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Susan L McElroy, Anna I Guerdjikova, Nicole Mori, Anne M O'MeliaLindner Center of HOPE, Mason, and Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, OH, USAAbstract: Growing evidence suggests that pharmacotherapy may be beneficial for some patients with binge eating disorder (BED), an eating disorder characterized by repetitive episodes of uncontrollable consumption of abnormally large amounts of food without inappropriate weight loss behaviors. In this paper, we provide a brief overview of BED and review the rationales and data supporting the effectiveness of specific medications or medication classes in treating patients with BED. We conclude by summarizing these data, discussing the role of pharmacotherapy in the BED treatment armamentarium, and suggesting future areas for research.Keywords: binge eating disorder, pharmacotherapy, medication management

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10-7) and PKP4 (P=8.67 × 10-7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10-3]), SCZ (rg=0.34 [P=4.37 × 10-5]) and MDD (rg=0.57 [P=1.04 × 10-3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.

Objective: This report examined the characteristics of subjects interested in binge eating disorder (BED) pharmacotherapy trails who were ineligible for participation. Methods: Data on 2685 potential subjects interested in participating in five different placebo-controlled monotherapy trails of BED were analysed. Results: Of the 2685 potential subjects, 1230 (45.8%) were ineligible because they did not meet entry criteria, 586 (21.8%) were eligible for participation, 531 (19.8%) were not interested in the study and 338 (12.6%) were not contacted. Among the 1230 ineligible candidates, 525 (42.7%) were taking exclusionary psychotropic medication, 305 (24.8%) did not meet specified BED criteria, 157 (12.7%) were out of the required age (n=83) or weight (n=74) range, 212 (17.2%) had prohibited medical (n=78) or psychiatric (n=134) disorders and 31 (2.5%) were participating in weight loss programmes. Discussion: Given the complexity of BED, future pharmacotherapy studies should examine a broader range of subjects, including subjects with subthreshold forms of BED, those with comorbid disorders and elderly subjects. Copyright c 2008 John Wiley & Sons, Ltd and Eating Disorders Association. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Bipolar spectrum disorders, which include bipolar I, bipolar II, and bipolar disorder not otherwise specified, frequently go unrecognized, undiagnosed, and untreated. This report describes the validation of a new brief self-report screening instrument for bipolar spectrum disorders called the Mood Disorder Questionnaire. METHOD: A total of 198 patients attending five outpatient clinics that primarily treat patients with mood disorders completed the Mood Disorder Questionnaire. A research professional, blind to the Mood Disorder Questionnaire results, conducted a telephone research diagnostic interview by means of the bipolar module of the Structured Clinical Interview for DSM-IV. RESULTS: A Mood Disorder Questionnaire screening score of 7 or more items yielded good sensitivity (0.73) and very good specificity (0.90). CONCLUSIONS: The Mood Disorder Questionnaire is a useful screening instrument for bipolar spectrum disorder in a psychiatric outpatient population. [ABSTRACT FROM AUTHOR]

The objective of this 12-week open-label flexible-dose study was to preliminarily assess the effectiveness of N-acetylcysteine (NAC) in bulimia nervosa (BN). The primary outcome was binge-purge episode frequency. Eight individuals with BN by DSM-IV criteria received NAC, but only two completed the study. NAC was not associated with significant reductions in frequency of binge-purge episodes or measures of clinical severity, eating, or mood pathology. In this trial, NAC was ineffective in BN and was associated with a high discontinuation rate. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is a heritable mental illness with complex etiology. While the largest published genome-wide association study identified 64 BD risk loci, the causal SNPs and genes within these loci remain unknown. We applied a suite of statistical and functional fine-mapping methods to these loci, and prioritized 17 likely causal SNPs for BD. We mapped these SNPs to genes, and investigated their likely functional consequences by integrating variant annotations, brain cell-type epigenomic annotations, brain quantitative trait loci, and results from rare variant exome sequencing in BD. Convergent lines of evidence supported the roles of genes involved in neurotransmission and neurodevelopment including SCN2A, TRANK1, DCLK3, INSYN2B, SYNE1, THSD7A, CACNA1B, TUBBP5, PLCB3, PRDX5, KCNK4, CRTC3, AP001453.3, TRPT1, FKBP2, DNAJC4, RASGRP1, FURIN, FES, DPH1, GSDMB, MED24 and THRA in BD. These represent promising candidates for functional experiments to understand biological mechanisms and therapeutic potential. Additionally, we demonstrated that fine-mapping effect sizes can improve performance of BD polygenic risk scores across diverse populations, and present a high-throughput fine-mapping pipeline (https://github.com/mkoromina/SAFFARI)., Competing Interests: Competing interests OAA has served as a speaker for Janssen, Lundbeck, and Sunovion and as a consultant for Cortechs.ai. SKS has served as speaker for Janssen, Takeda and Medice Arzneimittel Puetter GmbH & CoKG. EV has received grants and served as consultant, advisor or CME speaker for the following entities (unrelated to the present work): AB-Biotics, Abbott, Abbvie, Adamed, Angelini, Biogen, Biohaven, Boehringer Ingelheim, Casen-Recordati, Celon, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo Smith-Kline, Idorsia, Janssen, Johnson & Johnson, Lundbeck, Newron, Novartis, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris. PBM has received remuneration from Janssen (Australia) and Sanofi (Hangzhou) for lectures, and Janssen (Australia) for advisory board membership. MOD and MJO have received grants from Akrivia Health and Takeda Pharmaceuticals for work unrelated to this project.

The impact of childhood abuse on the presentation of bipolar disorder could be further elucidated by comparing the networks of affective symptoms among individuals with and with no history of childhood abuse. Data from 476 participants in the Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study were used to fit several regularised Gaussian Graphical Models. Differences in the presentation of depressive and manic symptoms were uncovered: only among participants with a history of childhood abuse, inadequacy and pessimism were central symptoms in the network of depressive symptoms, while racing thoughts was an important symptom in the network of manic symptoms. Following network theory, focusing treatments at the symptom-level and on central symptoms - like inadequacy, pessimism, and racing thoughts - could be an effective approach for managing affective symptoms among the sizeable proportion of people with bipolar disorder who have experienced childhood abuse. This study contributes a thorough investigation of the networks of affective symptoms among participants with and with no history of childhood abuse, albeit limited by the use of a binary, self-report measure of childhood abuse, thereby emphasising the importance of assessing for childhood abuse and taking needed steps towards identifying novel targets for treating bipolar disorder., Competing Interests: Declaration of competing interest ALW has received grant/research support from Deakin University and the Rotary Club of Geelong. MT has received grant/research support from Deakin University. OMD has received grant/research support from the Brain and Behavior Foundation, Simons Autism Foundation, Stanley Medical Research Institute, Deakin University, Lilly, NHMRC, and Australasian Society for Bipolar and Depressive Disorders (ASBDD)/Servier. OMD has also received in kind support from BioMedica Nutracuticals, NutritionCare and Bioceuticals. MB has received grant/research support from MRFF, NHMRC, Congressionally Directed Medical Research Programs (CDMRP) USA, AEDRTC Australian Eating Disorders Research and Translation Centre, Patient-Centered Outcomes Research Institute (PCORI), Baszucki Brain Research Fund, Danmarks Frie Forskningsfond. Psykiatrisk Center Kobenhavn, Stanley Medical Research Institute, Victorian Government Department of Jobs, Precincts and Regions, Wellcome Trust, Victorian Medical Research Acceleration Fund, Controversias Psiquiatria Barcelona, CRE, Victorian COVID-19 Research Fund, Consultancies: Lundbeck, Sandoz, Servier, Medisquire, HealthEd, ANZJP, EPA, Janssen, Medplan, RANZCP, Abbott India, ASCP, International Society of Bipolar Disorder, Precision Psychiatry, Penn State College of Medicine, Shanghai Mental Health Centre in the past 3 years – all unrelated to this work. LGS has received grant/research support from PCORI, NIH, HRSA, Tiny Blue Dot Foundation, and AFSP. She has also received support as a member of the Miliken Institute's Scientific Advisory Board as well as royalties form New Harbinger for her two, published books on bipolar disorder. MT was an employee of Lilly (1997 to 2008) and has received honoraria from or consulted for Abbott, Abbvie, AstraZeneca, Alkermes, Atai, Biohaven Pharmaceuticals, Squibb, Rapport Neurosciences, Lilly, Johnson & Johnson, Otsuka, Merck, Sunovion, Intra-Cellular Therapies, NeuroRX, Roche, Elan, Lundbeck, Teva, Minerva, Neurocrine Biosciences, NoemaPharma, Pfizer; his spouse was a full time employee at Lilly (1998–2013). MGM has received grant/research support from Janseen Pharmaceuticals. RCS has received grant/research support from the National Institutes of Mental Health, the Patient Centered Outcomes Research Institute, AbbVie Inc, Alto Pharmaceuticals, Boehringer Ingelheim, Denovo Biopharma, Gate Neuroscience, InMune Bio, Intra-cellular Therapies, Johnson & Johnson Innovative Medicine, LivaNova PLC, Navitor Pharmaceuticals, Neumora, Neurocrine Biosciences, Neurorx, Novartis AG, Otsuka Pharmaceuticals, Sumitomo Pharma America, and Supernus Pharmaceuticals. RCS has also consulted for Boehringer Ingelheim, Denovo Biopharma, Equulus Therapeutics, Evecxia Therapeutics LLC, Johnson & Johnson Innovative Medicine, Neurorx, Novartis AG, Otsuka Pharmaceuticals, Seelos Therapeutics, Inc., Sumitomo Pharma America, and Supernus Pharmaceuticals and has received royalties from Springer-Nature Group and Wolters-Kluwer NV. MJO has received grant/research support from Otsuka and is a consultant to Neurocrine, Inc., both unrelated to this work. In the last 10 years, DVI has served as a consultant for Alkermes, Allergan, Angelini, Autobahn, Axsome, Biogen, Boehringer Ingelheim, the Centers for Psychiatric Excellence, Clexio, Delix, Jazz, Lundbeck, Neumora, Otsuka, Precision Neuroscience, Relmada, Sage Therapeutics, and Sunovion. He has received grant/research support (paid to his institutions) from Alkermes, AstraZeneca, Brainsway, LiteCure, NeoSync, Otsuka, Roche, and Shire. SLM has been a consultant to or member of the scientific advisory boards of Axsome, Idorsia, Kallyope, Levo, Neurocrine, Novo Nordisk, Otsuka, Sunovion, and Takeda. She has been a principal or co-investigator on studies sponsored by Neurocrine, Novo Nordisk, Otsuka, and Sunovion. She is also an inventor on United States Patent No 6323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and along with the patent's assignee, University of Cincinnati, Cincinnati, Ohio, has received payments from Johnson & Johnson, which has exclusive rights under the patent. AT has received travel/grant support from NHMRC, AMP Foundation, Stroke Foundation, Hunter Medical Research Institute, Helen Macpherson Smith Trust, Schizophrenia Fellowship NSW, SMHR, ISAD, the University of Newcastle, and Deakin University. AAN is a consultant for Alkermes, Clexio, Ginger/Headspace Health, Janssen, Merck, Neuronetics, NeuroRx, Otsuka, Protagenics, SAGE, Sunovion, Unravel Bioscience, received honoraria from Belvior, EISAI, Psychiatric Annals Slack Publications, Wiley Depression and Anxiety, received royalties from Guilford Publications, Up-to-Date Wolters Kluwer Health, has been a scientific advisory board member for Altimate, Flow, Milken Center for Strategic Philanthropy, Myriad, and adjudication committee member for Novartis., (Copyright © 2024. Published by Elsevier B.V.)

Binge eating disorder (BED) is the most common specific eating disorder (ED). It is frequently associated with attention deficit hyperactivity disorder (ADHD), depression, bipolar disorder (BD), anxiety disorders, alcohol and nicotine use disorder, and obesity. The aim of this narrative review was to summarize the evidence for the pharmacological treatment of BED and its comorbid disorders. We recommend the ADHD medication lisdexamfetamine (LDX) and the antiepileptic and antimigraine drug topiramate for the pharmacological treatment of BED. However, only LDX is approved for the treatment of BED in some countries. Medications to treat diseases frequently comorbid with BED include atomoxetine and LDX for ADHD; citalopram, fluoxetine, sertraline, duloxetine, and venlafaxine for anxiety disorders and depression; aripiprazole for manic episodes of BD; lamotrigine, lirasidone and lumateperone for depressive episodes of BD; naltrexone for alcohol use disorder; bupropion for nicotine use disorder; and liraglutide, semaglutide, and the combination of bupropion and naltrexone for obesity. As obesity is a frequent health consequence of BED, weight gain-inducing medications, such as the atypical antipsychotics olanzapine or clozapine, the novel antidepressant mirtazapine and tricyclic antidepressants, and the mood stabilizer valproate should be avoided where possible. It is currently unclear whether the novel and promising glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) receptor agonists like tirzepatide and retatrutide help with BED and its comorbidities. However, these compounds have been reported to reduce binge eating in individuals with obesity or overweight., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Bipolar disorder is a chronic and complex polygenic disease with high rates of comorbidity. However, the independent contribution of either diagnosis or genetic risk of bipolar disorder to the medical comorbidity profile of individuals with the disease remains unresolved. Here, we conducted a multi-step phenome-wide association study (PheWAS) of bipolar disorder using phenomes derived from the electronic health records of participants enrolled in the Mayo Clinic Biobank and the Mayo Clinic Bipolar Disorder Biobank. First, we explored the conditions associated with a diagnosis of bipolar disorder by conducting a phenotype-based PheWAS followed by LASSO-penalized regression to account for correlations within the phenome. Then, we explored the conditions associated with bipolar disorder polygenic risk score (BD-PRS) using a PRS-based PheWAS with a sequential exclusion approach to account for the possibility that diagnosis, instead of genetic risk, may drive such associations. 53,386 participants (58.7% women) with a mean age at analysis of 67.8 years (SD = 15.6) were included. A bipolar disorder diagnosis (n = 1479) was associated with higher rates of psychiatric conditions, injuries and poisonings, endocrine/metabolic and neurological conditions, viral hepatitis C, and asthma. BD-PRS was associated with psychiatric comorbidities but, in contrast, had no positive associations with general medical conditions. While our findings warrant confirmation with longitudinal-prospective studies, the limited associations between bipolar disorder genetics and medical conditions suggest that shared environmental effects or environmental consequences of diagnosis may have a greater impact on the general medical comorbidity profile of individuals with bipolar disorder than its genetic risk., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Major depressive disorder (MDD) and obesity have a complex bidirectional relationship. However, most studies do not assess increased appetite or weight as a depressive symptom due to limitations in rating scales. Here we aimed to analyze frequently employed depressive-symptom scales and discuss the relevance of weight and appetite assessment items. To elaborate this perspective, we searched for validated questionnaires and scales evaluating depressive symptoms in English. We analyzed appetite and weight items from 20 depressive-symptoms rating scales. Only 8 of 20 rating scales assessed for increased weight or appetite. The scales reported in the literature as the most employed in antidepressants efficacy trials do not assess increased appetite or weight. The current use of rating scales limits our understanding of the relationship between MDD, antidepressants, and obesity. It is necessary to improve our weight and appetite measurements in MDD to clarify the respective impact of depressive symptoms and antidepressants on weight change.

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II., Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism., Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II., (© 2024. The Author(s).)

Background: Epidemiological data offer conflicting views of the natural course of binge-eating disorder (BED), with large retrospective studies suggesting a protracted course and small prospective studies suggesting a briefer duration. We thus examined changes in BED diagnostic status in a prospective, community-based study that was larger and more representative with respect to sex, age of onset, and body mass index (BMI) than prior multi-year prospective studies., Methods: Probands and relatives with current DSM-IV BED ( n = 156) from a family study of BED ('baseline') were selected for follow-up at 2.5 and 5 years. Probands were required to have BMI > 25 (women) or >27 (men). Diagnostic interviews and questionnaires were administered at all timepoints., Results: Of participants with follow-up data ( n = 137), 78.1% were female, and 11.7% and 88.3% reported identifying as Black and White, respectively. At baseline, their mean age was 47.2 years, and mean BMI was 36.1. At 2.5 (and 5) years, 61.3% (45.7%), 23.4% (32.6%), and 15.3% (21.7%) of assessed participants exhibited full, sub-threshold, and no BED, respectively. No participants displayed anorexia or bulimia nervosa at follow-up timepoints. Median time to remission (i.e. no BED) exceeded 60 months, and median time to relapse (i.e. sub-threshold or full BED) after remission was 30 months. Two classes of machine learning methods did not consistently outperform random guessing at predicting time to remission from baseline demographic and clinical variables., Conclusions: Among community-based adults with higher BMI, BED improves with time, but full remission often takes many years, and relapse is common.

Background: Obesity is common among persons with bipolar disorder (BD). Liraglutide 3.0 mg/d subcutaneous injection is indicated for chronic weight management and associated with minimal adverse neuropsychiatric effects. This study evaluated whether liraglutide 3 mg/d reduced body weight, improved metabolic factors and eating psychopathology, and was safe and well tolerated in persons with stable BD who were obese (body mass index [BMI] >30 kg/m 2 ) or overweight (BMI ≥27 kg/m 2 ) with at least one weight-related comorbidity., Methods: This was a 40-week, randomized (1:1 ratio), placebo-controlled, double-blind, parallel-group, 2-arm clinical trial of liraglutide targeted to 3.0 mg/d (in combination with a reduced-calorie diet and increased physical activity) in 60 participants with stable BD who were obese or overweight. Primary outcome was percent change in body weight from baseline to study end. Secondary outcomes included percentage of patients who lost ≥5% of baseline body weight, and changes in metabolic variables and measures of eating psychopathology., Results: There were no significant baseline differences between the 29 liraglutide recipients and the 31 placebo recipients, except that liraglutide recipients had higher levels of binge eating and lower levels of high-density lipoprotein cholesterol. Compared with placebo, liraglutide was associated with significantly greater reductions in percent change in body weight, percentage of participants who lost at least 5% of body weight, and reductions in weight, BMI, hemoglobin A 1c levels, binge eating, and hunger. Liraglutide was well tolerated., Conclusions: Liraglutide 3 mg/d may be efficacious and safe for weight loss in individuals with stable BD and obesity or overweight., Trial Registration: ClinicalTrials.gov (NCT03158805)., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Converging theoretical frameworks suggest a role and a therapeutic potential for spinal interoceptive pathways in major depressive disorder (MDD). Here, we aimed to evaluate the antidepressant effects and tolerability of transcutaneous spinal direct current stimulation (tsDCS) in MDD. This was a double-blind, randomized, sham-controlled, parallel group, pilot clinical trial in unmedicated adults with moderate MDD. Twenty participants were randomly allocated (1:1 ratio) to receive "active" 2.5 mA or "sham" anodal tsDCS sessions with a thoracic (anode; T10)/right shoulder (cathode) electrode montage 3 times/week for 8 weeks. Change in depression severity (MADRS) scores (prespecified primary outcome) and secondary clinical outcomes were analyzed with ANOVA models. An E-Field model was generated using the active tsDCS parameters. Compared to sham (n = 9), the active tsDCS group (n = 10) showed a greater baseline to endpoint decrease in MADRS score with a large effect size (-14.6 ± 2.5 vs. -21.7 ± 2.3, p = 0.040, d = 0.86). Additionally, compared to sham, active tsDCS induced a greater decrease in MADRS "reported sadness" item (-1.8 ± 0.4 vs. -3.2 ± 0.4, p = 0.012), and a greater cumulative decrease in pre/post tsDCS session diastolic blood pressure change from baseline to endpoint (group difference: 7.9 ± 3.7 mmHg, p = 0.039). Statistical trends in the same direction were observed for MADRS "pessimistic thoughts" item and week-8 CGI-I scores. No group differences were observed in adverse events (AEs) and no serious AEs occurred. The current flow simulation showed electric field at strength within the neuromodulation range (max. ~0.45 V/m) reaching the thoracic spinal gray matter. The results from this pilot study suggest that tsDCS is feasible, well-tolerated, and shows therapeutic potential in MDD. This work also provides the initial framework for the cautious exploration of non-invasive spinal cord neuromodulation in the context of mental health research and therapeutics. The underlying mechanisms warrant further investigation. Clinicaltrials.gov registration: NCT03433339 URL: https://clinicaltrials.gov/ct2/show/NCT03433339 ., (© 2023. The Author(s).)

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD., (© 2024. The Author(s).)

There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD. We conducted a genome-wide association study (GWAS) and polygenic score analysis of TEM and tested its association in a subset of BD-type I patients treated with SSRIs or SNRIs. Our results did not identify any genome-wide significant variants although, we found that a higher polygenic score (PGS) for antidepressant response in MDD was associated with higher odds of TEM in BD. Future studies with larger transdiagnostic depressed cohorts treated with antidepressants are encouraged to identify a neurobiological mechanism associated with a spectrum of depression improvement from response to emergent mania., (© 2024. The Author(s).)

Glucagon-like peptide-1 receptor agonists (GLP-1As) are being used as approved or off-label treatments for weight loss. As such, there has been increasing concern about the potential for GLP-1As to impact eating disorder (ED) symptomatology. This article seeks to (1) review the current state of knowledge regarding GLP-1As and ED symptomatology; (2) provide recommendations for future research; and (3) guide ED clinicians in how to discuss GLP-1As in clinical practice. Although evidence is limited, it is possible that GLP-1As could exacerbate, or contribute to the development of, ED pathology and negatively impact ED treatment. Preliminary research on the use of GLP-1As to treat binge eating has been conducted; however, studies have design limitations and additional research is needed. Therefore, at the current time there is not sufficient evidence to support the use of GLP-1s to treat ED symptoms. In summary, more research is required before negative or positive conclusions can be drawn about the impact of GLP-1As on EDs psychopathology. Herein, we provide specific recommendations for future research and a guide to help clinicians navigate discussions with their clients about GLP-1As. A client handout is also provided. PUBLIC SIGNIFICANCE: Despite glucagon-like peptide-1 receptor agonists (GLP-1As; e.g., semaglutide) increasingly being the topic of clinical and public discourse, little is known about their potential impact on ED symptoms. It is possible that GLP-1As could maintain, worsen, or improve ED symptoms. This article reviews the limited literature on GLP-1As and ED symptoms, recommends future research, and provides clinicians with a guide for discussing GLP-1As with ED clients., (© 2023 The Authors. International Journal of Eating Disorders published by Wiley Periodicals LLC.)

Objectives: This study examined the use of a self-monitoring/self-management smartphone application (app) for patients with bipolar disorder. The app was specifically designed with patient-centered computational software system based on concepts from nonlinear systems (chaos) theory., Methods: This was a randomized, active comparator study of use of the KIOS app compared to an existing free app that has high utilization rates known as eMoods, over 52 weeks, and performed in three academic centers. Patients were evaluated monthly utilizing the Bipolar Inventory of Symptoms Schedule (BISS). The primary outcome measure was the persistence of using the app over the year of the study., Results: Patients assigned to KIOS persisted in the study longer than those assigned to eMoods; 57 patients (87.70%) in the KIOS group versus 42 (73.69%) in the eMoods group completed the study (p = 0.03). By 52 weeks, significantly more of KIOS group (84.4%) versus eMoods group (54%) entered data into their programs (χ 2  = 14.2, df = 1, p = 0.0002). Patient satisfaction for KIOS was greater (F = 5.21, df = 1, 108, p = 0.025) with a standardized effect size (Cohen's d) of 0.41. There was no difference in clinical outcome at the end of the study between the two groups., Conclusions: This is the first randomized comparison study comparing two apps for the self-monitoring/self-management of bipolar disorder. The study revealed greater patient satisfaction and greater adherence to a patient-centered software program (KIOS) than a monitoring program that does not provide feedback (eMoods)., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: This Phase II, placebo-controlled, double-blind study investigated the efficacy, safety, and tolerability of nivasorexant in the treatment of adults with moderate to severe binge-eating disorder (BED)., Methods: Adults meeting the DSM-5 BED criteria were randomized 1:1 to placebo or nivasorexant (100 mg b.i.d.). The primary endpoint was the change from baseline to Week 12 in the number of binge eating (BE) days per week. Exploratory efficacy endpoints included cessation of BE in the last 4 weeks of treatment; and change from baseline to Week 12 in the number of BE episodes/week, the clinician global impression (CGI) of change, the Yale-Brown Obsessive-Compulsive Scale modified for BE, and the Hamilton rating scale for depression (HAMD-17). Key safety outcomes included treatment-emergent adverse events (TEAEs) and adverse events of special interest (i.e., somnolence and fatigue)., Results: Sixty-eight participants were randomized to each treatment arm. The change from baseline to Week 12 in the number of BE days/week was the same for placebo (least squares mean [LSM]: -2.93) and nivasorexant (LSM: -2.93), with no difference between the treatment groups (LSM difference = .000 [95% confidence interval (CI): -.69, .69], p = .9992). Furthermore, no differences between treatment groups were observed in the exploratory efficacy endpoints. Nivasorexant was well tolerated; the overall incidence of TEAEs was balanced between treatment groups, and the frequency of somnolence and fatigue in the nivasorexant group were similar to placebo., Discussion: In this proof-of-concept study, 100 mg b.i.d. nivasorexant did not improve BE in adults with moderate to severe BED., Public Significance: The results of this Phase II study indicate that nivasorexant was well tolerated in adults with BED, but did not improve binge eating behavior over placebo. Further research is needed to improve our understanding of the role of the orexin-1 receptor in BED., (© 2023 Wiley Periodicals LLC.)

Objectives: The authors compared the switch rate into hypomania/mania in depressed patients treated with second-generation antidepressants who had either bipolar I or bipolar II disorder., Methods: In a 10-week trial, 184 outpatients with bipolar depression (134 with bipolar I disorder, 48 with bipolar II disorder, two with bipolar disorder not otherwise specified) were treated with one of three antidepressants as an adjunct to mood stabilizers. The patients' switch rates were assessed. Switch was defined as a Young Mania Rating Scale (YMRS) score >13 or a Clinical Global Impression (CGI) mania score ≥3 (mildly ill)., Results: Depressed subjects with bipolar II disorder had a significantly lower acute switch rate into hypomania/mania when either YMRS or CGI criteria were used to define switch., Conclusions: These data suggest that depressed patients with bipolar II disorder are less vulnerable than those with bipolar I disorder to switch into hypomania/mania when treated with an antidepressant adjunctive to a mood stabilizer.Reprinted from Am J Psychiatry 2006; 163:313-315 , with permission from American Psychiatric Association Publishing. Copyright © 2006., (Copyright © 2023 by the American Psychiatric Association.)