This study examines the prospective associations of alcohol and drug misuse with suicidal behaviors among service members who have left active duty. We also evaluate potential moderating effects of other risk factors and whether substance misuse signals increased risk of transitioning from thinking about to attempting suicide.

US Army veterans and deactivated reservists (N = 6,811) completed surveys in 2016–2018 (T1) and 2018–2019 (T2). Weights-adjusted logistic regression was used to estimate the associations of binge drinking, smoking/vaping, cannabis use, prescription drug abuse, illicit drug use, alcohol use disorder (AUD), and drug use disorder (DUD) at T1 with suicide ideation, plan, and attempt at T2. Interaction models tested for moderation of these associations by sex, depression, and recency of separation/deactivation. Suicide attempt models were also fit in the subgroup with ideation at T1 (n = 1,527).

In models controlling for socio-demographic characteristics and prior suicidality, binge drinking, cannabis use, prescription drug abuse, illicit drug use, and AUD were associated with subsequent suicidal ideation (AORs = 1.42–2.60, ps < .01). Binge drinking, AUD, and DUD were associated with subsequent suicide plan (AORs = 1.23–1.95, ps < .05). None of the substance use variables had a main effect on suicide attempt; however, interaction models suggested certain types of drug use predicted attempts among those without depression. Additionally, the effects of smoking/vaping and AUD differed by sex. Substance misuse did not predict the transition from ideation to attempt.

Alcohol and drug misuse are associated with subsequent suicidal behaviors in this population. Awareness of differences across sex and depression status may inform suicide risk assessment.

Cognitive impairment is a common feature of multiple sclerosis (MS), and its severity may be influenced by several factors, such as biological sex and levels of cognitive reserve (CR). The relationship between sex, CR, and cognition has not yet been fully investigated. Therefore, the present study aimed to explore sex differences in CR building and the effect of sex and CR on cognitive performance in MS.

233 participants underwent the Brief Repeatable Battery of Neuropsychological Tests (BRB-N), the Stroop test, and the Cognitive Reserve Scale. The t-test was performed to compare sociodemographic variables, Italian adaptation of the Cognitive Reserve Scale, and cognitive test scores between sexes. To evaluate the effect of CR and sex and their interaction on cognitive performance several models of multivariate analyses of covariance were performed (dependent variables: all subtests of Brief Repeatable Battery of Neuropsychological Tests and Stroop scores; independent variables: sex and CR). Covariates included age, Expanded Disability Status Scale, and BDI-II scores.

Women showed higher levels of CR, particularly in daily activities (t = −5.848, p<.001), hobbies (t = −2.591, p = .010), and social life (t = −2.362, p = .011). Sex differences were noted in verbal memory and fluency (with women outperforming men) and processing speed (with men performing better than women). Multivariate analyses revealed a nonsignificant interaction between CR and sex on cognition (Λ=.950, F(10,260)=.813, p = .617, ηp2 = .050).

CR and sex seemed to affect cognitive performance independently in pwMS. This highlights the importance of considering both factors in cognitive assessment, and that both sexes may benefit from specific psychoeducational training aimed at increasing CR levels.

Access to “big data” is a boon for researchers, fostering collaboration and resource-sharing to accelerate advancements across fields. Yet, disentangling complex datasets has been hindered by methodological limitations, calling for alternative, interdisciplinary approaches to parse manifold multi-directional pathways between clinical features, particularly for highly heterogeneous autism spectrum disorder (ASD). Despite a long history of male-bias in ASD prevalence, no consensus has been reached regarding mechanisms underlying sex-related discrepancies.

Applying a novel network-theory-based approach, we extracted data-driven, clinically-relevant insights from a well-characterized sample (http://sfari.org/simons-simplex-collection) of autistic males (N = 2175, Age = 8.9 ± 3.5 years) and females (N = 334, Age = 9.2 ± 3.7 years). Expert clinical review of exploratory factor analysis (EFA) results yielded factors of interest in sensory, social, and restricted and repetitive behavior domains. To offset inherent confounds of sample imbalance, we identified a comparison subgroup of males (N = 331) matched to females (by age, IQ). We applied data-driven causal discovery analysis (CDA) using Greedy Fast Causal Inference (GFCI) on three groups (all females, all males, matched males). Structural equation modeling (SEM) extracted measures of model-fit and effect sizes for causal relationships between sex, age-at-enrollment, and IQ on EFA-determined factors.

We identified potential targets for intervention at nodes with mediating or indirect effects. For example, in the female and matched male groups, analyses suggest mitigating RRB domain behaviors may lead to downstream reductions in oppositional and self-injurious behaviors.

Our investigation unveiled sex-specific directional relationships that inform our understanding of differing needs and outcomes associated with biological sex in autism and may serve to further development of targeted interventions.

Obesity-related cardiometabolic comorbidity is common in major depressive disorder (MDD). However, sex differences and MDD recurrence may modify the MDD-obesity-link.

Sex-specific associations of MDD recurrence (single [MDDS] or recurrent episodes [MDDR]) and obesity-related traits were analyzed in 4.100 adults (51.6% women) from a cross-sectional population-based cohort in Germany (SHIP-Trend-0). DSM-IV-based lifetime MDD diagnoses and MDD recurrence status were obtained through diagnostic interviews. Obesity-related outcomes included anthropometrics (weight, body mass index, waist- and hip-circumference, waist-to-hip ratio, waist-to-height ratio), bioelectrical impedance analysis of body fat mass and fat-free mass, and subcutaneous (SAT) and visceral adipose tissue (VAT) from abdominal magnetic resonance imaging. Sex-stratified linear regression models predicting obesity-related traits from MDD recurrence status were adjusted for age, education, and current depressive symptoms.

790 participants (19.3%) fulfilled lifetime MDD criteria (23.8% women vs. 14.5% men, p<0.001). In women, MDDS was inversely associated with anthropometric indicators of general and central obesity, while MDDR was positively associated with all obesity-related traits, except waist-to-hip ratio and fat-free mass. In women, MDDR versus MDDS was associated with higher levels of obesity across all outcomes except fat-free mass. In men, MDD was positively associated with SAT regardless of MDD recurrence. Additionally, lifetime MDD was positively associated with VAT in men. Results remained significant in sensitivity analyses after exclusion of participants with current use of antidepressants.

The MDD-obesity association is modified by MDD recurrence and sex independent of current depressive symptoms. Accounting for sex and MDD recurrence may identify individuals with MDD at increased cardiometabolic risk.

Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.

As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.

Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.

Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Gambling disorder (GD) and bulimic spectrum eating disorders (BSDs) not only share numerous psychopathological, neurobiological, and comorbidity features but also are distinguished by the presence of inappropriate behaviours related to impulsivity and compulsivity. This study aimed to emphasise the differences and similarities in the main impulsivity and compulsivity features between GD and BSD patients, and to analyse the potential influence of sex in these domains.

Using self-reported and neurocognitive measures, we assessed different impulsive–compulsive components in a sample of 218 female and male patients (59 with BSD and 159 with GD) and 150 healthy controls.

We observed that GD and BSDs exhibited elevated levels of impulsivity and compulsivity in all the dimensions compared to healthy controls. Moreover, these disorders showed differences in several personality traits, such as high novelty seeking in GD, and low persistence and high harm avoidance in BSDs. In addition, patients with BSDs also displayed a trend towards greater impulsive choice than GD patients. Regarding sex effects, GD women presented higher overall impulsivity and compulsivity than GD men. Nevertheless, no sex differences were found in BSDs.

Clinical interventions should consider these deficits to enhance their effectiveness, including adjunctive treatment to target these difficulties. Our findings also provide support to the relevance of sex in GD, which should also be considered in clinical interventions.

Previous research suggests an increase in schizophrenia population attributable risk fraction (PARF) for cannabis use disorder (CUD). However, sex and age variations in CUD and schizophrenia suggest the importance of examining differences in PARFs in sex and age subgroups.

We conducted a nationwide Danish register-based cohort study including all individuals aged 16–49 at some point during 1972–2021. CUD and schizophrenia status was obtained from the registers. Hazard ratios (HR), incidence risk ratios (IRR), and PARFs were estimated. Joinpoint analyses were applied to sex-specific PARFs.

We examined 6 907 859 individuals with 45 327 cases of incident schizophrenia during follow-up across 129 521 260 person-years. The overall adjusted HR (aHR) for CUD on schizophrenia was slightly higher among males (aHR = 2.42, 95% CI 2.33–2.52) than females (aHR = 2.02, 95% CI 1.89–2.17); however, among 16–20-year-olds, the adjusted IRR (aIRR) for males was more than twice that for females (males: aIRR = 3.84, 95% CI 3.43–4.29; females: aIRR = 1.81, 95% CI 1.53–2.15). During 1972–2021, the annual average percentage change in PARFs for CUD in schizophrenia incidence was 4.8 among males (95% CI 4.3–5.3; p < 0.0001) and 3.2 among females (95% CI 2.5–3.8; p < 0.0001). In 2021, among males, PARF was 15%; among females, it was around 4%.

Young males might be particularly susceptible to the effects of cannabis on schizophrenia. At a population level, assuming causality, one-fifth of cases of schizophrenia among young males might be prevented by averting CUD. Results highlight the importance of early detection and treatment of CUD and policy decisions regarding cannabis use and access, particularly for 16–25-year-olds.

Studies that examined sex differences in first-episode patients consistently show that males compared to females have poor premorbid adjustment, earlier age of onset, worse clinical characteristics, and poorer outcomes. However, little is known about potential mediators that could explain these sex differences.

Our sample consisted of 137 individuals with first episode schizophrenia (males, n = 105; 77%) with a mean age of 22.1(s.d. = 4.1) years and mean education of 12.5(s.d. = 1.7) years. At entry, patients were within 2 years of their first psychotic episode onset. Baseline assessments were conducted for premorbid adjustment, symptoms, cognitive functioning, insight, and at 6-months for role and social functioning.

Males as compared to females had poorer premorbid adjustment across several key developmental periods (p < 0.01), an earlier age of onset [M = 20.3(3.3) v. 22.8(5.6), p = 0.002], more negative symptoms (p = 0.044), poorer insight (p = 0.031), and poorer baseline and 6-month role (p = 0.002) and social functioning (p = 0.034). Several of these variables in which males showed impairment were significant predictors of 6-month role and social functioning. Premorbid adjustment and insight mediated the relationship between sex and role and social functioning at 6-months, but not negative symptoms.

Males compared to females were at lower levels across several key premorbid and clinical domains which are strongly associated with functional outcome supporting the hypothesis that males might have a more disabling form of schizophrenia. The relationship between sex with role and social functioning was mediated through premorbid adjustment and insight suggesting pathways for understanding why females might have a less disabling form of schizophrenia.

This study aims to address a gap in the data on cognitive sex differences in persons living with Parkinson disease (PD). There is some evidence that cognitive dysfunction is more severe in male PD, however data on episodic memory and processing speed is incomplete.

One hundred and sixty-seven individuals with a diagnosis of PD were included in this study. Fifty-six of those individuals identified as female. The California Verbal Learning Test 1st edition and the Wechsler Memory Scale 3rd edition were used to evaluate verbal and visuospatial episodic memory and the Wechsler Adult Intelligence Scale 3rd edition was used to evaluate processing speed. Multivariate analysis of covariance was used to identify sex-specific differences across groups.

Our results show that males with PD performed significantly worse than females in verbal and visuospatial recall as well as a trend for the processing speed task of coding.

Our finding of superior performance among females with PD in verbal episodic memory is consistent with reports in both healthy and PD individuals; however, females outperforming males in measures of visuospatial episodic memory is unique to PD. Cognitive deficits preferentially affecting males appear to be associated with frontal lobe-related function. Therefore, males may represent a disease subgroup more susceptible to disease mechanisms affecting frontal lobe deterioration and cognitive disturbances in PD.