Project description:Individuals with bipolar disorder are at increased risk for cardiovascular diseases. Most studies have described increases in cardiometabolic risk indicators (CMRIs) using clinical cut-off values. Further, there are no longitudinal studies on CMRIs. We aimed to investigate continuous measures of CMRIs in individuals with bipolar disorder and controls using both cross-sectional and longitudinal data. We used data from the Swedish St. Göran Bipolar project. Study individuals were examined at baseline and after a median of 6 and 7 years for the control and patient group, respectively. Data were collected December 2005-December 2020. The cohort included 281 individuals with bipolar disorder (mean age 39 years, 59% women) and 114 controls (mean age 38 years, 55% women). Of those, 155 patients and 74 controls also provided follow-up data. At baseline, individuals with bipolar disorder had significantly higher mean values of waist-to-hip ratio (WHR) (β = 0.142, p = 0.001), body mass index (β = 0.150, p = 0.006), plasma triacylglycerol (TAG) (β = 0.218, p < 0.001), total/plasma high-density lipoprotein-cholesterol (TChol/HDL-C) ratio (β = 0.103, p = 0.03), TAG/HDL-C ratio (β = 0.151, p = 0.006), and non-HDL-C (β = 0.168, p = 0.001) than controls. Most CMRIs remained higher in the patient group at follow-up. The difference between patients and controls increased over time for WHR (0.005 unit/year, p < 0.001), and systolic (1.1 mm Hg/year, p = 0.002) and diastolic (0.8 mm Hg/year, p < 0.001) blood pressure. Individuals with bipolar disorder displayed persistently higher levels of nearly all included CMRIs. Over time, a subset of CMRIs worsened in patients relative to controls. This suggests that active measures to counter cardiovascular risk in persons with bipolar disorder should be considered.
Project description:BackgroundPeople with bipolar disorder (BPD) are more likely to die prematurely, which is partly attributed to comorbid cardiometabolic traits. Previous studies report cardiometabolic abnormalities in BPD, but their shared aetiology remains poorly understood. This study examined the phenotypic associations and shared genetic aetiology between BPD and various cardiometabolic traits.MethodsIn a subset of the UK Biobank sample (N = 61 508) we investigated phenotypic associations between BPD (ncases = 4186) and cardiometabolic traits, represented by biomarkers, anthropometric traits and cardiometabolic diseases. To determine shared genetic aetiology in European ancestry, polygenic risk scores (PRS) and genetic correlations were calculated between BPD and cardiometabolic traits.ResultsSeveral traits were significantly associated with increased risk for BPD, namely low total cholesterol, low high-density lipoprotein cholesterol, high triglycerides, high glycated haemoglobin, low systolic blood pressure, high body mass index, high waist-to-hip ratio; and stroke, coronary artery disease and type 2 diabetes diagnosis. BPD was associated with higher polygenic risk for triglycerides, waist-to-hip ratio, coronary artery disease and type 2 diabetes. Shared genetic aetiology persisted for coronary artery disease, when correcting PRS associations for cardiometabolic base phenotypes. Associations were not replicated using genetic correlations.ConclusionsThis large study identified increased phenotypic cardiometabolic abnormalities in BPD participants. It is found that the comorbidity of coronary artery disease may be based on shared genetic aetiology. These results motivate hypothesis-driven research to consider individual cardiometabolic traits rather than a composite metabolic syndrome when attempting to disentangle driving mechanisms of cardiometabolic abnormalities in BPD.
Project description:BackgroundWeb-based resources can support people with bipolar disorder (BD) to improve their knowledge and self-management. However, publicly available resources are heterogeneous in terms of their quality and ease of use. Characterizing digital health literacy (the skillset that enable people to navigate and make use of health information in a web-based context) in BD will support the development of educational resources.ObjectiveThe aim of this study was to develop understanding of digital health literacy and its predictors in people with BD.MethodsA web-based survey was used to explore self-reported digital health literacy (as measured by the e-Health Literacy Scale [eHEALS]) in people with BD. Multiple regression analysis was used to evaluate potential predictors, including demographic/clinical characteristics and technology use.ResultsA total of 919 respondents (77.9% female; mean age 36.9 years) completed the survey. Older age (β=0.09; P=.01), postgraduate education (β=0.11; P=.01), and current use of self-management apps related to BD (β=0.13; P<.001) were associated with higher eHEALS ratings.ConclusionsLevels of self-reported digital health literacy were comparable or higher than other studies in the general population and specific physical/mental health conditions. However, individuals with BD who are younger, have completed less education, or are less familiar with mental health apps may require extra support to safely and productively navigate web-based health resources. Relevant educational initiatives are discussed. Future studies should evaluate skill development interventions for less digitally literate groups.
Project description:The molecular events underlying the development, manifestation, and course of schizophrenia, bipolar disorder, and major depressive disorder span from embryonic life to advanced age. However, little is known about the early dynamics of gene expression in these disorders due to their relatively late manifestation. To address this, we conducted a secondary analysis of post-mortem prefrontal cortex datasets using bioinformatics and machine learning techniques to identify differentially expressed gene modules associated with aging and the diseases, determine their time-perturbation points, and assess enrichment with expression quantitative trait loci (eQTL) genes. Our findings revealed early, mid, and late deregulation of expression of functional gene modules involved in neurodevelopment, plasticity, homeostasis, and immune response. This supports the hypothesis that multiple hits throughout life contribute to disease manifestation rather than a single early-life event. Moreover, the time-perturbed functional gene modules were associated with genetic loci affecting gene expression, highlighting the role of genetic factors in gene expression dynamics and the development of disease phenotypes. Our findings emphasize the importance of investigating time-dependent perturbations in gene expression before the age of onset in elucidating the molecular mechanisms of psychiatric disorders.
Project description:IntroductionThis systematic review explores the hypothesis that various lipid categories and lipid metabolism-related genomic variations link to mental disorders, seeking potential clinically useful markers.MethodsWe searched PubMed, Scopus, and PsycInfo databases until October 12th, 2024, using terms related to lipidomics, lipid-related genomics, and different mental disorders, i.e., Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizophrenia (SCZ), and Obsessive-Compulsive Disorder (OCD). Eligible studies were assessed. Extracted data included author, year, methodology, outcomes, genes, and lipids linked to disorders. Bias and evidence certainty were evaluated. The systematic review adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and a registered protocol (PROSPERO: CRD42023438862).ResultsA total of 27 studies were included. SCZ showed alterations in 77 lipids, including triglycerides (TG), ceramides, and phosphatidylcholine, while MDD and BD exhibited 97 and 47 altered lipids, respectively, with overlap among disorders. Shared genes, such as ABCA13, DGKZ, and FADS, and pathways involving inflammation, lipid metabolism, and mitochondrial function were identified. OCD was associated with sphingolipid signaling and peroxisomal metabolism.DiscussionLipid signatures in MDD, BD, and SCZ shed light on underlying processes. Further research is needed to validate biomarkers and refine their clinical applications in precision psychiatry.
Project description:Purpose of study is revealing significant differences in serum proteomes in schizophrenia, bipolar disorder (BD), and matched healthy controls. The sample preparation included affinity removing of six major proteins, separation by 1D electrophoresis, in-gel tryptic hydrolysis, and LC-MS/MS peptide analysis using LTQ Orbitrap Velos mass spectrometer. When comparing proteome profiles, different unique protein sets were revealed (absent in other groups): 22 proteins typical for schizophrenia, and 20 – for BD. Protein set in schizophrenia was mostly associated with nucleic acid and protein metabolism, immune response, cell communication, and cell growth and maintenance. Protein set in BD was mostly associated with cell growth and maintenance, nucleic acid metabolism regulation, immune response, protein metabolism, transport and cell communication. Concentrations of ankyrin repeat domain-containing protein 12 (ANKRD12), coagulation factor XIII, and cadherin 5 in serum samples were determined by ELISA. Significant difference between three groups was revealed in ANKRD12 concentration (p=0.02), with maximum elevation of ANKRD12 concentration (median level) in schizophrenia followed by BD. Cadherin 5 concentration differed significantly (p=0.035) between schizophrenic patients with prevailing positive symptoms (4.78 [2.71;7.12] ng/ml) and those with prevailing negative symptoms (1.86 [0.001;4.11] ng/ml). Our results are presumably useful for discovering the new pathways involved in endogenous psychotic disorders.
Project description:ObjectiveBipolar disorder (BD) is highly heritable. Neuroimaging studies comparing unaffected youth at high familial risk for BD (i.e., those with a first-degree relative with the disorder; termed "high-risk" [HR]) to "low-risk" (LR) youth (i.e., those without a first-degree relative with BD) and to patients with BD may help identify potential brain-based markers associated with risk (i.e., regions where HR+BD≠LR), resilience (HR≠BD+LR), or illness (BD≠HR+LR).MethodDuring functional magnetic resonance imaging (fMRI), 99 youths (i.e., adolescents and young adults) aged 9.8 to 24.8 years (36 BD, 22 HR, 41 LR) performed a task probing face emotion labeling, previously shown to be impaired behaviorally in youth with BD and HR youth.ResultsWe found three patterns of results. Candidate risk endophenotypes (i.e., where BD and HR shared deficits) included dysfunction in higher-order face processing regions (e.g., middle temporal gyrus, dorsolateral prefrontal cortex). Candidate resilience markers and disorder sequelae (where HR and BD, respectively, show unique alterations relative to the other two groups) included different patterns of neural responses across other regions mediating face processing (e.g., fusiform), executive function (e.g., inferior frontal gyrus), and social cognition (e.g., default network, superior temporal sulcus, temporo-parietal junction).ConclusionIf replicated in longitudinal studies and with additional populations, neural patterns suggesting risk endophenotypes could be used to identify individuals at risk for BD who may benefit from prevention measures. Moreover, information about risk and resilience markers could be used to develop novel treatments that recruit neural markers of resilience and attenuate neural patterns associated with risk. Clinical trial registration information-Studies of Brain Function and Course of Illness in Pediatric Bipolar Disorder and Child and Adolescent Bipolar Disorder Brain Imaging and Treatment Study; http://clinicaltrials.gov/; NCT00025935 and NCT00006177.
Project description:BackgroundIt is unclear how those with bipolar disorder (BD) have been affected by the coronavirus (COVID-19) pandemic. This study aimed to obtain a more detailed understanding of the current mental health needs of these individuals, which is important for both the development of intervention strategies to better manage patient distress and to better prepare for similar circumstances in future.MethodsThe sample comprised 43 individuals with a verified diagnosis of BD and 24 healthy controls. Data about pandemic-related mental health support use, socio-demographics, mood, lifestyle, social rhythm and subjective cognitive dysfunction data were collected and compared between groups. Inter-relationships between scores were also examined.ResultsNo between-group differences were found in terms of age, sex, living situation, job loss or reduced work hours due to COVID-19. Most patients with BD reported a history of ongoing formal psychological support (68.3%), with most continuing this support throughout the pandemic (82.1%). A large, statistically significant pandemic-related increase in subjective cognitive dysfunction was evident in the BD group. Subjective cognitive dysfunction was significantly associated with negative symptomology, suicidal thoughts, and quality of life ratings.LimitationsData was collected in self-report format in an online survey and objective symptom measures were not used at this time CONCLUSION: The absenceof substantial differences between patients and controls in terms of mood symptoms, COVID-19 fear or lifestyle factors and social rhythms suggests a degree of resilience in BD patients; despite large pandemic related increases in subjective cognitive dysfunction.
Project description:The study was designed to validate use of electronic health records (EHRs) for diagnosing bipolar disorder and classifying control subjects.EHR data were obtained from a health care system of more than 4.6 million patients spanning more than 20 years. Experienced clinicians reviewed charts to identify text features and coded data consistent or inconsistent with a diagnosis of bipolar disorder. Natural language processing was used to train a diagnostic algorithm with 95% specificity for classifying bipolar disorder. Filtered coded data were used to derive three additional classification rules for case subjects and one for control subjects. The positive predictive value (PPV) of EHR-based bipolar disorder and subphenotype diagnoses was calculated against diagnoses from direct semistructured interviews of 190 patients by trained clinicians blind to EHR diagnosis.The PPV of bipolar disorder defined by natural language processing was 0.85. Coded classification based on strict filtering achieved a value of 0.79, but classifications based on less stringent criteria performed less well. No EHR-classified control subject received a diagnosis of bipolar disorder on the basis of direct interview (PPV=1.0). For most subphenotypes, values exceeded 0.80. The EHR-based classifications were used to accrue 4,500 bipolar disorder cases and 5,000 controls for genetic analyses.Semiautomated mining of EHRs can be used to ascertain bipolar disorder patients and control subjects with high specificity and predictive value compared with diagnostic interviews. EHRs provide a powerful resource for high-throughput phenotyping for genetic and clinical research.
Project description:Cognitive deficits in executive function and memory among individuals with bipolar disorder (BD) are well-documented; however, only recently have efforts begun to address whether such cognitive deficits can be ameliorated through cognitive training. This pilot study examined the effects of a top-down, cognitive reasoning training program in adults with BD on both brain and cognitive measures. Twenty-seven participants (11 males, 16 females), aged 21-70 years old, completed the study. Participants completed neurocognitive testing and functional magnetic resonance imaging (fMRI) before and after training, consisting of 8 h (2 h/week) of training in small groups. The training delivered information processing strategies that were implemented and applicable to a variety of daily living contexts. Results indicated that participants showed significant gains in the primary outcome measure of complex abstraction, also referred to as gist reasoning, as well as in untrained domains of executive function and memory. We found a significant increase in resting cerebral blood flow (CBF) in left inferior frontal gyrus after cognitive training. We also found that resting CBF in the right frontal middle gyrus correlated positively with performance on the measure of complex abstraction. This feasibility study provides promising evidence that short-term reasoning training can enhance cognitive performance and brain health in adults with BD. These data motivate further efforts to explore adjuvant therapeutics to improve cognitive performance and underlying brain systems in bipolar, as well as other psychiatric disorders. Clinicaltrials.gov Identifier: NCT02843282, http://www.clinicaltrials.gov/ct2/show/NCT02843282.