Impairment In Bipolar Disorder Research Articles

ADHD medications for cognitive impairment in bipolar disorders.

ADHD medications for cognitive impairment in bipolar disorders.

Impulsivity and neural correlates of response inhibition in bipolar disorder and their unaffected relatives: A MEG study

BackgroundResponse inhibition is a core cognitive impairment in bipolar disorder (BD), leading to increased impulsivity in BD. However, the relationship between the neural mechanisms underlying impaired response inhibition and impulsivity in BD is not yet clear. Individuals who are genetically predisposed to BD give a way of identifying potential endophenotypes. MethodsA total of 97 participants, including 39 patients with BD, 22 unaffected relatives (UR) of patients with BD, and 36 healthy controls performed a Go/No-Go task during magnetoencephalography. We carried out time-frequency and connectivity analysis on MEG data. ResultsDecreased beta power, prolonged latency and increased peak frequency in rIFG, decreased beta power in pre-SMA and reduced rIFG-to-pre-SMA connectivity were found in BD relative to healthy controls. In the UR group, we found a decrease in the beta power of pre-SMA and prolonged latency of rIFG. Furthermore, increased motor impulsiveness in BD was related to abnormal alterations in beta oscillatory activity of rIFG and functional connectivity between rIFG and pre-SMA. ConclusionsHypoactivity activity in rIFG and impaired dominant role of rIFG in the prefrontal control network may underlie the neuropathology of response inhibition dysfunction, resulting increased motor impulsivity in BD. Our findings point to measuring rIFG dysfunction as a potential means of identifying individuals at genetic high risk for transition to BD disease expression.

State- and trait-related dysfunctions in bipolar disorder across different mood states: a graph theory study.

The interplay between state- and trait-related disruptions in structural networks remains unclear in bipolar disorder (BD), but graph theory can offer insights into global and local network changes. We sought to use diffusion-tensor imaging (DTI) and graph theory approaches to analyze structural topological properties across distinct mood states and identify high-risk individuals by examining state- and trait-related impairments in BD. We studied changes in white matter network among patients with BD and healthy controls, exploring relationships with clinical variables. Secondary analysis involved comparing patients with BD with unaffected people at high genetic risk for BD. We included 152 patients with BD, including 52 with depressive BD (DBD), 64 with euthymic BD (EBD) and 36 with manic BD (MBD); we also included 75 healthy controls. Secondary analyses involved 27 unaffected people at high genetic risk for BD. Patients with DBD and MBD exhibited significantly lower global efficiencies than those with EBD and healthy controls, with patients with DBD showing the lowest global efficiencies. In addition, patients with DBD displayed impaired local efficiency and normalized clustering coefficient (γ). At a global level, γ correlated negatively with depression and anxiety. Compared with healthy controls, and across mood states, patients with BD showed abnormal shortest path lengths in the frontolimbic circuit, a trend mirrored among those at high genetic risk for BD. Considerations include medication effects, absence of recorded BD episode counts and the cross-sectional nature of the study. Mood-specific whole-brain network metrics could serve as potential biomarkers in BD for transitions between mood states. Moreover, these findings contribute to evidence of trait-related frontolimbic circuit irregularities, shedding light on underlying pathophysiological mechanisms in BD.

Factors associated with the discrepancy between objective and subjective cognitive impairment in bipolar disorder

ObjectiveThe aim of this study is to evaluate the discrepancy between objective cognitive measures and cognitive subjective complaints in a sample of euthymic patients with bipolar disorder (BD). MethodsOne hundred and sixteen participants (83 euthymic patients with BD and 33 healthy controls) were enrolled for this study. Patients were assessed with a comprehensive neuropsychological battery and they also reported their subjective cognitive complaints with the Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA). The discrepancy between objective and subjective data was calculated using a novel methodology proposed in a previous study (Miskowiak, 2016). Statistical analyses included Pearson correlations and multiple linear regression. ResultsHigher number of previous depressive episodes was identified as one variable associated with the global sensitivity composite score (Beta = 0.25; t = 2.1; p = 0.04) and with the verbal learning and memory sensitivity score (Beta = 0.26; t = 2.16; p = 0.03). That is, patients with more previous depressive episodes tend to over-report cognitive complaints. In contrast, higher number of previous hospitalizations was associated with stoicism in the global total score (Beta = −0.27; t = −2.24: p = 0.029) and in the domain of attention/processing speed (Beta = −0.34; t = −2.52; p = 0.016), indicating patients with more hospitalizations tend to report less cognitive complaints. DiscussionOur study identified some factors that might help to explain the discrepancy between objective and subjective cognitive measures in BD, including number of previous depressive episodes and number of previous hospitalizations. This highlights the need of the combined use of both types of cognitive measures to make an accurate assessment of cognitive dysfunctions and their effective treatment.

Predictors of Functional Impairment in Bipolar Disorder: Results From 13 Cohorts From Seven Countries by the Global Bipolar Cohort Collaborative.

Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well-characterized samples of individuals with BD. Thirteen cohorts from 7 countries included n = 5882 individuals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived "higher versus lower function" as the dependent variable and selected clinical and demographic variables as predictors. We found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning. The bipolar clinical research community is poised to work together to characterize the multi-dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large-scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every individual with this illness.Reprinted from Bipolar Disord 2022; 24:709-719, with permission from John Wiley and Sons. Copyright © 2022.

Aberrant resting-state functional connectivity underlies cognitive and functional impairments in remitted patients with 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.

Functioning in older adults with bipolar disorder: A report on recommendations by the International Society of bipolar disorder (ISBD) older adults with bipolar disorder (OABD) task force.

Despite the importance of psychosocial functioning impairment in Bipolar Disorder (BD), its role among Older Adults with BD (OABD) is not well known. The development of guidelines for the assessment of psychosocial functioning helps to facilitate a better understanding of OABD and can lead to better tailored interventions to improve the clinical outcomes of this population. Through a series of virtual meetings, experts from eight countries in the International Society of Bipolar Disorder (ISBD) on OABD task force developed recommendations for the assessment of psychosocial functioning. We present (1) a conceptualization of functioning in OABD and differences compared with younger patients; (2) factors related to functioning in OABD; (3) current measures of functioning in OABD and their strengths and limitations; and, (4) other potential sources of information to assess functioning. The task force created recommendations for assessing functioning in OABD. Current instruments are limited, so measures specifically designed for OABD, such as the validated FAST-O scale, should be more widely adopted. Following the proposed recommendations for assessment can improve research and clinical care in OABD and potentially lead to better treatment outcomes.

Association of childhood trauma with cognitive impairment and structural brain alterations in remitted patients with bipolar disorder

BackgroundCognitive impairment affects many patients with bipolar disorder (BD). No pro-cognitive treatment with robust efficacy exists partly due to limited insight into underlying neurobiological abnormalities. MethodsThis magnetic resonance imaging (MRI) study investigates structural neuronal correlates of cognitive impairment in BD by comparing brain measures in a large sample of cognitively impaired versus cognitively intact patients with BD or cognitively impaired patients with major depressive disorder (MDD) and healthy controls (HC). Participants underwent neuropsychological assessments and MRI scans. The cognitively impaired and – intact BD and MDD patient groups were compared with each other and HC regarding prefrontal cortex measures, hippocampus shape/volume, and total cerebral white (WM) and grey matter (GM). ResultsCognitively impaired BD patients showed lower total cerebral WM volume than HC, which scaled with poorer global cognitive performance and more childhood trauma. Cognitively impaired BD patients also showed lower adjusted GM volume and thickness in the frontopolar cortex than HC but greater adjusted GM volume in the temporal cortex than cognitively normal BD patients. Cognitively impaired BD patients showed decreased cingulate volume than cognitively impaired MDD patients. Hippocampal measures were similar across all groups. LimitationsThe cross-sectional study design prevented insights into causal relationships. ConclusionsLower total cerebral WM and regional frontopolar and temporal GM abnormalities may constitute structural neuronal correlates of cognitive impairment in BD, of which the WM deficits scale with the degree of childhood trauma. The results deepen the understanding of cognitive impairment in BD and provide a neuronal target for pro-cognitive treatment development.

Cerebrospinal fluid erythropoietin, oxidative stress, and cognitive functions in patients with bipolar disorder and healthy control participants: A longitudinal case-control study

Persistent cognitive impairments occur in a large proportion of patients with bipolar disorder (BD) but their underlying pathological cellular processes are unclear. The aims of this longitudinal study of BD and healthy control (HC) participants were to investigate (i) the association of brain erythropoietin (EPO) and oxidative stress with cognitive functions and (ii) the changes in brain EPO during and after affective episodes. Participants underwent neurocognitive testing, lumbar punctures for cerebrospinal fluid (CSF) sampling and provided urine spot tests at baseline (all), after an affective episode (patients) and after one year (all). EPO was assayed in the CSF and oxidative stress metabolites related to RNA and DNA damage (8-dihydroguanosine [8-oxo-Guo], 8-hydroxy-2-deoxyguanosine [8-oxo-dG]) were assayed in the CSF and spot urine. Data was available for analyses for 60 BD and 37 HC participants. In unadjusted primary analyses, verbal memory decreased with increasing concentrations of CSF EPO and oxidative stress. In unadjusted explorative analyses, poorer verbal memory and psychomotor speed were associated with higher levels of oxidative stress. However, no associations between cognitive functions and CSF levels of EPO or oxidative stress were observed after adjustment for multiple testing. CSF EPO concentrations were unchanged during and after affective episodes. While CSF EPO correlated negatively with CSF DNA damage marker 8-oxo-dG, this association rendered non-significant after adjusting for multiple testing. In conclusion, EPO and oxidative stress do not seem to be robustly related to cognitive status in BD. Further insight into the cellular processes involved in cognitive impairments in BD is necessary to pave the way for novel therapeutic strategies to improve patients’ cognitive outcomes.

The interaction of the oxytocin receptor gene and child abuse subtypes on social cognition in euthymic patients with bipolar disorder type I.

Most studies on cognitive impairment in bipolar disorder have neglected the role of early stress, despite the high frequency of childhood maltreatment in this clinical group. The aim of this study was to establish a connection between a history of emotional, physical, and sexual abuse in childhood and social cognition (SC) in patients with bipolar disorder type I (BD-I) in euthymia, and to test a possible moderating effect of the single nucleotide polymorphism rs53576 in the oxytocin receptor gene (OXTR). One hundred and one participants were included in this study. History of child abuse was evaluated using the Childhood Trauma Questionnaire-Short Form. Cognitive functioning was appraised using The Awareness of Social Inference Test (social cognition). The interaction effect between the independent variables OXTR rs53576 (AA/AG and GG) and the absence or presence of any one type of child maltreatment or a combination of types was analyzed using a generalized linear model regression. BD-I patients who had been victims of physical and emotional abuse in childhood and were carriers of the GG genotype at OXTR rs53576 displayed greater SC alterations, specifically in emotion recognition. This gene-environment interaction finding suggests a differential susceptibility model of a genetic variants that can be plausibly associated with SC functioning and might help to identify at-risk clinical subgroups within a diagnostic category. Future research aimed at testing the interlevel impact of early stress constitutes an ethical-clinical duty given the high rates of childhood maltreatment reported in BD-I patients.

An update on potential pharmacotherapies for cognitive impairment in bipolar disorder

ABSTRACT Introduction Cognitive impairment is a core feature of bipolar disorder (BD) that impedes recovery by preventing the return to optimal socio-occupational functioning and reducing quality of life. Presently, there are no efficacious treatments for cognitive impairment in BD, but many pharmacological interventions are being considered as they have the potential to target the underlying pathophysiology of the disorder. Areas covered This review summarizes the available evidence for pharmacological interventions for cognitive impairment in bipolar disorder. We searched PubMed, MedLine, and PsycInfo from inception to December 1st, 2022. Traditional treatments, such as lithium, anticonvulsants (lamotrigine), antipsychotics (aripiprazole, asenapine, cariprazine, lurasidone, and olanzapine), antidepressants (vortioxetine, fluoxetine, and tianeptine) and psychostimulants (modafinil), and emerging interventions, such as acetylcholinesterase inhibitors (galantamine and donepezil), dopamine agonists (pramipexole), erythropoietin, glucocorticoid receptor antagonists (mifepristone), immune modulators (infliximab, minocycline and doxycycline), ketamine, metabolic agents (insulin, metformin, and liraglutide), probiotic supplements, and Withania somnifera are discussed. Expert opinion The investigation of interventions for cognitive impairment in BD is a relatively under-researched area. In the past, methodological pitfalls in BD cognition trials have also been a critical limiting factor. Expanding on the existing literature and identifying novel pharmacological and non-pharmacological treatments for cognitive impairment in BD should be a priority.

Reductions in regional theta power and fronto-parietal theta-gamma phase-amplitude coupling during gaze processing in bipolar disorder

Impaired social cognition is common in bipolar disorder (BD) and predicts poor functional outcomes. A critical determinant of social cognition is the ability to discriminate others’ gaze direction, and its alteration may contribute to functional impairment in BD. However, the neural mechanisms underlying gaze processing in BD are unclear. Because neural oscillations are crucial neurobiological mechanisms supporting cognition, we aimed to understand their role in gaze processing in BD. Using electroencephalography (EEG) data recorded during a gaze discrimination task for 38 BD and 34 controls (HC), we examined: theta and gamma power over bilateral posterior and midline anterior locations associated with early face processing and higher-level cognitive processing, and theta-gamma phase-amplitude coupling (PAC) between locations. Compared to HC, BD showed reduced midline-anterior and left-posterior theta power, and diminished bottom-up/top-down theta-gamma PAC between anterior/posterior sites. Reduced theta power and theta-gamma PAC related to slower response times. These findings suggest that altered theta oscillations and anterior-posterior cross-frequency coupling between areas associated with higher-level cognition and early face processing may underlie impaired gaze processing in BD. This is a crucial step towards translational research that may inform novel social cognitive interventions (e.g., neuromodulation to target specific oscillatory dynamics) to improve functioning in BD.

C-reactive protein levels and cognitive functions in patients with bipolar disorder

IntroductionThe pathophysiology of bipolar disorder (BD) is complex and remains uncertain to this day.Several hypotheses have been suggested, including the involvement of inflammatory mechanisms in its pathogenesis and in eventual cognitive impairment. C-reactive protein (CRP) is one of the most commonly used inflammatory markers. High-sensitivity CRP (hs- CRP) is a more sensitive marker.ObjectivesWe aimed to examine hs-CRP levels in patients with BD, and to investigate its relationship with cognitive functions.MethodsWe conducted a cross-sectional study between June 2016 and July 2018 on drug-free BD patients. These participants were hospitalized at the “C” Psychiatry department of HediChaker University Hospital in Sfax-Tunisia which accepts only male patients. The diagnosis of BP disorder was established according to DSM-5 criteria.We used the Montreal Cognitive Assessment (MoCA) scale to assess cognitive functions in our patients, and blood samples were collected to analyze hs-CRP levels.ResultsOur study included 33 patients whose median age was 33 years, with an interquartile range of 27.5-44 years. The majority (90.3%) were diagnosed with type I of bipolar disorder and 9.7% were diagnosed with type II. At the time of the study, 82.4% had a maniac episode and 17.6% had a depressive one.The median MOCA scale score was 24 with an interquartile range of 19-26, and the analysis of hs-CRP values revealed a median level of 2.1 (interquartile range: 1.2-7.3).There was no significant correlation between hs-CRP levels and MOCA scores nor its domains. Table 1 shows the results of this correlation analysis.Table1:correlation results between hs-CRP levels and MOCA domains MOCA Visuospatial and executive functions naming attention language abstraction memoryorientation hs-CRPr=0.1570.031-0.092-0.0200.0990.0710.055-0.151p=0.4150.8730.6360.9180.6100.7140.7750.435We also did not find any significant difference in hs-CRP levels between patients with depressive and maniac episodes.ConclusionsOur study showed no significant relationship between inflammation and cognitive impairment in bipolar disorder. Further research is needed to better investigate the role of inflammatory processes in this disorder.Disclosure of InterestNone Declared

Association between uric acid and cognitive dysfunction: A cross-sectional study with newly diagnosed, drug-naïve with bipolar disorder

BackgroundCognitive impairment is one of the major symptoms of individuals with bipolar disorder (BD). Purine system disorders may play an important role in cognitive dysfunction. So far, the relationship between cognitive deficits and purinergic metabolism in BD has been seldom discussed in previous studies. This study aims to explore its relevance and potential biological mechanisms. MethodsIn this cross-sectional study, 205 first time diagnosed drug-naive individuals with BD and 97 healthy volunteers were recruited. The uric acid(UA) level was measured using automatic biochemical analyzer, and cognitive function was assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Stroop color-word test. In addition, general information and clinical symptoms were collected and evaluated. ResultsIn this study, the UA level of BD group (U = 8475.000, p = 0.038) was found to be significantly higher than that of the healthy controls, but the scores of RBANS (t = −11.302, p < 0.001) and Stroop color-word test (t = −6.962, p < 0.001) were significantly lower than that of the healthy controls. In gender subgroup analysis, females had lower UA level and higher RBANS scores. In correlation analysis, the cognitive function of individuals with BD was found to present a significant negative correlation with UA level in attention (r = −0.23, p = 0.001) and delayed memory(r = −0.16, p = 0.022). LimitationsThis is a cross-sectional design. ConclusionElevated UA levels may be a potential mechanism of cognitive impairment in BD. This provides a new possible strategy for the prevention and treatment of cognitive impairment in BD.

Altered intrinsic brain activity and cognitive impairment in euthymic, unmedicated individuals with bipolar disorder.

Cognitive impairment in euthymic bipolar disorder (BD) contributes to poor functional outcomes. Resting-state magnetic resonance imaging (MRI)may help us understand the neurobiology of cognitive impairment in BD. Here, forty unmedicated euthymic BD patients and thirty-nine healthy controls were recruited, undergoing MRI scans and neuropsychological measures. The amplitude of low-frequency fluctuation (ALFF) and ALFF-based functional connectivity (FC) analysis was employed to explore the potential alterations of neural activity. Voxel-wised correlation was calculated between clinical and cognitive variables and abnormal brain activity. Compared with healthy controls, euthymic BD patients showed worse cognitive performance in Trail Making Test, Digit Span Test, and Stroop Color-Word Test (SCWT). The euthymic BD group had significantly lower ALFF in the left medial frontal gyrus, right middle frontal gyrus, right postcentral gyrus, and left superior frontal gyrus. Furthermore, we found decreased ALFF values in the right middle frontal gyrus that was negatively correlated with cognitive inhibition, (r=-0.43, P=0.015). ALFF-based FC analysis showed that BD group showed significantly decreased FC between the right middle frontal gyrus (seed) and left middle temporal gyrus and left medial frontal gyrus, (Two-tailed, PFWE < 0.05, TFCE corrected). The findings demonstrated that individuals with BD during the euthymic phase exhibited decreased ALFF and hypoconnectivity of key brain areas within the frontoparietal network. These altered spontaneous brain activity in euthymic BD patients may be involved in the pathophysiology mechanism of cognitive deficits.

Efficacy and Safety of Bilateral Sequential Theta Burst Transcranial Magnetic Stimulation in Bipolar Depression: Result From an Observational Study

The majority of functional impairment in bipolar disorder occurs during the depressed phase of illness, which is frequently resistant to established interventions. In attempting to meet the ongoing need for experimental treatments, transcranial magnetic stimulation (TMS) trials have had varying effects on bipolar depression. The variable efficacy of TMS for bipolar depression highlights an unmet need to define the most optimal TMS settings for the specific syndrome of bipolar depression, and suggests the need for augmented TMS paradigms.

Subjective cognitive impairment and its relationship to sleep impairment, anxiety severity, and depressive symptoms in individuals with bipolar disorder

Individuals with bipolar disorder commonly report cognitive impairment which is associated with several psychosocial factors (e.g., mood symptoms). Within this study, we investigated the relationship between these psychosocial factors and the perception of cognitive impairment in individuals with bipolar disorder. We measured the relationship between subjective cognitive impairment and mood symptoms, quality of life, age, gender, bipolar disorder subtype, anxiety and sleep disturbance in 140 individuals with bipolar disorder with a mixed linear regression model. Our primary outcome measures were obtained via National Institute of Health (NIH)-sponsored PROMIS cognition scores. Results from the model suggest that both the PROMIS Cognitive Function and Cognitive Function-Abilities scores were significantly negatively correlated with sleep disturbance and depression symptoms (p≤0.05). PROMIS Cognitive Function was also significantly negatively correlated with anxiety (p≤0.05). Limitations of this study include the absence of a healthy control group, limited demographic diversity, and cross-sectional study design. Perceived cognitive impairment in individuals with bipolar disorder is associated with increased sleep disturbance, depression, and anxiety. Future studies with objective cognitive measures combined with PROMIS self-report scores might further clarify the expression of cognitive impairment in bipolar disorder.

Cognitive profiles in bipolar I disorder and associated risk factors: Using Wechsler adult intelligence scale-IV.

BackgroundDespite the growing evidence of cognitive impairments in bipolar disorder (BD), little work has evaluated cognitive performances utilizing the latest version of the Wechsler Intelligence Scale-IV (WAIS-IV), which is one of the most widely used neurocognitive assessments in clinical settings. Furthermore, clinical characteristics or demographic features that negatively affect the cognitive functioning of BD were not systematically compared or evaluated. Accordingly, the present study aimed to examine the cognitive profile of bipolar I disorder (BD-I) patients and associated risk factors.MethodsParticipants included 45 patients, diagnosed with BD-I, current or most recent episode manic, and matching 46 healthy controls (HC). Cognitive performance was evaluated via WAIS-IV, and clinical characteristics of the BD-I group were examined via multiple self- and clinician-report questionnaires.ResultsMultivariate analysis of covariance (MANCOVA) results indicated that the BD-I group demonstrated significantly poorer performance compared to the HC group in subtests and indexes that reflect working memory and processing speed abilities. Redundancy analysis revealed that overall symptom severity, manic symptom severity, and anxiety were significant predictors of cognitive performance in BD-I, while age of onset, past mood disorder history, depression severity, and impulsiveness showed comparatively smaller predictive values.ConclusionThe current study suggests cognitive deterioration in the cognitive proficiency area while generalized ability, including verbal comprehension and most of the perceptual reasoning skills, remain intact in BD-I. The identified risk factors of cognitive performance provide specific clinical recommendations for intervention and clinical decision-making.

Epigenetic GrimAge acceleration and cognitive impairment in bipolar disorder

Bipolar disorder (BD) has been previously associated with clinical signs of premature aging, including accelerated epigenetic aging in blood and brain, and a steeper age-related decline in cognitive function. However, the clinical drivers and cognitive correlates of epigenetic aging in BD are still unknown. We aimed to investigate the relationship between multiple measures of epigenetic aging acceleration with clinical, functioning, and cognitive outcomes in patients with BD and controls. Blood genome-wide DNA methylation levels were measured in BD patients (n = 153) and matched healthy controls (n = 50) with the Infinium MethylationEPIC BeadChip (Illumina). Epigenetic age estimates were calculated using an online tool, including the recently developed lifespan predictor GrimAge, and analyzed with generalized linear models controlling for demographic variables and blood cell proportions. BD was significantly associated with greater GrimAge acceleration (AgeAccelGrim, β=0.197, p = 0.009), and significant group-dependent interactions were found between AgeAccelGrim and blood cell proportions (CD4+ T-lymphocytes, monocytes, granulocytes, and B-cells). Within patients, higher AgeAccelGrim was associated with worse cognitive function in multiple domains (short-term affective memory (β=-0.078, p = 0.030), short-term non-affective memory (β=-0.088, p = 0.018), inhibition (β=0.064, p = 0.046), and problem solving (β=-0.067, p = 0.034)), age of first diagnosis with any mood disorder (β=-0.076, p = 0.039) or BD (β=-0.102, p = 0.016), as well as with current non-smoking status (β=-0.392, p < 0.001). Overall, our findings support the contribution of epigenetic factors to the aging-related cognitive decline and premature mortality reported in BD patients, with an important driving effect of smoking in this population.

Retinal Thickness as a biomarker of cognitive impairment in bipolar disorder

IntroductionOcular Coherence Tomography (OCT) to measure retinal thickness is the current method to observe neurological impairment in neurodegenerative diseases [1] and in mental disorders [2] due to the composition of the retina itself as an anatomic extension of the brain.There can be found some factors to improve the resilience like the years of study.Objectives Our aim is to evaluate cognitive and clinical impairment in Bipolar Disorder and see the correlation to the retinal thinning.MethodsTwenty-seven patients diagnosed with Bipolar Disorder were assessed in the context of the FINEXT programme (3). Selective attention, executive functions and verbal memory were measured among other variables. Using the OCT technique, we measured the thickness of the ppRNFL, the RFNL, GCL and IPL layers in the macula in both eyes through several radial segments. Partial correlations were performed with Bonferroni correction (p≤0.006) adjusted for age and academic status except for the variable years of study which was adjusted for age.ResultsSignificant direct correlations were observed between: - The study-years and the thickness of the retina in the NO and RFNL. -Selective attention and GCL and RFNL layers. -Executive function and the GCL and IPL.ConclusionsWe can observe some preliminar results showing a significant correlation between some layers of the retina, upper segments more frequently, and the outcomes of the neurocognitive assessment. We can see a relationship as well between years of study and the thickness of the Retinal Nerve Fibre Layer in the retina and optic nerve head, the axons of the neurons in the eye.DisclosureNo significant relationships.