Journal of Affective Disorders Reports

Background: Nursing documentation is an essential component of nursing practice that has a potential to improve patient care outcome. Poor documentation of nursing care activities among nurses has been shown to have negative impacts on the health care quality. The aim of this study was to assess documentation practice and associated factors among nurses working in Felege Hiwot comprehensive specialized hospital from August 1 to August 30, 2025. Method: Institutional based cross sectional study design was employed. The data was checked for completeness, coded and entered in epi -data version 3.1 and analysis was made by STATA version 14. Binary logistic regression analysis was computed to assess associations of factors with documentation practice. Variables with p- value less than 0.25 in Bivariable analysis was entered to final model and P < 0.05 at 95% confidence interval was considered as statistically significant. Odds ratio was used to show strength of association. Result: Out of the 349 respondents, 209 (59.9%) were females. In this study 40.1% of nurses had good documentation practice. Educational level, MSc (AOR, 95%CI; 10.3(3.4-31.8)), attitude (AOR, 95%CI; 2.6(1.5-4.7)), number of patient care (AOR, 95%CI; 5.6(1.9-16.3)) and Knowledge (AOR< 95%CI; 3.7(2.1-6.2)) were statistically associated with documentation practice. Conclusion and recommendation: Poor documentation practice was due to the identified factors. So, it is better to put further effort toward improving documentation practice through providing training on standards of documentation and enhancing the favorable attitude of nurses toward documentation practice. Keywords: Documentation, Nursing care, nursing record of patient care.

BackgroundTranscranial alternating current stimulation (tACS) is a promising non-pharmacological intervention for major depressive disorder (MDD), but its effects on endogenous alpha oscillatory dynamics and their relationship to clinical improvement remain unclear. MethodsIn this double-blind, sham-controlled randomized clinical trial, 20 adults with MDD received five consecutive days of prefrontal 10 Hz tACS or sham. Resting 128-channel EEG was acquired before stimulation on Day 1 (D1), Day 5 (D5), and two-week follow-up. Changes in alpha power spectral density were quantified at the stimulation frequency (10 Hz) and at each participants individual alpha frequency (IAF), using prefrontal regions of interest and whole-head topographical analyses. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS-17). ResultsBetween-group comparisons revealed no significant differences in prefrontal alpha power changes at either 10 Hz or IAF during the intervention week or at follow-up, although right prefrontal 10 Hz power showed a trend-level reduction with tACS. In contrast, within the tACS group, greater reductions in prefrontal IAF power were associated with greater HDRS-17 improvement from D1 to follow-up, and early IAF power suppression during the intervention week predicted later symptom improvement. Whole-head analyses identified a posterior cluster of reduced 10 Hz power at follow-up in the tACS group relative to sham, whereas clinically relevant correlations were specific to IAF power and distributed across frontal-central and parietal electrodes. Depression scores improved over time in both groups, with greater reductions in HDRS-17 scores observed in the tACS group. ConclusionsFindings suggest that five days of 10 Hz tACS engages depression-relevant alpha mechanisms, with symptom improvement linked specifically to modulation of alpha power at IAF. Results support personalization of tACS in future trials.

BackgroundIntermittent theta burst stimulation (iTBS) and H-coil repetitive transcranial magnetic stimulation (rTMS) are FDA-cleared treatments for major depression; yet their comparative effectiveness in treatment-resistant depression (TRD) has not been evaluated in randomized trials. This pilot randomized trial was designed to obtain preliminary comparative estimates and to explore whether baseline cognitive functioning relates to early remission. MethodsTwenty-eight adults with TRD were randomized to six weeks of iTBS delivered to the dorsolateral prefrontal cortex (DLPFC) using a figure-8 coil (n=15) or H-coil rTMS delivered to the dorsomedial prefrontal cortex (DMPFC) using a H7-coil (n=13). The primary outcome was change in 17-item Hamilton Depression Rating Scale (HRSD-17) score from baseline to week 6, analyzed with ANCOVA. Additional outcomes included response, remission, and symptom trajectories through week 18. Exploratory analyses examined the association between baseline cognitive functioning, such as executive functions and memory, and remission. ResultsTwenty-five participants completed all 30 sessions. Adjusted week-6 HRSD-17 scores did not differ between groups (mean difference -0.40, 95% CI -5.23 to 4.43; p=.865). Response rates were 40.0% for iTBS and 50.0% for H-coil (p>.60), and remission rates were identical across groups (20.0%). Remitters showed higher baseline executive functioning than non-remitters in exploratory analyses, although these associations were not confirmed in adjusted models. ConclusionIn this pilot trial, iTBS and H7-coil rTMS showed symptom improvement, with no clear between-group pattern. Exploratory findings suggest a potential signal involving executive functioning that warrants further investigation. These results inform the feasibility and design of larger comparative trials. Trial registrationClinicalTrials.gov (NCT05902312)

BackgroundAntidepressants exert their therapeutic effects through ameliorating negative emotional biases that underpin depression. However, therapeutic gains may depend upon restructuring how emotional information is processed. This can be achieved through Cognitive Bias Modification (CBM), a technique for positively shifting recognition of emotional facial expressions. Here, we examined how CBM modifies emotional processing circuits in individuals with depression who were taking Selective Serotonin Reuptake Inhibitors (SSRIs). MethodsA double-blind Randomised Controlled Trial was conducted in 84 participants with depression who had recently started SSRI medication. Participants received five sessions of active or sham CBM over one week before fMRI scanning where they viewed emotional faces (happy, fearful, sad). ResultsAcross all emotional expressions, greater Blood Oxygen Level Dependent (BOLD) signal was observed in the inferior occipital gyrus for the active compared to sham CBM. Emotional-specific effects were observed in the medial Prefrontal Cortex (mPFC), with reduced BOLD signal in the active (compared to sham) group for viewing happy vs. fearful faces. Changes in BOLD signal were also associated with individual differences in response to CBM. Enhanced functional connectivity between mPFC and right Dorsolateral Prefrontal Cortex (rDLPFC) predicted improvement in depressive symptoms four weeks later. ConclusionsThese results indicate that CBM modifies the neural circuits involved in emotion processing in people with depression currently taking antidepressants. Converting these changes in emotional perception to improved depressive symptoms was related to changing mPFC-rDLPFC connectivity. Future trials are needed to test CBMs clinical utility as a simple, affordable and accessible adjunct therapy for depression.

Numerous studies have shown that adults with depression have distinct oculomotor alterations during saccade tasks, but whether similar alterations occur in adolescents is largely unknown. The purpose of this study was to test if eye-tracking during a structured saccade task could distinguish a group of adolescents with depression from healthy controls. We hypothesized that, due to overlapping circuitry between depression pathology and the oculomotor system, adolescents with depression would show alterations in fixation, saccade, and pupil behaviour. 51 adolescents with depression and 66 age-matched healthy controls completed the Interleaved Pro- and Anti-Saccade Task (IPAST) and several self-reported questionnaires for psychiatric symptoms. Oculomotor outcomes included fixation acquisition, fixation breaks, correct rate, saccadic reaction time, rate of correct express-latency pro-saccades, rate of express- and regular-latency anti-saccade errors, baseline pupil size, as well as pupil constriction and dilation sizes following task instruction. In comparison to healthy controls, adolescents with depression displayed impairments acquiring fixation (p<.001), made more fixation breaks in pro- (p=.023) and anti-saccade trials (p=.005), more anti-saccade errors (p=.013), more express-latency saccades overall (ps=.016), had a smaller pupil constriction in pro-saccade trials (p=.047) and had a smaller pupil dilation in pro- (p=.011) and anti-saccade trials (p=.041). No differences were found for saccadic reaction time, rate of correct pro-saccades, rate of regular-latency anti-saccade errors, pupil constriction size during anti-saccade trials, or baseline pupil size. Patients had psychiatric comorbidities and were using psychotropic medication. While this reflected clinical reality, these factors may have influenced oculomotor behaviour. Adolescents with depression had altered fixation, saccade, and pupil behaviour during IPAST. Given that many cases of adolescent depression remain undetected, accessible and objective screening approaches are highly needed. This oculomotor phenotype may be used in the development of such a screening tool to detect those at risk.

Esketamine is a fast-acting antidepressant drug which induces acute psychoactive effects. The most frequent is a dissociative state which seems unrelated to therapeutic efficacy. Other esketamine-induced effects, including psychedelic-like mystical experiences, have been poorly studied in terms of phenomenology and frequency, and may carry specific therapeutic relevance. In this study, we characterised esketamine-induced mystical experiences in relation with clinical outcomes. We conducted a longitudinal observational study and systematically measured acute subjective effects in patients receiving esketamine for treatment-resistant depression after each administration across the induction phase. A total of 45 patients were included, from two independent centres, totalling 352 esketamine administrations. Principal Component Analysis (PCA) supported the validity of the Mystical Experience Questionnaire (MEQ-30) for assessing esketamine-induced subjective effects, with components recovering dimensions previously validated with classic psychedelics. Mystical experiences (MEQ-30 score above 60) occurred in 58% of patients, with high inter- and intra-individual variability in frequency, intensity, and phenomenology across sessions. Higher mean and peak MEQ scores were associated with greater improvement in Montgomery-Asberg Depression Rating Scale scores from pre- to post-treatment, whereas the intensity of dissociative or other non-mystical effects was not. Positive mood and mystical MEQ dimensions in particular predicted therapeutic outcomes. Baseline spirituality also significantly predicted treatment outcomes and peak MEQ scores in the first week of treatment. These findings add to the growing body of evidence suggesting that psychedelic-like mystical experiences may be associated to therapeutic efficacy, not only in classic psychedelic-assisted therapy, but also in esketamine treatment.

Digital therapeutics for mental health often face low patient engagement, which limits their clinical impact. Interventions that deliver treatment using a video game medium may improve engagement and therapeutic efficacy, but the putative emergence of gaming-related problems remains a concern among clinical stakeholders. We examined whether long-term engagement with Meliora, a video game therapeutic for adult major depressive disorder, was associated with changes in gaming-related problems in a three-arm randomized controlled trial. The intention-to-treat cohort (n = 1,001) had a mean age of 33.4 years (SD 9.3) and 64% were female. The Gaming Addiction Scale (GAS-7) scores decreased from baseline (week 0) to post-intervention (week 12) in the Meliora arm (p = 8.1x10-4) and in the treatment-as-usual arm (p = 6.0x10-6), with no significant change observed in the Sham arm (p = 0.39). Changes in GAS-7 scores were not associated with intervention use hours (Meliora: p = 0.17; Sham: p = 0.28) or with experienced immersion (Meliora: p = 0.93; Sham: p = 0.19). Deterioration analysis found worsening rates from baseline to post-intervention low and comparable across study arms. Analyses in the per-protocol completer cohort ([&ge;]24 h use) corroborated these findings, indicating that even higher use did not lead to increases in gaming-related problems. These results provide evidence that long-term use of a video game therapeutic does not increase gaming-related problems when risks are properly mitigated, suggesting that video games may provide a safe medium for digital therapeutics. Author summaryMany patients use digital therapeutics insufficiently or drop out early, which limits their effectiveness and applicability in healthcare. Video game therapeutics deliver the treatment using an interactive video game as a medium to improve both engagement and therapeutic efficacy. However, extended use of video game therapeutics could inadvertently increase gaming-related problems. We examined whether long-term use of Meliora, a video game therapeutic for adults living with depression, was associated with increased gaming-related problems. We found that using Meliora or a highly similar Sham device did not increase gaming-related problems. Changes in gaming-related problems were not associated with the amount of time participants used the interventions, suggesting that typical use patterns are safe. We also found no relationship between experienced immersion and changes in gaming-related problems, suggesting that subjective immersion is distinct from problematic gaming. This study provides the first clinical evidence that extended engagement with a video game therapeutic does not increase gaming-related problems. These findings suggest that video games can be a safe medium for digital therapeutics in healthcare.

BackgroundThe frontoparietal network (FPN) has been strongly implicated in both the development of and recovery from major depressive disorder (MDD), making it a promising target for transcranial magnetic stimulation (TMS) therapy of MDD. However, commonly used TMS targeting approaches often co-stimulate multiple neighboring functional brain networks to varying degrees across individuals. We therefore aimed to develop a clinically feasible, standardized TMS coil placement that enables stronger and more selective stimulation of the FPN without requiring individual neuroimaging or neuronavigation. MethodsWe optimized the placement of a prototypical figure-of-eight coil in a population-based brain template by maximizing simulated electric field (E-field) strength within a representative FPN cluster. Based on this optimized placement, we derived a practical heuristic using EEG electrode positions and simple scalp measurements. The FPN-optimized placement and its heuristic were validated by comparing E-field hotspot coverage of the FPN and other functional networks against a clinically established, standard coil placement (Beam F3 method) in precisely mapped brains of 20 healthy individuals (15 female) and 20 patients with MDD (7 female). We further assessed robustness of FPN stimulation to coil tilt inaccuracies and the role of coil orientation. ResultsThe optimized heuristic places the center of the coil over the F5 electrode and orients its handle along the F5-AF7 axis. This placement yielded significantly stronger and more selective FPN coverage than the established clinical approach. Targeting was largely robust to tilt inaccuracies but sensitive to rotational deviations. DiscussionThis scalp-based F5-AF7 TMS coil placement enables selective and reliable targeting of the frontoparietal depression network in routine clinical settings. Whether it improves antidepressant efficacy compared to established targeting strategies should be evaluated in future clinical trials.

BackgroundAs digital communication becomes central to daily life, psychotherapy increasingly has access to patients electronic media data. While digital phenotyping has been widely studied, less is known about whether incorporating personal communication data, such as text messages, improves clinical outcomes in psychotherapy. ObjectiveTo determine whether integrating personalized text message data into psychotherapy improves depression, anxiety, health related quality of life, and therapeutic alliance, and to examine whether increased access to collateral information influences clinical decision making. MethodsThe Electronic Media and its Impact on Psychotherapy EMAP study was a randomized controlled trial conducted in adult and geriatric outpatient and partial hospitalization settings at an academic psychiatric hospital. Participants receiving psychotherapy for primary depression or anxiety N = 101 were randomized to Electronic Media Enhanced Therapy EME n = 52 or Treatment as Usual TAU n = 49. In EME, research staff reviewed participants text messages prior to sessions using personalized mood related key terms and presented aggregated findings on a HIPAA compliant clinician dashboard. TAU participants received standard care without message review. Outcomes included change scores for PHQ 9, GAD 7, SF 36, and Working Alliance Inventory Short Revised WAI SR. Linear regression and nonparametric tests compared groups. Moderation analyses assessed whether frequency of information access influenced treatment changes. ResultsNo significant between group differences were observed in anxiety or working alliance. Among participants with SF 36 follow up data n = 65 EME participants demonstrated greater improvement in the pain subscale. Greater frequency of information access was associated with increased treatment related changes in the EME group. Access to additional collateral information was associated with more clinical actions but not improved distal outcomes. ConclusionsIntegrating personalized text message data into short term psychotherapy did not significantly improve depression or anxiety, and neither improved nor worsened therapeutic alliance. However, access to greater amounts of collateral information including electronic media influenced clinical decision making, suggesting nuanced and context dependent effects.

Objective: Major depressive episodes frequently show limited response to first-line treatments, motivating the search for objective biomarkers. EEG/ECG-based support tools aggregating electrophysiological predictors may guide treatment selection. We examined whether antidepressant treatments concordant with an EEG/ECG-biomarker report were associated with higher response rates. Methods: We retrospectively analyzed adults with ICD-10 depressive disorder or bipolar depression treated with electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), (es)ketamine, or selective serotonin reuptake inhibitors (SSRIs) between 2022 and 2024. Resting-state EEG with simultaneous ECG generated individualized biomarker reports with modality-specific response likelihoods. Treatment chosen by clinical teams was classified as concordant or non-concordant; response was derived from routinely collected clinical scales. Results: Among 153 patients (ECT n=53, rTMS n=48, (es)ketamine n=36, SSRIs n=16), response rates were higher for concordant vs non-concordant treatments: ECT 70% vs 50%, rTMS 30% vs 13%, (es)ketamine 31% vs 10%, and SSRIs 100% vs 11%. Overall, 46% (42/92) of concordant vs. 26% (14/54) of non-concordant patients responded (absolute difference +20 percentage points; relative increase {approx}77%; number needed to treat {approx}5). Conclusion: Concordance with EEG/ECG biomarkers correlated with higher treatment response, warranting confirmation in prospective trials. Significance: EEG/ECG-based decision support may enhance antidepressant treatment response in everyday clinical practice.

ImportancePain is inherently aversive but provides emotional relief for individuals engaging in non-suicidal self-injury (NSSI). Despite the high prevalence and severity of NSSI, the neural mechanisms underlying pain processing in individuals with NSSI remain poorly understood. ObjectiveTo compare brain structure and functional connectivity between individuals with NSSI and controls and to relate brain function to pain inhibition. DesignCross-sectional, experimental. SettingMR Center at the Karolinska University Hospital in Stockholm, Sweden. ParticipantsWomen aged 18-35 years with NSSI (n=41) or matched healthy controls (n=40). ExposuresEngagment in self-injury [&ge;] 5 days during the last year. Main outcomes and measuresMagnetic Resonance Imaging (MRI) was used to examine brain structure and function related to pain regulation in individuals with NSSI (n=41) and healthy controls (n=40). The experimental pain test Conditioned Pain Modulation (CPM) was used to determine descending pain inhibition. ResultsWe found higher connectivity between the brains somatomotor networks and subcortical areas during resting-state functional MRI in NSSI compared to controls (P=.009; Bonferroni corrected), particularly involving the thalamus and caudate nucleus. The connectivity was linked to the level of descending pain inhibition during CPM. There was no difference between NSSI and controls regarding brain morphometry. Conclusions and relevanceOur findings suggest that individuals with NSSI may rely more on sensory-motor activations to regulate emotions. This study provides the first evidence linking specific brain circuits to pain regulation and self-injury behavior, highlighting potential pathways for more effective treatments for NSSI and related mental health conditions.

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder with changes in motivation to work for rewards being a core symptom. Transcutaneous vagus nerve stimulation (tVNS) has emerged as a promising therapy but its effects on the core features of MDD, such as changes in motivation, remained relatively unexplored. In this randomised, single-blind, cross-over, controlled trial, we used a grip strength effort task to investigate how tVNS impacted choices to exert different levels of physical effort for varying monetary rewards in MDD patients (n=53) and a non-depressed control group (n=45). Compared to sham stimulation, tVNS enhanced the efficiency with which participants with severe depressive symptoms allocated physical effort for rewards (reward-effort efficiency). These effects were not seen in participants with less severe symptoms. Specifically, we found that the effect of tVNS on reward-effort efficiency was driven by reduced unnecessary effort, i.e., a reduction in choices to exert additional effort when this was not required to gain a larger reward. These findings suggest a potential motivational mechanism by which tVNS exerts its therapeutic effects in MDD. Determining whether the effects of tVNS are linked to broader changes in executive functioning, such as improvements in cognitive flexibility in MDD, should be a key aim for future work.

Abstract Background Insomnia is a major public health problem affecting an estimated 852 million adults worldwide. Current pharmacological treatments, including benzodiazepines and Z-drugs, carry serious risks of dependency, cognitive impairment, and adverse events. These limitations have driven growing interest in complementary and alternative therapies, particularly herbal sedatives, which are perceived as natural and safer. However, evidence on their safety and efficacy remains insufficient and patchy. Objective: This review evaluated the effectiveness of lesser known herbal sedatives for insomnia. Methods The protocol was registered with PROSPERO (CRD420251101795). Eligibility was defined using the PICO framework: Population: adults aged [&ge;]18 years with insomnia; Interventions: Passiflora incarnata, Hawthorn, Melissa officinalis, Chamomile, Viola odorata, Nelumbo nucifera, Rhodiola rosea, and Eschscholtzia californica. Comparators: placebo or usual care; Primary and Secondary Outcomes: sleep quality (Pittsburgh Sleep Quality Index, Insomnia Severity Index, Epworth Sleepiness Scale), sleep duration, and sleep latency. Databases and registers were searched from January 2005 to July 2025. Randomized controlled trials, nonrandomized controlled trials, clinical trials, and observational studies were included. Five reviewers independently screened studies. Data extraction used a structured Excel spreadsheet. Risk of bias was assessed using RoB 2.0 for randomized trials and ROBINS-I V2 for nonrandomized studies. Random-effects meta-analyses (DerSimonian and Laird) were conducted in RevMan. Narrative synthesis followed SWiM guidelines. Results From 1,294 records, 32 studies met eligibility criteria. Meta-analysis of 23 RCTs demonstrated a statistically significant pooled effect favouring herbal sedatives (SMD -0.77, 95% CI -1.14 to -0.40, p=0.0001), with substantial heterogeneity (I square=92%). Subgroup analysis showed larger effects for chamomile (SMD -1.06) and Melissa officinalis (SMD -0.66). Most RCTs had high overall risk of bias; nonrandomized studies predominantly had critical risk of bias. Conclusions This systematic review provides preliminary evidence that several herbal sedatives, particularly chamomile and Melissa officinalis, may improve insomnia-related outcomes. However, methodological weaknesses, high risk of bias, and substantial heterogeneity limit evidence strength. Future research requires standardized extracts, large multicentre RCTs, and extended follow-up.

Importance: Conventional repetitive transcranial magnetic stimulation (rTMS) can be ineffective in individuals who have previously failed brain stimulation, ketamine and/or multiple lines of therapies. Modern accelerated rTMS protocols using image-guided targets have not been systematically investigated in these individuals. The goal of this study was to assess the feasibility and efficacy of personalized, connectivity-guided, accelerated intermittent theta-burst stimulation (iTBS) in patients with treatment-resistant depression (TRD) of varying refractoriness. Objective: To assess whether connectivity-guided, accelerated iTBS produces significant reductions in depression severity, and to what extent this benefit extends to ultra treatment-resistant depression (UTRD). Design: This was an open-label feasibility trial of connectivity-guided, accelerated iTBS in patients with TRD. Two distinct groups of participants were recruited from a neurosurgical-psychiatry clinic with UTRD and an interventional psychiatry clinic with TRD. Patients were stratified into a priori treatment-resistance subgroups. Patients received five days of open-label treatment. Outcome measures were collected immediately prior to and after treatment, as well as at 4- and 12-weeks post-treatment. Setting: This trial (NCT05813093) was conducted between November 2023 and July 2025 at Sunnybrook Health Sciences Centre in Toronto, Ontario, Canada. Participants: Patients with major depressive disorder. A total of 96 participants were screened, with 73 meeting eligibility criteria (UTRD=30, TRD=43). One withdrew due to inability to tolerate the baseline MRI, and the other withdrew voluntarily prior to treatment. Intervention: Participants underwent a neuronavigated accelerated iTBS (600 pulses) protocol using personalized left dorsolateral prefrontal cortex (dlPFC) targets derived from functional magnetic resonance imaging (fMRI), comprising eight daily treatments, repeated over five days. Main Outcomes: Primary outcomes were i) change in Hamilton Depression Rating Scale (HAM-D17) from baseline to the end of the fifth day of treatment, and ii) the difference in change in HAM-D17 between UTRD and TRD subgroups. Results: Connectivity-guided fMRI targeting yielded personalized targets clustered around the anterolateral dlPFC. Accelerated iTBS elicited rapid antidepressant effects ({Delta}HAM-D17 -9.01 [SD 6.06], t = -12.45, p < 0.001) regardless of treatment-resistance group ({Delta}HAM-D17 -9.64 [SD 5.94] vs -8.10 [SD 6.12], t = -1.05, p = 0.299), which were sustained up to 12 weeks after treatment. Overall response and remission rates at the end of treatment were 40.8% and 16.9%. Self-report scales revealed broad symptomatic relief outside of core depressive symptoms. Conclusions & Relevance: This study demonstrated that fMRI connectivity-guided, accelerated iTBS induces sustained antidepressant effects and broader psychiatric benefits in patients across the spectrum of TRD. In a cohort unlikely to respond to most antidepressant therapies, connectivity-guided, accelerated iTBS offers a safe, well-tolerated option that can achieve benefit, or when ineffective, allow patients to expeditiously proceed with subsequent therapies than conventional rTMS. Trial Registration: This clinical trial was registered at clinicaltrials.gov with NCT05813093.

BackgroundMajor depression affects at least 10% of adults, yet evidence-based treatments have modest clinical effectiveness and acceptability. In recent years, outdoor swimming has grown increasingly popular and emerging quantitative and qualitative evidence suggests potential as an intervention for depression, however, there is yet to be a full-scale randomised controlled trial (RCT). This is a protocol to assess the safety and test the clinical- and cost-effectiveness of an 8-session outdoor swimming course (in addition to usual care) on depression symptom severity in adults experiencing major depression, in comparison to usual care alone. MethodsThis study is a pragmatic, parallel group, superiority RCT with 1:1 allocation comparing the outdoor swimming intervention (in addition to treatment as usual) with treatment as usual, aiming to recruit 480 adult participants meeting diagnostic criteria for major depression. Recruitment will take place across 21 sites with blind post treatment and follow up assessments. The primary outcome is depression symptom severity at T1 post-intervention, 12 weeks post-randomisation (the primary end point) using the Patient Health Questionnaire 9 (PHQ-9). Secondary clinical outcomes are anxiety (Generalised Anxiety Disorder 7 at T1 and T2 [38 weeks post-randomisation] and PHQ-9 at T2), mindfulness is measured as a potential mechanism at all timepoints (Five Facet Mindfulness Questionnaire 15). Health economic measures at all time points are: EQ-5D-5L, Recovering Quality of Life (ReQoL), Client Service Receipt Inventory and the Productivity Cost Questionnaire. A qualitative study will examine the experience of participants during and after the swim course. DiscussionIf the 8-session outdoor swim course is safe, clinically- and cost-effective, findings will support national implementation, offering an evidence-based intervention to those affected by depression, while potentially reducing healthcare costs. Furthermore, this may pave the way for other outdoor activities to support people with poor mental health to be developed and evaluated as interventions. Trial registrationControlled trial registration number is ISRCTN registration number 24759023. Registered on 21 February 2024 (https://www.isrctn.com/ISRCTN24759023). Administrative informationNote: Numbers enclosed in braces within this protocol correspond to SPIRIT checklist item numbers. The sequence of items has been adjusted to group related content together. (https://www.consort-spirit.org/). O_TBL View this table: org.highwire.dtl.DTLVardef@7f6ff8org.highwire.dtl.DTLVardef@900309org.highwire.dtl.DTLVardef@b75bc0org.highwire.dtl.DTLVardef@1e8d410org.highwire.dtl.DTLVardef@ba71ac_HPS_FORMAT_FIGEXP M_TBL C_TBL Plain Language Summary BackgroundDepression is very common,with at least 1 in 10 people having an episode of depression during their lifetime. Many people believe that outdoor swimming can improve depression. There is some research that suggests outdoor swimming is helpful for depression, but we do not yet have enough evidence to be sure. OUTSIDE 2 is a large research study that aims to find out whether outdoor swimming can help people with depression. AimThe aim of this study is to find out if taking part in an 8-session outdoor swimming course, along with usual care, is safe, helps improve depression, and is good value for money. We will compare people who do the swimming course (alongside their usual care) with people who only receive their usual care. In our study we will also talk to participants about their experiences. We want to understand how the outdoor swimming course affects their depression, and how the activity itself might help them feel better. Describe your research plan, includingPeople who are interested in taking part in the study can visit our website (outside2.co.uk) to read more information and sign up. Once someone agrees to join, they will be randomly placed into one of two groups available at their location to keep the study fair. One group will take part in eight one-hour outdoor swimming sessions in a small group. They will continue with their usual care for depression, which may include talking therapies, antidepressant medication, or community activities. The other group will continue with usual care only during the study. After the study ends, they will be offered the same outdoor swimming course, so no one misses out. The swimming sessions will be led by experienced swimming coaches who will help participants build confidence in the water and learn important water safety skills. During the study, all participants will complete questionnaires about their symptoms of depression, overall mental health, and use of health services. They will do these before they are put in a group, right after the swimming course or usual care period and six months later. Participants in the swimming group will also be asked to keep a diary about their experiences during the course. Researchers may visit some sessions to ask participants about how they are finding the swimming and how it affects their mood. Swim coaches will record attendance at each session and describe what activities were included. This helps the research team understand exactly what took place during each class. Knowledge mobilisationWe want to make sure that the information we learn from this study reaches many different people, not just scientists. To do this, we will share our findings in several ways. We will create a Podcast mini-series, an animated video as well as research papers. Using these different methods helps us share our findings with many groups, including adults in the community, mental health professionals, people working in the swimming industry, scientists, and policymakers. By sharing the results in several ways, more people can understand if and how outdoor swimming might support recovery from depression and mental health more broadly, and it increases the chance that the study will make a real difference, whatever it finds.

Evidence-based psychotherapies are first-line treatments for psychiatric disorders, yet response rates remain suboptimal. Noninvasive brain stimulation (NIBS) may augment psychotherapy by modulating treatment-engaged circuits. We conducted a systematic review and meta-analysis of randomized controlled trials comparing active NIBS plus evidence-based psychotherapy versus sham NIBS plus psychotherapy. Following Cochrane methods, we searched six databases through February 2025, screening 1,017 records. Twenty-eight trials (31 treatment arms; 1,506 participants) met inclusion criteria. Active NIBS combined with psychotherapy produced significantly greater symptom improvement than sham NIBS with psychotherapy (standardized mean difference = -0.38, 95% confidence interval [-0.68, -0.08]), with substantial heterogeneity. Moderator analyses revealed critical implementation parameters: repetitive transcranial magnetic stimulation (rTMS) showed significant benefit while transcranial direct current stimulation did not. Non-concurrent delivery--stimulation before or after psychotherapy sessions--was significantly effective, whereas concurrent administration was not. Among psychotherapy modalities, cognitive behavioral therapy combined with NIBS produced significant benefit. Human-delivered psychotherapy, but not computerized formats, significantly enhanced outcomes. By diagnosis, significant effects were observed only for anxiety disorders. Secondary analyses revealed significant anxiety symptom reduction specific to rTMS. Treatment integrity was under-reported: only 39.3% of studies used fully manualized protocols and 10.7% documented therapist adherence. Non-concurrent rTMS paired with human-delivered, manualized cognitive behavioral therapy emerges as the most effective strategy, particularly for anxiety disorders. These findings provide an evidence-based framework for optimizing combined treatment protocols and highlight the need for standardized psychotherapy fidelity monitoring in future trials.

BackgroundMajor depressive disorder (MDD), a leading cause of disability worldwide, exhibits substantial heterogeneity in treatment outcomes. Patients who do not respond to standard antidepressant therapy account for the majority of MDDs disease burden. Risk factors have been implicated in treatment response, including genes impacting on how antidepressants are metabolised. Yet, despite its clinical importance, risk factors for treatment-resistant depression (TRD) remain unexplored in low- and middle-income countries (LMIC). We used data from the DIVERGE study on MDD to investigate the risk factors of TRD in Pakistan. MethodsDIVERGE is a genetic epidemiological study that recruited adult MDD patients ([&ge;]18 years) between Sep 27,2021 to Jun 30, 2025, from psychiatric care facilities across Pakistan. Detailed phenotypic information was collected by trained interviewers and blood samples taken. Infinium Global Diversity Array with Enhanced PGx-8 from Illumina was used for genotyping followed by DRAGEN calling to infer metaboliser phenotypes for Cytochrome P450 (CYP) enzyme genes. We defined TRD as minimal to no improvement after [&ge;]12 weeks of adherent antidepressant therapy. We conducted multi-level logistic regression to test the association of demographic, clinical and pharmacogenetic variables with TRD. FindingsAmong 3,677 eligible patients, polypharmacy was rampant; 86% were prescribed another psychotropic drug along with an antidepressant. Psychological therapies were uncommon (6%) while 49% of patients had previously visited to a religious leader/faith healer in relation to their mental health problems. TRD was experienced by 34% (95%CI: 32-36%) patients. The TRD group was characterised by more psychotic symptoms and suicidal behaviour (OR=1.39, 95%CI=1.04-1.84, p=0.02; OR=1.03, 95%CI=1.01-1.05, p=0.005). Social support (OR=0.55, 95%CI=0.44-0.69, p=1.4x10-7) and parents being first cousins (OR=0.81, 95%CI=0.69-0.96, p=0.01) were associated with lower odds of TRD. In 1,085 patients with CYP enzyme data, poor (OR=1.85, 95%CI=1.11-3.07, p=0.01) and ultra-rapid (OR=3.11, 95%CI=1.59-6.12, p=0.0009) metabolizers for CYP2C19 had increased risk of TRD compared with normal metabolisers. InterpretationThere was an excessive use of polypharmacy in the treatment of depression while psychological therapies were uncommon highlighting the need for more evidence-based practice. This first large study of MDD from Pakistan uncovered the importance of culture-specific forms of social support in preventing TRD, highlighting opportunities for interventions in low-income settings. Pharmacogenetic markers can be leveraged to predict TRD.

Despite the global prevalence of postpartum depression (PPD), current referral uptake rates are far from satisfactory. While some qualitative studies have investigated factors affecting PPD referrals, a gap in quantitative analysis remains. Addressing this, our study utilized a discrete choice experiment (DCE) to understand the procedural elements influencing PPD referral uptake among diagnosed women. The DCE was conducted via home visits by healthcare providers and a comprehensive mobile app questionnaire. We constructed seven distinct referral attributes to explore participants' preferences, analyzed using mixed logit models and latent class analysis. This analysis identified key determinants and revealed the heterogeneities in referral preferences. A total of 698 individuals completed the DCE questionnaire. All assessed attributes, except for Accompaniment (going to clinic with a family member), were important determinants of preference. Participants generally preferred referrals to psychiatric clinics, face-to-face consultations, lower costs, and shorter waiting times. Significantly, participants' personal and socio-demographic characteristics also played a critical role in their referral preferences. Latent class analysis categorized participants into four distinct groups based on their preferences, with treatment cost and waiting times being the most decisive factors. In conclusion, the preference for PPD referrals is predominantly driven by convenience and access to specialist care. To enhance referral uptake, developing flexible and personalized referral programs that cater to these preferences is crucial.

Introduction Experiential acceptance refers to the capacity to be open to internal experiences without attempting to change or avoid them. Although acceptance is a core emotion regulation strategy within mindfulness- and acceptance-based interventions (MABIs) and a protective factor for mental health, its conceptualization and implementation remain unclear and ambiguous. The aim of this study was to clarify and develop a comprehensive model of accepting anxiety. Method Twenty-six participants from a non-clinical sample with prior experience in MABIs took part in semi-structured interviews exploring their experience of accepting anxiety. Data collection and analysis followed the principles of Grounded Theory to generate a data-driven model of the acceptance process. Results We identified a five-stage dynamic model involving distinct processes: (Stage 1) observing through the body with attentional focus on interoceptive experience; (Stage 2) identifying and acknowledging anxiety; (Stage 3) validating and normalizing the experience through validation and self-compassion; (Stage 4) not reacting characterized by decentering and nonreactivity; and (Stage 5) staying with the experience via exposure. We also identified facilitating factors that support engagement in the acceptance process. Conclusion These findings refine the understanding of acceptance as a multidimensional emotion regulation process by highlighting an active dynamic involving multiple mechanisms underlying the acceptance of anxiety. This model provides a framework for developing more targeted clinical interventions and for investigating individual and contextual variability in these subprocesses.

Background. Major depressive disorder (MDD) is characterized by altered frontal alpha oscillations. Transcranial alternating current stimulation (tACS) can normalize aberrant oscillations in MDD, yet the daily dynamics of tACS target engagement of alpha oscillations in depression remain unclear. Methods. In a double-blind randomized controlled trial (NCT03994081), 20 participants with MDD received verum or sham 10 Hz tACS (40 min/day, 5 days) targeted to left and right dorsolateral prefrontal cortex (F3/F4). High-density EEG was collected pre/post-stimulation each day to quantify within-session and cumulative changes in alpha power and functional connectivity (wPLI). Results. Verum stimulation produced late-emerging, session-specific alpha power decreases compared to sham, with robust day (D)4 post-pre reductions at both IAF and 10 Hz across frontal and parietal regions (t=-2.42 to -3.82, p<0.05; parietal t=-3.82, pFDR<0.05). Whole-brain topographical analysis confirmed a distinct condition x D4 effect at left prefrontal cortex (t=2.9, pFWE<0.05, cluster permutation). Connectivity changes emerged earlier and more transiently, with D2 bilateral frontal wPLI reductions (t=-2.53, p<0.05). Cumulative analyses (change from D1) showed significant wPLI decreases on D2 and D3 (t=-2.65 and t=-2.46; p<0.05). Exploratory clinical correlations showed that the D4 IAF power decrease was associated with increased reward sensitivity (spearman rho= -0.6, p<0.05, cluster-corrected). Conclusions. Alpha-tACS produced a temporally distinct neural response: an early, transient decrease in functional connectivity on D2, which may have driven a later suppression of left prefrontal alpha power on D4, correlated with clinical and behavioral improvements. These results delineate target engagement and validation mechanisms in a multi-day tACS trial, supporting optimized dosing in future tACS interventions.