Background:Bipolar disorder confers elevated cancer morbidity and mortality compared to the general population, yet bipolar disorder remains under-studied in oncology settings. Aims:This narrative review aimed to synthesize key considerations for psychiatrists and oncologists treating people with co-occurring bipolar disorder and cancer. Methods:A narrative review was performed to examine literature related to bipolar disorder in oncological care, focusing on outcomes, treatment-emergent mood symptoms, psychopharmacological interactions, and supportive interventions. Results:Bipolar disorder may adversely affect cancer care through reduced treatment engagement, diagnostic delays, and lower receipt of guideline-concordant oncologic therapy. Bipolar disorder is associated with increased risks of self-harm and suicide, as is receiving a cancer diagnosis. Cancer-related neurological conditions and treatments, including corticosteroids, antineoplastics, and interferon-alpha, may precipitate or worsen mood episodes. Mood stabilizers and antipsychotics carry clinically relevant risks including organ toxicity, electrolyte disturbances, cardiac effects, and immunosuppression. Nonpharmacologic strategies, particularly psychotherapy and maintenance of sleep stability, are essential care components. Discussion:Bipolar disorder has important implications for cancer treatment, while cancer and its therapies can destabilize mood and complicate psychiatric care. Early psychiatric care, close collaboration between oncology and psychiatry, careful medication selection and monitoring, attention to suicide risk and sleep, and psychosocial support are essential to improving care outcomes in this high-risk population. Future research addressing bipolar disorder as a distinct category within psycho-oncology rather than categorized under broader severe mental illness classifications will help further elucidate disorder-specific best practices.

BACKGROUND:People with a familial history for bipolar I disorder are at substantially elevated risk for developing the disorder, but the mechanisms underlying this risk remain unclear. We examined whether familial risk is associated with distinct neurocognitive phenotypes and whether these phenotypes are related to behavioral approach (BAS) and inhibition (BIS). METHODS:Participants were 180 youth with and without familial risk for bipolar I disorder. Latent profile analysis identified neurocognitive phenotypes based on scores from Cambridge Neuropsychological Test Automated Battery tasks. Multinomial logistic regression examined associations between familial risk and cognitive phenotype membership. Linear regression tested associations among phenotypes and BIS/BAS scores. Mediation analysis assessed whether cognitive phenotypes mediated associations between familial risk and motivational ratings. RESULTS:Four cognitive profiles were identified: Resilient, Slowed Reaction Time, Lower Working Memory, and Global Lower Performance. In adjusted pairwise comparisons, individuals in the Resilient compared with the Global Lower Performance profile were significantly less likely to have familial risk for bipolar disorder (OR = 0.2, p = 0.02). Other profiles were also less likely to have familial risk for bipolar disorder, but the association was not significant (p = 0.08). Familial risk was associated with lower BAS Drive overall; however, its indirect effect through the Global Lower Performance profile was positive and approached significance, suggesting a potential suppression pattern. CONCLUSION:Familial risk for bipolar I disorder may be associated with a cognitive phenotype characterized by global neurocognitive underperformance. Findings suggest that familial risk may influence motivational processes through multiple liability pathways.

Objective:To quantify associations between childhood maltreatment and emerging major depressive disorder (MDD) in adolescents/young adults with and without a first-degree family history of bipolar I disorder. Method:A total of 116 youths 14 to 21 years old were classified into a high-risk group (n = 58) based on at least 1 first-degree relative diagnosed with bipolar I disorder and a low-risk group (n = 58) based on no first- or second-degree family history of bipolar disorder. Childhood maltreatment was assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF). Psychiatric diagnoses were established with semistructured interviews. Logistic regression tested interactions between childhood maltreatment and familial risk, controlling for age and sex, as predictors of MDD. Results:Half of participants in the high-risk group exhibited current or past MDD compared with 24% of the low-risk group. Regression models showed that each 1-point increase in CTQ-SF total score was associated with a 7% increase in the odds of MDD (odds ratio [OR] = 1.07, 95% CI 1.01-1.17, p = .004). High-risk status conferred approximately 3 times greater odds of MDD vs low-risk status (OR = 3.04, 95% CI 1.14-8.43, p = .03). Each year of age increased risk of MDD by 34% (OR = 1.34, 95% CI 1.09-1.67, p = .01). The childhood maltreatment × familial risk interaction was not significant (p > .6). Conclusion:Childhood maltreatment and familial risk for bipolar I disorder independently increase the risk of MDD. Mitigating either risk factor independently could meaningfully reduce depression risk in at-risk youth. Diversity & Inclusion Statement:We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. 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. 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. 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.

Background The Global Bipolar Cohort (GBC) was established to identify existing bipolar disorder (BD) cohorts worldwide and foster collaborations focused on descriptive and analytic outcomes relevant to BD. A distributed analytic framework has been implemented to engage multiple sites without the need for central data pooling. This report describes the GBC endeavor and global functional impairment patterns. Cross-cohort comparisons of functional correlates are limited by heterogeneous measures and data-sharing constraints. Large, culturally diverse comparisons are needed to distinguish broadly reproducible correlates from cohort-specific effects. Participating sites completed a 28-item descriptive survey covering diagnostic methods, cognition, genetics, treatment, functioning, and follow-up strategies. We implemented a harmonized local logistic regression model of dichotomized functional outcome and shared summary statistics only. Results We identified 69 cohorts across five continents. Thirty-seven cohorts contributed functional outcome analyses from 17,130 participants. Outcome measures included clinician-rated disability scales and social indicators such as employment and marital status. The proportion classified with poor functioning ranged from 16% to 77% (mean 50%). In 32 of 37 cohorts, the overall regression model significantly explained variance in functioning. Current depressive symptoms were the most robust and reproducible correlate of poor functional outcome: they were assessed in 29 cohorts, significant in 22 (75.8%), ranked among the top three correlates in 22, and were the top-ranked correlates in 19. Associations between depressive burden and poor functioning were observed across clinician-rated disability scales and work or social indicators, and across geographically diverse cohorts. Comorbid substance use disorder and medication-related variables were associated with poorer functioning in subsets of cohorts, whereas sex, ancestry, bipolar subtype, psychosis history, and premorbid IQ showed weak or inconsistent associations. Cognitive measures, available in a minority of regression models, showed modest and non-uniform effects. Conclusions Across heterogeneous international cohorts, current depressive symptom burden emerged as the most consistent correlate of poor functioning in bipolar disorder. These findings replicate earlier multisite work at a larger scale, show that protocol-based distributed analyses can identify reproducible clinical signals without sharing individual-level data, and support prioritizing detection and treatment of depressive symptoms when aiming to improve real-world functioning. Future work should expand longitudinal harmonization and representation of under-studied populations.

Mood disorders are highly prevalent. Despite increased rates of treatment provision, treatment gaps are sustained by inadequate targeting of interventions and little emphasis on prevention. Here, the authors present an overview and analysis of the National Network of Depression Centers (NNDC) Mood Outcomes Program, which is both a measurement-based care program, with a standardized set of mood "vital signs" assessed as part of routine clinical care, and a learning health system. The authors analyzed all data collected since the program's inception in 2015 to assess whether baseline symptom severity, prior suicidal ideation or attempts, length of care, and longitudinal symptom severity differed across sociodemographic groups. The results show important treatment needs that are not being fulfilled. Most notably, the groups with the greatest symptom severity were not the groups with the most visits. Efforts to address systemic barriers that prevent access to mental health care are required. Given that the NNDC Mood Outcomes Program is integrated with clinical care, academic programs, and research at each site, the authors anticipate that the program is well suited to support efforts to dismantle systemic barriers to care.

BACKGROUND:Functional status may predict mood outcomes in youth at familial risk for bipolar disorder (BD). This study examined whether baseline functional status of at-risk youth is linked to clinical outcomes over 2-years. METHOD:Aretaeus (named for Aretaeus of Cappadocia) is a multicenter, prospective, observational study. Participants (15-25 years), all offspring of a parent with BD, were stratified by Global Assessment of Function (GAF) score into functionally impaired (GAF ≤ 70; Low-GAF) or not-impaired (GAF > 70; High-GAF) groups. The primary outcome was difference in time spent with clinically significant mood symptoms ([hypo]mania, depression) between groups, assessed using Longitudinal Interval Follow-up Evaluation Psychiatric Status Rating (LIFE-PSR). Outcomes were evaluated at baseline and every 3-months for 24-months. RESULTS:Of 223 eligible participants, 156 (70 %) completed the study. Completion rates were lower in the Low- vs. High-GAF group (60 % vs. 76 %; p = 0.008). Time spent with clinically significant mood symptoms was higher in Low- vs. High-GAF group at baseline (28 vs. 6 weeks, p < 0.0001) and 24-months (30 vs. 11 weeks, p = 0.009). Serious psychiatric adverse events (7.0 % vs. 1.0 %) and psychiatric medication use were more frequent in Low- vs. High-GAF group. BD and new-onset major depressive disorder diagnoses were similar between groups over 24-months. CONCLUSIONS:Baseline Functional impairment in at-risk youth was linked to more time spent with clinically relevant depressive symptoms. Low-GAF participants experienced mood symptoms for a greater period of time than High-GAF participants, suggesting that early functional impairment relates to poorer-clinical course. Assessing psychosocial function in at-risk individuals may help guide future care. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03017781.

Background:Dysregulated ventral prefrontal-subcortical networks are implicated in bipolar disorder, although how connectivity changes within these networks during the emergence and resolution of affective episodes is unclear. To address this knowledge gap, in this post-hoc study, we investigated longitudinal changes in prefrontal-subcortical connectivity during remission from mania in individuals with bipolar I disorder. Methods:We followed 35 individuals with bipolar I disorder through eight weeks of treatment for a manic episode. Using mixed models, we compared changes in ventral prefrontal-subcortical connectivity between individuals who remitted (n = 16, Young Mania Rating Scale/Hamilton Depression Rating Scale < 10 by week eight) and those who did not (n = 19) during emotional distractor conditions of the continuous performance task (CPT-END), a cognitive attentional task with emotional and neutral distractors; at baseline, one and eight weeks of treatment covarying for age and sex. Results:During the eight-week trial, significant group-by-time interactions were found between medial prefrontal cortex and right inferior frontal gyrus pars triangularis. There was also a group-by-time interaction in connectivity between prefrontal cortex and left thalamus, bilateral amygdala, and pregenual anterior cingulate cortex. Conclusion:These results highlight distinct ventral prefrontal-subcortical connectivity patterns characterizing the remitted state in bipolar disorder during tasks requiring focused attention amid emotional distractions. In the context of previous research, remission was associated with more normative connectivity between medial prefrontal and both thalamus and ventrolateral prefrontal cortex. However, while ventral prefrontal-paralimbic/limbic connectivity may show improvement with symptom remission, it may not fully normalize, suggesting residual functional abnormalities despite clinical recovery.

Learning Health Systems (LHSs) promise meaningful health care improvement through the ongoing use of data, including the lived experience of diverse constituents, such as people participating in and providing services. Most LHSs operate within a specific healthcare system, typically hospital-based, under a common electronic health record (EHR) and management structure. The Early Psychosis Intervention Network in Texas (EPINET-TX) is a novel case study of a developing LHS across 16 independent community mental health clinics operating state-funded coordinated specialty care (CSC) programs for early psychosis. EPINET-TX is a partnership among a multidisciplinary research hub and state and local entities. Grounded in participatory research frameworks, multiple strategies were utilized to align partners around learning goals, build data use competencies, enhance researchers' understanding of program context, and cultivate a continuous performance improvement mindset. Key strategies for developing a LHS culture included a) intentionally building collaborative relationships, b) establishing shared values and governance, c) collaborating in research and change-focused workgroups, and d) sharing learning and growth experiences. For CSC programs operating within the public mental health system, the LHS framework provides a promising model to foster quality improvement, innovation, and action-oriented participatory research.

OBJECTIVE:The United States is experiencing a mental health crisis among youths and young adults. Most serious mental health conditions emerge during the transition to adulthood, and unmet mental health needs continue to rise among young adults. Following Australia's success with headspace, several countries are implementing integrated youth mental health programs, which warrant evaluation in the United States. The purpose of this study was to detail the service engagement, acceptability, and preliminary outcomes of the Amplify integrated youth mental health clinic during its first year of operation. METHODS:The University of Texas at Austin Dell Medical School implemented Amplify in a community college setting. Participants completed online standardized self-report measures at enrollment and 60 and 180 days later. Staff recorded service delivery in an electronic health record. Data were analyzed for Amplify's first year of operation (January 1-December 31, 2023). RESULTS:During year 1, Amplify employed a program director, licensed clinical program manager, therapist, supported employment and education specialist, community navigator, part-time psychiatrist, and receptionist. Amplify delivered 1,308 services to 74 youths, 60 of whom consented to participate in the study. Most participated in two types of services. Mean±SD use per participant was 18±18 service units (i.e., sessions). Service satisfaction was high at 60 and 180 days. Mental distress significantly decreased from enrollment to 60 and to 180 days. CONCLUSIONS:More research on Amplify is needed to further operationalize the model and demonstrate its value to U.S. public and private health care systems and payers.

IntroductionAlcohol use disorder (AUD) occurs at higher rates in individuals with bipolar disorder compared to the general population. A paucity of data are available on specific mechanisms that may contribute to bipolar and AUD co-occurrence. We recently reported differences in alcohol expectancies and placebo response during alcohol administration in early-stage bipolar disorder, compared to healthy young adults. This current report investigated subjective and neural response following placebo beverage consumption in young adults with bipolar disorder.MethodsAs part of a within-subject placebo-controlled alcohol administration study, 54 young adults (53% with bipolar disorder type I, agemean + SD = 23 + 2 years, 64% female) completed resting state functional MRI (rsfMRI) scans at baseline (pre-beverage) and following placebo and alcohol consumption (counter-balanced). Participants completed subjective response measures during placebo and alcohol beverage conditions. Between-group differences in subjective response and placebo-related changes in functional connectivity of the Nucleus Accumbens (NAc) with other brain regions, compared to a pre-beverage rsfMRI baseline condition, were investigated. Fisher-transformed correlation coefficients between ROIs and seed-to-clusters showing a significant group-by-condition (placebo, pre-beverage rsfMRI) interaction were calculated. Associations with prospective alcohol use and problems were explored in a subgroup with longitudinal data.ResultsYoung adults with bipolar disorder reported greater intoxication during the placebo condition, compared to healthy young adults (main effects of group: p < 0.05). Compared to pre-beverage rsfMRI, the placebo condition related to increased connectivity between bilateral NAc and regions within the sensorimotor network in bipolar disorder. Comparison participants showed the opposite pattern of placebo-related changes in connectivity (group-by-condition, p-FDR < 0.05). Greater anxiolytic effects endorsed during placebo and associated increases in NAc functional connectivity related to greater alcohol use and alcohol problems at follow-up in bipolar disorder (p < 0.05).DiscussionResults suggest differences in placebo response in bipolar disorder, including distinct neural correlates, that may relate to prospective alcohol use/problems. Given the theoretical association between placebo response and self-reported alcohol expectancies, findings could open the door to interventions aimed at changing expectancies.

Early emotional experiences preceding the onset of bipolar disorder and potentially contributing to core symptoms of emotional liability and dysregulation are not well understood. We hypothesized that individuals with a higher familial risk for bipolar disorder I (i.e., high-risk) would exhibit early differences in emotional experiences compared to youth without such a family history (i.e., low-risk).

Background: Limitations in mental health resources behoove exploration of factors that may enhance treatment response. One such factor, resilience, has been minimally examined in bipolar disorder. Methods: With multi-level modeling of clinical care data, we examined associations among longitudinal measurements of resilience and mood rating trajectories in a sample of 100 individuals with bipolar disorder during 6 weeks of evidence-based pharmacotherapy and psychotherapy. Results: Individuals with high self-care subscale scores from the Resilience Questionnaire for Bipolar Disorder exhibited an improving rate of depression change -0.18 (SE = 0.04, p < .001) completing treatment with a subthreshold depression rating of 3.1 (SE = 1.39, p < .05). In contrast, treatment recipients who disagreed or were neutral towards self-care experienced worsening or no change in depression, respectively. This subscale also decreased mood elevation. Each one-point increase yielded a -0.27 (SE = 0.13 p < .05) point decrease in mania. Limitations: Resilience may develop longitudinally. In this study, it was examined during active treatment which was a relatively brief period of time. Conclusions: Higher bipolar resilience could identify individuals more likely to exhibit improvement in mood during bipolar specialty clinic treatment.