Substance use disorders (SUD) are more prevalent among males than females, but recent evidence suggests this gap is narrowing. This shift highlights the need to better understand sex differences in cognitive and psychological characteristics among individuals with SUD. This study aims to explore sex differences in self-reported executive functioning and psychological distress and their associations with severity of SUD symptoms among young adults in SUD treatment.

Data were collected from 97 inpatients (mean age = 23.3 ± 2.6 years) at a SUD treatment center for young adults in Oslo, Norway. Within two weeks of admission, participants completed questionnaires evaluating alcohol and drug-related problems, executive functioning, and psychological distress at intake. These measures were compared between males and females using Welch's t-tests, and the relationships between psychological distress and executive function and severity of drug-related problems were evaluated using Spearman's correlations and linear regression in the whole sample and within each sex.

Both males (n = 65) and females (n = 32) reported high levels of polysubstance use. A majority of the sample scored above the clinical cut-off levels for executive dysfunction (71%) and psychological distress (85%). Females reported more executive function challenges than males in several areas including emotional control (p_FDR < 0.001) and working memory (p_FDR = 0.003). Regression analyses demonstrated associations between increased executive dysfunction and psychological distress and severity of drug use disorder in the whole sample and among males.

These findings emphasize the high psychiatric comorbidity among SUD patients, with females showing elevated executive dysfunction alongside anxiety symptoms. Females in SUD treatment may represent a more clinically severe subgroup. Routine assessment of executive functioning is warranted, and future studies should clarify these associations and their relevance for targeted interventions.

Substance use disorders frequently co-occur with severe mental illness (SMI), and individuals with co-occurring diagnoses often experience greater clinical complexity and poorer treatment outcomes. However, little is known about treatment engagement and outcomes among patients with SMI receiving inpatient addiction treatment in detoxification and rehabilitation settings.

This retrospective cohort study examined patients admitted to an inpatient detoxification and rehabilitation unit at an urban academic behavioral health center between January 1 and March 31, 2024. SMI was defined as a history of a psychotic disorder, bipolar disorder, or prior psychiatric hospitalization. Sociodemographic characteristics, clinical history, treatment course, and post-discharge outcomes were extracted from the electronic medical record. Groups with and without SMI were compared using chi-square and independent-samples t-tests. Time to readmission was evaluated using Kaplan-Meier survival analysis. Multivariable logistic regression examined associations with readmission within one year.

Among 198 patients, 90 (45.5%) met criteria for SMI. Compared with those without SMI, patients with SMI had higher rates of trauma, violence history, unemployment, and prior detoxification or rehabilitation admissions. Despite these differences, there were no significant group differences in detoxification completion, transition to rehabilitation, rehabilitation completion, or length of stay. Readmission rates within one year did not differ between groups in bivariable analyses. In the primary adjusted analysis, SMI was associated with lower odds of readmission (OR = 0.49, 95% CI 0.25-0.98), while greater prior detoxification or rehabilitation utilization was associated with increased readmission risk (OR = 1.04 per admission). The association between SMI and readmission was attenuated in sensitivity analyses.

Patients with SMI admitted to inpatient detoxification and rehabilitation demonstrated greater psychosocial complexity but similar treatment engagement compared with patients without SMI. These findings suggest that structured inpatient addiction treatment settings may support comparable engagement in care among individuals with co-occurring severe psychiatric illness.

Post-traumatic stress disorder (PTSD) is characterized by negative affective symptoms, including anxiety, depression, anhedonia, and fear. The molecular mechanisms underlying these symptoms remain poorly understood. Phosphodiesterase 2A (PDE2A), a regulator of cyclic adenosine monophosphate (cAMP) signaling, has been implicated in neuropsychiatric disorders.

This study aimed to investigate the role of the PDE2A-cAMP-protein kinase A (PKA) signaling pathway in negative emotional behaviors induced by traumatic stress.

Transcriptomic datasets were analyzed to identify differentially expressed genes and enriched pathways. A rat PTSD model was established using single prolonged stress combined with foot shocks (SPS&S). Behavioral tests were performed, and PDE2A-cAMP-PKA signaling alterations in the amygdala were examined. The effects of PDE2A inhibitor Hcyb1 and the PKA inhibitor H89 were evaluated.

Bioinformatics analysis identified PDE2A as a hub gene associated with PTSD, with significant enrichment of the cAMP signaling pathway. SPS&S rats exhibited anxiety-, depression-like behaviors, and anhedonia, accompanied by increased PDE2A expression and reduced cAMP and phosphorylated PKA (p-PKA) levels in the amygdala. Hcyb1 treatment alleviated behavioral deficits, decreased PDE2A expression, and restored cAMP and p-PKA signaling. H89 blocked p-PKA activation and partially reversed the behavioral benefits of Hcyb1.

These findings suggest that amygdala PDE2A-cAMP-PKA signaling is associated with negative emotional behaviors in the SPS&S model. PDE2A inhibition may ameliorate behavioral deficits through PKA-related signaling. However, the peripheral blood transcriptomic data, lack of direct PDE2A activity and cAMP/cGMP measurements, and limited biochemical validation constrain mechanistic interpretation. Further studies using brain-derived datasets and comprehensive biochemical approaches are warranted.

Post-traumatic stress disorder (PTSD) has been linked to various alterations within the immune system, yet the metabolic programming of immune cells remains unexplored. In the current exploratory cross-sectional study, we interrogated immunometabolic function by applying cell-specific metabolic flow cytometry, serum biomarker profiling, and targeted gene expression analysis in peripheral blood mononuclear cells from patients with PTSD (n = 34) compared with healthy controls (n = 32). PTSD was associated with elevated serum IL-6 (p = 0.005) and higher glycolysis- and oxidative pentose phosphate pathway-related markers (identified by CITRUS/SAM using a prespecified FDR threshold of 1%): lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD) across adaptive and innate immune cell subsets (CD4⁺ T, CD8⁺ T, B cells, NK cells, monocytes; Cohen's d = 0.51-0.74). CD4⁺ T cells additionally showed elevated glucose transporter 1 (GLUT1, Cohen's d = 0.76), CD8⁺ T cells demonstrated enhanced carnitine palmitoyl transferase 1A (CPT1a, Cohen's d = 0.54) expression, and monocytes exhibited increased acetyl-CoA carboxylase (ACAC, Cohen's d = 0.69). Expression of inflammatory- and stress-related genes was largely comparable between groups. Together, these data provide preliminary evidence for immunometabolic alterations in PTSD at both cellular and systemic levels. These results could contribute to understanding potential pathophysiological mechanisms and support further investigation of immunometabolism in PTSD.

Early-life adversity increases vulnerability to affective disorders, but the neural alterations underlying sex-dependent susceptibility remain unclear. Here, C57BL/6J mouse pups underwent maternal separation (MS) for 3 h daily from postnatal day 1 to 10, and adult male and female offspring were assessed behaviorally. MS induced significant anxiety-like behavioral alterations in male offspring, whereas comparable anxiogenic changes were not detected in females. c-Fos-based regional screening identified the hippocampus as a candidate region. In males, the reduction in c-Fos-positive cells was further localized to the dorsal and ventral dentate gyrus (DG), whereas females showed no significant change in overall hippocampal c-Fos expression. Transcriptomic analysis of the hippocampus revealed enrichment of inflammation-related pathways and downregulation of neurogenesis-related signatures, whereas histological analyses demonstrated reduced adult DG neurogenesis, including decreased quiescent and activated neural stem cells and reduced DCX immunoreactivity. These neurogenic alterations were accompanied by microglial activation, increased hippocampal pro-inflammatory cytokine expression, reduced IL-10 expression, and increased microglia-neural stem cell proximity. Together, these findings indicate that early-life maternal separation is associated with anxiety-like behavioral alterations in male offspring accompanied by reduced DG neurogenesis and hippocampal inflammatory alterations.

Obsessive-compulsive disorder (OCD) is a chronic condition in which impaired inhibitory control and excessive error monitoring may contribute to maintenance of obsessions and compulsions. This mega-analysis investigates neural activation during response inhibition and error processing using adult (OCD=563; control=348) and child (OCD=83, control=114) data from the ENIGMA-OCD consortium and the ABCD study (probable OCD=343; control=361).

Individual participant data was uniformly processed using HALFpipe to extract statistical maps for response inhibition and error processing contrasts. Bayesian multilevel models were used to assess regional and whole-brain effects of OCD, and to examine the association between the OCD clinical profile and task-related activation.

Across inhibitory control tasks, both OCD and control participants showed robust activation in regions implicated in response inhibition and error processing. During response inhibition, compared to controls, adults with OCD showed stronger somatomotor cortex activation, while children with OCD showed stronger occipital cortex activation. Children with probable OCD from the ABCD cohort showed weaker activity in the frontoparietal network in the anterior insula/frontal operculum region. During error processing, relative to controls, adults with OCD showed weaker activation in fronto-striatal regions, while children with OCD showed stronger activation in frontoparietal and attention networks. Greater OCD symptom severity was associated with weaker task-related activation in adults and stronger activation in children during response inhibition.

Case-control differences in brain activation during inhibitory control varied by age group and task contrast. Symptom severity emerged as the main clinical correlate of activation during inhibition, suggesting that inhibitory control deficits in OCD may be both state-dependent and developmentally specific.

Homelessness and cannabis use may interconnect in complex ways. This study used a nationally representative sample of low-income U.S. veterans to investigate histories of homelessness and cannabis use, and their associations with clinically relevant variables.

Of 1031 veterans, 235 were categorized into three separate groups: history of lifetime homelessness but no lifetime cannabis use (HLS; n = 27 13.2%), no HLS but lifetime history of cannabis use (CU; n = 174, 73.2%), and both homelessness and cannabis use (HLS + CU; n = 34, 13.6%). Group-stratified bivariate and multivariate analyses were employed.

CU was related to residence in states where cannabis was legalized. Compared to CU and HLS, HLS + CU was more strongly associated with arrests, poor subjective health status, and more drugs used. Compared to CU only, HLS + CU was more strongly associated with higher trauma burden, current posttraumatic stress disorder and generalized anxiety disorder, suicidal behavior, history of arrest, and eviction. Compared to HLS only, HLS + CU was more strongly associated with current gambling. HLS + CU was associated with polydrug use, with stimulants being particularly common. Most veterans with HLS + CU reported receiving support from VA programs and services focused on homelessness.

Our findings suggest that homelessness may be more strongly associated with trauma-related and psychiatric concerns, whereas cannabis use may be more strongly associated with substance use and addictive behaviors. These results suggest the importance of integrated, trauma-informed, behavioral and substance use interventions targeting veterans with both histories of homelessness and cannabis use.

Psychiatric multimorbidity, defined as the co-occurrence of two or more psychiatric diagnoses, is increasingly recognized as a marker of clinical complexity. While prior research has examined psychiatric comorbidity in selected populations or via structured diagnostic interviews, less is known about the rates of psychiatric multimorbidity as documented in administrative claims. To address this gap, this study characterizes psychiatric multimorbidity within a statewide insured population. We conducted a cross-sectional analysis of the Massachusetts All-Payer Claims Database (2016-2018) including adults aged 21-64 years with at least one psychiatric diagnosis and insured by Medicaid or commercial insurance. Psychiatric disorders were identified using ICD-10-CM codes grouped into diagnostic categories, with complete code listings provided in supplementary material. Psychiatric multimorbidity was defined as ≥ 2 distinct psychiatric diagnoses documented within a calendar year. Substance use disorder diagnoses were unavailable due to APCD redaction policies and were excluded. Logistic regression models were used to examine associations of psychiatric multimorbidity with patient characteristics. The sample included 2,409,794 person-year observations representing 653,413 unique people with mental health disorders. 68.8% of the population had only one mental health disorder, 17.4% had two mental health disorders, and 13.8% had three or more mental health disorders. In multivariable analyses, females had higher odds of psychiatric multimorbidity compared to males (adjusted Odds Ratio (aOR) = 1.23, 95% CI = 1.22,1.24), and those with any medical comorbidity had higher odds of psychiatric multimorbidity compared to people without a medical comorbidity (aOR = 1.37, 95% CI = 1.36,1.38). Medicaid enrollment was associated with higher odds of psychiatric multimorbidity compared to those with commercial insurance (aOR = 1.25, 95% CI = 1.24,1.25). Those with serious mental illness had nearly nine times the odds of having psychiatric multimorbidity (aOR = 8.92, 95% CI = 8.84,8.99) compared to people without serious mental illness. This study extends prior population-based and specialty-care research by examining psychiatric multimorbidity in a statewide insured population spanning both public and private payers. In this sample, one in three individuals with a mental illness diagnosis had psychiatric multimorbidity. Findings underscore the complexity of psychiatric presentations in clinical care, highlight greater multimorbidity among Medicaid enrollees, and point to the need for integrated and patient-centered treatment approaches. Because substance use disorders were excluded, findings likely represent conservative estimates of psychiatric multimorbidity.

Neglected tropical diseases (NTDs) represent a major cause of preventable morbidity and are increasingly relevant in high-income settings because of migration, international travel, climate-sensitive vector expansion and persistent health inequities. However, NTDs-related knowledge and educational exposure among future and early-career physicians in Europe remain poorly documented. This study assessed NTDs-related knowledge, attitudes and practice-related experiences among medical students and residents in Italy.

We conducted a national multicenter cross-sectional survey through a structured and previously validated REDCap questionnaire distributed across 40 Italian universities covering all 20 Italian regions. The survey included demographic and academic variables, exposure to NTDs-related teaching, six clinical vignettes, ten theoretical knowledge questions, Likert-scale attitude items and practice-related experience questions. The questionnaire had undergone a multi-step validation process, including a two-round Delphi assessment with a multidisciplinary expert panel, external expert evaluation and psychometric testing. A basic knowledge threshold of ≥ 50% correct responses was defined a priori by consensus within the SIMET working group as an operational criterion for basic knowledge. A more stringent high-knowledge threshold was defined as ≥ 12 correct answers out of 16.

A total of 2,088 questionnaires were received; 267 (12.8%) were excluded because of incomplete or insufficient data, leaving 1,821 analyzable responses (87.2%), including 1,366 medical students (75.0%) and 455 residents (25.0%). Median age was 25 years (IQR 22-29) and 60.1% were female. Regarding formal curricular teaching, 40.7% of participants reported no hours of NTDs-related teaching, whereas only 8.5% reported more than 10 h. Only 38.6% reached the basic knowledge threshold and 32.7% correctly answered at least four out of six clinical vignettes. A much smaller proportion (8.7%) reached the high-knowledge threshold of ≥ 12/16 correct answers, with markedly higher attainment among residents than medical students (32.3% vs. 0.8%; p < 0.001). Nevertheless, attitudes were highly favorable: 92.4% supported mandatory inclusion of NTDs in educational curricula, 90.8% were willing to attend dedicated courses and 93.8% considered workshops useful. In multivariable analysis, increasing hours of formal NTDs-related teaching were associated with progressively higher odds of achieving the basic knowledge threshold (< 5 h: aOR 1.25, 95% CI 1.00-1.56; 5-10 h: aOR 1.63, 95% CI 1.24-2.13; >10 h: aOR 2.42, 95% CI 1.74-3.37), with a significant linear trend across categories (p for trend = 0.002). Participation in dedicated educational activities (aOR 1.84, 95% CI 1.49-2.27) and previous suspicion or diagnosis of an NTD case (aOR 1.52, 95% CI 1.18-1.96) were also independently associated with the outcome.

NTDs-related knowledge among medical students and residents in Italy remains suboptimal despite strong interest in additional training. Fewer than four in ten participants reached a basic knowledge threshold, and fewer than one in ten reached a high-knowledge threshold. These findings highlight the need to strengthen structured NTDs-related teaching in undergraduate and postgraduate medical curricula, with emphasis on clinical decision-making competencies.