Experiencing combat-related trauma can contribute to the development of conditions like posttraumatic stress disorder (PTSD) and depression, often leading some veterans to misuse substances as a coping mechanism. In turn, substance use exacerbates mental health issues and increases the risk for suicidal thoughts and behaviors. Military identity, a unique set of values, culture, and camaraderie within the Armed Forces, is hypothesized to further shape these relationships. Using data from 1,459 U.S. military Veterans, we examined whether three dimensions of military identity - idealism, professionalism, and individualism - moderated the associations between combat exposure, substance use, and suicide risk. Following a confirmatory factor analysis of military identity, logistic and multiple linear regression models were conducted to examine the moderating effects of each military identity domain on substance use and suicide risk, respectively. Our results revealed that strong idealism buffered the associations between combat exposure and both substance use and suicide risk, whereas higher levels of professionalism were associated with a weaker relationship between combat exposure and substance use but were not significantly related to suicide risk. Conversely, a highly individualistic military identity strengthened the association between combat exposure and substance use. These findings suggest that strengthening protective aspects of military identity through targeted interventions may enhance active-duty military members' and combat Veterans' overall well-being and reduce substance use and suicide risk.

The Towers of Kuwait-Arabic Neurocognitive Assessment (ToK-ArNA) was developed as a culturally relevant tool to assess executive functions (EF) and visuospatial (VS) abilities in the Omani population. This study established demographically adjusted normative data and evaluated the instrument's temporal stability through formal test-retest reliability analyses. A community sample of 138 cognitively intact Omani adults aged 50 years and above was enrolled. The ToK-ArNA consists of 12 problems scored independently for Time and Accuracy. Normative data were generated using multiple linear regression analysis and traditional stratification by sex, age group (50-64 vs. ≥ 65 years) and education level (0-5 vs. ≥ 6 years). Test-retest reliability was evaluated in a subsample (n = 29) across a 7-10 days interval using intraclass correlation coefficients (ICCs) and Pearson's correlations (r). Both age and education level significantly influenced time and accuracy scores across analyses (p < 0.001), with younger and more educated participants performing better. Sex was significantly associated with accuracy scores in the univariate analysis only, where men outperformed women. Test-retest reliability was good for Time scores (ICC = 0.76, r = 0.76, p < 0.001) but moderate for Accuracy scores (ICC = 0.45, r = 0.47, p = 0.010). This study provides the first normative framework for the ToK-ArNA, enhancing its clinical diagnostic utility. The findings demonstrate that age and education strongly affect executive performance, highlighting the necessity of demographically adjusted norms. The instrument exhibits acceptable temporal stability, particularly for Omani adults aged 50-65 years.

Animal-assisted interventions (AAI) represent complementary rehabilitative approaches designed to address a range of physical and mental health conditions. Among these, Equine-assisted interventions (EAI) offer structured opportunities for engagement through diverse activities conducted within naturalistic settings, thereby integrating therapeutic processes with ecological contexts.

Over the past years, our group has developed and implemented standardized AAI methodologies that are now embedded within comprehensive intervention planning. This overview summarizes the application of different rehabilitative programs based on EAI.

Our findings suggest that EAI can be effectively implemented across a heterogeneous spectrum of psychiatric disorders, contributing to recovery processes and social integration across the lifespan, from childhood to old age.

EAI represent innovative, ecologically grounded interventions with promising clinical potential. Further research involving larger, well-characterized samples is warranted to strengthen the evidence base and to expand the applicability of these promising complementary interventions.

Childhood maltreatment is a significant risk factor for adolescent depressive symptoms, yet the underlying psychological mechanisms remain insufficiently understood. Identifying mediating pathways through emotional processing deficits and social functioning impairments may inform targeted interventions.

This study examined whether alexithymia and social anxiety sequentially mediate the association between childhood maltreatment and depressive symptoms in Chinese adolescents.

A cross-sectional survey was conducted between February and April 2024 among 7,582 middle school students from 5 Chinese provinces. Participants completed validated questionnaires measuring childhood maltreatment (Childhood Trauma Questionnaire-Short Form), alexithymia (Perth Alexithymia Questionnaire), social anxiety (Social Anxiety subscale of the Self-Consciousness Scale), and depressive symptoms (Patient Health Questionnaire-9). Structural equation modeling with 5,000 bootstrap resamples was employed to test direct and indirect effects.

Childhood maltreatment showed a significant direct effect on depressive symptoms (β = .318, 95% CI [0.290, 0.346]). Both alexithymia (β = .049, 95% CI [0.041, 0.058]) and social anxiety (β = .039, 95% CI [0.031, 0.047]) independently mediated this relationship. Sequential mediation through alexithymia to social anxiety was also significant (β = .036, 95% CI [0.032, 0.041]).

Impaired emotional processing and heightened social anxiety represent important psychological mechanisms linking childhood maltreatment to adolescent depressive symptoms. These findings suggest that interventions targeting emotion regulation skills and social anxiety may help disrupt this developmental pathway. Longitudinal studies are needed to establish causal relationships.

Lysosomal dysfunction contributes to Alzheimer's disease (AD) by impairing protein clearance and promoting neuroinflammation. Cathepsin H (CTSH), a lysosomal protease, recently emerged as a protective AD locus. We investigated how CTSH is regulated and how it influences early AD pathophysiology.

We analyzed genomic, transcriptomic, and proteomic data from cerebrospinal fluid (CSF) and brain tissue across three independent clinical and post mortem cohorts to assess CTSH regulation, expression, and disease associations.

The coding variant rs2289702 acts as a cis-regulatory variant, altering CTSH mRNA and protein levels. The T allele associates with better cognition and reduced amyloid plaque burden. CSF CTSH correlates with total tau, phosphorylated tau181, neuronal markers, and multiple glial and complement-related inflammatory proteins.

CTSH tracks early neurodegenerative, synaptic, and inflammatory changes, and co-expression analyses link it to broader immune-metabolic pathways. The findings position CTSH as a genetically regulated contributor to AD pathophysiology.

Neurological and psychiatric disorders pose a persistent global health burden, with conventional therapies often providing inadequate relief. Transcranial ultrasound stimulation (TUS) has attracted considerable attention as a non-invasive neuromodulation technique offering high spatial resolution and the distinctive capacity to modulate deep brain regions.

This review synthesizes recent basic and clinical research on TUS across neurological and psychiatric disorders, and consolidates emerging evidence on its mechanisms, therapeutic applications, and safety considerations.

Emerging evidence suggests that TUS may drive sustained neural remodeling-including synaptic plasticity, neurogenesis, and anti-neuroinflammatory effects-raising the possibility that TUS could eventually contribute to disease-modifying strategies. However, disease modification by TUS has not yet been demonstrated in humans; the evidence supporting this possibility is derived predominantly from preclinical studies and remains a hypothesis requiring confirmation in large-scale, controlled clinical trials. Building on these frameworks, we further propose a working hypothesis-termed mechanotransduction-to-oscillation encoding-which posits a nonlinear encoding relationship between the pulse repetition frequency of TUS and the intrinsic oscillatory properties of the stimulated region.

This hypothesis remains largely speculative and is offered as a conceptual framework to generate testable predictions and guide future investigations. Together, these frameworks provide a cohesive strategy for advancing TUS from an exploratory neuromodulation technique toward a potentially clinically translatable precision intervention, while acknowledging that significant technical and clinical hurdles remain.

Depression is a global mental health disorder and is linked to impaired quality of life and increased risk of chronic diseases. Emerging evidence suggests that branched-chain amino acids (BCAAs), including valine, isoleucine and leucine, may influence neurobiological pathways involved in depression through modulation of neurotransmitter signaling.

A systematic literature search was conducted across multiple databases from their inception to April 2026. Studies evaluating BCAA supplementation or dietary intake in relation to depression were included. Cross-sectional studies, observational studies, retrospective studies, randomized controlled trials and case-control studies available in English were considered. Data extraction and quality assessment were conducted using the Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale.

Eleven studies involving 3902 participants were included. Seven studies reported a reduction in depressive symptoms following BCAA supplementation or higher dietary intake. Improvement was observed among elderly populations and patients with metabolic or chronic conditions. Observational studies demonstrated an inverse association between dietary BCAA intake and depression-related outcomes. However, several studies reported non-significant findings and heterogeneity existed regarding study design, participant characteristics, dosage and assessment methods. Evidence also suggested that combined exercise and BCAA interventions provide additional benefits.

Current evidence suggests that BCAAs may play a potential role in depression and mental health outcomes. Findings from intervention, dietary exposure and biomarker studies indicate a possible association between BCAAs and depressive symptoms; however, the available evidence remains heterogeneous and inconclusive. Further well-designed, adequately powered clinical trials are required to establish the therapeutic role of BCAAs in depression.

Posttraumatic stress disorder (PTSD) exhibits disrupted functional organization of brain networks involving sensory and association cortices. Connectome studies reveal a principal unimodal-to-transmodal gradient in the brain functional network that supports the spectrum from sensation to cognition. However, the disruption of the connectome gradient in PTSD and its associated transcriptional and neurotransmitter patterns remains poorly understood.

Using resting-state functional magnetic resonance imaging data from a cohort of 86 non-comorbid adult patients with PTSD caused by an earthquake and 86 trauma-exposed non-PTSD (TENP) controls who experienced the same disaster, we examined PTSD-related changes in the principal connectome gradient, their links to symptom severity and sex/age interactions, and brain-wide associations between gradient changes and microscale transcriptomic and neurotransmitter maps and macroscale cognitive function.

Compared with TENP controls, PTSD exhibited global topographic abnormalities in the principal unimodal-to-transmodal gradient, and focal aberrance mainly in the unimodal (visual network) and transmodal systems (limbic, ventral attention, and frontoparietal networks). Sex had no significant effects, while gradient decrease in the subcortical network is more prominent in adolescents with PTSD than adults. The PTSD-related gradients colocalized with brain-wide gene expression enriched in mitochondria and DNA/RNA metabolic process and corresponded with the distribution of dopamine, opioid, noradrenaline, and cholinergic neurotransmitter systems.

These findings highlight the dysfunctional connectome hierarchy in PTSD and its association with transcriptomic and molecular profiles, suggesting that early traumatization may more significantly impact the development of subcortical network. This work provides insight into the neurobiological basis of PTSD and indicates potential biomarkers for prediction and prevention.

Stroke is one of the leading causes of death and disability globally, with ischemic stroke comprising approximately 87% of all cases. Although reperfusion therapies such as tissue-type Plasminogen Activator (tPA) are currently available, their clinical utility is severely limited by narrow therapeutic time windows and the risk of hemorrhagic transformation. Recent advances have revealed that ischemic stroke is not merely a localized vascular occlusion but a systemic pathological event governed by the Neurovascular Unit (NVU), including neurons, glial cells (astrocytes and microglia), vascular cells (endothelial cells and pericytes), and peripheral immune cells. Therefore, understanding the alterations in these diverse cell types and their underlying mechanisms holds significant importance for developing effective treatments for stroke. This review integrates current knowledge on the complex intercellular communication mechanisms within the NVU and at its periphery. We discuss how the functional polarization of astrocytes (neurotoxic A1 vs. neuroprotective A2) and microglia (M1/M2 phenotypes) dictate neuronal fate and neuroinflammatory responses. Additionally, we describe NVU-mediated regulation of cerebral blood flow and BBB permeability, as well as the interplay between peripheral and central immune responses in the context of stroke. Furthermore, we highlight novel communication modalities, specifically exosomes, which shuttle miRNAs and proteins to modulate distal inflammation, and Tunneling Nanotubes (TNTs), which facilitate the direct intercellular transfer of vital organelles, such as mitochondria. These dynamic interactions represent critical nodes for therapeutic intervention. Taken together, targeting the interactions of intercellular communication represents a promising frontier for achieving comprehensive functional recovery after ischemic stroke.