Patterns of pharmacotherapy for bipolar disorder: A GBC survey.

OBJECTIVES: To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well-characterized individuals with BD in North America, Europe, and Australia. METHODS: Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta-analyses with generalized linear mixed methods were conducted to identify prescription patterns. RESULTS: This study included 10,351 individuals from North America (n = 3985), Europe (n = 3822), and Australia (n = 2544). Overall, participants were predominantly female (60%) with BD-I (60%; vs. BD-II = 33%). Cross-sectionally, mood-stabilizing anticonvulsants (44%), second-generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First-generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD-II (47%) compared to BD-I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort. CONCLUSIONS: Mood-stabilizing anticonvulsants, second-generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first-generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence-based guidelines to help improve treatment practices in BD.

Barriers to and facilitators of success for early and Mid-Career professionals focused on bipolar disorder: A global needs survey by the International Society for Bipolar Disorders.

INTRODUCTION: The International Society for Bipolar Disorders created the Early Mid-Career Committee (EMCC) to support career development of the next generation of researchers and clinicians specializing in bipolar disorder (BD). To develop new infrastructure and initiatives, the EMCC completed a Needs Survey of the current limitations and gaps that restrict recruitment and retention of researchers and clinicians focused on BD. METHODS: The EMCC Needs Survey was developed through an iterative process, relying on literature and content expertise of workgroup members. The survey included 8 domains: navigating transitional career stages, creating and fostering mentorship, research activities, raising academic profile, clinical-research balance, networking and collaboration, community engagement, work-life balance. The final survey was deployed from May to August 2022 and was available in English, Spanish, Portuguese, Italian, and Chinese. RESULTS: Three hundred participants across six continents completed the Needs Survey. Half of the participants self-identified as belonging to an underrepresented group in health-related sciences (i.e., from certain gender, racial, ethnic, cultural, or disadvantaged backgrounds including individuals with disabilities). Quantitative results and qualitative content analysis revealed key barriers to pursuing a research career focused on BD with unique challenges specific to scientific writing and grant funding. Participants highlighted mentorship as a key facilitator of success in research and clinical work. CONCLUSION: The results of the Needs Survey are a call to action to support early- and midcareer professionals pursuing a career in BD. Interventions required to address the identified barriers will take coordination, creativity, and resources to develop, implement, and encourage uptake but will have long-lasting benefits for research, clinical practice, and ultimately those affected by BD.

Alcohol use disorder conceptualizations and diagnoses reflect their sociopolitical context.

The present paper highlights how alcohol use disorder (AUD) conceptualizations and resulting diagnostic criteria have evolved over time in correspondence with interconnected sociopolitical influences in the United States. We highlight four illustrative examples of how DSM-defined alcoholism, abuse/dependence, and AUD have been influenced by sociopolitical factors. In doing so, we emphasize the importance of recognizing and understanding such sociopolitical factors in the application of AUD diagnoses. Last, we offer a roadmap to direct the process of future efforts toward the improved diagnosis of AUD, with an emphasis on pursuing falsifiability, acknowledging researchers' assumptions about human behavior, and collaborating across subfields. Such efforts that center the numerous mechanisms and functions of behavior, rather than signs or symptoms, have the potential to minimize sociopolitical influences in the development of diagnostic criteria and maximize the treatment utility of diagnoses.

A critical examination of multidimensionality within the Hypomanic Personality Scale.

BACKGROUND: The Hypomanic Personality Scale (HPS) assesses bipolar spectrum psychopathology and risk for bipolar disorders. Despite the developers' intent to create a scale that provides a unitary score, several studies have examined whether the HPS has a multidimensional structure. These models have been unable to identify a replicable multidimensional structure, with models varying from fairly similar to entirely dissimilar, and have suffered from theoretical and methodological concerns. PROCEDURES: We therefore examined the multidimensional structure of the HPS in a large undergraduate and adult sample (n = 5002). MAIN FINDINGS: We failed to reproduce factors with equal congruence to those of previously published models. PRINCIPLE CONCLUSIONS: We concluded that the HPS lacks factorial validity in previous research as a multidimensional measure of bipolar spectrum psychopathology. We further recommend the creation of a novel multidimensional assessment of bipolar spectrum psychopathology developed from a theoretically driven, comprehensive model, rather than examining a multidimensional model of a pre-existing measure, such as the HPS.

Variability in Sleep Is Associated with Trait-Based and Daily Measures of Bipolar Spectrum Psychopathology.

INTRODUCTION: Although sleep disturbances are well documented in bipolar spectrum disorders (BSDs), significantly less research has examined whether these disturbances are present in those at risk for developing BSDs or with subsyndromal symptoms. The present study examined associations between risk for BSDs, as measured by the Hypomanic Personality Scale (HPS), and sleep assessed using experience sampling. We assessed whether intraindividual variability in sleep was associated with affect, cognition, and behavior in daily life and potential directionality of these relationships. METHODS: 233 young adults oversampled for high scores on the HPS completed 14 days of experience sampling assessing total sleep time (TST), bed/rise time, sleep quality, affect (negative and positive affect), cognition (difficulty concentrating, racing thoughts), and behavior (impulsivity) in daily life. We used Dynamic Structural Equation Modeling (DSEM) to assess within-person links between sleep and bipolar spectrum psychopathology. RESULTS: HPS scores were associated with less TST, later bedtime, and more variable TST and bedtime. Variability in TST was associated with negative affect, difficulty concentrating/racing thoughts, and impulsivity. Within-person decreases in sleep were associated with next day increases in negative affect, stress, difficulty concentrating, and racing thoughts. LIMITATIONS: Measurement of sleep was limited. Future studies should examine both objective measures of sleep (e.g., actigraphy) and fragmentation in sleep. CONCLUSIONS: Risk for BSD was associated with similar patterns of sleep disruptions as seen in BSDs. Important dynamic links between sleep and bipolar spectrum psychopathology emerged indicating that sleep is an important target for improving symptoms of BSDs in daily life.

RZ Interval as an Impedance Cardiography Indicator of Effort-Related Cardiac Sympathetic Activity.

Research on effort and motivation commonly assesses how the sympathetic branch of the autonomic nervous system affects the cardiovascular system. The cardiac pre-ejection period (PEP), assessed via impedance cardiography, is a common outcome, but assessing PEP requires identifying subtle points on cardiac waveforms. The present research examined the psychometric value of the RZ interval (RZ), which has recently been proposed as an indicator of sympathetic activity, for effort research. Also known as the initial systolic time interval (ISTI), RZ is the time (in ms) between the ECG R peak and the dZ/dt Z peak. Unlike PEP, RZ involves salient waveform points that are easily and reliably identified. Data from two experiments evaluated the suitability of RZ for effort paradigms and compared it to a popular automated PEP method. In Studies 1 (n = 89) and 2 (n = 71), participants completed a standard appetitive task in which each correct response earned a small amount of cash. As expected, incentives significantly affected PEP and RZ in both experiments. PEP and RZ were highly correlated (all rs ≥ 0.89), and RZ consistently yielded a larger effect size than PEP. In Study 3, a quantitative synthesis of the experiments indicated that the effect size of RZ's response to incentives (Hedges's g = 0.432 [0.310, 0.554]) was roughly 15% larger than PEP's effect size (g = 0.376 [0.256, 0.496]). RZ thus appears promising for future research on sympathetic aspects of effort-related cardiac activity.

The convergence and divergence of impulsivity facets in daily life.

OBJECTIVE: Impulsivity appears to be best conceptualized as a multidimensional construct. For example, the UPPS-P model posits that there are five underlying facets of impulsivity. The present study examined the expression of the UPPS-P facets in daily life using experience sampling methodology. A specific goal of the study was to examine positive urgency, a facet added to the original UPPS model, and its convergence and divergence from the negative urgency facet. METHOD: A large nonclinical sample of young adults (n = 294) completed the UPPS-P scale and was signaled to complete questionnaires assessing daily affect, cognitions, sense of self, and impulsive behaviors eight times a day for 7 days. RESULTS: Results indicated that the UPPS-P facets are associated with disruptions in affect, cognitions, and behavior in daily life. Furthermore, all of the UPPS-P facets were associated with impulsivity in daily life. Contrary to expectation, positive urgency was associated with negative affect rather than positive affect and had a profile indistinguishable from negative urgency. CONCLUSIONS: These results generally support a four-factor model of multidimensional impulsivity with a general overall urgency factor instead of separate positive and negative urgency facets.

Measuring Cognition in Bipolar Disorder with Psychosis Using the MATRICS Consensus Cognitive Battery.

Given the substantial overlap in cognitive dysfunction between bipolar disorder (BD) and schizophrenia (SZ), we examined the utility of the MATRICS Consensus Cognitive Battery (MCCB)-developed for use in SZ-for the measurement of cognition in patients with BD with psychosis (BDP) and its association with community functioning. The MCCB, Multnomah Community Ability Scale, and measures of clinical symptoms were administered to participants with BDP (n=56), SZ (n=37), and healthy controls (HC) (n=57). Groups were compared on clinical and cognitive measures; linear regressions examined associations between MCCB and community functioning. BDP and SZ groups performed significantly worse than HC on most neurocognitive domains; BDP and HC did not differ on Social Cognition. Patients with BDP performed better than patients with SZ on most cognitive measures, although groups only differed on social cognition, working memory, verbal memory, and the composite after controlling for clinical variables. MCCB was not associated with community functioning. The MCCB is an appropriate measure of neurocognition in BDP but does not appear to capture social cognitive deficits in this population. The addition of appropriate social cognitive measures is recommended.

Dietary elimination therapy is an effective option for adults with eosinophilic esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is an immune-mediated disorder. Food elimination is an established treatment for children, but data in adults are limited. We aimed to determine the response of adults with EoE to dietary therapy. METHODS: This was a retrospective cohort study using the University of North Carolina EoE database from 2006 to 2012. Subjects were age 18 and older, had EoE by consensus guidelines, and had undergone dietary therapy either with a targeted elimination diet or a 6-food elimination diet (SFED). Outcomes were symptomatic, endoscopic, and histologic improvement. Demographic, endoscopic, symptomatic, and laboratory predictors of response to dietary therapy were assessed. RESULTS: Of 31 adults who underwent dietary therapy (mean age, 36 y; 48% male; 90% white; mean baseline eosinophil count, 78 eos/hpf), 22 had a targeted elimination diet and 9 had SFED. Symptoms improved in 71% (68% in targeted, 78% in SFED), and endoscopic appearance improved in 54% (53% in targeted, 56% in SFED). After dietary therapy, the mean eosinophil count decreased to 43 eos/hpf (P = .009). Eleven subjects (39%) responded with fewer than 15 eos/hpf (32% in targeted and 56% in SFED; P = .41). No clinical, endoscopic, or histologic factors predicted response to dietary therapy. Of the 11 responders, 9 underwent food re-introduction to identify trigger(s), and 4 (44%) reacted to dairy, 4 (44%) reacted to eggs, 2 (22%) reacted to wheat, 1 (11%) reacted to shellfish, 1 (11%) reacted to legumes, and 1 (11%) reacted to nuts. CONCLUSIONS: Dietary elimination is a successful treatment modality for adults with EoE. Further research should emphasize which factors can predict effective dietary therapy.

A phenotypic analysis shows that eosinophilic esophagitis is a progressive fibrostenotic disease.

BACKGROUND: Phenotypes of eosinophilic esophagitis (EoE) are not well-characterized. OBJECTIVE: To describe clinical features of patients with EoE with predefined phenotypes, determine predictors of these phenotypes, and make inferences about the natural history of EoE. DESIGN: Retrospective study. SETTING: Tertiary-care center. PATIENTS: Incident EoE cases from 2001 to 2011 that met consensus diagnostic guidelines. INTERVENTION: Review of records. MAIN OUTCOME MEASUREMENTS: Endoscopic phenotypes, including fibrostenotic, inflammatory, or mixed. Other groups of clinical characteristics examined included atopy, level of esophageal eosinophilia, and age of symptom onset. Multinomial logistic regression assessed predictors of phenotype status. RESULTS: Of 379 cases of EoE identified, there were no significant phenotypic differences by atopic status or level of eosinophilia. Those with the inflammatory phenotype were more likely to be younger than those with mixed or fibrostenotic (13 vs 29 vs 39 years, respectively; P < .001) and less likely to have dysphagia, food impaction, and esophageal dilation (P < .001 for all). The mean symptom length before diagnosis was shorter for inflammatory (5 vs 8 vs 8 years; P = .02). After multivariate analysis, age and dysphagia independently predicted phenotype. The odds ratio (OR) for fibrostenosis for each 10-year increase in age was 2.1 (95% CI, 1.7-2.7). The OR for dysphagia was 7.0 (95% CI, 2.6-18.6). LIMITATIONS: Retrospective, single-center study. CONCLUSION: In this large EoE cohort, the likelihood of fibrostenotic disease increased markedly with age. For every 10-year increase in age, the odds of having a fibrostenotic EoE phenotype more than doubled. This association suggests that the natural history of EoE is a progression from an inflammatory to a fibrostenotic disease.

Age as a predictor of cognitive decline in bipolar disorder.

OBJECTIVE: Cognitive dysfunction is a core feature of bipolar disorder (BD) in both adult and geriatric patients. However, little is known about whether cognitive functioning declines at a faster rate in patients with BD, and there are conflicting reports regarding the relationship between age and cognitive functioning in this population. This cross-sectional study examined the relationship between age and cognitive functioning in patients with BD. METHODS: Patients with BD I (N = 113) and healthy adults (N = 64) ages 18-87 completed measures of processing speed, attention, executive functioning, verbal fluency, and clinical symptomatology. Groupwise comparisons were used to examine differences between patients and the comparison group and adult and geriatric BD cohorts. A series of linear regressions was conducted to examine the relationship of age and cognitive functioning and clinical variables and cognition. RESULTS: Patients performed significantly worse than the comparison group on all neuropsychological measures. Age was a significant predictor of Trails A scores with older age associated with worse performance. CONCLUSIONS: Older age was associated with poorer performance on Trails A in patients with BD but not healthy adults. These results are suggestive of greater dysfunction in processing speed with older age in patients with BD compared with a healthy comparison group. Because cognitive functioning is associated with community outcomes, these findings suggest a need for treatments targeting cognitive symptoms across the life span. Future research exploring neurobiologic evidence for neurodegenerative processes in BD will pave the way for potential therapeutic interventions.

Beyond traditional metrics: A novel method for measuring mood instability in bipolar disorder.

Background: Clinical care for bipolar disorder (BD) has a narrow focus on prevention and remission of episodes with pre/post treatment reductions in symptom severity as the 'gold standard' for outcomes in clinical trials and measurement-based care strategies. The study aim was to provide a novel method for measuring outcomes in BD that has clinical utility and can stratify individuals with BD based on mood instability. Methods: Participants were 603 with a BD (n=385), other or non-affective disorder (n=71), or no psychiatric history (n=147) enrolled in an intensive longitudinal cohort for at least 10 years that collects patient reported outcomes measures (PROMs) assessing depression, (hypo)mania, anxiety, and functioning every two months. Mood instability was calculated as the within-person variance of PROMs and stratified into low, moderate, and high thresholds, respectively. Outcomes: Individuals with BD had significantly higher mood instability index's for depression, (hypo)mania, and anxiety compared to psychiatric comparisons (moderate effects, p's<.001) and healthy controls (large effects, p's<.001). A significantly greater proportion of individuals with BD fell into the moderate (depression: 52·8%; anxiety: 51·4%; (hypo)mania: 48·3%) and high instability thresholds (depression: 11·5%; anxiety: 9·1%; (hypo)mania: 10·8%) compared to psychiatric comparisons (moderate: 25·5 - 26·6%; high: 0% - 4·7%) and healthy controls (moderate: 2·9% - 17·1%; high: 0% - 1·4%). Being in the high or moderate instability threshold predicted worse health functioning (p's < .00, small to large effects). Interpretation: Mood instability, as measured in commonly used PROMs, characterized the course of illness over time, correlated with functional outcomes, and significantly differentiated those with BD from healthy controls and psychiatric comparisons. Results suggest a paradigm shift in monitoring outcomes in BD, by measuring mood instability as a primary outcome index.

An initial test of the contrast avoidance model in bipolar spectrum disorders.

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

Longitudinal dynamics between anxiety and depression in bipolar spectrum disorders.

Anxiety and depression are common among individuals with bipolar spectrum disorders (BSDs), with anxiety being a risk factor for depression and vice versa. While the harmful effects of these symptoms are well recognized, their temporal dynamics have not been fully tested. To address this gap, our study investigated bidirectional relationships between anxiety and depression in individuals with BSDs using data from the Prechter Longitudinal Study of Bipolar Disorder, collected over an average of 11 years. We included 651 participants with various BSD subtypes (BD I, BD II, BD not otherwise specified, and schizoaffective bipolar type), with at least 5 years' data for adequate statistical power in detecting temporal dynamics. Bimonthly measurements of anxiety and depression were analyzed using dynamic structural equation modeling. Beyond assessing autoregressive and cross-lagged effects, this study also investigated whether temporal dynamics differed based on demographic characteristics and the use of psychiatric medication. Our findings revealed that individuals with BSDs experienced significant fluctuations in anxiety and depression over time. In addition, we found significant autoregressive and cross-lagged effects of anxiety and depression. Comparison of the cross-lagged effects demonstrated that anxiety had a greater effect on subsequent depression than vice versa. Age and marital status impacted cross-lagged and autoregressive effects. Specifically, older participants had stronger temporal associations between depression and subsequent anxiety, while widowed participants exhibited a heightened impact of depression on subsequent depression. These results underscore the importance of early identification and integrative interventions aimed at addressing both anxiety and depression to mitigate subsequent symptoms in BSDs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Association of Positive, Negative, and Disorganized Schizotypy With the Temporal Dynamics of Schizotypic Experiences in Daily Life.

BACKGROUND AND HYPOTHESIS: Schizotypy is a useful and unifying construct for examining the etiology, development, and expression of schizophrenia-spectrum psychopathology. The positive, negative, and disorganized schizotypy dimensions are associated with distinct patterns of schizophrenia-spectrum symptoms and impairment. Furthermore, they are differentiated by mean levels of psychotic-like, suspicious, negative, and disorganized schizotypic experiences in daily life, and by temporal dynamics of affect. The schizotypy dimensions were thus hypothesized to be differentiated by the temporal dynamics of schizotypic experiences in daily life. STUDY DESIGN: The present study employed experience sampling methodology in a large nonclinically ascertained sample (n = 693) to examine the associations of multidimensional schizotypy with psychotic-like, suspicious, negative, and disorganized schizotypic experiences in daily life, as well as with their temporal dynamics (variability, reactivity, inertia, and instability). STUDY RESULTS: We replicated the mean-level associations between multidimensional schizotypy and schizotypic experiences in daily life. Furthermore, positive, negative, and disorganized schizotypy demonstrated hypothesized, differential patterns of temporal dynamics of schizotypic experiences. Disorganized schizotypy demonstrated the most robust associations, including intensity, variability, and inertia of disorganized schizotypic experiences. Disorganized schizotypy also moderated reactivity of psychotic-like and disorganized schizotypic experiences following previously reported stress. Positive schizotypy was associated with intensity and variability of psychotic-like experiences. Negative schizotypy was associated with intensity and variability of negative schizotypic experiences. CONCLUSIONS: The findings indicate that schizotypy dimensions can be differentiated by both mean levels and temporal patterns of psychotic-like, suspicious, negative, and disorganized schizotypic experiences in daily life, with disorganized schizotypy uniquely characterized by stress reactivity.