Background: Curiosity plays a fundamental role in human learning, development, and motivation, and emerging evidence suggests that reduced curiosity is linked to poorer mental health outcomes, including depressive symptoms (DS). However, to date, the majority of curiosity research relies on self-report assessments and thus risks biased reporting. Virtual reality (VR), a novel tool increasingly used within mental health research and treatment, might represent a potent tool for offering ecologically valid insights into curiosity-driven behaviors while circumventing issues related to self-report assessments, including demand characteristics and recall bias. Objective: The study aimed to enhance the assessment of curiosity by using a novel VR environment and to examine its relevance to DS. Specifically, we tested 2 hypotheses using a novel VR environment: first, that curiosity, as assessed through spontaneous exploratory interactions and behaviors in VR, positively correlates with self-reported curiosity, and second, that VR-based curiosity is inversely associated with DS. Methods: This exploratory study used an observational design that included 100 volunteers. All participants completed self-reported assessments of DS and curiosity before engaging in a novel VR scenario. Although progression in the virtual environment required solving cognitive tasks, these were embedded as structural elements rather than framed as the primary objective. Instead, participants’ free explorations and interactions with objects formed the basis for the 4 curiosity metrics used in this study. After VR exposure, participants completed a questionnaire assessing cybersickness symptoms. Results: Hypothesis 1 was not supported, as only one curiosity metric, namely object interactions, was positively associated with one aspect of curiosity relating to motivation to seek new knowledge and experiences. Further, diminishing significance after correction for multiple testing warranted caution. Results relating to hypothesis 2 indicated partial support, in that object interaction was significantly associated with DS while controlling for age, sex, and cybersickness levels. Sensitivity analyses showed no associations between object interactions and self-reported anxiety and stress symptoms. Conclusions: VR may be a potent tool for assessing exploratory behaviors in a controlled, yet ecologically valid, environment that avoids issues related to self-report. However, whether such motivations translate to established curiosity constructs warrants further research. This study also provided preliminary insights into how assessing exploratory interactions in VR may be a promising avenue that could enhance the understanding of the etiology and assessment of DS—particularly its early stages.
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<![CDATA[New analysis ranks lumateperone top for adjunctive MDD symptom relief, with minimal weight gain vs other atypical antipsychotics.]]>
Biomarker of Epigenetic Aging Could Signal Depression
Research led by New York University suggests a marker of epigenetic aging could be linked to depression.
The team found that accelerated aging of a type of white blood cell called a monocyte was significantly associated with the psychological and cognitive expressions of depression in a group of women with and without HIV.
“Depression is not a one-size-fits-all disorder—it can look really different from person to person, which is why it’s so important to consider varied presentations and not just a clinical label,” said lead researcher Nicole Beaulieu Perez, PhD, assistant professor at NYU Rory Meyers College of Nursing, in a press statement.
“Our study reveals unique biological underpinnings of mental health that are often obscured by broad diagnostic categories.”
As reported in The Journals of Gerontology Series A, the researchers analyzed blood samples and depression scores from 440 women, 261 living with HIV and 179 without, from the Women’s Interagency HIV Study. They tested women with HIV as people with this disease and others affecting the immune system are at greater risk of depression than the general public.
The team looked at biological aging using two epigenetic clocks: a broad multi-tissue clock and a monocyte-specific clock that measures chemical modifications to DNA in these cells.
Depression was measured using the CES-D questionnaire, which separates physical, bodily expressions of depression such as fatigue, appetite loss, and agitation from psychological and cognitive expressions of the disorder such as hopelessness, anhedonia, and feelings of failure.
Accelerated monocyte aging was significantly associated with the psychological and cognitive expressions of depression and with anhedonia specifically, even after adjusting for HIV status, race, and ethnicity. The broader multi-tissue Horvath clock showed no association with any depression domain, suggesting it is the monocyte-specific aging signal, not generalized biological aging, that tracks with mood and cognitive symptoms.
Diagnosis of depression relies largely on self-reported symptoms and not a specific physiological test. The finding that monocyte aging maps onto cognitive and mood symptoms rather than physical ones is counterintuitive, since monocytes are inflammatory cells that one might expect to track physical, inflammation-driven complaints like fatigue.
The study is small and cross-sectional, so causality cannot yet be established, but if the claims of the study were validated it could help to personalize treatment for depression in the future.
“The dynamics of monocyte aging and depression warrant further study to clarify mechanistic links,” conclude the authors.
“Our findings bring us a step closer to this goal of precision mental health care, especially for high-risk populations, by providing a biological framework that could guide future diagnosis and treatment,” adds Beaulieu Perez.
The post Biomarker of Epigenetic Aging Could Signal Depression appeared first on Inside Precision Medicine.
Excessive Internet use and depressive symptom levels in adolescents with depressive disorders: chain mediation of social anxiety and sleep quality
BackgroundAdolescents with depressive disorders are at elevated risk for adverse mental health outcomes, and excessive Internet use has been increasingly linked to greater symptom severity. Therefore, this study aimed to examine the chain mediating roles of social anxiety and sleep quality in the association between excessive Internet use and depressive symptoms among adolescents with depressive disorders.MethodsA cross-sectional design was used. A total of 266 Chinese adolescents with clinically diagnosed depressive disorders (M = 15.79 years, SD = 1.85; 71.4% female) were assessed using the Internet Addiction Test, Zung Self-Rating Depression Scale, Social Anxiety Scale for Children, and Pittsburgh Sleep Quality Index. Correlation analyses and bootstrapping methods were conducted using SPSS and the PROCESS macro to examine the chain mediating effects of social anxiety and sleep quality.ResultsThe total indirect effect of excessive Internet use on depressive symptoms accounted for 65.66% of the total effect. Specifically, the indirect effects via social anxiety and sleep quality accounted for 24.10% and 26.51% of the total effect, respectively. In addition, the chain mediating effect of social anxiety and sleep quality was significant, accounting for 14.76% of the total effect.ConclusionExcessive Internet use was positively associated with more severe depressive symptoms among adolescents with depressive disorders, both directly and indirectly through the chain mediating effects of social anxiety and sleep quality. These findings highlight potential targets for preventing and intervening in excessive Internet use among this population.
Distinct sleep-disordered breathing phenotypes in elderly patients with depressive disorder: links to hypoxemia severity and inflammatory burden
ObjectiveTo identify sleep-disordered breathing phenotypes in older adults with depressive disorder and obstructive sleep apnea-hypopnea syndrome (OSAHS) and to evaluate their associations with systemic inflammation.MethodsElderly patients with depressive disorder and OSAHS were consecutively enrolled from January to December 2025. A Gower distance matrix was constructed and phenotypes were derived using partitioning around medoids (PAM; k-medoids), with k selected based on silhouette, elbow criteria, and clinical interpretability. Blood samples were collected the morning after PSG to measure serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α).ResultsAmong 198 participants, k = 2 was selected based on internal validity metrics (silhouette and elbow) and clinical interpretability. Compared with the lower-hypoxia/less-severe OSAHS phenotype (Cluster 1, n = 92), the high-hypoxia/severe OSAHS phenotype (Cluster 2, n = 106) had higher BMI, HAMD-17, and ESS, and more severe AHI/ODI/TS90 with a lower LSaO2. The high-hypoxia/severe OSAHS phenotype also showed higher hs-CRP, IL-6, IL-1β, TNF-α, WBC, neutrophils, and NLR. The inflammatory burden score was higher in the high-hypoxia/severe OSAHS phenotype (β = 1.10 SD unadjusted; β = 1.67 SD adjusted for age, sex, BMI, comorbidity, smoking, drinking, education, and MoCA; β = 1.45 SD further adjusted for HAMD-17 and ESS; all P < 0.001). In men (n = 135), PAM clustering similarly identified two phenotypes differentiated mainly by AHI/ODI, with selective elevations in IL-1β and neutrophil counts.ConclusionsThe high-hypoxia/severe OSAHS phenotype in older adults with depressive disorder is independently associated with a higher systemic inflammatory burden.
Adverse childhood experiences and non-suicidal self-injury in adolescents: the roles of depressive symptoms and teacher care
BackgroundNon-suicidal self-injury (NSSI) has become an increasingly prominent mental health problem during adolescence and often co-occurs with depressive symptoms, anxiety, personality-related difficulties, and experiences of childhood trauma, forming a complex psychosocial risk structure. From a risk and protective factor perspective, the present study examined the associations among adverse childhood experiences (ACEs), depressive symptoms, perceived teacher care, and NSSI among Chinese adolescents.MethodsThe participants were 2,221 junior high school students from three schools in China. Data were collected using the Childhood Trauma Questionnaire, the Adolescent Non-Suicidal Self-Injury Questionnaire, a depression scale, and a teacher care scale.ResultsAdverse childhood experiences and depressive symptoms were significantly positively associated with NSSI, whereas perceived teacher care was significantly negatively associated with NSSI. Higher levels of ACE exposure and more severe depressive symptoms were associated with higher levels of NSSI, while higher levels of teacher care were associated with lower levels of NSSI. Moreover, among adolescents reporting higher levels of perceived teacher care, the positive associations between ACEs and NSSI and between depressive symptoms and NSSI were attenuated, suggesting that teacher care, as an external support resource in the school context, may play an important protective role.ConclusionsAdverse childhood experiences and depressive symptoms are important risk factors for adolescent NSSI, whereas teacher care plays a significant protective role in the school context. School-based prevention and intervention efforts should prioritize adolescents with high levels of ACE exposure and pronounced depressive symptoms, while strengthening teacher care to enhance protective resources. Future research should further explore how specific dimensions and timing of ACEs, trajectories of depressive symptoms, and multiple sources of social support jointly influence the development and maintenance of NSSI in adolescents.
Depressive Symptoms Are Associated with Altered Development of Amygdala-Ventrolateral Prefrontal Connectivity During Implicit Emotion Regulation Across Adolescence
Adolescence is characterized by extensive development in neural circuits that support emotion processing and regulation, and by increased risk for depression. While altered frontolimbic functioning during emotion processing has been implicated in youth with depression relative to healthy controls, the directions of the associations have been inconsistent.
Applicable Scenarios, Desired Features, and Risks of AI Psychotherapists in Depression Treatment From the Patient’s Perspective: Exploratory Qualitative Study
Background: Depression is a pervasive global mental health issue, yet access to trained professionals remains severely limited. With the rapid advancement of artificial intelligence (AI), digital tools are increasingly seen as a viable way to address this shortage. However, questions remain about how digital platforms for mental health care can be effectively designed. Objective: This study aimed to investigate, from an end user’s (patient’s) perspective, the potential use scenarios, desired features, and perceived risks of AI psychotherapists in depression treatment, providing design guidelines for their development. Methods: A grounded theory approach was applied to analyze qualitative responses from 452 individuals recruited via Amazon Mechanical Turk. Data were collected through a scenario-based online survey on AI-assisted depression treatment administered between March 2023 and May 2023. Participants responded to 3 open-ended questions regarding the potential use of AI in treating depression, the characteristics expected from an AI psychotherapist, and the associated perceived risks, along with demographic, control, and contextual measures. The open-ended responses were inductively coded into themes, with intercoder reliability established (Cohen κ=0.80). In addition, variations in themes were further examined across participant profiles, including social stigma, current depression severity, trust in an AI psychotherapist, and privacy awareness. Results: Participants envisioned AI psychotherapists across 5 primary scenarios: diagnosis, treatment, consultation, self-management, and companionship. Key desired features include professionalism, warmth, precision care, empathy, remote services, active listener, personalization, flexible treatment options, patience, trustworthiness, and basic treatment alternative, while critical concerns include diagnostic inaccuracy, treatment errors, privacy breach, lack of human interaction, technical malfunctions, and lack of emotional engagement. Based on these findings, a general MoSCoW (must have, should have, could have, and won’t have) prioritization framework was proposed to serve as a conceptual starting point for future AI system design and empirical validation in mental health care. Notably, feature prioritization varied across user profiles: individuals with higher stigma placed greater emphasis on privacy protection, those with more severe depression prioritized precision care and timely access, low-trust users de-emphasized remote services, and privacy-sensitive individuals showed reduced preference for features requiring extensive data disclosure. These patterns highlight the need for context-sensitive design. Conclusions: This study provides a patient-centered framework for designing AI psychotherapists and complements the existing literature by highlighting the importance of balancing clinical effectiveness with relational considerations. The findings offer actionable guidelines for designing AI mental health care tools that are aligned with user expectations and sensitive to individual differences.
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OTX-202 Smartphone App to Reduce Suicidal Ideation Among High-Risk Transition-Age Youth: Open-Label, Single-Arm, Phase 1 Clinical Trial
<strong>Background:</strong> The transition from adolescence to adulthood (18 to 25 years) is associated with an increased risk of suicidal ideation and behaviors. Suicide-focused cognitive behavioral therapies (CBTs) have been shown to significantly reduce suicidal ideation and behaviors but are not widely available to high-risk individuals. Digital therapeutics could improve access to these treatments. <strong>Objective:</strong> This study aimed to evaluate the acceptability, safety, and potential efficacy of OTX-202 among transition-age youth (18 to 25 years) receiving mental health care outside an inpatient hospital setting. <strong>Methods:</strong> In this phase 1 single-arm clinical trial, 59 transition-age youth with recent suicidal ideation or suicide attempts used OTX-202, a smartphone app designed to deliver suicide-focused CBT, concurrently with usual outpatient mental health care. After baseline, eligible patients completed 12 weekly assessments of suicidal ideation, depression, and anxiety. <strong>Results:</strong> From baseline to week 12, participants reported statistically significant, large reductions in suicidal ideation (mean difference –5.1, 95% CI –6.5 to –3.7; <i>d</i>=0.95). In total, 3 (5.1%; 95% CI 0%-11.2%) participants reported suicide attempts. Reductions in suicidal ideation and suicide attempt rates were consistent with results from previously published randomized clinical trials of suicide-focused CBTs. Participants rated OTX-202 in the 97th percentile of usability and completed a mean of 9.0 (SD 3.5) of 12 app modules, supporting the app’s acceptability. There were no patient deaths, device-related events, or severe adverse events, supporting the app’s safety. <strong>Conclusions:</strong> Results support the safety, acceptability, and potential efficacy of OTX-202 for reducing suicide risk among transition-age youth. <strong>Trial Registration:</strong> ClinicalTrials.gov NCT06008132; https://clinicaltrials.gov/study/NCT06008132
Tryptophan modulates the impact of prolactin on insomnia in perimenopausal women: a cross-sectional study
BackgroundInsomnia is highly prevalent among perimenopausal women and exerts detrimental effects on physical health, psychological well-being, and overall quality of life. However, its underlying mechanisms remain incompletely understood. This cross-sectional study aimed to identify factors associated with insomnia in perimenopausal women.MethodsA total of 187 perimenopausal women aged 45–55 years were enrolled. Insomnia, anxiety, and depression severity were assessed using the Insomnia Severity Index (ISI), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9), respectively. Serum levels of relevant amino acids and hormones were measured. Spearman correlation and linear regression analyses were performed to examine the associations among prolactin levels, tryptophan levels, insomnia, anxiety, and depression. Moderation analysis was further conducted to evaluate the potential moderating role of tryptophan in these relationships.ResultsSerum prolactin levels were positively associated with scores of ISI, GAD-7, and PHQ-9. Furthermore, prolactin levels were positively correlated with the severity of sleep-onset difficulties, sleep maintenance problems, noticeability of impairment, and sleep-related distress. Of note, serum tryptophan levels significantly moderated the association between prolactin levels and ISI scores (β = 0.227, 95% CI = 0.04–0.41, p = 0.0148). To wit, he positive relationship between prolactin levels and insomnia severity was stronger in perimenopausal women with higher serum tryptophan levels compared with those with lower levels.ConclusionsThe moderating effect of serum tryptophan on the relationship between prolactin levels and insomnia in perimenopausal women helps us understand the neuroendocrine mechanisms underlying perimenopausal insomnia and may inform future research on targeted preventive and therapeutic strategies.