Mindfulness trait and the potential mediating role of emotional regulation strategies in bipolar disorder / Mindfulness rasgo y el potencial papel mediador de las estrategias de regulación emocional en el trastorno bipolar

En este estudio transversal se investiga la asociación entre los principales síntomas del Trastorno bipolar (TB) y las dificultades asociadas a las estrategias de regulación emocional (ERE) adaptativas y desadaptativas. Además, este estudio examina los efectos mediadores de las ERE con el mindfulness rasgo y el TB. Método. Veinticuatro adultos con TB completaron la Escala de Conciencia de Atención Plena (MAAS), el Inventario de Depresión de Beck (BDI-II), la Escala de Autoevaluación de Manía de Altman (ARSM), el Inventario de Ansiedad Rasgo (STAI-R), y el Cuestionario de Regulación Emocional Cognitiva (CERQ). Resultados. El análisis de regresión múltiple mostró cómo la depresión se relacionaba significativa y positivamente con la autoculpabilización, mientras que la ansiedad rasgo estaba positivamente asociada con la autoculpabilización y el catastrofismo. En segundo lugar, el análisis de mediación mostró un efecto de mediación significativo para la autoculpabilidad en la relación entre mindfulness y depresión (a*b = -.15; ICB 95% [-.36, -.03]) y entre mindfulness y ansiedad rasgo (a*b = -.09; ICB 95% [-.27, -.01]). Conclusiones. Nuestros resultados informan del papel de la auto-culpabilidad y el catastrofismo en el TB y de cómo éstas podrían mediar significativamente entre el mindfulness rasgo y el TB. Estos resultados sugieren que una práctica de meditación enfocada en el catastrofismo y la autoculpabilidad puede ser especialmente útil para reducir los síntomas en los pacientes bipolares.(AU)

This cross-sectional study investigates the association between the main symptoms of Bipolar disorder (BD) and emotional regulation dif-ficulties in adaptive and maladaptive emotional regulation strategies (ERS). In addition, this study examines the possible mediating effects of ERS with dispositional mindfulnessand bipolar symptoms. Method.Twenty-four adults diagnosed with BD completed the Mindful Attention Awareness Scale (MAAS), the Beck Depression Inventory (BDI-II), the Altman Mania Self-Assessment Scale (ARSM), the Trait Anxiety Inventory (STAI-R), and the Cognitive Emotional Regulation Questionnaire (CERQ). Results. First, mul-tiple regression analysis showed how depression was significantly positively related to self-blame, whereas trait anxietywas positively associated with self-blame and catastrophizing. Second, the results of the mediation analy-sis have shown a significant mediation effect for the self-blamein the rela-tionship between mindfulnessand depression (a*b = -.15; BCI 95% [-.36, -.03]) and between mindfulnessand trait anxiety (a*b = -.09; BCI 95% [-.27, -.01]). Conclusions. Our results report the role of self-blame and catastrophiz-ing in BD and how these might significantly mediate between dispositional mindfulness and symptoms of depression and anxiety. These results suggest that a meditation practice focused on reducing catastrophizing and self-blame may be especially helpful for symptoms of depression and anxiety in bipolar patients.(AU)

Integrative ceRNA network analysis identifies unique and shared molecular signatures in Bipolar Disorder and Schizophrenia.

Bipolar Disorder (BPD) and Schizophrenia (SCZ) are complex psychiatric disorders with shared symptomatology and genetic risk factors. Understanding the molecular mechanisms underlying these disorders is crucial for refining diagnostic criteria and guiding targeted treatments. In this study, publicly available RNA-seq data from post-mortem samples of the basal ganglia's striatum were analyzed using an integrative computational approach to identify differentially expressed (DE) transcripts associated with SCZ and BPD. The analysis aimed to reveal both shared and distinct genes and long non-coding RNAs (lncRNAs) and to construct competitive endogenous RNA (ceRNA) networks within the striatum. Furthermore, the functional implications of these identified transcripts are explored, alongside their presence in established databases such as BipEx and SCHEMA. A significant outcome of our analysis was the identification of 21 DEmRNAs and 1 DElncRNA shared between BPD and SCZ across the Caudate, Putamen, and Nucleus Accumbens. Another noteworthy finding was the identification of Hub nodes within the ceRNA networks that were linked to major psychosis. Particularly, MED19, HNRNPC, MAGED4B, KDM5A, GOLGA7, CHASERR, hsa-miR-4778-3p, hsa-miR-4739, and hsa-miR-4685-5p emerged as potential biomarkers. These findings shed light on the common and unique molecular signatures underlying BPD and SCZ, offering significant potential for the advancement of diagnostic and therapeutic strategies tailored to these psychiatric disorders.

Association of cancer and schizophrenia, major depression and bipolar disorder: A Mendelian randomization study.

BACKGROUND: Schizophrenia, bipolar disorder and major depression have been reported to be associated with some cancers. However, the magnitude of the causal relationship between them remains unclear. This study aims to explore the potential association between three major mental diseases and the risk of some cancers. METHODS: We performed the two-sample Mendelian randomization(MR) analysis using publicly available genome-wide association studies (GWAS) statistics to investigate the causal relationship between these three mental diseases and some common types of cancers, including breast cancer, ovarian cancer, lung cancer, colorectal cancer, bladder cancer, prostate cancer, thyroid cancer, pancreatic cancer, malignant melanoma and glioma. We obtained genetic association estimates for schizophrenia, bipolar disorder and depression from the Psychiatric Genomics Consortium.The genetic association estimates for cancers were obtained from the UK Biobank, the MRC-IEU consortium and the GliomaScan consortium. RESULTS: After correction for heterogeneity and horizontal pleiotropy, we detected suggestive evidence for the association between thyroid cancer and genetically predicted schizophrenia (OR = 1.543, 95% CI: 1.023-2.328, P = 0.039), and thyroid cancer and major depression (OR = 3.573, 95% CI: 1.068-11.953, P = 0.039). No evidence of causal effects of schizophrenia, major depression and bipolar disorder on other types of cancers. CONCLUSIONS: Our findings suggest the association of schizophrenia and major depression and the development of thyroid cancer.

Pharmacological Mechanism of Herbal Interventions for Bipolar Disorder.

Bipolar disorder is a neuropsychiatric disease characterized by an abundance of undesired ideas and thoughts associated with recurrent episodes of mania or hypomania and depression. Alterations in the circuits, including the prefrontal cortex, striatum, and limbic system, regulate mood and cause variation in several crucial neurotransmitters, including serotonin, dopamine, GABA, and glutamate. Imbalances in dopamine levels have been implicated in the manic phase, while variance in serotonin is linked to depressive episodes. The precise pathophysiology of bipolar disorder is still unknown. Though different treatments are available, like lithium, risperidone, valproic acid, etc., which are widely used, they come with certain limitations, including narrow therapeutic index, hypothyroidism, weight gain, extrapyramidal symptoms, etc. The interest in herbal- based treatments for bipolar disorder arises from the desire for alternative, potentially more natural, and holistic approaches with fewer side effects. The current review focuses on the potential effects of herbal drugs and their derivatives to alleviate the symptoms of bipolar disorder.

Early specialised treatment for bipolar disorder: Long-term follow-up from the early intervention in affective disorders (EIA) randomised controlled trial.

BACKGROUND: It is unclear whether treatment early after onset in bipolar disorder may improve the long-term illness course. The early intervention in affective disorders (EIA) randomised controlled trial found that 2-years treatment in a specialised mood disorder clinic combining evidence-based pharmacological treatment with group psychoeducation improved clinical outcomes compared with standard treatment in patients with bipolar disorder discharged after their 1st, 2nd, or 3rd hospital admission. We aimed to assess the 16 years long-term outcomes after randomisation of the participants in the EIA trial. METHODS: Data were obtained by linking nation-wide Danish population-based registers. All 158 participants of the EIA trial (Trial Registration Number NCT00253071) were followed from time of randomisation (2005-2009) to end of study (31 December 2021). The primary outcome was risk of psychiatric readmission. Secondary outcomes were total admissions and costs, medication use, intentional self-harm or suicide attempt or suicide, and socio-economic measures. RESULTS: The absolute mean risk of psychiatric readmission was 49.3% in the intervention group and 59.8% in the control group, with no statistically significant difference between the groups (b = -0.10, 95% CI: -0.26 to 0.047, p = 0.18). Compared with the control group, patients in the intervention group had numerically fewer total admission days (mean (SD) 44 (77) versus 62 (109)), lower total cost of psychiatric hospital admissions and hospital-based outpatient visits (mean (SD) 22,001 (36793) euros versus 29,822 (52671) euros) and higher use of lithium and antipsychotics, but the differences were not statistically significant. Fewer patients in the intervention group had an event of intentional self-harm or suicide attempt or suicide during follow-up (OR 0.25, 95% CI: 0.15-0.40, p < 0.001) compared with the control group and more patients in the intervention group used antiepileptics (OR 2.21, 95% CI: 1.08-4.60, p = 0.031). CONCLUSION: Analyses of very long-term outcomes of the EIA trial may potentially indicate a beneficial effect of the intervention at the long term but were likely underpowered to detect a more subtle effect and for most outcomes the differences between groups were not statistically significant.

Posterior cingulate and medial prefrontal excitation-inhibition balance in euthymic bipolar disorder.

BACKGROUND: Persistent cognitive deficits and functional impairments are associated with bipolar disorder (BD), even during the euthymic phase. The dysfunction of default mode network (DMN) is critical for self-referential and emotional mental processes and is implicated in BD. The current study aims to explore the balance of excitatory and inhibitory neurotransmitters, i.e. glutamate and γ-aminobutyric acid (GABA), in hubs of the DMN during the euthymic patients with BD (euBD). METHOD: Thirty-four euBD and 55 healthy controls (HC) were recruited to the study. Using proton magnetic resonance spectroscopy (1H-MRS), glutamate (with PRESS sequence) and GABA levels (with MEGAPRESS sequence) were measured in the medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and the posterior cingulate gyrus (PCC). Measured concentrations of excitatory glutamate/glutamine (Glx) and inhibitory GABA were used to calculate the excitatory/inhibitory (E/I) ratio. Executive and attentional functions were respectively assessed using the Wisconsin card-sorting test and continuous performance test. RESULTS: euBD performed worse on attentional function than controls (p = 0.001). Compared to controls, euBD had higher E/I ratios in the PCC (p = 0.023), mainly driven by a higher Glx level in the PCC of euBD (p = 0.002). Only in the BD group, a marginally significant negative association between the mPFC E/I ratio (Glx/GABA) and executive function was observed (p = 0.068). CONCLUSIONS: Disturbed E/I balance, particularly elevated Glx/GABA ratio in PCC is observed in euBD. The E/I balance in hubs of DMN may serve as potential biomarkers for euBD, which may also contribute to their poorer executive function.

Cardiovascular mortality in bipolar disorder: Population-based cohort study.

BACKGROUND: Limited evidence base on cause-specific excess cardiovascular disease (CVD) mortality in bipolar disorder (BD) is a barrier to developing preventive interventions aimed at reducing the persistent mortality gap in BD. OBJECTIVE: To investigate cause-specific CVD mortality in BD. METHODS: We identified all individuals aged 15+ years during 2004-2018 with a diagnosis of BD using Finnish nationwide routine data. Standardised mortality ratios (SMR) with 95% confidence intervals (CI) were calculated using the mortality rates in the general population as weights. RESULTS: 53,273 individuals with BD (57% women; median age at BD diagnosis, 40 years), were followed up for 428,426 person-years (median, 8.2 years). There were 5988 deaths due to any cause, of which 26% were due to CVD. The leading cause of absolute excess CVD mortality was coronary artery disease (CAD). The leading causes of relative excess mortality were cardiomegaly (SMR, 4.51; 95% CI, 3.58-5.43), venous thromboembolism (3.03; 2.26-3.81), cardiomyopathy (2.46; 1.95-2.97), and hypertensive heart disease (2.12; 1.71-2.54). The leading causes of absolute CVD mortality showed markedly lower relative excess, including CAD (1.47; 1.34-1.61), ischaemic stroke (1.31; 1.06-1.54), and acute myocardial infarction (1.12; 0.98-1.25). Due to the higher relative excess mortality, structural and functional heart disorders contributed as much as atherosclerotic and ischaemic disorders to the absolute excess mortality. CONCLUSIONS: Cardiomyopathy and hypertensive heart disease as the leading causes of relative excess mortality emphasise the contribution of structural and functional heart disorders to the overall excess mortality alongside coronary artery disease. Interventions targeted at these modifiable causes of death should be priorities in the prevention of premature excess CVD mortality in BD.

Factors associated with sexual dysfunction in patients with bipolar disorder.

OBJECTIVES: The aims of our study were to assess the sexual function in men with bipolar disorder type 1 in remission and to determine the various sociodemographic, clinical and therapeutic factors associated with sexual dysfunction. METHODS: We conducted a cross-sectional study over an 18-month period (January 2020-June 2021) in which we included men followed up for bipolar disorder type 1 in the euthymic phase strictly defined by a score <8 on the Young Mania Rating Scale and a score ≤7 on the Hamilton Depression Rating Scale. Sexual function was assessed using the Arizona Sexual Experiences Scale (Asex) in its Arabic-validated version. RESULTS: Sixty patients were included in the study. The mean age was 42.5 (SD=11.1) years. Among the patients, 68% had sexual dysfunction according to the total score of the Asex scale. According to univariate analysis, several factors were significantly associated with sexual dysfunction in patients with bipolar disorder type 1: age (P=0.001), total number of hospitalizations for thymic relapse (P=0.015), total number of depressive episodes (P=0.006) and depressive dominant polarity (P=0.046). The factors identified as modifying sexuality according to the total score of the Asex scale by multivariate analysis were age at first antipsychotic prescription: P=0.01; ORa=1.109; 95% CI [1.021-1.206] and number of hospitalizations for thymic relapse: P=0.015; ORa=1.259; 95% CI [1.046-1.546]. CONCLUSION: Studies assessing factors associated with sexual dysfunction in patients with bipolar disorder type 1 in euthymia were mostly concerned with the effects of psychotropic drugs on sexual function, with factors inherent in bipolar illness itself not widely addressed in the literature. According to the results of our study, sexual dysfunction in patients with bipolar disorder in the euthymic phase is frequent and significantly associated with clinical factors inherent in the bipolar illness itself and its course.

A replication study of sHLA-E influence on schizophrenia and bipolar disorder.

OBJECTIVES: Schizophrenia (SZ) and bipolar disorders (BP) are chronic and severe neuropsychiatric diseases. These disorders are tightly related to immune deregulations. In the current study, we intended to replicate the previously reported involvement of the soluble HLA-E isoforms (sHLA-E) in the risk of developing the two conditions along with disease severity in a Tunisian population group. PATIENTS AND METHODS: One hundred and twenty-four patients with schizophrenia and 121 with bipolar disorder meeting the DSM-IV criteria along 111 healthy controls were included in this present case-control study. The soluble HLA-E isoforms circulating levels were measured using the ELISA method. The statistical analyses were performed using Kruskal-Wallis and Wilcoxon rank sum tests by R software and GraphPad prism 9. RESULTS: We found that the sHLA-E circulating levels were significantly higher in BP patients as compared to healthy controls (P<0.0001) and that such increases were mainly observed in patients during an acute phase of their disease (P<0.0001). In SZ patients, while we failed to observe an association with the levels of sHLA-E in the entire SZ sample, we found that high sHLA-E levels characterized stabilized patients in comparison with those during an acute episode (P=0.022). Finally, we did not observe any association between sHLA-E circulating levels and symptoms assessed by the classical clinical scales either in BP or SZ patients. CONCLUSION: Overall, the present findings replicate in a Tunisian population group the previously demonstrated implication of sHLA-E circulating levels in the risk of developing BP or SZ in a French patient cohort. Such replication allows to consider HLA-E as a potent and true inflammatory marker in the context of the two disorders.

Gene-gene interaction analysis for age at onset of bipolar disorder in a Korean population.

BACKGROUND: Multiple genes might interact to determine the age at onset of bipolar disorder. We investigated gene-gene interactions related to age at onset of bipolar disorder in the Korean population, using genome-wide association study (GWAS) data. METHODS: The study population consisted of 303 patients with bipolar disorder. First, the top 1000 significant single-nucleotide polymorphisms (SNPs) associated with age at onset of bipolar disorder were selected through single SNP analysis by simple linear regression. Subsequently, the QMDR method was used to find gene-gene interactions. RESULTS: The best 10 SNPs from simple regression were located in chromosome 1, 2, 3, 10, 11, 14, 19, and 21. Only five SNPs were found in several genes, such as FOXN3, KIAA1217, OPCML, CAMSAP2, and PTPRS. On QMDR analyses, five pairs of SNPs showed significant interactions with a CVC exceeding 1/5 in a two-locus model. The best interaction was found for the pair of rs60830549 and rs12952733 (CVC = 1/5, P < 1E-07). In three-locus models, four combinations of SNPs showed significant associations with age at onset, with a CVC of >1/5. The best three-locus combination was rs60830549, rs12952733, and rs12952733 (CVC = 2/5, P < 1E-6). The SNPs showing significant interactions were located in the KIAA1217, RBFOX3, SDK2, CYP19A1, NTM, SMYD3, and RBFOX1 genes. CONCLUSIONS: Our analysis confirmed genetic interactions influencing the age of onset for bipolar disorder and identified several potential candidate genes. Further exploration of the functions of these promising genes, which may have multiple roles within the neuronal network, is necessary.

Investigating the increased risk of schizophrenia and bipolar disorders in relatives of ADHD probands using colocalization analysis of common genetic variants.

BACKGROUND: Relatives of ADHD probands are known to be at increased risk of schizophrenia and bipolar disorder, suggesting shared genetic factors. In this study, we aim to identify shared common risk variants (i.e., Single-Nucleotide Polymorphisms, SNPs) between ADHD and schizophrenia, and between ADHD and bipolar disorder. METHODS: With the summary data from three GWAS, one on ADHD (20,183 cases with ADHD and 35,191 controls), another on schizophrenia (76,755 cases with schizophrenia and 243,649 controls) and another on bipolar disorder (41,917 cases with bipolar disorder and 371,549 controls), we used colocalization analysis to identify SNPs shared by ADHD and schizophrenia, and SNPs shared by ADHD and bipolar disorder. Functional genomic analyses were then conducted on these two sets of shared common genetic variants. RESULTS: We found that three of the 12 SNPs associated with ADHD colocalized with schizophrenia SNPs and one of the 12 SNPs associated with ADHD colocalized with bipolar disorder. Only 0.4% of the SNPs associated with schizophrenia (2 out of 431) and 2.3% of the SNPs associated with bipolar disorder (2 out of 86), colocalized with ADHD SNPs. Some genes mapped to these shared genetic variants (SCN2A and UNC5D) are involved in the development of the nervous system. CONCLUSIONS: Using colocalization analysis, the present study uncovers shared genetic variants associated with ADHD and schizophrenia as well as ADHD and bipolar disorder, and may at least partially explain the increased risk of schizophrenia and bipolar disorder in relatives of ADHD probands.

Comparative analysis of resting-state EEG-based multiscale entropy between schizophrenia and bipolar disorder.

BACKGROUND: Studies that use nonlinear methods to identify abnormal brain dynamics in patients with psychiatric disorders are limited. This study investigated brain dynamics based on EEG using multiscale entropy (MSE) analysis in patients with schizophrenia (SZ) and bipolar disorder (BD). METHODS: The eyes-closed resting-state EEG data were collected from 51 patients with SZ, 51 patients with BD, and 51 healthy controls (HCs). Patients with BD were further categorized into type I (n = 23) and type II (n = 16), and then compared with patients with SZ. A sample entropy-based MSE was evaluated from the bilateral frontal, central, and parieto-occipital regions using 30-s artifact-free EEG data for each individual. Correlation analyses of MSE values and psychiatric symptoms were performed. RESULTS: For patients with SZ, higher MSE values were observed at higher-scale factors (i.e., 41-70) across all regions compared with both HCs and patients with BD. Furthermore, there were positive correlations between the MSE values in the left frontal and parieto-occipital regions and PANSS scores. For patients with BD, higher MSE values were observed at middle-scale factors (i.e., 13-40) in the bilateral frontal and central regions compared with HCs. Patients with BD type I exhibited higher MSE values at higher-scale factors across all regions compared with those with BD type II. In BD type I, positive correlations were found between MSE values in all left regions and YMRS scores. CONCLUSIONS: Patients with psychiatric disorders exhibited group-dependent MSE characteristics. These results suggest that MSE features may be useful biomarkers that reflect pathophysiological characteristics.

Causal role of immune cells in major depressive disorder and bipolar disorder: Mendelian randomization (MR) study.

BACKGROUND: Major depressive disorder (MDD) and bipolar disorder (BD) are prevalent psychiatric conditions linked to inflammatory processes. However, it is unclear whether associations of immune cells with these disorders are likely to be causal. METHODS: We used two-sample Mendelian randomization (MR) approach to investigate the relationship between 731 immune cells and the risk of MDD and BD. Rigorous sensitivity analyses are conducted to assess the reliability, heterogeneity, and horizontal pleiotropy of the findings. RESULTS: Genetically-predicted CD27 on IgD+ CD38- unswitched memory B cell (inverse variance weighting (IVW): odds ratio (OR) [95 %]: 1.017 [1.007 to 1.027], p = 0.001), CD27 on IgD+ CD24+ B cell (IVW: OR [95 %]: 1.021 [1.011 to 1.031], p = 4.821E-05) and other 12 immune cells were associated with increased risk of MDD in MR, while HLA DR++ monocyte %leukocyte (IVW: OR [95 %]: 0.973 [0.948 to 0.998], p = 0.038), CD4 on Central Memory CD4+ T cell (IVW: OR [95 %]: 0.979 [0.963 to 0.995], p = 0.011) and other 13 immune cells were associated with decreased risk of MDD in MR. Additionally, CD33+ HLA DR+ Absolute Count (IVW: OR [95 %]: 1.022[1.007 to 1.036], p = 0.007), CD28+ CD45RA- CD8+ T cell %T cell (IVW: OR [95 %]: 1.024 [1.008 to 1.041], p = 0.004) and other 18 immune cells were associated with increased risk of BD in MR, while CD62L on CD62L+ myeloid Dendritic Cell (IVW: OR [95 %]: 0.926 [0.871 to 0.985], p = 0.014), IgD- CD27- B cell %lymphocyte (IVW: OR [95 %]: 0.918 [0.880 to 0.956], p = 4.654E-05) and other 13 immune cells were associated with decreased risk of BD in MR. CONCLUSIONS: This MR study provides robust evidence supporting a causal relationship between immune cells and the susceptibility to MDD and BD, offering valuable insights for future clinical investigations. Experimental studies are also required to further examine causality, mechanisms, and treatment potential for these immune cells for MDD and BD.

Principal component analysis as an efficient method for capturing multivariate brain signatures of complex disorders-ENIGMA study in people with bipolar disorders and obesity.

Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. PRACTITIONER POINTS: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.

Reported Personality Traits and Histories of Childhood Maltreatment in Borderline Personality Disorder and Bipolar 2 Disorder: A Comparative Study.

This study compared borderline personality disorder (BPD) and bipolar 2 disorder (BP 2 disorder) with respect to reported childhood trauma and Five-Factor personality traits using the Childhood Trauma Questionnaire (CTQ) and the NEO Five-Factor Inventory (NEO-FFI). Participants were 50 men and women, aged 18-45, with DSM-5-diagnosed BPD and 50 men and women in the same age group with DSM-5-diagnosed BP 2 disorder. Participants could not meet criteria for both BPD and BP 2 disorder. Borderline participants had significantly higher scores on the neuroticism subscale and significantly lower scores on the agreeableness subscale of the NEO-FFI. After correction for multiple comparisons, there were no between-group differences on CTQ scores. Study results suggest that BPD and BP 2 disorder differ primarily with respect to underlying temperament/genetic architecture and that environmental factors have only a limited role in the differential etiologies of the two disorders.

Disrupted default mode network connectivity in bipolar disorder: a resting-state fMRI study.

BACKGROUND: Theoretical and empirical evidence indicates the critical role of the default mode network (DMN) in the pathophysiology of the bipolar disorder (BD). This study aims to identify the specific brain regions of the DMN that is impaired in patients with BD. METHODS: A total of 56 patients with BD and 71 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Three commonly used functional indices, i.e., fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree centrality (DC), were utilized to identify the brain region showing abnormal spontaneous brain activity in patients with BD. Then, this region served as the seed region for resting-state functional connectivity (rsFC) analysis. RESULTS: Compared to the HC group, the BD group showed reduced fALFF, ReHo, and DC values in the left precuneus. Moreover, patients exhibited decreased rsFCs within the left precuneus and between the left precuneus and the medial prefrontal cortex. Additionally, there was diminished negative connectivity between the left precuneus and the left putamen, extending to the left insula (putamen/insula). The abnormalities in DMN functional connectivity were confirmed through various analysis strategies. CONCLUSIONS: Our findings provide convergent evidence for the abnormalities in the DMN, particularly located in the left precuneus. Decreased functional connectivity within the DMN and the reduced anticorrelation between the DMN and the salience network are found in patients with BD. These findings suggest that the DMN is a key aspect for understanding the neural basis of BD, and the altered functional patterns of DMN may be a potential candidate biomarker for diagnosis of BD.

Global trends and hotspots in pain associated with bipolar disorder in the last 20 years: a bibliometric analysis.

Purpose: The prevalence of comorbid pain and Bipolar Disorder in clinical practice continues to be high, with an increasing number of related publications. However, no study has used bibliometric methods to analyze the research progress and knowledge structure in this field. Our research is dedicated to systematically exploring the global trends and focal points in scientific research on pain comorbidity with bipolar disorder from 2003 to 2023, with the goal of contributing to the field. Methods: Relevant publications in this field were retrieved from the Web of Science core collection database (WOSSCC). And we used VOSviewer, CiteSpace, and the R package "Bibliometrix" for bibliometric analysis. Results: A total of 485 publications (including 360 articles and 125 reviews) from 66 countries, 1019 institutions, were included in this study. Univ Toront and Kings Coll London are the leading research institutions in this field. J Affect Disorders contributed the largest number of articles, and is the most co-cited journal. Of the 2,537 scholars who participated in the study, Stubbs B, Vancampfort D, and Abdin E had the largest number of articles. Stubbs B is the most co-cited author. "chronic pain," "neuropathic pain," "psychological pain" are the keywords in the research. Conclusion: This is the first bibliometric analysis of pain-related bipolar disorder. There is growing interest in the area of pain and comorbid bipolar disorder. Focusing on different types of pain in bipolar disorder and emphasizing pain management in bipolar disorder are research hotspots and future trends. The study of pain related bipolar disorder still has significant potential for development, and we look forward to more high-quality research in the future.

Homocysteine levels in first-episode patients with psychiatric disorders.

A high homocysteine (Hcy) level is a risk factor for schizophrenia, depression, and bipolar disorder. However, the role of hyperhomocysteinemia as either an independent factor or an auxiliary contributor to specific psychiatric symptoms or disorders remains unclear. This study aimed to examine Hcy levels in first-episode inpatients with psychotic symptoms and various psychiatric diseases to elucidate the association between Hcy levels and psychiatric disorders. This study enrolled 191 patients (aged 18-40 years) with psychiatric disorders. Seventy-five patients were diagnosed with schizophrenia, 48 with acute and transient psychotic disorders, 36 with manic episodes with psychosis, 32 with major depressive episodes with psychosis, and 56 healthy controls. Serum Hcy levels were measured using the enzyme cycle method. A Hcy concentration level of > 15 µmol/L was defined as hyperhomocysteinemia. Hcy levels were significantly higher in first-episode patients with psychiatric disorders compared to healthy controls (5.99 ± 3.60 vs. 19.78 ± 16.61 vs. 15.50 ± 9.08 vs. 20.00 ± 11.33 vs. 16.22 ± 12.06, F = 12.778, P < 0.001). Hcy levels were significantly higher in males with schizophrenia, acute and transient psychotic disorder, and major depressive disorder but not in mania [schizophrenia, (t = -4.727, P < 0.001); acute and transient psychotic disorders, (t = -3.389, P = 0.001); major depressive episode with psychosis, (t = -3.796, P < 0.001); manic episodes with psychosis, (t = -1.684, P = 0.101)]. However, serum Hcy levels were not significantly different among the psychiatric disorder groups (F = 0.139, P = 0.968). Multivariate linear regression showed that males had an increased risk for homocysteinemia. (95% CI = 8.192-15.370, P < 0.001). These results suggest that first-episode patients with psychiatric disorders have higher Hcy levels than in the general population, and men are at greater risk for psychiatric disorders. In conclusion, elevated Hcy levels may contribute to the pathogenesis of first-episode patients with psychotic symptoms.

Beyond the Window of Risk? The Dutch Bipolar Offspring Study: 22-Year Follow-Up.

OBJECTIVE: Adolescent offspring of parents with bipolar disorder (BD) are at high risk to develop BD and other psychopathology, yet, it remains unknown how this risk continues into middle adulthood. We aim to determine the window of risk for BD and other psychopathology in offspring of parents with BD followed from adolescence into adulthood. METHOD: This study reports on the 22-year follow-up assessment of the Dutch Bipolar Offspring Study, a fixed cohort study of 140 participants, established in 1997. Offspring (n=100; mean age of 38.28 years, SD=2.74) of parents with BD-I or BD-II were assessed at baseline, 1-, 5-, 12-, and 22-year follow-up. RESULTS: No new BD onsets occurred since the 12-year follow-up (lifetime prevalence=11-13%; BD-I=4%; BD-II=7%). Lifetime prevalence of any mood disorder is 65%, for major depressive disorder (MDD) 36%, and for recurrent mood episodes 37%. Prevalence of MDD more than doubled in the past decade. Point prevalence of any psychopathology peaked between 20-25 years (38-46%) subsiding to 29-35% per year after age 30. Overall, 71% of offspring contacted mental health services since the last assessment. CONCLUSION: The risk for homotypic transmission of BD in offspring of parents with BD is highest during adolescence. The heterotypic risk for mood disorder onset and recurrences continues over the life course. Severe mood disorders are often preceded by milder psychopathology, emphasizing the need for early identification and interventions. This study allows for better understanding of the onset and course of mood disorders and specific windows of risk in a familial high-risk population.

Childhood maltreatment and suicide attempts in major depression and bipolar disorders in South Korea: A prospective nationwide cohort study.

BACKGROUND: Childhood maltreatment (CM) is prevalent among patients with mood disorders and considered an important risk factor for suicide in the general population. Despite mood disorders being implicated in up to 60 % of completed suicides, the predictive role of CM on suicide attempt (SA) among early mood disorder patients remains poorly understood. METHODS: We enrolled 480 participants diagnosed with early-onset major depressive disorder (MDD), bipolar I disorder (BD I), and bipolar II disorder (BD II). Over an average of 60 weeks, participants underwent follow-up assessments at 12-week intervals. Using multivariate logistic regression, we examined the association between CM and SA history at baseline. Further, the Cox proportional hazard model assessed the predictive role of childhood maltreatment in SA during follow-up. RESULTS: At baseline, 38 % of the total participants reported SA history, with a follow-up prevalence of 10 %. Childhood maltreatment was significantly associated with past SAs and was a robust predictor of future SA, adjusting for relevant clinical risk factors. Emotional abuse and sexual abuse related to SA history, and physical abuse increased future SA risk. LIMITATIONS: Potential biases in reporting SA and childhood maltreatment, along with unexplored factors such as additional environmental and familial risks, may affect the study's findings. CONCLUSIONS: Childhood maltreatment emerged as a robust predictor of SA among early-onset mood disorder patients. Systematic evaluation of CM early in the clinical process may be crucial for effective risk management. Additionally, our findings highlight the importance of implementing proactive interventions for CM to prevent the onset of adverse psychological trajectories.