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Open research questions in Bipolar Disorder and Treatment

252 unresolved questions extracted from the limitations and future-work sections of 1,849 Bipolar Disorder and Treatment papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Further research is needed to investigate the relationship between cognitive function and occupational outcomes in bipolar disorder and ADHD. Future studies could examine the effects of interventions on cognitive and occupational functioning in these populations. Research could also explore the underlying mechanisms of cognitive impairments in bipolar disorder and ADHD.

    Cognitive and occupational functioning in bipolar disorder and ADHD: impact of comorbidity · 2026 · DOI

  • The lack of understanding of cognitive and occupational functioning in individuals with bipolar disorder, ADHD, and comorbid bipolar disorder + ADHD. The need to characterise cognitive profiles and examine associations between cognitive and occupational functioning in these conditions.

    Cognitive and occupational functioning in bipolar disorder and ADHD: impact of comorbidity · 2026 · DOI

  • the study lacked generalisability to real-world clinical settings due to restrictive exclusion criteria, - patients enrolled in RCTs typically differ from routine clinical populations, - the study did not involve people with lived experience of bipolar disorder in every phase

    Real-world effectiveness of mono- and combination therapies of mood stabilisers and antipsychotics in bipolar disorder: nationwide, within-individual study of 315 046 patients · 2026 · DOI

  • the potential impact of lithium on end-organ function - the need to minimise the risks associated with lithium use - the decline in lithium's popularity despite its efficacy

    Lithium: challenges of being king · 2026 · DOI

  • Lack of clear biomarker to aid in lithium response prediction, - Limited profitability of lithium for pharmaceutical industry, - Ongoing mystery as to lithium's mechanism of action

    Lithium: challenges of being king · 2026 · DOI

  • The logistical burden of regular venous blood sampling and laboratory monitoring. The need for accurate and reliable measurement of lithium levels. The requirement for patient-operated home-based testing.

    Acceptability and accuracy of point-of-care monitoring of lithium levels · 2026 · DOI

  • further studies are needed to assess the long-term effectiveness of POCT for lithium, - research is needed to determine the cost-effectiveness of POCT for lithium, - studies are needed to evaluate the use of POCT for lithium in different clinical settings, - further research is needed to assess the potential of POCT for patient-operated home-based testing

    Acceptability and accuracy of point-of-care monitoring of lithium levels · 2026 · DOI

  • The study identifies challenges in measuring irritability and psychopathology in adolescents, including the need for reliable and valid measurement scales. The study also notes the challenge of addressing missing data, using Little's Missing Completely at Random test to determine the appropriateness of the data.

    Domain Generality or Domain Specificity? The Associations Between Family Adversity, Irritability, and Psychopathology in Adolescence · 2026 · DOI

  • The paper identifies a gap in the understanding of the associations between family adversity, irritability, and psychopathology in adolescents. The study aims to address this gap by examining the domain-general and domain-specific associations between irritability and psychopathology.

    Domain Generality or Domain Specificity? The Associations Between Family Adversity, Irritability, and Psychopathology in Adolescence · 2026 · DOI

  • There is a need to understand the association between elevated levels of child irritability and functional impairment. Prior work has not fully explored the relationship between parent mental health, behavior, and family functioning with child irritability.

    A Person-Centred Approach to Determine the Links Between Parent Mental Health, Behavior and Family Functioning with Child Irritability · 2026 · DOI

  • Further clarification of the cross-generational transmission of MD and BD, - Examination of risks in offspring of non-intact families, - Investigation of the effects of parental illness on MD→BD conversions

    The risk for major depression and bipolar disorder in the offspring of informative parental mating types: a Swedish population-based study · 2026 · DOI

  • Prior studies have not systematically examined the conversion of major depression to bipolar disorder in relatives. There is a lack of examination of risks in offspring of different parental mating types. The representativeness of cases in prior studies has varied.

    The risk for major depression and bipolar disorder in the offspring of informative parental mating types: a Swedish population-based study · 2026 · DOI

  • Larger, longitudinal studies with repeated measures are needed to examine time-varying associations between CRP and suicide risk among youth with BD - Studies should examine the association of CRP with suicide risk in other populations - Research should investigate the mechanisms underlying the association between CRP and suicide risk

    Elevated C-reactive protein is associated with suicide attempts in youth with bipolar disorder · 2026 · DOI

  • There is a lack of knowledge about the association of CRP with suicidality in youth with bipolar disorder. Prior studies have investigated CRP in relation to bipolar disorder and suicidality independently, but not in the context of youth with bipolar disorder. There is a need for studies that examine the relationship between CRP and suicide attempts in a clinical sample of youth with bipolar disorder.

    Elevated C-reactive protein is associated with suicide attempts in youth with bipolar disorder · 2026 · DOI

  • The complexity of deriving a composite measure of metabolic health from various components. The challenge of accurately predicting BrainAGE using machine learning. The need to control for potential confounding variables, such as symptoms and medications.

    The role of metabolic health in neurostructural and cognitive alterations in bipolar disorders · 2026 · DOI

  • Further research is needed to investigate the relationship between metabolic health and brain/cognitive impairments in BD, - Future studies should examine the effects of metabolic monitoring and screening on brain health and cognitive functioning in BD

    The role of metabolic health in neurostructural and cognitive alterations in bipolar disorders · 2026 · DOI

  • Investigating the neurocognitive underpinnings of cognitive constructs in PBD. Developing more effective pro-cognitive interventions for PBD. Examining the relationship between WM dysfunction and other cognitive impairments in PBD.

    Impaired visuospatial working memory but preserved attentional control in bipolar disorder · 2025 · DOI

  • The lack of understanding of the underlying neurocognitive architecture of bipolar disorder. The absence of sufficiently effective pro-cognitive interventions for bipolar disorder.

    Impaired visuospatial working memory but preserved attentional control in bipolar disorder · 2025 · DOI

  • The complexity of measuring social exclusion. The need for novel socially-focused interventions to improve survival in people with severe mental illness. The challenge of addressing the lack of integrated services and poorer quality care for people with severe mental illness.

    Social exclusion as a determinant of excess mortality in people with schizophrenia-spectrum and bipolar disorders: retrospective cohort study in 0.5 million people · 2025 · DOI

  • The relationship dimension of social exclusion plays an important role in minimizing suicide risk as well as deaths from natural causes, - This will be explored in future work

    Social exclusion as a determinant of excess mortality in people with schizophrenia-spectrum and bipolar disorders: retrospective cohort study in 0.5 million people · 2025 · DOI

  • The paper identifies a gap in the understanding of neural subgroups in unaffected first-degree relatives of patients with bipolar disorder. Previous fMRI studies have yielded incongruent findings on emotion regulation in unaffected relatives. The study aims to address this gap by examining neural subgroups using hierarchical cluster analysis.

    Neural subgroups in unaffected first-degree relatives of patients with bipolar disorder during emotion regulation · 2025 · DOI

  • Thirdly, the cross-sectional design of the current study is insufficient to elucidate the longitudinal effects of the aberrant neural activity in the UR subgroups, but this remains to be investigated in the longitudinal part of the study.

    Neural subgroups in unaffected first-degree relatives of patients with bipolar disorder during emotion regulation · 2025 · DOI

  • Further investigation of IIV in BD is needed, - Investigation of the relationship between IIV and other clinical variables, - Longitudinal studies to examine the stability of IIV over time

    Characterizing intraindividual variability in bipolar disorder: links to cognition, white matter microstructure, and clinical variables · 2025 · DOI

  • Most cognitive research on BD has analyzed case-control differences in measures of central tendency, which may not capture individual fluctuations in cognitive performance. There is a need to examine intraindividual variability in BD and its associations with cognitive measures and white matter microstructure.

    Characterizing intraindividual variability in bipolar disorder: links to cognition, white matter microstructure, and clinical variables · 2025 · DOI

  • The complexity of measuring metabolites in the brain using proton magnetic resonance spectroscopy. The challenge of assessing emotion recognition and prefrontal function in individuals with euthymic bipolar disorder. The need to control for potential confounding factors, such as age and sex, when comparing emotion recognition and prefrontal function between BD and HC groups.

    Executive function mediates prefrontal excitation–inhibition balance and emotion recognition in euthymic bipolar disorder · 2025 · DOI

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252 open questions have been extracted from the limitations and future-work passages of 1,849 Bipolar Disorder and Treatment papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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