Identifying neural mechanisms underlying harm avoidance and incompleteness in OCD and other psychiatric disorders is critical for improving diagnostic precision and developing targeted treatments. However, little is known about the neural pathways underlying these symptom dimensions across clinical populations. The goal of this study was to use diffusion MRI to replicate and extend prior findings in OCD to a transdiagnostic sample of healthy controls (HC) and individuals with Obsessive-Compulsive Disorder (OCD), Obsessive-Compulsive Personality Disorder (OCPD), and non-OCD disorders (e.g., anxiety, post-traumatic stress disorder). Connections between prefrontal (dorsomedial, dorsolateral, ventromedial, and ventrolateral) and subcortical regions (thalamus and striatum) were reconstructed using whole brain tractography in 38 HC (mean age [SD] = 30.97 [10.62), 47 OCD (mean age [SD] = 32.34 [12.23]), 21 OCPD (mean age [SD] = 35.67 [14.65]), and 20 Non-OCD (mean age [SD] = 35.90 [14.26]) participants. Fractional anisotropy (FA) was derived for each connection. Harm avoidance and incompleteness symptom dimensions were assessed using the Obsessive-Compulsive Trait Core Dimensions Questionnaire. In a first replication model, including individuals with OCD and HC, higher left (β = 0.29, P = 0.009, Q = 0.048) and right (β = 0.30, P = 0.005, Q = 0.0048) dorsomedial PFC-thalamus FA was associated with higher harm avoidance, with the left connection also associated with higher incompleteness (β = 0.29, P = 0.009, Q = 0.048). In additional models adding in OCPD and non-OCD participants, only associations among left (β = 0.20, P = 0.027, Q = 0.040) and right (β = 0.18, P = 0.035, Q = 0.045) dorsomedial PFC-thalamus FA and harm avoidance remained significant. There were no associations involving PFC-striatum connections. Dorsomedial PFC-thalamus FA was associated with harm avoidance, but less so with incompleteness. Our findings suggest that higher dorsomedial PFC-thalamic FA is associated with higher harm avoidance across diagnostic groups, providing transdiagnostic neural targets for future treatment developments.

Cognitive deficits are a hallmark of Alzheimer's disease (AD), and effective treatments remain elusive. Transcranial alternating current stimulation (tACS), a non-invasive technique, has shown potential in improving cognitive function across various populations, but further research is needed to investigate its efficacy in AD. In a randomized, double-blind, sham-controlled pilot trial, 36 mild AD patients received active or sham theta-tACS (8 Hz, 1.6 mA, 20-min daily) during n-back task for two weeks, followed by a 10-week follow-up. Cognitive assessments and resting-state EEG were analyzed at baseline, after-treatment, and follow-up. The results showed that the active group demonstrated significant cognitive improvements after treatment (MMSE: t (15) =-3.273, p = 0.005, Cohen's d = 0.82), particularly in short-term memory (MMSE-recall: Z = -2.11, p = 0.035, r = 0.53), with maintained benefits after 10 weeks. In contrast, the sham group exhibited long-term cognitive decline (MMSE: t (4) = 3.586, p = 0.023, Cohen's d = -1.60). EEG analysis revealed reduced gamma power (t (23) = 2.689, p = 0.013, Cohen's d = 1.077) and theta connectivity in active group, particularly in the frontotemporal regions (F4/F7: t (23) = 2.467, p = 0.021, Cohen's d = 0.988; F4/T3: t (23) = 2.465, p = 0.022, Cohen's d = 0.987), which was correlated with cognitive improvements (R = -0.57, p = 0.043). In conclusion, tACS combining cognitive training may offer cognitive benefits in mild AD by modulating neural activity, though further studies are needed to clarify its mechanisms.

Cognitive deficits across multiple domains are prevalent in patients with schizophrenia (PWS), and metabolic syndrome (MetS) may significantly contribute to this impairment. To clarify the complex relationships between individual MetS components and multidimensional cognitive dysfunction in PWS, we conducted a multicenter study involving 727 clinically stable patients recruited from ten psychiatric hospitals. Cognitive function was assessed using the Chinese Brief Cognitive Test (C-BCT). We employed network analysis and structural equation modeling (SEM) to explore these associations, with machine learning techniques applied for further validation. The results revealed statistically significant differences in several cognitive domains between patients with and without dyslipidemia (DL). Patients with hypertension (HT) also exhibited overall poorer cognitive performance. Network analysis indicated meaningful distinctions between patients presenting two or more MetS components (MetS-2+) and those without, showing a sparser network configuration in the MetS-2+ group. Across both groups, the Symbol Coding task demonstrated the highest strength centrality. SEM indicated that metabolic indicators, specifically DL and HT, mediated the relationship between clinical symptoms and cognitive function. Furthermore, a transformer-based machine learning model performed effectively in predicting cognitive dimensions, supporting the predictive utility of MetS components for multidimensional cognitive outcomes. In summary, specific MetS components, particularly DL and HT, show intricate associations with cognitive function in stable-phase PWS. Our findings suggest that management of HT in this population may represent a potential pathway for cognitive enhancement and improved social functioning. Trial registration: MR-11-23-007343.

Recent clinical breakthroughs hold great promise for the application of psilocybin in the treatments of psychological disorders, such as depression, addiction, and obsessive-compulsive disorder. Psilocybin is a psychedelic whose metabolite, psilocin, is a 5-HT_2A receptor agonist. Nevertheless, the underlying mechanisms for the effects of psilocybin on the brain are not fully illustrated, and cell type-specific and circuit effects of psilocybin are not fully understood. Here, we combined single-nucleus RNA-seq with functional assays to study the long-term effects of psilocybin on the orbitofrontal cortex (OFC) of male mouse, a brain region vulnerable to psychological disorders such as depression. We found that a single dose of psilocybin induced long-term genetic and functional changes in neurons of the OFC, and the layer 5 pyramidal neurons showed the most significant changes. The layer 5 pyramidal neurons in the OFC showed reduced expressions of glutamate receptors and the gene expressions of multiple intercellular signaling pathways involved in the excitatory synapse formation and maintenance after psilocybin injection, which was consistent with the decreased excitatory synaptic transmission of these neurons. Meanwhile, both Parvalbumin- and Somatostatin-positive inhibitory neurons of the OFC showed meager changes after psilocybin injection. Furthermore, knockdown of 5-HT_2A receptor in the layer 5 pyramidal neurons but not the Parvalbumin-positive inhibitory neurons abated psilocybin-induced functional changes and the anti-depressant effect. Together, these results showed the cell type-specific mechanisms of psilocybin and shed light on the brain region difference in the effect of psychedelics.

Parenting programs are effective in promoting positive changes and improving the mental health of children and parents. However, low program uptake undermines the incorporation of these programs into routine community settings. Therefore, we examined whether redesigning the program flyer using insight from consumer science could increase parental participation. In this randomized controlled trial, 164 preschools were randomly assigned to a control condition or one of four experimental conditions. Parents of children in each condition were invited to participate in a universal parenting program using either the usual flyer used by local practitioners (control flyer) or one of four new flyers. The new flyers were designed based on prior research findings on why parents participate in universal parenting programs. Because fathers and mothers have been shown to have different reasons for attending parenting programs, we tailored the flyers separately for mothers and fathers. The four flyers were one mother-specific flyer, one father-specific flyer and two mixed-content flyers. The number of participants recruited varied significantly across the flyers. Overall, the redesigned mother-specific and father-specific flyers, but not the mixed-content flyers, outperformed the control flyer in recruiting parents. In addition, compared with the two mixed-content flyers, the mother-specific flyer attracted significantly more mothers and the father-specific flyer attracted more fathers. However, we found no difference between the two specific flyers themselves. Simple direct-to-consumer (DTC) marketing strategies tailored specifically to mothers or fathers can potentially increase program uptake. Future studies should further examine the importance of the visual and content of DTC messages.

Personal recovery is an increasingly used outcome for evaluating the effect of interventions on mental health disorders like affective and anxiety disorders, emphasizing living a meaningful life despite psychiatric challenges. The Recovery Assessment Scale (RAS) is a widely used measure of personal recovery with strong psychometric properties, but evidence for its sensitivity to change is limited. We conducted a systematic review and meta-analysis of 27 randomized controlled trials, found through systematic search on December 8th, 2022, which was updated in March 2024, to evaluate whether the RAS is sensitive to measuring change after interventions. Among the included randomized controlled trials, several focused on affective disorders, allowing us to examine the RAS in diagnostic groups directly relevant to affective disorder research. Results showed that participants in intervention groups demonstrated significantly greater pre-post changes in RAS scores compared to control groups for total RAS scores, with a small overall effect size (hedges g = 0.249). This effect was moderated by participants' diagnoses, but not by the specific RAS version, length of follow-up period, significant clinical outcome measured or baseline RAS scores. No significant findings were found for subdomain scores. Our results demonstrate that the RAS can detect change in a randomized controlled setting, although this design cannot fully isolate intervention effects from the instrument's inherent responsiveness. A better understanding of the scale's ability to capture changes in personal recovery can inform the development of more effective, personalized interventions, ultimately improving the well-being and quality of life of individuals with psychiatric disorders.

Anxiety is highly prevalent and undertreated in first-episode schizophrenia(FES), but repetitive transcranial magnetic stimulation(rTMS) data for this comorbidity are scarce. The orbitofrontal cortex(OFC) is a key anxiety-regulating node, supporting its potential as a target. This study aimed to explore 1-Hz right OFC-rTMS's symptom-specific effects on FES mood.

This is a secondary analysis of a randomized controlled trial. Participants were drug-naive FES patients randomized to the active rTMS group(n = 51) or sham group(n = 45). All completed 20 intervention sessions, 20 sessions of active OFC-rTMS or sham, with 4-week follow-up, initiating oral olanzapine(10-20 mg/day) concurrently with the first rTMS session. Mood symptoms were assessed using the 24-item Hamilton Depression Rating Scale(HAMD) and the 14-item Hamilton Anxiety Rating Scale(HAMA). Psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale(PANSS). The main outcome was the changes in HAMD and HAMA scores from baseline to 2 weeks and 4 weeks.

The active group showed greater PANSS total(t = -3.260, p = 0.002; Cohen's d = 0.672) and subscale improvements vs. the sham group. Repeated-measures ANOVA(controlling for covariates) revealed significant Time×Group interactions for HAMA total(F = 4.698, p = 0.010; partial η² = 0.059) and psychic anxiety(F = 5.735, p = 0.004; partial η² = 0.072), but not somatic anxiety. For HAMD, only anxiety/somatization(F = 8.397, p = 0.031; partial η² = 0.099) and cognitive impairment(F = 6.240, p = 0.002; partial η² = 0.076) showed interactions, with no specific effects on overall depressive symptoms. In the sham group, HAMD anxiety/somatization correlated with all PANSS subscales(r = 0.311-0.477, p < 0.05), but this correlation was absent in the active group(all p > 0.05).

Right OFC-rTMS improves FES anxiety (not depression), supporting it as a targeted non-pharmacological option.

Emerging evidence suggests that adolescents with depression may experience cognitive dysfunction. However, studies are primarily cross-sectional and few in number. This study examines the temporal association of depression and cognitive function among participants of the Adolescent Brain Cognitive Development Study.

Participants were recruited from the community and completed self-report of depressive symptoms and semi-structured psychiatric diagnostic interview. Cognitive function was examined using validated, reliable measures across five domains (working memory, long-term memory, attention, executive function, and language), over three time points (baseline, year 2, and year 4). The relationship between depression and cognitive domain was examined using multiple linear regression for cross-sectional associations and random intercept cross-lagged panel models for longitudinal associations, controlling for covariates.

Participants (n = 10,552) had a mean age of 9.9 ± 0.6 years, and 48% were female. Cross-sectionally, depressive symptoms were inversely associated with working memory, long-term memory, attention, and executive function at baseline (all βs - 0.02 to -0.03). Higher depressive symptoms at baseline predicted lower attention at year 2 (β = -0.82). Lower attention at year 2 predicted higher depressive symptoms at year 4 (β = -0.94). No significant long-term effects were found between depressive symptoms and working memory, long-term memory, or executive function.

Cross-sectional associations between depression and cognition were not replicated in longitudinal analyses, with the exception of inattention, in which reciprocal associations over time were found. Longitudinal research in clinical settings is needed to better understand the impact of adolescence depression on attention and related social and educational outcomes.

LGBTQIA+ (Lesbian, Gay, Bisexual, Transgender, Queer, Intersex, and Asexual +) individuals face higher rates of posttraumatic stress disorder (PTSD) due to increased trauma exposure. Further, they may experience factors that complicate treatment, like exposure to minority stress and increased substance use. No prior large-scale clinical trial has compared the effectiveness of PTSD treatments among LGBTQIA+ populations.

We are conducting a comparative effectiveness study that will compare two evidence-based psychotherapeutic interventions to reduce PTSD and depression symptoms and improve quality of life in LGBTQIA+ populations. Treatment dropout and satisfaction will be compared between the interventions. Minority stress and substance use will be examined as moderators for treatment effectiveness. We will also examine heterogeneity of treatment effects by gender subgroups, participant residence (urban versus suburban or rural), and race and ethnicity.

Participants will be recruited from community mental health settings, from the community, and through organizations throughout California. Eligibility will be based on PTSD symptom severity as determined by PTSD Checklist for DSM-5 (PCL-5) scores ≥33 during an initial phone screening. Each participant will be randomized to receive either Cognitive Processing Therapy (CPT) or STAIR Narrative Therapy (SNT). Study participants will complete survey assessments at baseline, 3 months, 6 months, and 12 months.

This study will fill critical research gaps to inform effective PTSD treatments for LGBTQIA+ communities.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a multifactorial and incompletely understood etiology. Identifying exposures associated with reduced AD risk may help generate mechanistic hypotheses and inform future prevention strategies. To investigate such associations, we analyzed electronic health records from a national Israeli health provider, retrospectively comparing 9,124 individuals with AD to 18,248 matched controls. We systematically screened prior medication purchases recorded up to 10 years before diagnosis. Significant associations, adjusted for residual confounding, were further evaluated in the TriNetX network, where large propensity score-matched cohorts were compared for incident dementia following medication exposure or vaccination. Among all exposures assessed, strong protective associations were observed for atovaquone-proguanil, an antiprotozoal agent with established activity against Toxoplasma gondii, and for two different varicella-zoster virus (VZV) vaccines. These associations persisted after adjustment for demographic factors, comorbidities, and baseline healthcare utilization, and were independently reproduced in TriNetX across three strata of exposure age (50-59, 60-69, 70-79 years). In addition, T. gondii seropositivity was associated with increased dementia risk among individuals tested. In exploratory analyses, the magnitude of the association between atovaquone-proguanil and subsequent dementia appeared to differ according to prior VZV vaccination status, suggesting a possible interaction between protozoal suppression and antiviral immunity. Together, these findings provide population-level evidence consistent with a latent T. gondii-related mechanism in AD pathogenesis, and highlight testable targets for future mechanistic and interventional research.