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Early symptomatic improvement may predict treatment response in bipolar I disorder. Cariprazine has demonstrated early treatment effects in bipolar I depression and mania studies; therefore, we assessed whether early improvement with cariprazine predicts eventual treatment response. Post hoc analyses used pooled data from randomized, double-blind, placebo-controlled bipolar I depression (NCT02670538 , NCT02670551) and mania (NCT00488618 , NCT01058096 , NCT01058668) trials. In depression studies (cariprazine 1.5 mg/d, 3 mg/d, or placebo), early improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A) total scores (≥25 % improvement at day 15) and subsequent depressive/anxiety symptom response status (≥50 % improvement at week 6) were assessed. In mania studies (cariprazine 3–12 mg/d or placebo), early improvement in Young Mania Rating Scale (YMRS) total scores (≥25 % improvement at day 7) and manic symptom response status (≥50 % improvement at week 3) were assessed. Patients with bipolar I depression and early MADRS improvement were approximately 4- to 6-times as likely to achieve MADRS or HAM-A response than those without early improvement; patients with early HAM-A improvement were approximately 3- to 4-times as likely to achieve MADRS or HAM-A response. A subset of patients without early improvement with cariprazine 1.5 mg/d (20 %–31 %) subsequently responded following up-titration. Patients with mania and early YMRS improvement were approximately 5 times more likely to have manic symptom response than those without early improvement. Post hoc analysis; relatively short study durations; flexible-dosing (mania studies). Early symptom improvement with cariprazine may inform therapeutic decisions for patients with bipolar I disorder. • Early improvement with cariprazine predicted week 6 bipolar I depression response. • Early improvement in manic symptoms was also predictive of week 3 mania response. • Some patients without early improvement responded after cariprazine up-titration. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) has a high disease burden and the highest mortality risk in BD comes from suicide. Bipolar disorder type II (BD-II) has been described as a milder form of bipolar disorder; however, extant literature is inconsistent with this description and instead describe illness burden and notably suicidality comparable to persons with bipolar I disorder (BD-I). Towards quantifying the hazard of BD-II, herein we aim via systematic review and meta-analysis to evaluate the rates of completed suicide in BD-I and BD-II. We conducted a literature search on PubMed, OVID (Embase, Medline) and PsychINFO databases from inception to June 30th, 2023, according to PRISMA guidelines. Articles were selected based on the predetermined eligibility criteria. A meta-analysis was performed, comparing the risk of completed suicide between individuals diagnosed with BD-I to BD-II. Four out of eight studies reported higher suicide completion rates in persons living with BD-II when compared to persons living with BD-I; however, two of the studies reported non-significance. Two studies reported significantly higher suicide completion rates for BD-I than BD-II. The pooled odds ratio of BD-II suicide rates to BD-I was 1.00 [95 % CI = 0.75, 1.34]. The overarching limitation is the small number of studies and heterogeneity of studies that report on suicide completion in BD-I and BD-II. Our study underscores the severity of BD-II, with a risk for suicide not dissimilar from BD-I. The greater propensity to depression, comorbidity and rapid-cycling course reported in BD-II are contributing factors to the significant mortality hazard in BD-II. • Data on risk for completed suicide in bipolar disorders type I and-II are limited. • Therefore, we conducted a systematic review and meta-analysis on the topic. • We found similar risk of completed suicide in bipolar disorder type I and -II. • Bipolar disorder type II should be considered as severe as bipolar disorder type I. • Large high-quality studies on suicide risk in bipolar disorder types are warranted. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Investigating the shared brain protein and genetic components of schizophrenia (SCZ) and bipolar I disorder (BD-I) presents a unique opportunity to understand the underlying pathophysiological processes and pinpoint potential drug targets. Study Design To identify overlapping susceptibility brain proteins in SCZ and BD-I, we carried out proteome-wide association studies (PWAS) and Mendelian Randomization (MR) by integrating human brain protein quantitative trait loci with large-scale genome-wide association studies for both disorders. We utilized transcriptome-wide association studies (TWAS) to determine the consistency of mRNA-protein dysregulation in both disorders. We applied pleiotropy-informed conditional false discovery rate (pleioFDR) analysis to identify common risk genetic loci for SCZ and BD-I. Additionally, we performed a cell-type-specific analysis in the human brain to detect risk genes notably enriched in distinct brain cell types. The impact of risk gene overexpression on dendritic arborization and axon length in neurons was also examined. Study Results Our PWAS identified 42 proteins associated with SCZ and 14 with BD-I, among which NEK4, HARS2, SUGP1, and DUS2 were common to both conditions. TWAS and MR analysis verified the significant risk gene NEK4 for both SCZ and BD-I. PleioFDR analysis further supported genetic risk loci associated with NEK4 for both conditions. The cell-type specificity analysis revealed that NEK4 is expressed on the surface of glutamatergic neurons, and its overexpression enhances dendritic arborization and axon length in cultured primary neurons. Conclusions These findings underscore a shared genetic origin for SCZ and BD-I, offering novel insights for potential therapeutic target identification. [ABSTRACT FROM AUTHOR]

Patients with bipolar I disorder may experience mood destabilization or treatment-emergent affective switch (TEAS) from one symptom pole to the other spontaneously or following treatment. Optimal treatment should address symptoms from both poles without precipitating destabilization. These were pooled post hoc analyses of data from randomized, double-blind, placebo-controlled studies of cariprazine 3–12 mg/d for bipolar I mania (NCT00488618 , NCT01058096 , NCT01058668) and cariprazine 1.5 mg/d or 3 mg/d for bipolar I depression (NCT01396447 , NCT02670538 , NCT02670551). Changes from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 6 and Young Mania Rating Scale (YMRS) total score at week 3 were analyzed in each indication using a mixed-effects model for repeated measures. Percentages of patients with increasing levels of endpoint response and TEAS (bipolar mania = MADRS total score ≥ 19; bipolar depression = YMRS score ≥ 16) were determined. Cariprazine significantly reduced manic and depressive symptoms in patients with bipolar I disorder mood episodes. In patients with a manic episode and up to mild baseline depressive symptoms, cariprazine also significantly reduced depressive symptoms. In patients with a depressive episode and manic symptoms in remission at baseline, numerical reduction (without statistical significance) in YMRS indicated no worsening of mania. In both indications, cariprazine-treated patients had numerically greater response rates (presenting symptom pole) than placebo-treated patients; lower percentages of cariprazine- than placebo-treated patients had TEAS at visits where data were collected. Post hoc analysis. Results suggested that cariprazine had full-spectrum efficacy across symptoms from both poles in patients with bipolar I disorder mood episodes; TEAS risk was low. Patient-level response suggested that improvement was clinically relevant. • Patients with bipolar I disorder may experience treatment-related mood instability • Treatment should address symptoms from both poles, without causing affective switch • Results suggest cariprazine has full-spectrum symptom efficacy in bipolar I disorder • With cariprazine treatment, risk of treatment-emergent affective switch was low [ABSTRACT FROM AUTHOR]

INTRODUCTION: This study aimed to investigate the correlation between the early onset (EO) of Bipolar I Disorder (BD-I) and alexithymia, as well as the association between alexithymia and the clinical features of BD. METHODS: A total of 83 individuals diagnosed with BD-I under remission were randomly selected for inclusion in the study. Among them, 39 were diagnosed before (EO) and 44 were diagnosed after 18 years of age. The participants were assessed with the Socio-demographic Data Form, Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HAM-D), and Toronto Alexithymia Scale (TAS). RESULTS: In the EO group, the TAS total score, difficulty describing feelings subscale score, difficulty identifying feeling score, and externally oriented thinking score were significantly higher compared to the group diagnosed after age 18. Furthermore, the EO group exhibited a higher number of hospitalizations, a greater total number of attacks, an increased number of depressive attacks, manic attacks, extended disease duration, along with a higher incidence of suicide attempts and self-harm. DISCUSSION AND CONCLUSION: Our results indicate that early-onset in BD-I is correlated with elevated alexithymia levels, and is associated with prolonged disease duration, increased episode frequency, and a heightened incidence of suicide attempts among the affected individuals.

Background: Neurological soft signs (NSSs), minor physical anomalies (MPAs), and oculomotor abnormalities were plausible biomarkers in bipolar disorder (BD). However, specific impairments in these markers in patients after the first episode mania (FEM), in comparison with first-degree relatives (high risk [HR]) of BD and healthy subjects (health control [HC]) are sparse. Aim of the study: This study aimed at examining NSSs, MPAs, and oculomotor abnormalities in remitted adult subjects following FEM and HR subjects in comparison with matched healthy controls. Investigated when taken together, could serve as composite endophenotype for BD. Methods: NSSs, MPAs, and oculomotor abnormalities were evaluated in FEM (n = 31), HR (n = 31), and HC (n = 30) subjects, matched for age (years) (p = 0.44) and sex (p = 0.70) using neurological evaluation scale, Waldrop's physical anomaly scale and eye tracking (SPEM) and antisaccades (AS) paradigms, respectively. Results: Significant differences were found between groups on NSSs, MPAs, and oculomotor parameters. Abnormalities are higher in FEM subjects compared to HR and HC subjects. Using linear discriminant analysis, all 3 markers combined accurately classified 72% of the original 82 subjects (79·2% BD, 56·70% HR, and 82·1% HC subjects). Conclusions: AS and SPEM could enhance the utility of NSSs, and MPAs as markers for BD. The presence of these abnormalities in FEM suggests their role in understanding the etiopathogenesis of BD in patients who are in the early course of illness. These have the potential to be composite endophenotypes and have further utility in early identification in BD. Plain Language Summary Title: Eye movement abnormalities and Atypical Neurodevelopmental markers as Composite Measurable components in the pathway between disease manifestation and genetics in Bipolar I Disorder Plain Language Summary: Why was the study done? Neurological soft signs, Minor physical anomalies, and eye-movement abnormalities are known disease makers of Bipolar disorder but their utility in being intermediate markers between the disease manifestation and genetics has not been studied before. Hence we took up this study with the above aim. What did the researchers do? We compared the above-mentioned biomarkers between the patients diagnosed with first-episode mania (considered as early bipolar), the high-risk population (people with a family history of bipolar), and healthy subjects (without any self or family history of any psychiatric illnesses). Each group had 30 participants. We wanted to see if these markers taken together could predict the groups or classify the subjects into the three groups accurately. What did the researchers find? We found that in all the biomarkers there was a significant group difference between the the three groups. The abnormalities showed a pattern wherein they are higher in the first episode mania group compared to at-risk, and higher in at-risk compared to healthy subjects. When all these markers were combined and linear discriminant analysis was run, we noted they accurately classified 72% of the original participants (79·2% first episode bipolar 56·70% High risk, and 82·1% Healthy Subjects). What do the findings mean? The above findings indicate that the eye-movement or oculomotor abnormalities enhance the utility of neurodevelopmental markers as biomarkers of bipolar disorder. The presence of these abnormalities fairly early in the disease also means that they have a role in the etiopathogenesis of bipolar disorder. All the markers taken together can be composite measurable components in the pathway between disease manifestation and genetics in Bipolar I Disorder, and thus help in early identification. [ABSTRACT FROM AUTHOR]

Abstract Background To explore the demographic and clinical features of current depressive episode that discriminate patients diagnosed with major depressive disorder (MDD) from those with bipolar I (BP-I) and bipolar II (BP-II) disorder who were misdiagnosed as having MDD . Methods The Mini-International Neuropsychiatric Interview (MINI) assessment was performed to establish DSM-IV diagnoses of MDD, and BP-I and BP-II, previously being misdiagnosed as MDD. Demographics, depressive symptoms and psychiatric comorbidities were compared between 1463 patients with BP-I, BP-II and MDD from 8 psychiatric settings in mainland China. A multinomial logistic regression model was performed to assess clinical correlates of diagnoses. Results A total of 14.5% of the enrolled patients initially diagnosed with MDD were eventually diagnosed with BP. Broad illness characteristics including younger age, higher prevalence of recurrence, concurrent dysthymia, suicidal attempts, agitation, psychotic features and psychiatric comorbidities, as well as lower prevalence of insomnia, weight loss and somatic symptoms were featured by patients with BP-I and/or BP-I, compared to those with MDD. Comparisons between BP-I and BP-II versus MDD indicated distinct symptom profiles and comorbidity patterns with more differences being observed between BP-II and MDD, than between BP-I and MDD . Conclusion The results provide evidence of clinically distinguishing characteristics between misdiagnosed BP-I and BP- II versus MDD. The findings have implications for guiding more accurate diagnoses of bipolar disorders.

Background: To explore the demographic and clinical features of current depressive episode that discriminate patients diagnosed with major depressive disorder (MDD) from those with bipolar I (BP-I) and bipolar II (BP-II) disorder who were misdiagnosed as having MDD. Methods: The Mini-International Neuropsychiatric Interview (MINI) assessment was performed to establish DSM-IV diagnoses of MDD, and BP-I and BP-II, previously being misdiagnosed as MDD. Demographics, depressive symptoms and psychiatric comorbidities were compared between 1463 patients with BP-I, BP-II and MDD from 8 psychiatric settings in mainland China. A multinomial logistic regression model was performed to assess clinical correlates of diagnoses. Results: A total of 14.5% of the enrolled patients initially diagnosed with MDD were eventually diagnosed with BP. Broad illness characteristics including younger age, higher prevalence of recurrence, concurrent dysthymia, suicidal attempts, agitation, psychotic features and psychiatric comorbidities, as well as lower prevalence of insomnia, weight loss and somatic symptoms were featured by patients with BP-I and/or BP-I, compared to those with MDD. Comparisons between BP-I and BP-II versus MDD indicated distinct symptom profiles and comorbidity patterns with more differences being observed between BP-II and MDD, than between BP-I and MDD. Conclusion: The results provide evidence of clinically distinguishing characteristics between misdiagnosed BP-I and BP- II versus MDD. The findings have implications for guiding more accurate diagnoses of bipolar disorders. [ABSTRACT FROM AUTHOR]

Objective: Accurate information on the frequency and prevalence of manic or mixed episodes is important for therapeutic, prognostic, and safety concerns. We aimed to estimate the risk of relapse of manic and mixed episodes after delivery in women with bipolar I disorder or schizoaffective disorder—bipolar type. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, a comprehensive literature search in PubMed, PsycINFO, Embase, and Cochrane databases was carried out on November 17, 2022, using the terms ((bipolar disorder) OR (manic depressive illness)) AND (mania)) AND (postpartum)) AND (recurrence)) AND (relapse). The search was updated on March 29, 2023. Case studies and qualitative analyses were excluded. Twelve studies reporting on 3595 deliveries in 2183 women were included in the quantitative analysis. Results: The overall pooled estimate of postpartum relapse risk was 39% (95% CI = 29, 49; Q(11) = 211.08, p < 0.001; I2 = 96.31%). Among those who had a relapse, the pooled estimate of risk for manic and mixed episodes was 38% (95% CI = 28, 50; Q(11) = 101.17, p < 0.001; I2 = 91.06%). Using data from the nine studies that reported the percentage of medication use during pregnancy, we estimated a meta‐regression model with the percent medication use as a continuous explanatory variable. The estimated prevalence of relapse was 58.1% (95% CI, 9.6 to 39.3 to 76.8) for studies with no medication use and 25.9% (95% CI, 10.5–41.3) for studies with 100% medication use. The difference between the two prevalence estimates was statistically significant, z = −2.099, p = 0.0359. Conclusions: Our findings suggest an overall pooled estimate of postpartum relapse risk of 39%, while the pooled estimate of risk for manic and mixed episodes was 38%. These findings highlight the need to educate patients with bipolar I disorder, and their healthcare professionals about the high risk of relapse of manic or mixed episodes after delivery. [ABSTRACT FROM AUTHOR]

Introduction: Research has indicated that individuals diagnosed with bipolar disorder (BD) might experience alterations in their olfaction or levels of serum tumor necrosis factor-α (TNF-α), but no studies have investigated olfactory function and serum TNF-α in BD patients simultaneously. Moreover, there is a lack of existing research that compares the longitudinal olfactory function between individuals with manic and euthymic BD I. Methods: Patients with manic BD I (BDM, n=44) and healthy controls (HCs, n=32) were evaluated symptoms (measured via the Young Manic Rating Scale, YRMS), social function (measured via the Global Assessment Function, GAF), serum TNFa, and olfactory function (via the Sniffin’ Sticks test) including olfactory sensitivity (OS) and olfactory identification (OI). The BDM patients were followed up to the remission period and re-evaluated again. We compared OS, OI and serum TNF-α in manic and euthymic patients with BD I and HCs. We examined the correlation between olfactory function and symptoms, social function, and serum TNF-α in patients with BD I. Results: The BDM patients exhibited significantly lower OS and OI compared to the HCs (Z = −2.235, P = 0.025; t = −6.005, P < 0.001), while a positive correlation was observed between OS and GAF score (r = 0.313, P = 0.039). The OS in the BD I remission group (n=25) exhibited significantly superior performance compared to the BDM group (t = −4.056, P < 0.001), and the same as that in the HCs (P = 0.503). The change in OS showed a positive correlation with the decrease in YMRS score (r = 0.445, P = 0.026), and a negative correlation with the course of disease (r = -0.594, P = 0.002). The TNF-α in BD I patients was significantly lower compared to HCs (P < 0.001), and not significantly correlated with olfactory function (all P > 0.05). Conclusion: The findings suggest that OS and OI are impaired in BDM patients, and the impaired OS in those patients can be recovered in the remission stage. OI may serve as a potential characteristic marker of BD. OS might be useful as an index for BDM treatment efficacy and prognosis. [ABSTRACT FROM AUTHOR]

This naturalistic clinical study aims to investigate differences between newly diagnosed patients with bipolar type I (BDI) and bipolar type II (BDII) disorders in socio-demographic and clinical characteristics, affective symptoms, cognition, functioning and comorbidity with personality disorders. The BD diagnosis and type were confirmed using the Schedules for Clinical Assessment in Neuropsychiatry. Affective symptoms were assessed with the Young Mania Rating Scale, the Hamilton Depression Rating Scale, the Major Depressive Index, and the Altman Self-Rating Mania Scale. Functional impairment was assessed with the Functional Assessment Short Test. Cognitive impairment was evaluated by the Screen for Cognitive Impairment in Psychiatry and the Cognitive Complaints in Bipolar Disorder Rating Assessment. Finally, comorbid personality disorders were assessed with the Standardized Assessment of Personality-Abbreviated Scale and structured interview Structured Clinical Interview for DSM-disorders. 383 newly diagnosed patients were included (BDI: n = 125; BDII: n = 258). Against expectations, we found no more depressive symptoms in BDII compared with BDI nor any differences in cognitive, childhood trauma or overall functional impairment. The only difference was lower occupational impairment in the BDII group. The self-reported measures of cognitive difficulties and childhood trauma involved potential bias (recall or other). Despite BD being newly diagnosed a diagnostic delay was observed. Patients newly diagnosed with BDII and BDI had similar burdens of depressive symptoms and cognitive and overall functional impairment, however patients with BDI had lower occupational functioning. No statistically significant difference was found in prevalence of comorbid personality disorders between patients with BDI and BDII. • Prevalence of depressive symptoms did not differ between patients newly diagnosed with BD I and II. • Cognitive impairments were similar in patients newly diagnosed with BD I and II. • Personality disorder prevalence was higher in patients with newly diagnosed BD II. • Similar functional impairments overall were found in BD I and II. • Patients newly diagnosed with BD type I had lower occupational functioning. [ABSTRACT FROM AUTHOR]

Introduction: The current research aimed to determine the dominant draft scenario of the life of women with bipolar I disorder. Materials and Methods: This qualitative research was a phenomenological study, and we collected the data using Colaizzi's method. We interviewed 21 female patients with bipolar I disorder admitted to the neuropsychiatric department of three hospitals in Isfahan City, Iran, in 2020, and the life scenarios of the subjects were investigated. The triangulation method was used to obtain the validity and reliability of the research findings. Results: The scenarios were categorized into high, medium, and low repetition. The most frequent codes included suicide (26 repetitions) with the subcategories of suicidal thoughts, despair of life, and feeling close to death. Codes with moderate repetition included negative emotions (18 repetitions) with the subcategories of feeling like others are strangers to you, feeling rejected, uninterested in life, liking dark colors, and feeling empty. The less frequent codes included negative actions (11 repetitions) with the subcategories of self-sacrifice, suppression of hearing from others, sexual abuse, self-mutilation, running away from home, substance use, and difficulty in life. Conclusion: The findings showed that the dominant scenario in women with bipolar disorder, based on high frequency, was the "do not exist" scenario. [ABSTRACT FROM AUTHOR]

Objective: To compare neurofunctional responses in emotional and attentional networks of psychostimulant-free ADHD youth with and without familial risk for bipolar I disorder (BD). Methods: ADHD youth with (high-risk, HR, n = 48) and without (low-risk, LR, n = 50) a first-degree relative with BD and healthy controls (n = 46) underwent functional magnetic resonance imaging while performing a continuous performance task with emotional distracters. Region-of-interest analyses were performed for bilateral amygdala (AMY), ventrolateral (VLPFC) and dorsolateral (DLPFC) prefrontal cortex, and anterior (ACC) and posterior cingulate cortex (PCC). Results: Compared with HC, HR, but not LR, exhibited predominantly left-lateralized AMY, VLPFC, DLPFC, PCC, and rostral ACC hyperactivation to emotional distractors, whereas LR exhibited right VLPFC and bilateral dorsal ACC hypoactivation to attentional targets. Regional responses correlated with emotional and attention symptoms. Conclusion: Aberrant neurofunctional responses during emotional and attentional processing differentiate ADHD youth with and without a family history of BD and correlate with relevant symptoms ratings. [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.

AbstractThe immediate social microcosm surrounding diagnosed individuals are often neglected. Partners of persons with bipolar I disorder experience positive and challenging experiences of occupational engagement, informed by their partner role. Guided by Interpretive Phenomenological Analysis (IPA), in-depth interviews unearthed participants’ lived experiences to highlight challenging experiences of occupational engagement, including, unmet occupational needs, occupational disharmony, and imbalance. Protective factors enhancing occupational engagement included satisfactorily achieving occupational needs and the experience of autotelic meaning. This study consolidated that exploring, understanding, and addressing occupational needs for everyone, including secondarily affected populations, should be a focus of occupational therapists. [ABSTRACT FROM AUTHOR]

Objective: To compare demographic characteristics, clinical characteristics, therapeutic characteristics and physiological indicators of patients with bipolar I disorder and bipolar II disorder. Methods: A total of 381 patients with bipolar disorder(BD) diagnosed by the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-5) were selected, including 302 patients with BD-I (79.27%), 74 patients with BD-II (19.42%) and 5 patients with other specific and related disorders (1.31%). Demographic and clinical characteristics were collected with self-designed clinical information questionnaire. Multivariate logistic regression and multivariate linear regression analysis were used for analysis. Results: Compared with patients with BD-II, patients with BD-I had more risk to have psychotic features (OR = 5. 75, 95% CI: 2. 82-11. 76), longer disease duration, and more repeated transcranial magnetic therapy (OR = 3. 09, 95% CI: 1. 02-9.35), higher uric acid, total cholesterol and high-density lipoprotein. BD-I in Han nationality was more common (OR = 11. 50, 95% CI: 1. 76-75.30), and had lower education level (OR = 10. 22, 95% CI: 1. 1689.77), and less family history of psychosis (OR = 2. 34, 95% CI: 1. 01 5. 42). Conclusion: There are significant differences between BD-I and BD-II in demographic and clinical characteristics, treatment status, and physiological indicators, which could provide clues for exploring the pathogenesis of bipolar disorder. [ABSTRACT FROM AUTHOR]

Matthew Harlin,1,&ast; Craig Chepke,2,3,&ast; Frank Larsen,4,&ast; Karimah S Bell Lynum,5,&ast; Sanjeda R Chumki,5,&ast; Heather Fitzgerald,6,&ast; Pedro Such,7,&ast; Jessica Madera-McDonough,8,&ast; Murat Yildirim,7,&ast; Moeen Panni,8,&ast; Stephen R Saklad9,&ast; 1Quantitative Pharmacology, Clinical Pharmacology, Early Phase & Translational Medicine, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, NJ, USA; 2Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, NC, USA; 3Excel Psychiatric Associates, Huntersville, NC, USA; 4Pharmacokinetic and Pharmacodynamic Modelling & Simulation, H. Lundbeck A/S, Valby, Denmark; 5US Medical Affairs, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, NJ, USA; 6Medical Affairs, Lundbeck LLC, Deerfield, IL, USA; 7Medical Affairs, H. Lundbeck A/S, Valby, Denmark; 8Global Medical Affairs, Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, NJ, USA; 9Division of Pharmacotherapy, College of Pharmacy, The University of Texas at Austin, San Antonio, TX, USA&ast;These authors contributed equally to this workCorrespondence: Matthew Harlin, Otsuka Pharmaceutical Development & Commercialization Inc., 508 Carnegie Center Dr, Princeton, NJ, 08540, USA, Tel +1-240-683-3055, Email Matthew.Harlin@otsuka-us.comAbstract: Aripiprazole 2-month ready-to-use 960 mg (Ari 2MRTU 960) is a novel long-acting injectable (LAI) formulation of aripiprazole monohydrate for administration once every 2 months, developed for the treatment of schizophrenia or maintenance monotherapy treatment of bipolar I disorder in adults (indication will vary by country). Aripiprazole lauroxil 1064 mg (AL 1064) is an LAI formulation of aripiprazole lauroxil, an aripiprazole prodrug, for administration once every 2 months, indicated for the treatment of schizophrenia in adults. This analysis provides an indirect comparison of aripiprazole plasma concentrations following multiple doses of either formulation. Clinical trial data were used to determine average steady-state aripiprazole plasma concentration (Cavg,ss), maximum aripiprazole plasma concentration (Cmax), and other pharmacokinetic parameters of either formulation following four administrations (96 patients received Ari 2MRTU 960; 28 patients received AL 1064). All pharmacokinetic parameters were considered in the context of a minimum aripiprazole therapeutic concentration (Cmin) of ≥ 95 ng/mL. An exposure–response analysis using data from two Phase III trials of aripiprazole once-monthly (an aripiprazole monohydrate LAI, administered monthly), showed that patients with a Cmin ≥ 95 ng/mL are 4.41 times less likely to relapse than patients with a Cmin < 95 ng/mL. A similar analysis has not been performed for AL 1064. However, consensus guidelines for therapeutic drug monitoring recommend a range of 100– 350 ng/mL for aripiprazole. Following four administrations, mean (standard deviation [SD]) Cavg,ss over the 2-month dosing interval was 263 (133) ng/mL for Ari 2MRTU 960 and 140.7 (57.3) ng/mL for AL 1064. Mean (SD) Cmax during the fourth dosing interval was 342 (157) ng/mL for Ari 2MRTU 960 and 188.8 (79.8) ng/mL for AL 1064. This indirect comparison showed that, following four administrations, Ari 2MRTU 960 and AL 1064 delivered mean aripiprazole plasma concentrations that remained above the minimum therapeutic concentration of aripiprazole over the 2-month dosing interval.Keywords: antipsychotic, bipolar I disorder, long-acting injectable, schizophrenia

AbstractBipolar disorder is typically diagnosed in the teenage to early adulthood years. During this age, many individuals are students pursuing a college degree. Students developing the symptoms of bipolar disorder have a harder time navigating college and have significant difficulties transitioning back to school after psychiatric hospitalization, potentially influencing quality of life. Despite this, little attention has been given to the academic needs of hospitalized college students. This paper discusses the case of a 21-year-old female with a history of bipolar I disorder who was hospitalized for treatment of a manic episode. We discuss interventions to accommodate her educational needs during hospitalization to help minimize her academic load and ease her transition back to college. With this case study, we address the lack of well-established systems to reacclimate hospitalized college students and propose solutions to mitigate the hardships of transitioning from hospitalization back to the rigors of being a student. [ABSTRACT FROM AUTHOR]

Abstract Background The occurrence of psychotic features within mood episodes in patients with bipolar I disorder (BD I) has been associated in some studies with a more severe clinical and socio-professional profile. In contrast, other studies establishing the associations of psychotic features in BD I, and in particular of mood-congruent (MC) and mood-incongruent (MI) features, with clinical characteristics have yielded contradictory results. However, many pre-existing studies have been affected by serious methodological limitations. Using a sample of thoroughly assessed patients with BD I our aims were to: (1) establish the proportion of those with MI and MC features, and (2) compare BD I patients with and without psychotic features as well as those with MI to those with MC features on a wide array of socio-demographic and clinical characteristics including course, psychiatric comorbidity and treatment. Methods A sample of 162 treated patients with BD I (60.5% female, mean age = 41.4 (s.d: 10.2) years) was recruited within a large family study of mood disorders. Clinical, course and treatment characteristics relied on information elicited through direct diagnostic interviews, family history reports and medical records. Results (1) A total of 96 patients (59.3%) had experienced psychotic features over their lifetime. Among them, 44.8% revealed MI features at least once in their lives. (2) Patients with psychotic features were much less likely to be professionally active, revealed alcohol abuse more frequently and used health care, particularly inpatient treatment, more frequently than those without psychotic features. Within patients with psychotic symptoms, those with MI features showed more clinical severity in terms of a higher likelihood of reporting hallucinations, suicidal attempts and comorbid cannabis dependence. Conclusion Our data provide additional support for both the distinction between BD-I with and without psychotic features as well as the distinction between MI and MC psychotic features. The more severe course of patients with psychotic features, and particularly those with MI psychotic features, highlights the need for thorough psychopathological evaluations to assess the presence of these symptoms to install appropriate treatment.

Laura A Tan, Nileshkumar Gajipara, Lei Sun, Maria Bacolod, Ying Zhou, Mark Namchuk, Jacobi I Cunningham Alkermes, Inc, Waltham, MA, USACorrespondence: Laura A Tan, Alkermes, Inc, 852 Winter St, Waltham, MA, 02451, USA, Tel +1 781-609-6390, Email laura.tan@alkermes.comIntroduction: The atypical antipsychotic olanzapine is approved for the treatment of schizophrenia and bipolar I disorder; however, weight gain and metabolic dysregulation associated with olanzapine therapy have limited its clinical utility. In clinical studies, treatment with the combination of olanzapine and the opioid receptor antagonist samidorphan (OLZ/SAM) mitigated olanzapine-associated weight gain while providing antipsychotic efficacy similar to that of olanzapine. Although samidorphan is structurally similar to the opioid receptor antagonist naltrexone, the two differ in their pharmacokinetics and in vitro binding affinities to mu, delta, and kappa opioid receptors (MOR, DOR, and KOR, respectively). The objective of this series of nonclinical studies was to compare the in vivo binding profiles of samidorphan and naltrexone and their receptor occupancies at MOR, DOR, and KOR in rat brains.Methods: Male rats were injected with samidorphan or naltrexone to obtain total and unbound plasma and brain concentrations representing levels observed in humans at clinically relevant oral doses. Subsequently, samidorphan and naltrexone brain receptor occupancy at MOR, DOR, and KOR was measured using ultra-performance liquid chromatography and high-resolution accurate-mass mass spectrometry.Results: A dose-dependent increase in samidorphan occupancy was observed at MOR, DOR, and KOR (EC50: 5.1, 54.7, and 42.9 nM, respectively). Occupancy of naltrexone at MOR (EC50: 15.5 nM) and KOR was dose dependent; minimal DOR occupancy was detected. At the clinically relevant unbound brain concentration of 23.1 nM, samidorphan bound to MOR, DOR, and KOR with 93.2%, 36.1%, and 41.9% occupancy, respectively. At 33.5 nM, naltrexone bound to MOR and KOR with 79.4% and 9.4% occupancy, respectively, with no binding at DOR.Discussion: At clinically relevant concentrations, samidorphan occupied MOR, DOR, and KOR, whereas naltrexone occupied only MOR and KOR. The binding profile of samidorphan differs from that of naltrexone, with potential clinical implications.Keywords: ALKS 3831, bipolar I disorder, Lybalvi, olanzapine, opioid receptor, schizophrenia

Background: Mood disorder is one of the common causes, for which psychiatric consultations are sought. A better understanding of the factors that lead to repeated admissions, increased relapse rates, and concurrent substance dependence is necessary for the development of interventions that may reduce the likelihood of adverse effects in patient with bipolar I disorder. Aims and Objectives: The aims of this study were as follows: (1) To study the correlation between the reasons for relapse and substance use with various sociodemographic factors in patients having bipolar I disorders and (2) to find out the correlation between reasons for relapse, substance use, and severity of illness. Materials and Methods: This was a cross-sectional single interview study, in which 67 consecutive patients having bipolar I disorder and admitted in psychiatry ward were admitted on the basis of a pre-defined inclusion and exclusion criteria. The details about psychiatric, relapse-related symptoms, substance use-related symptoms, as well as other aspects of clinical profile were taken. Results: Out of 67 patients, 51 (76.1%) were male and 16 (23.8%) were female. Mean age of the participants was 30.43 years (S.D.=9.05). Sleep disturbance was seen in all patients (67) and was also the most common symptom. It was followed by psychomotor disturbances in 60 (89.5%) of the patients. Among 67 patients included in the study, substance use was seen among 28 (41.7%) of the patients. Substance use was significantly associated with age of the patients and occupation (P=0.03 each). The age group of more than 30 years (57.7%) had significantly higher substance use compared to those

Objective: Predicting disease relapse and early intervention could reduce symptom severity. We attempted to identify potential indicators that predict the duration to next admission for an acute affective episode in patients with bipolar I disorder. Methods: We mathematically defined the duration to next psychiatric admission and performed single-variate regressions using historical data of 101 patients with bipolar I disorder to screen for potential variables for further multivariate regressions. Results: Age of onset, total psychiatric admissions, length of lithium use, and carbamazepine use during the psychiatric hospitalization contributed to the next psychiatric admission duration positively. The all-in-one found that hyperlipidemia during the psychiatric hospitalization demonstrated a negative contribution to the duration to next psychiatric admission; the last duration to psychiatric admission, lithium and carbamazepine uses during the psychiatric hospitalization, and heart rate on the discharge day positively contributed to the duration to next admission. Conclusion: We identified essential variables that may predict the duration of bipolar I patients' next psychiatric admission. The correlation of a faster heartbeat and a normal lipid profile in delaying the next onset highlights the importance of managing these parameters when treating bipolar I disorder. [ABSTRACT FROM AUTHOR]

• Lumateperone 42 mg significantly improved MADRS total score in bipolar depression. • Six-weeks lumateperone 42 mg monotherapy significantly improved all 10 MADRS items. • Most MADRS items significantly improved in Bipolar I (9 items) and II (8) subgroups. • Lumateperone 42 mg significantly improved the MADRS anhedonia factor. • Lumateperone is effective to treat a broad range of bipolar depression symptoms. A recent Phase 3, randomized, double-blind, placebo-controlled study established that lumateperone 42-mg monotherapy significantly improved symptoms of depression in patients with bipolar depression. This manuscript reports prespecified secondary and post hoc efficacy analyses. Patients with bipolar I or bipolar II disorder experiencing a major depressive episode were randomized 1:1 to lumateperone 42 mg or placebo, administered orally once daily for 6 weeks. Prespecified analyses evaluated change from baseline to Day 43 in individual Montgomery-Åsberg Depression Rating Scale (MADRS) item scores in the modified intent-to-treat population (mITT) and bipolar I and bipolar II disorder subgroups. Post hoc analyses investigated the MADRS anhedonia factor and categorical shifts in MADRS item scores. In the mITT, there was significant improvement from baseline to Day 43 with lumateperone 42 mg compared with placebo for all 10 MADRS items; most MADRS items significantly improved in subgroups with bipolar I (9 items) and bipolar II disorder (8 items). A significantly higher proportion of patients receiving lumateperone compared with placebo shifted from baseline MADRS item score ≥4 to ≤2 at end of treatment in Reported Sadness, Reduced Sleep, Concentration Difficulties, Lassitude, Inability to Feel, and Pessimistic Thoughts. Lumateperone significantly improved the MADRS anhedonia factor from baseline to Day 43 compared with placebo in the mITT (effect size, −0.47) and subgroups with bipolar I (−0.36) and bipolar II disorder (−0.90). Lumateperone 42 mg treatment significantly improved depression symptoms compared with placebo, with consistent efficacy across a broad range of symptoms in people with bipolar I and bipolar II disorder. [ABSTRACT FROM AUTHOR]

Abstract Background Lamotrigine is approved as a maintenance therapy for bipolar I disorder in many countries, including China in 2021. This study evaluated the efficacy and safety of lamotrigine in controlling relapse and/or recurrence of mood episodes in Chinese patients with bipolar I disorder. Methods Patients aged ≥ 18 years with bipolar I disorder who met response criteria (Clinical Global Impression–Severity [CGI-S] score of ≤ 3 for ≥ 4 consecutive weeks) during treatment with lamotrigine in a 6–16 week open-label (OL) phase, and who were maintained for ≥ 1 week on lamotrigine 200 mg/day monotherapy, were randomised (1:1) to continue receiving lamotrigine 200 mg/day or switch to placebo in a 36-week randomised double-blind (RD) phase. The primary efficacy outcome measure was time from entry into the RD phase to intervention for relapse and/or recurrence of a mood episode (TIME). Post hoc analyses assessed the impact of OL baseline mood severity on TIME. Safety assessments were conducted throughout the study. Results Of 420 patients treated in the OL phase, 264 were randomised to receive lamotrigine (n = 131) or placebo (n = 133). Overall, 112 patients had an intervention for relapse and/or recurrence of a mood episode (lamotrigine, n = 50/130 [38.5%]; placebo, n = 62/133 [46.6%]), with no significant difference in TIME between groups (adjusted hazard ratio [95% confidence interval (CI)] 0.93 [0.64, 1.35]; p = 0.701). Post hoc analyses indicated a significant difference in TIME, favouring lamotrigine over placebo, for patients with baseline CGI-S score ≥ 4 (hazard ratio [95% CI] 0.52 [0.30, 0.89]; p = 0.018) and with baseline Hamilton Depression Rating Scale ≥ 18 or Young Mania Rating Scale ≥ 10 (0.44 [hazard ratio [95% CI] 0.25, 0.78]; p = 0.005). Lamotrigine was well tolerated with no new safety signals. Conclusions Lamotrigine was not significantly superior to placebo in preventing relapse and/or recurrence of mood episodes in this study of Chinese patients with bipolar I disorder but post hoc analyses suggested a therapeutic benefit in patients with moderate/severe mood symptoms at baseline. The discrepancy between these findings and the positive findings of the pivotal studies may be attributable to the symptom severity of the bipolar patients recruited, a high dropout rate, and the comparatively short duration of the RD phase rather than race/ethnicity differences. Clinical trial registration ClinicalTrial.gov Identifier NCT01602510; 21st May 2012; https://clinicaltrials.gov/ct2/show/NCT01602510 .

Background: There is a paucity of literature on the relationship between pre-existing mental health conditions and coronavirus disease-2019 (COVID-19) outcomes. The aim was to examine the association between pre-existing mental health diagnosis and COVID-19 outcomes (positive screen, hospitalization, mortality). Methods: Electronic medical record data for 30 976 adults tested for COVID-19 between March 2020 and 10th July 2020 was analyzed. COVID-19 outcomes included positive screen, hospitalization among screened positive, and mortality among screened positive and hospitalized. Primary independent variable, mental health disorders, was based on ICD-10 codes categorized as bipolar, internalizing, externalizing, and psychoses. Descriptive statistics were calculated, unadjusted and adjusted logistic regression and Cox proportional hazard models were used to investigate the relationship between each mental health disorder and COVID-19 outcomes. Results: Adults with externalizing (odds ratio (OR) 0.67, 95%CI 0.57–0.79) and internalizing disorders (OR 0.78, 95% CI 0.70–0.88) had lower odds of having a positive COVID-19 test in fully adjusted models. Adults with bipolar disorder had significantly higher odds of hospitalization in fully adjusted models (OR 4.27, 95% CI 2.06–8.86), and odds of hospitalization were significantly higher among those with externalizing disorders after adjusting for demographics (OR 1.71, 95% CI 1.23–2.38). Mortality was significantly higher in the fully adjusted model for patients with bipolar disorder (hazard ratio 2.67, 95% CI 1.07–6.67). Conclusions: Adults with mental health disorders, while less likely to test positive for COVID-19, were more likely to be hospitalized and to die in the hospital. Study results suggest the importance of developing interventions that incorporate elements designed to address smoking cessation, nutrition and physical activity counseling and other needs specific to this population to improve COVID-19 outcomes. [ABSTRACT FROM AUTHOR]

Background: The occurrence of psychotic features within mood episodes in patients with bipolar I disorder (BD I) has been associated in some studies with a more severe clinical and socio-professional profile. In contrast, other studies establishing the associations of psychotic features in BD I, and in particular of mood-congruent (MC) and mood-incongruent (MI) features, with clinical characteristics have yielded contradictory results. However, many pre-existing studies have been affected by serious methodological limitations. Using a sample of thoroughly assessed patients with BD I our aims were to: (1) establish the proportion of those with MI and MC features, and (2) compare BD I patients with and without psychotic features as well as those with MI to those with MC features on a wide array of socio-demographic and clinical characteristics including course, psychiatric comorbidity and treatment. Methods: A sample of 162 treated patients with BD I (60.5% female, mean age = 41.4 (s.d: 10.2) years) was recruited within a large family study of mood disorders. Clinical, course and treatment characteristics relied on information elicited through direct diagnostic interviews, family history reports and medical records. Results: (1) A total of 96 patients (59.3%) had experienced psychotic features over their lifetime. Among them, 44.8% revealed MI features at least once in their lives. (2) Patients with psychotic features were much less likely to be professionally active, revealed alcohol abuse more frequently and used health care, particularly inpatient treatment, more frequently than those without psychotic features. Within patients with psychotic symptoms, those with MI features showed more clinical severity in terms of a higher likelihood of reporting hallucinations, suicidal attempts and comorbid cannabis dependence. Conclusion: Our data provide additional support for both the distinction between BD-I with and without psychotic features as well as the distinction between MI and MC psychotic features. The more severe course of patients with psychotic features, and particularly those with MI psychotic features, highlights the need for thorough psychopathological evaluations to assess the presence of these symptoms to install appropriate treatment. [ABSTRACT FROM AUTHOR]

Purpose: The Purpose of this study was to investigate the role of reward sensitivity and cognitive insight in the recovery from type 1 bipolar disorder with the mediating role of working memory. Method: This cross-sectional study was conducted on a sample of 126 patients with type 1 bipolar disorder in the manic phase who were referred to psychiatric offices and were selected using available sampling method. Sample subjects were reassessed for mania severity 30 days after completing the questionnaires and initial assessment. Data were analyzed using structural equation modeling in Smartpls-3 software. Findings: The results showed that reward sensitivity has a significant and negative effect on recovery from disorder and working memory. Working memory also has a significant and positive effect on recovery from the disorder. Cognitive insight has no significant effect on working memory and recovery from the disorder. [ABSTRACT FROM AUTHOR]

Bhaskar Rege,1 Jonathan M Meyer2 1Pharmaceutical & Early Stage Clinical Development, Alkermes, Inc., Waltham, MA, USA; 2Department of Psychiatry, University of California, San Diego, CA, USACorrespondence: Bhaskar Rege, Alkermes, Inc., 852 Winter Street, Waltham, MA, 02451, USA, Email Bhaskar.Rege@alkermes.com

Abstract Background Long-acting injectable antipsychotics (LAIs) are an essential maintenance treatment option for individuals with schizophrenia or bipolar I disorder (BP-I). This report summarizes a roundtable discussion on the impact of COVID-19 on the mental healthcare landscape and use of LAIs for individuals with schizophrenia or BP-I. Methods Ten experts and stakeholders from diverse fields of healthcare participated in a roundtable discussion on the impact of the COVID-19 pandemic, treatment challenges, and gaps in healthcare for individuals with schizophrenia or BP-I, informed by a literature search. Results Individuals with schizophrenia or BP-I are at increased risk of COVID-19 infection and increased risk of mortality after COVID-19 diagnosis. LAI prescriptions decreased early on in the pandemic, driven by a decrease in face-to-face consultations. Mental healthcare services are adapting with increased use of telehealth and home-based treatment. Clinical workflows to provide consistent, in-person LAI services include screening for COVID-19 exposure and infection, minimizing contact, and ensuring mask-wearing by individuals and staff. The importance of continued in-person visits for LAIs needs to be discussed so that staff can share that information with patients, their caregivers, and families. A fully integrated, collaborative-care model is the most important aspect of care for individuals with schizophrenia or BP-I during and after the COVID-19 pandemic. Conclusions The COVID-19 pandemic has highlighted the importance of a fully integrated collaborative-care model to ensure regular, routine healthcare contact and access to prescribed treatments and services for individuals with schizophrenia and BP-I.

Background: Misdiagnosis of bipolar I disorder (BP-I) as major depressive disorder (MDD) is common. This study evaluated healthcare resource utilization (HRU) and costs among BP-I patients who were initially misdiagnosed with MDD (misdiagnosed BP-I cohort) versus patients diagnosed with BP-I without a known prior MDD diagnosis (BP-I only cohort).Methods: Data from IBM® MarketScan® Research Databases were used. The index date was the first MDD diagnosis for misdiagnosed patients or first BP-I diagnosis for BP-I only patients. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. All-cause and mental health (MH)-related HRU and costs were compared between weighted cohorts using rate ratios (RRs) and mean cost differences, respectively. Outcomes were reported per patient-year (PPY). Confidence intervals and P-values were calculated using non-parametric bootstrap procedures.Results: Overall, 14,729 misdiagnosed BP-I and 16,072 BP-I only patients met criteria. Baseline characteristics were balanced across weighted cohorts. Misdiagnosed BP-I patients had significantly higher rates of hospitalizations, emergency room visits, and outpatient visits than BP-I only patients during follow-up (all-cause RRs: 1.94, 1.33, and 1.38, respectively, all P < .001; MH-related RRs: 2.19, 1.77, and 1.77, respectively, all P < .001). Similarly, misdiagnosed BP-I patients incurred significantly higher total healthcare costs PPY over follow-up (all-cause: $21,202 vs $14,661, cost difference = $6541; MH-related: $12,901 vs $6749, cost difference = $6152; both P < .001). Cost differences were even higher during the first year (all-cause = $7146; MH-related = $6619; both P < .001).Limitations: Claims database (e.g., coding inaccuracies); generalizability to uninsured patients.Conclusions: The prompt and correct diagnosis of BP-I may significantly reduce HRU and costs. [ABSTRACT FROM AUTHOR]

Objective: To identify clinical and central features that differentiate ADHD youth with and without familial risk for bipolar I disorder (BD). Methods: Psychostimulant-free ADHD youth (10–18 years) with and without a first-degree relative with BD and healthy controls were enrolled. Bilateral ventrolateral prefrontal cortex (VLPFC) proton magnetic resonance spectroscopy (1H MRS) scans and a range of symptom ratings were performed. Results: A total of n = 145 youth were enrolled. ADHD youth with a family history of BD exhibited greater manic and depressive symptom severity, ADHD hyperactivity/impulsive symptom severity, and higher parent-reported ratings of dysregulation compared with ADHD youth without a BD family history. Although VLPFC metabolite levels did not differ across groups, choline levels in the left VLPFC correlated with different symptom ratings. Conclusion: Symptom profiles including more severe mood and externalizing symptoms, but not VLPFC neurochemistry, differentiate psychostimulant-free ADHD youth with and without a family history of BD. [ABSTRACT FROM AUTHOR]

Background: Despite the growing evidence of cognitive impairments in bipolar disorder (BD), little work has evaluated cognitive performances utilizing the latest version of the Wechsler Intelligence Scale-IV (WAIS-IV), which is one of the most widely used neurocognitive assessments in clinical settings. Furthermore, clinical characteristics or demographic features that negatively affect the cognitive functioning of BD were not systematically compared or evaluated. Accordingly, the present study aimed to examine the cognitive profile of bipolar I disorder (BD-I) patients and associated risk factors. Methods: Participants included 45 patients, diagnosed with BD-I, current or most recent episode manic, and matching 46 healthy controls (HC). Cognitive performance was evaluated via WAIS-IV, and clinical characteristics of the BD-I group were examined via multiple self- and clinician-report questionnaires. Results: Multivariate analysis of covariance (MANCOVA) results indicated that the BD-I group demonstrated significantly poorer performance compared to the HC group in subtests and indexes that reflect working memory and processing speed abilities. Redundancy analysis revealed that overall symptom severity, manic symptom severity, and anxiety were significant predictors of cognitive performance in BD-I, while age of onset, past mood disorder history, depression severity, and impulsiveness showed comparatively smaller predictive values. Conclusion: The current study suggests cognitive deterioration in the cognitive proficiency area while generalized ability, including verbal comprehension and most of the perceptual reasoning skills, remain intact in BD-I. The identified risk factors of cognitive performance provide specific clinical recommendations for intervention and clinical decision-making. [ABSTRACT FROM AUTHOR]

Objective: To describe the longer-term effectiveness, safety, and tolerability of open-label ziprasidone in children and adolescents with bipolar I disorder (BD-I). Methods: A subset of 23 participants aged 10-17 years, who were previously treated in a multi-site, 4-week randomized controlled trial received open-label ziprasidone (20-80 mg twice a day) for up to 26 weeks. Results: The most common adverse events (AEs) were fatigue (30%), somnolence (17%), and nausea (13%). Effects on weight, body mass index, and metabolic parameters (glucose, cholesterol, and triglycerides) were minimal. No participant had a Fridericia-corrected QT interval ≥ 460 msec or a change from baseline of ≥60 msec, and there were no cardiac-related AEs. Both the participants who continued ziprasidone and those who initiated ziprasidone in the open-label extension showed improvements in their symptoms of mania. Conclusions: The overall findings of the study are consistent with the accumulating knowledge on the safety profile of ziprasidone in the acute and long-term treatment of children and adolescents with BD-I, in the midst of a manic episode. ClinicalTrial.gov ID: NCT03768726. [ABSTRACT FROM AUTHOR]

Objective: Cariprazine is a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist approved to treat adults with schizophrenia and manic/mixed or depressive episodes associated with bipolar I disorder. This sequential-cohort, dose-escalation study was the first to evaluate the pharmacokinetic, safety, and tolerability profile of cariprazine and its two major active metabolites, desmethyl-cariprazine (DCAR) and didesmethyl-cariprazine (DDCAR), in pediatric patients with schizophrenia or bipolar I disorder. Methods: This phase I open-label study enrolled patients with schizophrenia (13-17 years of age) or bipolar I disorder (10-17 years of age). Patients met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for schizophrenia or bipolar I disorder and had Positive and Negative Syndrome Scale (PANSS) total scores ≥70 or Young Mania Rating Scale (YMRS) total scores ≥20. Patients were assigned to one of four treatment groups to receive 6 weeks of cariprazine treatment through slow titration to 1.5, 3, or 4.5 mg/d or fast titration to 4.5 mg/d. Pharmacokinetics, adverse events (AEs), and various safety parameters were analyzed. Efficacy was evaluated as an exploratory outcome. Results: A total of 50 participants were enrolled. Based on mean trough levels, steady state appeared to be reached within 1-2 weeks for cariprazine and DCAR and within 4-5 weeks for DDCAR. Systemic exposure of cariprazine, DCAR, and DDCAR generally increased approximately in proportion to the increases in dose from 1.5 to 4.5 mg/d. The most frequent treatment-related, treatment-emergent AEs included sedation, parkinsonism, tremor, dystonia, and blurred vision. Improvements from baseline on the PANSS and YMRS were observed throughout treatment. Conclusion: In this first investigation of cariprazine in a pediatric population with schizophrenia or bipolar disorder, pharmacokinetic parameters were consistent with those observed in adults. Cariprazine appeared to be safe and tolerable in children and adolescents. [ABSTRACT FROM AUTHOR]

Background: Mood disorder is one of the common causes, for which psychiatric consultations are sought. A better understanding of the factors that lead to repeated admissions, increased relapse rates, and concurrent substance dependence is necessary for the development of interventions that may reduce the likelihood of adverse effects in patient with bipolar I disorder. Aims and Objectives: The aims of this study were as follows: (1) To study the correlation between the reasons for relapse and substance use with various sociodemographic factors in patients having bipolar I disorders and (2) to find out the correlation between reasons for relapse, substance use, and severity of illness. Materials and Methods: This was a cross-sectional single interview study, in which 67 consecutive patients having bipolar I disorder and admitted in psychiatry ward were admitted on the basis of a pre-defined inclusion and exclusion criteria. The details about psychiatric, relapse-related symptoms, substance use-related symptoms, as well as other aspects of clinical profile were taken. Results: Out of 67 patients, 51 (76.1%) were male and 16 (23.8%) were female. Mean age of the participants was 30.43 years (S.D.=9.05). Sleep disturbance was seen in all patients (67) and was also the most common symptom. It was followed by psychomotor disturbances in 60 (89.5%) of the patients. Among 67 patients included in the study, substance use was seen among 28 (41.7%) of the patients. Substance use was significantly associated with age of the patients and occupation (P=0.03 each). The age group of more than 30 years (57.7%) had significantly higher substance use compared to those <30 years (31.7%). Conclusion: Concurrent substance use is associated with increased risk of relapse and readmissions in cases of patients with bipolar I disorders. A thorough history is necessary to rule out substance use in these cases. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to explore the long‐term efficacy of a psychoeducational family intervention (PFI) in bipolar I disorder at one and five years post‐intervention in terms of improvement of: (1) patients' symptoms and global functioning and (2) relatives' objective and subjective burden and coping strategies. Methods: This is a multicentre, real‐world, controlled, outpatient trial. Recruited patients and key‐relatives were consecutively allocated to the experimental intervention or treatment as usual. Patients were assessed at baseline, and after one and five years. Results: One hundred and thirty‐seventh number families have been recruited; 70 have been allocated to the experimental intervention, and 67 have been allocated to the control group. We observed an increasing positive effect of the PFI on patients' clinical status, global functioning and objective and subjective burden after one year. We also found a reduction in the levels of relatives' objective and subjective burden and a significant improvement in the levels of perceived professional support and of coping strategies. The efficacy of PFI on patients' clinical status was maintained at five years from the end of the intervention, in terms of relapses, hospitalizations and suicide attempts. Conclusions: The study showed that the provision of PFI in real‐world settings is associated with a significant improvement of patients' and relatives' mental health and psychosocial functioning in the long term. We found that the clinical efficacy of the intervention, in terms of reduction of patients' relapses, hospitalization and suicide attempts, persists after 5 years. It is advisable that PFI is provided to patients with BD I in routine practice. [ABSTRACT FROM AUTHOR]

The purpose of this summary is to explain key findings from a study that included people with bipolar I disorder, as described in two separate articles (see the 'Further Information' section for more details). The study compared a new formulation of aripiprazole, given as an injection once every 2 months, with a once‑monthly injection of aripiprazole., (© The Author(s), 2024.)

Purpose: This study quantified the burdens of bipolar I disorder (BP-I) by examining patient characteristics, health-related quality of life (HRQoL), health care resource utilization (HCRU), and costs of patients with versus without BP-I. Additionally, these outcomes were assessed across BP-I severity levels., Methods: A retrospective, cross-sectional analysis of the 2020 National Health and Wellness Survey was conducted. Adults who self-reported a physician diagnosis of BP-I were assigned to the BP-I cohort, with severity-specific subgroups (mild, moderate, severe) created for analysis. A separate cohort of participants without BP-I or MDD was used for comparison. Exclusion criteria included a schizophrenia diagnosis. Bivariate analyses compared demographic and socioeconomic characteristics between cohorts. HRQoL (Short Form-36v2 Health Survey [SF36v2] mental and physical component scores, EuroQol Five-Dimension Visual Analogue Scale [EQ-5D VAS]), HCRU (health care provider visits, emergency department visits, hospitalizations), and annualized costs (direct and indirect) were evaluated for participants with versus without BP-I as well as across BP-I severity subgroups using multivariate analyses adjusted for key baseline differences. Because BP-I is often misdiagnosed as MDD, outcomes were evaluated in a subgroup of participants with MDD who according to the Mood Disorder Questionnaire screened as having probable BP-I (ie, potentially misdiagnosed BP-I) and were compared with the BP-I severity subgroups., Findings: Cohorts included 818 participants with BP-I (mild = 336, moderate = 285, severe = 197) and 53,021 participants without BP-I. Participants with BP-I reported significantly lower HRQoL scores on the SF-36v2 and EQ-5D VAS (all measures, P < 0.001), and increasing BP-I severity was predictive of declining HRQoL. Participants with BP-I had significantly greater HCRU (all measures, P < 0.05) than participants without BP-I and increasing BP-I severity was associated with greater HCRU versus the mild BP-I cohort (all measures, P < 0.05). Participants with BP-I incurred significantly greater total direct (P < 0.01) and indirect (P < 0.001) costs versus participants without BP-I. Direct costs were incrementally higher across BP-I severity, while indirect costs were high across all groups but did not differ significantly. Participants with potentially misdiagnosed BP-I (n = 302) had similar HRQoL to those with mild-to-moderate BP-I and similar HCRU and direct costs to those with mild BP-I., Implications: These results demonstrate the substantial clinical and economic burdens associated with BP-I, and these negative impacts generally increase with BP-I severity. The study also suggests that despite not having the diagnosis of BP-I, burdens of potentially misdiagnosed patients are similar to those with mild-to-moderate BP-I. Together, these results reveal substantial and diverse unmet needs among adults with BP-I., Competing Interests: Declaration of competing interest L. Culpepper has served as an advisor or consultant for AbbVie Pharmaceuticals, Allergan Pharmaceuticals, Eisai Pharmaceuticals, Takeda, and Supernus Pharmaceuticals; owns stock in M-3 Information, LLC; and has received royalties from UpToDate and Oxford University Press and receives payment from Physicians Postgraduate Press as Editor in Chief of the Primary Care Companion for CNS Diseases. A. Martin is an employee of Cerner Enviza, which was funded by AbbVie to perform the analysis. A. Harrington was an employee of AbbVie at the time of the study and may hold stock. S.W. Wade is a partner in Wade Outcomes Research and Consulting and a consultant for AbbVie. M. Parikh is an employee of AbbVie and may hold stock, (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Hereditary angioedema (HAE) is a rare autosomal dominant disorder caused by the deficiency or dysfunction of C1 esterase inhibitors. We present a case of a female in her 50s with HAE and bipolar affective disorder (BPAD). She has experienced severe depressive and manic episodes with significant disruption to her life. She has also had potentially life-threatening episodes of recurrent angioedema with severe facial and body swelling and post-pharyngeal symptoms.She presented to us with a depressive episode with suicidal ideation. Her angioedema was flared by both psychological stressors and psychotropic medications. Choosing the correct mood stabiliser without triggering angioedema was a major challenge in her treatment. Also, psychosocial interventions and frequent liaison with her immunology team were necessary to provide her with optimum care in the community. Here, we discuss the challenges we faced and how we overcame them in managing this rare presentation of coexisting BPAD and HAE., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract Background Major contributors to the global burden of bipolar disorders (BD) are the early age at onset (AAO) and the co-occurrence of non-mood disorders before and after the onset of BD. Using data from two independent cohorts from Europe and the USA, we investigated whether the trajectories of BD-I onset and patterns of psychiatric comorbidities differed in (a) individuals with or without a family history (FH) of BD, or (b) probands and parents who both had BD-I. Methods First, we estimated cumulative probabilities and AAO of comorbid mental disorders in familial and non-familial cases of BD-I (Europe, n = 573), and sex-matched proband-parent pairs of BD-I cases (USA, n = 194). Then we used time to onset analyses to compare overall AAO of BD-I and AAO according to onset polarity. Next, we examined associations between AAO and polarity of onset of BD-I according to individual experiences of comorbidities. This included analysis of the density of antecedent events (defined as the number of antecedent comorbidities per year of exposure to mental illness per individual) and time trend analysis of trajectory paths plotted for the subgroups included in each cohort (using R2 goodness of fit analysis). Results Earlier AAO of BD-I was found in FH versus non-FH cases (log rank test = 7.63; p = 0.006) and in probands versus parents with BD-I (log rank test = 15.31; p = 0.001). In the European cohort, AAO of BD-I was significantly associated with factors such as: FH of BD (hazard ratio [HR]: 0.60), earlier AAO of first non-mood disorder (HR: 0.93) and greater number of comorbidities (HR: 0.74). In the USA cohort, probands with BD-I had an earlier AAO for depressive and manic episodes and AAO was also associated with e.g., number of comorbidities (HR: 0.65) and year of birth (HR: 2.44). Trajectory path analysis indicated significant differences in density of antecedents between subgroups within each cohort. However, the time trend R2 analysis was significantly different for the European cohort only. Conclusions Estimating density of antecedent events and comparing trajectory plots for different BD subgroups are informative adjuncts to established statistical approaches and may offer additional insights that enhance understanding of the evolution of BD-I.

Background: Lamotrigine is approved as a maintenance therapy for bipolar I disorder in many countries, including China in 2021. This study evaluated the efficacy and safety of lamotrigine in controlling relapse and/or recurrence of mood episodes in Chinese patients with bipolar I disorder. Methods: Patients aged ≥ 18 years with bipolar I disorder who met response criteria (Clinical Global Impression–Severity [CGI-S] score of ≤ 3 for ≥ 4 consecutive weeks) during treatment with lamotrigine in a 6–16 week open-label (OL) phase, and who were maintained for ≥ 1 week on lamotrigine 200 mg/day monotherapy, were randomised (1:1) to continue receiving lamotrigine 200 mg/day or switch to placebo in a 36-week randomised double-blind (RD) phase. The primary efficacy outcome measure was time from entry into the RD phase to intervention for relapse and/or recurrence of a mood episode (TIME). Post hoc analyses assessed the impact of OL baseline mood severity on TIME. Safety assessments were conducted throughout the study. Results: Of 420 patients treated in the OL phase, 264 were randomised to receive lamotrigine (n = 131) or placebo (n = 133). Overall, 112 patients had an intervention for relapse and/or recurrence of a mood episode (lamotrigine, n = 50/130 [38.5%]; placebo, n = 62/133 [46.6%]), with no significant difference in TIME between groups (adjusted hazard ratio [95% confidence interval (CI)] 0.93 [0.64, 1.35]; p = 0.701). Post hoc analyses indicated a significant difference in TIME, favouring lamotrigine over placebo, for patients with baseline CGI-S score ≥ 4 (hazard ratio [95% CI] 0.52 [0.30, 0.89]; p = 0.018) and with baseline Hamilton Depression Rating Scale ≥ 18 or Young Mania Rating Scale ≥ 10 (0.44 [hazard ratio [95% CI] 0.25, 0.78]; p = 0.005). Lamotrigine was well tolerated with no new safety signals. Conclusions: Lamotrigine was not significantly superior to placebo in preventing relapse and/or recurrence of mood episodes in this study of Chinese patients with bipolar I disorder but post hoc analyses suggested a therapeutic benefit in patients with moderate/severe mood symptoms at baseline. The discrepancy between these findings and the positive findings of the pivotal studies may be attributable to the symptom severity of the bipolar patients recruited, a high dropout rate, and the comparatively short duration of the RD phase rather than race/ethnicity differences. Clinical trial registration ClinicalTrial.gov Identifier NCT01602510; 21st May 2012; https://clinicaltrials.gov/ct2/show/NCT01602510. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation and brain structural abnormalities are found in bipolar disorder (BD). Elevated levels of cytokines and chemokines have been detected in the serum and cerebrospinal fluid of patients with BD. This study investigated the association between peripheral inflammatory markers and brain subregion volumes in BD patients. Methods: Euthymic patients with bipolar I disorder (BD-I) aged 20–45 years underwent whole-brain magnetic resonance imaging. Plasma levels of monocyte chemoattractant protein-1 (MCP-1), chitinase-3-like protein 1 (also known as YKL-40), fractalkine (FKN), soluble tumour necrosis factor receptor-1 (sTNF-R1), interleukin-1β, and transforming growth factor-β1 were measured on the day of neuroimaging. Clinical data were obtained from medical records and interviewing patients and reliable others. Results: We recruited 31 patients with a mean age of 29.5 years. In multivariate regression analysis, plasma level YKL-40, a chemokine, was the most common inflammatory marker among these measurements displaying significantly negative association with the volume of various brain subareas across the frontal, temporal, and parietal lobes. Higher YKL-40 and sTNF-R1 levels were both significantly associated with lower volumes of the left anterior cingulum, left frontal lobe, right superior temporal gyrus, and supramarginal gyrus. A greater number of total lifetime mood episodes were also associated with smaller volumes of the right caudate nucleus and bilateral frontal lobes. Conclusions: The volume of brain regions known to be relevant to BD-I may be diminished in relation to higher plasma level of YKL-40, sTNF-R1, and more lifetime mood episodes. Macrophage and macrophage-like cells may be involved in brain volume reduction among BD-I patients. [ABSTRACT FROM AUTHOR]

Objective: Bipolar I disorder (BD-I) is a type of bipolar spectrum disorder characterized by manic or mixed episodes. Detecting microRNA regulations as epigenetic actors in BD-I is important to elucidate the pathogenesis of the disease and reveal the potential of microRNAs (miRNAs) as biomarkers. Methods: We evaluated the expression profile of six candidate miRNAs (hsa-miR-145-5p, hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p, and hsa-miR-4725) in patients with BD-I and in healthy controls (aged 11-50 years). We also determined the potential target genes of these miRNAs through in silico analysis. The diagnostic values of the miRNAs were calculated through receiver operating characteristic curve analysis. Results: Four miRNAs were upregulated (hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p) and hsa-miR-145-5p was downregulated in patients (p < 0.001). The target gene analyses showed that hsa-miR-145-5p specifically targets the dopamine decarboxylase (DDC) gene. The area under the curve of hsa-miR-145-5p was 0.987. Conclusion: Differential expression of five miRNAs in peripheral blood may be associated with the pathogenesis of BD-I, and hsa-miR-145-5p has potential as a BD-I biomarker. This miRNA can be used in dopamine-serotonin regulation and dose adjustment in drug therapy via the DDC gene. [ABSTRACT FROM AUTHOR]

Introduction Bipolar disorder (BD) is associated to high personal and social burden, impaired social functioning and high levels of disability. Recent studies have showed that relapse rates are significantly reduced in those patients whose families receive psychoeducational interventions. Even though most of available evidences are related to the short-term efficacy of psychoeducational family interventions (PFI). No evidence is available on medium and long-term efficacy. Objectives This study aims to assess the efficacy after one and five years of PFI in BD in terms of: 1) improvement of patients’ symptoms and global functioning; 2) improvement of relatives’ objective and subjective burden and coping strategies. Methods A multicenter, controlled, outpatient trial has been conducted in BD patients and their key relatives, recruited in 11 Italian mental health centers. Patient’s clinical status, social and personal functioning, burden of illness, and relative’s burden and coping strategies were assessed with specific instruments at baseline, after 1 year and after 5 years. Results 137 families were recruited, 70 allocated to the experimental intervention. After one year, an increasing positive effect on patients’ clinical status, global functioning and objective and subjective burden was found. Moreover, were observed a reduced number of relapses and of hospitalizations after five years, compared to the control group. A reduction in the levels of family burden and an improvement of their coping strategies were also observed. Conclusions Positive effects of the experimental intervention persist over the mid and long-term period. PFI should be provided in mental health centres to patients with BD and their relatives. Disclosure No significant relationships.

Objective: Bipolar I disorder (BD-I) is a type of bipolar spectrum disorder characterized by manic or mixed episodes. Detecting microRNA regulations as epigenetic actors in BD-I is important to elucidate the pathogenesis of the disease and reveal the potential of microRNAs (miRNAs) as biomarkers. Methods: We evaluated the expression profile of six candidate miRNAs (hsa-miR-145-5p, hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p, and hsa-miR-4725) in patients with BD-I and in healthy controls (aged 11-50 years). We also determined the potential target genes of these miRNAs through in silico analysis. The diagnostic values of the miRNAs were calculated through receiver operating characteristic curve analysis. Results: Four miRNAs were upregulated (hsa-miR-376a-3p, hsa-miR-3680-5p, hsa-miR-4253-5p, hsa-miR-4482-3p) and hsa-miR-145-5p was downregulated in patients (p < 0.001). The target gene analyses showed that hsa-miR-145-5p specifically targets the dopamine decarboxylase (DDC) gene. The area under the curve of hsa-miR-145-5p was 0.987. Conclusion: Differential expression of five miRNAs in peripheral blood may be associated with the pathogenesis of BD-I, and hsa-miR-145-5p has potential as a BD-I biomarker. This miRNA can be used in dopamine-serotonin regulation and dose adjustment in drug therapy via the DDC gene.

Abstract Background This study aimed to identify the clinical characteristic of prodromal symptoms in Chinese patients with bipolar disorder (BD), prior to the first affective episode. It further aimed to characterize the prodromal traits between bipolar disorder type I (BD-I) and type II (BD-II). Methods 120 individuals with BD-I (n = 92) and BD- II (n = 28) were recruited to the study. Semi-structured interviews were then administered to evaluate prodromal symptoms in patients, within 3 years of BD onset, by using the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R). Results In the prodromal phase of the first depressive episode, patients with BD-II experienced more prodromal symptoms (p = 0.0028) compared to BD-I. Additionally, more frequent predictors were reported in patients with BD-II than BD-I including educational and occupational dysfunction (p = 0.0023), social isolation (p

This document is a letter to the editor of the American Journal of Psychiatry discussing the role of atypical antipsychotics in weight gain during bipolar disorder treatment. The author suggests that the paper on weight gain in bipolar patients should have mentioned the role of atypical antipsychotics, which are known to cause weight gain. They also mention the option of using non-atypical mood stabilizers that are less likely to cause weight gain. The authors of the original study acknowledge the feedback and agree that the usage of atypical antipsychotics could contribute to the observed trends in weight gain. They emphasize the importance of providing training on the use of lithium, a mood stabilizer that is less prone to cause weight gain. [Extracted from the article]

• There is a strong comorbidity between PTSD and Bipolar Disorder. • Veterans with Bipolar do not typically receive adequate care for PTSD. • CPT was effective for a female veteran with comorbid Bipolar I and PTSD. • CPT helped increase motivation for medication compliance. There is a strong comorbidity between Posttraumatic Stress Disorder (PTSD) and bipolar disorder. Unfortunately, there is lack of dissemination regarding modifications of evidence-based therapies for PTSD among individuals with comorbid bipolar I disorder. Cognitive Processing Therapy (CPT) is one such evidence-based, gold-standard psychotherapy for PTSD that can be modified to address a wide-scope of symptoms either directly, or indirectly, related to traumatic events. This case study describes a female veteran with PTSD and comorbid bipolar I disorder who received CPT. Modifications of CPT were implemented during the later phase of therapy and were related to the management of hypomanic symptoms, medication adherence, and anxiety related to her self-trust and control regarding future manic episodes. The patient exhibited few symptoms of PTSD or depression at a 3-month follow-up and reported that CPT simultaneously helped her manage symptoms of bipolar disorder. A description the patient, necessary modifications, and strategies to address comorbid PTSD and bipolar I disorder are provided. [ABSTRACT FROM AUTHOR]

Hypersexuality is related to functions of personality and emotion and is a salient symptom of bipolar I disorder especially during manic episode. However, it is uncertain whether bipolar I disorder with (BW) and without (BO) hypersexuality exhibits different cerebral activations under external emotion stimuli. In 54 healthy volunteers, 27 BW and 26 BO patients, we administered the visual oddball event-related potentials (ERPs) under external emotions of Disgust, Erotica, Fear, Happiness, Neutral, and Sadness. Participants' concurrent states of mania, hypomania, and depression were also evaluated. The N1 latencies under Erotica and Happiness were prolonged, and the P3b amplitudes under Fear and Sadness were decreased in BW; the P3b amplitudes under Fear were increased in BO. The parietal, frontal, and occipital activations were found in BW, and the frontal and temporal activations in BO under different external emotional stimuli, respectively. Some ERP components were correlated with the concurrent affective states in three groups of participants. The primary perception under Erotica and Happiness, and voluntary attention under Fear and Sadness, were impaired in BW, while the voluntary attention under Fear was impaired in BO. Our study indicates different patterns of visual attentional deficits under different external emotions in BW and BO. [ABSTRACT FROM AUTHOR]