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Aim: Bipolar disorder (BD) and borderline personality disorder (BPD) are both serious psychiatric conditions that elevate the risk for harmful outcomes. Although these conditions represent distinct diagnostic entities, existing research suggests that approximately 20% of individuals with BD meet the criteria for comorbid BPD. Individuals with comorbid BD/BPD appear to have a markedly more severe and phenomenologically distinct clinical course when compared with those with BD alone. However, treatments have generally not been tested in this specific population, and currently, no formal treatment guidelines exist for this subgroup of patients. Method: In the current paper, we review the epidemiological and descriptive research characterizing those with comorbid BD/BPD and discuss the impact of this comorbidity on psychosocial treatment. We also review current findings on evidence‐based treatments for BD and BPD that show promise in treating those with comorbid BD/BPD. Results: In our review of the literature, we highlight the importance of recognizing this comorbidity and discuss avenues for developing and integrating evidence‐based treatment approaches for this understudied clinical population. Conclusions: Although formal trials of interventions targeted to comorbid BD/BPD are limited, there is promising evidence regarding the possibility of using or integrating existing evidence‐based approaches for this population. There are also several areas of clinical practice improvement and future research directions that stem from this literature. [ABSTRACT FROM AUTHOR]

Background: Childhood trauma affects the course of mood disorders. Researchers are now considering childhood trauma as an influential factor in the treatment of mood disorders. However, the role of childhood trauma in the treatment of bipolar disorder remains understudied. Methods: The effect of childhood trauma on treatment outcomes was evaluated among participants randomised to treatment with lithium or quetiapine in the Clinical and Health Outcomes Initiatives in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE) study by clinician assessment. Mixed effects linear regression models were used to analyse rates of improvement in symptom severity (assessed with the Bipolar Inventory of Symptoms Scale and the Clinical Global Impression Scale for Bipolar Disorder) and functional impairment (assessed with the Longitudinal Interval Follow‐up Evaluation‐Range of Impaired Functioning Tool). Results: A history of any childhood trauma was reported by 52.7% of the sample (N = 476). Although participants with a history of any childhood trauma presented with greater symptom severity and functional impairment at most study visits, participants with and without a history of any childhood trauma showed similar rates of improvement in symptom severity and functional impairment over the 24 weeks of treatment. Conclusion: This is the first study to explore the association between childhood trauma and treatment outcomes during treatment with lithium or quetiapine in the context of a randomised trial. In Bipolar CHOICE, a history of childhood trauma did not inhibit improvement in symptom severity or functional impairment. Nevertheless, these findings need replication across different settings. [ABSTRACT FROM AUTHOR]

Objectives: The association of bipolar disorder with early and excessive cardiovascular disease was identified over a century ago. Nonetheless, the vascular‐bipolar link remains underrecognized, particularly with regard to how this link can contribute to our understanding of pathogenesis and treatment. Methods: An international group of experts completed a selective review of the literature, distilling core themes, identifying limitations and gaps in the literature, and highlighting future directions to bridge these gaps. Results: The association between bipolar disorder and vascular disease is large in magnitude, consistent across studies, and independent of confounding variables where assessed. The vascular‐bipolar link is multifactorial and is difficult to study given the latency between the onset of bipolar disorder, often in adolescence or early adulthood, and subsequent vascular disease, which usually occurs decades later. As a result, studies have often focused on risk factors for vascular disease or intermediate phenotypes, such as structural and functional vascular imaging measures. There is interest in identifying the most relevant mediators of this relationship, including lifestyle (eg, smoking, diet, exercise), medications, and systemic biological mediators (eg, inflammation). Nonetheless, there is a paucity of treatment studies that deliberately engage these mediators, and thus far no treatment studies have focused on engaging vascular imaging targets. Conclusions: Further research focused on the vascular‐bipolar link holds promise for gleaning insights regarding the underlying causes of bipolar disorder, identifying novel treatment approaches, and mitigating disparities in cardiovascular outcomes for people with bipolar disorder. [ABSTRACT FROM AUTHOR]

Objectives: Lithium and quetiapine are known to be effective treatments for bipolar disorder. However, little information is available to inform prediction of response to these medications. Machine‐learning methods can identify predictors of response by examining variables simultaneously. Further evaluation of models on a test sample can estimate how well these models would generalize to other samples. Methods: Data (N = 482) were drawn from a randomized clinical trial of outpatients with bipolar I or II disorder who received adjunctive personalized treatment plus either lithium or quetiapine. Elastic net regularization (ENR) was used to generate models for lithium and quetiapine; these models were evaluated on a test set. Results: Predictions from the lithium model explained 17.4% of the variance in actual observed scores of patients who received lithium in the test set, while predictions from the quetiapine model explained 32.1% of the variance of patients that received quetiapine. Of the baseline variables selected, those with the largest parameter estimates were: severity of mania; attention‐deficit/hyperactivity disorder (ADHD) comorbidity; nonsuicidal self‐injurious behavior; employment; and comorbidity with each of two anxiety disorders (social phobia/society anxiety and agoraphobia). Predictive accuracy of the ENR model outperformed the simple and basic theoretical models. Conclusion: ENR is an effective approach for building optimal and generalizable models. Variables identified through this methodology can inform future research on predictors of response to lithium and quetiapine, as well as future modeling efforts of treatment choice in bipolar disorder. [ABSTRACT FROM AUTHOR]

Introduction: Depressive episodes are often prevalent among patients with bipolar disorder, but little is known regarding the differential patterns of development over time. We aimed to determine and characterize trajectories of depressive symptoms among adults with bipolar disorder during 6 months of systematic treatment. Methods: The pragmatic clinical trial, Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (CHOICE), randomized 482 outpatients with bipolar disorder to lithium or quetiapine. Depressive symptoms were rated at up to 9 visits using the Montgomery‐Asberg Depression Rating Scale (MADRS). Growth mixture modeling was utilized to identify trajectories and multinomial regression analysis estimated associations with potential predictors. Results: Four distinct trajectories of depressive symptoms were identified. The responding class (60.3%) with a rapid reduction and subsequent low level; the partial‐responding class (18.4%) with an initial reduction followed by an increase during the remaining weeks; the fluctuating class (11.6%) with a fluctuation in depressive symptoms; and the non‐responding class (9.7%) with sustained moderate‐severe depressive symptoms. Bipolar type I predicted membership of the non‐responding class and randomization to quetiapine predicted membership of either the responding or the non‐responding class. Conclusion: Approximately 30% experienced a partial or fluctuating course, and almost 10% had a chronic course with moderate‐severe depression during 6 months. Patients diagnosed with bipolar type 1 had higher risk of being categorized into a class with a worse outcome. While no differences in average overall outcomes occurred between the lithium and quetiapine groups, trajectory analysis revealed that the lithium group had more variable courses. [ABSTRACT FROM AUTHOR]

Objectives: Bipolar disorders (BD) are characterized by emotion and cognitive dysregulation. Mapping deficits in the neurocircuitry of cognitive‐affective regulation allows for potential identification of intervention targets. This study used functional MRI data in BD patients and healthy controls during performance on a task requiring cognitive and inhibitory control superimposed on affective images, assessing cognitive and affective interference. Methods: Functional MRI data were collected from 39 BD patients and 36 healthy controls during performance on the Multi‐Source Interference Task overlaid on images from the International Affective Picture System (MSIT‐IAPS). Analyses examined patterns of activation in a priori regions implicated in cognitive and emotional processing. Functional connectivity to the anterior insula during task performance was also examined, given this region's role in emotion‐cognition integration. Results: BD patients showed significantly less activation during cognitive interference trials in inferior parietal lobule, dorsomedial prefrontal cortex, anterior insula, mid‐cingulate, and ventrolateral prefrontal cortex regardless of affective valence. BD patients showed deviations in functional connectivity with anterior insula in regions of the default mode and frontoparietal control networks during negatively valenced cognitive interference trials. Conclusions: Our findings show disruptions in cognitive regulation and inhibitory control in BD patients in the presence of irrelevant affective distractors. Results of this study suggest one pathway to dysregulation in BD is through inefficient integration of affective and cognitive information, and highlight the importance of developing interventions that target emotion‐cognition integration in BD. [ABSTRACT FROM AUTHOR]

Background and Objectives: Substance use disorders (SUDs) are present in up to 70% of patients with bipolar disorder (BD) and contribute to high rates of disability, morbidity, and treatment non-adherence. Despite this prevalence, few trials have investigated targeted psychosocial interventions for comorbid BD and SUDs.Methods: Using PubMed and PsycINFO, we conducted a search of the literature up to January 2018 for psychosocial interventions targeted to patients with comorbid BD and SUDs. We identified eight total trials. Of these studies, four randomized and two open trials targeted the types of substance use (alcohol and illicit drugs) of primary concern to mood stability; the remaining two studies, both open trials, targeted smoking cessation.Results: None of the randomized trials provided consistent evidence for management of both mood symptoms and substance use though integrated group therapy (IGT) demonstrated consistent beneficial effects on substance use outcomes. Other treatments showed benefit for mood symptoms without benefits for alcohol or illicit substance use. Small pilot studies of combined treatments for smoking cessation provided some initial promise.Conclusions: At present, IGT is the most-well validated and efficacious approach if substance use is targeted in an initial treatment phase. For a subsequent phase, additional psychosocial BD treatments may be needed for mood and functioning benefits.Scientific Significance: This review synthesizes the psychosocial interventions that have been conducted in comorbid BD and SUDs while also providing a perspective on which intervention elements are helpful for addressing substance use versus mood symptoms in patients with these co-occurring conditions. (Am J Addict 2018;27:188-201). [ABSTRACT FROM AUTHOR]

Reports of the demise of CBT for bipolar disorder have been greatly exaggerated: a response to Samamé In the recent debate piece, "The rise and fall of cognitive-behavioral approaches to the treatment of bipolar disorder: A critical overview from a quaternary prevention perspective,"1 Cecilia Samamé proposes a "non-recommendation" status for cognitive-behavioral therapies (CBT) for bipolar disorder (BD). Furthermore, no treatment occurs in a vacuum, and CBT for BD must be assessed in the context of other available treatment options. [Extracted from the article]

Background and Objectives: Topiramate is effective for alcohol use disorders (AUDs) among non-psychiatric patients. We examined topiramate for treating comorbid AUDs in bipolar disorder (BD).Methods: Twelve participants were randomized to topiramate or placebo for 12 weeks.Results: The topiramate group, with two out of five participants (40%) completing treatment, experienced less improvement in drinking patterns than the placebo group, with five out of seven participants (71%) completing treatment.Discussion and Conclusions: Topiramate did not improve drinking behavior and was not well-tolerated. This study failed to recruit adequately. Problems surrounding high attrition, a small study sample, and missing data preclude interpretation of study findings.Scientific Significance: This is the first randomized, placebo-controlled trial of topiramate for AUDs in BD. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated an association between cigarette smoking and depressive symptoms, as well as between cigarette smoking and (hypo)manic symptoms. Participants completed self-report assessments evaluating psychiatric history, depressive symptoms (via the Patient Health Questionnaire - 9), and (hypo)manic symptoms (via the Altman Self-Rating Mania Scale). [Extracted from the article]

Objectives Individuals with bipolar disorder have high rates of other medical comorbidity, which is associated with higher mortality rates and worse course of illness. The present study examined common predictors of medical comorbidity. Methods The Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE) enrolled 482 participants with bipolar I or bipolar II disorder in a six-month, randomized comparative effectiveness trial. Baseline assessments included current and lifetime DSM- IV- TR diagnoses, demographic information, psychiatric and medical history, severity of psychiatric symptoms, level of functioning, and a fasting blood draw. Medical comorbidities were categorized into two groups: cardiometabolic (e.g., diabetes, hyperlipidemia, and metabolic syndrome) and non-cardiovascular (e.g., seizures, asthma, and cancer). Additionally, we looked at comorbid substance use (e.g., smoking and drug dependence). Results We found that 96.3% of participants had at least one other medical comorbidity. Older age predicted a greater likelihood of having a cardiometabolic condition. Early age of onset of bipolar symptoms was associated with a lower chance of having a cardiometabolic condition, but a greater chance of having other types of medical comorbidity. Additional predictors of other medical comorbidities in bipolar disorder included more time spent depressed, less time spent manic/hypomanic, and longer duration of illness. Medications associated with weight gain were associated with low high-density lipoprotein and abnormal triglycerides. Conclusions There appears to be a substantial medical burden associated with bipolar disorder, highlighting the need for collaborative care among psychiatric and general medical providers to address both psychiatric and other medical needs concomitantly in this group of patients. [ABSTRACT FROM AUTHOR]

McMurrich S, Sylvia LG, Dupuy JM, Peckham AD, Peters AT, Deckersbach T, Perlis RH. Course, outcomes, and psychosocial interventions for first-episode mania. Bipolar Disord 2012: 14: 797-808. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: The course of bipolar disorder tends to worsen over time, highlighting the importance of early intervention. Despite the recognized need for adjunctive psychosocial treatments in first-episode mania, very few studies have evaluated psychological interventions for this period of significant risk. In this empirical review, we evaluate existing research on first-episode bipolar disorder, compare this body of research to parallel studies of first-episode schizophrenia, and identify strategies for future research. Methods: A comprehensive literature search of the MEDLINE and PsychINFO databases was conducted to identify studies of first-episode mania, as well as first-episode schizophrenia. Recovery and relapse rates were compared across studies. Results: In contrast to a number of studies of first-episode schizophrenia, the authors identified only seven independent programs assessing first-episode mania. Findings from these studies suggest that, while pharmacological treatment helps patients achieve recovery from acute episodes, it fails to bring patients to sustained remission. Early psychosocial intervention may be imperative in reducing residual symptoms, preventing recurrence of mood episodes, and improving psychosocial functioning. However, very few studies of psychosocial interventions for first-episode mania have been systematically studied. Conclusions: Studies of first-episode mania indicate a gap between syndromal/symptomatic and functional recovery. Novel psychosocial interventions for first-episode mania may help bridge this gap, but require controlled study. [ABSTRACT FROM AUTHOR]

The extent to which stress generation occurs in bipolar spectrum disorders (BSD) is not well understood. The present study examined whether 75 BSD participants experienced elevated rates of behavior-dependent life events, as compared with 38 normal control participants. Within the BSD group, we also examined whether depressive or hypomanic symptoms prospectively predicted increases in various types of negative and positive life events. Results indicated that BSD participants experienced overall increases in behavior-dependent events over the follow-up, as compared with normal controls. At the symptom level, the event generation process occurred in more specific event domains. Results suggest that the stress generation theory of unipolar depression can be extended to BSD and that the type of generated events may be polarity-specific. © 2010 Wiley Periodicals, Inc. J Clin Psychol: 66: 1–20, 2010. [ABSTRACT FROM AUTHOR]

Reilly-Harrington NA, DeBonis D, Leon AC, Sylvia L, Perlis R, Lewis D, Sachs GS. The interactive computer interview for mania. Bipolar Disord 2010: 12: 521–527. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: The Interactive Computer Interview for Mania (ICI-M) is a computer-administered interview that presents probes to assess symptom severity and utilizes a scoring algorithm to select follow-up questions and rate subject responses in accordance with rating scale anchor points. The current study examines the acceptability, feasibility, and reliability of the ICI-M as a potential method for evaluating the performance of human raters. Methods: Participants with a diagnosis of bipolar I or II disorder completed both a live interview of the Young Mania Rating Scale with a human rater (LR) and the ICI-M. A panel of three expert raters reviewed each videotaped LR and assigned a consensus rating (CR). Participants completed a modified version of the Client Satisfaction Questionnaire to assess each method. Results: Intraclass correlation coefficients were 0.91 between the ICI-M and CR and 0.97 between the LR and CR (n = 100), providing empirical support for the inter-rater reliability of each approach. Coefficient alphas indicated comparable internal consistency reliability: ICI-M = 0.82, LR = 0.83, and CR = 0.84. The ICI-M was significantly more sensitive in detecting symptomatology than the LR (p < 0.001) and the CR (p < 0.001), and resulted in significantly higher ratings than CR on mood, speech, psychotic content, and disruptive-aggressive behavior. While participants endorsed significantly higher overall satisfaction with LR, no significant differences emerged between ICI-M and LR regarding willingness to participate again or ability to understand the questions. Conclusions: The ICI-M is a well-accepted and reliable method for assessing manic symptoms. The ICI-M is a tool with adequate sensitivity to elicit symptoms and rate severity and is recommended as a tool to monitor and improve rater performance, not as a replacement of a human rater. [ABSTRACT FROM AUTHOR]

Objectives: Research suggests that bipolar disorder individuals may have less social rhythm regularity than normal controls and that this may contribute to their affective symptoms and episodes. This study examined whether regularity prospectively predicted time to onset of major depressive, hypomanic and manic episodes in a sample with bipolar spectrum disorders. Methods: We recruited 414 undergraduate students from Temple University and University of Wisconsin diagnosed with cyclothymia, bipolar II disorder, or with no affective disorder (normal controls). Participants completed the Social Rhythm Metric at Time 1 and structured interviews approximately every four months for an average follow-up period of 33 months. Results: Participants diagnosed with cyclothymia and bipolar II disorder reported significantly fewer regular activities than normal controls, and approximately half of these participants experienced a worsening course of their illness over the study duration. Survival analyses indicated that both diagnosis and social rhythm regularity significantly predicted the time to participants’ first prospective onset of major depressive, hypomanic and manic episodes. Conclusion: Consistent with the social zeitgeber theory, bipolar spectrum participants reported less social rhythm regularity than normal controls, which prospectively predicted the survival time to affective episodes. [ABSTRACT FROM AUTHOR]

The social zeitgeber theory emphasizes the importance that social rhythm regularity may play in promoting internal synchronization of circadian rhythms in individuals with or at risk for bipolar spectrum disorders. This study examined the relationship of lifestyle regularity, affective symptomatology, and sleep in 71 individuals exhibiting cyclothymic mood and behavior patterns. Participants were randomly assigned to either an experimental group in which they were encouraged to regulate their daily routines or to a control group. Participants in the experimental group were able to successfully regulate their daily schedules. Although relationships between regularity and severity of depressive symptoms, across-day variances in mood and behavior, and sleep duration were identified during baseline, increased lifestyle regularity did not differentially result in changes in these variables. © 2008 Wiley Periodicals, Inc. J Clin Psychol 64: 1–19, 2008. [ABSTRACT FROM AUTHOR]

Post et al[1] provide a call for consideration of a polypharmacy approach to later-stage and treatment-refractory bipolar patients, discussing potential future directions in the pharmacological management of bipolar disorder that can be delivered alongside a program involving psychosocial and lifestyle approaches. Manualized psychosocial interventions - such as cognitive-behavioral therapy, psychoeducation, family-focused therapy, mindfulness-based cognitive therapy, and dialectical behavior therapy - have been shown to reduce symptoms and improve outcomes in randomized, controlled studies of more homogeneous samples of bipolar disorder (for a review, see Ref. [2]). This is also the case for studies of integrated manualized psychosocial treatment developed for patients with bipolar disorder and anxiety as well as for patients with bipolar disorder and overweight/obesity status. [Extracted from the article]