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Studies on bipolar disorder (BD) have suggested that exposure to childhood trauma (CT) and rapid cycling BD (RC-BD) are associated with earlier onset and overall worse prognosis. The association between CT exposure and RC-BD in patients from low/middle-income countries has not been sufficiently characterized. Therefore, we performed a case–control study of patients with RC-BD (n = 35), patients without RC-BD (n = 35), and healthy controls (HC) (n = 105) in a low/middle-income country, Colombia, to evaluate CT exposure and RC-BD for clinical associations. We reported a significant number of patients with RC-BD exposed to physical abuse and/or sexual abuse compared with patients without RC-BD during the course of illness. In addition, CT exposure and RC-BD were associated with an earlier age of onset and delayed diagnosis and treatment. In the future, recognition of early CT exposure in populations at risk for BD may help tailor precise interventions and thus change the course of illness and worse prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Affective instability represents an important, transdiagnostic biobehavioural dimension of mental ill health and clinical outcome. The causes of affective instability remain unclear. This systematic review and meta‐analysis evaluated the extent to which exposure to childhood adversity is associated with affective instability across psychiatric disorders, and which forms of adversity are most strongly associated with affective instability. Methods: The review followed a published protocol (PROSPERO: CRD42020168676). Searches in Medline, Embase and PsychInfo identified studies using quantitative measures of childhood adversity and affective instability, published between January 1980 and July 2023. Data were analysed using a random effects meta‐analysis separately for each outcome, namely affective lability, emotion dysregulation, and rapid cycling. The Mixed‐Methods Appraisal Tool was used to appraise the quality of the literature. Results: The search identified 36 studies involving 8431 participants. All reports focused on cross‐sectional associations. We did not identify any prospective longitudinal research. The analysis showed small, but statistically significant effects of childhood adversity on affective lability (r = 0.09, 95% CI 0.02, 0.17), emotion dysregulation (r = 0.25, 95% CI 0.19, 0.32), and rapid cycling (OR = 1.39; 95% CI 1.14, 1.70). When considering adversity subtypes, emotional abuse showed the strongest effect on affective lability (r = 0.16, 95% CI 0.07, 0.24) and emotion dysregulation (r = 0.32, 95% CI 0.19, 0.44). Quality assessment scores were generally low. Most studies failed to control for confounding factors or offer assurances around the representativeness of the samples. Conclusions: The findings suggest that childhood adversity, particularly emotional abuse, is associated emotional instability in adulthood, but further prospective longitudinal research is needed to confirm causality. The findings have implications for the prevention and treatment of affective instability across psychiatric disorders. [ABSTRACT FROM AUTHOR]

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.

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 FROM AUTHOR]

Bipolar disorder is heterogeneous in phenomenology, illness trajectory, and response to treatment. Despite evidence for the efficacy of multimodal-ity interventions, the majority of persons affected by this disorder do not achieve and sustain full syndromal recovery. It is eagerly anticipated that combining datasets across various information sources (e.g., hierarchical "multi-omic" measures, electronic health records), analyzed using advanced computational methods (e.g., machine learning), will inform future diagnosis and treatment selection. In the interim, identifying clinically meaningful subgroups of persons with the disorder having differential response to specific treatments at point-of-care is an empirical priority. This paper endeavours to synthesize salient domains in the clinical characterization of the adult patient with bipolar disorder, with the overarching aim to improve health outcomes by informing patient management and treatment considerations. Extant data indicate that characterizing select domains in bipolar disorder provides actionable information and guides shared decision making. For example, it is robustly established that the presence of mixed features - especially during depressive episodes - and of physical and psychiatric comorbidities informs illness trajectory, response to treatment, and suicide risk. In addition, early environmental exposures (e.g., sexual and physical abuse, emotional neglect) are highly associated with more complicated illness presentations, inviting the need for developmentally-oriented and integrated treatment approaches. There have been significant advances in validating subtypes of bipolar disorder (e.g., bipolar I vs. II disorder), particularly in regard to pharmacological interventions. As with other severe mental disorders, social functioning, interpersonal/family relationships and internalized stigma are domains highly relevant to relapse risk, health outcomes, and quality of life. The elevated standardized mortality ratio for completed suicide and suicidal behaviour in bipolar disorder invites the need for characterization of this domain in all patients. The framework of this paper is to describe all the above salient domains, providing a synthesis of extant literature and recommendations for decision support tools and clinical metrics that can be implemented at point-of-care.

Predominant Polarity (PP) is an established specifier of Bipolar Disorder (BD), holding significant clinical implications. Nevertheless, there exists no consensus on how to incorporate mixed states into PP, leaving patients prone to mixed recurrences that are unclassified. In a comprehensive study involving 701 euthymic BD patients, we sought to redefine PP by introducing a novel metric, the "mixed tendency", and establish a practical threshold to identify patients with a "mixed phenotype". Furthermore, we investigated potential associations between the mixed phenotype and specific PP categories. Our findings revealed that the mixed tendency correlated significantly with early BD type I, lifetime suicide attempts, self-aggressive behaviour, and lifetime number of affective episodes (>5). Using a ROC curve analysis, we determined an optimal cut-off point for the mixed tendency at 0.228, suggesting that patients with ~25% of lifetime mixed episodes relative to total affective episodes should be identified as having a mixed phenotype. Notably, the mixed phenotype was positively associated with undetermined PP and negatively with manic and depressive PP. This study introduces a promising approach to incorporating mixed episodes into the PP definition, potentially enabling tailored interventions for patients with a substantial history of mixed episodes. However, further research in large, longitudinal cohorts is essential to validate these findings. [ABSTRACT FROM AUTHOR]

The efficacy and safety of lurasidone monotherapy in patients with bipolar I depression with or without rapid cycling has not been previously investigated. We performed subgroup analysis (rapid cycling/non-rapid cycling) of pooled data from two 6-week, randomized, double-blind, placebo-controlled trials of lurasidone monotherapy (20–60 mg/day or 80–120 mg/day). Analyses included mean change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Safety assessments included the number of treatment-emergent adverse events (TEAEs) and laboratory assessments. Of 1024 patients randomized, 85 were rapid cycling. Mean change in MADRS total score in patients with non-rapid cycling and rapid cycling, respectively, was −14.8 (effect size = 0.47) and − 12.8 (effect size = 0.04) in the lurasidone 20–60 mg/day group, −14.3 (effect size = 0.41) and − 13.0 (effect size = 0.02) in the lurasidone 80–120 mg/day group and −10.6 and −13.3 in the placebo group. The most common TEAE in each subgroup was akathisia in both lurasidone groups. Treatment-emergent mania was reported only in a small number of rapid cycling and non-rapid cycling patients. This was a post-hoc analysis of a short-term study that excluded patients with ≥8 cycles in the past year. In patients with non-rapid cycling bipolar depression, lurasidone monotherapy significantly improved depressive symptoms relative to placebo at both the 20–60 mg/day and 80–120 mg/day doses. In patients with rapid cycling, both doses of lurasidone displayed depressive symptom score reduction from baseline, but significant improvement was not observed likely due to high levels of improvement on placebo and small sample size. • Monotherapy with lurasidone was highly efficacious for non-rapid cycling patients with bipolar depression. • In rapid cycling, lurasidone reduced depressive symptoms but not significantly due to high levels of improvement on placebo. • On both lurasidone and placebo, akathisia occurred more frequently in rapid-cycling than in non-rapid-cycling patients. • Treatment-emergent mania was reported only in a small number of rapid cycling and non-rapid cycling patients. [ABSTRACT FROM AUTHOR]

Background: The distinction between bipolar I and bipolar II disorder and its treatment implications have been a matter of ongoing debate. The aim of this study was to examine differences between patients with bipolar I and II disorders with particular emphasis on the early phases of the disorders. Methods: 808 subjects diagnosed with bipolar I (N = 587) or bipolar II disorder (N = 221) according to DSM-IV criteria were recruited between April 1994 and March 2022 from tertiary-level mood disorder clinics. Sociodemographic and clinical variables concerning psychiatric and medical comorbidities, family history, illness course, suicidal behavior, and response to treatment were compared between the bipolar disorder types. Results: Bipolar II disorder patients were more frequently women, older, married or widowed. Bipolar II disorder was associated with later "bipolar" presentation, higher age at first (hypo)mania and treatment, less frequent referral after a single episode, and more episodes before lithium treatment. A higher proportion of first-degree relatives of bipolar II patients were affected by major depression and anxiety disorders. The course of bipolar II disorder was typically characterized by depressive onset, early depressive episodes, multiple depressive recurrences, and depressive predominant polarity; less often by (hypo)mania or (hypo)mania-depression cycles at onset or during the early course. The lifetime clinical course was more frequently rated as chronic fluctuating than episodic. More patients with bipolar II disorder had a history of rapid cycling and/or high number of episodes. Mood stabilizers and antipsychotics were prescribed less frequently during the early course of bipolar II disorder, while antidepressants were more common. We found no differences in global functioning, lifetime suicide attempts, family history of suicide, age at onset of mood disorders and depressive episodes, and lithium response. Conclusions: Differences between bipolar I and II disorders are not limited to the severity of (hypo)manic syndromes but include patterns of clinical course and family history. Caution in the use of potentially mood-destabilizing agents is warranted during the early course of bipolar II disorder. [ABSTRACT FROM AUTHOR]

Objective: In patients with bipolar disorder (BD), rapid cycling (RC) presents a risk for a more severe illness, while euthymia (EUT) has a better prognosis. This study focused on the progression of RC and EUT, which are contrasting phenomenology, and aimed to clarify the influence of patient backgrounds and prescription patterns on these different progressions, using a large sample from the first and second iterations of a multicenter treatment survey for BD in psychiatric clinics (MUSUBI). Methods: In the cross-sectional study (MUSUBI), a questionnaire based on a retrospective medical record survey of consecutive BD cases (N = 2,650) was distributed. The first survey was conducted in 2016, and the second one in 2017. The questionnaire collected information on patient backgrounds, current episodes, and clinical and prescribing characteristics. Results: In the first survey, 10.6% of the participants had RC and 3.6% had RC for two consecutive years, which correlated with BP I (Bipolar disorder type I), suicidal ideation, duration of illness, and the use of lithium carbonate and antipsychotic medications. Possible risk factors for switching to RC were comorbid developmental disorders and the prescription of anxiolytics and sleep medication. Moreover, 16.4% of the participants presented EUT in the first survey, and 11.0% presented EUT for two consecutive years. Possible factors for achieving EUT included older age; employment; fewer psychotic symptoms and comorbid personality disorders; fewer antidepressants, antipsychotics, and anxiolytics, and more lithium prescriptions. Conclusion: RC and EUT generally exhibit conflicting characteristics, and the conflicting social backgrounds and factors contributing to their outcomes were distinctive. Understanding these clinical characteristics may be helpful in clinical practice for management of patients with BD. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the relationship between junior and senior high school students' cycling behavior, attitudes to traffic and attitude to daily life examining the effects of their gender and age on the behaviour, and to explore the underlying psychological determinants. Past studies on automobile driving have reported that the lower the level of a driver' attitude to safety, the higher the frequency of his/her risky behaviour and near-accident or accident involvement experience; that male and young drivers' level of safety behaviour is lower and they tend to exhibit risky behaviour more frequently than other drivers. It has also been reported that errors and lapses may correspond to accident experience. Although there has not been much research on riding of mopeds and bicycles, it has reported similar results. We conducted a survey on 2,077 junior and senior high school students, asking them to evaluate their traffic-related attitude/experience, behaviour as a cyclist, and their attitude to daily life. Factor analysis led us to extract three factors: "risky cycling", "social desirability", and "near accident". Drivers with weaker "social desirability" characteristic had a stronger tendency to "risky cycling". And it was also shown that the stronger the tendency towards "risky cycling", the more frequent the "near accident" experience occurred. Further, factor analysis focused only on items of cycling behaviour derived two factors: "distracted cycling" and "rapid cycling". Analysis of the correlation of these two factors and the aforementioned three factors showed that cyclists with a stronger tendency to "risky cycling" and weaker tendency to "social desirability" had a stronger tendency to "distracted cycling" and "rapid cycling". It was also shown that the higher the factor score of "risky cycling", the more frequent was the "near accident" experience. The number of accidents while cycling was found to be related to the factors "risky cycling", "social desirability", "near accident", "distracted cycling", and "rapid cycling". Based on the result above, it was speculated that the psychological determinants of cycling and car driving might be common, and it was considered that traffic safety education on cycling for junior and senior high school students is also effective for later car driving.

Bipolar Disorder (BD) is a mental disorder with emotional highs (euphoria) and lows, diagnosed especially in teenage years and early adulthood, which can cause cyclings containing manic (hypomanic) episodes and major depressive episodes. Nowadays, the suicide death rate of BD increases dramatically, thus BD has attracted more attention of society. So far, numerous studies have argued that it is heavily influenced by genetics, and BDNF (Brain-Derived Neurotrophic Factor) and ANK3 (Ankyrin 3) are regarded as the most important risk factors to BD susceptibility. Furthermore, BDNF and ANK3 both play a key role in central nervous system, which means a small mutation or change of them will induce some significant consequences. This article summarizes some researches about the association between BDNF and BD and its typical rapid cycling, as well as the potential effects of ANK3's cis-regulation and its variants. In addition, it introduces some information about how cis-regulation of ANK3 affects the susceptibility of BD and how some remarkable variants of ANK3 may contribute to BD. But also noteworthy is the fact that existing research results are far from enough, and there are still a great deal of effort that should be devoted to figure out the exact mechanism of BD, which must be beneficial for human health and improvement for relevant treatment and medicine. [ABSTRACT FROM AUTHOR]

As a safe neuromodulation therapy, rTMS is applied to treat a variety of psychiatric and neurological disorders. Additionally, both aripiprazole and sodium valproate are effective in the treatment of rapid cycling bipolar disorder. This case reports a female patient with a 17-year history of bipolar disorder who developed rapidcirculation bipolar disorder 5 years prior to presentation. After combined treatment with rTMS, aripiprazole, and sodium valproate, the patient's mood remained stable and she was able to live and work normally. [ABSTRACT FROM AUTHOR]

Bipolar Disorder (BD) is a mental disorder with emotional highs (euphoria) and lows, diagnosed especially in teenage years and early adulthood, which can cause cyclings containing manic (hypomanic) episodes and major depressive episodes. Nowadays, the suicide death rate of BD increases dramatically, thus BD has attracted more attention of society. So far, numerous studies have argued that it is heavily influenced by genetics, and BDNF (Brain-Derived Neurotrophic Factor) and ANK3 (Ankyrin 3) are regarded as the most important risk factors to BD susceptibility. Furthermore, BDNF and ANK3 both play a key role in central nervous system, which means a small mutation or change of them will induce some significant consequences. This article summarizes some researches about the association between BDNF and BD and its typical rapid cycling, as well as the potential effects of ANK3's cis-regulation and its variants. In addition, it introduces some information about how cis-regulation of ANK3 affects the susceptibility of BD and how some remarkable variants of ANK3 may contribute to BD. But also noteworthy is the fact that existing research results are far from enough, and there are still a great deal of effort that should be devoted to figure out the exact mechanism of BD, which must be beneficial for human health and improvement for relevant treatment and medicine. [ABSTRACT FROM AUTHOR]

ObjectivesThis report describes the first comparative double-blind, placebo-controlled trial of levothyroxine (L-T4 ) and triiodothyronine (T3 ) as adjunctive treatments in rapid cycling bipolar disorder.MethodsThirty-two treatment-resistant, rapid cycling patients who had failed a trial of lithium were randomized into three treatment arms: L-T4 , T3 , or placebo. They were followed for ≥4 months with weekly clinical and endocrine assessments.ResultsThere were no statistically significant differences between the groups in age, gender, duration of illness, or thyroid status. Markov chain analyses were employed to assess treatment effects on cycling patterns among mood states (euthymia, depression, mania, and mixed). Within groups, post-treatment the L-T4 group spent significantly less time depressed or in a mixed state and greater time euthymic. The T3 and placebo groups did not differ significantly pre- and post-treatment in any mood state, although the pattern of effects was the same for the T3 group as for the L-T4 group. Between groups, the L-T4 group had a significantly greater increase in time euthymic and decrease in time in the mixed state than the placebo group. Other group differences were not significant, although they were in the expected direction.ConclusionsThe findings in this first double-blind study directly comparing the effects of L-T4 and T3 therapy against placebo provide evidence for the benefit of adjunctive L-T4 in alleviating resistant depression, reducing time in mixed states and increasing time euthymic. Adjunctive T3 did not show statistically significant evidence of benefit over placebo in reducing the time spent in disturbed mood states.

Bipolar affective disorder is a chronic mental disorder, characterized by mood swings alternating between depression and manic or hypomanic episodes. Unfortunately, in some patients pharmacological treatment is not effective, and a certain group of patients shows treatment resistance. Therefore, other treatment methods are sought after, including a change in diet. The most promising is the ketogenic diet. In the presented case study of a male patient, thanks to the introduction of the ketogenic diet, full remission of the disease was achieved, doses of lamotrigine were reduced and quetiapine was completely discontinued. Previously, neither lamotrigine monotherapy nor combined treatment with quetiapine achieved euthymia. The effects of the diet may be related to, among others, the influence on ionic channels and increase in blood acidity (similar to the use of mood stabilizers), increase in gamma-aminobutyric acid (GABA) concentration, modulation of GABAA receptors, effects on the concentration of catecholamines, blocking of AMPA receptors by medium-chain fatty acids, with significant share of omega-3 fatty acids, reduction in insulin levels, and changes in the gut microbiota. The ketogenic diet influences glutamate metabolism and nerve cell metabolism, which uses ketone bodies as energy sources. Ketosis can also stimulate biogenesis of mitochondria, improve brain metabolism, act as a neuroprotective factor, as well as increase glutathione synthesis and reduce oxidative stress. Due to the limited size of the present study, literature review includes selected papers published in the last two decades in the PubMed and Google Scholar scientific literature databases, in English and Polish, with the following key words: ketogenic diet, bipolar affective disorder, depression, schizophrenia. [ABSTRACT FROM AUTHOR]

Objectives: Rapid cycling is a common and disabling phenomenon in individuals with bipolar disorders. In the absence of a recent literature examination, this systematic review and meta‐analysis aimed to synthesise the evidence of efficacy, acceptability and tolerability of treatments for individuals with rapid cycling bipolar disorder (RCBD). Method: A systematic search was conducted to identify randomised controlled trials assigning participants with RCBD to pharmacological and/or non‐pharmacological interventions. Study inclusion and data extraction were undertaken by two reviewers independently. The primary outcome was continuous within‐subject RCBD illness severity before and after treatment. Pre‐post random effects meta‐analyses were conducted for each outcome/intervention arm studied, generating a standardised effect size (hedge's g) and 95% confidence interval (CI). Results: A total of 34 articles describing 30 studies were included. A total of 16 separate pharmacological treatments were examined in contrast to 1 psychological therapy study. Only quetiapine and lamotrigine were assessed in >5 studies. By assessing 95% CI overlap of within‐subject efficacy effects compared to placebo, the only interventions suggesting significant depression benefits (placebo g = 0.60) were olanzapine (with/without fluoxetine; g = 1.01), citalopram (g = 1.10) and venlafaxine (g = 2.48). For mania, benefits were indicated for quetiapine (g = 1.01), olanzapine (g = 1.19) and aripiprazole (g = 1.09), versus placebo (g = 0.33). Most of these effect sizes were from only one trial per treatment. Heterogeneity between studies was variable, and 20% were rated to have a high risk of bias. Conclusions: While many interventions appeared efficacious, there was a lack of robust evidence for most treatments. Given the limited and heterogeneous evidence base, the optimal treatment strategies for people with RCBD are yet to be established. [ABSTRACT FROM AUTHOR]

Improved upstream titres in therapeutic monoclonal antibody (mAb) production have shifted capacity constraints to the downstream process. The consideration of membrane-based chromatographic devices as a debottlenecking option is gaining increasing attention with the recent introduction of high-capacity bind and elute membranes. We have evaluated the performance and scalability of the Sartobind® Rapid A affinity membrane (1 mL) for high-productivity mAb capture. For scalability assessment, a 75 mL prototype device was used to process 100 L of clarified cell culture harvest (CH) on a novel multi-use rapid cycling chromatography system (MU-RCC). MabSelect™ PrismA (4.7 mL) was used as a benchmark comparator for Protein A (ProtA) resin studies. Results show that in addition to a productivity gain of >10×, process and product quality attributes were either improved or comparable to the benchmark. Concentrations of eluate pools were 7.5× less than that of the benchmark, with the comparatively higher bulk volume likely to cause handling challenges at process scale. The MU-RCC system is capable of membrane operation at pilot scale with comparable product quality profile to the 1 mL device. The Sartobind® Rapid A membrane is a scalable alternative to conventional ProtA resin chromatography for the isolation and purification of mAbs from harvested cell culture media.

Objectives: Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the clinician. The aim of this paper is to give an overview of the evidence-based treatment options for rapid cycling.Methods: A systematic search on Pubmed, Embase and Cochrane databases from inception until December 2021 was conducted according to the PRISMA guidelines. An additional search on clinicaltrials.gov was done. References of retrieved papers and key reviews were hand-searched. Randomized controlled trials including at least 10 patients with bipolar disorder, rapid cycling, reporting an objective outcome measure were selected.Results: Our search, initially revealing 1330 articles, resulted in 16 papers about treatment of an acute mood episode, relapse prevention or both. Lithium, anticonvulsants, second generation antipsychotics, antidepressants and thyroid hormone were assessed as treatment options in the presented data. Evidence supporting the use of aripiprazole, olanzapine, quetiapine, valproate and lamotrigine for treatment of rapid cycling bipolar disorder was found.Limitations: Small sample sizes, different index episodes and variety of outcome measures.Conclusion: Evidence regarding treatment of rapid cycling remains scarce. Evidence supports the use of aripiprazole, olanzapine, and valproate for acute manic or mixed episodes, quetiapine for acute depressive episodes and aripiprazole and lamotrigine for relapse prevention. Given the paucity of available evidence, and the burden that accompanies rapid cycling, future research is warranted. [ABSTRACT FROM AUTHOR]

Bipolar patients in the United States (US) compared to those from the Netherlands and Germany (here abbrev. as "Europe") have more Axis I comorbidities and more poor prognosis factors such as early onset and psychosocial adversity in childhood. We wished to examine whether these differences also extended to Axis II personality disorders (PDs). 793 outpatients with bipolar disorder diagnosed by SCID gave informed consent for participating in a prospective longitudinal follow up study with clinician ratings at each visit. They completed detailed patient questionnaires and a 99 item personality disorder inventory (PDQ-4). US versus European differences in PDs were examined in univariate analyses and then logistic regressions, controlling for severity of depression, age, gender, and other poor prognosis factors. In the univariate analysis, 7 PDs were more prevalent in the US than in Europe, including antisocial, avoidant, borderline, depressive, histrionic, obsessive compulsive, and schizoid PDs. In the multivariate analysis, the last 4 of these PDs remained independently greater in the US than Europe. Although limited by use of self report and other potentially confounding factors, multiple PDs were more prevalent in the US than in Europe, but these preliminary findings need to be confirmed using other methodologies. Other poor prognosis factors are prevalent in the US, including early age of onset, more childhood adversity, anxiety and substance abuse comorbidity, and more episodes and rapid cycling. The interactions among these variables in relationship to the more adverse course of illness in the US than in Europe require further study. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the relationship between junior and senior high school students' cycling behavior, attitudes to traffic and attitude to daily life examining the effects of their gender and age on the behaviour, and to explore the underlying psychological determinants. Past studies on automobile driving have reported that the lower the level of a driver' attitude to safety, the higher the frequency of his/her risky behaviour and near-accident or accident involvement experience; that male and young drivers' level of safety behaviour is lower and they tend to exhibit risky behaviour more frequently than other drivers. It has also been reported that errors and lapses may correspond to accident experience. Although there has not been much research on riding of mopeds and bicycles, it has reported similar results. We conducted a survey on 2,077 junior and senior high school students, asking them to evaluate their traffic-related attitude/experience, behaviour as a cyclist, and their attitude to daily life. Factor analysis led us to extract three factors: "risky cycling", "social desirability", and "near accident". Drivers with weaker "social desirability" characteristic had a stronger tendency to "risky cycling". And it was also shown that the stronger the tendency towards "risky cycling", the more frequent the "near accident" experience occurred. Further, factor analysis focused only on items of cycling behaviour derived two factors: "distracted cycling" and "rapid cycling". Analysis of the correlation of these two factors and the aforementioned three factors showed that cyclists with a stronger tendency to "risky cycling" and weaker tendency to "social desirability" had a stronger tendency to "distracted cycling" and "rapid cycling". It was also shown that the higher the factor score of "risky cycling", the more frequent was the "near accident" experience. The number of accidents while cycling was found to be related to the factors "risky cycling", "social desirability", "near accident", "distracted cycling", and "rapid cycling". Based on the result above, it was speculated that the psychological determinants of cycling and car driving might be common, and it was considered that traffic safety education on cycling for junior and senior high school students is also effective for later car driving. [ABSTRACT FROM AUTHOR]

Introduction Bipolar disorder is a frequent and particularly severe psychiatric pathology that causes significant morbidity and mortality. The rapid cycling forms are more severe in terms of their expression, evolutionary course, therapeutic responses and associated comorbidities. Objectives The aim of this study is to conduct a descriptive assessment of therapeutic characteristics in patients with rapid cycling bipolar disorder. Methods Our work involved a population of 97 patients followed for bipolar disorder diagnosed according to DSM5 criteria, including 37 patients meeting the specification “with rapid cycles”. The patients were divided into two groups: - Group of patients with bipolar disorder with rapid cycles (TBCR) - Group of patients with bipolar disorder without rapid cycling (TBNCR). We compared the therapeutic features among these two groups. Results The dominant polarity was depressive in patients with rapid cycles. They required more mood stabilizers. A greater proportion of them had received treatment with serotonin reuptake inhibitor antidepressants. They were more likely to use hypnotics such as antihistamines and zolpidem. Conclusions Rapid cycling TB is a relatively common clinical modality that should be investigated and identified.The use of antidepressants is associated with this course of the disease. Their utilization in the treatment of bipolar depression must be thoughtful and well studied Disclosure No significant relationships.

Rapid cycling (RC) burdens bipolar disorder (BD) patients further by causing more severe disability and increased suicidality. Because diagnosing RC can be challenging, RC patients are at risk of rapid decline due to delayed suitable treatment. Here, we aimed to identify the differences in the circulating cell-free DNA (cfDNA) methylome between BD patients with and without RC. The cfDNA methylome could potentially be developed as a diagnostic test for BD RC. We extracted cfDNA from plasma samples of BD1 patients (46 RC and 47 non-RC). cfDNA methylation levels were measured by 850K Infinium MethylationEPIC array. Principal component analysis (PCA) was conducted to assess global differences in methylome. cfDNA methylation levels were compared between RC groups using a linear model adjusted for age and sex. PCA suggested differences in methylation profiles between RC groups (p = 0.039) although no significant differentially methylated probes (DMPs; q > 0.15) were found. The top four CpG sites which differed between groups at p < 1E-05 were located in CGGPB1 , PEX10 , NR0B2 , and TP53I11. Gene set enrichment analysis (GSEA) on top DMPs (p < 0.05) showed significant enrichment of gene sets related to nervous system tissues, such as neurons, synapse, and glutamate neurotransmission. Other top notable gene sets were related to parathyroid regulation and calcium signaling. To conclude, our study demonstrated the feasibility of utilizing a microarray method to identify circulating cfDNA methylation sites associated with BD RC and found the top differentially methylated CpG sites were mostly related to the nervous system and the parathyroid. [ABSTRACT FROM AUTHOR]

Rapid cycling (RC) burdens bipolar disorder (BD) patients further by causing more severe disability and increased suicidality. Because diagnosing RC can be challenging, RC patients are at risk of rapid decline due to delayed suitable treatment. Here, we aimed to identify the differences in the circulating cell-free DNA (cfDNA) methylome between BD patients with and without RC. The cfDNA methylome could potentially be developed as a diagnostic test for BD RC. We extracted cfDNA from plasma samples of BD1 patients (46 RC and 47 non-RC). cfDNA methylation levels were measured by 850K Infinium MethylationEPIC array. Principal component analysis (PCA) was conducted to assess global differences in methylome. cfDNA methylation levels were compared between RC groups using a linear model adjusted for age and sex. PCA suggested differences in methylation profiles between RC groups (p = 0.039) although no significant differentially methylated probes (DMPs; q > 0.15) were found. The top four CpG sites which differed between groups at p < 1E-05 were located in CGGPB1, PEX10, NR0B2, and TP53I11. Gene set enrichment analysis (GSEA) on top DMPs (p < 0.05) showed significant enrichment of gene sets related to nervous system tissues, such as neurons, synapse, and glutamate neurotransmission. Other top notable gene sets were related to parathyroid regulation and calcium signaling. To conclude, our study demonstrated the feasibility of utilizing a microarray method to identify circulating cfDNA methylation sites associated with BD RC and found the top differentially methylated CpG sites were mostly related to the nervous system and the parathyroid.

Thyroid hormone (TH) augmentation, although commonly used for major depression, is sparingly used for bipolar disorder (BD) after the failure of mood-stabilizing agents. While the exact mechanisms of thyroid hormone action in BD remains unclear, central thyroid hormone deficit has been postulated as a mechanism for rapid cycling. This systematic review—conducted in accordance with the PRISMA guidelines—of eight studies synthesizes the evidence for TH augmentation in BD. A systematic search of the Ovid MEDLINE, Embase, PsycINFO, and Cochrane databases was conducted for randomized controlled trials (RCT), open-label trials, and observational studies of levothyroxine (LT4) and triiodothyronine (T3) for BD. Open-label studies of high dose LT4 augmentation for bipolar depression and rapid cycling showed improvement in depression outcomes and reduction in recurrence, respectively. However, an RCT of high-dose LT4 did not show benefit in contrast to placebo. An RCT comparing LT4, T3, and placebo showed benefit only in rapid-cycling bipolar women. A meta-analysis could not be completed due to significant differences in study designs, interventions, and outcomes. Our systematic review shows mixed evidence and a lack of high-quality studies. The initial promise of supratherapeutic LT4 augmentation from open-label trials has not been consistently replicated in RCTs. Limited data are available for T3. The studies did not report significant thyrotoxicosis, and TH augmentation were well tolerated. Therefore, TH augmentation, especially with supratherapeutic doses, should be reserved for highly treatment-resistant bipolar depression and rapid-cycling BD.

Abstract Background Conclusions regarding the association between antithyroid antibodies or thyroid dysfunction and rapid cycling bipolar disorder (RCBD) have been conflicting. Previous studies suggest that the impact of antithyroid antibodies on mental wellbeing seems to be independent of thyroid function. Here, we investigated their independent association with RCBD in a large, well-defined population of bipolar disorder (BD). Methods Fast serum levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid Stimulating Hormone (TSH), TPO-abs and Tg-abs were simultaneously measured in 352 patients with BD. Clinical features of BD were collected through semi-structural interview conducted by trained interviewers with background of psychiatric education. Results Neither hypothyroidism nor hyperthyroidism was significantly associated with RCBD. Both TPO-abs and Tg-abs were significantly related to RCBD, even after controlling for gender, age, marriage status, education, antidepressants treatment, comorbidity of thyroid diseases, and thyroid function (serum levels of FT3, FT4 and TSH). Although TPO-abs and Tg-abs were highly correlated with each other, binary logistic regression with forward LR selected TPO-abs, instead of Tg-abs, to be associated with RCBD. TPO-abs was significantly, independently of Tg-abs, associated with hyperthyroidism, while Tg-abs was marginally significantly related to hypothyroidism at the presence of TPO-abs. Conclusion TPO-abs might be treated as a biomarker of RCBD. Further exploring the underlying mechanism might help understand the nature of RCBD and find out new treatment target for it.

Abstract Background Bipolar disorder (BD) affects both sexes, but important sex differences exist with respect to its symptoms and comorbidities. For example, rapid cycling (RC) is more prevalent in females, and alcohol use disorder (AUD) is more prevalent in males. We hypothesize that X chromosome variants may be associated with sex-specific characteristics of BD. Few studies have explored the role of the X chromosome in BD, which is complicated by X chromosome inactivation (XCI). This process achieves “dosage compensation” for many X chromosome genes by silencing one of the two copies in females, and most statistical methods either ignore that XCI occurs or falsely assume that one copy is inactivated at all loci. We introduce new statistical methods that do not make these assumptions. Methods We investigated this hypothesis in 1001 BD patients from the Genetic Association Information Network (GAIN) and 957 BD patients from the Mayo Clinic Bipolar Disorder Biobank. We examined the association of over 14,000 X chromosome single nucleotide polymorphisms (SNPs) with sex-associated BD traits using two statistical approaches that account for whether a SNP may be undergoing or escaping XCI. In the “XCI-informed approach,” we fit a sex-adjusted logistic regression model assuming additive genetic effects where we coded the SNP either assuming one copy is expressed or two copies are expressed based on prior knowledge about which regions are inactivated. In the “XCI-robust approach,” we fit a logistic regression model with sex, SNP, and SNP-sex interaction effects that is flexible to whether the region is inactivated or escaping XCI. Results Using the “XCI-informed approach,” which considers only the main effect of SNP and does not allow the SNP effect to differ by sex, no significant associations were identified for any of the phenotypes. Using the “XCI-robust approach,” intergenic SNP rs5932307 was associated with BD (P = 8.3 × 10−8), with a stronger effect in females (odds ratio in males (ORM) = 1.13, odds ratio in females for a change of two allele copies (ORW2) = 3.86). Conclusion X chromosome association studies should employ methods which account for its unique biology. Future work is needed to validate the identified associations with BD, to formally assess the performance of both approaches under different true genetic architectures, and to apply these approaches to study sex differences in other conditions.

Objectives: The "Bipolar Disorders: Improving Diagnosis, Guidance, and Education" (BRIDGE‐II‐Mix) study aimed to estimate the frequency of mixed states in patients with a major depressive episode (MDE) according to different definitions and to compare their clinical validity, looking into specific features such as rapid cycling (RC). Methods: Psychiatric symptoms, socio‐demographic, and clinical variables were collected from a sample of 2811 MDE patients, of which 726 (25.8%) were diagnosed with bipolar disorder (BD). The characteristics of bipolar patients with RC (BD‐RC) and without (BD‐NRC) RC were compared. Results: Of 726 BD patients, 159 (21.9%) met DSM‐5 criteria for RC. BD‐RC group presented a higher number of lifetime depressive episodes (p < 0.001) with shorter duration of depressive episodes, and more psychiatric comorbidities, as well as higher rates of atypical features (p = 0.016) and concomitant (hypo)manic symptoms (irritable mood (p = 0.001); risky behavior (p = 0.005); impulsivity (p = 0.006); and psychomotor agitation (p = 0.029)). Patients with RC had a worse functioning (p = 0.033), more obesity (p = 0.003), and were significantly more likely to be treated with three or more drugs (p = 0.007). Conclusions: Important clinical differences between bipolar patients with and without a RC include more depressive morbidity, higher incidence of anxiety disorders, addiction, bulimia, and borderline personality disorder, as well as atypical features during depression and symptoms such as irritability, risky behavior, impulsivity, and agitation. RC patients had poorer functioning than patients without RC, more obesity, and had to be treated with more drugs. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic low-grade inflammation is believed to contribute, at least in a subset of patients, to the development of bipolar disorder (BD). In this context, the most investigated biological marker is the acute phase response molecule, C-reactive protein (CRP). While the genetic diversity of CRP was amply studied in various pathological settings, little is known in BD. Methods 568 BD patients along with 163 healthy controls (HC) were genotyped for the following single-nucleotide polymorphisms (SNPs) on the CRP gene: intron rs1417938 (+ 29) T/A, 3′-UTR rs1130864 (+ 1444) G/A, and downstream rs1205 (+ 1846) (C/T). The statistical analysis was performed using Chi-square testing and consisted of comparisons of allele/genotype frequencies between patients and controls and within patient sub-groups according to BD clinical phenotypes and the presence of thyroid disorders. Results We found that the frequencies of the studied SNPs were similar in BD and HC groups. However, the CRP rs1130864 A allele carrier state was significantly more frequent: (i) in BD patients with thyroid disorders than in those without (pc = 0.046), especially among females (pc = 0.01) and independently of lithium treatment, (ii) in BD patients with rapid cycling than in those without (pc = 0.004). Conclusions Overall, our findings suggest the possibility that CRP genetic diversity may contribute to the development of auto-immune comorbid disorders and rapid cycling, both proxy of BD severity. Such findings, if replicated, may allow to predict complex clinical presentations of the disease, a possible step towards precision medicine in psychiatry.

Rapid cycling (RC) presents a risk of greater severity in bipolar disorder (BD), whereas patients with one-year euthymia (OYE) have better prognosis. The purpose of this study was to identify the clinical background and prescription characteristics of patients in the two opposing states of current RC and OYE from a large sample (N = 2609) in a multicenter treatment survey on BD in psychiatric clinics (MUSUBI). MUSIBI was a cross-sectional study wherein questionnaires, based on a retrospective medical record survey of consecutive cases of BD, were distributed to 176 outpatient clinics. The questionnaire collected information on patient background, current episode, and clinical and prescription characteristics. OYE was defined as the presence of a euthymic state for at least 12 months. In this study, current RC (9.7% frequency) was significantly higher in females, had a younger age of onset, functional impairments, and a higher rate of neurodevelopmental disorder and physical comorbidity compared to non-RC patients. OYE (19.4% frequency) was associated with a lower proportion of females, older age, higher occupational status, and lower rate of suicide ideation, psychotic symptoms, personality disorder, and alcohol or substance abuse. Mood stabilizers were prescribed in ≥80% of cases, while antipsychotics were prescribed in half of the cases (more in RC and less in OYE). Antidepressant prescription rates were lower in OYE than in RC. RC and OYE generally show opposing characteristics, but the details of the opposite parameters are distinctive. Clinicians can help predict the progression of BD by understanding the clinical background and characteristics of these opposing clinical features. • Clinical characteristics of rapid cycling (RC) and (one-year euthymia) OYE analysis in a large sample (N = 2609). • RC was associated with female sex, younger age of onset, neurodevelopmental disorders, and physical comorbidity. • OYE was associated with male, older age, occupational status and lower rate of personality disorders and alcohol abuse. • Antidepressant prescription rates were comparable for RC and lower for OYE. [ABSTRACT FROM AUTHOR]

Purpose: Vagus nerve stimulation (VNS) is an effective adjunctive therapy for drug-resistant epilepsy. Nevertheless, information is lacking regarding optimization of stimulation parameters to improve efficacy. Our study examines the safety and efficacy of rapid duty cycle VNS (OFF time ≤1.1 minute keeping duty cycle less than 50%) in pediatric cohort with intractable epilepsy.Methods: Retrospective chart review of 50 patients (one to 17 years) with drug-resistant epilepsy treated with VNS between 2010 and 2015 at a single pediatric epilepsy center. Safety and tolerability data were aggregated across all patient visits to determine frequency of adverse events between differing duty cycles. We also compared seizure reduction rates for each patient at (1) last regular duty cycle visit, (2) first rapid duty cycle visit, and (3) last recorded rapid duty cycle visit.Results: Rapid duty cycle was well tolerated, with no adverse events reported in 96.6% patient encounters. At the last visit before switching to rapid duty cycle 45.5% patients were showing response to VNS (seizure reduction rates ≥50%). This rate increased to 77.3% after switching to rapid duty cycle and remained at 77.4% at the last rapid duty cycle visit. Fifteen patients (34.1%) became responders to VNS after switching to rapid cycling; another 19 (43.2%) maintained their response with mostly improved seizure reduction rates. In only a few instances, responders became nonresponders after switching to rapid duty cycle.Conclusions: Rapid duty cycle VNS is probably safe and well tolerated; it may also be more efficacious than regular cycling VNS in some patients. This study highlights the necessity of prospective, long-term, double-blinded studies for understanding the advantages of this VNS modality. [ABSTRACT FROM AUTHOR]

Background: This study reports the effects of acupuncture treatment on depression and anxiety symptoms for 3 different bipolar disorder (BD) pathologies., Case: Case 1: A 35-year-old man was diagnosed with BD type 2. His depressive symptoms appeared 17 years ago. He did not meet the diagnostic criteria for anxiety disorder (AD) in the Mini International Neuropsychiatric Interview (MINI). Case 2: A 32-year-old woman was diagnosed with BD type 2 with AD. Her depressive symptoms appeared 5 years ago. MINI indicated panic-, social anxiety-, and generalized AD. Case 3: A 42-year-old woman was diagnosed with rapid cycling BD. She developed depressive and hypomanic symptoms and visited our hospital 18 years ago. Acupuncture treatment was performed weekly for 12 weeks. Depression and anxiety symptoms were evaluated using the Himorogi Self-Rating Depression Scale (HSDS) and Himorogi Self-Rating Anxiety Scale (HSAS), respectively., Results: Case 1: The HSAS score did not improve significantly, but the HSDS score decreased from 22 points at baseline to 9 points at the 12th visit. Case 2: The HSDS score did not improve, and the HSAS score remained high from 26 points at baseline to 25 points at the 12th visit. Case 3: During the acupuncture period, both HSDS and HSAS scores fluctuated greatly, and the patient experienced repeated episodes of depression and hypomania., Conclusions: The response to acupuncture treatment may differ according to the classification and pathology of BD, and it may be desirable to perform the acupuncture treatment after evaluating the pathology and estimating the prognosis., Competing Interests: No competing financial interests exist., (Copyright 2024, Mary Ann Liebert, Inc., publishers.)

Objective: Literature indicates that rapid cycling (RC) feature in bipolar disorder (BD) has been associated with worse disorder outcome and more severe disability. We aimed to investigate factors that affect or involved in vulnerability to increase rapid cycling in the previous 12 months. Methods: This is a cross-sectional study. Patients (n=380) were recruited from an outpatients clinic of a general hospital. Diagnostic interviews were performed with Structured Clinical Interview for DSM-IV Disorders (SCID-I) and SCID-II. Sociodemographic Form, Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAM-D) were applied. RC was defined as presence four or more mood episodes in the previous 12 months. Patients were arranged as whether having rapid cycling bipolar disorder (RCBD) or not. RCBD was compared to the group of non-RCBD patients regarding the sociodemographic and clinical data. Results: Study group showed a female preponderance (65.0%). Sixty patients (15.8%) had RC in the previous 12 months. There were statistically significant differences between two groups regarding in number of suicide attempts, family history of mood disorders, psychotic depression, number of antidepressants utilized, manic, depressive, mixed and total number of episodes. Discussion: The presence of RC in the previous 12 months was found correlated with specific clinical features closely related to worse outcome in the course of BD. Further studies are needed to clarify disease-related factors in patient groups with a standard definition of homogeneous RCBD. [ABSTRACT FROM AUTHOR]

Background: Patients with bipolar disorder demonstrate sex differences in clinical presentation, particularly in the sub-phenotypes related to periodicity of mood episodes, such as rapid cycling. Additionally, recent studies have linked P2RX7 gene variants with the risk of rapid cycling in clinical cohorts of patients with bipolar disorder, as well as other mood disorders. However, little is known about potential sex differences in the relationship between variants in P2RX7 and bipolar disorder.Methods: We investigated sex-specific genetic associations between variants of P2RX7 (rs1621388 and rs2230912) in 756 patients with bipolar disorder and 787 control patients matched on age, sex, and ancestry. We examined sex-specific genetic associations with bipolar disorder by comparing cases and controls, as well as rapid cycling of mood episodes in cases. Findings were replicated in an independent dataset.Results: P2RX7 variants implying an increased pore activity were more common in bipolar disorder, in females but not in males. Neither P2RX7 variants associated with rapid cycling among bipolar patients.Limitations: Low sample size limited power for tests of SNP by sex interaction, and data about the onset of rapid cycling and the timing of medication use were not available.Conclusion: The effects of P2RX7 variants on bipolar disorder may be sex-specific, with increased P2X7 activity potentially elevating risk for bipolar disorder in females. Future research to examine the effect of P2RX7 on bipolar disorder should consider sex-specific effects. [ABSTRACT FROM AUTHOR]

Objective: Bipolar Disorder (BD) is characterized by deregulated adaptive immune processes. Recent genome‐wide association studies (GWAS) implicate the major histocompatibility complex (MHC) region in BD. The present study investigates the potential influence of variations in human leukocyte antigen (HLA) on BD risk and/or clinical presentations. This may have relevance to the dysregulated inflammatory processes commonly found in BD. Method: DNAs from 475 BD patients and 195 healthy controls (HC) were genotyped for classical HLA class I and II loci. Results: We found that: (i) the HLA‐A*02~B*44~DRB1*07 sub‐haplotype is less prevalent in BD, vs. HC (pc = 2.4 × 10−2); (ii) the 57.1 and the 8.1‐derived ancestral haplotypes i.e. HLA‐A*02~B*57~Cw*06~DRB1*07~DQB1*09 and HLA‐A*02~B*08~Cw*07 are associated with rapid cycling (pc = 1.9 × 10−3 and 1.05 × 10−2, respectively); (iii) the 8.1AH‐derived HLA class II‐DRB*03~HLA‐DQB1*02 sub‐haplotype is more frequent in BD patients with a history of suicidal behaviors (pc = 2.1 × 10−2); and (iv) disease onset by an hypomanic episode or by psychotic symptoms are, respectively, more frequent in BD patients bearing the 7.1 AH‐derived A*03~B*07~DRB1*15 sub‐haplotype (pc = 8.5 × 10−3) and the HLA‐A*02~B*07~DRB1*15 sub‐haplotype (pc = 4.0 × 10−2). Conclusion: Corroborating the established link between these HLA haplotypes/sub haplotypes and common immune disorders, our findings suggest possible HLA‐mediated proinflammatory processes operating in BD. [ABSTRACT FROM AUTHOR]

Objectives: This report describes the first comparative double‐blind, placebo‐controlled trial of levothyroxine (L‐T4) and triiodothyronine (T3) as adjunctive treatments in rapid cycling bipolar disorder. Methods: Thirty‐two treatment‐resistant, rapid cycling patients who had failed a trial of lithium were randomized into three treatment arms: L‐T4, T3, or placebo. They were followed for ≥4 months with weekly clinical and endocrine assessments. Results: There were no statistically significant differences between the groups in age, gender, duration of illness, or thyroid status. Markov chain analyses were employed to assess treatment effects on cycling patterns among mood states (euthymia, depression, mania, and mixed). Within groups, post‐treatment the L‐T4 group spent significantly less time depressed or in a mixed state and greater time euthymic. The T3 and placebo groups did not differ significantly pre‐ and post‐treatment in any mood state, although the pattern of effects was the same for the T3 group as for the L‐T4 group. Between groups, the L‐T4 group had a significantly greater increase in time euthymic and decrease in time in the mixed state than the placebo group. Other group differences were not significant, although they were in the expected direction. Conclusions: The findings in this first double‐blind study directly comparing the effects of L‐T4 and T3 therapy against placebo provide evidence for the benefit of adjunctive L‐T4 in alleviating resistant depression, reducing time in mixed states and increasing time euthymic. Adjunctive T3 did not show statistically significant evidence of benefit over placebo in reducing the time spent in disturbed mood states. [ABSTRACT FROM AUTHOR]

Objectives: This report describes the first comparative double‐blind, placebo‐controlled trial of levothyroxine (L‐T4) and triiodothyronine (T3) as adjunctive treatments in rapid cycling bipolar disorder. Methods: Thirty‐two treatment‐resistant, rapid cycling patients who had failed a trial of lithium were randomized into three treatment arms: L‐T4, T3, or placebo. They were followed for ≥4 months with weekly clinical and endocrine assessments. Results: There were no statistically significant differences between the groups in age, gender, duration of illness, or thyroid status. Markov chain analyses were employed to assess treatment effects on cycling patterns among mood states (euthymia, depression, mania, and mixed). Within groups, post‐treatment the L‐T4 group spent significantly less time depressed or in a mixed state and greater time euthymic. The T3 and placebo groups did not differ significantly pre‐ and post‐treatment in any mood state, although the pattern of effects was the same for the T3 group as for the L‐T4 group. Between groups, the L‐T4 group had a significantly greater increase in time euthymic and decrease in time in the mixed state than the placebo group. Other group differences were not significant, although they were in the expected direction. Conclusions: The findings in this first double‐blind study directly comparing the effects of L‐T4 and T3 therapy against placebo provide evidence for the benefit of adjunctive L‐T4 in alleviating resistant depression, reducing time in mixed states and increasing time euthymic. Adjunctive T3 did not show statistically significant evidence of benefit over placebo in reducing the time spent in disturbed mood states. [ABSTRACT FROM AUTHOR]

The relationship of personality disorder (PD) psychopathology to the course of bipolar disorder remains inadequately described. After giving informed consent, more than 782 outpatients with bipolar disorder rated themselves on the 99-item Personality Disorder Questionnaire, Version 4 (PDQ4) when depressed or euthymic. They also rated six poor prognosis factors (PPFs). The relationships of the PPFs to the total PDQ4 score were examined by a linear regression. Even after correcting for the higher PDQ4 scores observed when patients were suffering depression, the PDQ4 was significantly related to a history of child abuse, early age of onset, an anxiety disorder comorbidity, rapid cycling, and 20 or more previous episodes, but not substance abuse. The data suggest close relationships between the total burden of PD psychopathology and correlates of an adverse outcome of bipolar disorder. The nature of this of association and approaches to treatment of comorbid PD remain to be further explored. [ABSTRACT FROM AUTHOR]

Background: Chronic low-grade inflammation is believed to contribute, at least in a subset of patients, to the development of bipolar disorder (BD). In this context, the most investigated biological marker is the acute phase response molecule, C-reactive protein (CRP). While the genetic diversity of CRP was amply studied in various pathological settings, little is known in BD. Methods: 568 BD patients along with 163 healthy controls (HC) were genotyped for the following single-nucleotide polymorphisms (SNPs) on the CRP gene: intron rs1417938 (+ 29) T/A, 3′-UTR rs1130864 (+ 1444) G/A, and downstream rs1205 (+ 1846) (C/T). The statistical analysis was performed using Chi-square testing and consisted of comparisons of allele/genotype frequencies between patients and controls and within patient sub-groups according to BD clinical phenotypes and the presence of thyroid disorders. Results: We found that the frequencies of the studied SNPs were similar in BD and HC groups. However, the CRP rs1130864 A allele carrier state was significantly more frequent: (i) in BD patients with thyroid disorders than in those without ( pc = 0.046), especially among females ( pc = 0.01) and independently of lithium treatment, (ii) in BD patients with rapid cycling than in those without ( pc = 0.004). Conclusions: Overall, our findings suggest the possibility that CRP genetic diversity may contribute to the development of auto-immune comorbid disorders and rapid cycling, both proxy of BD severity. Such findings, if replicated, may allow to predict complex clinical presentations of the disease, a possible step towards precision medicine in psychiatry. [ABSTRACT FROM AUTHOR]

Objectives: To compare the relative influence (RI) of individual predictors for lifetime attempted suicide between adults with bipolar I (BDBD-I) and bipolar II disorder (BDBD-II).Methods: We conducted an analysis of data from 1465 enrollees in the Mayo Clinic Bipolar Disorder Biobank. Demographic and clinical variables and history of attempted suicide were ascertained using standardized questionnaires. Height and weight were assessed to determine body mass index (BMI); obesity was defined as BMI ≥30kg/m2. The frequencies of these variables were compared between persons with and without self-reported lifetime suicide attempts both overall, and within BD-I and BD-II subgroups. Gradient boosting machine (GBM) models were used to quantify the RI of study variables on the risk of lifetime attempted suicide.Results: Nearly one-third of patients reported having a lifetime suicide attempt. Attempted suicide rates were higher in patients with BD-I than BD-II, but absolute differences were small. Lifetime attempted suicide was associated with female sex, BD-I subtype, psychiatric and substance use comorbidities, binge eating behavior, lifetime history of rapid cycling, other indicators of adverse illness course, and early age of bipolar illness onset in the entire cohort. Differences in the rank-ordering of RI for predictors of attempted suicide between BD-I and BD-II patients were modest. Rapid cycling was a strong risk factor for attempted suicide, particularly in men with BD-I.Limitations: Actively psychotic or suicidal patients needing psychiatric hospitalization were initially excluded, but were approached after these acute psychiatric problems resolved.Conclusions: The prevalence of lifetime attempted suicide was significantly higher in BD-I than BD-II in this large, cross-sectional cohort. Predictors of attempted suicide were similar in BD-I and BD-II subgroups. [ABSTRACT FROM AUTHOR]