People with bipolar disorder (BD) have an increased risk of premature mortality and the respiratory mortality rate is higher than those of the general population. To date, however, the evidence on respiratory disease in this population has not been meta-analyzed. We systematically review and meta-analyze the frequency of respiratory diseases in patients with BD and to compare prevalence and odds ratio (OR) with the general population. The systematic literature search was conducted in Pubmed, PsycINFO, Scielo and Scopus, with snowball search of reference and citation lists. Inclusion criteria were studies reporting diagnoses of respiratory diseases (asthma, chronic obstructive pulmonary disease (COPD), pneumonia, lung cancer and tuberculosis) in people with BD according to operationalized criteria and where possible, control group. Of the 2158 articles screened, 20 including 962,352 people with BD and 37,340,405 control group, met the inclusion criteria. In people with BD, the prevalence of COPD was 9.14% (95%CI: 6.61-12.5%), asthma 6.4% (95%CI: 4.56-8.91%), pneumonia 2.78% (95%CI: 2.51-3.08%) and lung cancer 0.44% (95%CI:0.23-0.84%). Compared to the general population, people with BD had significantly higher rates of COPD (OR: 1.73; 95% CI: 1.40-2.14), showing an increased rate in younger and female patients; asthma (OR: 1.91, 95% CI: 1.25-2.94), with a greater rate in younger patients; and pneumonia (OR: 2.82, 95% CI: 1.33-5.99). In the first meta-analysis on the topic, BD was associated with an increased risk of respiratory illness versus the general population. In COPD and asthma, young people and women are at particular risk. Prevention programs are urgently needed.

To evaluate the cost-effectiveness of repetitive transcranial magnetic stimulation (rTMS) as an adjunct to standard care from an Australian health sector perspective, compared to standard care alone for adults with treatment-resistant bipolar depression (TRBD).

An economic model was developed to estimate the cost per disability-adjusted life-year (DALY) averted and quality-adjusted life-year (QALY) gained for rTMS added to standard care compared to standard care alone, for adults with TRBD. The model simulated the time in three health states (mania, depression, residual) over one year. Response to rTMS was sourced from a meta-analysis, converted to a relative risk and used to modify the time in the depressed state. Uncertainty and sensitivity tested the robustness of results.

Base-case incremental cost-effectiveness ratios (ICERs) were $72,299 per DALY averted (95 % Uncertainty Interval (UI): $60,915 to $86,668) and $46,623 per QALY gained (95 % UI: $39,676 - $55,161). At a willingness to pay (WTP) threshold of $96,000 per DALY averted, the base-case had a 100 % probability of being marginally cost-effective. At a WTP threshold of $64,000 per QALY gained, the base-case had a 100 % probability of being cost-effective. Sensitivity analyses decreasing the number of sessions provided, increasing the disability weight or the time spent in the depression state for standard care improved the ICERs for rTMS.

Dependent on the outcome measure utilised and assumptions, rTMS would be considered a very cost-effective or marginally cost-effective adjunct to standard care for TRBD compared to standard care alone.

Face-to-face cognitive behavioral therapy (CBT) is effective in the management of depression symptoms in unipolar and bipolar spectrum disorders. Though, compared to electronic adaptations of CBT (eCBT), it carries several accessibility limitations. Furthermore, unlike eCBT for depression symptoms (eCBTg), eCBT specific for bipolar depression (eCBT-Bipol) remains largely understudied. Thus, supplementing this gap, this systematic review and network meta-analysis (NMA) synthesized the available literature on eCBT for the treatment of unipolar and bipolar depression symptoms.

MEDLINE, CINAHL, PsycINFO, EMBASE, and Cochrane were searched for relevant randomized controlled trials (RCTs) on eCBTg and eCBT-Bipol The review followed PRISMA guidelines and used the Cochrane risk of bias tool and GRADE criteria for quality assessment. Effect sizes were summarized using standardized mean differences (SMDs) and risk ratios (RRs).

eCBT-Bipol was comparable to eCBTg (SMD: 0.05, 95 % CI: -0.18; 0.28) and other psychotherapeutic interventions (SMD: 0.14, 95 % CI: -0.07; 0.35) for the management of mild to moderate depression symptoms. eCBT-Bipol was significantly more effective than attention controls (SMD: 0.35, 95 % CI: 0.11; 0.59), treatment as usual (SMD: 0.55, 95 % CI: 0.21; 0.90) and no intervention controls (SMD: 0.66, 95 % CI: 0.40; 0.93) in mitigating symptoms.

The scarcity of eCBT-Bipol studies impacted the quality of the evidence in terms of risk of bias and imprecision.

The findings of this systematic review suggest that eCBT-Bipol has comparable effectiveness to eCBTg in managing depressive symptoms of unipolar and bipolar spectrum disorder. Though, they also highlighted the need for more studies on eCBT-Bipol.

The Australian Genetics of Bipolar Disorder Study is a nation-wide cohort of adults living with bipolar disorder. The study aims to detect the relationships between genetic risk, symptom severity, and the lifetime prevalence of bipolar disorder, treatment response and medication side effects, and patterns and costs of health care usage.

A total of 6682 participants (68.3% female; aged 44.8 ± 13.6 years [range = 18-90]) were recruited in three waves: a nation-wide media campaign, a mail-out based on prescriptions for lithium carbonate and through the Australian Genetics of Depression Study. Participants completed a self-report questionnaire. A total of 4706 (70%) participants provided a saliva sample and were genotyped and 5506 (82%) consented to record linkage of their Pharmaceutical and Medicare Benefits Schedule data.

Most participants were living with bipolar I disorder (n = 4068) while 1622 participants were living with bipolar II disorder and 992 with sub-threshold bipolar disorder. The mean age of bipolar disorder diagnosis was 32.7 ± 11.6 years but was younger in bipolar I (p = 2.0E-26) and females (p = 5.7E-23). Excluding depression with onset prior to bipolar disorder diagnosis, 64.5% of participants reported one or more co-occurring psychiatric disorders: most commonly generalised anxiety disorder (43.5%) and posttraumatic stress disorder (20.7%). Adverse drug reactions were common and resulted in discontinuation rates ranging from 33.4% for lithium to 63.0% for carbamazepine.

Our findings highlight the high rate of comorbidities and adverse drug reactions among adults living with bipolar disorder in the general Australian population. Future genomic analyses focus on identifying genetic variants influencing pharmacotherapy treatment response and side effects.

Bipolar disorder (BD) is a highly prevalent psychiatric condition that can significantly impact every aspect of a person's life if left untreated. A subtype of BD, Bipolar disorder II (BD-II) is characterized by long depressive episodes and residual depression symptoms, with short-lived hypomanic episodes. Medication and psychotherapy, such as cognitive behavioral therapy (CBT), are the main treatment options for BD-II. CBT specific for BD-II involves the recognition of warning signs, potentially triggering stimuli, and the development of coping skills to increase euthymic periods and improve global functioning. However, access to in-person CBT may be limited by several barriers including low availability, high costs and geographical limitations. Thus, online adaptations of CBT (e-CBT) have become a promising solution to address these treatment barriers Nevertheless, e-CBT for the treatment of BD-II remains understudied.

The proposed study aims to establish the first e-CBT program specific for the treatment of BD-II with residual depressive symptoms. The primary objective of this study will be to determine the effect of e-CBT in managing BD symptomatology. The secondary objective will be to assess the effects of this e-CBT program on quality of life, and resilience. The tertiary objective will involve gathering user feedback using a post-treatment survey to support the continuous improvement and optimization of the proposed program.

Adult participants (n = 170) with a confirmed diagnosis of BD-II experiencing residual depressive symptoms will be randomly assigned to either the e-CBT plus TAU (n = 85) group or the TAU (n = 85) control group. Participants in the control group will be able to participate in the online program after the first 13 weeks. The e-CBT program will consist of 13 weekly online modules designed following a validated CBT framework. Participants will complete module-related homework and receive asynchronous personalized feedback from a therapist. TAU will consist of standard treatment services conducted outside of the current research study. Depression and manic symptoms quality of life and resiliency will be assessed using clinically validated symptomatology questionnaires at baseline, week 6, and week 13.

The study received ethics approval in March 2020 and participant recruitment is expected to begin in February 2023 through targeted advertisements and physician referrals. Data collection and analysis are expected to conclude by December 2024. Linear and binomial regression (continuous and categorical outcomes respectively) will be conducted along with qualitative interpretive methods.

The findings will be the first on the effectiveness of delivering e-CBT for patients with BD-II with residual depressive symptoms. This approach can provide an innovative method to address barriers to in-person psychotherapy by increasing accessibility and decreasing costs.

clinicaltrials.gov (NCT04664257); clinicaltrials.gov/ct2/show/NCT04664257.

Internet-delivered psychosocial interventions can overcome barriers to face-to-face psychosocial care, but limited evidence supports their cost-effectiveness for people with bipolar disorders (BDs).

This study aimed to conduct within-trial cost-effectiveness and cost-utility analyses of an internet-based intervention for people with BD, MoodSwings 2.0, from an Australian health sector perspective.

MoodSwings 2.0 included an economic evaluation alongside an international, parallel, and individually stratified randomized controlled trial comparing an internet-based discussion forum (control; group 1), a discussion forum plus internet-based psychoeducation (group 2), and a discussion forum plus psychoeducation and cognitive behavioral tools (group 3). The trial enrolled adults (aged 21 to 65 years) with a diagnosis of BD assessed by telephone using a structured clinical interview. Health sector costs included intervention delivery and additional health care resources used by participants over the 12-month trial follow-up. Outcomes included depression symptoms measured by the Montgomery-Åsberg Depression Rating Scale (MADRS; the trial primary outcome) and quality-adjusted life years (QALYs) calculated using the short-form 6-dimension instrument derived from the 12-item version of the short-form health survey. Average incremental cost-effectiveness (cost per MADRS score) and cost-utility (cost per QALY) ratios were calculated using estimated mean differences between intervention and control groups from linear mixed effects models in the base case.

In total, 304 participants were randomized. Average health sector cost was lowest for group 2 (Aus $9431, SD Aus $8540; Aus $1=US $0.7058) compared with the control group (Aus $15,175, SD Aus $17,206) and group 3 (Aus $15,518, SD Aus $30,523), but none was statistically significantly different. The average QALYs were not significantly different among the groups (group 1: 0.627, SD 0.062; group 2: 0.618, SD 0.094; and group 3: 0.622, SD 0.087). The MADRS scores were previously shown to differ significantly between group 2 and the control group at all follow-up time points (P<.05). Group 2 was dominant (lower costs and greater effects) compared with the control group for average incremental cost per point decrease in MADRS score over 12 months (95% CI dominated to Aus $331). Average cost per point change in MADRS score for group 3 versus the control group was dominant (95% CI dominant to Aus $22,585). Group 2 was dominant (95% CI Aus $43,000 to dominant) over the control group based on lower average health sector cost and average QALY benefit of 0.012 (95% CI -0.009 to 0.033). Group 3, compared with the control group, had an average incremental cost-effectiveness ratio of dominant (95% CI dominated to Aus $19,978).

Web-based psychoeducation through MoodSwings 2.0 has the potential to be a cost-effective intervention for people with BD. Additional research is needed to understand the lack of effectiveness for the addition of cognitive behavioral tools with the group 3 intervention.

Bipolar disorders (BDs) have high morbidity. The first onset of 27.7% of BDs occurs in children under 13 years and of 37.6% occurs in adolescents between 13 and 18 years. However, not all of the pediatric and adolescent patients with BD receive therapy in time. Therefore, studies about pediatric and adolescent patients with disorders have aroused increased attention in the scientific community. Pediatric and adolescent patients with BD present with a high prevalence rate (0.9-3.9%), and the pathogenic factors are mostly due to genetics and the environment; however, the pathological mechanisms remain unclear. Pediatric and adolescent patients with BD manifest differently from adults with BDs and the use of scales can be helpful for diagnosis and treatment evaluation. Pediatric and adolescent patients with BDs have been confirmed to have a high comorbidity rate with many other kinds of disorders. Both medication and psychological therapies have been shown to be safe and efficient methods for the treatment of BD. This review summarizes the research status related to the epidemiology, pathogenic factors, clinical manifestations, comorbidities, diagnostic and treatment scales, medications, and psychological therapies associated with BDs.

Bipolar disorder is a highly heritable psychiatric condition for which specific genetic factors remain largely unknown. In the present study, we used combined whole-exome sequencing and linkage analysis to identify risk loci and dissect the contribution of common and rare variants in families with a high density of illness.

Overall, 117 participants from 15 Australian extended families with bipolar disorder (72 with affective disorder, including 50 with bipolar disorder type I or II, 13 with schizoaffective disorder-manic type and 9 with recurrent unipolar disorder) underwent whole-exome sequencing. We performed genome-wide linkage analysis using MERLIN and conditional linkage analysis using LAMP. We assessed the contribution of potentially functional rare variants using a genebased segregation test.

We identified a significant linkage peak on chromosome 10q11-q21 (maximal single nucleotide polymorphism = rs10761725; exponential logarithm of the odds [LODexp] = 3.03; empirical p = 0.046). The linkage interval spanned 36 protein-coding genes, including a gene associated with bipolar disorder, ankyrin 3 (ANK3). Conditional linkage analysis showed that common ANK3 risk variants previously identified in genome-wide association studies - or variants in linkage disequilibrium with those variants - did not explain the linkage signal (rs10994397 LOD = 0.63; rs9804190 LOD = 0.04). A family-based segregation test with 34 rare variants from 14 genes under the linkage interval suggested rare variant contributions of 3 brain-expressed genes: NRBF2 (p = 0.005), PCDH15 (p = 0.002) and ANK3 (p = 0.014).

We did not examine non-coding variants, but they may explain the remaining linkage signal.

Combining family-based linkage analysis with next-generation sequencing data is effective for identifying putative disease genes and specific risk variants in complex disorders. We identified rare missense variants in ANK3, PCDH15 and NRBF2 that could confer disease risk, providing valuable targets for functional characterization.

Obsessive-compulsive disorder (OCD) is often comorbid with Bipolar Disorder (BD), complicating its presentation and management. OCD prevalence rates in BD vary widely across studies and recent meta-analyses.

We performed a comprehensive systematic review and meta-analysis of studies reporting cross-sectional or lifetime OCD prevalence in BD, assessed by meta-regression various determinants of estimated prevalence and compared it with major depressive disorder (MDD) patients and general population subjects included in extracted studies.

Relevant articles published up to January 2019 in PubMed/MEDLINE were retrieved. Prevalence rates underwent Freeman-Tukey double arcsine transformation before meta-analysis.

We included 29 studies reporting cross-sectional prevalence (N = 6109) and 39 studies reporting lifetime prevalence (N = 8205); eight studies reported both. The pooled lifetime and cross-sectional prevalence of comorbid OCD in BD was estimated at 10.9% (95% CI: 7.8-14.4%) and 11.2% (7.6-15.3%), respectively, in the random-effects model. Respective estimates in the general population were 2.5% and 1.6%. Study setting (epidemiological or clinical), diagnostic criteria and procedures, gender, BD subtype and remission status could not explain heterogeneity of prevalence estimates in meta-regressions. Age had a small yet significant negative correlation with lifetime prevalence. OCD prevalence in BD was not significantly different than in MDD.

Search was limited to English-language literature.

Lifetime OCD prevalence in BD was 4.4 times higher than in the general population. Cross-sectional prevalence was as high as lifetime, suggesting that OCD in BD is more chronic/ persistent than in the general population, where cross-sectional stands at about two thirds the lifetime prevalence.

Bipolar disorder (BD) and alcohol use disorder (AUD) are two major independent causes of psychopathology in the general population. The prevalence of AUD in BD is high. Identifying the clinical and demographic features of patients with BD who may develop AUD could help with early identification and intervention.

Data from 238 patients diagnosed with BD were gathered on alcohol use, social demographics, longitudinal course of BD, clinical features of the most severe lifetime manic and depressive episodes, comorbid physical diseases, anxiety disorders, and other substance use disorders.

We found that 74 of 238 BD patients had AUD (67 with alcohol dependence and 7 with alcohol abuse). Bivariate logistic regression analysis and multivariate logistic regression analysis found that the best predictors of AUD in patients with BD were being male (OR = 2.086, 95% CI = 1.094-3.979, p = 0.001), younger (OR = 0.965, 95% CI = 0.935-0.996, p = 0.026), and comorbidity with other unclassified substance dependence (OR = 10.817, 95% CI = 1.238-94.550, p = 0.031).

Male, younger current age, and having other substance use disorders were independently associated with AUD.

More than half of patients with bipolar disorder (BD) experience anxiety, which is associated with impaired functioning. In patients with BD, the present study aimed (1) to validate daily patient-reported symptoms of anxiety measured using smartphones against clinically rated symptoms of anxiety, (2) to estimate the prevalence of anxiety symptoms, and (3) to investigate the associations between patient-reported anxiety symptoms and stress, quality of life and functioning.

A total of 84 patients with BD evaluated their anxiety symptoms daily for nine months using a smartphone-based system. Data on clinically evaluated symptoms of anxiety and functioning and patient-reported stress and quality of life were collected from each patient at five fixed time points during follow-up.

The patients presented mild affective symptoms only. The reporting of anxiety symptoms was evaluated for validity according to clinically evaluated anxiety scores based on the two anxiety sub-items of the Hamilton Depression Rating Scale. The patients experienced symptoms of anxiety 19.3% of the time. There were statistically significant associations between anxiety and stress, quality of life and functioning (all p-values < 0.0001).

In patients with BD in full or partial remission, the self-reporting of anxiety symptoms using smartphones was validated. Anxiety is associated with increased stress, decreased quality of life and functioning even during full or partial remission. Identifying anxiety symptoms thus has clinical impact, which suggests that smartphones may serve as a valid tool.

Over the last three decades burgeoning research has shown that anxiety disorder comorbidity is not only highly prevalent in bipolar disorder (BD), but it also adversely impacts the course, outcome, and treatment of BD. The present review provides an overview of the current trends in research on comorbid anxiety and BDs based on prior reviews and meta-analyses (n = 103), epidemiological surveys, and large-scale clinical studies. The results reiterated the fact that at least half of those with BD are likely to develop an anxiety disorder in their lifetimes and a third of them will manifest an anxiety disorder at any point of time. All types of anxiety disorders were equally common in BD. However, there was a wide variation in rates across different sources, with most of this discrepancy being accounted for by methodological differences between reports. Comorbid anxiety disorders negatively impacted the presentation and course of BD. This unfavourable clinical profile led to poorer outcome and functioning and impeded treatment of BD. Despite the extensive body of research there was paucity of data on aetiology and treatment of anxiety disorder comorbidity in BD. Nevertheless, the substantial burden and unique characteristics of this comorbidity has important clinical and research implications.

Introduction: Vitamin D inadequacy or deficiency (VDID) has been reported in a high percentage of otherwise healthy individuals. Factors that may contribute to the high prevalence of VDID in people with mental disorders include diet low in vitamin D, poor sunlight exposure, decrease in cutaneous vitamin D synthesis, intake of certain medications, poor mobility, excessive alcohol intake, and tobacco smoking. VDID has been correlated to a host of adverse conditions, including rickets, osteoporosis, osteomalacia, muscle diseases, depression, cognitive dysfunction, and even certain cancers. Objectives: The purpose of this study was to report the prevalence and correlates of vitamin D inadequacy in a sample of 290 psychiatric patients admitted to inpatient or day hospital treatment at the University of Siena Medical Center. Methods: We retrospectively evaluated the prevalence of VDID in 290 psychiatric inpatients' medical records during the year 2017 and evaluated the correlates of VDID in patients with mental illness. Results: Two hundred and seventy two out of two hundred and ninety patients (94%) showed VDID. Physical activity and regular diet were positively correlated with vitamin D levels whereas age, tobacco smoking, PTH, alkaline phosphatase levels were negatively correlated. Statistically significant differences were found among smokers and non-smokers in all study groups. Conclusions: VDID was highly prevalent in our sample. In addition to vitamin D supplementation, psychosocial intervention able to promote and help sustain physical activity, appropriate diet, quitting smoking and sensible sun exposure to prevent and treat VDID in patients with mental health should be implemented, tested, and introduced in our clinical practice.

This meta-analysis aimed to update existing data on the comparison of prevalence rates of psychopathology primarily among offspring with at least one parent with bipolar disorder (BD) and offspring of parents without psychiatric illness. Seventeen studies were derived from a systematic search of PsychInfo, Medline, Scopus and Embase. Inclusion criteria were use of a control offspring group, standardized diagnostic procedures and reporting of clear frequency data. Risk of psychopathology was estimated by aggregating frequency data from selected studies. Compared to control offspring, high-risk BD offspring are nine times more likely to have a bipolar-type disorder, almost two and a half times more likely to develop a non-BD affective disorder and over two times more likely to develop at least one anxiety disorder. High-risk offspring also showed a significant increased risk of other non-mood psychopathology such as attention deficit hyperactivity disorder (ADHD), any type of behavioral disorder and substance use disorder (SUDs). Risk of developing a broad range of affective and non-affective psychopathology is significantly higher in high-risk BD offspring. Identifying clinical presentations of this genetically high-risk cohort is important in establishing appropriate preventative treatment.

Bipolar disorder (BD) is a complex psychiatric condition with high heritability, the genetic architecture of which likely comprises both common variants of small effect and rare variants of higher penetrance, the latter of which are largely unknown. Extended families with high density of illness provide an opportunity to map novel risk genes or consolidate evidence for existing candidates, by identifying genes carrying pathogenic rare variants. We performed whole-exome sequencing (WES) in 15 BD families (117 subjects, of whom 72 were affected), augmented with copy number variant (CNV) microarray data, to examine contributions of multiple classes of rare genetic variants within a familial context. Linkage analysis and haplotype reconstruction using WES-derived genotypes enabled exclusion of false-positive single-nucleotide variants (SNVs), CNV inheritance estimation, de novo variant identification and candidate gene prioritization. We found that rare predicted pathogenic variants shared among ≥3 affected relatives were overrepresented in postsynaptic density (PSD) genes (P = 0.002), with no enrichment in unaffected relatives. Genome-wide burden of likely gene-disruptive variants was no different in affected vs. unaffected relatives (P = 0.24), but correlated significantly with age of onset (P = 0.017), suggesting that a high disruptive variant burden may expedite symptom onset. The number of de novo variants was no different in affected vs. unaffected offspring (P = 0.89). We observed heterogeneity within and between families, with the most likely genetic model involving alleles of modest effect and reduced penetrance: a possible exception being a truncating X-linked mutation in IRS4 within a family-specific linkage peak. Genetic approaches combining WES, CNV and linkage analyses in extended families are promising strategies for gene discovery.

Objective: Bipolar disorder is highly comorbid with anxiety disorders, however current and lifetime comorbidity patterns of each anxiety disorder and their associated features are not well studied. Here, we aimed to conduct a meta-analysis and meta-regression study of current evidence. Method: We searched PubMed to access relevant articles published until September 2015, using the keywords "Bipolar disorder" or "Affective Psychosis" or "manic depressive" separately with "generalized anxiety," "panic disorder," "social phobia," "obsessive compulsive," and "anxiety." Variables for associated features and prevalence of anxiety disorders were carefully extracted. Results: Lifetime any anxiety disorder comorbidity in BD was 40.5%; panic disorder (PD) 18.1%, generalized anxiety disorder (GAD) 13.3%, social anxiety disorder (SAD) 13.5% and obsessive compulsive disorder (OCD) 9.7%. Current any anxiety disorder comorbidity in BD is 38.2%; GAD is 15.2%, PD 13.3%, SAD 11.7%, and OCD 9.9%. When studies reporting data about comorbidities in BDI or BDII were analyzed separately, lifetime any anxiety disorder comorbidity in BDI and BDII were 38% and 34%, PD was 15% and 15%, GAD was 14% and 16.6%, SAD was 8% and 13%, OCD was 8% and 10%, respectively. Current any DSM anxiety disorder comorbidity in BDI or BDII were 31% and 37%, PD was 9% and 13%, GAD was 8% and 12%, SAD was 7% and 11%, and OCD was 8% and 7%, respectively. The percentage of manic patients and age of onset of BD tended to have a significant impact on anxiety disorders. Percentage of BD I patients significantly decreased the prevalence of panic disorder and social anxiety disorder. A higher rate of substance use disorder was associated with greater BD-SAD comorbidity. History of psychotic features significantly affected current PD and GAD. Conclusions: Anxiety disorder comorbidity is high in BD with somewhat lower rates in BDI vs BDII. Age of onset, substance use disorders, and percentage of patients in a manic episode or with psychotic features influences anxiety disorder comorbidity.

Bipolar disorder (BD) is characterized by a dysregulation of affect and impaired integration of emotion with cognition. These traits are also expressed in probands at high genetic risk of BD. The inferior frontal gyrus (IFG) is a key cortical hub in the circuits of emotion and cognitive control, and it has been frequently associated with BD. Here, we studied resting-state functional connectivity of the left IFG in participants with BD and in those at increased genetic risk.

Using resting-state functional magnetic resonance imaging we compared 49 young BD participants, 71 individuals with at least one first-degree relative with BD (at-risk), and 80 control subjects. We performed between-group analyses of the functional connectivity of the left IFG and used graph theory to study its local functional network topology. We also used machine learning to study classification based solely on the functional connectivity of the IFG.

In BD, the left IFG was functionally dysconnected from a network of regions, including bilateral insulae, ventrolateral prefrontal gyri, superior temporal gyri, and the putamen (p < .001). A small network incorporating neighboring insular regions and the anterior cingulate cortex showed weaker functional connectivity in at-risk than control participants (p < .006). These constellations of regions overlapped with frontolimbic regions that a machine learning classifier selected as predicting group membership with an accuracy significantly greater than chance.

Functional dysconnectivity of the IFG from regions involved in emotional regulation may represent a trait abnormality for BD and could potentially aid clinical diagnosis.

Anxiety disorders are highly prevalent in people with bipolar disorder, but it is not clear how many have anxiety disorders even at times when they are free of major mood episodes. We aimed to establish what proportion of euthymic individuals with bipolar disorder meet diagnostic criteria for anxiety disorders.

We performed a random-effects meta-analysis of prevalence rates of current DSM-III- and DSM-IV-defined anxiety disorders (panic disorder, agoraphobia, social anxiety disorder, generalized anxiety disorder, specific phobia, obsessive-compulsive disorder, post-traumatic stress disorder, and anxiety disorder not otherwise specified) in euthymic adults with bipolar disorder in studies published by 31 December 2015.

Across 10 samples with 2120 individuals with bipolar disorder, 34.7% met diagnostic criteria for one or more anxiety disorders during euthymia [95% confidence interval (CI) 23.9-45.5%]. Direct comparison of 189 euthymic individuals with bipolar disorder and 17 109 population controls across three studies showed a 4.6-fold increase (risk ratio 4.60, 95% CI 2.37-8.92, p < 0.001) in prevalence of anxiety disorders in those with bipolar disorder.

These findings suggest that anxiety disorders are common in people with bipolar disorder even when their mood is adequately controlled. Euthymic people with bipolar disorder should be routinely assessed for anxiety disorders and anxiety-focused treatment should be initiated if indicated.

Life stress is a major predictor of the course of bipolar disorder. Few studies have used laboratory paradigms to examine stress reactivity in bipolar disorder, and none have assessed autonomic reactivity to laboratory stressors. In the present investigation we sought to address this gap in the literature. Participants, 27 diagnosed with bipolar I disorder and 24 controls with no history of mood disorder, were asked to complete a complex working memory task presented as "a test of general intelligence." Self-reported emotions were assessed at baseline and after participants were given task instructions; autonomic physiology was assessed at baseline and continuously during the stressor task. Compared to controls, individuals with bipolar disorder reported greater increases in pretask anxiety from baseline and showed greater cardiovascular threat reactivity during the task. Group differences in cardiovascular threat reactivity were significantly correlated with comorbid anxiety in the bipolar group. Our results suggest that a multimethod approach to assessing stress reactivity-including the use of physiological parameters that differentiate between maladaptive and adaptive profiles of stress responding-can yield valuable information regarding stress sensitivity and its associations with negative affectivity in bipolar disorder. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Previous studies have found an increased prevalence of atopic diseases among patients with major depression and bipolar disorder. But the temporal association between atopic diseases in adolescence and the subsequent risk of developing mood disorders has been rarely investigated.

Using the Taiwan National Health Insurance Research Databases, 5075 adolescents with atopic diseases (atopic cohort) and 44,729 without (non-atopic cohort) aged between 10 and 17 in 2000 were enrolled into our study and followed to the end of 2010. Subjects who developed major depression or bipolar disorder during the follow-up were identified.

The atopic cohort had an increased risk of developing major depression (HR: 2.45, 95% CI: 1.93~3.11) and bipolar disorder (HR: 2.51, 95% CI: 1.71~3.67) compared to the non-atopic cohort, with a dose-dependent relationship between having a greater number of atopic comorbidities and a greater likelihood of major depression (1 atopic disease: HR: 1.80, 95% CI: 1.29~2.50; 2 atopic comorbidities: HR: 2.42, 95% CI: 1.93~3.04;≥3 atopic comorbidities: HR: 3.79, 95% CI: 3.05~4.72) and bipolar disorder (HR: 1.40, 95% CI: 0.57~3.44; HR: 2.81, 95% CI: 1.68~4.68; HR: 3.02, 95% CI: 1.69~5.38).

Having atopic diseases in adolescence increased the risk of developing major depression and bipolar disorder in later life. Further studies may be required to clarify the underlying mechanism between atopy and mood disorders, and to investigate whether prompt intervention may decrease the risk of subsequent mood disorders.

Bipolar disorder (BD) is one of the most serious psychiatric disorders in the world, but its pathophysiology is still unclear. Regulation of neurotrophic factors have been thought to play a role in this process. There have been inconsistent findings regarding the differences in blood neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) between patients with BD and healthy controls (HCs). The aim of the current meta-analysis is to examine the changes in the levels of NT-3 and NT-4/5 in BD patients at different affective states. Eight articles (including 465 BD patients and 353 HCs) were included in the analysis, and their results were pooled by using a random effects model. We found the levels of both NT-3 (p = 0.0046) and NT-4/5 (p = 0.0003) were significantly increased in BD patients, compared to HCs. Through subgroup analysis, this increase persisted only in patients in depressed state (p = 0.0038 for NT-3 and p = 0.0001 for NT-4/5), but not in manic or euthymic state. In addition, we found the differences in NT-3 and NT-4/5 were significantly associated with the duration of illness, but not by the mean age or female proportion. Our results suggest a state-dependent increase in NT-3 and NT-4/5 levels in patients with BD. Further studies are needed to examine dynamic changes of these neurotrophins in BD patients along the disease course.

People with bipolar disorder (BD) have a mortality gap of up to 20 years compared to the general population. Physical conditions, such as cardiovascular disease (CVD) and cancer, cause the majority of excess deaths in psychiatric populations and are the leading causes of mortality in people with BD. However, comparatively little attention has been paid to reducing the risk of physical conditions in psychiatric populations. Unhealthy lifestyle behaviors are among the potentially modifiable risk factors for a range of commonly comorbid chronic medical conditions, including CVD, diabetes, and obesity. This systematic review will identify and evaluate the available evidence for effective interventions to reduce risk and promote healthy lifestyle behaviors in BD.

We will search MEDLINE, Embase, PsychINFO, Cochrane Database of Systematic Reviews, and CINAHL for published research studies (with at least an abstract published in English) that evaluate behavioral or psychosocial interventions to address the following lifestyle factors in people with BD: tobacco use, physical inactivity, unhealthy diet, overweight or obesity, sleep-wake disturbance, and alcohol/other drug use. Primary outcomes for the review will be changes in tobacco use, level of physical activity, diet quality, sleep quality, alcohol use, and illicit drug use. Data on each primary outcome will be synthesized across available studies in that lifestyle area (e.g., tobacco abstinence, cigarettes smoked per day), and panel of research and clinical experts in each of the target lifestyle behaviors and those experienced with clinical and research with individuals with BD will determine how best to represent data related to that primary outcome. Seven members of the systematic review team will extract data, synthesize the evidence, and rate it for quality. Evidence will be synthesized via a narrative description of the behavioral interventions and their effectiveness in improving the healthy lifestyle behaviors in people with BD.

The planned review will synthesize and evaluate the available evidence regarding the behavioral or psychosocial treatment of lifestyle-related behaviors in people with BD. From this review, we will identify gaps in our existing knowledge and research evidence about the management of unhealthy lifestyle behaviors in people with BD. We will also identify potential opportunities to address lifestyle behaviors in BD, with a view to reducing the burden of physical ill-health in this population.

PROSPERO CRD42015019993.

Asthma and bipolar disorder (BD) are 2 distinct diseases that share similar pathophysiology. This study aimed to determine their relationship thorough a meta-analysis of articles on their comorbidity rate. The aim of the study is to examine the overall prevalence rate of BD in asthmatic patients and of asthma in BD patients compared to healthy controls. Electronic research of PubMed and ClinicalTrials.gov was performed. Articles discussing the prevalence rate of BD in patients with/without asthma and the prevalence rate of asthma in those with/without BD, as well as clinical trials in humans and case-controlled trials or cohort studies, were all included. Case reports or series and nonclinical trials were excluded. Through a random-effects model, a meta-analysis of the results of 4 studies comparing the prevalence rate of BD in patients with/without asthma, and in 6 studies comparing the prevalence rate of asthma in subjects with/without BD were performed. There were significantly higher prevalence rates of BD in asthmatic patients than in healthy controls (P < 0.001) and of asthma in BD patients than in healthy controls (P < 0.001). Only the patient's mean age significantly modulated the odds ratio of the prevalence rate of asthma in BD patients (slope = 0.015, P < 0.001). Only 10 studies were included and most were cross-sectional studies. The possible confounding effect of medication on BD or asthma onset was not investigated. Any possible etiology of the comorbidity was also not determined. This meta-analysis highlights the importance of the significantly high comorbid rate of BD and asthma, and the positive association with age. Special attention must be given to the comorbidity of asthma and BD, especially in older patients.

To investigate the use of transcranial direct current stimulation (tDCS) for enhancing working memory and sustained attention in euthymic patients with bipolar disorder.

Fifteen patients with bipolar disorder received anodal left prefrontal tDCS with an extracephalic cathode (prefrontal condition), anodal left prefrontal and cathodal cerebellar tDCS (fronto-cerebellar condition), and sham tDCS given 'online' during performance on a working memory and sustained attention task in an intra-individual, cross-over, sham-controlled experimental design. Exploratory cluster analyses examined responders and non-responders for the different active tDCS conditions on both tasks.

For working memory, approximately one-third of patients in both active tDCS conditions showed performance improvement. For sustained attention, three of 15 patients showed performance improvement with prefrontal tDCS. Responders to active tDCS for working memory performed more poorly on the task during sham tDCS compared to non-responders.

A single session of active prefrontal or fronto-cerebellar tDCS failed to improve working memory or sustained attention performance in euthymic patients with bipolar disorder. Several important considerations are discussed in relation to future studies investigating tDCS for enhancing cognition in patients with bipolar disorder.

Anxiety disorders are increasingly recognised as an important determinant of outcomes in patients with bipolar disorder. However, a reliable estimate of their prevalence is still missing, because the published prevalence of anxiety disorders in individuals with bipolar disorder varies widely. In this study, we aimed to quantify the lifetime prevalence of anxiety disorders in individuals with bipolar disorder and compare it with rates in people without the disorder.

We searched the Web of Knowledge and Medline (through the PubMed interface) for articles published in any language from the database inception dates up until June 1, 2014, using a combination of the word "bipolar" and search terms for anxiety disorders. We included studies that reported original data about the lifetime prevalence of DSM-III and DSM-IV anxiety disorders in adults with bipolar disorder that recruited participants irrespective of comorbidities and that used a validated diagnostic interview to establish the diagnoses of bipolar disorder and at least one anxiety disorder. We excluded studies that reported only the current prevalence or if we were unable to establish whether they described current or lifetime prevalence, and those with discrepancies in the data that could not be resolved by contacting the authors. We did a random-effects meta-analysis of lifetime prevalence of DSM-III and DSM-IV anxiety disorders in adults with bipolar disorder, in which we quantified the lifetime prevalence of any anxiety disorder in people with bipolar disorder. We compared this prevalence in people with bipolar I disorder versus those with bipolar II disorder, and in people with bipolar disorder versus population controls.

Data from 40 studies, including 14 914 individuals from North America, Europe, Australia, South America, and Asia, indicate that the lifetime prevalence of anxiety disorders in individuals with bipolar disorder is 45% (95% CI 40-51). Direct comparison in five samples with a total of 1378 individuals with bipolar disorder and 56 812 population controls without bipolar disorder indicates a three-fold increase (risk ratio [RR] 3·22 [95% CI 2·41-4·29]; p<0·0001) in the prevalence of anxiety disorders in those with bipolar disorder. 13 studies that included both individuals with bipolar I disorder (n=4270) and those with bipolar II disorder (n=1939) showed no difference in the lifetime prevalence of anxiety disorders between these subtypes (RR 1·07 [95% CI 0·96-1·20]; p=0·223). We noted significant heterogeneity among included studies that was not accounted for by reported differences in study characteristics.

People with bipolar disorder are at increased risk of anxiety disorders compared with those without bipolar disorder; nearly one in two has an anxiety disorder in their lifetime. Anxiety disorders should therefore be assessed alongside the mood symptoms in patients with bipolar disorder.

Capital Health Research Fund.

Bipolar disorder (BD) is common in clinical psychiatric practice, and several studies have estimated its prevalence to range from 0.5 to 5% in community-based samples. However, no systematic review and meta-analysis of the prevalence of BD type 1 and type 2 has been published in the literature. We carried out a systematic review and meta-analysis of the lifetime and 1-year prevalence of BD type 1 and type 2 and assessed whether the prevalence of BD changed according to the diagnostic criteria adopted (DSM-III, DSM-III-R vs. DSM-IV).

We searched MEDLINE, Scopus, Web of Science, PsycINFO, and the reference lists of identified studies. The analyses included 25 population- or community-based studies and 276,221 participants.

The pooled lifetime prevalence of BD type 1 was 1.06% (95% confidence interval [95%CI] 0.81-1.31) and that of BD type 2 was 1.57% (95%CI 1.15-1.99). The pooled 1-year prevalence was 0.71% (95%CI 0.56-0.86) for BD type 1 and 0.50% (95%CI 0.35-0.64) for BD type 2. Subgroup analysis showed a significantly higher lifetime prevalence of BD type 1 according to the DSM-IV criteria compared to the DSM-III and DSM-IIIR criteria (p < 0.001).

This meta-analysis confirms that estimates of BD type 1 and type 2 prevalence are low in the general population. The increase in prevalence from DSM-III and DSM-III-R to DSM-IV may reflect different factors, such as minor changes in diagnostic operationalization, use of different assessment instruments, or even a genuine increase in the prevalence of BD.

The Internet is used to deliver information on many psychiatric disorders such as bipolar disorder. This paper reports on the results of a 12-months randomised controlled trial, which examined the efficacy of an Internet-based preventive program for bipolar disorder, adjunctive to usual pharmacological management.

Participants were recruited by completing an online screening questionnaire accessed through the Black Dog Institute and Sentiens websites based in Australia. The treatment was predominantly psycho-educational with cognitive behavioral therapy optional elements. The attention control treatment comprised directing subjects to a variety of websites focused on 'healthy living'. Time to recurrence was determined using Kaplan-Meier survival analysis. The main outcome measures were recurrence as defined by: (i) depressive and/or hypomanic symptomatology and functional capacity (using Beck Depression Inventory, Internal State Scale and Sheehan Disability Scale) and (ii) hospitalization.

Two-hundred-and-thirty-three subjects were randomized to the active or control treatment groups. There were no significant differences between the active and control treatment groups on any of the definitions of recurrence.

Reliance on an online self-report tool to confirm diagnosis and hospitalization rates may have potentially allowed for inclusion of individuals with other diagnoses such as borderline personality disorder. The 'attention control' treatment may have included more 'active' components than intended.

This is the first report examining the efficacy of a randomized controlled web-based psychological intervention in a large sample of subjects with bipolar disorder. The potential reasons for failing to demonstrate a significant difference compared to the active control are discussed.

Psychiatric disorders including anxiety, depression, somatization, obsessive compulsive, and bipolar disorders are recognized as causing the biggest burden of disease worldwide.

In this study, we aimed to assess the prevalence and burden of common mental disorders at Primary Health Care Centers (PHCC) using the World Health Organization Composite International Diagnostic Interview (WHO-CIDI) in the Qatari population, aged 18-65 who attended Primary Health Care (PHC) settings.

A prospective cross-sectional study conducted during November 2011 to October 2012.

Primary Health Care Centers of the Supreme Council of Health, Qatar.

A total of 2,000 Qatari subjects aged 18-65 years were approached; 1475 (73.3%) agreed to participate.

Prevalence and severity of International Classification of Disease-10 disorders were assessed with the WHO-CIDI (Version 3.0).

Of the 1475 participants, 830 (56.3%) were females and 645 (43.7%) was males. One-third were aged 35-49 years 558 (37.8%). The three most common disorders were major depression disorders (18.31%), any anxiety disorders (17.3%), any mood disorders (16.95%), followed by separation anxiety disorders (15.25%), personality disorder (14.1%). In the present study, prevalence in women was significantly higher than men for the most common psychiatric disorders, specifically generalized anxiety disorder, panic disorder, social phobia, specific phobias, obsessive compulsive disorders, posttraumatic disorder, somatization, major depressive disorder, bipolar disorder, dysthymia, and oppositional defiant disorder. Of the total 20% had only one psychiatric diagnosis and 12% had two disorders, 9.7% respondents with three diagnoses, and finally 4.3% of respondents had four or more diagnoses.

One-fifth of all adults who attended the PHCC (20%) had at least one psychiatric diagnosis. The CIDI is a useful instrument for psychiatric diagnosis in community settings such as PHC clinics, clinical research and intervention studies. There is an urgent need to not only assess prevalence, but also risk factors, burden, treatment gaps and outcomes to obtain evidence for policy making.

Current diagnostic criteria define bipolar I (BP I) and bipolar II (BP II) disorders as distinct conditions, differing only slightly by clinical features. This review seeks to identify commonalities and differentiating features across the two sub-types, and emphasize that differences in causes and treatments are likely to be highly dependent on the diagnostic criteria used to define and differentiate the two conditions. We undertake a literature review of candidate clinical features that might be anticipated to vary or be shared across BP I and BP II disorders, and consider the impact of DSM definition on such applied findings. Studies respecting DSM-IV differentiation of BP I and BP II disorders have generated relatively few differences across the conditions, which may reflect definitional similarity or commonalities across the two conditions. As DSM-5 decision rules are similar to those used by DSM-IV to differentiate BP I and BP II disorders, we argue for application studies employing DSM-5 decisions to examine the differential impact of three features that weight BP I assignment (i.e. psychosis, hospitalization and/or impairment) and examine other sets of differentiating criteria.