BACKGROUND:Depression and anxiety disorders and symptoms are among the leading causes of disability and global disease burden in young people. Scalable, unified interventions are required to address subthreshold emotional symptoms in adolescents as a preventive strategy. This study evaluated the effectiveness of a transdiagnostic treatment for adolescents with subthreshold emotional symptoms. METHODS:A multicenter, two-arm, randomized controlled trial was conducted. The Unified Protocol for Adolescents (UP-A) was compared with an active control consisting of protocolized progressive relaxation. A total of 676 adolescents (72.6% female; Mage = 13.77; SD = 1.39; range = 12-18 years) participated in the study. Primary outcomes were self-reported depressive and anxiety symptoms at postintervention, 6 months, and 12 months. The trial is registered with ClinicalTrials.gov (NCT05322642). RESULTS:Three hundred seventy-eight participants were allocated to the UP-A group and 298 to the control group. Adherence was high in both conditions (≈78% attended >70% of sessions). Both interventions showed significant reductions in depressive and anxiety symptoms over time, with no significant between-group differences. At 12 months, the UP-A group showed marginally lower depressive symptoms and neuroticism. Significant treatment effects favoring the UP-A were observed for hyperactivity, conduct problems, and total mental health difficulties. Improvements were maintained across most outcomes at both follow-ups. CONCLUSIONS:The comparable improvements observed across both conditions suggest that structured, group-based school interventions may help reduce emotional symptoms in adolescents with subthreshold presentations, rather than reflecting the superiority of a specific protocol. These findings support their potential for broad dissemination within stepped-care frameworks and for enhancing accessibility and real-world effectiveness of evidence-based treatments.
BACKGROUND:Recent increases in common mental disorder prevalence could partly reflect greater persistence of existing disorders. We examined 3-year persistence for anxiety, mood, and substance use disorders, defined as meeting diagnostic criteria at baseline and again during 3-year follow-up. We compared persistence rates with those observed 12 years earlier and investigated (changes in) determinants of persistence. METHODS:Data were from the third Netherlands Mental Health Survey and Incidence Study (NEMESIS-3), a population-based study (N = 6,194; 18-75 years; interviewed 2019-2022 and 2023-2024). A slightly modified Composite International Diagnostic Interview 3.0 assessed DSM-5 and DSM-IV diagnoses. Persistence was described from two perspectives: narrow (presence of a mental disorder of the same diagnostic category during follow-up) and broad (presence of any anxiety, mood, and/or substance use disorder during follow-up). Twelve-year trends were examined by comparing DSM-IV persistence in NEMESIS-3 with NEMESIS-2 (N = 6,646; interviewed 2007-2009 and 2010-2012) among adults aged 18-64 years. RESULTS:In NEMESIS-3, 3-year narrow persistence was 41.6% for anxiety, 48.0% for mood, and 40.3% for substance use disorders. Broad persistence was higher: 57.1%, 63.2%, and 55.1%, respectively. Persistence increased in 12 years across all disorder groups: broad persistence for any mental disorder was 42.7% in NEMESIS-2 and 57.9% in NEMESIS-3. Higher broad persistence was significantly associated with younger age, living in a city, childhood trauma, and near-daily drug use in multivariable analyses. These associations were stable over time. CONCLUSIONS:Three-year persistence of common mental disorders is substantial and has increased compared with 12 years earlier, suggesting growing challenges for treatment and long-term care.
BACKGROUND:Fluctuations in ovarian hormones are associated with changes in mood and emotional well-being. However, the neural mechanisms linking endocrine states and affective regulation remain poorly understood. We aimed to investigate how endogenous estradiol and progesterone modulate brain representations underlying emotion-action control in healthy young women. METHODS:A total of 116 naturally cycling women performed an approach-avoidance task with emotional facial expressions during functional magnetic resonance imaging. Multivoxel pattern analyses were used to examine the neural encoding of emotion-action contingencies, i.e., classifying task conditions from multivariate activation patterns. We then tested whether salivary concentrations of estradiol and progesterone were associated with classification accuracy in various brain regions. RESULTS:Participants responded more slowly and less accurately when approaching angry faces or avoiding happy ones, reflecting control over automatic emotional tendencies. Multivoxel decoding revealed that task conditions could be reliably distinguished from activation patterns in the lateral frontal pole (FPl), striatum, central insula, dorsal and ventral cerebellum, primary visual cortex, and periaqueductal gray. Importantly, higher progesterone levels were correlated with reduced classification accuracy in the FPl (r=-.26, p=.006) and striatum (r=-.26, p=.007), and lower FPl decodability was linked to poorer mood during the preceding week (r=-.25, p=.011). Moreover, decoding accuracy in the FPl fully mediated the indirect association between progesterone and worse mood (R2=7.1%). CONCLUSIONS:These findings suggest that progesterone-related alterations in frontostriatal affective representations may contribute to mood variation.
BACKGROUND:Virtual reality (VR) has been widely used in outpatient psychiatric services and has demonstrated benefits across several clinical diagnoses, but its use and effects in inpatient settings remain to be explored. This systematic review aimed to examine the use of VR during psychiatric hospitalization, including types of VR applications, barriers and facilitators of implementation, and effects on various outcomes. METHODS:The review was registered in PROSPERO (#CRD42023446524). Following PRISMA guidelines, databases (Ovid, SciVerse, Web of Science, Cochrane Library, ProQuest, and WorldCat) were searched from 1983 to 2025 using keywords related to VR and psychiatric disorders. Studies involving the use of VR with psychiatric inpatients (≥85%) were included. Descriptive statistics and narrative syntheses were used to summarize findings. Study quality was assessed with the Mixed Methods Appraisal Tool. RESULTS:After full-text screening, 37 studies (N = 1,004) met inclusion criteria. VR was used for both assessment and intervention, with cognitive-behavioral therapy/exposure (35%) and assessment (24%) being the most frequently used. VR use in inpatient units appeared feasible, acceptable, and safe for inpatients and clinicians, though findings remain preliminary. Several facilitators (e.g. adequate staff training and supervision) and common barriers (e.g. technical difficulties and limited resources) were identified. The most consistent improvements were observed in clinical symptoms (e.g. anxiety) compared with psychosocial, cognitive, and physiological outcomes. CONCLUSIONS:These findings suggest that inpatient settings represent a promising, yet understudied context for VR-based assessments and interventions. High-quality trials and systematic reporting of implementation are needed in future studies to inform research and clinical practice.
BACKGROUND:Compared with heterosexual persons, non-heterosexual persons have worse mental health. Sexual Minority Stress Theory (SMST) explains the disparity as resulting from stigma and discrimination. To the extent that heterosexual genetic relatives reared with non-heterosexual persons also have worse mental health, SMST is falsified. We conducted a systematic meta-analysis of studies containing family-genetic comparison data to interrogate the empirical support for SMST. METHOD:We systematically identified 17 empirical studies in which twins or non-twin siblings reported on both their sexual orientation and their mental health. Subsequently, we conducted a multilevel meta-analysis, focusing on the degree to which any sexual orientation disparity in mental health diminished with genetic relatedness. RESULTS:Most of the mental health disparities between non-heterosexual and heterosexual persons were eliminated after controlling for family-genetic factors. CONCLUSIONS:The mental health disparity between non-heterosexual and heterosexual persons is reduced by up to two-thirds once familial background factors are accounted for by comparing monozygotic twins discordant for sexual orientation. This suggests that shared familial causes, and not minority stress, are the most important causes of mental health disparities in non-heterosexual persons.
BACKGROUND:Major depressive disorder and generalized anxiety disorder frequently co-occur, leading to heterogeneous presentations that complicate diagnosis and treatment. While diagnostic categories often obscure symptom variability, network approaches offer a powerful way to examine how symptoms relate to one another within and across conditions. By identifying symptom clusters, these methods can provide insights into potential mechanisms of comorbidity and symptom maintenance and may ultimately help guide more personalized treatment. METHODS:We examined patients (N = 33,675) seeking treatment for anxiety or depression through a message-based psychotherapy platform. Participants completed standardized measures of anxiety (GAD-7) and depression (PHQ-9) at baseline. We estimated a Gaussian Graphical Model of anxiety and depressive symptoms and identified overlapping symptom clusters using a modified Walktrap algorithm. We assigned patients to clusters based on presenting symptoms. In a subsample (n = 10,718), we examined the relationship between baseline cluster probabilities and three outcome trajectories over 12 weeks of treatment. RESULTS:We found four baseline symptom clusters relating to Affective Dysregulation, Worries, Neurovegetative symptoms, and Hyperarousal. Affective Dysregulation and Neurovegetative clusters were associated with poorer outcomes, whereas Worries and Hyperarousal were associated with recovery over partial improvement; Hyperarousal also differentiated recovery from non-response. CONCLUSIONS:Symptom clusters derived from standard screening measures were associated with differential treatment trajectories. Targeting these symptom configurations may be particularly effective at disrupting multiple symptom pathways. Future research should examine whether personalized treatment strategies that consider symptom clusters based on simple screening in practice settings yield greater clinical improvement than traditional diagnostic categories.
Auditory-verbal signal detection tasks (AV-SDTs) are used to study hallucinatory experiences (HEs) in clinical and nonclinical groups, assessing perceptual decision making under ambiguous auditory conditions. Existing findings suggest that HEs are associated with response biases. However, effects sizes and subgroup differences remain unclear. This meta-analysis synthesized findings to quantify associations between HEs and AV-SDT performance, testing differences within clinical and nonclinical populations. Systematic searches identified studies published between January 1985 and April 2025. Reference lists were screened and authors contacted. Eligible studies examined associations between hallucinations or hallucination-proneness and AV-SDT performance using between-group or correlational designs. Data comprising 1,391 participants were pooled from 5 clinical (210 patients), and 10 non-clinical (1,181 participants) studies. Moderate-to-large effects were found between HEs and response bias across aggregate (g = -0.56 [95% CI: -0.84, -0.28, p = .001]), clinical (g = -0.88 [95% CI: -1.58, -0.17, p = .026]), and nonclinical (g = -0.43 [95% CI: -0.74, -0.11, p = .013]) subgroup models. Perceptual sensitivity was reduced in nonclinical (g = -0.17 [95% CI: -0.28, -0.07, p = .004]), but not clinical (g = 0.37 [95% CI: -0.00, 0.75, p = .050]), hallucinating samples. HEs are consistently associated with a liberal response bias across populations. HEs in nonclinical samples were linked to reduced perceptual sensitivity although this was not supported in clinical groups, potentially due to limited data. Findings highlight methodological gaps in AV-SDT research, including variability in design and hallucination assessment, underscoring the need for standardized approaches to improve generalizability across studies.
Psychiatric disorders are complex conditions involving multifactorial, nonlinear causal dynamics, which make effective treatment challenging. To address this complexity, a framework is proposed that distinguishes between types of causality: permissive causality, which pertains to factors affecting the likelihood of an outcome occurring, and instructive causality, which refers to factors shaping the specific features of the outcome. In this framework, when considering an individual as a complex adaptive system, causal processes within the individual are permissive, whereas causal processes outside the individual can be either permissive or instructive in relation to the individual's global emergent outcomes. Accordingly, when dealing with mental states or complex behaviors, biological substrates - from genes to brain areas - operate through permissive causality, shaping a space of possibilities rather than instructing a specific outcome. By contrast, contextual factors - such as life challenges or subjective appraisal - can also operate through instructive causality, steering behavior and mental states toward specific trajectories. Therapeutic strategies should harness the synergistic interplay between these types of causality, targeting biological substrates to enable transitions in mental states, and leveraging contextual factors to steer these transitions toward mental well-being. Recognizing such interplay holds promise for developing innovative and effective approaches in precision psychiatry, especially for treatments enhancing plasticity - which itself operates through permissive causality - including antidepressants and psychedelics.
BACKGROUND:Neurodevelopmental disorder traits are associated with a range of psychosocial difficulties, yet the longitudinal processes linking these traits to mental health remain insufficiently explored. This study examined developmental associations among autism spectrum disorder (ASD) traits, attention-deficit/hyperactivity disorder (ADHD) traits, social maladjustment, and mental health from childhood through adolescence. METHODS:Longitudinal data were drawn from 9,619 students across 11 grade cohorts in mainstream classrooms. Cross-lagged structural equation modeling was used to estimate independent longitudinal associations among ASD traits, ADHD traits, social maladjustment, and mental health, while controlling for confounding factors. ASD and ADHD traits were modeled simultaneously to clarify their unique developmental patterns. RESULTS:ASD traits were consistently associated with later internalizing problems and peer difficulties. ADHD traits were associated with later internalizing and externalizing problems, as well as academic challenges and strained teacher-parent relationships. These associations differed by trait type, suggesting distinct developmental pathways. Several bidirectional associations also emerged: poorer mental health was associated with subsequent social maladjustment, which was subsequently linked to persistent developmental difficulties. CONCLUSIONS:The findings indicate that social maladjustment is involved in the longitudinal associations between developmental disorder traits and mental health and may shape developmental trajectories. These results highlight the need for comprehensive support approaches that consider peer relationships, learning environments, and family-school relationships.
BACKGROUND:Since the 1940s, the concept of autism has undergone marked changes, and autism spectrum disorder (ASD) is a wildly heterogenous condition. At the same time, the prevalence of ASD has increased massively. METHODS:This essay considers possible reasons for the changes and their consequences. RESULTS:Among drivers for the increase in prevalence are cultural changes, such as the desire for inclusion, harm avoidance, reliance on self-report, and the acceptance of masking. These have all led to a lowering of the diagnostic threshold. Furthermore, the popularity of the concept of autism boosted numbers via self-diagnosis and a search for identity. CONCLUSIONS:Marked differences now exist between those first diagnosed in childhood and others first diagnosed in adolescence or adulthood. The time has come to examine reasons for these conceptual changes and the consequences for clinical practice and research.
BACKGROUND:Adverse health behaviors, such as physical inactivity and smoking, constitute a potential pathway connecting loneliness to poor mental and physical health. No prior study has investigated the dynamic interplay between loneliness and a broad range of health behaviors across the first half of life. METHODS:We used data from a Norwegian population-based cohort study (n = 3,072) spanning 28 years from adolescence to midlife. Applying a propensity score-based causal inference approach, we examined bidirectional prospective associations between loneliness and health behaviors, comprising alcohol use, body mass index (BMI), smoking, and physical exercise. RESULTS:Loneliness in adolescence was associated with lowered physical exercise (mean difference: -14.13 minutes/week, 95% CI: -26.54 to -1.72), and loneliness during young adulthood was linked to increased BMI (0.37 points, 0.12-0.63). In the reverse direction, moderate alcohol use (-0.07 SD, -0.13 to -0.01 and - 0.19 SD, -0.33 to -0.05), smoking (-0.12 SD, -0.23 to -0.01), and moderate physical exercise (-0.16 SD, -0.26 to -0.07 and - 0.07 SD, -0.14 to -0.01) during adolescence and emerging adulthood were linked to reduced loneliness. All other associations were consistent with a null effect. CONCLUSIONS:Our results provide limited support for the causal effects of loneliness on health behaviors across the first half of life. By contrast, findings in the reverse direction suggest that health behaviors in young people - whether health-promoting or risky - are socially embedded and may facilitate socializing. To tackle youth loneliness, public health policies should promote equitable access to health-promoting behaviors.
Background Although adverse childhood experiences (ACEs) have been related to poorer lifespan health, their association with DNA methylation-based indicators of biological aging during adolescence remains incompletely understood, particularly across intersecting social positions. To address this gap, we used an intersectional race-sex approach to identify ACE patterns and examine their associations with biological aging in adolescence.Method Participants (n = 1,655) were drawn from the Future of Families and Child Wellbeing Study, a racially diverse urban U.S. birth cohort. ACEs were measured prospectively from ages 3 to 9 and modeled using latent class analysis with measurement invariance testing across six intersecting race-sex groups. Biological aging was assessed using saliva-derived DNA methylation measures at ages 9 and 15, and for change from age 9 to 15 using PhenoAge, GrimAge, and DunedinPACE.Results Two ACE classes emerged within each racial/ethnic group. Among Black participants, females showed higher PhenoAge estimates than males across classes at ages 9 and 15 and for longitudinal change. Among White participants, females in the Single-Parent Poverty & Maternal Substance Use class showed higher PhenoAge estimates at age 9 than females in the Maternal Substance Use class, although this difference was not observed at age 15 or for longitudinal change. Findings for GrimAge and DunedinPACE were less consistent.Conclusion Prospectively measured ACE configurations showed selective associations with adolescent DNA methylation-based aging measures, most consistently for PhenoAge. Findings support intersectional, person-centered approaches to identifying heterogeneity in early biological risk and underscore the need for caution in interpreting clock-specific findings in youth.
BACKGROUND:Among military veterans, loneliness is common and associated with poorer mental and physical health and functioning. Epidemiological studies have revealed bidirectional, longitudinal associations between loneliness and posttraumatic stress disorder (PTSD). Little is known about loneliness among treatment-seeking veterans, how loneliness impacts PTSD symptom change during treatment, and whether loneliness has differential associations with specific PTSD symptom clusters. METHOD:Data were derived from the Veterans Outcome Assessment, an annual, repeated-measures (baseline and 3-month follow-up) telephone survey of patients beginning new episodes of mental health care in the Department of Veterans Affairs. Participants were 1,155 veterans (23% women) entering PTSD specialty care. We tested whether baseline loneliness predicted change in total PTSD symptom severity and according to the five-factor Dysphoric Arousal model of PTSD using hierarchical regressions in which we statistically adjusted for demographics and mental health encounters. RESULTS:Loneliness decreased between baseline and 3-month follow-up (d = 0.39). Baseline loneliness predicted change in PTSD for the dysphoric arousal and negative alterations in cognitions and mood symptom clusters, with lonelier veterans demonstrating more PTSD change between baseline and follow-up. However, lonelier veterans also had more severe PTSD symptoms at both timepoints. This pattern of results held even after accounting for different types of treatment encounters between timepoints. CONCLUSIONS:While lonelier veterans have more severe PTSD symptoms, they also make greater improvements in symptoms salient to interpersonal functioning over time. Assessment of loneliness should be incorporated into PTSD treatment planning and considered as a treatment target that could be addressed to promote recovery.
BACKGROUND:Post-stroke depression (PSD) is the most common neuropsychological complication in stroke survivors. While psychological interventions are promising non-pharmacological treatments, the most effective intervention type, as well as their mid- to long-term efficacy and effectiveness across PSD severity levels, remains unclear. This study aims to compare the efficacy of psychological interventions for PSD, focusing on overall effectiveness, mid- to long-term efficacy, and effectiveness across PSD severity levels. METHODS:We systematically searched seven databases for randomized controlled trials (RCTs) of psychological interventions targeting depression in stroke survivors. The primary outcome was depression symptom reduction. Post-intervention, mid- to long-term data were analyzed. A frequentist network meta-analysis (NMA) with random effects was conducted in Stata 17.0. Subgroup analyses by PSD severity were performed. RESULTS:Thirty-eight RCTs involving 3106 participants were included. Post-intervention, third-wave therapies (Hedges' g = -1.08, 95% CI: -1.62 to -0.55) significantly improved PSD compared to treatment as usual. At mid- to long-term follow-up, third-wave therapies (Hedges' g = -0.82, 95% CI: -1.25 to -0.39) maintained significant effects. Relaxation therapy significantly ameliorated mild PSD (Hedges' g = -0.77, 95% CI: -1.27 to -0.27); for moderate-to-severe PSD, no significant effects were observed. CONCLUSIONS:Third-wave therapies are potentially effective for PSD, showing sustained mid- to long-term benefits. Relaxation therapy seems to be most effective for mild PSD, while no significant effects were observed for moderate-to-severe PSD. However, the NMA showed high heterogeneity and generally low to very low evidence certainty for most comparisons, the findings should be interpreted with caution.
BACKGROUND:The prevalence and burden of depression are increasing among young people. Despite this, relatively few treatments specifically target this critical developmental period, and under-addressed mental health difficulties in youth often have lifelong consequences. Social isolation is commonly reported by young adults and is both a risk and maintenance factor for depression. There is a need for accessible, engaging interventions that can reduce depressive symptoms and improve social connectedness. METHODS:Building on evidence of the therapeutic potential of social dance-based activities for depression, this randomized controlled trial evaluated the efficacy of an 8-week salsa dance intervention for young adults (aged 18-24 years) with mild to moderately severe depressive symptoms. 121 participants were randomly assigned to either a salsa intervention or a waitlist control. Participants completed the Patient Health Questionnaire (PHQ-9), a validated measure of depressive symptoms, and additional mental health measures at baseline, during, and after the intervention. RESULTS:Participants in the salsa dance condition showed a significantly greater reduction in depressive symptoms than the waitlist control, with a -2.45 PHQ-9 point between-group difference, exceeding the criterion for clinical significance. Both groups reported improvements in social anxiety, generalized anxiety, loneliness, and daily happiness, but salsa participants had significantly greater reductions in social anxiety and greater improvements in daily happiness. CONCLUSIONS:These findings support the value of social dance as a novel, accessible intervention for reducing depressive symptoms. Implementing such programs within a suite of wellbeing-oriented interventions for young people could provide cost-effective mental health benefits.
BACKGROUND:Alcohol, nicotine, and cannabis use problems have a poorer prognosis when they co-occur with internalizing distress (INT). One hypothesis to account for the association between INT and alcohol and substance use problems (SUP) is that people engage in heavy substance use to reduce aversive affective states characteristic of INT (e.g. affective reinforcement). Whether INT operates as a cause or a shared liability with SUP (e.g. shared genetic and environmental risk) over and above an alternative cause (e.g. externalizing problems, EXT) remains unclear. METHODS:We tested INT as a developmental pathway for SUP by applying a prospective, co-twin control approach to the Minnesota Twin and Family Study sample (n = 1881 twin pairs). A multilevel modeling framework was used to estimate the between-twin pair effect and the within-twin pair effect of INT over and above EXT on separate SUP outcomes (i.e. alcohol, nicotine, and cannabis use problems) from adolescence (age 14) to young adulthood (age 29). RESULTS:We failed to detect any non-familial causal effects of INT on SUPs. Instead, their associations were due to common genetic and shared environmental influences. In contrast, EXT had consistent non-familial causal influences on alcohol and cannabis use in adolescence and young adulthood. CONCLUSIONS:The link between INT and SUPs is primarily due to shared, familial influences while EXT likely serves as a unique determinant, with elevated EXT increasing selection into situations that pose SUP risk (e.g. peer environments that normalize and sustain heavy use) over and above common genetic influences.
Background Cognitive complaints in body dysmorphic disorder (BDD) remain poorly characterized. This study examined subjective cognitive complaints across clinical and community BDD samples.Methods A two-stage exploratory design was used. Study 1 included a clinically diagnosed BDD sample (n = 15) and healthy controls (n = 29). Study 2 comprised a large international community sample reporting clinically significant BDD symptoms (N = 433). Participants completed BodyThink, an exploratory BDD-focused measure of subjective cognitive complaints. In Study 1, additional clinical and performance-based cognitive measures contextualized subjective reports.Results Across both studies, endorsed items spanned multiple cognitive domains, with processing speed, attention, memory, executive functioning, and social cognition items consistently reported. Processing speed complaints were particularly salient. In Study 1, individuals with BDD reported markedly elevated cognitive complaints relative to controls, with large group differences (d = 1.64-1.95) on both BodyThink and an established measure of subjective cognition. Cognitive complaints showed a preliminary association with perceived social self-efficacy (rho = -.71) but not with BDD symptom severity, objective cognitive performance, or emotional distress. Across both samples, social cognition items were disproportionately endorsed during symptom exacerbation.Conclusions Individuals with BDD reported markedly elevated cognitive complaints relative to controls, with substantial individual variation. Patterns were broadly consistent across symptom severity, with social cognition difficulties showing greater salience during symptom exacerbation. The variability in complaints highlights the importance of individualized assessment, while associations with perceived social self-efficacy suggest that cognitive complaints may reflect negatively biased self-appraisals that may be relevant to treatment engagement.
Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive technique engaging vagal afferents that may enhance cognition, but results vary across domains and samples. Following PRISMA, seven databases (inception-October 2025) plus registries and gray literature were searched. Random-effects meta-analyses (REML; Hedges' g) were complemented by Bayesian hierarchical models and sensitivity analyses. Fifty-three studies were included; 30 contributed quantitative data (>1,500 participants). taVNS was associated with improved cognitive performance overall (g = 0.41, 95% CI: 0.30-0.53; I2 = 51.4%). Effects were moderate for executive functions (g = 0.46, 95% CI: 0.27-0.65; I2 = 9.5%) and cognitive flexibility/learning (g = 0.53, 95% CI: 0.32-0.75; I2 = 52.9%), and small for working memory/attention (g = 0.19, 95% CI: 0.04-0.33; I2 = 14.9%). Social cognition/emotion regulation showed larger but imprecise effects (k = 3; g = 0.80, 95% CI: 0.07-1.52; I2 = 82.1%). Clinical samples benefited similarly (k = 7; g = 0.55, 95% CI: 0.31-0.79; I2 = 29.5%), with no difference from healthy cohorts (β = -0.001, p = .994). High-intensity protocols (>1.0 mA) yielded larger effects; mode, duration, and site were not moderators. Bayesian models supported effects (P [μ > 0] ≥ 0.93). taVNS is associated with statistically significant improvements in cognitive performance, strongest for executive control and adaptive learning. We propose a Vagal Neurocognitive Integration Model linking LC-NE arousal modulation to prefrontal control. Future diagnosis-specific, adequately powered trials with multimodal neuroimaging should refine mechanisms and dose-response.
