Cognitive Functioning In Bipolar Disorder Research Articles

Cognitive performance in bipolar disorder: Comparison between individuals with and without suicide attempts and healthy controls

IntroductionBipolar disorder (BD) presents an elevated risk of suicide. One hypothesis for this is that cognitive impairments contribute to suicidal behavior. However, the relationship between cognition and suicidal behavior in BD remains unclear. ObjectiveTo compare cognitive performance in individuals with BD with previous suicide attempts vs no attempt vs healthy controls (HC). MethodsWe included 306 participants: 101 individuals with BD (49 with previous suicide attempts and 52 without attempts) and 205 HC. Participants underwent a clinical interview and neuropsychological evaluation. We assessed cognitive performance in social cognition, episodic verbal memory, working memory, processing speed, executive functioning, sustained attention, and intelligence. Afterwards, individuals with BD were separated between groups with and without suicide attempts. We then compared cognitive performance and clinical characteritics between groups. ResultsIndividuals with BD who attempted suicide had more hospitalizations, higher prevalence of psychiatric family history, and overall greater functional impairment. Regarding cognition, HC outperformed both BD groups, with the exception of social cognition and Stroop Color-Word and interference weighted score. However, there were no significant differences in cognitive performance among both BD groups. LimitationsCross-sectional design and dichotomization between suicide attempt vs. no attempt ConclusionsBD with previous suicide attempt present worse clinical outcomes and higher illness severity. Nevertheless, there were no cognitive differences among individuals with BD with and without suicide attempts. Both BD groups may share a vulnerability for cognitive impairment, but not for clinical and functional outcomes. Our results point to significant heterogeneity among clinical and functioning areas of BD.

Cognition in Bipolar Disorder: An Update for Clinicians.

Bipolar disorder is associated with cognitive deficits, which persist across mood states and affect functional outcomes. This article provides an overview of recent progress in measuring cognition in bipolar disorder and its implications for both research and clinical practice. The authors summarize work conducted over the past decade that has helped guide researchers and clinicians in the appropriate measurement of cognitive functioning in bipolar disorder, the design of research studies targeting this domain for treatment, and the implementation of screening and psychoeducational tools in the clinic. Much of this work was conducted by the International Society for Bipolar Disorders Targeting Cognition Task Force. Here, the authors also highlight the need for clinicians to be informed about this aspect of illness and to be equipped with the necessary information to assess, track, and intervene on cognitive problems when appropriate. Finally, the article identifies gaps in the literature and suggests potential future directions for research in this area.

Telomere length and verbal learning in bipolar disorders

IntroductionRecent studies indicate accelerated ageing processes, shorter telomere length and poorer cognitive functioning in patients with bipolar disorder. The neurobiology underlying cognitive function in bipolar disorder is yet to be established. We anticipated that accelerated ageing as indicated by shortened telomere length, would be associated with reduced cognitive performance in bipolar disorder, particularly for ageing sensitive functions such as memory and learning. MethodsThe study consisted of 647 participants (bipolar disorder [n = 246] and healthy controls [n = 401]). All participants underwent a standardized neuropsychological test battery, including working memory, executive functioning, processing speed, verbal learning, and verbal memory. Leucocyte telomere length was measured via blood and determined by quantitative real-time Polymerase Chain Reaction (qPCR) providing a telomere to single copy ratio (T/S ratio). The T/S ratio was used as an estimate of the mean telomere length of each participant. All analyses were adjusted for medication, Daily Defined Dose (DDD), chronological age, sex, and ethnicity. ResultsPatients had shorter telomere lengths than healthy controls (Cohen's d = 0.11, p = 0.01). Within patients', a positive association was observed for verbal learning and telomere length (β = 0.14, p = 0.025), along with a trend for verbal memory and telomere length (β = 0.11, p = 0.07). No other associations were observed for telomere length and cognitive functioning in the patient or the control group (p > 0.1). ConclusionOur study may suggest poorer brain health in bipolar disorder as indexed by shorter telomere length and reduced learning correlates. However, the role of telomere length on cognitive functioning in bipolar disorder seems limited.

Long-term course of cognitive functioning in bipolar disorder: A ten-year follow-up study.

Cognitive impairments are common in bipolar disorder (BD), but the long-term course remains understudied. Longitudinal data on cognitive functioning from the start of the first treatment could help clarify pathophysiological processes that shape the illness outcome. We here aim to investigate the 10-year cognitive course in BD compared to healthy controls (HC) and the effects of clinical symptoms on cognitive trajectories. Fifty-six BD participants recruited within their first year of treatment and 108 HC completed clinical and cognitive assessments at baseline and 10-year follow-up. We derived eight cognitive domain scores and a cognitive composite score, which were further investigated using linear mixed model analyses. Correlation analyses were used to assess associations between the composite score and depressive, manic and psychotic symptoms. BD participants performed poorer than HCs in all domains except mental speed and verbal fluency. Verbal learning and memory, verbal fluency and the composite score improved over time in both BD participants and HC, while short-term memory, mental speed, psychomotor speed and working memory were stable. We found no significant correlations between cognition and symptom level at either time point in BD participants. We found evidence of long-term cognitive stability or improvement in BD participants from first treatment to 10-year follow-up. Though the BD group was impaired in all domains except mental speed and verbal fluency, the change in cognitive functioning was parallel to that of HCs. These findings are not consistent with the notion of neuroprogression in BD.

Targeted visual cortex stimulation (TVCS): a novel neuro-navigated repetitive transcranial magnetic stimulation mode for improving cognitive function in bipolar disorder

A more effective and better-tolerated site for repetitive transcranial magnetic stimulation (rTMS) for treating cognitive dysfunction in patients with bipolar disorder (BD) is needed. The primary visual cortex (V1) may represent a suitable site. To investigate the use of the V1, which is functionally linked to the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), as a potential site for improving cognitive function in BD. Seed-based functional connectivity (FC) analysis was used to locate targets in the V1 that had significant FC with the DLPFC and ACC. Subjects were randomly assigned to 4 groups, namely, the DLPFC active-sham rTMS (A1), DLPFC sham-active rTMS (A2), ACC active-sham rTMS (B1), and ACC sham-active rTMS groups (B2). The intervention included the rTMS treatment once daily, with five treatments a week for four weeks. The A1 and B1 groups received 10 days of active rTMS treatment followed by 10 days of sham rTMS treatment. The A2 and B2 groups received the opposite. The primary outcomes were changes in the scores of five tests in the THINC-integrated tool (THINC-it) at week 2 (W2) and week 4 (W4). The secondary outcomes were changes in the FC between the DLPFC/ACC and the whole brain at W2 and W4. Of the original 93 patients with BD recruited, 86 were finally included, and 73 finished the trial. Significant interactions between time and intervention type (Active/Sham) were observed in the scores of the accuracy of the Symbol Check in the THINC-it tests at baseline (W0) and W2 in groups B1 and B2 (F = 4.736, p = 0.037) using a repeated-measures analysis of covariance approach. Group B1 scored higher in the accuracy of Symbol Check at W2 compared with W0 (p < 0.001), while the scores of group B2 did not differ significantly between W0 and W2. No significant interactions between time and intervention mode were seen between groups A1 and A2, nor was any within-group significance of FC between DLPFC/ACC and the whole brain observed between baseline (W0) and W2/W4 in any group. One participant in group B1 experienced disease progression after 10 active and 2 sham rTMS sessions. The present study demonstrated that V1, functionally correlated with ACC, is a potentially effective rTMS stimulation target for improving neurocognitive function in BD patients. Further investigation using larger samples is required to confirm the clinical efficacy of TVCS.

Negative mood states as a correlate of cognitive performance and self-assessment of cognitive performance in bipolar disorder versus schizophrenia

IntroductionMood states have been reported to manifest a cross-sectional correlation with self-assessment accuracy across functional domains and psychiatric conditions. Ecological momentary assessment (EMA) provides a strategy to examine the momentary course and correlates of mood states. This study tested the association of moods assessed longitudinally with accuracy of immediate self-assessments of cognitive test performance in participants with schizophrenia and bipolar disorder. Methods240 well-diagnosed participants with schizophrenia and bipolar disorder completed a subset of tests from the MATRICS Consensus Cognitive Battery and an immediate self-assessment of cognitive performance. Differences between actual and self-reported performance were used to index the accuracy of self-assessment. Daily smartphone EMA, 3× per day for 30 days, sampled participants´ momentary moods (sad, happy, relaxed, anxious), aggregated into positive affect and negative affect (NA). ResultsBipolar participants had better cognitive performance, but both samples had equivalent mis-estimation. Repeated-measures analyses found that NA did not manifest significant variability over time either between or within participants in the two diagnostic groups. Within-group analyses found that higher average NA was associated with greater mis-estimation and poorer cognitive performance in participants with bipolar disorder, but not in those with schizophrenia. ConclusionNegative moods had a significant association with impairments in self-assessment of cognitive performance in participants with bipolar disorder. Our study did not confirm previous cross-sectional findings of more accurate self-assessment associated with greater NA in schizophrenia. These findings suggest that cross-sectional assessments, particularly self-reports, may lead to different results than aggregated data from longitudinal evaluations.

A cross-sectional study of cognitive performance in bipolar disorder across the lifespan: the cog-BD project.

Neuroprogressive models of the trajectory of cognitive dysfunction in patients with bipolar disorder (BD) have been proposed. However, few studies have explored the relationships among clinical characteristics of BD, cognitive dysfunction, and aging. We conducted a cross-sectional analysis in euthymic participants with the MATRICS Cognitive Consensus Battery, the Trail Making Test B, the Stroop Test, and the Wechsler Test of Adult Reading. Age- and gender-equated control participants without a mental disorder ['Healthy Controls' - HC)] were assessed similarly. We compared cognitive performance both globally and in seven domains in four groups: younger BD (age ⩽49 years; n = 70), older BD (age ⩾50 years; n = 48), younger HC (n = 153), and older HC (n = 44). We also compared the BD and HC groups using age as a continuous measure. We controlled for relevant covariates and applied a Bonferroni correction. Our results support both an early impairment ('early hit') model and an accelerated aging model: impairment in attention/vigilance, processing speed, and executive function/working memory were congruent with the accelerated aging hypothesis whereas impairment in verbal memory was congruent with an early impairment model. BD and HC participants exhibited similar age-related decline in reasoning/problem solving and visuospatial memory. There were no age- or diagnosis-related differences in social cognition. Our findings support that different cognitive domains are affected differently by BD and aging. Longitudinal studies are needed to explore trajectories of cognitive performance in BD across the lifespan.

A one-year view on the association of metabolic syndrome and cognitive function in bipolar disorder – Preliminary data

BackgroundIndividuals with bipolar disorder have a high prevalence of metabolic syndrome and an increased risk for cognitive deficits. The aim of this longitudinal study was to investigate the trajectory of cognitive decline in dependence of metabolic syndrome over a one-year interval. Methods52 well-diagnosed individuals with bipolar disorder, euthymic at baseline and follow-up (n = 17 with metabolic syndrome vs. n = 35 without metabolic syndrome) were investigated with a comprehensive neurocognitive test battery (Trail Making Test A/B, Digit Symbol Test, California Verbal Leaning Test, or the Verbal Learning and Memory Test respectively) twice within the interval of one year. ResultsPatients with bipolar disorder and additional metabolic syndrome performed significantly worse in the domain of psychomotor and processing speed/attention than patients without metabolic syndrome at test point one. No deteriorating effects of metabolic syndrome on the cognitive domain scores and overall cognitive performance were found at the one-year follow up. However, no cognitive decline could be reported in both groups. LimitationsTime interval, small sample size and selection of metabolic syndrome affected patients were the major limitations of this study. ConclusionThere was no association of metabolic syndrome on the one-year trajectory of cognitive function in bipolar disorder. Future studies should expand the observation period and investigate larger samples.

Future approaches to investigating cognitive functioning in bipolar disorder.

Future approaches to investigating cognitive functioning in bipolar disorder.

Cognitive subgroups and their longitudinal trajectories in bipolar disorder.

IntroductionCognitive functioning in bipolar disorder is heterogeneous with evidence for multiple subgroups. However, cognitive subgroup change patterns over time remains unknown. While prior work suggests minimal differences in cognitive functioning patterns over time between those with bipolar disorder and controls, group‐based analyses may obscure unique subgroup‐based changes.Material and MethodsParticipants diagnosed with bipolar disorder (I, II, NOS; n = 568) and unaffected controls (n = 234) completed baseline, one‐ and five‐year neuropsychological assessments. Data reduction techniques were used to limit the number of neuropsychological variables. Bipolar disorder participant baseline neuropsychological data were entered into hierarchical cluster analyses and resultant clusters were entered in multilevel models, which tested for differences in baseline and longitudinal cognitive changes in cognition among the cluster groups and with controls.ResultsResults were consistent with bipolar disorder participants forming three subgroups with high (n = 209), mid (n = 259), and low (n = 100) cognition. These groups were associated with unique clinical characteristics. Multilevel models demonstrated that over a five‐year period, the low group improved, relative to the high and mid groups, and with controls, in auditory memory. Over the five‐year period, the mid group, in comparison with the high group, improved in visual memory; additionally, the high group remained stable, in comparison with a slight decline in the control group, in inhibitory control.ConclusionThese results demonstrate that cognition‐based subgroups of bipolar disorder participants have minimal differences in their longitudinal course in relation to each other and with unaffected controls.

Gut Microbial Dysbiosis and Cognitive Impairment in Bipolar Disorder: Current Evidence.

Recent studies have reported that the gut microbiota influences mood and cognitive function through the gut-brain axis, which is involved in the pathophysiology of neurocognitive and mental disorders, including Parkinson’s disease, Alzheimer’s disease, and schizophrenia. These disorders have similar pathophysiology to that of cognitive dysfunction in bipolar disorder (BD), including neuroinflammation and dysregulation of various neurotransmitters (i.e., serotonin and dopamine). There is also emerging evidence of alterations in the gut microbial composition of patients with BD, suggesting that gut microbial dysbiosis contributes to disease progression and cognitive impairment in BD. Therefore, microbiota-centered treatment might be an effective adjuvant therapy for BD-related cognitive impairment. Given that studies focusing on connections between the gut microbiota and BD-related cognitive impairment are lagging behind those on other neurocognitive disorders, this review sought to explore the potential mechanisms of how gut microbial dysbiosis affects cognitive function in BD and identify potential microbiota-centered treatment.

Nutrition, Overweight, and Cognition in Euthymic Bipolar Individuals Compared to Healthy Controls.

Bipolar disorder (BD) is associated with impairments in cognitive functions, in which metabolic factors, e.g., overweight, seem to play a significant role. The aim of this study was to investigate the association between nutritional factors and cognitive performance in euthymic individuals with BD. A study cohort of 56 euthymic individuals with BD was compared to a sample of 53 mentally healthy controls. To assess cognitive function, the following tests were applied: California Verbal Learning Test, Trail Making Test A/B, d2 Test of Attention-Revised, and Stroop’s Color-Word Interference Test. Furthermore, a 4-day food record was processed to evaluate dietary intake of macronutrients, specific micronutrients, and food diversity. Body mass index and waist to height ratio were calculated to assess overweight and central obesity. Results showed no nutritional differences between individuals with BD and controls. Individuals with BD performed worse in the d2 test than controls. Hierarchical regression analyses yielded no association between cognitive and nutritional parameters. However, waist to height ratio was negatively correlated with almost all cognitive tests. Central obesity seems to affect cognitive functioning in BD, while the lack of finding differences in nutritional data might be due to problems when collecting data and the small sample size. Consequently, further studies focusing on objectively measuring food intake with adequate sample size are needed.

Cognitive Dysfunction in Mood Disorder: Similarities and Differences Between Depression Subtypes

Cognitive dysfunction is common in depression. Depression is heterogeneous conditions that comprise biologically diverse subtypes. This manuscript reviewed the similarities and differences in cognitive function between major depressive disorder (MDD) and bipolar disorder (BD). Relatively few studies have compared the cognitive function in BD and MDD; furthermore, the differences might exist between BD types I and II. The neurobiological background of cognitive impairment in MDD and BD involves structural and functional disturbances in neural circuits, as well as disturbances in the connectivity of cognitive networks. Several clinical factors such as symptom severity, onset age, premorbid IQ, psychotic features, and illness course may influence cognitive dysfunction in depression. To understand the differences between the cognitive dysfunctions of MDD and BD, the aforementioned features should be controlled. Setting a standard of evaluating cognitive functions in various mood disorders will be a critical step for future studies. [ Psychiatr Ann . 2022;52(3):100–104.]

Differential association of cortisol with visual memory/learning and executive function in Bipolar Disorder

The association of cortisol with cognition has been understudied in Bipolar Disorder (BD); available evidence is inconsistent while it is unknown whether cortisol's effects vary across neurocognitive domains implicating different brain structures. This study aimed to examine the association of cortisol with two cognitive tasks targeting visual memory and executive function (planning) in BD, related to the hippocampus and prefrontal lobe, respectively. Cambridge Neuropsychological Test Automated Battery (CANTAB) tasks targeting paired associative learning (PAL) and planning (Stockings of Cambridge; SOC) were administered to 60 BD type I patients. Basal serum cortisol was also measured. Higher cortisol was associated with worse performance in PAL, but not SOC, after controlling for gender, education, illness duration and treatment with mood stabilizers. This is the first study to examine the association of cortisol with neurocognitive function in BD while controlling for clinicodemographic and treatment-related factors. We found a significant association of cortisol with hippocampal-related visual memory/learning but not with prefrontal lobe-related executive function, suggesting domain-specific underlying mechanisms of cognitive dysfunction in BD. Future studies should further explore cortisol's brain structure-specific effects on cognitive functioning in BD.

Effect of Pharmacological and Neurostimulation Interventions for Cognitive Domains in Patients with Bipolar Disorder: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

IntroductionThe priority of interventions to alleviate cognitive deficits in patients with bipolar disorder (BD) is inconclusive. We systematically evaluate the efficacy of pharmacological or neurostimulation interventions for cognitive function in BD through a network meta-analysis.MethodsThe PubMed, PsycINFO, Embase, and Cochrane Library databases were searched from database inception to September 30, 2021. Following PRISMA guidelines, all eligible studies were randomized controlled trials of adult bipolar patients that provided detailed cognitive outcomes. Studies were excluded if participants limited to comorbid substance use disorder or the intervention was a psychotherapy. Network meta-analysis comparing different interventions was conducted for 8 cognitive domains. Partially ordered set with Hasse diagram was used to resolve conflicting rankings between outcomes. The study was preregistered on PROSPERO database (CRD42020152044).ResultsTotal 21 RCTs including 42 tests for assessing intervention effects on cognition were retrieved. Adjunctive erythropoietin (SMD = 0.61, 95% CI = 0.00–1.23), Withania somnifera (SMD = 0.58, 95% CI = 0.03–1.13), and galantamine (SMD = 1.22, 95% CI = 0.10–2.35) was more beneficial for attention, working memory, and verbal learning in euthymic BD patients than treatment as usual, respectively. Hasse diagram suggested ranking of choice when multiple domains were combined.ConclusionConsiderable variability in measurements of cognitive domains in BD was observed, and no intervention resulted in superior benefits across all domains. We suggested interventions priority can be tailored according to individual patients’ cognitive deficits. As current findings from relatively small and heterogeneous dataset, future trials with consensus should be applied for building further evidence.

Characterization and interrelationships of theory of mind, socially competitive emotions and affective empathy in bipolar disorder.

Evidence shows impaired theory of mind (ToM) in patients with bipolar disorder (BD), yet research examining its cognitive and affective components simultaneously is sparse. Moreover, recognition of socially competitive 'fortune of others' emotions (e.g. envy/gloat) may be related to ToM, but has not been assessed in BD. Finally, if and how ToM and 'fortune of others' emotions relate to affective empathy in BD is currently unclear. This study aimed to address these points. 64 BD patients and 34 healthy controls completed the Yoni task, a visual task assessing first- and second-order cognitive and affective ToM as well as 'fortune of others' emotions. The Toronto Empathy Questionnaire was used to assess self-reported affective empathy. Patients with BD showed no deficits in cognitive and affective ToM or recognition of 'fortune of others' emotions. The ability to infer 'fortune of others' emotions correlated with several ToM measures, indicating that these functions are part of the same system. Patients with BD reported similar levels of affective empathy to healthy controls, and this was not related to ToM or 'fortune of others' emotions, suggesting that affective empathy represents a separate social domain. These findings highlight areas of spared social functioning in BD, which may be utilized in therapeutic strategies. Our results suggest theory of mind and empathy may represent areas of potentially spared cognitive functioning in BD. As many BD patients have experienced adversity during developmental periods in which theory of mind and empathy develop, our findings suggest that these abilities may be markers of resilience in the disorder. Our findings are important for the formulation of therapeutic interventions for BD, which may include considering practical ways that a patients' knowledge of intact ToM and empathy could be utilized to reduce self-stigma and promote self-efficacy, improved well-being and functioning.

Long-term trajectory of cognitive performance in people with bipolar disorder and controls: 6-year longitudinal study.

Cross-sectional studies have found impaired cognitive functioning in patients with bipolar disorder, but long-term longitudinal studies are scarce. The aims of this study were to examine the 6-year longitudinal course of cognitive functioning in patients with bipolar disorder and healthy controls. Subsets of patients were examined to investigate possible differences in cognitive trajectories. Patients with bipolar I disorder (n = 44) or bipolar II disorder (n = 28) and healthy controls (n = 59) were tested with a comprehensive cognitive test battery at baseline and retested after 6 years. We conducted repeated measures ANCOVAs with group as a between-subject factor and tested the significance of group and time interaction. By and large, the change in cognitive functioning between baseline and follow-up did not differ significantly between participants with bipolar disorder and healthy controls. Comparing subsets of patients, for example those with bipolar I and II disorder and those with and without manic episodes during follow-up, did not reveal subgroups more vulnerable to cognitive decline. Cognitive performance remained stable in patients with bipolar disorder over a 6-year period and evolved similarly to healthy controls. These findings argue against the notion of a general progressive decline in cognitive functioning in bipolar disorder.

Repetitive transcranial magnetic stimulation for cognitive function in adults with bipolar disorder: A pilot study

BackgroundCognitive deficits are prevalent in bipolar disorder and are a significant contributor to negative patient-reported outcomes. Herein we conducted a pilot study of repetitive transcranial magnetic stimulation (rTMS) to improve cognitive function in adults with bipolar disorder. MethodsThe study was a triple-blinded, randomized, placebo-control trial. Participants (aged 18 to 60) with a diagnosis of DSM-5-defined bipolar disorder (I or II) were recruited and randomized (N=36) to receive either a sham treatment (n=20) or an active rTMS treatment (n=16). Patients completed the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) at baseline and 1-2 weeks after the rTMS intervention. ResultsA significant group by time interaction was observed in the Hopkins Verbal Learning Test-Revised (HVLT-R), (F (1, 34) = 17.0, p < 0.001, partial η2 = 0.33). Post-hoc analysis revealed that although both groups did not significantly differ at baseline (p = 0.58), patients in the active rTMS group significantly improved following neurostimulation (p = 0.02) for HVLT-R. Moreover, within-subject analysis indicated that the active rTMS group significantly improved in score from pre-treatment to post-treatment (p < 0.001), while the sham group did not improve (p = 0.94) for HVLT-R. No significant differences were seen in the other cognitive measures. LimitationsThe study was conducted in a small sample . ConclusionThis pilot study, which was intended to establish feasibility, suggests that rTMS may offer benefit in select domains of cognitive functioning in bipolar disorder. None of the measures across subdomains revealed a dyscognitive effect.

Disentangling the Effects of Chronic Cannabis on Cognition in Bipolar Disorder

Although well-studied in schizophrenia, little is known about how cannabis use affects cognitive function in bipolar disorder (BD). Chronic, heavy cannabis use is highly prevalent among people with BD. Although associated with poor health outcomes, many people with BD report using cannabis to ameliorate their symptoms. Research also suggests possible pathophysiological interactions between the endocannabinoid and dopaminergic systems that contribute to effects on cognition. We sought to delineate the effects of chronic cannabis use on cognitive functions relevant to BD and cannabis.

Depth-Specific Changes in Age-Related Trajectory of Intracortical Myelin in Bipolar Disorder

MR signal intensity related to intracortical myelin (ICM) has been shown to be associated with specific clinical characteristics and cognitive performance in bipolar disorder (BD) and that ICM follows a quadratic age trajectory from 17-45 years old. Here we examine depth-specific differences in age-related trajectories of ICM in both BD and HC participants and clinical associations of ICM in BD.