Mental Illness Research, Education and Clinical Centers

Influenza A subclade K viruses caused high infection rates in the 2025/2026 Northern Hemisphere season, raising concerns about antigenic drift and reduced vaccine effectiveness. We measured antibody responses in matched human pre- and post-vaccination sera against a vaccine-like as well as subclade K isolates. Pre-existing immunity to subclade K variants was noted with seasonal influenza vaccination boosting titers two-fold against subclade K and three-fold against the vaccine-like strain, indicating little antigenic drift. These data contrast ferret-based predictions of marked antigenic drift.

Multimodal imaging studies that combine temporally and spatially precise methods can enhance understanding of reward neurocircuitry by revealing how signals specifically time-locked to reward processing substages relate to functional network-level activity. Prior reward studies that require decision making and/or motor responses to obtain rewards may complicate efforts to isolate basic reward responses from higher-order functions that support reward attainment. Here, we take an integrated, multimodal approach to evaluate anticipatory and consummatory reward processing substages, while minimizing demands on higher-order cognitive and motor processes. Functional magnetic resonance imaging (fMRI) and electrophysiological (EEG) data were separately recorded from 52 adults playing a simple, slot machine task, with reward outcomes independent of performance. Joint Independent Component Analyses (jICAs) were conducted with EEG-based event-related potential (ERP) difference waveforms and fMRI contrast images specific to reward anticipation and outcome processing substages. Resulting joint independent components (JICs) segregated reward processing substages, indicating significant co-modulation between temporal ERP and spatial fMRI signals (p < 0.001). During Reward Anticipation, a JIC with the temporal signature of the stimulus preceding negativity (SPN) ERP component covaried with fMRI activation in bilateral supplementary motor areas (pre-SMA/SMA) and inferior fronto-insular salience network regions implicated in attentional orienting and shifting. During Reward Feedback, JICs with the temporal signature of the reward positivity (RewP) ERP component covaried with fMRI activation in dorsal anterior cingulate cortex (dACC), ventral striatum, SMA, and inferior frontal cortex, extending to the insula. Further, trait reward sensitivity correlated with jICA-informed Win > Loss brain activations during Reward Feedback (p = 0.016). Our findings demonstrate that temporally precise electrophysiological and spatially rich hemodynamic measures of reward processing converge to map onto specific substages of reward-related brain processes. ERP and fMRI signaling during reward feedback support covariation of the RewP with dACC-striatal reward networks while the SPN covaried with fMRI signal in pre-SMA/SMA and inferior fronto-insular regions implicated in motor planning, salience, and attention.

Research on couple typologies has advanced our understanding of the communication patterns that distinguish happy from distressed partners. However, this work has suffered from a lack of conceptual and methodological cohesion and replication in large, heterogeneous samples, resulting in idiosyncratic typologies with limited generalizability beyond their initial development. The present study replicates and extends prior research by testing the external validity of previous communication typologies in a multisite sample of couples. We combined data from 13 studies that used the Rapid Marital Interaction Coding System to observe communication during mixed-gender couples' 10-min conflict interactions (N = 1,957). We used latent profile analysis to examine men's and women's (a) positive, negative, and neutral behavior and (b) positive and negative reciprocity. Groups were compared on relationship satisfaction and intimate partner violence to further characterize differences among couple subtypes. A five-class solution revealed couples whose communication can be described as (a) task-oriented (low positivity/negativity, high neutral problem discussion; 53%), (b) warm (high positivity/low negativity; 24%), (c) hostile (low positivity/high negativity; 9%), (d) expressive (high positivity/negativity; 7%), and (e) warm-but-reactive (high positivity/low negativity, high negative reciprocity; 6%). Men and women reported the highest levels of satisfaction in the warm, task-oriented, and warm-but-reactive groups. Intimate partner violence was highest in the hostile and expressive groups. These outcomes are largely concordant with the previous findings and should increase the field's confidence in the generalizability of earlier typologies. Our findings also raise new questions about the heterogeneous nature of communication among happy couples. We discuss these questions and their clinical implications. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Veterans experiencing homelessness have elevated rates of traumatic brain injury (TBI) diagnoses. There remains limited research on subsets of homeless Veterans, including Native Hawaiian and Pacific Islander (NHPI) Veterans. Department of Veterans Affairs (VA) electronic medical records of 724 752 Veterans who accessed Veterans Health Administration (VHA) homeless services from January 2005-December 2018 were examined. Of the total sample, 1177 identified as NHPI, with comparator samples of non-NHPI (n=723 575) and White (n=418 085) Veterans also generated. Rates of TBI were compared between NHPI Veterans relative to non-NHPI Veterans, as well as between NHPI and White Veterans (a subset of the non-NHPI Veteran sample). NHPI homeless Veterans were more likely to have a documented TBI diagnosis relative to non-NHPI homeless Veterans (AOR=1.82, 95% CI: 1.57-2.11), including the White homeless Veteran subgroup specifically (AOR=1.51, 95% CI: 1.30-1.75). This persisted in the presence of several covariates, including sex, ethnicity, rurality, VA service-connected disability, posttraumatic stress disorder, depression, and VHA mental health and general service use. NHPI homeless Veterans were also significantly less likely to utilize VHA services, suggesting an important gap in health service delivery. Results support potentially heightened risk for TBI among NHPI homeless Veterans, and a need to elucidate if such injuries occur during or outside of military service. Alternatively, given potential sociocultural differences, understanding the experience and expression of TBI sequelae among NHPI homeless Veterans is essential. Further research is requisite to understand how to optimally engage homeless NHPI Veterans in care to ensure TBI-related sequelae are adequately identified and addressed.

Traumatic brain injuries (TBI) frequently occur and can lead to lasting negative cognitive, physical, and mental health outcomes. The biological response to even mild TBIs (mTBI) includes well-characterized inflammatory sequelae that start immediately post-injury, remain for weeks, and can develop into long-term systemic inflammation. Studies have shown that TBI influences multiple physiological systems, including the gastrointestinal tract, through bidirectional communication modulated, in part, by the gut microbiome. Brainstem functioning post-TBI, as measured by acoustic startle sensorimotor processing, might play a role in this feedback loop. The current study investigated pre- to post-TBI (lateral fluid percussion injury model) changes in microbial communities and acoustic startle response in male and female rats. That is, the influence of mTBI on gut microbiome and sensorimotor processing was explored to examine: 1) overall and sex-specific differences in the gut microbiome and taxa in response to mTBI; 2) overall and sex-specific differences in sensorimotor processing following mTBI; and 3) associations between the gut microbiome and sensorimotor processing. Results showed mTBI had a limited effect on microbial diversity overall, and the same was observed in males and females independently. Yet, mTBI was associated with differences in 13 genus-level taxa. Further evaluation highlighted that 11 of the 13 genus-level taxa were sex-specific, with several being known to have short-chain fatty acid-producing capabilities. Alterations in sensorimotor processing were identified following mTBI; however, no sex-specific differences were evident. In addition, no associations were observed between sensorimotor processing and the gut microbiome. This study contributes longitudinal and sex-specific findings to the growing body of research examining the diverse effects of mTBI on the brain and gut microbial communities.

Migraine is a neurovascular disorder that poses a high burden to Veterans, who face a greater risk than sex-matched individuals in the general population. Genetic research on migraine in Veterans and its link to psychiatric comorbidities is limited. We present a meta-analysis of a genome-wide association study (GWAS) of migraine in a predominantly male sample of over 433,000 Veterans, including 87,859 cases, from the Million Veteran Program (MVP), identifying 49 genome-wide significant loci, with 36 novel to this study, of which 7 replicated in an independent prior GWAS (after Bonferroni correction for number of loci tested). Our analyses revealed 283 genes, including some newly associated with migraine: MAML3, CELF4, IRX1, ASXL1, SPOCD1, CXCL, and TLR4. In silico analyses showed enrichment in brain and uterine tissues, which may reflect broader hormonal or neuroendocrine pathways. Compared to previous migraine GWAS, our results show minimal vascular tissue enrichment, potentially reflecting the sample composition, which was predominantly men and Veterans. Migraine SNP-based heritability was 10% for men and 16% for women, and several sex-specific loci were identified through sex-stratified analyses. Despite high genetic correlations with neuropsychiatric disorders – including post-traumatic stress disorder, depression, and traumatic brain injury – Mendelian randomization analyses found no causal links. Finally, we prioritized potential migraine drug targets, including losmapimod (which reduces production of toxic DUX4 protein) and TLR4 antagonists.

"Personalized" interventions based on patients' "biomarkers" may be valuable for treatments that benefit only subsets of patients. The NMDA antagonist, memantine, slows clinical progression of Alzheimer's disease (AD); this effect is heterogeneous in magnitude and duration. This study tested whether acute cognitive or neurophysiological responses to memantine challenge predicted sensitivity to memantine's therapeutic effects. Thirty individuals with mild-to-moderate severity AD (M:F = 13:17) and 24 comparably aged healthy subjects (HCS) (M:F = 12:12) were enrolled. Participants with AD were characterized on 9 experimental measures and their changes after acute memantine "challenge" (20 mg). We then assessed whether acute memantine effects on these measures predicted clinical change over a 24-week open-label trial of memantine. Baseline cognitive (Repeatable Battery for the Assessment of Neuropsychological Status) and neurophysiological measures (prepulse inhibition, P3a latency and auditory steady state response power and coherence) were impaired in participants with AD (p's<0.05-0.0001); neurophysiological deficits were modestly reduced by acute memantine challenge. As a group, participants with AD showed no significant clinical changes across 24 weeks of memantine treatment; subgroups exhibited either small gains or deterioration. With one exception (mismatch negativity latency, p < 0.017), sensitivity of experimental measures to acute memantine challenge did not significantly predict clinical sensitivity to memantine. In summary, a challenge dose design identified neurophysiological measures sensitive to memantine in mild-to-moderate severity AD; acute memantine effects on one measure weakly predicted clinical outcomes over 24 weeks. Impairment in specific measures among participants with AD, and their opposition by memantine, might inform future efforts to identify treatment biomarkers in AD.

Burn injury produces a complex biological response across multiple organ and biological systems. Nonetheless current understanding regarding the neurologic response to burn injury is limited. Research suggests that disruption of the blood-brain barrier (BBB) may play a role in central nervous system (CNS) damage following burn trauma. As such, the purpose of this study was to investigate systemic circulating biomarkers, frequently associated with neuronal injury, to gain an understanding of their relationship to burn injury severity. Blood from fifty-six patients admitted to the burn intensive care units was taken within 24 hours and analyzed for four CNS-related biomarkers in plasma (i.e., ubiquitin C-terminal hydrolase L1 [UCH-L1], tau protein, glial fibrillary acidic protein [GFAP], and neurofilament light [NfL]). Clinical information regarding demographics, burn severity, and health outcomes were also obtained. We observed increased burn severity, as measured by total burn surface area (TBSA), was significantly associated with increased UCH-L1, NfL, and tau. GFAP was not associated with burn severity. In a predictive model of days spent in the hospital after injury, accuracy of the four CNS-related biomarkers was only improved by 1% when TBSA was included (i.e., 38.3% accuracy with only biomarkers vs. 39.4% accuracy with biomarkers and TBSA). Overall, findings from this novel study highlight an association between burn injury severity and CNS-related biomarkers, thereby providing a foundation for future studies to explore both potential mechanisms associated with burn-related neurologic damage and associated functional impairments.

Noncoding variants increase neuropsychiatric disease risk, but our understanding of their cell-type-specific role remains incomplete. We conducted large-scale chromatin accessibility profiling of neurons and non-neurons from 2 neocortical regions in 1,393 libraries. We observed substantial differences in neuronal chromatin accessibility between schizophrenia (SCZ) cases and controls, with upregulated open chromatin regions (OCRs) in neurons associated with SCZ risk loci. A comparison of SCZ-associated OCRs with fetal brain-specific OCRs revealed a strong correlation between upregulated changes in SCZ chromatin and openness in fetal cortical brains, linking disease-related chromatin alterations to neurodevelopment. Here we show that a prominent neuronal trans-regulatory domain containing upregulated OCRs consolidates key neurodevelopmental chromatin signatures and is enriched for immature glutamatergic neurons. These findings link altered adult cortical chromatin states to early developmental mechanisms in SCZ. This study provides a comprehensive cell-type-resolved chromatin accessibility resource for the human cortex and offers insights into the regulatory architecture underlying SCZ risk.

Relapse prevention is a major goal of schizophrenia treatment. However, there is no standard definition of relapse. To address this, the authors reviewed recent approaches and developed consensus criteria to operationally define relapse. To evaluate current criteria, a systematic review was performed of randomized controlled trials of relapse conducted from 2012 to 2024. To develop consensus criteria, the authors used a multiphase Delphi approach involving over 100 experts from 37 countries, including people with lived experience of relapse. The review showed only two pairs of studies that used the same criteria. Clinical judgment alone was sufficient to define relapse in 85% of studies, and 58% used relative symptom change. The recommended criteria cover the pre-baseline, baseline, and relapse components with optimum and minimum criteria and provide a reporting checklist. The recommendations include using standardized, validated measures that can be applied across settings, and using absolute symptom change. The authors also identify criteria that should not be used and make reporting recommendations, including for specific symptom domains (positive, negative, or cognitive) and across symptom domains, hospitalization, home treatment, and risky, violent, or suicidal behavior. There are limitations and heterogeneity in current definitions of relapse, which limit study comparisons, potentially bias meta-analyses, and question the validity of some studies. Adopting the consensus recommendations for a standardized approach should improve the validity and reliability of study outcomes, facilitate cross-study comparisons, and also standardize research into risk factors for relapse.