Migraine is a prevalent and debilitating neurological disorder that significantly affects quality of life. While pharmacological treatments exist, they can have limitations such as side effects, contraindications, and incomplete relief, prompting interest in non-pharmacological approaches for better symptom management.

This study aimed to assess the effectiveness of alternate nostril breathing (ANB) as a non-pharmacological intervention to reduce the frequency and severity of migraine attacks and associated disability in adult patients.

A single-center, open-label, two-arm, parallel-group randomized controlled trial was conducted at six Family Health Centers (FHCs) of Dokuz Eylul University, Izmir, Turkey. A total of 86 migraine patients aged 18–50 years, diagnosed with migraine based on ICD-10 criteria, were randomized into control (n = 43) and intervention (n = 43) groups. The intervention group practiced ANB three times daily for three months, while the control group continued their usual care. The primary outcomes were changes in migraine frequency and severity. Secondary outcomes included changes in migraine-related disability, both outcomes measured using the Migraine Disability Assessment Scale (MIDAS).

The intervention group showed a significant reduction in migraine attack frequency (P = 0.002) and MIDAS scores (P = 0.003) compared to the control group. Both groups experienced a reduction in attack severity (P = 0.001), though no significant difference was observed between the groups (P = 0.074). Within-group comparisons showed significant improvements in attack frequency, severity, and MIDAS scores in the intervention group (P = 0.001 for all).

ANB significantly reduced migraine frequency and disability, making it a promising non-invasive and accessible treatment option for migraine management. Further research with longer follow-up periods is needed to explore its long-term effects and broader applicability.

Evidence suggests that death anxiety is a transdiagnostic construct underlying numerous anxiety-related conditions. A previous phase I trial of Overcome Death Anxiety (ODA), a novel online stand-alone psychological intervention to reduce death anxiety, demonstrated preliminary evidence of efficacy and acceptability in a clinical population. However, this trial was limited by a small sample size (n=20).

To further evaluate the efficacy of this intervention in reducing death anxiety in a clinical population, compared with a waitlist control.

This paper describes the protocol of a phase II randomized controlled, unblinded trial of ODA. A total sample of 256 adults living in Australia, diagnosed with an anxiety-related condition, will be recruited. These participants will be randomised to ODA or a waitlist control. Primary outcomes will be measured as changes in scores on death anxiety questionnaires, reflecting treatment efficacy. The secondary outcomes to be measured are depression, anxiety, stress, suicidality, insomnia, and meaning of life, as well as feedback about treatment program acceptability. This trial will assess the efficacy of ODA for reducing death anxiety in a population diagnosed with various anxiety-related conditions, as well as the overall acceptability and tolerability of the intervention.

This study will provide evidence to evaluate the efficacy of ODA in people diagnosed with an anxiety-related condition.

Stigma of mental health conditions hinders recovery and well-being. The Honest, Open, Proud (HOP) program shows promise in reducing stigma but there is uncertainty about the feasibility of a randomized trial to evaluate a peer-delivered, individual adaptation of HOP for psychosis (Let's Talk).

A multi-site, Prospective Randomized Open Blinded Evaluation (PROBE) design, feasibility randomised controlled trial (RCT) comparing the peer-delivered intervention (Let's Talk) to treatment as usual (TAU). Follow-up was 2.5 and 6 months. Randomization was via a web-based system, with permuted blocks of random size. Up to 10 sessions of the intervention over 10 weeks were offered. The primary outcome was feasibility data (recruitment, retention, intervention attendance). Primary outcomes were analyzed by intention to treat. Safety outcomes were reported by as treated status. The study was prospectively registered: https://doi.org/10.1186/ISRCTN17197043.

149 patients were referred to the study and 70 were recruited. 35 were randomly assigned to intervention + TAU and 35 to TAU. Recruitment was 93% of the target sample size. Retention rate was high (81% at 2.5 months primary endpoint), and intervention attendance rate was high (83%). 21% of 33 patients in Let's talk + TAU had an adverse event and 16% of 37 patients in TAU. One serious adverse event (pre-randomization) was partially related and expected.

This is the first trial to show that it is feasible and safe to conduct a RCT of HOP adapted for people with psychosis and individual delivery. An adequately powered trial is required to provide robust evidence.

Schools are central places for adolescent social lives, which is a major factor greatly affecting adolescent mental health; school climate (i.e. quality of the school social environments) can be a proximal social determinant for adolescent mental health. Supportive school environments may serve as a protective factor during crises like COVID-19, which disrupt social lives and worsen adolescent mental health. This is the first study examining whether the pandemic effects differed based on the levels of school climate on depressive symptoms (DS) and psychotic experiences (PEs) among adolescents.

School climate (score range: 0–28), DS (0–26), and PEs (0–5) were self-reported in a population-based cohort (Tokyo Teen Cohort; N = 3171) at four timepoints (10y, 12y, 14y, and 16y) before and during COVID-19. COVID-19 occurred midway through the 16y survey, allowing us to examine its impact and interaction effect with school climate while accounting for within-person changes over time using mixed-effects models.

Significant interaction effects were found on DS (unstandardized coefficient [B] = −0.166, 95% confidence interval [CI] −0.225 to −0.107) and PEs (B = −0.020, 95% CI −0.028 to −0.012). The pandemic effects were not significant for adolescents with high school climate scores (around the 80th percentile or higher), although the pandemic significantly worsened these outcomes among the overall sample.

The negative mental health effects of the pandemic were significantly mitigated among adolescents experiencing a supportive school climate. A positive school climate can protect adolescent mental health during challenging social conditions, such as pandemics.

Psychodrama (PD), supported by extensive global research, is increasingly becoming a vital method for alleviating psychological symptoms and promoting mental well-being in diverse populations across China. However, comprehensive evidence based on rigorous interventions is currently lacking.

This article systematically reviews the literature on randomized controlled experimental intervention studies of PD in the Chinese Mainland from 1982 to 2023.

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework, this article included seven studies (N = 332, 25 effect sizes). The results demonstrate that PD interventions have a promotional effect (standardized mean difference SMD = 0.768, 95% CI [0.591, 0.946]) across different age groups and settings in randomized controlled trial interventions. In accordance with previous literature, we categorized the effect sizes into two major groups: illness reduction (IR) and health promotion (HP). Subgroup analysis based on these two categories revealed consistent findings. In the IR category, the overall effect size was notably significant (SMD = −0.711, 95% CI [−0.976, −0.446]), and in the HP category, the overall effect was also highly significant (SMD = 0.889, 95% CI [0.705, 1.074]). This finding aligns with previous research in other nations, supporting the significant effectiveness of PD as a counseling method in alleviating psychological illnesses and promoting mental health within the Chinese context.

PD serves not only as a therapeutic tool but also as a preventive and developmental intervention. Moving forward, there is a call for increased emphasis on standardized and randomized controlled experimental studies to further the advancement of PD within China.

Childhood bullying is a public health priority. We evaluated the effectiveness and costs of KiVa, a whole-school anti-bullying program that targets the peer context.

A two-arm pragmatic multicenter cluster randomized controlled trial with embedded economic evaluation. Schools were randomized to KiVa-intervention or usual practice (UP), stratified on school size and Free School Meals eligibility. KiVa was delivered by trained teachers across one school year. Follow-up was at 12 months post randomization. Primary outcome: student-reported bullying-victimization; secondary outcomes: self-reported bullying-perpetration, participant roles in bullying, empathy and teacher-reported Strengths and Difficulties Questionnaire. Outcomes were analyzed using multilevel linear and logistic regression models.

Between 8/11/2019–12/02/2021, 118 primary schools were recruited in four trial sites, 11 111 students in primary analysis (KiVa-intervention: n = 5944; 49.6% female; UP: n = 5167, 49.0% female). At baseline, 21.6% of students reported being bullied in the UP group and 20.3% in the KiVa-intervention group, reducing to 20.7% in the UP group and 17.7% in the KiVa-intervention group at follow-up (odds ratio 0.87; 95% confidence interval 0.78 to 0.97, p value = 0.009). Students in the KiVa group had significantly higher empathy and reduced peer problems. We found no differences in bullying perpetration, school wellbeing, emotional or behavioral problems. A priori subgroup analyses revealed no differences in effectiveness by socioeconomic gradient, or by gender. KiVa costs £20.78 more per pupil than usual practice in the first year, and £1.65 more per pupil in subsequent years.

The KiVa anti-bullying program is effective at reducing bullying victimization with small-moderate effects of public health importance.

The study was funded by the UK National Institute for Health and Care Research (NIHR) Public Health Research program (17-92-11). Intervention costs were funded by the Rayne Foundation, GwE North Wales Regional School Improvement Service, Children's Services, Devon County Council and HSBC Global Services (UK) Ltd.

Self-guided Internet-based cognitive behavior therapy (iCBT) for migraine interventions could improve access to care, but there is poor evidence of their efficacy.

A three-arm randomized controlled trial compared: iCBT focused on psychoeducation, self-monitoring and skills training (SPHERE), iCBT focused on identifying and managing personal headache triggers (PRISM) and a waitlist control. The primary treatment outcome was a ≥ 50% reduction in monthly headache days at 4 months post-randomization.

428 participants were randomized (mean age = 30.1). 240 participants (56.2%) provided outcome data at 4 months. Intention-to-treat (ITT) analysis with missing data imputed demonstrated that the proportion of responders with a ≥ 50% reduction was similar between combined iCBTs and waitlist (48.5/285, 17% vs. 16.6/143, 11.6%, p = 0.20), but analysis of completers showed both iCBT programs to be superior to the waitlist (24/108, 22.2% vs. 13/113, 11.5%, p = 0.047). ITT analysis with missing data imputed showed no difference between the two iCBTs (SPHERE: 24.8/143, 17.3% vs. PRISM: 23.7/142, 16.7%, p = 0.99). Uptake rates of the iCBTs were high (76.9% and 81.69% logged in at least once into SPHERE and PRISM, respectively), but adherence was low (out of those who logged in at least once, 19.01% [21/110] completed at least 50% modules in SPHERE and 7.76% [9/116] set a goal for trying out a given trigger-specific recommendation in PRISM). Acceptability ratings were intermediate.

Self-guided iCBTs were not found to be superior in our primary ITT analysis. Low adherence could explain the lack of effects as completer analysis showed effects for both interventions. Enhancement of adherence should be a focus of future research.

In VIVRE (NCT04448431), vortioxetine was associated with significantly higher rates of symptomatic and functional remission, better daily and social functioning, and greater treatment satisfaction than desvenlafaxine in patients with major depressive disorder (MDD) and partial response to selective serotonin reuptake inhibitor (SSRI) therapy. This analysis further explored the relative improvement in patient functioning with vortioxetine versus desvenlafaxine.

VIVRE was a randomized, double-blind study of vortioxetine (10 or 20 mg/day) versus desvenlafaxine (50 mg/day) in adults with MDD and partial response to initial SSRI monotherapy. Mean percentage changes from baseline to week 8 in Functioning Assessment Short Test (FAST) total and domain scores were analyzed by treatment group in the overall population and in working patients.

In the overall population, the mean reduction in FAST total score from baseline after 8 weeks of treatment was 37.2% in vortioxetine-treated patients versus 31.8% in desvenlafaxine-treated patients (P = 0.04). Significantly greater improvements versus desvenlafaxine were seen in vortioxetine-treated patients for FAST autonomy, cognitive functioning, and interpersonal-relationships scores (all P < 0.05). In working patients, the mean reduction in FAST total score from baseline at week 8 was 38.7% versus 32.1% in the vortioxetine and desvenlafaxine groups, respectively (P = 0.04). Significant correlations were seen between absolute changes in patient functioning, and those in depression severity and health-related quality of life.

Vortioxetine was significantly better than desvenlafaxine in improving overall functioning as well as daily, social, and cognitive functioning in patients with MDD with inadequate response to prior SSRI therapy.

Theory and research indicated that executive functioning (EF) correlated with, preceded, and stemmed from worry in generalized anxiety disorder (GAD). The present secondary analysis (Zainal & Newman, 2023b) thus determined whether EF domains mediated the effect of a 14-day (5 prompts/day) mindfulness ecological momentary intervention (MEMI) against a self-monitoring control (SM) for GAD.

Participants (N = 110) diagnosed with GAD completed self-reported (Attentional Control Scale, GAD Questionnaire, Perseverative Cognitions Questionnaire) and performance-based tests (Letter-Number Sequencing, Stroop, Trail Making Test-B, Verbal Fluency) at baseline, post-treatment, and one-month follow-up (1MFU). Causal mediation analyses determined if pre-post changes in EF domains preceded and mediated the effect of MEMI against SM on pre-1MFU changes in GAD severity and trait repetitive negative thinking (RNT).

MEMI was more efficacious than SM in improving pre–post inhibition (β = −2.075, 95% [−3.388, −0.762], p = .002), working memory (β = 0.512, 95% [0.012, 1.011], p = .045), and set-shifting (β = −2.916, 95% [−5.142, −0.691], p = .010) but not verbal fluency and attentional control. Within groups, MEMI but not SM produced improvements in all examined pre–post EF outcomes except attentional control. Only pre–post improvements in inhibition mediated the effect of MEMI against SM on pre-1MFU reductions in GAD severity (β = −0.605, 95% [−1.357, −0.044], p = .030; proportion mediated = 7.1%) and trait RNT (β = −0.024, 95% [−0.054, −0.001], p = .040; proportion mediated = 7.4%). These patterns remained after conducting sensitivity analyses with non-linear mediator-outcome relations.

Optimizing MEMI for GAD might entail specifically boosting inhibition plausibly by augmenting it with dialectical behavioral therapy, encouraging high-intensity physical exercises, and targeting negative emotional contrast avoidance.

Approximately five million individuals have traumatic injuries annually. Implementing prehospital blood-component transfusion (PHBT), encompassing packed red blood cells (p-RBCs), plasma, or platelets, facilitates early hemostatic volume replacement following trauma. The lack of uniform PHBT guidelines persists, relying on diverse parameters and physician experience.

This study aims to evaluate the efficacy of various components of PHBT, including p-RBCs and plasma, on mortality and hematologic-related outcomes in traumatic patients.

A comprehensive search strategy was executed to identify pertinent literature comparing the transfusion of p-RBCs, plasma, or a combination of both with standard resuscitation care in traumatized patients. Eligible studies underwent independent screening, and pertinent data were systematically extracted. The analysis employed pooled risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous variables, each accompanied by their respective 95% confidence intervals (CI).

Forty studies were included in the qualitative analysis, while 26 of them were included in the quantitative analysis. Solely P-RBCs alone or combined with plasma showed no substantial effect on 24-hour or long-term mortality (RR = 1.13; 95% CI, 0.68 - 1.88; P = .63). Conversely, plasma transfusion alone exhibited a 28% reduction in 24-hour mortality with a RR of 0.72 (95% CI, 0.53 - 0.99; P = .04). In-hospital mortality and length of hospital stay were mostly unaffected by p-RBCs or p-RBCs plus plasma, except for a notable three-day reduction in length of hospital stay with p-RBCs alone (MD = -3.00; 95% CI, -5.01 to -0.99; P = .003). Hematological parameter analysis revealed nuanced effects, including a four-unit increase in RBC requirements with p-RBCs (MD = 3.95; 95% CI, 0.69 - 7.21; P = .02) and a substantial reduction in plasma requirements with plasma transfusion (MD = -0.73; 95% CI, -1.28 to -0.17; P = .01).

This study revealed that plasma transfusion alone was associated with a substantial decrease in 24-hour mortality. Meanwhile, p-RBCs alone or combined with plasma did not significantly impact 24-hour or long-term mortality. In-hospital mortality and length of hospital stay were generally unaffected by p-RBCs or p-RBCs plus plasma, except for a substantial reduction in length of hospital stay with p-RBCs alone.

Despite high levels of psychological distress, mental health service use among Syrian refugees in urban settings is low. To address the mental healthcare gap, the World Health Organization developed group problem management plus (gPM+), a scalable psychological intervention delivered by non-specialist peer facilitators. The study aimed to evaluate the effectiveness of gPM+ in reducing symptoms of depression and anxiety among Syrian refugees in Istanbul, Türkiye.

A randomized controlled trial was conducted among 368 distressed (Kessler Psychological Distress Scale, K10 > 15) adult Syrian refugees with impaired functioning (World Health Organization Disability Assessment Schedule, WHODAS 2.0 > 16). Participants were recruited between August 2019 and September 2020 through a non-governmental organization providing services to refugees. Participants were randomly allocated to gPM+ and enhanced care as usual (gPM+/E-CAU) (184 participants) or E-CAU only (184 participants). Primary outcomes were symptoms of depression and anxiety (Hopkins Symptom Checklist (HSCL-25)) at 3-month follow-up. Secondary outcomes were post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-5; PCL-5), functional impairment (WHODAS 2.0), and self-identified problems (psychological outcome profiles).

Intent-to-treat analyses showed no significant effect of gPM+ on symptoms of anxiety, depression, PTSD and self-identified problems. Yet, there was a significant reduction in functional impairment in gPM+/E-CAU compared to E-CAU at 3-month follow-up (adjusted mean difference 1.66, 95 % CI 0.04, 3.27, p = 0.045, d = 0.19). Post-hoc subgroup analyses among participants with probable baseline depression or anxiety showed that there was a small but significant reduction in depression (adjusted mean difference −0.17, 95 % CI −0.32, −0.02, p = 0.028, d = 0.27) and anxiety (adjusted mean difference −0.21, 95 % CI −0.37, −0.05, p = 0.009, d = 0.30) symptoms comparing gPM+/E-CAU to E-CAU only at 1-week post assessment, but not at 3-month follow-up. There was a significant difference between conditions on functional impairment at 3-month follow-up, favouring gPM+/E-CAU condition (adjusted mean difference −1.98, 95 % CI −3.93, −0.02, p = 0.048, d = 0.26).

In this study in an urban setting in Türkiye, gPM+ did not alleviate symptoms of depression and anxiety among Syrian refugees experiencing psychological distress and daily living difficulties. However, participants with higher distress at baseline seemed to benefit from gPM+, but treatment gains disappeared in the long term. Current findings highlight the potential benefit of tailored psychosocial interventions for highly distressed refugees in volatile low-resource settings.

Sleep pattern alteration is a core feature of bipolar disorder (BD), often challenging to treat and affecting clinical outcomes. Suvorexant, a hypnotic agent that decreases wakefulness, has shown promising results in treating primary insomnia. To date, data on its use in BD are lacking. This study evaluated the efficacy and tolerability of adjunctive suvorexant for treatment-resistant insomnia in BD patients.

Thirty-six BD outpatients (19 BDI, 69.4% female, 48.9 [±15.2] years) were randomized for 1 week to double-blind suvorexant (10–20 mg/day) versus placebo. Then, all subjects who completed the randomized phase were offered open suvorexant for 3 months. Subjective total sleep time (sTST) and objective total sleep time (oTST) were assessed.

During the randomized control trial (RCT) phase, an overall increase in the oTST emerged, which was statistically significant for the Cole–Kripke algorithm (p = 0.035). The comparison between the suvorexant and placebo groups was limited by significant differences between measurements at baseline. During the open phase, no significant improvement was detected relative to either sTST and oTST. No adverse events nor major intolerances were reported.

Efficacy results are inconsistent. During the RCT phase, only a small increase in the objective oTST emerged, while during the open phase, no significant improvement was detected. While this is the first ever study of suvorexant in BD-related insomnia, the limitation of the small sample and the high rate of dropouts limits the generalizability of these findings. Larger studies are needed to assess suvorexant in treating BD-related insomnia.

Problematic drinking frequently co-occurs with depression among young adults, but often remains unaddressed in depression treatment. Evidence is insufficient on whether digital alcohol interventions can be effective in this young comorbid population. In a randomized controlled trial, we examined the effectiveness of Beating the Booze (BtB), an add-on digital alcohol intervention to complement depression treatment for young adults.

Participants were randomized to BtB + depression treatment as usual (BTB + TAU, n = 81) or TAU (n = 82). The primary outcome was treatment response, a combined measure for alcohol and depression after 6-month follow-up. Secondary outcomes were number of weekly drinks (Timeline Follow-back) and depressive symptoms (Center for Epidemiologic Studies Depression scale). Treatment response was analyzed using generalized linear modeling and secondary outcomes using robust linear mixed modeling.

Low treatment response was found due to lower than expected depression remission rates. No statistically significant between-group effect was found for treatment response after 6-month follow-up (odds ratio 2.86, p = 0.089, 95% confidence interval [CI] 0.85–9.63). For our secondary outcomes, statistically significant larger reductions in weekly drinks were found in the intervention group after 3-month (B = −4.00, p = 0.009, 95% CI −6.97 to −1.02, d = 0.27) and 6-month follow-up (B = −3.20, p = 0.032, 95% CI −6.13 to −0.27, d = 0.23). We found no statistically significant between-group differences on depressive symptoms after 3-month (B = −0.57, p = 0.732, 95% CI −3.83 to 2.69) nor after 6-month follow-up (B = −0.44, p = 0.793, 95% CI −3.69 to 2.82).

The add-on digital alcohol intervention was effective in reducing alcohol use, but not in reducing depressive symptoms and treatment response among young adults with co-occurring depressive disorders and problematic alcohol use.

Pre-registered on October 29, 2019 in the Overview of Medical Research in the Netherlands (OMON), formerly the Dutch Trial Register(https://onderzoekmetmensen.nl/en/trial/49219).

Theories propose that judgment of and reactivity to inner experiences are mediators of the effect of mindfulness-based interventions on generalized anxiety disorder (GAD). However, no study has tested such theories using brief, mindfulness ecological momentary intervention (MEMI). We thus tested these theories using a 14-day MEMI versus self-monitoring app (SM) control for GAD.

Participants (N = 110) completed self-reports of trait mindfulness (Five Facet Mindfulness Questionnaire), GAD severity (GAD-Questionnaire-IV), and trait perseverative cognitions (Perseverative Cognitions Questionnaire) at prerandomization, posttreatment, and 1-month follow-up (1MFU). Counterfactual mediation analyses with temporal precedence were conducted.

Improvement in pre–post mindfulness domains (acceptance of emotions, describing feelings accurately, acting with awareness, judgment of inner experience, and reactivity to inner experience) predicted pre-1MFU reduction in GAD severity and pre-1MFU reduction in trait perseverative cognitions from MEMI but not SM. MEMI reduced pre–post reactivity to inner experiences (but not other mindfulness domains) significantly more than SM. Only reduced pre–post reactivity significantly mediated stronger efficacy of MEMI over SM on pre-1MFU reductions in GAD severity (indirect effect: β = −2.970 [−5.034, −0.904], p = .008; b path: β = −3.313 [−6.350, −0.276], p = .033; percentage mediated: 30.5%) and trait perseverative cognitions (indirect effect: β = −0.153 [−0.254, −0.044], p = .008; b path: β = −0.145 [−0.260, −0.030], p = .014; percentage mediated: 42.7%). Other trait mindfulness domains were non-significant mediators.

Reactivity to inner experience might be a mindfulness-based intervention change mechanism and should be targeted to optimize brief MEMIs for GAD.

Addressing aggressive behavior in adolescence is a key step toward preventing violence and associated social and economic costs in adulthood. This study examined the secondary effects of the personality-targeted substance use preventive program Preventure on aggressive behavior from ages 13 to 20.

In total, 339 young people from nine independent schools (M age = 13.03 years, s.d. = 0.47, range = 12–15) who rated highly on one of the four personality traits associated with increased substance use and other emotional/behavioral symptoms (i.e. impulsivity, anxiety sensitivity, sensation seeking, and negative thinking) were included in the analyses (n = 145 in Preventure, n = 194 in control). Self-report assessments were administered at baseline and follow-up (6 months, 1, 2, 3, 5.5, and 7 years). Overall aggression and subtypes of aggressive behaviors (proactive, reactive) were examined using multilevel mixed-effects analysis accounting for school-level clustering.

Across the 7-year follow-up period, the average yearly reduction in the frequency of aggressive behaviors (b = −0.42; 95% confidence interval [CI] −0.64 to −0.20; p < 0.001), reactive aggression (b = −0.22; 95% CI 0.35 to −0.10; p = 0.001), and proactive aggression (b = −0.14; 95% CI −0.23 to −0.05; p = 0.002) was greater for the Preventure group compared to the control group.

The study suggests a brief personality-targeted intervention may have long-term impacts on aggression among young people; however, this interpretation is limited by imbalance of sex ratios between study groups.

Eating disorder (ED) research has embraced a network perspective of psychopathology, which proposes that psychiatric disorders can be conceptualized as a complex system of interacting symptoms. However, existing intervention studies using the network perspective have failed to find that symptom reductions coincide with reductions in strength of associations among these symptoms. We propose that this may reflect failure of alignment between network theory and study design and analysis. We offer hypotheses for specific symptom associations expected to be disrupted by an app-based intervention, and test sensitivity of a range of statistical metrics for identifying this intervention-induced disruption.

Data were analyzed from individuals with recurrent binge eating who participated in a randomized controlled trial of a cognitive-behavioral smartphone application. Participants were categorized into one of three groups: waitlist (n = 155), intervention responder (n = 49), and intervention non-responder (n = 77). Several statistical tests (bivariate associations, network-derived strength statistics, network invariance tests) were compared in ability to identify change in network structure.

Hypothesized disruption to specific symptom associations was observed through change in bivariate correlations from baseline to post-intervention among the responder group but were not evident from symptom and whole-of-network based network analysis statistics. Effects were masked when the intervention group was assessed together, ignoring heterogeneity in treatment responsiveness.

Findings are consistent with our contention that study design and analytic approach influence the ability to test network theory predictions with fidelity. We conclude by offering key recommendations for future network theory-driven interventional studies.

Growing evidence points to the pivotal role of vitamin D in the pathophysiology and treatment of major depressive disorder (MDD). However, there is a paucity of longitudinal research investigating the effects of vitamin D supplementation on the brain of MDD patients.

We conducted a double-blind randomized controlled trial in 46 MDD patients, who were randomly allocated into either VD (antidepressant medication + vitamin D supplementation) or NVD (antidepressant medication + placebos) groups. Data from diffusion tensor imaging, resting-state functional MRI, serum vitamin D concentration, and clinical symptoms were obtained at baseline and after an average of 7 months of intervention.

Both VD and NVD groups showed significant improvement in depression and anxiety symptoms but with no significant differences between the two groups. However, a greater increase in serum vitamin D concentration was found to be associated with greater improvement in depression and anxiety symptoms in VD group. More importantly, neuroimaging data demonstrated disrupted white matter integrity of right inferior fronto-occipital fasciculus along with decreased functional connectivity between right frontoparietal and medial visual networks after intervention in NVD group, but no changes in VD group.

These findings suggest that vitamin D supplementation as adjunctive therapy to antidepressants may not only contribute to improvement in clinical symptoms but also help preserve brain structural and functional connectivity in MDD patients.