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The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we performed an exploratory study of the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. Overall, we observed relatively weak associations (p

BackgroundBipolar disorder (BD) conveys the highest risk of suicide of all mental disorders. We sought to externally validate a risk calculator (RC) of suicide attempts developed in youth with BD from the Course and Outcome of Bipolar Youth (COBY) study in an adult sample.MethodsA prospective cohort of adults with BD from the National Institute of Mental Health Collaborative Depression Study (CDS; N = 427; mean (+/- SD) age at intake (36 +/- 13 years)) was secondarily analyzed to validate the COBY RC for one-year risk of suicide attempts/deaths. Nine of the ten predictor variables from the COBY RC were available in the CDS and used: age, age of mood disorder onset, first and second (partial) degree family history of suicide, history of psychotic symptoms, substance use disorder, prior suicide attempt, socioeconomic status, and non-suicidal self-injury (prospectively, incompletely at baseline).ResultsOver a mean (SD) follow-up of 19 (10) years, 29 % of the CDS sample attempted suicide. The RC predicted suicide attempts/deaths over one-year follow-up with an area under the receiver operating characteristic curve (AUC) of 0.78 (95 % CI 0.75-0.80). The RC performed slightly better in those with a younger age of mood disorder onset.LimitationsClinical samples may limit generalizability; the RC does not assess more acute suicide risk.ConclusionsOne-year risk of suicide attempts/deaths can be predicted with acceptable accuracy in youth and adults with BD, comparable to commonly used RCs to predict cardiovascular risk. This RC may help identify higher-risk individuals with BD for personalized treatment and research. https://cobysuicideattemptsrc.shinyapps.io/Shiny.

BACKGROUND AND HYPOTHESIS: People with serious mental illness (SMI; psychotic and affective disorders with psychosis) are at an increased risk of suicide, yet there is limited research on the correlates of suicide in SMI. Social cognitive impairments are common among people with SMI and several studies have examined social cognition and suicidal ideation (SI) and behavior. This systematic review aims to evaluate the links between various domains of social cognition, SI, and suicidal behavior in SMI. STUDY DESIGN: Electronic databases (PubMed and PsycInfo) were searched through June 2023. Records obtained through this search (N = 618) were screened by 2 independent reviewers according to inclusion criteria. Relevant data were extracted, and study quality was assessed. STUDY RESULTS: Studies (N = 16) from 12 independent samples were included in the systematic review (N = 2631, sample sizes ranged from N = 20 to N = 593). Assessments of social cognition and SI and behavior varied widely between studies. Broadly, effects were mixed. Better emotion recognition of negative affect was linked to SI and a history of suicide attempts, though there is little consistent evidence for the relationship of emotion recognition and SI or behavior. On the other hand, better theory of mind ability was linked to SI and a history of suicide attempts. Furthermore, negative attributional bias was linked to current SI, but not a history of SI or attempt. CONCLUSIONS: This review suggests mixed associations between social cognition, SI, and behavior in SMI. Future research should evaluate additional mediators and moderators of social cognition and suicide, employing prospective designs.

We examined the role of menopausal status in daily mood and cognitive performance among women with bipolar disorder (BD) compared to healthy comparison women. We analyzed the association of menopausal status, bipolar diagnosis, and their interaction on daily mood assessed by mobile surveys and attentional performance measured multiple times over 2 weeks. Menopausal status was associated with more daily negative affect in women with BD, but not related to attentional performance.

According to the operational diagnostic criteria, psychiatric disorders such as schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and autism spectrum disorder (ASD) are classified based on symptoms. While its cluster of symptoms defines each of these psychiatric disorders, there is also an overlap in symptoms between the disorders. We hypothesized that there are also similarities and differences in cortical structural neuroimaging features among these psychiatric disorders. T1-weighted magnetic resonance imaging scans were performed for 5,549 subjects recruited from 14 sites. Effect sizes were determined using a linear regression model within each protocol, and these effect sizes were meta-analyzed. The similarity of the differences in cortical thickness and surface area of each disorder group was calculated using cosine similarity, which was calculated from the effect sizes of each cortical regions. The thinnest cortex was found in SZ, followed by BD and MDD. The cosine similarity values between disorders were 0.943 for SZ and BD, 0.959 for SZ and MDD, and 0.943 for BD and MDD, which indicated that a common pattern of cortical thickness alterations was found among SZ, BD, and MDD. Additionally, a generally smaller cortical surface area was found in SZ and MDD than in BD, and the effect was larger in SZ. The cosine similarity values between disorders were 0.945 for SZ and MDD, 0.867 for SZ and ASD, and 0.811 for MDD and ASD, which indicated a common pattern of cortical surface area alterations among SZ, MDD, and ASD. Patterns of alterations in cortical thickness and surface area were revealed in the four major psychiatric disorders. To our knowledge, this is the first report of a cross-disorder analysis conducted on four major psychiatric disorders. Cross-disorder brain imaging research can help to advance our understanding of the pathogenesis of psychiatric disorders and common symptoms.

Bipolar disorder (BD) is a neuropsychiatric mood disorder manifested by recurrent episodes of mania and depression. More than half of BD patients are non-responsive to lithium, the first-line treatment drug, complicating BD clinical management. Given its unknown etiology, it is pertinent to understand the genetic signatures that lead to variability in lithium response. We discovered a set of differentially expressed genes (DEGs) from the lymphoblastoid cell lines (LCLs) of 10 controls and 19 BD patients belonging mainly to the immunoglobulin gene family that can be used as potential biomarkers to diagnose and treat BD. Importantly, we trained machine learning algorithms on our datasets that predicted the lithium response of BD subtypes with minimal errors, even when used on a different cohort of 24 BD patients acquired by a different laboratory. This proves the scalability of our methodology for predicting lithium response in BD and for a prompt and suitable decision on therapeutic interventions.

OBJECTIVE: Family-focused therapy (FFT) is associated with enhanced outcomes in youth with bipolar and depressive disorders, but has not been evaluated in conjunction with mobile health tools. In symptomatic adolescents whose parents had histories of mood disorders, we examined whether the effects of telehealth-based FFT were augmented by mobile health apps that emphasized mood tracking and family coping skills. METHOD: Participants (aged 13-19 years) had active mood symptoms and a parent with major depressive or bipolar disorder. Participants received 12 sessions in 18 weeks of telehealth FFT, with random assignment to (1) a mobile app (MyCoachConnect, MCC) that enabled mood tracking, reviews of session content, and text reminders to practice mood management and family communication skills (FFT-MCC); or (2) a mobile app that enabled mood tracking only (FFT-Track). Independent evaluators assessed youth every 9 weeks over 6 months on depressive symptoms (primary outcome), anxiety, and psychosocial functioning. RESULTS: Participants (N = 65; mean age 15.8 ± 1.6 years) significantly improved in depressive symptoms over 6 months (F1,170 = 45.02, p < .0001; ή2 = 0.21, 95% CI = 0.11-0.31), but there were no effects of treatment condition or treatment by time interactions on depression scores. When secondary outcome measures were considered, the subgroup of youth with bipolar spectrum disorders showed greater improvements in anxiety and global functioning in FFT-MCC compared with FFT-Track. CONCLUSION: Youth in the early stages of mood disorder may benefit from FFT enhanced by mobile health apps. Collaborations between researchers and information technologists on mobile app design and user experience may lead to increases in engagement among adolescents. CLINICAL TRIAL REGISTRATION INFORMATION: Technology Enhanced Family Treatment; https://clinicaltrials.gov/; NCT03913013.

Risky decision-making is a common, heritable endophenotype seen across many psychiatric disorders. Its underlying genetic architecture is incompletely explored. We examined behavior in the Balloon Analogue Risk Task (BART), which tests risky decision-making, in two independent samples of European ancestry. One sample (n = 1138) comprised healthy participants and some psychiatric patients (53 schizophrenia, 42 bipolar disorder, 47 ADHD); the other (n = 911) excluded for recent treatment of various psychiatric disorders but not ADHD. Participants provided DNA and performed the BART, indexed by mean adjusted pumps. We constructed a polygenic risk score (PRS) for discovery in each dataset and tested it in the other as replication. Subsequently, a genome-wide MEGA-analysis, combining both samples, tested genetic correlation with risk-taking self-report in the UK Biobank sample and psychiatric phenotypes characterized by risk-taking (ADHD, Bipolar Disorder, Alcohol Use Disorder, prior cannabis use) in the Psychiatric Genomics Consortium. The PRS for BART performance in one dataset predicted task performance in the replication sample (r = 0.13, p = 0.000012, pFDR = 0.000052), as did the reciprocal analysis (r = 0.09, p = 0.0083, pFDR=0.04). Excluding participants with psychiatric diagnoses produced similar results. The MEGA-GWAS identified a single SNP (rs12023073; p = 3.24 × 10-8) near IGSF21, a protein involved in inhibitory brain synapses; replication samples are needed to validate this result. A PRS for self-reported cannabis use (p = 0.00047, pFDR = 0.0053), but not self-reported risk-taking or psychiatric disorder status, predicted behavior on the BART in our MEGA-GWAS sample. The findings reveal polygenic architecture of risky decision-making as measured by the BART and highlight its overlap with cannabis use.

Introduction Studies indicate that long-acting injectable antipsychotics (LAIAs) reduce the risk of relapse and hospitalization compared with oral antipsychotics (APs) in adults. Oral formulations of APs are well-studied in the pediatric population, but little is known regarding the off-label use of LAIAs in this population. Methods This retrospective chart review evaluated readmission rates for pediatric patients admitted to a psychiatric ward in a large academic hospital between January 1, 2015, and December 1, 2022, requiring AP therapy. The experimental group included patients initiated on LAIA therapy, and the control group included patients initiated on a new oral AP. Patients were matched by several clinical factors. Results Each group consisted of 38 patients. For the primary outcome, hospital readmission rates at 3 months, the LAIA group had a 13.2% readmission rate compared with 26.3% in the comparator group (p = .153). In months 4 through 6, there was a 5.3% versus 15.8% readmission rate, respectively (p = .139). In months 7 through 12, it was 7.9% versus 18.4% (p = .179). There were significantly fewer cumulative readmissions at the 1-year mark in the LAIA group (N = 9, 23.7%) compared with the oral AP group (N = 18, 47.4%) (p = .031). No statistically significant differences were seen in hospital length of stay although results numerically favored LAIA. Discussion In a pediatric population, the administration of an LAIA when compared with the oral equivalent resulted in numerically fewer hospital readmissions, decreased length of stay, and fewer adverse effects, but these effects were not statistically significant except for cumulative readmissions at 1 year.

Nursing Approach to an Individual Diagnosed with Bipolar Disorder Based on Watson's Theory of Human Caring: A Case Report

Abstract Background Bipolar disorder (BD) is a severe mental disorder related to neurocognitive deficits. Exposure to childhood trauma is associated with worse cognitive performance. Different compositions of childhood trauma in BD and their impacts on cognition are rarely reported. Methods We used the Brief Assessment of Cognition in Affective Disorders (BAC-A) to assess cognitive performance and the Chinese version of the Short Form of the Childhood Trauma Questionnaire (C-CTQ-SF) to assess childhood trauma experience among 55 euthymic BD patients. Cluster analysis was applied to dissect their childhood trauma experiences, which revealed three distinct clusters: a low trauma group, neglect-focus group, and multiple-trauma-experience group. We compared the cognitive function between the three clusters and used a generalized linear model to evaluate the impact of childhood neglect on cognitive domains. Results The neglect-focus cluster showed prominent exposures to physical and emotional neglect (41.8%). BD patients in this cluster performed worse in BAC-A compared with patients in the multiple trauma cluster, especially in working memory and processing speed. The neglect-focus group revealed a significant negative effect on the composite score (ß = -0.904, p = 0.025) and working memory (ß = -1.150, p = 0.002) after adjusting sex, age, education year, BMI and total psychotropic defined daily dose. Conclusions Distinct patterns of childhood trauma experience are seen in BD patients and are related with different cognitive profiles. Early exposure of neglect-focus trauma was associated with the worst cognitive performance in current study. Further studies investigating the intensity of the neglect, as well as individual resilience and coping mechanisms in BD, are warranted.

Abstract Background Bipolar disorder (BD) and schizophrenia (SZ) are the two main mental disorders with unknown etiology that significantly impact individuals’ quality of life. The potential pro-inflammatory role in their pathogenesis is postulated and Human Endogenous Retrovirus W (HERV-W) is an emerging candidate to modulate this pathogenic finding. HERVs, ancient retroviruses in the human genome, may play roles in inflammation and disease pathogenesis. Despite HERVs’ involvement in autoimmune diseases, their influence on mental disorders remains underexplored. Therefore, the aim of this study was to assess the level of HERV-W-env expression and the systemic inflammatory profile through the concentration of IL-2, IL-4, IL-6, IL-10, TNF-α and INF-γ cytokines in BD and SZ patients. Results All participants showed HERV-W-env expression, but its expression was higher in mental disorder patients (p

Abstract Introduction Bipolar disorder (BD) is a chronic psychiatric disorder that combines hypomania or mania and depression. The study aims to investigate the research areas associated with cognitive function in bipolar disorder and identify current research hotspots and frontier areas in this field. Methodology Publications related to cognitive function in BD from 2012 to 2022 were searched on the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace, and Scimago Graphica were used to conduct this bibliometric analysis. Results A total of 989 articles on cognitive function in BD were included in this review. These articles were mainly from the United States, China, Canada, Spain and the United Kingdom. Our results showed that the journal “Journal of Affective Disorders” published the most articles. Apart from “Biploar disorder” and “cognitive function”, the terms “Schizophrenia”, “Meta analysis”, “Rating scale” were also the most frequently used keywords. The research on cognitive function in bipolar disorder primarily focused on the following aspects: subgroup, individual, validation and pathophysiology. Conclusions The current concerns and hotspots in the filed are: “neurocognitive impairment”, “subgroup”, “1st degree relative”, “mania”, “individual” and “validation”. Future research is likely to focus on the following four themes: “Studies of the bipolar disorder and cognitive subgroups”, “intra-individual variability”, “Validation of cognitive function tool” and “Combined with pathology or other fields”.

Guodong Yang,1– 3 Shuang Zhou,4 Yue Feng,5 Jiaran Lang,1– 3 Yaxin Chen,1– 3 Huipeng Ren1– 3 1Mental Health Center, Hebei Medical University and Hebei Technical Innovation Center for Mental Health Assessment and Intervention, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 3Department of Psychiatry, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 4The Sixth People’s Hospital of Hebei Province, Baoding, Hebei, 071000, People’s Republic of China; 5Maternity & Child Care Center of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of ChinaCorrespondence: Huipeng Ren, The First Hospital of Hebei Medical University, 89 Donggang Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email renhuipeng@126.comPurpose: In clinical work, it has been found that the prevalence of hyperuricemia (HUA) is significantly higher in younger patients with psychiatric disorders, but there are few studies in this area. The present study aims to evaluate the prevalence of HUA and the relationship between the HUA and age in hospitalized patients with psychiatric disorders in the real world, and to provide a theoretical basis for clinical staff to pay attention to the metabolic indicators of younger patients and for future related studies.Methods: This is a cross-sectional evaluation of a cohort of 1761 patients with psychiatric disorders of hospitalized. The categories of disorders designed for study included: Depression, Bipolar disorder, Schizophrenia, Anxiety, Obsessive-Compulsive disorder, Acute and transient psychotic disorder, Dissociative(conversion) disorders, Conduct disorders and Tic disorders. In addition, based on age, the participants are stratified into three groups. The authors used Kruskal–Wallis tests, chi-square tests, and multiple linear logistic regression to verify the relationship between HUA and age among hospitalized patients with psychiatric disorders.Results: Overall, the estimated prevalence of HUA was 35.4%. The prevalence of HUA was significantly higher in individuals with 17 years and under compared to those with 45 years and above (P < 0.001). After adjusting for confounders, the prevalence of HUA remained higher at 17 years and under than at 45 years and above. Bipolar disorder can lead to an increased prevalence of HUA (P< 0.05).Conclusion: The prevalence of HUA was higher in hospitalized patients with psychiatric disorders, and the prevalence was inversely proportional to age.Keywords: hyperuricemia, uric acid, age, psychiatric disorders, bipolar disorder

Abstract Background Bipolar disorder is a broad diagnostic construct associated with significant phenotypic and genetic heterogeneity challenging progress in clinical practice and discovery research. Prospective studies of well-characterized patients and their family members have identified lithium responsive (LiR) and lithium non-responsive (LiNR) subtypes that hold promise for advancement. Method In this narrative review, relevant observations from published longitudinal studies of well-characterized bipolar patients and their families spanning six decades are highlighted. DSM diagnoses based on SADS-L interviews were decided in blind consensus reviews by expert clinicians. Genetic, neurobiological, and psychosocial factors were investigated in subsets of well-characterized probands and adult relatives. Systematic maintenance trials of lithium, antipsychotics, and lamotrigine were carried out. Clinical profiles that included detailed histories of the clinical course, symptom sets and disorders segregating in families were documented. Offspring of LiR and LiNR families were repeatedly assessed up to 20 years using KSADS-PL format interviews and DSM diagnoses and sub-threshold symptoms were decided by expert clinicians in blind consensus reviews using all available clinical and research data. Results A characteristic clinical profile differentiated bipolar patients who responded to lithium stabilization from those who did not. The LiR subtype was characterized by a recurrent fully remitting course predominated by depressive episodes and a positive family history of episodic remitting mood disorders, and not schizophrenia. Response to lithium clustered in families and the characteristic clinical profile predicted lithium response, with the episodic remitting course being a strong correlate. There is accumulating evidence that genetic and neurobiological markers differ between LiR and LiNR subtypes. Further, offspring of bipolar parents subdivided by lithium response differed in developmental history, clinical antecedents and early course of mood disorders. Moreover, the nature of the emergent course bred true from parent to offspring, independent of the nature of emergent psychopathology. Conclusions Bipolar disorders are heterogeneous and response to long-term lithium is associated with a familial subtype with characteristic course, treatment response, family history and likely pathogenesis. Incorporating distinctive clinical profiles that index valid bipolar subtypes into routine practice and research will improve patient outcomes and advance the development and translation of novel treatment targets to improve prevention and early intervention.

Abstract Background Rapid cycling bipolar disorder (RCBD), characterized by four or more episodes per year, is a complex subtype of bipolar disorder (BD) with poorly understood characteristics. Method This multicenter, observational, longitudinal cohort study enrolled 520 BD patients across seven psychiatric institutions in China from January 2013 to January 2014. Participants were divided into RCBD and non-RCBD (NRCBD) groups based on the frequency of mood episodes in the preceding year. Data collection utilized a standardized form, supplemented by a medical record review, focusing on sociodemographic, clinical, and treatment characteristics. Statistical analysis involved independent samples t-tests, Kruskal–Wallis H tests, Chi-square or Fisher's exact tests, with Bonferroni correction applied to account for multiple comparisons, and multivariable logistic regression to identify characteristics associated with RCBD. Results Among the BD cohort, 9.4% were identified as current RCBD. Compared to NRCBD, RCBD patients had a shorter duration from the first psychiatric consultation to the diagnosis of BD, a reduced duration of their longest period of euthymia, a lower proportion of lifetime hospitalization history due to BD, and less use of electroconvulsive therapy (ECT) within the last 12 months. Additionally, they presented higher baseline scores on the Mood Disorder Questionnaire (MDQ) and the Brief 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). However, after applying the Bonferroni correction, these differences were not statistically significant. Multivariable logistic regression analysis identified three factors that were independently associated with RCBD: time from first psychiatric consultation to BD diagnosis (Odds Ratio [OR] = 0.512, P = 0.0416), lifetime hospitalization history due to BD (OR = 0.516, P = 0.0476), and ECT treatment within the past 12 months (OR = 0.293, P = 0.0472). Conclusion This study revealed that the duration from first psychiatric consultation to BD diagnosis, lifetime hospitalization history due to BD, and ECT treatment in the past year were associated with RCBD. Recognizing these factors could contribute to enhance the early identification and clinical outcomes of RCBD. Trial Registration Number Registry ClinicalTrials.gov NCT01770704. Date of Registration: First posted on January 18, 2013.

Abstract Background Major depressive disease (MDD), schizophrenia (SCZ), and bipolar disorder (BD) are common psychiatric disorders, and their relationship with thyroid cancer has been of great interest. This study aimed to investigate the potential causal effects of MDD, SCZ, BD, and thyroid cancer. Methods We used publicly available summary statistics from large-scale genome-wide association studies to select genetic variant loci associated with MDD, SCZ, BD, and thyroid cancer as instrumental variables (IVs), which were quality controlled and clustered. Additionally, we used three Mendelian randomization (MR) methods, inverse variance weighted (IVW), MR–Egger regression and weighted median estimator (WME) methods, to estimate the bidirectional causal relationship between psychiatric disorders and thyroid cancer. In addition, we performed heterogeneity and multivariate tests to verify the validity of the IVs. Results We used two-sample bidirectional MR analysis to determine whether there was a positive causal association between MDD and thyroid cancer risk. The results of the IVW analysis (OR = 3.956 95% CI = 1.177–13.299; P = 0.026) and the WME method (OR = 5.563 95% CI = 0.998–31.008; P = 0.050) confirmed that MDD may increase the risk of thyroid cancer. Additionally, our study revealed a correlation between genetic susceptibility to SCZ and thyroid cancer (OR = 1.532 95% CI = 1.123–2.088; P = 0.007). The results of the WME method analysis based on the median estimate (OR = 1.599 95% CI = 1.014–2.521; P = 0.043) also suggested that SCZ may increase the risk of thyroid cancer. Furthermore, our study did not find a causal relationship between BD and thyroid cancer incidence. In addition, the results of reverse MR analysis showed no significant causal relationships between thyroid cancer and MDD, SCZ, or BD (P > 0.05), ruling out the possibility of reverse causality. Conclusions This MR method analysis provides new evidence that MDD and SCZ may be positively associated with thyroid cancer risk while also revealing a correlation between BD and thyroid cancer. These results may have important implications for public health policy and clinical practice. Future studies will help elucidate the biological mechanisms of these associations and potential confounders.

Amaç: Bu çalışma, bipolar bozukluk hastalarının başa çıkma stratejileri ile işlevsellik düzeyleri arasındaki ilişkiyi belirlemeyi amaçlamaktadır. Yöntemler: Bu çalışma tanımlayıcı ve ilişki arayıcı bir çalışmadır. Çalışma, Mart 2017-Ocak 2018 tarihleri arasında Doğu Anadolu Bölgesi'ndeki bir hastanenin psikiyatri polikliniğine başvuran bipolar bozukluk tanılı hastalar ile yapılmıştır. Bulgular: Bu çalışmada FAST puanı ortalaması ile “duygulara odaklanma ve dışa vurma”, “madde kullanımı”, “kabullenme”, “yarışmacı etkinlikleri bastırma”, “dine yönelme”, “inkar”, “ davranışsal ilgiyi kesme, olumlu yeniden yorumlama, duygusal sosyal desteği kullanma ve planlama arasında pozitif yönde anlamlı bir ilişki bulunmuştur. Sonuç: Hastaların kullandıkları başa çıkma stratejilerinin işlevsellik düzeylerinde etkili olduğu görülmüştür.

Abstract Background Bipolar disorder (BD) is a severe mental disorder with heavy disease burden. Females with BD are special populations who suffer a lot from childhood trauma, social support, cognitive deficits, and suicidality. In this study, the relationship among childhood trauma, social support, and clinical symptoms of BD was investigated and the risk factors for suicidality were explored in female patients with BD. Methods This study included 57 drug-naive female BD patients, 64 female BD patients with long-term medication, and 50 age-matched female healthy controls. Childhood trauma, social support, clinical symptoms, cognition, and suicidality (suicide ideation, suicide plan, suicide attempt, suicide frequency) were measured with scales. Results Compared with healthy controls, females with BD showed higher levels of childhood trauma and suicidality, and lower levels of social support and cognitive deficits. In the drug-naïve BD group, social support mediated the relationship between childhood trauma and insomnia symptoms (indirect effect: ab = 0.025). In the BD with long-term medication group, mania symptom was associated with suicide plan (OR = 1.127, p = 0.030), childhood trauma was associated with suicide attempt (OR = 1.088, p = 0.018), and years of education (OR = 0.773, p = 0.028), childhood trauma (OR = 1.059, p = 0.009), and delayed memory (OR= 1.091, p= 0.016) was associated with suicide frequency (OR = 1.091, p = 0.016). Conclusions This study provides initial evidence that social support partially explains the relationship between childhood trauma and clinical symptoms in females with BD. Additionally, mania symptoms, childhood trauma, and delayed memory were risk factors for suicidality. Interventions providing social support and improving cognitive function may be beneficial for females with BD who are exposed to childhood trauma and with high suicide risk.

Abstract The majority of research into the mental health benefits of blue space (outdoor places where water is a central feature) has focussed on the associations between neighbourhood exposure to these spaces and population‐level incidence of unipolar depression or anxiety disorder. There has been little exploration of the therapeutic use of blue space by those navigating bipolar, schizophrenia or other psychotic conditions. Knowledge arising from such an exploration could assist in the design and optimisation of nature‐based care for people with these conditions, as well as with self‐management. We conducted semi‐structured online and telephone interviews with 19 adults who self‐reported experience of these conditions. Interviews were conducted in the United Kingdom from August to December 2021. We describe four of the key interpretive themes identified via an in‐depth inductive thematic analysis of the interview transcripts to highlight how participants sought out moments of affective sanctuary through their blue encounters. Blue spaces were described as having the potential to reset the mind, emotions and body. This was in part due to their socially undemanding nature, and ability to provide respite from a socially stressful world. Participants described developing a blue identity, whereby a sense of attachment to and shared history with these places was articulated as well as incorporating blue spaces into self‐ and emotion‐regulation practices. Finally, participants described experiences of and recommendations for a therapeutic blue intervention. The role of biodiversity in contributing to the benefits of blue spaces was implied primarily in terms of perceived soundscapes, but also through visual observations. Synthesis and applications. Blue care for people with bipolar, schizophrenia or other psychotic conditions should consider the need that some individuals have for solitude and proximity to their home when they visit blue spaces, as well as individual differences in the features of blue space interactions that provide the greatest benefit. Read the free Plain Language Summary for this article on the Journal blog.

Objectives: On 11 March 2020, the World Health Organization (WHO) announced the detection of a new virus epidemic in Wuhan, China. Many studies have shown that the SARS-CoV-2 virus can cause mental disorders, such as anxiety, depression, and bipolar disorder. Here, we presented a case without a history of psychiatric illness. After contracting COVID-19 Case Presentation: A 40-year-old woman was hospitalized for ten days and then discharged. However, on the fourth day following her discharge, the patient exhibited talkative, energetic, and distractible behavior. She believed herself to be God’s daughter with the ability to cure COVID-19, leading to abnormal behaviors and necessitating readmission. Treatment was started with haloperidol 5 mg, sodium valproate 500 g, and clonazepam 2 mg. By the 17th day, the patient’s mania rating scale score had decreased. Discussion: This case report underscores the significance of viral diseases as triggering and exacerbating factors in bipolar disorder. It also emphasizes the importance of considering viral infections as potential causes of psychiatric symptoms in individuals with COVID-19.

Abstract Background Multiple traumatic experiences, particularly in childhood, may predict and be a risk factor for the development of complex post-traumatic stress disorder (cPTSD). Unfortunately, individuals with bipolar disorder (BP) are more likely to have suffered traumatic events than the general population. Consequently, cPTSD could be comorbid with BD, and this may negatively affect psychopathological manifestations. To date, no one has explored whether such comorbidity also affects the response to treatment with mood stabilizers in BD patients. Results Here, a cross-sectional study was carried out by comparing the response to treatment, measured by the Alda scale, in a cohort of 344 patients diagnosed with BD type I and II, screened for the presence (or absence) of cPTSD using the International Trauma Questionnaire. The main result that emerged from the present study is the poorer response to mood stabilizers in BD patients with comorbid cPTSD compared with BD patients without cPTSD. Conclusions The results collected suggest the need for an add-on therapy focused on trauma in BD patients. This could represent an area of future interest in clinical research, capable of leading to more precise and quicker diagnoses as well as suggesting better tailored and more effective treatments.

Background One of the most robust risk factors for developing a mood disorder is having a parent with a mood disorder. Unfortunately, mechanisms explaining the transmission of mood disorders from one generation to the next remain largely elusive. Since timely intervention is associated with a better outcome and prognosis, early detection of intergenerational transmission of mood disorders is of paramount importance. Here, we describe the design of the Mood and Resilience in Offspring (MARIO) cohort study in which we investigate: 1. differences in clinical, biological and environmental (e.g., psychosocial factors, substance use or stressful life events) risk and resilience factors in children of parents with and without mood disorders, and 2. mechanisms of intergenerational transmission of mood disorders via clinical, biological and environmental risk and resilience factors. Methods MARIO is an observational, longitudinal cohort study that aims to include 450 offspring of parents with a mood disorder (uni- or bipolar mood disorders) and 100-150 offspring of parents without a mood disorder aged 10-25 years. Power analyses indicate that this sample size is sufficient to detect small to medium sized effects. Offspring are recruited via existing Dutch studies involving patients with a mood disorder and healthy controls, for which detailed clinical, environmental and biological data of the index-parent (i.e., the initially identified parent with or without a mood disorder) is available. Over a period of three years, four assessments will take place, in which extensive clinical, biological and environmental data and data on risk and resilience are collected through e.g., blood sampling, face-to-face interviews, online questionnaires, actigraphy and Experience Sampling Method assessment. For co-parents, information on demographics, mental disorder status and a DNA-sample are collected. Discussion The MARIO cohort study is a large longitudinal cohort study among offspring of parents with and without mood disorders. A unique aspect is the collection of granular data on clinical, biological and environmental risk and resilience factors in offspring, in addition to available parental data on many similar factors. We aim to investigate the mechanisms underlying intergenerational transmission of mood disorders, which will ultimately lead to better outcomes for offspring at high familial risk.

Abstract Background The suicide rate in bipolar disorder (BD) is among the highest across all psychiatric disorders. Identifying modifiable variables that relate to suicidal thoughts and behaviors (STBs) in BD may inform prevention strategies. Social connectedness is a modifiable variable found to relate to STBs in the general population, but differences exist across subgroups of the general population and findings specifically in BD have been equivocal. We aimed to clarify how perceived social connectedness relates to STBs in BD. Method 146 adults (86 BD, 60 healthy controls) completed clinical interviews (Hamilton Depression Rating Scale; Structured Clinical Interview for DSM-5) and self-report measures of loneliness (UCLA Loneliness Scale) and social support (Interpersonal Support Evaluation List). Analyses explored differences in indicators of social connectedness (loneliness and social support) between BD participants and healthy controls, and explored relationships between STBs (lifetime suicide attempts and current suicidal ideation) and indicators of social connectedness in BD participants. Results BD participants reported significantly higher loneliness and lower social support than healthy controls. In BD participants, perceived social support was significantly related to both ever having attempted suicide and number of lifetime attempts. Interestingly, perceived loneliness, but not social support, was significantly associated with current suicidal ideation. Conclusions Findings expand the evidence base supporting a relationship between perceived social connectedness and STBs in BD. They suggest that this modifiable variable could be a fruitful treatment target for preventing STBs in BD.

Abstract Background The Racing and Crowded Thoughts Questionnaire (RCTQ-13) is the most widely used specific scale for the measurement of racing thoughts, but there is currently no Spanish version that allow the evaluation in Spanish-speaking patients. The objective of this study is to translate, adapt, and validate the RCTQ-13 in a Colombian population with affective disorders. Methods The questionnaire was translated and back-translated, and corrections were implemented following a pilot test to improve comprehensibility. We included patients with Bipolar I Disorder and with Major depressive disorder seen in three centers in the city of Medellín, Colombia. We evaluate structural validity with confirmatory factor analysis, internal consistency, and test-retest reliability. Construct validity was also assessed with the comparison between euthymic, maniac, and depressive episodes and the correlation with worry, rumination, and mania scales. Responsiveness was measured 1 month after the first evaluation. Based on item response theory (IRT), we also estimated item difficulty, discrimination, and fit using a generalized partial credit model. Results Two hundred fifty subjects were included. Confirmatory factor analysis revealed that the three-factor structure of the scale was appropriate. Internal consistency was adequate for the entire scale (Cronbach’s alpha = 0.95, 95% CI: 0.94-0.96) and for each factor. Test-retest reliability was good (intraclass correlation coefficient = 0.82, 95%IC: 0.70-0.88). For construct validity, we observed differences between patients with different types of affective episodes, a moderate positive correlation with the Penn State Worry Scale (r = 0.55) and the Ruminative Response Scale (r = 0.42), and a low negative correlation with the Young Mania Rating Scale (r = − 0.10). Responsiveness was proved to be adequate. Under IRT, the response thresholds for the response options are organized for all items. The infit was adequate for all items and the outfit was acceptable. Conclusions The Spanish version of the RCTQ-13 is a reliable, valid, and responsive scale and can be used for the clinical assessment of the construct of racing and crowded thoughts in patients with the spectrum of affective disorders in whom this experience can be expressed with different nuances. Further research is needed to expand the relationship with rumination and worry.

Bipolar disorder is a chronic and common psychiatric disease that causes poor quality of life and loss of functionality. Although lithium remains in the first place in the acute mania and maintenance treatment of bipolar disorder, its mechanism of action is still unclear. In addition, the response to lithium varies widely among patients. Up to 30-55% of patients with bipolar disorder do not benefit from lithium treatment or experience side effects that cause them to discontinue the treatment. As a result of the studies carried out to date, some clinical variables that predict the difference in lithium response among individuals have been identified, but consistent results have not been obtained. Difficulties in detecting lithium response over clinical variables, lack of consistent peripheral and neuroimaging markers, and familial clustering of the disease and treatment response led researchers to conduct genetic studies. Researchers have primarily focused on candidate gene studies. However, whole genome association studies have begun to be performed due to the inadequacy of candidate gene studies in detecting the lithium response, which is estimated to be polygenic. Data on lithium response and some single nucleotide polymorphisms, noncoding RNAs, and polygenic risk score associations were acquired from these studies. Recently, researchers have been working to elucidate the epigenetic mechanisms involved in gene-environment interaction. In this article, both clinical features and both prominent genetic and epigenetic markers associated with lithium response are reviewed and critical points that should be considered in future research are emphasized.

Abstract Background The phenomenon of preventing the recurrences of mood disorders by the long-term lithium administration was discovered sixty years ago. Such a property of lithium has been unequivocally confirmed in subsequent years, and the procedure makes nowadays the gold standard for the pharmacological prophylaxis of bipolar disorder (BD). The efficacy of lithium prophylaxis surpasses other mood stabilizers, and the drug has the longest record as far as the duration of its administration is concerned. The continuation of lithium administration in case of good response could be a lifetime and last for several decades. The stability of lithium prophylactic efficacy in most patients is pretty steady. However, resuming lithium after its discontinuation may, in some patients, be less efficient. Main body In the article, the clinical and biological factors connected with the prophylactic efficacy of long-term lithium administration are listed. Next, the adverse and beneficial side effects of such longitudinal treatment are presented. The main problems of long-term lithium therapy, which could make an obstacle to lithium continuation, are connected with lithium’s adverse effects on the kidney and, to lesser extent, on thyroid and parathyroid functions. In the paper, the management of these adversities is proposed. Finally, the case reports of three patients who have completed 50 years of lithium therapy are described. Conclusions The authors of the paper reckon that in the case of good response, lithium can be given indefinitely. Given the appropriate candidates for such therapy and successful management of the adverse effects, ultra-long term lithium therapy is possible and beneficial for such patients.

Abstract Aim The etiology of bipolar disorder (BD) remains unknown; however, lipid abnormalities in BD have received increasing attention in recent years. In this study, we examined the expression levels of enzyme proteins associated with the metabolic pathway of phosphoinositides (PIs) and their downstream effectors, protein kinase B (Akt1) and glycogen synthase kinase 3β (GSK3β), which have been assumed to be the targets of mood stabilizers such as lithium, in the postmortem brains of patients with BD. Methods The protein expression levels of phosphatidylinositol 4‐phosphate 5‐kinase type‐1 gamma (PIP5K1C), phosphatidylinositol 4‐kinase alpha (PIK4CA), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), Akt1, and GSK3β were measured using enzyme‐linked immunosorbent assays and multiplex fluorescent bead‐based immunoassays in the prefrontal cortex (PFC). Specifically, PTEN, Akt1, GSK3β, and PIP5K1C were measured in seven BD patients and 48 controls. Additionally, PIK4CA was analyzed in 10 cases and 34 controls. Results PTEN expression levels were markedly decreased in the PFCs of patients with BD, whereas those of Akt and GSK3β were prominently elevated. Moreover, patients medicated with lithium exhibited higher Akt1 expression levels and lower PTEN expression levels in comparison with the untreated group. Conclusion Our results suggest that the expression levels of Akt1/GSK3β and its upstream regulator PTEN are considerably altered.

Abstract Steroid-induced neuropsychiatric sequelae are common, and pose significant risks to people usually receiving glucocorticoids in the context of physical illness. Steroid-induced mania and hypomania are the most common of the acute complications, yet despite great progress in understandings in neurophysiology there are no recent studies which review the factors which might predict who will experience this severe complication, nor are there consensus guidelines on management. We report the unusual case of a woman in her 50s admitted to a psychiatric unit with steroid-induced mania despite compliance with two mood stabilisers, several days after the administration of a Dexamethasone and Docetaxel chemotherapy regime adjunctive to lumpectomy for breast cancer. She had previously been diagnosed with an organic affective disorder (with classical bipolar 1 pattern) following severe ventriculitis related to ventricular drain insertion for obstructive hydrocephalus secondary to a colloid cyst. She had no psychiatric illness before this brain injury, but has a maternal history of idiopathic bipolar 1 affective disorder. Her episode of steroid-induced mania resolved following use of sedative medications, continuation of her existing mood stabilisers, and reductions of the steroid dosing in collaboration with her oncology team, which also protected her from further manic relapses during continued chemotherapy. Established mental illness, a family history, and acquired brain injury may reflect risk factors for steroid-induced mania through currently unclear pathways. Future epidemiological studies could better confirm these observations, and basic neuroscience may look to further explore the role of extrinsic glucocorticoids in the pathophysiology of affective disorders.

Abstract Background Reports at the beginning of the COVID-19 pandemic suggested differences in COVID-19-associated mortality between individuals with serious mental disorders (SMD) and the population at large. Aim To compare the pattern of COVID-19-associated mortality in individuals with and without SMD in Sweden over the two main pandemic years. Methods We compared the pattern of COVID-19-associated mortality in individuals with and without SMD in Sweden during 2020 and 2021. For SMD, we included psychotic disorder, bipolar disorder, and severe depression. The analysis was based on summary data from the Swedish Board of Health and Welfare covering the entire adult Swedish population. Results The overall relative risk (RR) for experiencing a COVID-19-associated death was 1.66 (CI 1.50–1.83; p

Abstract Background An increasing number of adults over 60 years old are presenting with requests for treatment of attention-deficit/hyperactivity disorder (ADHD). However, the prevalence of ADHD in older adults in geriatrics is unknown. Further, comorbid bipolar disorder and adult ADHD are likely underrecognized with many patients only receiving treatment for one of these conditions. The occurrence of bipolar disorder with geriatric onset ADHD is unknown. Case presentation A 64-year-old Hispanic woman with a psychiatric history of bipolar I disorder (diagnosed in early adulthood) was diagnosed with ADHD suspected of geriatric onset, and able to be successfully managed on concurrent mood stabilizers and psychostimulant medication. Conclusions The findings of this case report emphasize the importance of appropriately recognizing and treating comorbid ADHD and bipolar disorder in any age group, including the geriatric population for which this occurrence appears to be very rare. Additionally, this case report demonstrates the safe utilization of psychostimulant medications in a geriatric patient with bipolar disorder without inducing a manic episode or other significant adverse reactions.

Abstract Toxoplasma gondii (TOXO) infection typically results in chronic latency due to its ability to form cysts in the brain and other organs. Latent toxoplasmosis could promote innate immune responses and impact brain function. A large body of evidence has linked TOXO infection to severe mental illness (SMI). We hypothesized that TOXO immunoglobulin G (IgG) seropositivity, reflecting previous infection and current latency, is associated with increased circulating neuron-specific enolase (NSE), a marker of brain damage, and interleukin-18 (IL-18), an innate immune marker, mainly in SMI. We included 735 patients with SMI (schizophrenia or bipolar spectrum) (mean age 32 years, 47% women), and 518 healthy controls (HC) (mean age 33 years, 43% women). TOXO IgG, expressed as seropositivity/seronegativity, NSE and IL-18 were measured with immunoassays. We searched for main and interaction effects of TOXO, patient/control status and sex on NSE and IL-18. In the whole sample as well as among patients and HC separately, IL-18 and NSE concentrations were positively correlated (p

Objective: This study aimed to describe the clinical and psychiatric characteristics of older outpatients with bipolar disorder (BD), including psychiatric history (age of onset of symptoms,length of time with the illness, and number of psychiatric hospitalizations), mood state, and cognitive function. Methods: This was a cross-sectional study where clinical and demographic data were obtained by a psychiatric interview with each patient and family members as well as by a review of medical records. The sample consisted of 20 individuals aged 60 years or older with a diagnosis of BD type I according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition. Descriptive data analysis was performed, with categorical variables expressed as absolute and relative frequencies. Results: No patient had manic or depressive symptoms at the time of the evaluation; 15(75.0%) had an early onset while 5 (25.0%) had a late onset of the disease. Nine patients(45.0%) showed no cognitive decline whereas 11 (55.0%) showed mild cognitive impairment. Conclusions: This study presents an understudied group of patients with BD. Considering the personal impact and burden on the health system related to this psychiatric condition, it is recommended that further studies be conducted in this area to better evaluate this growing population.

Individuals with mood disorders are predisposed to metabolic dysfunction, while those with metabolic dysregulation such as diabetes and obesity experience more severe depressive symptoms. Both metabolic dysfunction and mood disorders are independently associated with cognitive deficits. Therefore, given their close association, this study aimed to explore the association between metabolic dysfunction in individuals with mood disorders in relation to cognitive outcomes. A comprehensive search comprised of these three domains was carried out; a random-effects meta-analysis pooling mean cognitive outcomes was conducted (PROSPERO ID: CRD42022295765). Sixty-three studies were included in this review; 26 were synthesized in a quantitative meta-analysis. Comorbid metabolic dysregulation was associated with significantly lower global cognition among individuals with mood disorders. These trends were significant within each mood disorder subgroup, including major depressive disorder, bipolar disorder, and self-report depression/depressive symptoms. Type 2 diabetes was associated with the lowest cognitive performance in individuals with mood disorders, followed by peripheral insulin resistance, body mass index ⩾25 kg/m2, and metabolic syndrome. Significant reduction in scores was also observed among individual cognitive domains (in descending order) of working memory, attention, executive function, processing speed, verbal memory, and visual memory. These findings demonstrate the detrimental effects of comorbid metabolic dysfunction in individuals with mood disorders. Further research is required to understand the underlying mechanisms connecting mood disorders, metabolism, and cognition. [ABSTRACT FROM AUTHOR]

Background: Although diagnostic instability in first-episode psychosis (FEP) is of major concern, little is known about its determinants. This very long-term follow-up study aimed to examine the diagnostic stability of FEP diagnoses, the baseline predictors of diagnostic change and the timing of diagnostic change. Methods: This was a longitudinal and naturalistic study of 243 subjects with FEP who were assessed at baseline and reassessed after a mean follow-up of 21 years. The diagnostic stability of DSM-5 psychotic disorders was examined using prospective and retrospective consistencies, logistic regression was used to establish the predictors of diagnostic change, and survival analysis was used to compare time to diagnostic change across diagnostic categories. Results: The overall diagnostic stability was 47.7%. Schizophrenia and bipolar disorder were the most stable diagnoses, with other categories having low stability. Predictors of diagnostic change to schizophrenia included a family history of schizophrenia, obstetric complications, developmental delay, poor premorbid functioning in several domains, long duration of untreated continuous psychosis, spontaneous dyskinesia, lack of psychosocial stressors, longer duration of index admission, and poor early treatment response. Most of these variables also predicted diagnostic change to bipolar disorder but in the opposite direction and with lesser effect sizes. There were no significant differences between specific diagnoses regarding time to diagnostic change. At 10-year follow-up, around 80% of the diagnoses had changed. Conclusions: FEP diagnoses other than schizophrenia or bipolar disorder should be considered as provisional. Considering baseline predictors of diagnostic change may help to enhance diagnostic accuracy and guide therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objectives: Bipolar disorder (BD) is a prevalent psychological disorder associated with depressive symptoms. Transcranial direct current stimulation (tDCS) is a portable and non-invasive technique for brain stimulation. The present study was conducted to determine the effectiveness of the combined treatment of tDCS and routine medication on the symptoms of depression, anxiety, and anger in BD adolescents. Methods: In this double-blind randomized clinical trial study, forty adolescents with BD referred to the outpatient clinic of child and psychiatry of Golestan Ahvaz Teaching Hospital were included. Eligible patients aged 12 - 18 years were randomly divided into 2 groups receiving routine medications plus active tDCS (intervention group) or routine medications plus sham tDCS (control group). Transcranial direct current stimulation intervention with an intensity of 2 mA was applied to the dorsolateral prefrontal cortex in two sessions for 20 minutes each day, for 5 consecutive days. Data were collected at baseline, one week, and one month after the start of the intervention using the Hamilton Depression Rating Scale (HDRS-21), Hamilton Anxiety Rating Scale (HDRS), and State-Trait Anger Expression Inventory. Results: Based on our findings, age and gender were not considerably different between the two groups (P = 0.592, P = 0.1, respectively). In both groups, scores of depression (control: 12.25 ± 3.97, intervention: 0.75 ± 1.44, mean [SD]), anxiety (13.55 ± 2.58, 25.0 ± 0.55), and anger (52.65 ± 8.27, 47.25 ± 4.86) improved significantly one month after treatment (P < 0.0001). After one month of treatment, the severity of bipolar symptoms in the intervention group (slightly: 10%, moderately: 50%, and markedly: 40%) improved significantly compared to the control group (slightly: 15%, moderately: 10%, and markedly: 0%) (P < 0.0001). The improvement rate of HDRS in the intervention group was 81.29% and 95.24% at one week and one month after treatment, while these values were 8.41% and 23.04% in the control group, respectively (P < 0.0001). All patients tolerated the treatment well without serious side effects. There was no significant difference between the side effects observed in both groups (P = 0.185). Conclusions: The combination of tDCS with routine medications can reduce depressive symptoms and improve bipolar symptoms. Therefore, tDCS add-on could be an effective, safe, and tolerable intervention for bipolar depression. [ABSTRACT FROM AUTHOR]

Study results supported that immuno-inflammatory pathways in the brain and environment contribute to the etiopathogenesis of bipolar disorder (BD), a chronic affective disease. Our study aimed to assess the relationship between BD risk and interleukin 2 (IL2) and interleukin 2 receptor subunit alpha (IL2RA) variants in a Turkish population. Genomic DNA from 86 diagnosed BD patients and 100 healthy blood donors was extracted. IL2RA rs2104286, IL2 rs2069762, and IL2 rs2069763 variants were genotyped using the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. It was compared to the relationship between the genotype distributions of these variants and clinical characteristics. Results were evaluated statistically. A statistically significant difference in the genotype distribution of the IL2RA rs2104286 variant was found between patients and controls. There was no GG genotype in the patient group. The IL2RA rs2104286 AA genotype was more common in the patient group than the controls, and the AG genotype was higher in the controls compared to the patients (p = 0.001, p = 0.001, respectively). The IL2 rs2069762 and IL2 rs2069763 genotype distributions did not differ between the patient and control groups (p > 0.05). We found that the clinical global impression severity (CGI-S) score was higher in those with IL2 rs2069762 TG and GG genotypes. In this study, we showed for the first time that the genotype distribution of IL2RA rs2104286 and IL2 rs2069762 is associated with BD susceptibility and CGI-S score in a Turkish population. [ABSTRACT FROM AUTHOR]

Inflammation impairs cognitive function in healthy individuals and people with psychiatric disorders, such as bipolar disorder (BD). This effect may also impact emotion recognition, a fundamental element of social cognition. Our study aimed to investigate the relationships between pro-inflammatory cytokines and emotion recognition in euthymic BD patients and healthy controls (HCs). We recruited forty-four euthymic BD patients and forty healthy controls (HCs) and measured their inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and TNF-α. We applied validated cognitive tasks, the Wisconsin Card-Sorting Test (WCST) and Continuous Performance Test (CPT), and a social cognitive task for emotion recognition, Diagnostic Analyses of Nonverbal Accuracy, Taiwanese Version (DANVA-2-TW). We analyzed the relationships between cytokines and cognition and then explored possible predictive factors of sadness recognition accuracy. Regarding pro-inflammatory cytokines, TNF-α was elevated in euthymic BD patients relative to HCs. In euthymic BD patients only, higher TNF-α levels were associated with lower accuracy of sadness recognition. Regression analysis revealed that TNF-α was an independent predictive factor of sadness recognition in patients with euthymic BD when neurocognition was controlled for. Conclusions : We demonstrated that enhanced inflammation, indicated by increased TNF-α, was an independent predictive factor of impaired sadness recognition in BD patients but not in HCs. Our findings suggested a direct influence of TNF-α on sadness recognition and indicated vulnerability to depression in euthymic BD patients with chronic inflammation. [ABSTRACT FROM AUTHOR]

The Contrast Avoidance Model suggests that individuals sensitive to negative emotional shifts use prior increases in negative affect to prevent further escalation in response to adverse situations, while the heightened negative affect amplifies positive emotional contrasts when encountering unexpected positive events. Individuals with bipolar spectrum disorders (BSDs), characterized by shifts between (hypo)manic and depressive episodes, may undergo more salient emotional contrasts. Drawing from the Contrast Avoidance Model, the shifts from depression to (hypo)mania can be conceptualized as positive emotional contrasts, potentially heightening the perceived pleasure during (hypo)manic episodes. On the other hand, the shifts from (hypo)manic to depressive episodes can be viewed as negative emotional contrasts, contributing to the challenges associated with depressive states. Despite the intriguing potential of this interplay, the link between the Contrast Avoidance Model and BSDs has never been empirically tested. Our study addressed this gap by examining group differences in contrast avoidance traits between individuals with BSDs, unipolar depression, and healthy controls in a large cohort study (N = 536). Results indicated that individuals with BSDs exhibited significantly higher scores in the total, and Discomfort with Negative Emotional Shifts and Avoidance of Negative Emotional Contrasts/Enhancement of Positive Emotional Contrasts factors, as well as separate item scores on the Contrast Avoidance Questionnaire-General Emotion (CAQ-GE), compared to those with unipolar depression and healthy controls. Although marginal, the BD II subtype demonstrated a stronger inclination to avoid negative emotional contrasts compared to BD I. These findings suggest that contrast avoidance may be a psychological mechanism implicated in BSDs. • Bipolar spectrum disorders (BSDs) are associated with the Contrast Avoidance Model. • The BSD group exhibited significantly greater contrast avoidance traits. • Bipolar II showed greater avoidance of negative emotional contrasts than bipolar I. [ABSTRACT FROM AUTHOR]

Medical comorbidity, particularly cardiovascular diseases, contributes to high rates of hospital admission and early mortality in people with schizophrenia. The 30 days following hospital discharge represents a critical period for mitigating adverse outcomes. This study examined the odds of successful community discharge among Veterans with schizophrenia compared to those with major affective disorders and those without serious mental illness (SMI) after a heart failure hospital admission. Data for Veterans hospitalized for heart failure were obtained from the Veterans Health Administration (VHA) and Centers for Medicare & Medicaid Services between 2011 and 2019. Psychiatric diagnoses and medical comorbidities were assessed in the year prior to hospitalization. Successful community discharge was defined as remaining in the community without hospital readmission, death, or hospice for 30 days after hospital discharge. Logistic regression analyses adjusting for relevant factors were used to examine whether individuals with a schizophrenia diagnosis showed lower odds of successful community discharge versus both comparison groups. Out of 309,750 total Veterans in the sample, 7377 (2.4%) had schizophrenia or schizoaffective disorder and 32,472 (10.5%) had major affective disorders (bipolar disorder or recurrent major depressive disorder). Results from adjusted logistic regression analyses demonstrated significantly lower odds of successful community discharge for Veterans with schizophrenia compared to the non-SMI (Odds Ratio [OR]: 0.63; 95% Confidence Interval [CI]: 0.60, 0.66) and major affective disorders (OR: 0.65, 95%; CI: 0.62, 0.69) groups. Intervention efforts should target the transition from hospital to home in the subgroup of Veterans with schizophrenia. [ABSTRACT FROM AUTHOR]

Increased levels of inflammation markers have been found in the peripheral tissue of individuals with bipolar disorder (BD), especially during mood episodes. Previous studies found distinctive inflammatory profiles across different brain regions, but potential associations with clinical symptoms are still lacking. This study aims to evaluate the association of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate of individuals with BD. Levels of IL-1β, IL-6, IL-17A, cortisol, and C-reactive protein (CRP) were measured in the hippocampus and anterior cingulate of 14 BD individuals and their non-psychiatric controls. Neuropsychiatric symptoms present in the three months before death were assessed using the Neuropsychiatric Inventory (NPI). In the BD group, greater NPI scores were associated with higher IL-6 in the hippocampus (p = 0.011) and cingulate (p = 0.038) and higher IL-1β (p = 0.039) in the hippocampus. After adjusting for age, sex and CDR, IL-1β and IL-6 were still associated with higher NPI in the hippocampus. In correlation analysis considering both BD and their controls, moderate positive associations were found between NPI and IL-6 and cortisol in the hippocampus (p < 0.001 and p = 0.006) and cingulate (p = 0.024 and p = 0.016), IL-1β (p < 0.001) and IL-17A in the hippocampus (p = 0.002). No difference in inflammatory markers was found according to type of psychotropic medication used. Hence, in individuals with BD, neuropsychiatric symptoms were differently associated with specific inflammatory cytokines and CRP in the hippocampus and cingulate. These results suggest that the neuroinflammatory changes occurring in BD may be more complex than previously expected and could be associated with clinical manifestations. • Relationship between brain inflammation and symptomatology in BD is still unknown. • We sought for neuroinflammation and neuropsychiatric symptoms across brain regions. • Neuropsychiatric symptoms associate with neuroinflammation in brain-specific manners. • Neuroinflammatory changes occurring in BD may underlie clinical symptoms. [ABSTRACT FROM AUTHOR]

• Immune dysregulation was present in patients with newly diagnosed bipolar disorder (BD) • Higher levels of pro-inflammatory markers in patients with BD compared with HC. • Higher levels of anti-inflammatory markers in patients with BD compared with HC. • MDC levels were higher in patients with BD compared with HC and UR. • A composite marker discriminated BD from HC with an AUC of 0.76. Substantial evidence emphasizes immune dysregulation in patients with bipolar disorder (BD). However, whether immune dysregulation is present already in the early illness stages of BD or even precedes development of BD is largely unknown. In this study we compared immune and vascular stress markers in patients newly diagnosed with BD, their unaffected first-degree relatives (UR) and healthy control individuals (HC) and investigated the ability a composite immune and vascular stress marker to discriminate between the three groups of participants. In a unique sample including 373 patients newly diagnosed with BD, 95 UR and 190 HC, we compared 47 immune and vascular stress markers at the baseline visit in the ongoing longitudinal Bipolar Illness Onset study. For comparison of individual immune and vascular stress markers between groups, we applied linear mixed models, whereas the composite immune and vascular stress marker was investigated using the SuperLearner ensemble-method. Compared with HC, patients newly diagnosed with BD had higher levels of the anti-inflammatory interleukin-1 receptor antagonist (IL-1RA) and IL-10, and of the pro-inflammatory IL-6, eotaxin, monocyte chemoattractant protein-1 (MCP-1), MCP-4, Macrophage Derived Chemokine (MDC), and Thymus and Activation-Regulated Chemokine (TARC) in analyses adjusted for sex and age ranging from 26 % higher levels of IL-6 (1.26, 95 %CI: [1.12–1.43], p < 0.001, adjusted p = 0.009) and IL-10 (1.26, 95 %CI: [1.09–1.46], p = 0.002, adjusted p = 0.049), respectively, to 9 % higher eotaxin levels (1.09, 95 %CI: [1.04–1.15], p = 0.001, adjusted p = 0.024). Of these, MDC levels were 12 % higher in BD compared with UR (1.12, 95 %CI: [1.02–1.22], p = 0.001, adjusted p = 0.024). For all other markers, UR showed no difference from patients with BD or HC. Based on a data-driven model, a composite marker including all 47 immune and vascular stress markers, sex, age, BMI, smoking status, and alcohol intake, discriminated patients with BD from HC with a with an area under the receiver operating curve (AUC) of 0.76 (95 % CI: 0.75–0.77) Higher levels of pro-inflammatory and anti-inflammatory immune markers are present in patients newly diagnosed with BD but not in UR compared with HC, supporting immune dysregulation playing a role in the pathophysiology of BD. [ABSTRACT FROM AUTHOR]

• Covariance between cognition (measures of speed, verbal learning) & peripheral markers (YKL-40, CRP, sTNFR1, MIF, CatS). • YKL-40 secretion was dysregulated in iPSC-derived astrocytes and neural progenitor cells in SZ relative to HC. • YKL-40 and related signalling pathway genes was dysregulated in a high inflammatory subgroup in postmortem brain samples. • Potential pathophysiological role for YKL-40 in cognitive impairment in transdiagnostic SZ/BD subgroups. Recent findings link cognitive impairment and inflammatory-immune dysregulation in schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, heterogeneity and translation between the periphery and central (blood-to-brain) mechanisms remains a challenge. Starting with a large SZ, BD and healthy control cohort (n = 1235), we aimed to i) identify candidate peripheral markers (n = 25) associated with cognitive domains (n = 9) and elucidate heterogenous immune-cognitive patterns, ii) evaluate the regulation of candidate markers using human induced pluripotent stem cell (iPSC)-derived astrocytes and neural progenitor cells (n = 10), and iii) evaluate candidate marker messenger RNA expression in leukocytes using microarray in available data from a subsample of the main cohort (n = 776), and in available RNA-sequencing deconvolution analysis of postmortem brain samples (n = 474) from the CommonMind Consortium (CMC). We identified transdiagnostic subgroups based on covariance between cognitive domains (measures of speed and verbal learning) and peripheral markers reflecting inflammatory response (CRP, sTNFR1, YKL-40), innate immune activation (MIF) and extracellular matrix remodelling (YKL-40, CatS). Of the candidate markers there was considerable variance in secretion of YKL-40 in iPSC-derived astrocytes and neural progenitor cells in SZ compared to HC. Further, we provide evidence of dysregulated RNA expression of genes encoding YKL-40 and related signalling pathways in a high neuroinflammatory subgroup in the postmortem brain samples. Our findings suggest a relationship between peripheral inflammatory-immune activity and cognitive impairment, and highlight YKL-40 as a potential marker of cognitive functioning in a subgroup of individuals with severe mental illness. [ABSTRACT FROM AUTHOR]

• Immune-inflammatory mechanisms are promising targets for antidepressant pharmacology. • In a randomized controlled trial low-dose IL-2 significantly improved antidepressant response. • IL-2 rapidly expanded the population of Treg, Th2, and Naive CD4+/CD8 + immune cell counts. • Strengthening in the T cell system predicted antidepressant response. Immune-inflammatory mechanisms are promising targets for antidepressant pharmacology. Immune cell abnormalities have been reported in mood disorders showing a partial T cell defect. Following this line of reasoning we defined an antidepressant potentiation treatment with add-on low-dose interleukin 2 (IL-2). IL-2 is a T-cell growth factor which has proven anti-inflammatory efficacy in autoimmune conditions, increasing thymic production of naïve CD4 + T cells, and possibly correcting the partial T cell defect observed in mood disorders. We performed a single-center, randomised, double-blind, placebo-controlled phase II trial evaluating the safety, clinical efficacy and biological responses of low-dose IL-2 in depressed patients with major depressive (MDD) or bipolar disorder (BD). 36 consecutively recruited inpatients at the Mood Disorder Unit were randomised in a 2:1 ratio to receive either aldesleukin (12 MDD and 12 BD) or placebo (6 MDD and 6 BD). Active treatment significantly potentiated antidepressant response to ongoing SSRI/SNRI treatment in both diagnostic groups, and expanded the population of T regulatory, T helper 2, and percentage of Naive CD4+/CD8 + immune cells. Changes in cell frequences were rapidly induced in the first five days of treatment, and predicted the later improvement of depression severity. No serious adverse effect was observed. This is the first randomised control trial (RCT) evidence supporting the hypothesis that treatment to strengthen the T cell system could be a successful way to correct the immuno-inflammatory abnormalities associated with mood disorders, and potentiate antidepressant response. [ABSTRACT FROM AUTHOR]

Objective: The genome‐wide association studies (GWAS) analysis, the most successful technique for discovering disease‐related genetic variation, has some statistical concerns, including multiple testing, the correlation among variants (single‐nucleotide polymorphisms) based on linkage disequilibrium and omitting the important variants when fitting the model with just one variant. To eliminate these problems in a small sample‐size study, we used a sparse Bayesian learning model for finding bipolar disorder (BD) genetic variants. Methods: This study used the Wellcome Trust Case Control Consortium data set, including 1998 BD cases and 1500 control samples, and after quality control, 380,628 variants were analysed. In this GWAS, a Bayesian logistic model with hierarchical shrinkage spike and slab priors was used, with all variants considered simultaneously in one model. In order to decrease the computational burden, an alternative inferential method, Bayesian variational inference, has been used. Results: Thirteen variants were selected as associated with BD. The three of them (rs7572953, rs1378850 and rs4148944) were reported in previous GWAS. Eight of which were related to hemogram parameters, such as lymphocyte percentage, plateletcrit and haemoglobin concentration. Among selected related genes, GABPA, ELF3 and JAM2 were enriched in the platelet‐derived growth factor pathway. These three genes, along with APP, ARL8A, CDH23 and GPR37L1, could be differential diagnostic variants for BD. Conclusions: By reducing the statistical restrictions of GWAS analysis, the application of the Bayesian variational spike and slab models can offer insight into the genetic link with BD even with a small sample size. To uncover related variations with other traits, this model needs to be further examined. [ABSTRACT FROM AUTHOR]

Refugees are at increased risk of non-affective psychotic disorders, but it is unclear whether this extends to affective psychotic disorders [APD] or non-psychotic bipolar disorder [NPB]. We conducted a nationwide cohort study in Sweden of all refugees, non-refugee migrants and the Swedish-born population, born 1 Jan 1984–31 Dec 2016. We followed participants from age 14 years until first ICD-10 diagnosis of APD or NPB. We fitted Cox proportional hazards models to estimate hazard ratios [HR] and 95 % confidence intervals [95%CI], adjusted for age, sex and family income. Models were additionally stratified by region-of-origin. We followed 1.3 million people for 15.1 million person-years, including 2428 new APD cases (rate: 16.0 per 100,000 person-years; 95%CI: 15.4–16.7) and 9425 NPB cases (rate: 63.8; 95%CI: 62.6–65.1). Rates of APD were higher in refugee (HR adjusted : 2.07; 95%CI: 1.55–2.78) and non-refugee migrants (HR adjusted : 1.40; 95%CI: 1.16–1.68), but lower for NPBs for refugee (HR adjusted : 0.24; 95%CI: 0.16–0.38) and non-refugee migrants (HR adjusted : 0.34; 95%CI: 0.28–0.41), compared with the Swedish-born. APD rates were elevated for both migrant groups from Asia and sub-Saharan Africa, but not other regions. Migrant groups from all regions-of-origin experienced lower rates of NPB. Income may have been on the causal pathway making adjustment inappropriate. Refugees experience elevated rates of APD compared with Swedish-born and non-refugee migrants, but lower rates of NPB. This specificity of excess risk warrants clinical and public health investment in appropriate psychosis care for these vulnerable populations. • Rates of affective psychotic disorders were 1.47 and 2.07 times higher for non-refugee and refugee migrants, respectively, than Swedes • After adjustment for income, rates remained 1.49 times higher amongst refugees • Migrant groups experienced lower rates of non-psychotic bipolar disorder than Swedes • Rates were elevated most in migrants from sub-Saharan Africa and refugees from Asia [ABSTRACT FROM AUTHOR]