TLR2-R677W and TLR1-R80T could be strongly associated with higher risk of BD. Interestingly, TLR2-R677W could be a genetic marker for BD in females. However, further studies with larger groups are needed to confirm these findings.

The development in rating-based executive functions in children at familial high risk of schizophrenia or bipolar disorder from age 7 to age 11: the Danish high risk and resilience study.

Executive functions (EF) deficits are well documented in children at familial high risk of schizophrenia (FHR-SZ), and to a lesser degree in children at familial high risk of bipolar disorder (FHR-BP). The aim of this study was to assess EF development in preadolescent children at FHR-SZ, FHR-BP and population-based controls (PBC) using a multi-informant rating scale. A total of 519 children (FHR-SZ, n = 201; FHR-BP, n = 119; PBC, n = 199) participated at age 7, at age 11 or at both time points. Caregivers and teachers completed the Behavior Rating Inventory of Executive Functions (BRIEF). The developmental pattern from age 7 to age 11, did not differ between groups. At age 11, caregivers and teachers rated children at FHR-SZ as having widespread EF deficits. A higher proportion of children at FHR-SZ had clinically significant scores on the General executive composite (GEC) and all BRIEF indices compared to PBC. According to the caregivers, children at FHR-BP had significantly more EF deficits than PBC on 9 out of 13 BRIEF scales, whereas according to teachers, they only had significantly more deficits on one subdomain (Initiate). Likewise, caregivers rated a significantly higher proportion of children at FHR-BP above the clinical cut-off on the GEC and Metacognition index, compared to PBC, whereas there were no significant differences according to teachers. This study highlights the relevance of including multi-informant rating scales in the assessment of EF in children at FHR-SZ and FHR-BP. The results imply a need to identify children at high risk who would benefit from targeted intervention.

Early interventions for youth at high risk for bipolar disorder.

Early interventions for youth at high risk for bipolar disorder.

Mood Instability in Youth at High Risk for Bipolar Disorder.

Mood instability is associated with the onset of bipolar disorder (BD) in youth with a family history of the illness. In a clinical trial with youth at high risk for BD, we examined the association between mood instability and symptomatic, psychosocial, and familial functioning over an average of 2 years. Youth (aged 9-17 years) with major depressive disorder or other specified BD, current mood symptoms, and a family history of BD were rated by parents on a mood instability scale. Participants were randomly assigned to 4 months of family-focused therapy or enhanced care psychoeducation, both with medication management as needed. Independent evaluators rated youth every 4-6 months for up to 4 years on symptom severity and psychosocial functioning, whereas parents rated mood instability of the youth and levels of family conflict. High-risk youth (N= 114; mean age 13.3 ± 2.6 years; 72 female) were followed for an average of 104.3 ± 65.8 weeks (range, 0-255 weeks) after randomization. Youth with other specified BD (vs major depressive disorder), younger age, earlier symptom onset, more severe mood symptoms, lower psychosocial functioning, and more familial conflict over time had higher mood instability ratings throughout the study period. Mood instability mediated the association between baseline diagnosis and mother/offspring conflict at follow-up (Z= 2.88, p= .004, αβ= 0.19, 95% CI= 0.06-0.32). Psychosocial interventions did not moderate these associations. A questionnaire measure of mood instability tracked closely with symptomatic, psychosocial, and family functioning in youth at high risk for BD. Interventions that are successful in reducing mood instability may enhance long-term outcomes among high-risk youth. Early Intervention for Youth at Risk for Bipolar Disorder; https://clinicaltrials.gov/; NCT01483391.

31.1 Mood Instability and Family Functioning in Youth at High Risk for Bipolar Disorder

Children and teens with depression and early signs of mania are at high risk for the onset of bipolar disorder (BD), especially if they have a family history of the disorder. In this study, we examined predictors of outcome in a randomized trial of family-focused therapy (FFT) for high-risk youth, with a focus on measures that can be easily adapted to practice settings.

Risk of pain disorders in offspring of parents with substance use disorders.

Individuals with substance use disorders (SUD) have higher risk of developing pain disorders. This study aimed to investigate the risk of major psychiatric disorders (MPD), SUD, and pain disorders among their offspring. This study used data from the Taiwan National Health Research Database. The case cohort included participants who had a parent diagnosed with SUD. The matched control cohort was offspring of parents without any SUD or major psychiatric disorder (MPD). Poisson regression was applied to estimate the risk of MPD, SUD, and pain disorder between case and control cohorts. We recruited 13,840 cases and 138,400 matched controls. After adjusting for demographic characteristics and family history of psychiatric disorder, the offspring of parents with SUD had higher risk for bipolar disorder (reported as risk ratio with 95% confidence interval: 2.48, 1.79-3.43), depressive disorder (2.22, 1.94-2.52), SUD (2.53, 2.18-2.92), and alcohol use disorder (1.43, 1.16-1.76) than controls. With adjustments of demographic characteristics, individual MPD, and family history of psychiatric disorder, they also presented higher risk than controls for several pain disorders, including migraine (1.43, 1.15-1.78), fibromyalgia (1.21, 1.03-1.42), dorsopathies (1.20, 1.06-1.37), dysmenorrhea (1.16, 1.04-1.29), irritable bowel syndrome (1.26, 1.11-1.43), and dyspepsia (1.14, 1.02-1.27). Clinicians should be aware of the influence of parental SUD on the elevated risk for MPD, SUD, and pain disorders in their offspring.

Effects of family intervention on psychosocial functioning and mood symptoms of youth at high risk for bipolar disorder.

Family-focused therapy (FFT) is associated with reduced rates of mood episodes among youth at high risk for bipolar disorder (BD). In a randomized trial of FFT compared to a psychoeducation-only treatment (enhanced care, EC), we sought to determine if changes in psychosocial functioning mediate mood improvements among high-risk youth. 119 youths with active mood symptoms and a family history of BD were randomized to either 4 months of FFT or EC. Participants were rated on mood symptom severity and provided self-ratings of psychosocial functioning across domains of family, social-emotional, and school functioning. Repeated measures mixed modeling and bootstrapped mediational analyses evaluated the effects of treatment conditions and psychosocial functioning on mood improvements immediately posttreatment and over 2 years of follow-up. Youths in FFT reported greater improvements in family functioning over 24 months compared to those in EC, F(5, 76.8) = 3.1, p < .05. Improvements in family functioning partially mediated participants' improvements in depressive symptoms, B = -0.22, p < .01; 95% CI [-0.55, -0.02]. The effects of FFT versus EC on family functioning were stronger among youth with comorbid anxiety and externalizing disorders than among youth without these comorbid disorders. The findings suggest a temporal link between changes in youths' perceptions of family functioning and improvements in depressive symptoms among high-risk youth in FFT. Family conflict and cohesion are important treatment targets for youth who present with early signs of BD. Future studies should examine whether changes in observational measures of family interaction precede improvements in mood among high-risk youth. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Association Between Early Risk Factors and Level of Functioning at Age Seven in Children at Familial Risk for Schizophrenia Or Bipolar Disorder - the Danish High Risk and Resilience Study VIA 7.

Facing multiple risk factors, relative to single risk factor exposure early in life can have great implications for negative child development. We aim to examine whether the prevalence of early risk factors is higher among children with familial high risk for schizophrenia or bipolar disorder compared to controls. Further, to investigate the association between number of early risk factors and level of functioning at age seven, and whether this possible association is different in children with familial high risk compared to controls. The Danish High Risk and Resilience Study VIA 7 is a population-based cohort study of children of parents diagnosed with schizophrenia (N = 202), bipolar disorder (N = 120) and controls (N = 200). We conducted a semi-structured anamnestic interview with the child's primary caregiver to assess early risk factors from pregnancy to age four. We used the Children's Global Assessment Scale to measure level of functioning at age seven. 13 out of 17 risk factors were more prevalent in children at familial high risk for schizophrenia and 7 out of 17 risk factors were more prevalent in children at familial high risk for bipolar disorder compared to controls. Level of functioning decreased 2.7 (95% CI, 2.2; 3.3)-points per risk factor, but the association was not significantly different across the three groups (p = 0.09). Our results showed that children at age seven with familial high risk for schizophrenia or bipolar disorder experience a greater number of early risk factors. A higher number of early risk factors were associated with lower level of functioning at age seven. However, the association is not different for children with familial high risk or controls.

The German research consortium for the study of bipolar disorder (BipoLife): a magnetic resonance imaging study protocol

BackgroundBipolar disorder is one of the most severe mental disorders. Its chronic course is associated with high rates of morbidity and mortality, a high risk of suicide and poor social and occupational outcomes. Despite the great advances over the last decades in understanding mental disorders, the mechanisms underlying bipolar disorder at the neural network level still remain elusive. This has severe consequences for clinical practice, for instance by inadequate diagnoses or delayed treatments. The German research consortium BipoLife aims to shed light on the mechanisms underlying bipolar disorders. It was established in 2015 and incorporates ten university hospitals across Germany. Its research projects focus in particular on individuals at high risk of bipolar disorder, young patients in the early stages of the disease and patients with an unstable highly relapsing course and/or with acute suicidal ideation.MethodsFunctional and structural magnetic resonance imaging (MRI) data was acquired across nine sites within three different studies. Obtaining neuroimaging data in a multicenter setting requires among others the harmonization of the acquisition protocol, the standardization of paradigms and the implementation of regular quality control procedures. The present article outlines the MRI imaging protocols, the acquisition parameters, the imaging paradigms, the neuroimaging quality assessment procedures and the number of recruited subjects.DiscussionThe careful implementation of a MRI study protocol as well as the adherence to well-defined quality assessment procedures is one key benchmark in the evaluation of the overall quality of large-scale multicenter imaging studies. This article contributes to the BipoLife project by outlining the rationale and the design of the MRI study protocol. It helps to set the necessary standards for follow-up analyses and provides the technical details for an in-depth understanding of follow-up publications.

A commentary on youth onset bipolar disorder.

Given ongoing disagreement about the diagnosis of pediatric bipolar disorder, we sought to illuminate key empirical findings regarding the condition in children and adolescents. We conducted a review of extant studies of the diagnosis, course, and treatment of bipolar disorder in children and adolescents. Bipolar disorder is a lifelong, familial condition with frequent onset in childhood or adolescence. Secular trends indicate that globally, the onset of puberty is occurring earlier, which may contribute to increased identification of mood disorders in younger populations. Despite opinions to the contrary, bipolar disorder has been observed in youth around the world, not just in the U.S. Discrete and episodic manic symptoms occur on a continuum/spectrum of severity and duration. Clinicians may be just as likely to miss mania (false negatives) as overcall it (false positives). As is true in adults, periodicity and heterogeneity are defining features of early onset bipolar disorder. Youth who are misdiagnosed and undiagnosed tend to do poorly over the long term. Youth with and at risk for bipolar disorder are frequently exposed to maltreatment, abuse, and bullying. Fortunately, there are now many evidence-based interventions that have been studied in thousands of youth with or at high risk for bipolar disorder, demonstrating large effect sizes for evaluated treatments versus comparative treatments. Identifying optimal methods for the evaluation and treatment of bipolar disorder in children and adolescents represents important advances in the field. Recognizing the occurrence of mania symptoms in youth is pivotal for improving outcomes in patients living with bipolar disorder.

7.4 Distress Response and Neural Processing of Social Exclusion in Youth at High Risk for Bipolar Disorder

Anxiety may be an initial clinical symptom in youth at familial risk for bipolar disorder (BD). Social exclusion is a key source of anxiety among youth, but little is known about the neural underpinnings of social exclusion in youth at familial risk for BD. We therefore examined the functional neural correlates of social exclusion in youth at familial risk for BD.

Impulsivity and Sleep Disturbance Predict Next-Day Mood Symptoms in a Sample at High Risk for Bipolar Disorder: An EMA Study

Impulsivity and Sleep Disturbance Predict Next-Day Mood Symptoms in a Sample at High Risk for Bipolar Disorder: An EMA Study

Social impairment in relation to clinical symptoms in youth at high risk for bipolar disorder.

Social impairment is common in individuals with bipolar disorder (BD), although its role in youths at high-risk for BD (i.e., mood symptoms in the context of a family history of BD) is not well understood. Social impairment takes many forms including social withdrawal, relational aggression, physical aggression, and victimization. The aim of this study was to explore the links between social impairment and clinical symptoms in youth at high-risk for BD. The sample included 127 youths with elevations in mood symptoms (depression or hypomania) and at least one first and/or second degree relative with BD. Measures of youths' current psychopathology (i.e., depressive and manic severity, suicidality, anxiety, and attention-deficit/hyperactivity disorder [ADHD]) were regressed onto youths' self-reports of social impairment (i.e., social withdrawal, relational aggression, physical aggression, and victimization). Depressive symptoms, suicidal ideation, and anxiety symptoms were related to social withdrawal. Suicidal ideation was also related to reactive aggression. ADHD symptoms related to reactive and proactive aggression as well as relational victimization. Manic symptoms were not associated with social impairment in this sample. Although cross-sectional, study findings point to potential treatment targets related to social functioning. Specifically, social withdrawal should be a target for treatment of childhood depressive and anxiety symptoms. Treatments that focus on social skills and cognitive functioning deficits associated with BD may also have clinical utility.

Neural changes in youth at high risk for bipolar disorder undergoing family-focused therapy or psychoeducation.

Patients with mood disorders may benefit from psychosocial interventions through changes in brain networks underlying emotion processing. In this study, we used functional magnetic resonance imaging (fMRI) to investigate treatment-related changes in emotion processing networks in youth at familial high risk for bipolar disorder (BD). Youth, ages 9-17, were randomly assigned to family-focused therapy for high-risk youth (FFT-HR) or an active comparison treatment, Enhanced Care (EC). Before and after these 4-month treatments, participants underwent fMRI while viewing happy, fearful, and calm facial expressions. Twenty youth in FFT-HR and 20 in EC were included in analyses of pre- to post-treatment changes in activation across the whole brain. Significant clusters were assessed for correlation with mood symptom improvement. In the dorsolateral prefrontal cortex (DLPFC), activation increased from pre- to post-treatment in the FFT-HR group and decreased in the EC group. Insula activation decreased in the FFT-HR group and did not change in the EC group. Across both treatments, decreasing activation in the hippocampus and amygdala was correlated with pre- to post-treatment improvement in hypomania, while increasing activation in the DLPFC was correlated with pre- to post-treatment improvement in depression. Psychosocial treatment addresses abnormalities in emotion regulation networks in youth at high risk for BD. Increased prefrontal cortex activation suggests enhanced emotion regulation from pre- to post-treatment with FFT-HR. Improvements in family interactions may facilitate the development of prefrontal resources that provide protection against future mood episodes.