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.

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.

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.

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).

Antidepressant use and risk of intubation or death in hospitalized patients with COVID-19: A retrospective cohort study of clinical effectiveness.

Initial controlled trials of the serotonergic antidepressant fluvoxamine showed promise for treatment of mild to moderate COVID-19 in outpatients, although more recent outpatient data have been less encouraging. Turning to studies of hospitalized patients, a retrospective cohort study by Hoertel and associates in 2021 found a markedly reduced risk of intubation or death among patients hospitalized with COVID-19 who were receiving serotonergic antidepressants at the time of admission vs. those not receiving antidepressants. In an attempt to replicate these latter findings, we performed a similarly designed study of 500 individuals hospitalized with COVID-19 in a large academic hospital system who were taking a serotonergic antidepressant at the time of admission compared with two groups (N = 573 and N = 593) not receiving an antidepressant. In analyses controlling for demographic and clinical variables, we found no significant difference in effect between the antidepressant group and either of the two comparison groups [hazard ratios (95% CI) for intubation or death 1.1 (0.83-1.5) and 1.1 (0.86-1.5); and for death alone 1.3 (0.93-1.8) and 1.1 (0.85-1.7)]. Examining the results of our study, along with those of Hoertel et al. and three additional retrospective cohort studies in inpatients published in the interim, the data permit only very limited conclusions, with the findings on the effect of serotonergic antidepressants ranging from a strongly protective effect to no effect. Although there are numerous threats to validity that might account for this wide range of findings, we could not identify any principal factor or set of factors that could clearly explain the differences.

Pilot development and feasibility of telehealth Community Reinforcement and Family Training (CRAFT) for early psychosis and substance use.

Substance use is associated with poor outcomes for individuals with early psychosis. Community Reinforcement and Family Training (CRAFT) is an evidence-based approach that helps families to reduce substance use, engage in treatment, and improve family wellbeing, but it has not yet been studied for psychosis and substance use. The present study aimed to develop and evaluate a telehealth intervention utilizing CRAFT for families experiencing early psychosis and substance use. Twenty family members completed six to eight telehealth sessions of CRAFT adapted for early psychosis (CRAFT-EP). Participants completed an assessment battery at baseline, mid- and post-intervention, a three-month follow-up, surveys after each session, and a focus group to measure mean percentage of sessions completed, mean program satisfaction ratings, telehealth preference, and qualitative feedback. Participants had 100% session completion, and program satisfaction was at or near excellent for 99% of sessions. Half of participants preferred a primarily virtual hybrid program, whereas 45% preferred exclusively virtual visits. Communication was the most helpful topic, and participants requested additional written examples and resources. CRAFT-EP is feasible and acceptable to serve as the active intervention in a pilot randomized controlled trial comparing treatment as usual plus CRAFT-EP to treatment as usual.

Using Wearable Cameras to Investigate Health-Related Daily Life Experiences: A Literature Review of Precautions and Risks in Empirical Studies.

Automated, wearable cameras can benefit health-related research by capturing accurate and objective information about individuals' daily experiences. However, wearable cameras present unique privacy- and confidentiality-related risks due to the possibility of the images capturing identifying or sensitive information from participants and third parties. Although best practice guidelines for ethical research with wearable cameras have been published, limited information exists on the risks of studies using wearable cameras. The aim of this literature review was to survey risks related to using wearable cameras, and precautions taken to reduce those risks, as reported in empirical research. Forty-five publications, comprising 36 independent studies, were reviewed, and findings revealed that participants' primary concerns with using wearable cameras included physical inconvenience and discomfort in certain situations (e.g., public settings). None of the studies reviewed reported any serious adverse events. Although it is possible that reported findings do not include all risks experienced by participants in research with wearable cameras, our findings suggest a low level of risk to participants. However, it is important that investigators adopt recommended precautions, which can promote autonomy and reduce risks, including participant discomfort.

Measuring Ostracism-Induced Changes in Consumption of Palatable Food: Feasibility of a Novel Behavioral Task.

Purpose: Ostracism is a highly aversive interpersonal experience. Previous research suggests that it can increase consumption of highly palatable food in some individuals, but decrease it in others. Thus, we developed the Cyberball-Milkshake Task (CMT), to facilitate research investigating individual differences in ostracism's effects on consumption of highly palatable food. We present data on feasibility for the CMT in a sample of young adult women. Materials and Methods: Participants were 22 women, 18-30 years old, reporting very low or very high levels of emotional eating at screening. Participants performed the CMT, which consisted of 12 trials. Each trial included: playing a round of Cyberball (a computerized game of catch with fictitious "other participants" programmed to either include or exclude the participant); viewing a chocolate image; and then consuming a participant-determined amount of milkshake. Participants subsequently played an additional inclusion and exclusion round of Cyberball, each immediately followed by questionnaires assessing current mood and recent Cyberball experience. Results: Cyberball exclusion (vs. inclusion) was associated with large, significant increases in reported ostracism and threats to self-esteem; exclusion's effects on affect were in the expected direction (e.g., increased negative affect), but generally small and non-significant. Milkshake intake was measurable for 95% of participants, on 96% of trials. Intake decreased quadratically across trials, with a steep negative slope for low trial numbers that decreased to the point of being flat for the highest trial numbers. Discussion: The CMT is a generally feasible approach to investigating ostracism's effects on consumption of highly palatable food. The feasibility (and validity) of the CMT may benefit from modification (e.g., fewer trials and longer rounds of Cyberball). Future research should examine whether performance on a modified version of the CMT predicts real-world behavior in a larger sample.

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).

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.

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, Flexible-Dose Clinical Trial.

OBJECTIVE: Binge-eating disorder (BED) is the most prevalent eating disorder; however, few evidence-based treatments are available. The aim of this study was to evaluate the efficacy and safety of dasotraline, a novel dopamine and norepinephrine reuptake inhibitor, in adults with BED. METHODS: Patients with a DSM-5 diagnosis of BED (intent-to-treat sample, N = 315) were randomized to 12 weeks of double-blind treatment with once-daily, flexible doses (4, 6, or 8 mg/d) of dasotraline or placebo. Primary endpoint was change in diary-based assessment of number of binge-eating days per week at week 12. Key secondary endpoints included changes from baseline in Clinical Global Impressions-Severity of Illness scale (CGI-S) and Yale-Brown Obsessive Compulsive Scale Modified for Binge-Eating (YBOCS-BE) and percentage of subjects with cessation of binge eating in the final 4 weeks. RESULTS: Treatment with dasotraline was associated with a significantly greater reduction in binge-eating days per week at study endpoint (vs placebo; least squares mean [SE] difference score, -0.99 [0.17]; P < .0001; effect size [ES], 0.74). Significant endpoint improvement was observed for the 3 key secondary measures, CGI-S (P < .0001; ES, 0.95), YBOCS-BE (P < .0001; ES, 0.96), and 4-week cessation of binge eating (46.5% vs 20.6%; P < .0001). The most common adverse events in the dasotraline vs placebo groups were insomnia (44.6% vs 8.1%), dry mouth (27.4% vs 5.0%), decreased appetite (19.7% vs 6.9%), and anxiety (17.8% vs 2.5%). Discontinuation due to adverse events occurred in 11.3% of patients on dasotraline vs 2.5% on placebo. CONCLUSIONS: The results of this placebo-controlled, double-blind study found dasotraline to be an efficacious, safe, and generally well-tolerated treatment for BED. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02564588.

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.

Targeted Treatment of Individuals With Psychosis Carrying a Copy Number Variant Containing a Genomic Triplication of the Glycine Decarboxylase Gene.

BACKGROUND: The increased mutational burden for rare structural genomic variants in schizophrenia and other neurodevelopmental disorders has so far not yielded therapies targeting the biological effects of specific mutations. We identified two carriers (mother and son) of a triplication of the gene encoding glycine decarboxylase, GLDC, presumably resulting in reduced availability of the N-methyl-D-aspartate receptor coagonists glycine and D-serine and N-methyl-D-aspartate receptor hypofunction. Both carriers had a diagnosis of a psychotic disorder. METHODS: We carried out two double-blind, placebo-controlled clinical trials of N-methyl-D-aspartate receptor augmentation of psychotropic drug treatment in these two individuals. Glycine was used in the first clinical trial, and D-cycloserine was used in the second one. RESULTS: Glycine or D-cycloserine augmentation of psychotropic drug treatment each improved psychotic and mood symptoms in placebo-controlled trials. CONCLUSIONS: These results provide two independent proof-of-principle demonstrations of symptom relief by targeting a specific genotype and explicitly link an individual mutation to the pathophysiology of psychosis and treatment response.

Supraphysiologic-dose anabolic-androgenic steroid use: A risk factor for dementia?

Supraphysiologic-dose anabolic-androgenic steroid (AAS) use is associated with physiologic, cognitive, and brain abnormalities similar to those found in people at risk for developing Alzheimer's Disease and its related dementias (AD/ADRD), which are associated with high brain ß-amyloid (Aß) and hyperphosphorylated tau (tau-P) protein levels. Supraphysiologic-dose AAS induces androgen abnormalities and excess oxidative stress, which have been linked to increased and decreased expression or activity of proteins that synthesize and eliminate, respectively, Aß and tau-P. Aß and tau-P accumulation may begin soon after initiating supraphysiologic-dose AAS use, which typically occurs in the early 20s, and their accumulation may be accelerated by other psychoactive substance use, which is common among non-medical AAS users. Accordingly, the widespread use of supraphysiologic-dose AAS may increase the numbers of people who develop dementia. Early diagnosis and correction of sex-steroid level abnormalities and excess oxidative stress could attenuate risk for developing AD/ADRD in supraphysiologic-dose AAS users, in people with other substance use disorders, and in people with low sex-steroid levels or excess oxidative stress associated with aging.