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BIOCARD framework: integrating fecal bile acids, lipids, and metabolites to assess response to a cardiovascular health intervention.

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality, particularly in under-resourced populations. Although nutritional interventions are important for CVD prevention, their outcomes are commonly evaluated using conventional clinical and behavioral indicators, which may not fully capture early molecular responses. In this study, we developed the BIOCARD framework, an exploratory fecal multi-omics platform integrating bile acids, lipids, and metabolites to evaluate intervention outcomes related to cardiovascular health. Fecal samples were collected from caregiver-child participants enrolled in a 10-week randomized controlled trial comparing a multicomponent garden-based intervention (SHA) with an education-only control group (MSP). Fecal polar metabolites, lipids, and bile acids were analyzed by UHPLC-HRMS-based approaches and integrated with conventional health indicators. Traditional clinical indicators in the present study showed limited sensitivity for detecting intervention-related differences. In contrast, fecal multi-omics analyzes revealed intervention-associated differences in metabolites, lipids, and bile acids, with children showing more apparent molecular variation than parents. Network analysis further revealed associations between selected molecular features and cardiovascular-related indicators, including blood pressure, body fat, skin carotenoids, and Healthy Eating Index scores. Together, these findings suggest that the BIOCARD framework may serve as an exploratory molecular approach to complement traditional outcome measures and improve the evaluation of nutritional interventions for cardiovascular health.

Humans

Empathic Accuracy and Behavioral Empathy After a Moderate Dose of Beer.

OBJECTIVES: Empathic accuracy (EA) represents a person's ability to correctly infer the emotions of another person. One past study in men found lower EA for positive emotions after a moderate dose of hard liquor compared to after placebo, particularly among non-hazardous drinkers. The present study aimed to replicate this finding, using a moderate dose of beer and a mixed design. Moreover, we added a novel measure of behavioral empathy. METHODS: Participants (62% men) completed the Alcohol Use Disorders Identification Test, Empathy Quotient, and Revised Drinking Motives Questionnaire. Before and after drinking either beer (6.6% alcohol, n = 28) or its 0.0% equivalent (placebo, n = 38), they watched videoclips of targets talking about emotional autobiographical events and rated how targets felt while talking. Behavioral empathy was assessed by presenting participants with painful scenarios and asking whether they would help the people in pain. RESULTS: The previous finding of lower EA for positive emotions after alcohol was not replicated. Nonetheless, after alcohol non-hazardous drinkers were less willing to help people in pain. Trait affective empathy (i.e., a person's long-term disposition to experience emotional responses congruent to another's feelings) and the drinking to cope motive did not significantly moderate the findings. CONCLUSIONS: Although alcohol may alter empathy, its effects are not consistent and may depend on the dose and type of alcohol consumed. The moderating roles of trait empathy and trait aggressivity deserves further study.

Humans

Does impulsivity predict treatment outcomes in PTSD with borderline personality disorder features? Results from a randomized clinical trial.

BACKGROUND: Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). However, a substantial proportion of clients do not respond adequately or drop out of therapy prematurely. This has sparked interest in identifying individual-level predictors of treatment outcomes, including improvement in PTSD severity and dropout. Impulsivity may be a predictor because it may interfere with key therapeutic processes, such as cognitive restructuring and emotional processing. Consequently, we present a hypothesis-driven secondary analysis of a 15-month randomized clinical trial comparing Dialectical Behavior Therapy for PTSD (DBT-PTSD) and Cognitive Processing Therapy (CPT) in women with childhood abuse-related PTSD and borderline personality disorder features to test whether impulsivity, assessed at baseline, predicts PTSD improvement and dropout. We further explore whether the dimensions of impulsivity (non-planning, attentional impulsivity, and motor impulsivity) differentially affect the outcomes in DBT-PTSD vs. CPT. METHODS: A total of 193 cis women with PTSD related to childhood abuse and borderline personality disorder features were assessed using the Clinician-Administered PTSD Scale (CAPS) and the Barratt Impulsiveness Scale (BIS-10). Separate probit models and general linear models were applied to predict dropout and pre-to-post changes in PTSD severity (ΔCAPS) from total impulsivity and subscale scores, i.e. non-planning, attentional and motor impulsivity. RESULTS: Overall, dropout rates were higher for participants with higher baseline impulsivity scores (p = 0.049), particularly for those with higher non-planning impulsivity (p = 0.012). In participants randomized to CPT improvement in PTSD symptom severity (ΔCAPS) was negatively related to baseline total impulsivity (p = 0.021). In participants randomized to DBT-PTSD this relation was not significant. CONCLUSIONS: The results suggest that impulsivity may predict treatment outcomes. Specifically, patients with elevated impulsivity may be less likely to respond adequately to CPT. If replicated, these findings have implications for personalization of treatment.

Humans

Dissociating behavioral, neural and experiential effects of prefrontal HD-tDCS during conflict resolution.

Inconsistent evidence regarding the cognitive effects of transcranial direct current stimulation (tDCS) highlights the need for more comprehensive approaches to assess its impact. This study aimed to investigate the effects of high-definition tDCS (HD-tDCS) on conflict resolution by combining behavioral, neural, and subjective experience measures. Sixty participants were randomly assigned to anodal, cathodal, or sham HD-tDCS groups and completed a 30-min flanker task. EEG was recorded during the first and last blocks (without stimulation), while stimulation was applied during the intermediate blocks of the task. Using a multidimensional methodological approach including Drift-Diffusion Modeling (DDM), EEG spectral analysis, Lempel-Ziv complexity, and Temporal Experience Tracing (TET), we assessed the cognitive, neural, and phenomenological effects of stimulation. Behavioral results indicated no significant improvements in reaction times or accuracy across the stimulation groups. Similarly, DDM parameters showed no effect of HD-tDCS on latent cognitive processes. However, EEG data revealed a significant reduction in neural complexity in the anodal group during resting-state, suggesting a stabilization or reorganization of neural dynamics. Subjective experience analysis identified two distinct clusters of task-related feelings, though time spent in these experiential states did not differ between groups. Interestingly, sensation of stimulation was significantly higher for anodal stimulation than sham when analyzed as a single dimension. Despite null behavioral effects, this study provides important insights into the neural and subjective responses to HD-tDCS and highlights the value of integrating complementary multidimensional approaches to better characterize brain stimulation effects. These findings contribute to the ongoing debate about the efficacy of tDCS in cognitive enhancement.

Humans

Hippocampal teneurin-4 knockdown promotes depression-like behavioral phenotypes by disrupting oligodendrocyte differentiation in mice.

Depression is one of the most prevalent mental disorders worldwide. The limited clinical efficacy of current antidepressants highlights identifying new therapeutic targets. Emerging evidence suggests that dysfunction of oligodendrocyte lineage cells contributes to the pathophysiology of depression. Teneurin-4 (Tenm4), a transmembrane protein that promotes oligodendrocyte differentiation and myelination, has been implicated in psychiatric disorders in genome-wide association studies; however, its causal role remains unclear. To determine whether Tenm4 contributes to depressive-like behavioral phenotypes, we examined Tenm4 protein expression in mice exposed to repeated forced swimming stress and generated hippocampal Tenm4 knockdown (Tenm4KD) mice. Chronic stress reduced Tenm4 expression levels in the hippocampus. Mice with hippocampus-specific Tenm4KD exhibited depressive-like behaviors, accompanied by reduced hippocampal myelin basic protein. Importantly, administration of clemastine, a myelin formation promoter, inhibited the reduction of myelin and attenuated depression-like behavioral phenotypes. Immunohistochemical analysis showed that Tenm4KD significantly decreased the number of mature oligodendrocyte cells and increased in the number of oligodendrocyte precursor cells, without changes in the total number of oligodendrocyte lineage cells. This study provides the first evidence that hippocampal Tenm4 deficiency induces depression-like behavior phenotypes through impaired oligodendrocyte differentiation and promoting demyelination. Our results identify Tenm4 as a molecular regulator of stress-induced behavioral phenotypes and suggest that it might represent a potential therapeutic target for mood disorders associated with demyelination.

Animals

Perinatal depression, maternal thyroid status and fetus/infant health and development: A systematic review.

BACKGROUND: Thyroid hormones are known to influence both maternal depression and child developmental outcomes, while maternal depression independently affects child outcomes. The potential interaction between thyroid dysfunction and depression in shaping child development remains insufficiently explored. The present study addresses such interplay. METHODS: Following PRISMA 2020 and JBI guidelines, three databases were searched through December 2025 for primary studies on maternal thyroid status, perinatal depression, and child development. Risk of bias (RoB) was assessed using validated tools. Due to clinical and methodological heterogeneity, data were synthesized narratively following SWiM guidelines. RESULTS: Eleven studies were included. Beyond independent risks for preterm birth and behavioral problems, limited evidence supports a synergistic model, while most studies likely reflect the simple co-occurrence of risks. Maternal thyroid peroxidase antibodies (TPO-Ab) were associated with child externalizing problems exclusively in the presence of clinical depression. High depressive symptoms also attenuated the cognitive benefits of prenatal iodine supplementation. Thyroid status appears to function as a risk moderator rather than a mediator. However, 50% of observational studies presented high RoB, primarily due to participant attrition. CONCLUSION: Findings are still scarce to support a synergistic risk model where specific maternal thyroid parameters (i.e. thyroid autoimmunity and iodine status) may moderate the impact of depressive symptoms on child development. Despite the high RoB in half of the studies, results highlight the need for integrated screening protocols. Simultaneously assessing mental health and thyroid status may optimize risk stratification for high-risk mother-infant dyads.

Female

Post-trial 12-month follow-up of TRACE (targeted research on addictive and compulsive eating) randomised controlled trial participants: A brief report.

Few treatment interventions for addictive eating have evaluated long-term effectiveness. This post-trial follow-up study evaluates secondary changes in addictive eating symptoms and quality of life at 12-months in a sample of individuals who participated in the TRACE (Targeted Research for Addictive and Compulsive Eating) RCT. Thirty-three adults out of possible 144 (82% female), median age 53 years, randomised to either the active intervention (five telehealth sessions delivered over 3-months), passive intervention (self-guided workbook) or control group completed an online post-trial survey. Pre- and immediate post-intervention (3-months) outcomes were compared to 12-months post-trial outcomes. Positive effects reported in the short term showed a rebound effect at post-trial follow-up in ∼50% of participants. The findings suggest that longer term support is needed to maintain changes in addictive eating behaviours and improve quality of life. Future research is needed to identify optimal intervention durations and support options for sustained change. Australian New Zealand Clinical Trials Registry (ACTRN12621001079831).

Humans

Health bill beneath the plastic feast: A phthalate contamination alert from takeout food containers.

The rapid growth of takeout food consumption in China has raised concerns regarding exposure to phthalic acid esters (PAEs) from food packaging. This study investigated the presence, source, contribution, and health risk of PAEs in commonly used takeout containers. Widespread contamination was observed, with total PAE concentrations ranging from below the limit of detection to 222,000 ng/g. Diisobutyl phthalate (DIBP), dibutyl phthalate (DBP), and bis(2-ethylhexyl) phthalate (DEHP) were identified as the predominant compounds, accounting for 7.50 %, 14.7 %, and 18.7 % of the total concentration, respectively. These PAEs may originated from additives during manufacturing and potential contamination of raw materials. Human exposure assessment showed that daily exposure doses of DIBP, DBP, and DEHP via container ranged from 0.00 to 2340 ng/(kg·day) among frequent takeout consumers, contributing substantially to overall PAE body burdens. To further assess exposure and associated risks, a nationwide online questionnaire survey was conducted across China. Based on this national-scale behavioral dataset, the health risks among Chinese residents were evaluated. Although the modeled non-carcinogenic risks of DIBP, DBP, and DEHP remained within acceptable limits, the simulation suggested that approximately 70 % of participants may experience potential exceedance of the carcinogenic risk threshold for DEHP. The frequency of takeout food consumption was identified as the most important factor affecting PAE exposure. These findings underscore the importance of limiting takeout frequency and reducing reliance on plastic containers to mitigate health risks. This study provides scientific evidence to support the development of safer packaging materials and informs public health strategies.

Phthalic Acids

Association between cumulative social disadvantage, as measured by the social determinants of health score, and epilepsy: a cross-sectional study.

BACKGROUND: Social determinants of health (SDoH) shape access to care, health behaviors, and long-term outcomes, yet their cumulative relationship with epilepsy has not been well quantified. This study examined whether a composite SDoH score was associated with epilepsy in adults. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey 2013-2018. The SDoH score ranged from 0 to 8 and summarized eight unfavorable social conditions. Epilepsy was identified using medication-based ascertainment. Survey-weighted logistic regression models were applied to evaluate the association between SDoH score and epilepsy. Restricted cubic spline, subgroup, sensitivity, and receiver operating characteristic analyses were also performed. RESULTS: A total of 13,119 participants were included, of whom 114 had epilepsy. Participants with epilepsy had a higher mean SDoH score than those without epilepsy (3.41&#xa0;&#xb1;&#xa0;0.24 vs. 2.35&#xa0;&#xb1;&#xa0;0.06, P&#xa0;<&#xa0;0.001). In the fully adjusted model, each 1-point increase in SDoH score was associated with 31% higher odds of epilepsy (OR 1.31, 95% CI 1.16-1.48). Compared with the low-score group (0-2), the adjusted odds ratios were 2.09 (95% CI 1.06-4.15) for scores of 3-5 and 2.67 (95% CI 1.34-5.33) for scores of 6-8. Spline analysis showed a significant overall association without evidence of nonlinearity. Adding SDoH components to demographic variables improved model discrimination (AUC 0.731 vs. 0.589, P for difference <0.001). CONCLUSION: Greater cumulative social disadvantage, as reflected by the SDoH score, was associated with higher odds of epilepsy.

Humans

Neuroimaging anxious children and adolescents before and after cognitive behavioral therapy: a systematic review.

OBJECTIVE: This systematic review investigates brain changes in youths with anxiety disorders following cognitive behavioral therapy (CBT) and neural markers that predict CBT responses. METHODS: We conducted a systematic search using the electronic databases PubMed, Web of Science, and ProQuest. The inclusion deadline was set to October 27, 2025. We included fifteen peer-reviewed neuroimaging studies that examined the effects of CBT in youths under 19 years old with a primary clinical diagnosis of an anxiety disorder based on DSM-5 criteria. RESULTS: Although the existing literature is marked by substantial diversity in methods and outcomes, task-related neural response in the anterior cingulate cortex (ACC, 2/8, 25.0%), insula (1/8, 12.5%) increased from pre to post CBT and these changes were further correlated with clinical symptom improvements. Moreover, CBT outcomes were predicted by pre-treatment activity or connectivity in the ACC and amygdala (3/13, 23.0%). A smaller proportion of studies (2/13, 15.3%) found that activity or connectivity in the insula, precuneus/cuneus, postcentral gyrus, and activity or structure in the nucleus accumbens (NAcc) predicted response to CBT. The low consistency of these findings was driven by methodological variability, low reliability of the neural markers, and relatively small sample sizes. CONCLUSIONS: This review highlights promises of neural predictors and outcomes to enhance anxiety disorder treatments in children and adolescents, facilitating future personalized and effective CBT. Beyond this initial promise, the field is hindered by methodological inconsistencies and limited replications. While longitudinal and personalized approaches are important next steps, the central challenge remains: identifying neural markers that are both reliable and robust.

Adolescent

Relationships among mechanisms in psychosocial treatments for chronic pain: mechanism to mechanism lagged effects and relationships with outcomes.

Results suggest that psychosocial treatments for chronic pain work via several mechanisms, and that they often do so to similar degrees and in similar ways. Extant research, however, has focused on individual and/or independent effects of mechanisms on outcomes. Whether successful outcomes are also partly because of sequential and meaningful relationships among and between mechanisms-mechanism-to-mechanism effects-has not been examined. Secondary analyses were conducted of an RCT that compared cognitive therapy, mindfulness-based stress reduction, and behavior therapy to treatment as usual in a sample (N = 521) of people with chronic low back pain. Results of hierarchical linear modeling revealed that (1) Treatment Condition &#xd7; Mechanism interactions predicting changes in other mechanisms were nonsignificant; (2) lagged prior session mechanism changes predicted next session changes in another mechanism; (3) lagged relationships between pain catastrophizing and pain self-efficacy were reciprocal, whereas links between lagged pain catastrophizing and mindfulness changes and lagged pain catastrophizing changes and behavioral activation changes were unidirectional; and (4) individual differences in the strengths of mechanism-to-mechanism relationships predicted pre- to post-treatment changes in outcomes. Results reveal heretofore hidden therapeutic processes that cognitive therapy, mindfulness-based stress reduction, and behavior therapy may share. Namely, that mechanism-to-mechanism lagged effects do indeed emerge beyond mechanism-to-outcome effects. Findings show not only that mechanisms may change in definable sequences relative to each other but that individual differences in the strengths of mechanism-to-mechanism relationships may themselves be predictive of outcomes.

Humans

Driving Under the Influence of Cannabis Among U.S. Young Adults Who Use Cannabis: Evidence From the 2021-2024 National Survey on Drug Use and Health.

PURPOSE: To estimate the prevalence of driving under the influence of cannabis (DUIC) and identify associated factors among U.S. young adult drivers reporting past-year cannabis use. METHODS: This cross-sectional study analyzed pooled 2021-2024 National Survey on Drug Use and Health. The analytic data were restricted to drivers aged 18-25 years who reported past-year cannabis use (N = unweighted 17,141; weighted N = 10,814,381). The outcome was self-reported past-year DUIC. Independent variables included demographics, substance use, mental health, cannabis-related perceptions, and driving behaviors. These relationships were assessed by modified Poisson regression. RESULTS: The weighted prevalence of DUIC was 28.0%, representing approximately over three million young adults. DUIC prevalence increased with cannabis use frequency, from 2.51 times higher among those using cannabis 12-49 days (adjusted prevalence ratio [APR]: 2.51; 95% confidence interval [CI]: 2.29-2.75) to 3.63 times higher among those reporting use on 300-365 days (APR: 3.63; 95% CI: 3.60-3.76), compared with those using cannabis 1-11 days. Cannabis use disorder (APR: 2.34; 95% CI: 2.06-2.65), simultaneous alcohol and cannabis use (APR: 1.29; 95% CI: 1.28-1.30), and perceived easy cannabis availability (APR: 2.36; 95% CI: 2.33-2.39) were also associated with higher prevalence of DUIC. Nonenrollment in school and living in a state with a medical cannabis law were associated with lower DUIC prevalence. DISCUSSION: DUIC is highly prevalent among U.S. young adults who use cannabis, with a clear graded association across categories of cannabis use frequency. Public health interventions should address frequent use, cannabis use disorder, alcohol-cannabis co-use, and perceived cannabis availability.

Humans

Catecholaminergic Contributions to Inhibitory Control Following Physical Fatigue: Behavioral and Neurophysiological Findings.

Acute physical fatigue can impair cognitive control, yet its underlying neurochemical mechanisms remain unclear. This study investigated whether catecholaminergic modulation influences behavioral and neural markers of inhibitory control following physical fatigue. Eighteen healthy, recreationally active adults (9 males, 9 females; 23.4&#xa0;&#xb1;&#xa0;2.2&#xa0;years) completed a randomized, triple-blind, placebo-controlled crossover study. On separate visits, participants received methylphenidate (MPH; 20&#xa0;mg; a dopamine and noradrenaline reuptake inhibitor), reboxetine (REB; 8&#xa0;mg; a noradrenaline reuptake inhibitor), or placebo. Physical fatigue was induced by repeated bilateral leg extensions to task failure. Cognitive performance was assessed before and after physical fatigue using a Go/No-Go task with electroencephalographic recording. Behavioral outcomes included reaction time and accuracy, while event-related potentials measured neural stages of response execution and inhibition (N2 and P3). Mixed-effects models were used for statistical analysis. For No-Go trials, a significant MPH&#xa0;&#xd7;&#xa0;Time interaction was observed for accuracy (p&#xa0;=&#xa0;0.008), with improved post-fatigue performance following MPH administration (p&#xa0;=&#xa0;0.048). At the neural level, MPH was associated with shorter fronto-central No-Go N2 latency (p&#xa0;=&#xa0;0.038) and altered fatigue-related changes in No-Go P3 latency (p&#xa0;=&#xa0;0.047). REB did not produce comparable behavioral or neural effects. These findings provide pharmacological evidence that catecholaminergic mechanisms contribute to inhibitory control following physical fatigue. The differential effects of MPH and REB suggest that selective noradrenergic enhancement alone is insufficient to maintain inhibitory control following physical fatigue. Instead, the findings implicate broader&#xa0;dopaminergic and noradrenergic mechanisms, potentially involving alterations in the temporal dynamics of inhibitory processing. TRIAL REGISTRATION: (G095422N and identifier NCT05880342).

Adult

Efficacy and safety of cannabinoid-based interventions for behavioral and cognitive symptoms in dementia: systematic review and meta-analysis.

BACKGROUND: Behavioral and cognitive symptoms are frequent in Alzheimer's disease and dementia, and available pharmacological options offer limited benefit. Cannabinoid-based therapies have been proposed as alternatives, but evidence remains inconclusive. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library through November 2025 for randomized controlled trials evaluating cannabinoids in Alzheimer's disease or dementia. Primary outcomes were agitation measured by the Cohen-Mansfield Agitation Inventory (CMAI) and neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory-Nursing Home version (NPI-NH). Secondary outcomes included cognition using the Mini-Mental State Examination (MMSE) and adverse events. Standardized Mean Differences (SMDs) and Risk Ratios (RRs) were synthesized using random-effects (REML) and Bayesian random-effects models. Risk of bias was evaluated with RoB 2, and certainty of evidence with GRADE. RESULTS: Nine trials (334 participants) met inclusion criteria. Cannabinoids did not improve CMAI (SMD -0.58, 95% CI -1.71 to 0.55; I2&#x2009;=&#x2009;84%), NPI-NH total (SMD -0.02, 95% CI -1.00 to 0.96; I2&#x2009;=&#x2009;67%), NPI-NH agitation (SMD -0.44, 95% CI -1.45 to 0.57; I2&#x2009;=&#x2009;48%), or MMSE (SMD 0.86, 95% CI -16.33 to 18.06; I2&#x2009;=&#x2009;96%). Bayesian posterior estimates were close to zero, supporting the absence of effect. Leave-one-out analyses reduced heterogeneity only after excluding influential trials but did not alter results. Certainty of evidence was moderate for behavioral outcomes and low for cognition. Overall adverse events were similar to placebo, while somnolence was more frequent with cannabinoids (RR 2.03, 95% CI 1.29-3.20). CONCLUSIONS: Cannabinoid-based therapies do not improve agitation, neuropsychiatric symptoms, or cognition in Alzheimer's disease and increase somnolence.

Humans

Space to grieve and grow: A systematic review of psychosocial interventions for people newly diagnosed with multiple sclerosis.

OBJECTIVE: This systematic review synthesized evidence from intervention studies published over the past 25 years that aimed to improve coping and psychosocial well-being among individuals early in the multiple sclerosis (MS) disease course. The goal was to evaluate intervention characteristics, theoretical foundations, and psychosocial outcomes, and to identify gaps for future research. METHODS: Following PRISMA guidelines, a comprehensive search was conducted across PubMed, CINAHL, PsycINFO, and Web of Science (2000-2025). Eligible studies included quantitative or mixed-methods interventions that addressed coping or psychosocial well-being among adults newly diagnosed with MS. Data extraction and quality assessment were completed independently by multiple reviewers using the Joanna Briggs Institute Critical Appraisal Tools. RESULTS: Seven studies (n&#x202f;=&#x202f;345) met inclusion criteria, representing cognitive-behavioral therapy, mindfulness, acceptance-based, and nurse- or peer-delivered interventions. The interval between diagnosis and intervention enrollment ranged from 14 days to >4 years, suggesting different phases of adjustment. All interventions produced significant short-term improvements in at least one psychosocial domain (e.g., anxiety, depression, stress, coping, or illness acceptance). However, sustained effects beyond 6-12 months were inconsistent. Common mechanisms across interventions included enhancing self-efficacy, stress management, and adaptive coping. CONCLUSIONS: The available evidence suggests that brief psychosocial interventions for adults in the early years after MS diagnosis are feasible and may provide short-term benefits for selected psychosocial outcomes. However, the evidence base remains limited, heterogeneous, and preliminary. Future studies should more clearly define diagnosis timing, use adequately powered designs and longer follow-up, and examine mechanisms of change.

Humans

The effect of tDCS on emotion-related risk-taking behavior and delay discounting in adults with ADHD.

INTRODUCTION: Adults with Attention Deficit Hyperactivity Disorder (ADHD) often engage in risky behaviors due to impaired decision-making processes. This study aims to investigate the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) on emotion-related risk-taking behavior and delay discounting in adults with ADHD. METHODS: Thirty adults with ADHD underwent three tDCS conditions, administered in a randomized order with at least one week between sessions: (1) left dlPFC anode/right vmPFC cathode, (2) left dlPFC cathode/right vmPFC anode, and (3) sham stimulation. In each session, participants completed the Delay Discounting Task (DDT) and the Modified Balloon Analogue Risk Task (mBART) under three emotional conditions (neutral, positive, and negative) which were induced using emotionally congruent photographs and sounds. Galvanic skin responses (GSR) were also recorded. In the DDT, both area under the curve (AUC) values and log-transformed discounting rates (log k) were calculated for small, medium, and large reward magnitudes (RM). Exploratory electric field modeling was also performed to characterize current distribution. RESULTS: The findings demonstrated task-specific effects of tDCS on decision-making. Although no overall tDCS effect was observed on DDT performance, significant tDCS&#x202f;&#xd7;&#x202f;RM interactions emerged, particularly for smaller rewards. In contrast, exploratory analyses suggested that tDCS affected all mBART scores. Emotional condition did not influence consistently behavioral performance in either task, whereas both emotional stimulation and tDCS significantly affected GSR responses. However, exploratory electric field modeling indicated a broad prefrontal current distribution extending beyond the intended cortical targets. CONCLUSIONS: These findings suggest preliminary evidence that prefrontal tDCS can influence risk-related decision-making and autonomic responses in adults with ADHD. However, its effects on delay discounting appear to be context-dependent and limited to specific RMs. Future studies combining neuroimaging with individualized electric field modeling are needed to clarify the neural mechanisms underlying the observed effects of tDCS and to optimize stimulation protocols in adults with ADHD.

Humans

Adjunctive intermittent theta-burst stimulation for first-episode schizophrenia: A randomized clinical trial.

BACKGROUND: The efficacy of intermittent theta-burst stimulation (iTBS) combined with pharmacotherapy and psychotherapy in first-episode schizophrenia remains unclear. This study evaluated adjunctive iTBS with risperidone and cognitive behavioral therapy (CBT) and explored serum biomarkers indicating treatment response. METHODS: In this randomized, assessor-blind trial, 100 first-episode schizophrenia patients received either iTBS plus risperidone and CBT (iTBS group, n = 50) or risperidone and CBT alone (control, n = 50) for 3 months. The primary outcome was change in PANSS total score at 4 weeks and 3 months. Response was defined as a &#x2265; 50 % PANSS reduction. Secondary outcomes included cognitive function (MCCB subtests) and serum GDNF, cortisol, and dehydroepiandrosterone sulfate (DHEA-S) levels. RESULTS: The iTBS group showed significantly greater reduction in PANSS total scores than controls at both 4 weeks and 3 months (mean difference at 3 months: -13.3, 95 % CI: -16.8 to -9.8; P < 0.001), with a higher responder rate (76 % vs. 48 %). Significant improvements across all cognitive domains were observed in the iTBS group (all P < 0.001). Post-treatment, the iTBS group exhibited higher GDNF and lower cortisol and DHEA-S levels (all P < 0.001). A combined biomarker panel demonstrated superior discriminative performance for treatment efficacy (AUC=0.865 after cross-validation). Adverse events were comparable between groups. CONCLUSIONS: Adding iTBS to risperidone and CBT significantly improves clinical symptoms and cognitive function in first-episode schizophrenia. The combination of GDNF, cortisol, and DHEA-S shows promise as a composite biomarker for treatment response, though sham-controlled validation is warranted.

Humans

Trade-offs in avian parental care: a review of theory and meta-analysis of brood size manipulations.

The selective forces shaping parental care have been studied for over 50&#x2009;years. While theoretical and experimental work has yielded qualitative progress, the large body of empirical work testing predictions about parental investment based on life-history trade-offs has yet to be synthesized. We first provide an overview of the core life-history theory exploring how selection might shape parental care. We then conduct a systematic review and meta-analysis on studies that experimentally manipulated brood size in birds, a widely used experimental approach to manipulate parental investment. We extracted 313 estimates from 62 studies representing 31 species of birds from 19 different families and tested key predictions on trade-offs in parental care derived from theory. Our analysis provides strong support for some predictions about life-history trade-offs in parental care, but weak or equivocal support for others. Specifically, we found that overall, avian parents respond to brood size manipulations as predicted by life-history theory: they increased care in response to brood enlargement, and decreased care in response to brood reductions. Furthermore, for the same relative manipulation size, responses to brood reductions were greater than responses to brood enlargements. This finding is consistent with predictions derived from life-history theory based on some types of non-linear utility curves. However, many predictions derived from theory are not well supported by our comparative analysis. Species' life-history traits such as clutch size (a measure of current reproduction), adult survival, and broods per year (two measures of future reproduction), explained little, if any, among-species variation in response to brood size manipulations. Several factors may explain this. We highlight that brood size manipulations may affect more than just perception of the value of current reproduction, such as altering parents' perception of predation risk. Importantly, these unintended consequences could lead to asymmetric responses like those we observed. Other common experimental approaches - such as hormone manipulations, altering a partner's effort, and food supplementation - often affect multiple traits or fitness components simultaneously, or may involve cues that poorly match the evolved mechanisms guiding parental behaviour. Our review of both theory and experimental approaches suggests that there are multiple opportunities for more precise experiments. We offer several recommendations for effective designs. One is improved understanding of the biology underlying the functions relating to costs and benefits, with careful consideration of not only how the manipulation will affect only one of those, but also the mechanisms that might alter how parents perceive the manipulation. We also emphasize general principles, such as assessing alternative hypotheses and devising multiple independent tests. Armed with these recommendations, we believe there are new opportunities to increase the strength of inference achieved from studies aimed at understanding the trade-offs affecting the evolution of parental care.

Animals