The natural course of binge-eating disorder: findings from a prospective, community-based study of adults.

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.

A study of long-term supraphysiologic-dose anabolic-androgenic steroid use on cognitive function in middle-aged men.

Background: Long-term use of supraphysiologic doses of anabolic-androgenic steroids (AAS) has been associated with impaired visuospatial memory in young men but little is known about its cognitive effects in middle-aged men.Objectives: We compared cognition in middle-aged men with histories of long-term AAS use and age-matched non-users.Methods: We administered cognitive tests from the CANTAB battery to 76 weightlifters aged 37-60 years (mean [SD] 48.5 [6.5] years), of whom 51 reported at least 2 years of cumulative AAS use and 25 reported no AAS exposure.Results: We found no significant AAS user versus non-user group differences on visuospatial, verbal memory, emotional recognition, or executive function tasks (corrected p's ≥ .00089; effect sizes ≤ .5).Conclusions: Our null visuospatial task findings contrast with our prior younger cohort study (mean age 37.1 [7.1] years), in which we found impaired visuospatial task performance in people who use AAS, and with other reports of cognitive impairments in younger men use AAS. Men who use AAS may develop early visuospatial memory deficits that stabilize by middle age while middle-aged non-users' performance may "catch up" due to normal age-related visuospatial declines. Similar effects could contribute to our null findings on other tasks. Between-study cohort substance use differences or environmental factor differences that modify cognition, such as study geographical location and time of year, also could contribute to our discordant findings. Since young adult male AAS users experience increased mortality from unnatural causes, improving our understanding of AAS cognitive effects in this age group is important.

Repeatability and reliability of GABA measurements with magnetic resonance spectroscopy in healthy young adults.

PURPOSE: Gamma-aminobutyric acid (GABA) abnormalities have been implicated in a range of neuropsychiatric disorders. Despite substantial interest in probing GABA in vivo, human imaging studies relying on magnetic resonance spectroscopy (MRS) have generally been hindered by technical challenges, including GABA's relatively low concentration and spectral overlap with other metabolites. Although past studies have shown moderate-to-strong test-retest repeatability and reliability of GABA within certain brain regions, many of these studies have been limited by small sample sizes. METHODS: GABA+ (macromolecular-contaminated) test-retest reliability and repeatability were assessed via a Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS) MRS sequence in the rostral anterior cingulate cortex (rACC; n = 21) and dorsolateral prefrontal cortex (dlPFC; n = 20) in healthy young adults. Data were collected on a 3T scanner (Siemens Prisma, Siemens Healthcare, Erlangen, Germany) and GABA+ results were reported in reference to both total creatine (GABA+/tCr) and water (GABA+/water). RESULTS: Results showed strong test-retest repeatability (mean GABA+/tCr coefficient of variation [CV] = 4.6%; mean GABA+/water CV = 4.0%) and reliability (GABA+/tCr intraclass correlation coefficient [ICC] = 0.77; GABA+/water ICC = 0.87) in the dlPFC. The rACC showed acceptable (but comparatively lower) repeatability (mean GABA+/tCr CV = 8.0%; mean GABA+/water CV = 7.5%), yet low-moderate reliability (GABA+/tCr ICC = 0.40; GABA+/water ICC = 0.44). CONCLUSION: The present study found excellent GABA+ MRS repeatability and reliability in the dlPFC. The rACC showed inferior results, possibly because of a combination of shimming impedance and measurement error. These data suggest that MEGA-PRESS can be utilized to reliably distinguish participants based on dlPFC GABA+ levels, whereas the mixed results in the rACC merit further investigation.

Efficacy and safety of dasotraline in adults with binge-eating disorder: a randomized, placebo-controlled, fixed-dose clinical trial.

OBJECTIVE: The aim of this fixed-dose study was to evaluate the efficacy and safety of dasotraline in the treatment of patients with binge-eating disorder (BED). METHODS: Patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for BED were randomized to 12 weeks of double-blind treatment with fixed doses of dasotraline (4 and 6 mg/d), or placebo. The primary efficacy endpoint was change in number of binge-eating (BE) days per week at week 12. Secondary efficacy endpoints included week 12 change on the BE CGI-Severity Scale (BE-CGI-S) and the Yale-Brown Obsessive-Compulsive Scale Modified for BE (YBOCS-BE). RESULTS: At week 12, treatment with dasotraline was associated with significant improvement in number of BE days per week on the dose of 6 mg/d (N = 162) vs placebo (N = 162; -3.47 vs -2.92; P = .0045), but not 4 mg/d (N = 161; -3.21). Improvement vs placebo was observed for dasotraline 6 and 4 mg/d, respectively, on the BE-CGI-S (effect size [ES]: 0.37 and 0.27) and on the YBOCS-BE total score (ES: 0.43 and 0.29). The most common adverse events on dasotraline were insomnia, dry mouth, headache, decreased appetite, nausea, and anxiety. Changes in blood pressure and pulse were minimal. CONCLUSION: Treatment with dasotraline 6 mg/d (but not 4 mg/d) was associated with significantly greater reduction in BE days per week. Both doses of dasotraline were generally safe and well-tolerated and resulted in global improvement on the BE-CGI-S, as well as improvement in BE related obsessional thoughts and compulsive behaviors on the YBOCS-BE. These results confirm the findings of a previous flexible dose study.

Review Article: Anabolic-Androgenic Steroids, Violence, and Crime: Two Cases and Literature Review.

BACKGROUND AND OBJECTIVES: Anabolic-androgenic steroid (AAS) use has become a major worldwide substance use disorder, affecting tens of millions of individuals. Importantly, it is now increasingly recognized that some individuals develop uncharacteristically violent or criminal behaviors when using AAS. We sought to summarize available information on this topic. METHODS: We reviewed the published literature on AAS-induced behavioral effects and augmented this information with extensive observations from our clinical and forensic experience. RESULTS: It is now generally accepted that some AAS users develop uncharacteristically violent or criminal behaviors while taking these drugs. Although these behaviors may partially reflect premorbid psychopathology, sociocultural factors, or expectational effects, accumulating evidence suggests that they are also attributable to biological effects of AAS themselves. The mechanism of these effects remains speculative, but preliminary data suggest a possible role for brain regions involved in emotional reactivity, such as the amygdala and regions involved in cognitive control, including the frontal cortex. For unknown reasons, these effects appear idiosyncratic; most AAS users display few behavioral effects, but a minority develops severe effects. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Professionals encountering AAS users in clinical or forensic settings should be alert to the possibility of AAS-induced violence or criminality and should employ strategies to assess whether AAS is indeed a contributory factor in a given case. Further research is needed to elucidate the mechanism of AAS-induced violence and to explain why only a subset of AAS users appears vulnerable to these effects. (Am J Addict 2021;00:00-00).

THE CHALLENGES OF METABOLIC SYNDROME IN EATING DISORDERS.

A number of studies have examined the association of the three major eating disorders - anorexia nervosa, bulimia nervosa, and binge-eating disorder - with metabolic syndrome, or with individual components of metabolic syndrome, such as obesity, type 2 diabetes, hypertension, and dyslipidemia. Present evidence suggests that anorexia nervosa confers no excess risk of metabolic syndrome and may be associated with lower risk of certain metabolic syndrome components, including obesity and type 2 diabetes. Bulimia nervosa shows associations with increased risk for metabolic syndrome components in some studies, but not in others. Binge-eating disorder, however, is strongly associated with increased risk for both metabolic syndrome and its components - and these associations appear to be mediated not only through elevated body weight, but also possible body-weight-independent factors. Given that binge-eating disorder is the most common eating disorder, treatment and prevention of metabolic syndrome in this group represents a significant clinical and public health challenge.

Aging male symptomatology and eating behavior.

OBJECTIVE: The literature on eating disorders in older males is still very limited. We assessed the relationship between aging male symptomatology and eating behavior in middle-aged and older men. METHOD: We distributed anonymous questionnaires to men aged 40-75 years living in or near Innsbruck, Austria, covering demographic items, current eating disorder symptoms (as defined by DSM-5), and associated measures of eating pathology, body image, and sports activity (including exercise addiction). We also administered the Aging Males' Symptoms scale (AMS), and classified respondents as "high-AMS" (AMS score ≥37; N = 82) or "low-AMS" (AMS score <37; N = 386). RESULTS: High-AMS men reported a significantly higher mean current BMI, a greater prevalence of eating disorder symptoms, higher scores on the Eating Disorder Examination Questionnaire, greater risk of exercise addiction, and more negative body image than low-AMS men. DISCUSSION: We found a marked association between aging-male symptomatology and eating-disorder symptomatology in aging men. Our findings suggest that clinicians should carefully inquire about eating disorder symptoms in men aged 40 and above reporting aging-male symptomatology. Importantly, several men in the study reported "purging" via excessive exercise (as opposed to the more common methods of vomiting or use of laxatives or diuretics), and therefore this should be a subject of inquiry in clinical evaluations. To pursue these findings, subsequent studies of eating disorders in older men should consider assessing endocrinological measures, particularly testosterone levels, and should use longitudinal designs.

Cardiovascular Toxicity of Illicit Anabolic-Androgenic Steroid Use.

BACKGROUND: Millions of individuals have used illicit anabolic-androgenic steroids (AAS), but the long-term cardiovascular associations of these drugs remain incompletely understood. METHODS: Using a cross-sectional cohort design, we recruited 140 experienced male weightlifters 34 to 54 years of age, comprising 86 men reporting ≥2 years of cumulative lifetime AAS use and 54 nonusing men. Using transthoracic echocardiography and coronary computed tomography angiography, we assessed 3 primary outcome measures: left ventricular (LV) systolic function (left ventricular ejection fraction), LV diastolic function (early relaxation velocity), and coronary atherosclerosis (coronary artery plaque volume). RESULTS: Compared with nonusers, AAS users demonstrated relatively reduced LV systolic function (mean±SD left ventricular ejection fraction = 52±11% versus 63±8%; P<0.001) and diastolic function (early relaxation velocity = 9.3±2.4 cm/second versus 11.1±2.0 cm/second; P<0.001). Users currently taking AAS at the time of evaluation (N=58) showed significantly reduced LV systolic (left ventricular ejection fraction = 49±10% versus 58±10%; P<0.001) and diastolic function (early relaxation velocity = 8.9±2.4 cm/second versus 10.1±2.4 cm/second; P=0.035) compared with users currently off-drug (N=28). In addition, AAS users demonstrated higher coronary artery plaque volume than nonusers (median [interquartile range] 3 [0, 174] mL3 versus 0 [0, 69] mL3; P=0.012). Lifetime AAS dose was strongly associated with coronary atherosclerotic burden (increase [95% confidence interval] in rank of plaque volume for each 10-year increase in cumulative duration of AAS use: 0.60 SD units [0.16-1.03 SD units]; P=0.008). CONCLUSIONS: Long-term AAS use appears to be associated with myocardial dysfunction and accelerated coronary atherosclerosis. These forms of AAS-associated adverse cardiovascular phenotypes may represent a previously underrecognized public-health problem.

Associations of anabolic-androgenic steroid use with other behavioral disorders: an analysis using directed acyclic graphs.

BACKGROUND: Anabolic-androgenic steroid (AAS) use is known to be associated with other psychiatric disorders, such as body image disorders, conduct disorder/sociopathy, and other substance use disorders (SUD) - but the causal pathways among these conditions remain poorly delineated. METHODS: We created a directed acyclic graph to diagram hypothesized relationships among AAS use and dependence, body image disorder (BID), conduct disorder/sociopathy, and other SUD. Using proportional hazards models, we then assessed potentially causal relationships among these variables, using a dataset of 233 male weightlifters, of whom 102 had used AAS. RESULTS: BID and conduct disorder/sociopathy both strongly contributed to the development of AAS use, but did not appear to contribute further to the progression from AAS use to AAS dependence. Other SUD beginning prior to first AAS use - whether broadly defined or restricted only to opioids - failed to show an effect on AAS use or progression to AAS dependence. Conversely, AAS use contributed significantly to the subsequent first-time development of opioid use disorders but did not significantly increase the risk for first-time development of non-opioid SUD, taken as a whole. CONCLUSIONS: Our analysis suggests that AAS use and other SUD are mutually attributable to underlying conduct disorder/sociopathy. SUD do not appear to represent a 'gateway' to subsequent AAS use. AAS use may represent a gateway to subsequent opioid use disorder, but probably not to other SUD.

Time course of the effects of lisdexamfetamine dimesylate in two phase 3, randomized, double-blind, placebo-controlled trials in adults with binge-eating disorder.

OBJECTIVE: This study examined the time course of efficacy-related endpoints for lisdexamfetamine dimesylate (LDX) versus placebo in adults with protocol-defined moderate to severe binge-eating disorder (BED). METHODS: In two 12-week, double-blind, placebo-controlled studies, adults meeting DSM-IV-TR BED criteria were randomized 1:1 to receive placebo or dose-optimized LDX (50 or 70 mg). Analyses across visits used mixed-effects models for repeated measures (binge eating days/week, binge eating episodes/week, Yale-Brown Obsessive Compulsive Scale modified for Binge Eating [Y-BOCS-BE] scores, percentage body weight change) and chi-square tests (Clinical Global Impressions-Improvement [CGI-I; from the perspective of BED symptoms] scale dichotomized as improved or not improved). These analyses were not part of the prespecified testing strategy, so reported p values are nominal (unadjusted and descriptive only). RESULTS: Least squares mean treatment differences for change from baseline in both studies favored LDX over placebo (all nominal p values < .001) starting at Week 1 for binge eating days/week, binge-eating episodes/week, and percentage weight change and at the first posttreatment assessment (Week 4) for Y-BOCS-BE total and domain scores. On the CGI-I, more participants on LDX than placebo were categorized as improved starting at Week 1 in both studies (both nominal p values < .001). Across these efficacy-related endpoints, the superiority of LDX over placebo was maintained at each posttreatment assessment in both studies (all nominal p values < .001). DISCUSSION: In adults with BED, LDX treatment appeared to be associated with improvement on efficacy measures as early as 1 week, which was maintained throughout the 12-week studies.

Lisdexamfetamine Dimesylate Effects on Binge Eating Behaviour and Obsessive-Compulsive and Impulsive Features in Adults with Binge Eating Disorder.

In a published 11-week, placebo-controlled trial, 50 and 70 mg/d lisdexamfetamine dimesylate (LDX), but not 30 mg/d LDX, significantly reduced binge eating days (primary endpoint) in adults with binge eating disorder (BED). This report provides descriptions of LDX effects on secondary endpoints (Binge Eating Scale [BES]; Three-Factor Eating Questionnaire [TFEQ]; Yale-Brown Obsessive Compulsive Scale modified for Binge Eating [Y-BOCS-BE]; and the Barratt Impulsiveness Scale, version 11 [BIS-11]) from that study. Week 11 least squares mean treatment differences favoured all LDX doses over placebo on the BES (p ≤ 0.03), TFEQ Disinhibition and Hunger subscales (all p < 0.05), and Y-BOCS-BE total, obsessive, and compulsive scales (all p ≤ 0.02) and on BIS-11 total score at 70 mg/d LDX (p = 0.015) and the TFEQ Cognitive Restraint subscale at 30 and 70 mg/d LDX (both p < 0.05). These findings indicate that LDX decreased global binge eating severity and obsessive-compulsive and impulsive features of BED in addition to binge eating days.

EFFECTIVENESS OF INPATIENT INSULIN ORDER SETS USING HUMAN INSULINS IN NONCRITICALLY ILL PATIENTS IN A RURAL HOSPITAL.

OBJECTIVE: Recent guidelines recommend a physiologic approach to non-intensive care unit (ICU) inpatient glucose management utilizing basal-bolus with correctional (BBC) insulin over traditional sliding-scale insulin monotherapy. Unfortunately, few studies exist using a BBC approach restricted to human insulins (regular and neutral protamine Hagedorn [NPH]). This study evaluated changes in provider prescribing patterns, effects on blood glucose, and safety with implementation of hospital order sets for BBC using human insulins. METHODS: Order sets were developed for non-ICU inpatients, consisting of basal, prandial, and correctional insulin using NPH and regular human insulins. Evaluation compared a 4-month period before (admissions, n = 274) with a 4-month period after order set availability (n = 302). Primary outcome was change in insulin prescribing patterns. Secondary outcomes included use of nonpreferred diabetes treatments, hemoglobin A1c testing, mean daily blood glucose, and incidence of hypoglycemia. RESULTS: Use of BBC insulin regimen increased from 10.6 to 27.5% after order set implementation (P<.001). Use of oral antihyperglycemic agents decreased from 24.1 to 14.9% after implementation (P = .006). Hemoglobin A1c testing rose from 50.0 to 62.3% after (P = .003). Mean daily blood glucose improved, with an estimated mean difference of 14.4 mg/dL (95% confidence interval, 2.2 to 26.5 mg/dL) over hospital days 3 through 9 (P = .02). There was no significant change in the incidence of moderate or severe hypoglycemia. CONCLUSION: Implementation of hospital-wide human insulin order sets led to improvements in prescribing practices and blood glucose control, without increasing the incidence of hypoglycemia. These order sets may be useful for facilities limited by formulary and cost considerations to the use of older human insulins.

Anti-Social Behaviors Associated with Anabolic-Androgenic Steroid Use among Male Adolescents.

Anabolic-androgenic steroids (AAS) have been linked to a range of problematic behaviors, but AAS use is still sometimes portrayed as more benign than other forms of classical drug abuse. To address this issue, we compared the prevalence of anti-social behaviors among adolescent AAS users, non-AAS illicit drug users, and drug non-users. We examined 3 waves (2004, 2008, and 2012) of self-reported cross-sectional data from a secondary school survey conducted in Stockholm, Sweden (total n = 19,773; response percentage, 79.6%). Across all survey years, the risk ratios for virtually all measured anti-social behaviors were significantly higher among AAS users compared to non-AAS illicit drug users and to drug non-users.

The lifetime prevalence of anabolic-androgenic steroid use and dependence in Americans: current best estimates.

BACKGROUND AND OBJECTIVES: Although various surveys have tracked the prevalence of anabolic-androgenic steroid (AAS) use in American teenagers and young adults, no recent surveys have assessed the lifetime prevalence of AAS use in Americans overall. We therefore analyzed serial youth-survey data to derive estimates of the lifetime prevalence of AAS use in the current American general population. METHODS: We first determined the distribution of age of onset of AAS use, based on pooled data from nine studies. Using this distribution, we then developed equations to project the eventual lifetime prevalence of AAS use among young survey respondents, once they aged and completed the period of risk for initiating AAS. We similarly calculated the denominator of lifetimes of risk for AAS use in the total American population. We next applied these equations to four independent national youth datasets to derive current American general-population estimates for lifetime AAS use. Finally, using data from 10 pooled studies, we estimated the lifetime prevalence of AAS dependence among AAS users. RESULTS: Age-of-onset studies consistently showed that AAS use begins later than most drugs, with only 22% of users (95% confidence interval: 19-25%) starting before age 20. Applying the age-of-onset findings to national youth datasets, we estimated that among Americans currently age 13-50 years, 2.9-4.0 million have used AAS. Within this group, roughly 1 million may have experienced AAS dependence. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Although subject to various limitations, our estimation techniques suggest a surprisinigly high prevalence of AAS use and dependence among Americans.

Readiness for treatment predicts depression outcomes in a partial hospital program.

Evidence-based interventions vary in effectiveness for individuals with depression, which has a large public health burden. Readiness for change or treatment can be an important individual difference predictor of depression outcomes. To inform public service initiatives targeting readiness for treatment, characterizing readiness across settings and levels of care is key. However, limited data exist on the role of readiness for treatment in acute psychiatric settings and in particular, partial hospital programs which are key points in the continuity of inpatient and outpatient care. The present study assessed readiness for treatment in terms of importance, confidence, and motivation to engage in a partial hospital program and tested whether higher levels of readiness were associated with better treatment outcomes among clients with depression. Participants (N = 192) with major depressive disorder rated their readiness for treatment (Readiness Rulers), depression (Patient Health Questionnaire-9), and global improvement (Clinical Global Impression Scale-Improvement Self-Report) while enrolled in a partial hospital program. Generalized linear regression models assessed the effect of baseline readiness on outcomes at discharge, adjusted for baseline level of the outcome, age, sex, race, and ethnicity. Greater baseline readiness predicted reduced depression and better global improvement at discharge. Higher confidence and motivation to engage in treatment, but not importance, were associated with better depression outcomes. Identifying and addressing readiness for treatment by leveraging public health systems and services (e.g., help lines, family interventions) prior to or upon starting a partial hospital program may be useful to maximize gains in treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Causal factors in childhood and adolescence leading to anabolic-androgenic steroid use: A machine learning approach.

Background: Prior research has demonstrated associations between anabolic-androgenic steroid (AAS) use and features from several childhood and adolescent psychosocial domains including body image concerns, antisocial traits, and low levels of parental care. However, prior approaches have been limited by their focus on individual features and lack of consideration of the relevant causal structure. Methods: We re-analyzed data from a previous cross-sectional cohort study of 232 male weightlifters aged 18-40, of whom 101 had used AAS. These men completed retrospective measures of features from their childhood and early adolescence, including body image concerns, eating disorder psychopathology, antisocial traits, substance use, and family relationships. Using an approach informed by principles of causal inference, we applied four machine-learning methods - lasso regression, elastic net regression, random forests, and gradient boosting - to predict AAS use. Results: The four methods yielded similar receiver operating curves, mean area under the curve (range 0.66 to 0.72), and sets of highly important features. Features related to adolescent body image concerns (especially muscle dysmorphia symptoms) were the strongest predictors. Other important features were adolescent rebellious behaviors; adolescent feelings of ineffectiveness and lack of interoceptive awareness; and low levels of paternal care. Conclusions: Applying machine learning within a causally informed approach to re-analyze data from a prior study of weightlifters, we identified six factors (most prominently those related to adolescent body image concerns) as proposed causal factors for the development of AAS use. Compared with the prior analyses, this approach achieved greater methodologic rigor and yielded stronger and broader findings.