National Institute of Mental Health

Approaches to strengthen Data-to-Care (D2C) models are needed. We tested an insurance-based D2C prescription model (D2C-Rx), which used antiretroviral therapy (ART) prescription claims to identify people with HIV who fail to fill ART prescriptions in a timely manner and to provide ART adherence support. The Antiretroviral Improvement among Medicaid EnrolleeS (AIMS) study was the first trial of an insurance-based D2C-Rx program. We describe AIMS study enrollment, focusing on patient-participants in the AIMS program arm. Virginia, United States. AIMS used Virginia Medicaid claims and HIV surveillance data to identify Medicaid enrollees with HIV who were without an ART prescription and their providers; study staff then provided targeted adherence support. The target patient-participant sample size was 1000. The outcome of interest was HIV viral suppression. The study encountered difficulty recruiting patient-participants. Low enrollment prompted major changes to the protocol, including revisions to study design, eligibility criteria, and recruitment methods. These changes were unsuccessful. The trial was terminated because of low patient-participant enrollment (n = 4). Reasons for low patient-participant enrollment may include phone-based recruitment approach, lengthy identity verification and consent procedures, and lack of participant compensation. Although we aimed to identify people with HIV without a current ART prescription refill, several participants reported having their medications available; this discrepancy suggests issues with unexpected participant behavior (eg, stockpiling) or timeliness and accuracy of prescription claims data. Future insurance-based D2C-Rx interventions should account for these challenges, be tailored to context, and be nimble enough to pivot to alternative recruitment methods when needed.

Acute alcohol use reduces brain glucose metabolism while increasing uptake of acetate, a byproduct of alcohol. This metabolic shift persists in individuals with alcohol use disorder (AUD) and may offer a treatment target. Recent studies show that ketone therapies can lessen alcohol withdrawal and cravings. In this study, we tested whether a single dose of a ketone ester (KE) supplement affects brain energy use and alcohol craving. Ten participants (five with AUD, five healthy controls) received two FDG-PET brain scans-one after taking 395 mg/kg KE and one at baseline-in a randomized order. Additionally, five AUD participants underwent magnetic resonance spectroscopy to measure cingulate β-hydroxybutyrate (BHB). KE lowered blood glucose and increased BHB in both groups. Brain scans revealed a 17% reduction in glucose metabolism, especially in the frontal, occipital, and cingulate cortices, as well as the hippocampus, amygdala, and insula. No major differences were observed between AUD and control groups. KE significantly reduced alcohol craving in AUD participants and tripled cingulate BHB levels. These findings suggest that a single KE dose can rapidly shift brain energy use from glucose to ketones, and may help reduce cravings in AUD, supporting its potential as a therapeutic approach.

After encountering a potentially dangerous stimulus, the human body and mind might react with a cascade of physiological, emotional, and cognitive responses to minimize impending harm. However, whether this system can be activated by modern (ontogenetic) threats to the same extent as by ancestral (evolutionary) threats remains uncertain, since the existing results are ambiguous. In this study, we aimed to compare the skin resistance (SR) response to ancestral and modern threats; the focal categories were venomous snakes, heights, airborne diseases, and firearms. We collected recordings of 119 participants, about 30 per threat category, supplemented by participants' rating of the stimuli according to elicited fear. Results showed that participants reacted (SR change) with higher probability to all experimental categories than to control stimuli, with the most frequent reactions to photos simulating the threat of heights, followed by snakes, firearms, and airborne diseases. The largest amplitudes, indicating response intensity, were observed for heights but also for venomous snakes. Further examination showed that higher subjective fear corresponded to an increased probability of SR change. Although the results suggest a slight advantage for ancestral threats, responses to the threat of heights differed in several respects from responses to snakes, demonstrating that ancestrality-based categorisation cannot capture all aspects of the response. Moreover, both ancestral and modern threats can evoke similar electrodermal responses, depending on subjective stimulus salience and/or threat relevance.

Attention-deficit/hyperactivity disorder (ADHD) often emerges in early childhood; however, objective validated biomarkers for its early detection remain limited. In this study, we aimed to identify pupil-based candidate physiological markers (i.e., physiological correlates) associated with ADHD-related traits in preschool- and early school-aged children. To this end, we recorded the pupil diameters of typically developing children without an ADHD diagnosis during a simple fixation task. From these data, we extracted multiple features, including the mean pupil size, temporal variability, and interocular asymmetry in both magnitude and variability. ADHD-related tendencies were assessed using the ADHD Rating Scale-5. Among the features analyzed, only the temporal variability of interocular asymmetry (VarLRdiff) showed a significant positive correlation with ADHD Rating Scale-5 total and subscale scores. This association likely reflects the combined effects of immature autonomic regulation and functional asymmetry in the neural circuits involving the locus coeruleus. In contrast, other pupil-based indices showed no significant correlations, potentially because of developmental ceiling effects and the short evaluation duration. These findings suggest that VarLRdiff may serve as a promising candidate physiological marker of ADHD-related traits in young children, requiring further validation. Future studies incorporating longer recordings, advanced analytical methods, and evaluation of test–retest stability, as well as longitudinal follow-up, are warranted to evaluate its potential utility for early screening, pending clinical and longitudinal validation.

We aimed to examine the psychometric properties of the second version of the Brief Evaluation of Psychosis Symptom Domains (BE-PSD-V2.0) and its correspondence with the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity scale (CGI-S) scores. This cross-sectional study was conducted at 18 institutes in Japan. We performed correlational analyses to test the convergent and divergent validity of the BE-PSD-V2.0. Inter-rater reliability was assessed using intraclass correlation coefficients (ICCs). The equipercentile equating method was employed to examine the linking of the BE-PSD-V2.0 with the PANSS and the CGI-S. A total of 353 patients with schizophrenia spectrum disorders were included. Spearman's rank correlation coefficients between the BE-PSD-V2.0 item scores and their corresponding PANSS factor scores ranged from 0.64 to 0.86, indicating sufficient convergent validity. These specific correlation coefficients were consistently the highest among all item-to-factor comparisons, indicating sufficient divergent validity. In 34 patients, ICCs for the BE-PSD-V2.0 itemand total scores ranged from 0.60 to 0.94, showing sufficient inter-rater reliability. Conversion tables were established between the BE-PSD-V2.0 total score and the PANSS total score, between the BE-PSD-V2.0 total score and the CGI-S score, and between the BE-PSD-V2.0 item scores and their corresponding PANSS factor scores. A correspondence between symptomatic remission criteria using the PANSS and BE-PSD-V2.0 was confirmed. The BE-PSD-V2.0 possesses sufficient psychometric properties and corresponds to the PANSS and CGI-S. It is a sound and reliable brief rating scale for assessing symptoms in schizophrenia spectrum disorders, and its established conversion correspondences facilitate score interpretation within existing clinical paradigms for both clinical practice and research.

Chronic pulmonary aspergillosis (CPA) is an important sequela of pulmonary tuberculosis (PTB), particularly in high-burden countries such as India. This study evaluated the diagnostic performance of the LDBio Aspergillus ICT lateral flow assay and western blot (WB) for CPA among post-TB patients in South India. In this prospective study (July 2023 to June 2025) conducted in Bengaluru, India, we enrolled adults with a history of PTB and persistent respiratory symptoms. CPA was diagnosed using the modified European Society for Clinical Microbiology and Infectious Diseases (ESCMID)-European Confederation of Medical Mycology (ECMM)-European Respiratory Society (ERS) criteria. All participants underwent comprehensive clinical evaluation; direct microscopy and culture of respiratory secretions; and testing with serum Aspergillus-specific IgG ELISA, ICT, WB, and galactomannan (GM). Of 132 post-TB patients, 107 (81%) were classified as CPA and 25 as non-CPA; 70 control sera were also included. ICT and WB were positive in 74% and 84% of CPA cases, respectively, outperforming ELISA (68%) and GM (30%). WB showed the highest sensitivity (84%, 95% CI: 75.8-90.5), whereas ICT demonstrated the highest specificity (94.7%, 95% CI: 88.1-98.3). Combining ICT and WB improved diagnostic accuracy (87.1%, 95% CI: 81.7-91.4) and yielded the highest discriminative power (Youden's index 0.805). WB displayed robust band-based differentiation, with strong reactivity in seropositive CPA. The agreement between ICT and WB was substantial (κ = 0.82). Latent class analysis estimated sensitivities of 92% (95% CI: 84-97) for ICT and 87% (95% CI: 77-94) for WB. These findings indicate that LDBio ICT and WB are robust diagnostic tools for CPA in post-TB patients and that their combined use offers optimal accuracy in resource-limited, high-burden settings.IMPORTANCEChronic pulmonary aspergillosis (CPA) is a serious but often overlooked complication in people who have previously been treated for tuberculosis. Many of these patients continue to struggle with cough, breathlessness, and lung damage; however, routine tests often fail to explain their symptoms. This study shows that CPA is extremely common in this high-risk group and demonstrates that two simple blood tests, the LDBio Aspergillus immunochromatographic test and western blot, can reliably identify the disease. Western blot detects CPA even in patients who typically test negative on standard methods, and using both tests together markedly improves accuracy. Because these tools are quick, inexpensive, and easy to perform, they offer a practical way to diagnose CPA earlier, especially in settings where advanced testing is unavailable. Early diagnosis allows timely antifungal treatment, which can greatly reduce illness and prevent unnecessary suffering among the growing number of TB survivors.

ABSTRACTThe medial subdivision of the inferior pulvinar (PIm) has been implicated in motion processing, visuomotor integration, and residual visual function, yet a comprehensive account of its cortical inputs remains unresolved. Previous studies often relied on indirect cortical injections or tracer deposits spanning multiple pulvinar subdivisions, limiting anatomical specificity. Here, we used MRI-guided, cytoarchitectonically restricted retrograde tracer injections to selectively target PI in the common marmoset (Callithrix jacchus) and systematically map its cortical afferents.Across four cases, retrogradely labeled neurons were widely distributed throughout occipital, temporal, parietal, and cingulate cortices, with a strong predominance in layer V, consistent with driver-like corticothalamic projections. Early and middle-tier visual areas (V1, V2, V3, V3A, V4, V6/DM) contributed substantial input, with labeling patterns corresponding to peripheral visual field representations. The middle temporal complex (MT, MTc, MST, FST) represented one of the densest sources of cortical projections. Prominent inputs also arose from posterior parietal regions, including LIP, MIP, VIP, AIP, and inferior parietal areas (e.g., PFG, OPt), linking PIm to visuospatial and action-related networks. Semi-quantitative analyses indicated that occipital cortex and the MT complex together accounted for approximately 60% of total cortical input, while parietal cortex contributed roughly 20%. Additional projections from retrosplenial and posterior cingulate cortices were observed.These findings identify PIm as a central integrative node embedded within distributed visual and visuomotor networks. Rather than functioning as a restricted visual relay, PIm appears positioned to coordinate motion, spatial, and action-relevant signals within cortico-thalamocortical circuits supporting adaptive visually-guided behavior.

There is growing evidence for the influence of weather on mental health at both the aggregate level indices of mental health statistics of hospitalizations, morbidity, and mortality, and individual level dynamics of mood states. Most research on this topic has focused on light exposure and depressed mood as the sole indicators of seasonal fluctuations of mood disorders. This paper evaluates the association between daily maximum outdoor temperature (DMOT) and contemporaneously reported mood, energy, anxiousness, and sleep quality assessed with Ecological Momentary Assessment (EMA) in a community-based sample of 452 people, aged 11 to 85years, comprising people with or without a history of mood disorders. After controlling for demographics, daily activity levels, and daytime cloud coverage as an index of light exposure, we found that higher DMOT was associated with better mood, increased energy, and better sleep quality among those with a history of mood disorders, particularly in the spring. These findings suggest that the dynamics of mood, energy, and sleep may underlie the aggregate population-level influences of temperature and correlated environmental influences on negative mental health outcomes, particularly among those with BD. Therefore, the conceptualization of risk and intervention for mood disorders should consider both the aggregate influences of temperature and light and associated environmental conditions, as well as individual-level sleep quality and energy as potential mechanisms for seasonal patterns of emotional states.