Cognitive impairment in bipolar disorder.

Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD. We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials. Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: twoinvolved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and onea serious risk of bias. Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.

An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta-analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view. Individual patient and control data were obtained from original authors for 11 measures from four common neuropsychological tests: California or Rey Verbal Learning Task (VLT), Trail Making Test (TMT), Digit Span and/or Wisconsin Card Sorting Task. Impairments were found for all 11 test-measures in the bipolar group after controlling for age, IQ and gender (Ps ≤ 0.001, E.S. = 0.26-0.63). Residual mood symptoms confound this result but cannot account for the effect sizes found. Impairments also seem unrelated to drug treatment. Some test-measures were weakly correlated with illness severity measures suggesting that some impairments may track illness progression. This reanalysis supports VLT, Digit Span and TMT as robust measures of cognitive impairments in bipolar disorder patients. The heterogeneity of some test results explains previous differences in meta-analyses. Better controlling for confounds suggests deficits may be smaller than previously reported but should be tracked longitudinally across illness progression and treatment.

Bipolar disorder is associated with deficits in cognitive functioning. The etiology of cognitive impairment in bipolar disorder may relate to both genetic and environmental factors. A valine/methionine polymorphism of the catechol O-methyltransferase gene at amino acid 158 (COMT Val158Met polymorphism) has been identified as a risk factor for cognitive impairment in schizophrenia. Serological evidence of infection with herpes simplex virus type 1 (HSV-1) has also been identified as a risk factor for cognitive impairment in bipolar disorder. We used Taqman technology to measure COMT Val158Met alleles in 107 individuals with bipolar disorder and in 95 controls. We also measured antibodies to HSV-1 in sera obtained from the same individuals. Cognitive functioning was assessed with the Repeatable Battery for the Assessment of Neuropsychological Status and the Letter-Number Sequencing Test. The effects of the COMT Val158Met polymorphism and antibodies to HSV-1 on cognitive functioning were analyzed with multinomial logistic regressions. The COMT Val158Val genotype and serological evidence of infection with HSV-1 are independent risk factors for cognitive impairment in individuals with bipolar disorder, particularly in the domains of immediate and delayed memory. Individuals with bipolar disorder with the COMT158 Val/Val genotype and serological evidence of HSV-1 infection were more than 85 times more likely to be in the lowest quintile of cognitive functioning when compared with the highest quintile when controlling for potential confounding variables such as symptom severity and education. Control individuals did not display this association. Both the COMT Val158Met polymorphism and serological evidence of HSV-1 infection affect cognitive functioning in individuals with bipolar disorder.

Bipolar disorder is a chronic, disabling disease that is characterized by the recurrence of thymic episodes. The role of the immune-inflammatory system in the etiopathogenesis of this affection arouses the interest of research. The aim of this work was to determine the plasma levels of the high sensitivity C reactive protein (hs-CRP) in patients with bipolar disorder in remission phase by comparing them to a control group.A case-control cross-sectional study was conducted from 56 subjects with bipolar disorder in clinical remission, and 56 volunteers and healthy control subjects.Mean plasma hs-CRP was significantly higher in patients with bipolar disorder than control subjects. In bipolar patients, a hs-CRP elevation was significantly associated with the disease severity item mean score.Through this study, bipolar disorder appears to be associated with a state of chronic inflammation. This should lead to randomized controlled trials evaluating the value of anti-inflammatory drugs in the management of bipolar disorder.

Bipolar disorder (BD) is commonly associated with cognitive impairments, that directly contribute to patients' functional disability. However, there is no effective treatment targeting cognition in BD. A key reason for the lack of pro-cognitive interventions is the limited insight into the brain correlates of cognitive impairments in these patients. This is the first study investigating the resting-state neural underpinnings of cognitive impairments in different neurocognitive subgroups of patients with BD. Patients with BD in full or partial remission and healthy controls (final sample of n = 144 and n = 50, respectively) underwent neuropsychological assessment and resting-state functional magnetic resonance imaging. We classified the patients into cognitively impaired (n = 83) and cognitively normal (n = 61) subgroups using hierarchical cluster analysis of the four cognitive domains. We used independent component analysis (ICA) to investigate the differences between the neurocognitive subgroups and healthy controls in resting-state functional connectivity (rsFC) in the default mode network (DMN), executive central network (ECN), and frontoparietal network (FPN). Cognitively impaired patients displayed greater positive rsFC within the DMN and less negative rsFC within the ECN than healthy controls. Across cognitively impaired patients, lower positive connectivity within DMN and lower negative rsFC within ECN correlated with worse global cognitive performance. Cognitive impairments in BD seem to be associated with a hyper-connectivity within the DMN, which may explain the failure to suppress task-irrelevant DMN activity during the cognitive performance, and blunted anticorrelation in the ECN. Thus, aberrant connectivity within the DMN and ECN may serve as brain targets for pro-cognitive interventions.

Background:Despite significant advances in pharmacological and psychological therapies for bipolar disorder, many people continue to have less than optimal outcomes, which are associated with significant disability and poor quality of life (QOL). This study aimed to assess the disability and QOL and factors associated with such suboptimal outcomes in subjects with bipolar disorder in remission.Methods:Consecutive patients diagnosed to have bipolar disorder in remission attending the Department of Psychiatry, MOSC Medical College, Kerala, India were recruited for the study. They were assessed using the International Classification of Diseases Diagnostic Criteria for Research-10, Hamilton Scale for Depression, Young's Mania Rating Scale, World Health Organization-QOL (WHO QOL-BREF), WHO-Disability Assessment Scale (WHO-DAS), and Kuppuswamy's scale for socioeconomic status assessment.Results:Eighty-four patients were evaluated. The mean total WHO-DAS score was 19.2 ± 2.09, the maximum disability in domain 4 (getting along) followed by domain 2 (mobility). The mean total WHO-QOL BREF score was 54.26 ± 2.85, the lowest subscore in domain 3 (social interactions). Disability scores were significantly associated with increasing age, female gender, not being an earning member of the family, and lower QOL scores. Poorer QOL scores were significantly associated with increasing age and higher disability score.Conclusions:Many bipolar patients in remission have significant disability and poorer QOL. There is a need for longitudinal studies to explore such associations and develop interventions to reduce the disability thereby enhancing the QOL.

Chronotype is trait-like construct reflecting long-term morningness-eveningness preferences. Higher eveningness scores are linked to sleep disturbances, night-eating, and addictive behaviors but remain understudied in subjects with bipolar disorder (BD). This study aimed to explore the clinical and behavioral factors associated with chronotype in a euthymic cohort with BD. Adult individuals (18-45 years) with DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition) diagnosis of BD in clinical remission (≥3 months) were enrolled, if they did not have current psychiatric or substance use disorder as per Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST score < 27). Participants were assessed using the validated Hindi version of Composite Scale of Morningness-Eveningness (CSM), the National Institute of Mental Health (NIMH)-Life Chart Method, IGLSI (International Group for Study of Lithium) Scale for typical/atypical features, Pittsburgh Sleep Quality Index, Cognitive complaints in BD Rating Assessment, Seasonal Pattern Assessment Questionnaire, Bipolar Eating Disorder Scale, Internet Disorder Scale, and Functioning Assessment Short Test. After data normalization, exploratory factor analysis was conducted using principal component analysis with varimax rotation on the study variables excluding the CSM. Subsequently, regression analysis was performed with CSM as the dependent variable. The mean age of the sample was 32.43 ± 7.68 years (n = 100; 35% females). Factor analysis revealed a latent structure with three factors: Factor 1 (global functioning), Factor 2 (disordered biological functions and rhythms), and Factor 3 (dysfunction due to sleep and internet use). The regression model was found to be statistically significant [F (3,96) = 5.520, P = 0.002; R2 = 0.147, adjusted R2 = 0.120). Factor-2 was a significant predictor of CSM score (B = -2.201, SE: 0.606, P < 0.001). For every unit increase in Factor 2 score, the CSM total score reduced on average by 2.2 units. This study highlights the role of disrupted sleep, eating behaviors, and seasonality in influencing the chronotype and their interconnectedness in individuals with BD.

IntroductionIn bipolar disorder, cognitive deficits persist across mood episodes and euthymia. Despite recent advances, cognitive impairment in bipolar disorder remains poorly understood. The presentation will focus on recent work where different approaches are used to clarify the role of cognitive deficits in bipolar disorder.ObjectivesFirst, we have examined the clinical relevance of cognitive impairments and examined if cognitive abilities differ between bipolar disorder subtypes and healthy controls. Second, we examined if cognitive abilities differ between individuals with bipolar disorder with and without attention-deficit hyperactivity disorder. Third, we examined the relationship between cognitive functioning and occupational functioning. Lastly, we examined if long-term changes in cognitive functioning in bipolar disorder patients differ from normal aging.MethodsThe St. Göran Bipolar Project is an interdisciplinary, prospective, naturalistic study of bipolar disorder. Patients were recruited and followed-up at two specialized out-patient clinics in Stockholm and Gothenburg, Sweden.ResultsWe showed that there is evidence for significant cognitive heterogeneity in bipolar disorder. Comorbid ADHD could not explain this heterogeneity. Moreover, we showed that excutive functioning is a powerful predictor of occupational functioning. The cognitive trajectory over a 6-year period did not differ between bipolar disorder patients and healthy controls.ConclusionsThere is no conclusive cognitive profile characterizing bipolar disorder. However, cognitive functioning is of great importance in understanding occupational functioning in bipolar disorder. Contrary to the assumption that cognitive impairments may be progressive we show that changes in cognitive functioning over time do not differ between patients and healthy controls.DisclosureNo significant relationships.

BackgroundThe International Society for Bipolar Disorders Targeting Cognition Task Force recommends the Screen for Cognitive Impairment in Psychiatry (SCIP) to screen for cognitive impairment in bipolar disorder. However, SCIP must be administered by a healthcare professional, which is often impossible due to time and resource constraints. Web-based, self-administered cognition screening tools may enable assessment and monitoring of patients’ cognition at a much larger scale to a reduced cost. For this purpose, we developed the Internet-Based Cognitive Assessment Tool (ICAT) as a modified web-based version of SCIP. This study aimed to investigate the sensitivity and validity of ICAT for cognition assessment in bipolar disorder. MethodThirty-five patients with bipolar disorder in full or partial remission and 35 healthy controls completed ICAT on a computer, the standard paper-and-pencil SCIP and a subjective cognition questionnaire and were rated for mood symptoms and functioning at the Copenhagen Affective Disorders Research Centre. ResultsPatients displayed cognitive impairments compared to controls on the ICAT (t (61)=3.67, p<.001, d=0.93). There was a strong correlation between ICAT and SCIP Total Scores (r(61)=.72, p<.000) and moderate to strong correlations on subtest scores (r=.48-.63, ps<.001). Across all participants, lower ICAT scores correlated with more subjective cognitive complaints (r(59)=-.43, p<.001) and poorer psychosocial functioning (r(62)=-.47, p<.001). ConclusionICAT is a sensitive and valid web-based tool for cognition assessment in patients with bipolar disorder. This highlights ICAT as a novel web-based cognition screening tool that is feasible for largescale assessment and monitoring of cognition in the clinical management of bipolar disorder.

Review for "Structural brain abnormalities associated with cognitive impairments in bipolar disorder"

Research on cognitive impairment in bipolar disorder (BD) has prompted significant insights about the illness. New studies challenge previous notions about the episodic nature of BD, and account for psychosocial disability unrelated to mood disturbance. This article provides a conceptual overview of the growing body of research on cognitive dysfunction in BD. We discuss the evidence in light of the complexity inherent in the connection between cognitive deficits and neurological abnormalities in BD. This article also addresses issues related to etiology, advancing an integration of neurological, clinical, cognitive, and psychosocial factors into a model that elucidates how these factors interact to negatively impact persons with BD with a more severe course of illness. Lastly, this article discusses implications for patient care and future considerations.

Aims: Previous comparisons of cognitive decline among patients with bipolar disorder (BD) and schizophrenia (SZ) have found somehow quite similar profiles of deficits, but results have varied between studies. Therefore an extensive and thoughtful systematic review of the matter is warranted.Methods: Studies were found through systematic search (PubMed) following PRISMA guidelines. To be included, studies must have assessed the following cognitive functions: executive functions, memory, IQ, attention-concentration, and perceptuomotor function. In order to make comparison between the two entities, studies should include BD patients with operationally defined euthymia, schizophrenic patients in remission, and third group of healthy control patients. Comparisons were made after controlling for years of schooling and residual affective symptoms.Results: We found that overall both SZ and BD patients present deficits on all neurocognitive measures compared to healthy controls. In particular, SZ patients show more severe and pervasive cognitive deficits while BD patients present a milder and more confined impairment. In addition, evidence from the literature suggests that SZ and BD patients share a similar cognitive impairment profile with different degrees of deficits. Therefore, the difference between the two groups seems to be more quantitative (degree of deficit) rather than qualitative (profile), supporting a dimensional approach to the two clinical entities. Limitations of the present review includes the impossibility to control for effects of medication, varying time required for assessment across studies, illness diagnosis reliability, and course severity.Conclusion: Patients with BD might exhibit a cognitive impairment that could be similar to SZ in terms of their profile, although patients with SZ may have more severe and widespread impairments.

Objectives This study examined cognition-immune interactions, specifically executive function, working memory, peripheral levels of tumour necrosis factor-alpha (TNF-α), and soluble tumour necrosis factor receptors-1 and −2 (sTNFR1 and 2) levels in bipolar disorder (BD) patients in comparison with controls. Methods Thirty-one BD participants and twenty-seven controls participated in the study. The neurocognitive assessment was performed through three of CogState Research BatteryTM tasks for executive function and working memory. Plasma levels of TNF-α, sTNFR1, and sTNFR2 were measured after overnight fasting. Sociodemographic data and symptom severity of depression and mania were assessed. Results BD presented a significantly worse performance in the working memory task (p = .005) and higher levels of TNF-α (p = .043) in comparison to controls. A trend level of significance was found for sTNFR1 between groups (p = .082). Among BD participants, there were significant correlations between sTNFR2 and neurocognitive tasks (Groton Maze Learning Task: ρ = .54, p = .002; Set-Shifting Task: ρ = .37, p = .042; and the Two-Back Task: ρ = –.49, p = .005), and between sTNFR1 and mania, depression and anxiety symptoms (respectively ρ = .37, p = .038; ρ = –.38, p = .037; and ρ = .42, p = .002). Conclusion TNF-α and its receptors might be an important variable in cognitive impairment in BD. Future studies might focus on the development of anti-inflammatory therapeutic targets for cognitive dysfunction in BD.

Mood disorders are often associated with persistent cognitive impairments. However, pro-cognitive treatments are essentially lacking. This is partially because of poor insight into the neurocircuitry abnormalities underlying these deficits and their change with illness progression. This functional magnetic resonance imaging (fMRI) study investigates the neuronal underpinnings of cognitive impairments and neuronal change after mood episodes in remitted patients with bipolar disorder (BD) using a hippocampus-based picture encoding paradigm. Remitted patients with BD (n=153) and healthy controls (n=52) were assessed with neuropsychological tests and underwent fMRI while performing a strategic picture encoding task. A subgroup of patients (n=43) were rescanned after 16 months. We conducted data-driven hierarchical cluster analysis of patients' neuropsychological data and compared encoding-related neuronal activity between the resulting neurocognitive subgroups. For patients with follow-up data, effects of mood episodes were assessed by comparing encoding-related neuronal activity change in BD patients with and without episode(s). Two neurocognitive subgroups were revealed: 91 patients displayed cognitive impairments while 62 patients were cognitively normal. No neuronal activity differences were observed between neurocognitive subgroups within the dorsal cognitive control network or hippocampus. However, exploratory whole-brain analysis revealed lower activity within a small region of middle temporal gyrus in impaired patients, which significantly correlated with poorer neuropsychological performance. No changes were observed in encoding-related neuronal activity or picture recall accuracy with the occurrence of mood episode(s) during the follow-up period. Memory encoding fMRI paradigms may not capture the neuronal underpinnings of cognitive impairment or effects of mood episodes.

Cognitive performance is impaired in euthymic Chinese patients with Bipolar 1 Disorder