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Physiology & Behavior

Elsevier BV

Preprints posted in the last 7 days, ranked by how well they match Physiology & Behavior's content profile, based on 30 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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Frequent vs single active bouts differentially affect movement behavior and energy balance in adults with overweight/obesity

Santo Andre, H. C.; Roux, E. L.; De Jong, N. P.; Smith, P. R.; Lange, A. H.; Mendez, C.; Zahariev, A.; Mamele, M. L.; Johnson, G.; Pan, Z.; Simon, C.; Bessesen, D. H.; Pinto, A. J.; Bergouignan, A.

2026-04-16 sports medicine 10.64898/2026.04.14.26350871 medRxiv
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Objective: To investigate the effects of breaking up prolonged sedentary behavior (SB) on daily movement behavior and energy balance in adults with overweight/obesity. Methods: Thirty participants (16F/14M; 34.2+-7.3y; 29.5+-3.2kg/m2) were randomized to either BREAK (nine hourly 5-min brisk walking bouts) or a duration-matched intervention, ONE (45-min brisk walking), both performed 5 days/week for 6 weeks. Pre- and post-intervention, daily SB and physical activity (PA; accelerometry), body composition (doubly labeled water [DLW]), total daily energy expenditure (TDEE; DLW), appetite, and fasting leptin were measured. Linear-mixed effects models tested time effects and time-by-group interactions. Results: Only BREAK reduced prolonged SB (-8%; interaction: p=0.043). Both groups shifted SB-PA composition toward greater moderate-to-vigorous PA with proportional reductions in SB and light PA (time: all p<0.012), which were associated with increases in TDEE (+0.67 MJ/d; time: p=0.040). Body and fat mass increased in ONE only (interaction: p=0.061 and p=0.055). No differences were noted in energy intake, appetite, or leptin levels. Conclusions: Spreading short PA bouts throughout the day increases MVPA and TDEE to the same extent as a traditional continuous PA bout. Future studies should investigate whether minor differences in body composition are driven by distinct behavioral/physiological compensations influenced by the daily pattern of PA/SB.

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Proteomic associations with eating behaviors in young adults: a twin study

Masip, G.; Drouard, G.; Kaprio, J.

2026-04-15 nutrition 10.64898/2026.04.14.26350850 medRxiv
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Introduction: Eating behaviors are consistently associated with weight-related traits, yet the biological factors contributing to individual differences in these behaviors remain poorly characterized. Plasma proteomics offers an opportunity to investigate the biological processes underlying eating behaviors. Methods: Participants were 730 young adult twins from the FinnTwin12 cohort. Eating behaviors were measured through self-report questionnaires, including the Three-Factor Eating Questionnaire-R18 and four additional items on eating styles. Associations between plasma proteins and eating behaviors were examined using generalized estimating equation models adjusted for age and sex, with additional analyses adjusting for body mass index (BMI). Within-pair analyses were conducted in both monozygotic (MZ) and dizygotic twin pairs to assess whether associations were influenced by genetic or environmental factors. Results: We identified 51 significant protein-eating behavior associations involving 35 unique proteins (FDR <0.05). We observed 19 associations for the item "overeating when feeling down" and 12 for the TFEQ factor of emotional eating. The identified proteins were predominantly enriched in immune system pathways, including the complement cascade and adaptive immune signaling. After further adjustment for BMI, 12 associations persisted, most of which were associated with eating-style items, suggesting that BMI had a substantial influence on protein-eating behavior associations. Within-pair analyses of MZ pairs indicated that several associations persist after accounting for genetic effects. Conclusion: Our study identifies plasma proteins associated with eating behaviors, largely involving immune-related pathways. While some associations attenuated in twin analyses, several persisted, suggesting environmental influences. These results highlight potential biomarker candidates and indicate that modifiable environmental factors may contribute to the proteomic profiles associated with eating behaviors, with possible implications for weight-related traits.

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Current but Not Former Smoking Is Associated With Higher HbA1c in Adults Without Diabetes

Manafa, C. C.; Manafa, P. O.; Okoli, N.; Okafor-Udah, C. O.; Adilih, S.; Ogo, N.; Adilih, N.-a. A.

2026-04-17 endocrinology 10.64898/2026.04.10.26350673 medRxiv
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AimWe examined associations between smoking and HbA1c among U.S. adults, and whether these associations vary by diabetes status. MethodsWe analyzed NHANES data from 2015-2018 for adults aged [&ge;]20 years. Smoking was assessed by self-report and serum cotinine. Survey-weighted multivariable linear regression was used to evaluate the association between smoking and HbA1c in the full population (N=9,214) and in adults without diabetes (N=7,328), adjusting for demographics, blood pressure, waist circumference, lipids, and C-reactive protein. ResultsAfter adjustment for cardiometabolic covariates, there was no significant association between smoking and HbA1c in the full population (former: {beta}=0.029%, p=0.30; current: {beta}=0.053%, p=0.13). Among adults without diabetes, former smoking was not associated with HbA1c, whereas current smoking remained significantly associated (former: {beta}=-0.001%, p=0.923; current: {beta}=0.067%, p<0.001). These findings were similar when cotinine was used as the exposure measure, with active smoking ([&ge;]3.0 ng/mL) associated with higher HbA1c among non-diabetic adults (p<0.001), but not in the full population. ConclusionsAmong adults without diabetes, current but not former smoking was associated with higher HbA1c. The absence of an association in former smokers suggests that this effect may attenuate following cessation. These findings support early cessation interventions and may inform cessation counseling and diabetes screening.

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Thoracostomy Tube Infections: Prevalence and Associated Clinical Characteristics at a Tertiary Hospital in Northern Tanzania

Rwomurushaka, E. S.; Damas, L.; Niccodem, E.; Mwakyembe, T. E.; Msuya, D.; Chilonga, K.; Sango, M.

2026-04-17 surgery 10.64898/2026.04.15.26350981 medRxiv
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Background: Chest tube infection is one of the complications of the tube thoracostomy. Infectious complications may develop in 2% to 25% of patients who undergo thoracotomy tube placement. The use of prophylactic antibiotics to prevent infections associated with thoracostomy tubes remains a subject of debate. Current practices in managing infections related to tube thoracostomy are hindered by the lack of comprehensive and localised data on the microbial profile and their resistance patterns. Objective: To determine the prevalence of thoracostomy tube infections and associated clinical characteristics among patients treated with a thoracostomy tube at KCMC Zonal Referral Hospital. Methodology: Prospective cohort study done at KCMC Zonal Referral Hospital. Include all patients undergoing thoracostomy tube insertion from September 2024 to April 2025. Results: A total of 84 patients underwent tube thoracostomy during the study time. Of these 22 (26.2%) developed SSI. Out of the 22 samples collected, 17 (77.3%) had positive culture results. The most commonly identified pathogens were Pseudomonas aeruginosa (41.2%) and Staphylococcus aureus (29.4%). The highest overall susceptibility was observed with amikacin, effective against 10 (58.8%) of the tested organisms. The most common resistance was observed against ceftazidime (56.3%) and piperacillin-tazobactam (50.0%). Prolonged chest tube duration (>7 days) was the strongest independent predictor of tube thoracostomy infection. Conclusion: This study revealed a high prevalence of tube thoracostomy infection. Prolonged tube duration and admission to a non-surgical ward care emerge as key risk factors for SSI. These findings underscore the importance of limiting chest tube duration when clinically feasible and ensuring optimal postoperative care environments to minimise the risk of infection.

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Bridging the Awareness Utilisation Gap in Reusable Menstrual Product Use Among Female Medical Students and Healthcare Professionals: A Cross-Sectional Study

Wami-Amadi, C. F.; Nonju, I. I.

2026-04-12 sexual and reproductive health 10.64898/2026.04.10.26350626 medRxiv
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Background: Reusable menstrual products provide sustainable and cost effective alternatives to disposable sanitary products; however, their adoption remains limited, even among healthcare professionals. Objectives: To assess awareness, knowledge, perceptions, and utilisation of reusable menstrual products among female medical students and healthcare professionals, and to identify predictors of willingness and use. Design: Cross sectional analytical study. Setting: An online survey was conducted among female medical students and healthcare professionals in Nigeria. Participants: A total of 203 female respondents aged 15 to 55 years. Intervention: Not applicable. Primary Outcome Measures: Utilisation of reusable menstrual products and willingness to adopt their use. Secondary Outcome Measures: Awareness, knowledge, perceptions, and barriers. Methods: Data were collected using a structured questionnaire and analysed using descriptive statistics, chi square tests, and logistic regression. Results: Awareness was high (96.06%), but utilisation was low, with 5.42% ever using and 4.43% currently using reusable products. About 31.53% were willing to use them. Respondent type was not associated with willingness (p = 0.735), although healthcare professionals had higher knowledge (p = 0.024). Positive perception predicted willingness (AOR = 7.58, 95% CI: 3.18 to 18.03, p < 0.001). Good knowledge (AOR = 14.96, p = 0.014) and increasing age (AOR = 1.28, p = 0.004) predicted utilisation. Conclusion: Despite high awareness, utilisation remains low. Perception influences willingness, while knowledge drives use. Targeted behavioural and educational interventions are needed. Keywords: Menstrual hygiene, reusable menstrual products, menstrual cup, sustainability, healthcare professionals

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A randomized, double blind, placebo controlled study evaluating the impact of Hericium erinaceus (Lions Mane) on cognitive performance and subjective wellbeing

Daoust, J.; Farrar, S.; Grant, A. D.; Erfe, M. C. B.; Oliver, P. L.; Luna, V.; Moos, J.; Craft, N.

2026-04-17 nutrition 10.64898/2026.04.13.26350781 medRxiv
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Hericium erinaceus (Lions Mane) is a functional mushroom with a long history of culinary and traditional use, as well as potential neurotrophic and mood modulating properties. Evidence for its effects on cognitive performance under real world conditions, however, remains limited. In this randomized, double blind, placebo controlled trial, adults aged 40 to 75 years with self reported cognitive difficulty completed a one week baseline followed by eight weeks of daily supplementation with 2 g of H. erinaceus fruiting body and mycelial biomass or placebo. Cognitive performance using a computerized battery, as well as daily subjective assessments of sleep and wellbeing, were collected remotely. 109 Participants were included in the primary analysis (H. erinaceus, n = 57; placebo, n = 52). H. erinaceus was associated with significantly greater improvement in visual attention and working memory (Juggle Factor task), subjective sleep quality, morning restedness, and mood compared with placebo (p < 0.05). No adverse events were reported in participants receiving H. erinaceus. Together, H. erinaceus supplementation modestly improved visual attention and was associated with faster improvements in sleep quality, restedness, and mood in adults with subjective cognitive concerns.

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An Exploratory Study on the Long-Term Impact of Voiding Cystourethrogram (VCUG)

McDonald, A.; Sullivan, K.

2026-04-17 pediatrics 10.64898/2026.04.15.26350983 medRxiv
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OBJECTIVE This study investigates the long-term impacts of childhood exposure to voiding cystourethrogram (VCUG), a diagnostic procedure for vesicoureteral reflux. Primary outcomes include long-term health outcomes, mental health disorders, healthcare avoidance, and participation in risky behaviors compared to a control group. METHODS A 9-month retrospective cohort study was conducted with adults who received most of their medical care in the U.S. Respondents self-reported health metrics, behaviors, and outcomes via a 20-minute survey. Respondents were divided into two groups: those who remembered undergoing at least one VCUG in childhood (VCUG group), and those who did not (control group). RESULTS Of 334 respondents, 204 (61%) were in the VCUG group (mean age: 29, 70% female) and 130 (39%) were controls (mean age: 34, 70% female). Notable findings include: 47% of VCUG respondents were diagnosed with depression compared to 27% of controls. 15% of female-born VCUG respondents reported they would never visit a gynecologist compared to 2% of controls. 34% of VCUG respondents smoked regularly compared to 5% of controls, and 11% of VCUG respondents regularly missed work compared to 1% of controls. These findings highlight the need for further research and clinical consideration of VCUG's long-term consequences. CONCLUSIONS This study suggests that the effects of childhood VCUG extend into adulthood. Our findings underscore the need to reassess informed consent protocols and consider full-scale studies to minimize bias.

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Clinical Application of CT-Guided Lung Nodule Localization Needles in Preoperative Localization of Small Pulmonary Nodules

Xu, R.; Dou, H.; Zhang, M.; Liu, Z.

2026-04-16 surgery 10.64898/2026.04.13.26350830 medRxiv
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Background: To investigate the safety and efficacy of CTguided lung nodule localization needles for the preoperative localization of small pulmonary nodules. Methods: A retrospective study was conducted on 102 patients with a total of 113 small pulmonary nodules who underwent preoperative localization at Jinan Fourth People's Hospital from January 2024 to December 2025. Nodule diameter and depth, localization time, the number of pleural punctures, the localization success rate, and postoperative complications (hook dislodgement, hemorrhage, and pneumothorax) were recorded. All patients underwent video assisted thoracoscopic surgery (VATS) after localization. Results: The mean nodule diameter was 0.97{+/-}0.36 cm, the mean depth was 1.26{+/-}0.48 cm, and the mean localization time was 9.8{+/-}3.65 minutes. The hook dislodgement rate was 0.98% (1/102), the intrapulmonary hemorrhage rate was 14.71% (15/102), and the pneumothorax rate was 16.67% (17/102). All pulmonary nodules were successfully resected by VATS at 73.82{+/-}13.83 minutes after localization, and no severe complications occurred. Conclusions: The use of a CTguided lung nodule localization needle for the preoperative localization of small pulmonary nodules decreases the time needed for intraoperative nodule detection and operation time. This strategy is a simple, safe, and accurate preoperative localization method that is worthy of increased clinical use.

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Cross-cultural adaptation and validation of the Japanese Charite Alarm Fatigue Questionnaire (CAFQa) among ICU nurses and physicians: a multicenter study

Sato, T.; Ishiseki, M.; Kataoka, Y.; Someko, H.; Sato, H.; Minami, K.; Kaneko, T.; Takeda, H.; Crosby, A.

2026-04-11 intensive care and critical care medicine 10.64898/2026.04.07.26350292 medRxiv
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ObjectivesAlarm fatigue is a patient safety concern in ICUs, yet no validated instrument exists to assess alarm fatigue among healthcare professionals in non-Western settings. This study aimed to cross-culturally adapt the Charite Alarm Fatigue Questionnaire (CAFQa) into Japanese and evaluate its reliability and validity among ICU nurses and physicians. MethodsThe Japanese CAFQa was cross-culturally adapted following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines, including forward translation, back-translation, expert panel review, and cognitive interviews. A multicenter cross-sectional validation study was performed across eight ICUs at five hospitals in Japan. A total of 129 participants (103 nurses and 26 physicians) completed the Japanese CAFQa, the NIOSH Brief Job Stress Questionnaire, and the Insomnia Severity Index (ISI). Structural validity, internal consistency, test-retest reliability (n = 102), convergent validity, and known-groups validity were assessed. ResultsCFA confirmed the two-factor structure with acceptable fit (CFI = 0.922, RMSEA = 0.041, SRMR = 0.076), with standardized factor loadings ranging from 0.33 to 0.82. The two factors were not correlated (r = 0.05). Cronbachs alpha was 0.688 for the overall scale, 0.805 for Alarm Stress, and 0.649 for Alarm Coping. Test-retest ICCs ranged from 0.616 to 0.753. The CAFQa total score correlated with the NIOSH total (r = 0.261) and the ISI total (r = 0.338). Healthcare professionals with [&ge;]4 years of ICU experience had higher Alarm Coping scores than those with 1-3 years (median 7.0 vs 6.5), and physicians scored higher on Alarm Coping than nurses (median 8.0 vs 7.0). ConclusionsThe Japanese CAFQa demonstrated acceptable structural validity, reliability, and convergent and known-groups validity, providing the first validated tool for quantitatively measuring alarm fatigue in Japan. Implications for Clinical PracticeThe Japanese CAFQa enables ICU managers to quantify alarm fatigue at individual and unit levels, identify high-risk staff, and evaluate the effectiveness of alarm management interventions.

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Combined Flywheel Resistance and Aerobic Exercise on Power output and Function in Chronic Kidney Disease: An Exploratory Study on the Influence of Physical Activity

Gollie, J.; Ryan, A. S.; Harris-Love, M. O.; Kokkinos, P.; Scholten, J.; Pugh, R. J.; Hazel, C. G.; Blackman, M. R.

2026-04-16 sports medicine 10.64898/2026.04.14.26350873 medRxiv
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Physical inactivity is common in chronic kidney disease (CKD) and is associated with poor neuromuscular and functional outcomes. Whether habitual physical activity (PA) influences adaptations to structured exercise in CKD remains unclear. This study examined if adaptations to combined flywheel resistance and aerobic exercise (FRE+AE) differed based on self-reported PA in Veterans with CKD stages 3 and 4. Twenty older male Veterans with CKD stages 3-4 (mean eGFR 37.9 +/- 10.2 mL/min/1.73 m2) were randomized to six weeks of FRE+AE (n=11) or health education (EDU; n=9). Participants were classified as meeting (Meets PA) or below (Low PA) weekly moderate intensity PA recommendations using the 7-day Physical Activity Recall. Outcomes included vastus lateralis muscle thickness (VL MT), knee extensor power output (60/s and 180/s), gait speed (GS), and five-repetition sit-to-stand (STS). FRE+AE increased VL MT (p=0.030), power output at 180/s (p=0.021), GS (p=0.001), and reduced STS time (p=0.012), with significant between-group differences versus EDU for VL MT (p=0.009) and GS (p=0.028). Low PA experienced greater increases in power output at 60/s (Hedges g; Low PA=0.44, Meets PA=0.25) and 180/s (Hedges g; Low PA=1.38, Meets PA=0.38) compared to Meets PA after FRE+AE. Conversely, Meets PA had greater improvements in GS (Hedges g; Low PA=0.93, Meets PA=1.29) and STS (Hedges g; Low PA=-0.72, Meets PA=-2.20) compared to Low PA. Six weeks of FRE+AE produced clinically meaningful neuromuscular and functional improvements in Veterans with CKD stages 3 and 4 irrespective of PA level, supporting FRE+AE as a feasible intervention in this population.

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Ultraprocessed foods elicit distinct metabolic and neural responses when compared to non-ultraprocessed foods

Hutelin, Z.; Ahrens, M.; Baugh, M. E.; Nartey, E.; Herald, D. L.; Hanlon, A. L.; DiFeliceantonio, A. G.

2026-04-11 nutrition 10.64898/2026.04.10.26350599 medRxiv
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Dietary patterns worldwide have shifted toward increased consumption of ultraprocessed foods (UPFs), which has been linked to higher disease burden. One mechanism proposed to impact both their consumption and contribution to metabolic disease is altered post-ingestive metabolic response in comparison to nutritionally similar foods. Here, we recruited 57 healthy-weight 18-45-year-old adults to examine the effects of food processing on postprandial metabolism and brain response. Despite nutritional matching, UPF meals evoked a greater insulinemic and energetic response with attenuated carbohydrate oxidation relative to non-UPF meals. Next, between-condition differences in peak carbohydrate oxidation were associated with mesolimbic and superior temporal gyrus activation in response to food cues. Finally, although food value did not differ between conditions, brain responses correlated with food valuation were positive for non-UPF but negative for UPF in visual cortex and striatum. These findings demonstrate that food processing influences post-ingestive metabolism in a way that could help explain long term health effects and differences in food reward through mechanisms beyond calories and macronutrient composition alone.

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Perceived vs. actual navigation ability: Differences between autistic and typically developing children

McKeown, D. J.; Cruzado, O. S.; Colombo, G.; Angus, D. J.; Schinazi, V. R.

2026-04-13 psychiatry and clinical psychology 10.64898/2026.04.09.26350542 medRxiv
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PurposeNavigational ability develops throughout childhood alongside the maturation of brain regions supporting egocentric and allocentric processing. In Autism Spectrum Disorder (ASD), atypical hippocampal development may impact flexible spatial memory; however, findings on navigational ability in autistic children remain inconsistent. This study aimed to compare both objective and perceived navigation ability in children with ASD and typically developing (TD) peers. MethodTwenty-six children with high-functioning ASD and twenty-five age- and gender-matched TD children (M_age = 12.04 years, SD = 1.64) completed a battery of navigational tasks from the Spatial Performance Assessment for Cognitive Evaluation (SPACE), including Path Integration, Egocentric Pointing, Mapping, Associative Memory, and Perspective Taking. Perceived navigation ability was assessed using the Santa Barbara Sense of Direction (SBSOD) scale. ResultsNo significant group differences were observed across any objective navigation tasks. However, children with ASD reported significantly lower perceived navigation ability compared to TD peers. ConclusionThese findings suggest a dissociation between perceived and actual navigational ability in ASD. By early adolescence, objective navigation performance appears intact, potentially reflecting sufficient maturation of underlying neural systems or the presence of compensatory mechanisms. The results underscore the importance of incorporating objective, task-based measures when assessing cognitive abilities in autistic populations.

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Plasma Neurofilament Light Chain and Glial Fibrillary Acidic Protein in Psychiatric Disorders: A Large-Scale Normative Modeling Study

Jacobsen, A. M.; Quednow, B. B.; Bavato, F.

2026-04-12 psychiatry and clinical psychology 10.64898/2026.04.08.26350391 medRxiv
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ImportanceBlood neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are entering clinical use in neurology as markers of neuroaxonal and astrocytic injury, but their utility in psychiatry is unclear. ObjectiveTo determine whether psychiatric diagnoses are associated with altered plasma NfL and GFAP levels. Design, Setting, and ParticipantsThis population-based study examined plasma NfL and GFAP among 47,495 participants from the UK Biobank (54.0% female; 93.5% White; mean [SD] age 56.8 [8.2] years) who provided blood samples and sociodemographic and clinical data between 2006 and 2010. Normative modeling was applied to assess associations between 7 lifetime psychiatric diagnostic categories and deviations from expected NfL and GFAP levels, while accounting for neurological diagnoses, cardiometabolic burden, and substance use. Data were analyzed between July 2025 and March 2026. Main Outcomes and MeasuresDeviations in plasma NfL and GFAP levels from normative predictions. ResultsRelative to the reference population, plasma NfL levels were higher among individuals with bipolar disorder (d=0.20; 95% CI, 0.03-0.37; p=0.03), recurrent depressive disorder (d=0.23; 95% CI, 0.07-0.38; p=0.009), and depressive episodes (d=0.06; 95% CI, 0.02-0.10; p=0.01), lower among individuals with anxiety disorders (d=-0.07; 95% CI, -0.12 to -0.02; p=0.008), but did not differ in schizophrenia spectrum, stress-related, or other psychiatric disorders. Plasma GFAP levels were not elevated in any psychiatric disorders. Variability in NfL levels was greater among individuals with schizophrenia spectrum disorders (variance ratio [VR]=1.30; p=0.005), depressive episodes (VR=1.06; p=0.006), and anxiety disorders (VR=1.08; p=0.005). Variability in GFAP levels was increased only in anxiety disorders (VR=1.08; p=0.01). Plasma NfL levels exceeding percentile-based normative thresholds were more common among individuals with schizophrenia spectrum disorders, bipolar disorder, recurrent depressive disorder, and depressive episodes. Neurological diagnoses, cardiometabolic burden, and substance use were associated with plasma NfL and GFAP levels. Conclusions and RelevanceThis study provides population-level evidence of plasma NfL elevation in bipolar and depressive disorders and increased variability in schizophrenia spectrum, bipolar and depressive disorders, supporting its potential as a biomarker in psychiatry and informing its ongoing neurological applications. Plasma GFAP levels, in contrast, were largely unaltered across psychiatric disorders. Key PointsO_ST_ABSQuestionC_ST_ABSAre plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels altered in psychiatric disorders? FindingsIn this cohort study including 47,495 individuals, normative modeling revealed that plasma NfL levels were elevated in bipolar and depressive disorders, whereas plasma GFAP levels were not elevated in any psychiatric disorder. Plasma NfL levels also showed higher variability in schizophrenia spectrum, bipolar, and depressive disorders. MeaningPlasma NfL shows distinct alterations in schizophrenia spectrum and affective disorders, supporting its further investigation as a biomarker in clinical psychiatry and highlighting the need to consider psychiatric comorbidity in neurological applications.

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A Replicable NeuroMark Template for Whole-Brain SPECT Reveals Data-Driven Perfusion Networks and Their Alterations in Schizophrenia

Harikumar, A.; Baker, B.; Amen, D.; Keator, D.; Calhoun, V. D.

2026-04-12 psychiatry and clinical psychology 10.64898/2026.04.08.26349985 medRxiv
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Single photon emission computed tomography (SPECT) is a highly specialized imaging modality that enables measurement of regional cerebral perfusion and, in particular, resting cerebral blood flow (rCBF). Recent technological advances have improved SPECT quantification and reliability, making it increasingly useful for studying rCBF abnormalities and perfusion network alterations in psychiatric and neurological disorders. To characterize large scale functional organization in SPECT data, data driven decomposition methods such as independent component analysis (ICA) have been used to extract covarying perfusion patterns that map onto interpretable brain networks. Blind ICA provides a data driven approach to estimate these networks without strong prior assumptions. More recently, a hybrid approach that leverages spatial priors to guide a spatially constrained ICA (sc ICA) have been used to fully automate the ICA analysis while also providing participant-specific network estimates. While this has been reliably demonstrated in fMRI with the NeuroMark template, there is currently no comparable SPECT template. A SPECT template would enable automatic estimation of functional SPECT networks with participant-specific expressions that correspond across participants and studies. The current study introduces a new replicable NeuroMark SPECT template for estimating canonical perfusion covariance patterns (networks). We first identify replicable SPECT networks using blind ICA applied to two large sample SPECT datasets. We then demonstrate the use of the resulting template by applying sc-ICA to an independent schizophrenia dataset. In sum, this work presents and shares the first NeuroMark SPECT template and demonstrating its utility in an independent cohort, providing a scalable and robust framework for network-based analyses.

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Gamma Neuromodulation Provides Therapeutic Potential in Neuropsychiatry: A Systematic Review and Meta-Analysis

Xu, M.; Philips, R.; Singavarapu, A.; Zheng, M.; Martin, D.; Nikolin, S.; Mutz, J.; Becker, A.; Firenze, R.; Tsai, L.-H.

2026-04-12 psychiatry and clinical psychology 10.64898/2026.04.10.26350641 medRxiv
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Background: Gamma oscillation dysfunction has been implicated in neuropsychiatric disorders. Restoring gamma oscillations via brain stimulation represents an emerging therapeutic approach. However, the strength of its clinical effects and treatment moderators remain unclear. Method: We conducted a systematic review and meta-analysis to examine the clinical effects of gamma neuromodulation in neuropsychiatric disorders. A literature search for controlled trials using gamma stimulation was performed across five databases up until April 2025. Effect sizes were calculated using Hedge's g. Separate analyses using the random-effects model examined the clinical effects in schizophrenia (SZ), major depressive disorder (MDD), bipolar disorder, and autism spectrum disorder. For SZ and MDD, subgroup analyses evaluated the effects of stimulation modality, stimulation frequency, treatment duration, and pulses per session. Result: Fifty-six studies met the inclusion criteria (NSZ = 943, NMDD = 916, NBD = 175, NASD = 232). In SZ, gamma stimulation was associated with improvements in positive (k = 10, g = -0.60, p < 0.001), negative (k = 12, g = -0.37, p = 0.03), depressive (k = 8, g = -0.39, p < 0.001), anxious symptoms (k = 5, g = -0.59, p < 0.001), and overall cognitive function (k = 7, g = 0.55, p < 0.001). Stimulation frequency and treatment duration moderated therapeutic effects. In MDD, reductions in depressive symptoms were observed (k = 23, g = -0.34, p = 0.007). Conclusion: Gamma neuromodulation showed moderate therapeutic benefits in SZ and MDD. Substantial heterogeneity likely reflects protocol differences, highlighting the need for well-powered future trials.

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Early-life adversity and markers of vulnerability to enduring pain in youth: a multimodal neuroimaging study of the ABCD cohort

Quide, Y.; Lim, T. E.; Gustin, S. M.

2026-04-11 psychiatry and clinical psychology 10.64898/2026.04.07.26350367 medRxiv
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BackgroundEarly-life adversity (ELA) is a risk factor for enduring pain in youth and is associated with alterations in brain morphology and function. However, it remains unclear whether ELA-related neurobiological changes contribute to the development of enduring pain in early adolescence. MethodsUsing data from the Adolescent Brain Cognitive Development (ABCD) Study, we examined multimodal magnetic resonance imaging (MRI) markers in children assessed at baseline (ages 9-11 years) and at 2-year follow-up (ages 11-13 years). ELA exposure was defined at baseline to maximise temporal separation between early adversity and later enduring pain. Participants with enduring pain at follow-up (n = 322) were compared to matched pain-free controls (n = 644). Structural MRI, diffusion MRI (fractional anisotropy, mean diffusivity), and resting-state functional connectivity data were analysed. Linear models tested main effects of enduring pain, ELA, and their interaction on brain metrics, controlling for relevant covariates. ResultsELA exposure was associated with smaller caudate and nucleus accumbens volumes, and reduced surface area of the left rostral middle frontal gyrus. No significant effects of enduring pain or ELA-by-enduring pain interaction were observed across grey matter, white matter, or functional connectivity measures. ConclusionsELA was associated with alterations in fronto-striatal regions in late childhood, but these changes were not linked to enduring pain in early adolescence. These findings suggest that ELA-related neurobiological alterations may represent early markers of vulnerability rather than concurrent correlates of enduring pain. Longitudinal follow-up is needed to determine whether these alterations contribute to later chronic pain risk.

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Racial Differences in Negative Symptoms of Schizophrenia: Examining the Role of Defeatist Beliefs and Discrimination

Spann, D. J.; Hall, L. M.; Moussa-Tooks, A.; Sheffield, J. M.

2026-04-11 psychiatry and clinical psychology 10.64898/2026.04.08.26350400 medRxiv
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BackgroundNegative symptoms are core features of schizophrenia that relate strongly to functional impairment, yet interventions targeting these symptoms remain largely ineffective. Emerging theoretical work highlights how environmental factors may shape and maintain negative symptoms. Although racial disparities in schizophrenia diagnosis among Black Americans are well documented and linked to racial stress and psychosis, the impact of racial stress on negative symptoms has not been examined. This study provides an initial test of a novel theory proposing that racial stress - here measured by racial discrimination - influences negative symptom severity through exacerbation of negative cognitions about the self, particularly defeatist performance beliefs (DPB). Study DesignParticipants diagnosed with schizophrenia-spectrum disorder (SSD) (N = 208; 80 Black, 128 White) completed the Positive and Negative Syndrome Scale (PANSS), the Defeatist Beliefs Scale, and self-report measures of subjective racial and ethnic discrimination (Racial and Ethnic Minority Scale and General Ethnic Discrimination Scale). Relationships among variables were tested using linear regression and mediation analysis. Study ResultsBlack participants exhibited significantly greater total and experiential negative symptoms than White participants with no group difference in DPB. Racial discrimination explained 46% of the relationship between race and negative symptoms. Among Black participants, higher DPB were associated with greater negative symptom severity. Discrimination was positively related to both DPB and negative symptoms. DPB partially mediated the relationship between discrimination and negative symptoms. ConclusionsFindings suggest that racial stress contributes to negative symptom severity via defeatist beliefs among Black individuals, highlighting potential targets for culturally informed interventions.

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MTHFR C677T polymorphism and promoter methylation in schizophrenia patients with type 2 diabetes mellitus: evidence from a Han Chinese cohort

Yang, C.; Li, R.; Wang, X.; Li, K.; Yuan, F.; Jia, X.; Zhang, R.; Zheng, J.

2026-04-13 psychiatry and clinical psychology 10.64898/2026.04.09.26350471 medRxiv
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Schizophrenia (SCZ) and type 2 diabetes mellitus (T2DM) are common comorbid disorders that severely impair patient prognosis and quality of life. This study aimed to explore the association between the methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and MTHFR promoter methylation in patients with comorbid SCZ and T2DM. A total of 120 participants were enrolled from Liaocheng Fourth Peoples Hospital between January 2025 and June 2025, comprising 30 subjects in each of the four groups: SCZ group, T2DM group, SCZ-T2DM comorbid (SCZ+T2DM) group, and healthy control (CTL) group. Corresponding primers were designed for genetic analysis, and methylation-specific PCR (MSP) was performed to detect the methylation level of the MTHFR promoter. Genotype distribution of the MTHFR C677T polymorphism was consistent with Hardy-Weinberg equilibrium (HWE) (p>0.05). The C677T polymorphism was significantly associated with an elevated risk of SCZ and T2DM comorbidity (p<0.05). Notably, the methylation rate of the MTHFR promoter in the SCZ+T2DM group (95.00%) was not significantly higher than that in the CTL group (90.00%) (p>0.05). In conclusion, the MTHFR gene may serve as a susceptibility gene for SCZ-T2DM comorbidity, whereas MTHFR promoter methylation is not associated with the pathogenesis of this comorbid condition. These results indicate that genetic variation in MTHFR, rather than promoter methylation, contributes critically to the comorbidity of SCZ and T2DM in the Han Chinese population. Our findings may provide novel molecular insights into their shared pathophysiology and inform future clinical strategies for patients with this complex phenotype.

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Years Lived without Chronic Diseases after Statutory Retirement - A Register Linkage Follow-up Study in Finland 2000-2021

Pietilainen, O.; Salonsalmi, A.; Rahkonen, O.; Lahelma, E.; Lallukka, T.

2026-04-13 public and global health 10.64898/2026.04.12.26348889 medRxiv
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Objectives: Longer lifespans lead to longer time on retirement, despite the efforts to raise the retirement age. Therefore, it is important to study how the retirement years can be spent without diseases. This study examined socioeconomic and sociodemographic differences in healthy years spent on retirement. Methods: We followed a cohort of retired Finnish municipal employees (N=4231, average follow-up 15.4 years) on national administrative registers for major chronic diseases: cancer, coronary heart disease, cerebrovascular disease, diabetes, asthma or chronic obstructive pulmonary disease, dementia, mental disorders, and alcohol-related disorders. Median healthy years on retirement and age at first occurrence of illness (ICD-10 and ATC-based) in each combination of sex, occupational class, and age of retirement were predicted using Royston-Parmar models. Prevalence rates for each diagnostic group were calculated. Results: Most healthy years on retirement were spent by women having worked in semi-professional jobs who retired at age 60-62 (median predicted healthy years 11.6, 95% CI 10.4-12.7). The least healthy years on retirement were spent by men having worked in routine non-manual jobs who retired after age 62 (median predicted healthy years 6.5, 95% CI 4.4-9.5). Diabetes was slightly more common among lower occupational class women, and dementia among manual working women having retired at age 60-62. Discussion: Healthy years on retirement are not enjoyed equally by women and men and those who retire early or later. Policies aiming to increase the retirement age should consider the effects of these gaps on retirees and the equitability of those effects.

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Policy Levers of HIV Control: Targeted Service Coverage, Financial Protection, and Estimated New HIV Infections in Southeast Asia, 2013-2022

Hung, J.; Smith, A.

2026-04-13 public and global health 10.64898/2026.04.11.26350590 medRxiv
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The global ambition to end the human immunodeficiency virus (HIV) epidemic requires understanding which system-level policy levers, enacted under the framework of Universal Health Coverage (UHC), are most effective in achieving both transmission reduction and diagnostic coverage. This study addresses an important evidence gap by quantifying the within-country association between measurable UHC policy indicators and the estimated rate of new HIV infections across nine Southeast Asian countries between 2013 and 2022. Employing a Fixed-Effects panel data methodology, the analysis controls for time-invariant national heterogeneity, ensuring reliable estimates of policy impact. We found that marginal changes in total current health expenditure (CHE) as a percentage of gross domestic product (GDP) were not statistically significantly associated with changes in HIV incidence. However, increases in the UHC Infectious Disease Service Coverage Index were statistically significantly associated with concurrent reductions in HIV incidence (p < 0.001), suggesting the efficacy of targeted service implementation as the principal driver of curbing new HIV infections. In addition, the UHC Reproductive, Maternal, Newborn, and Child Health Service Coverage Index exhibited a statistically significant positive association with changes in HIV incidence (p < 0.01), which is interpreted as a vital surveillance artefact resulting from expanded detection and reporting of previously undiagnosed HIV cases. Furthermore, out-of-pocket (OOP) health expenditure as a percentage of CHE showed a counter-intuitive negative association with changes in HIV incidence (p < 0.01), suggesting this metric primarily shows ongoing indirect cost burdens on the established patient cohort, or, alternatively, presents a diagnostic access barrier that results in lower case finding. These findings suggest that policymakers should prioritise investment in targeted infectious disease service efficacy over aggregate fiscal commitment and utilise integrated sexual health platforms for strengthened HIV surveillance and case identification.