May 2025

Objective: There is tremendous public health interest in cost-efficient, scalable interventions to improve post-disaster mental health. The authors examined the efficacy of Bounce Back Now (BBN), a mobile application, versus an enhanced usual care app (EUC). Methods: A population-based trial was conducted with a diverse sample of 1,357 adults affected by Hurricane Harvey, Irma, Maria, Florence, or Michael in 2017 and 2018. Participants were eligible if they were ≥18 years of age, had access to an Internet-accessible device, were English speaking, and lived in a hurricane-affected area. BBN is designed to address symptoms of posttraumatic stress, depression, and sleep disturbance using evidence-based techniques grounded in behavioral and cognitive principles. Depressive, posttraumatic stress, and sleep symptoms were measured. Results: Participants' accessing of the BBN and EUC apps was similar. Active engagement was significantly greater among BBN users than EUC users (d=0.31), but BBN users engaged more actively in coping skills activities than in more time-intensive elements designed to promote behavior change. Moderate symptom reduction was observed in both conditions; Cohen's d values for the 3-month postbaseline assessment ranged from 0.49 to 0.60 in the BBN condition and from 0.36 to 0.41 in the EUC condition. Latent change models revealed that BBN users had significantly greater reductions in depression, sleep difficulty, and PTSD symptoms than EUC users, and these differences were maintained at the 6-month and 12-month postbaseline assessments. Conclusions: Population impact is driven by reach and effectiveness. The potential reach of BBN is high, which heightens opportunity for population-level impact, but per-user symptom reduction was modest. Per-user impact may be improved by embedding digital health resources in the context of a broader health care strategy.

Objective: Rates of substance use disorders (SUDs) remain significantly above national targets for health promotion and disease prevention in Canada and the United States. This study investigated the 5-year SUD outcomes following a selective drug and alcohol prevention program targeting personality risk factors for adolescent substance misuse. Methods: The Co-Venture trial is a cluster randomized trial involving 31 high schools in the greater Montreal area that agreed to conduct annual health behavior surveys for 5 years on the entire 7th grade cohort of assenting students enrolled at the school in 2012 or 2013. Half of all schools were randomly assigned to be trained and assisted in the delivery of the personality-targeted PreVenture Program to all eligible 7th grade participants. The intervention consisted of a brief (two-session) group cognitive-behavioral intervention that is delivered in a personality-matched fashion to students who have elevated scores on one of four personality traits linked to early-onset substance misuse: impulsivity, sensation seeking, anxiety sensitivity, or hopelessness. Results: Mixed-effects multilevel Bayesian models were used to estimate the effect of the intervention on the year-by-year change in probability of SUD. When baseline differences were controlled for, a time-by-intervention interaction revealed positive growth in SUD rate for the control group (b=1.380, SE=0.143, odds ratio=3.97) and reduced growth for the intervention group (b=-0.423, SE=0.173, 95% CI=-0.771, -0.084, odds ratio=0.655), indicating a 35% reduction in the annual increase in SUD rate in the intervention condition relative to the control condition. Group differences in SUD rates were reliably nonzero (95% confidence) at the fourth and fifth year of assessment. Secondary analyses revealed no significant intervention effects on growth of anxiety, depression, or total mental health difficulties over the four follow-up periods. Conclusions: This study showed for the first time that personality-targeted interventions might protect against longer-term development of SUD.

Importance: Treatment-resistant depression (TRD) is a major challenge in mental health, affecting a significant number of patients and leading to considerable burdens. The etiological factors contributing to TRD are complex and not fully understood. Objective: To investigate the genetic factors associated with TRD using polygenic scores (PGS) across various traits and explore their potential role in the etiology of TRD using large-scale genomic data from the All of Us (AoU) Research Program. Design, setting, and participants: This study was a cohort design with observational data from participants in the AoU Research Program who have both electronic health records and genomic data. Data analysis was performed from March 27 to October 24, 2024. Exposures: PGS for 61 unique traits from 7 domains. Main outcomes and measures: Logistic regressions to test if PGS was associated with treatment-resistant depression (TRD) compared with treatment-responsive major depressive disorder (trMDD). Cox proportional hazard model was used to determine if the progressions from MDD to TRD were associated with PGS. Results: A total of 292 663 participants (median [IQR] age, 57 (41-69) years; 175 981 female [60.1%]) from the AoU Research Program were included in this analysis. In the discovery set (124 945 participants), 11 of the selected PGS were found to have stronger associations with TRD than with trMDD, encompassing PGS from domains in education, cognition, personality, sleep, and temperament. Genetic predisposition for insomnia (odds ratio [OR], 1.11; 95% CI, 1.07-1.15) and specific neuroticism (OR, 1.11; 95% CI, 1.07-1.16) traits were associated with increased TRD risk, whereas higher education (OR, 0.88; 95% CI, 0.85-0.91) and intelligence (OR, 0.91; 95% CI, 0.88-0.94) scores were protective. The associations held across different TRD definitions (meta-analytic R2 >83%) and were consistent across 2 other independent sets within AoU (the whole-genome sequencing Diversity dataset, 104 388, and Microarray dataset, 63 330). Among 28 964 individuals followed up over time, 3854 developed TRD within a mean of 944 days (95% CI, 883-992 days). All 11 previously identified and replicated PGS were found to be modulating the conversion rate from MDD to TRD. Conclusions and relevance: Results of this cohort study suggest that genetic predisposition related to neuroticism, cognitive function, and sleep patterns had a significant association with the development of TRD. These findings underscore the importance of considering psychosocial factors in managing and treating TRD. Future research should focus on integrating genetic data with clinical outcomes to enhance understanding of pathways leading to treatment resistance.

Importance: Maternal inflammation during pregnancy has been associated with an increased risk of neurodevelopmental disorders (NDDs), such as attention-deficit/hyperactivity disorder (ADHD) and autism, and cognitive deficits in early childhood. However, little is known about the contributions of a wider range of inflammatory proteins to this risk. Objective: To determine whether maternal inflammatory proteins during pregnancy are associated with the risk of NDDs and executive functions (EF) in middle childhood and to identify protein patterns associated with NDDs and EF. Design, setting, and participants: This was a 10-year follow-up cohort study of the Danish Copenhagen Prospective Studies on Asthma 2010 mother-child birth cohort, using plasma samples collected at week 24 in pregnancy, where 92 inflammatory proteins were assessed. NDDs and EF were assessed in the offspring at age 10 years, between January 2019 and December 2021. Mother-offspring dyads with available maternal prenatal inflammatory proteins during pregnancy and offspring NDD psychopathology data at follow-up were included. Data analyses took place between December 2023 and August 2024. Exposures: Levels of 92 inflammatory proteins from panel collected at week 24 during pregnancy. Main outcomes and measures: Categorical and dimensional psychopathology of NDDs (primary outcome) and EF (secondary outcome). Results: A total of 555 mothers (mean [SD] age, 32.4 [4.3] years) and their children (285 male [51%]) were included. The principal component analysis showed that higher levels of maternal inflammatory proteins depicted in principal component 1 were associated with a higher risk of any NDD (OR, 1.49; 95% CI, 1.15-1.94; P = .003), particularly autism (OR, 2.76; 95% CI, 1.45-5.63; P = .003) and ADHD with predominantly inattentive presentation (OR, 1.57; 95% CI, 1.05-2.39; P = .03). The single protein analysis showed that 18 of 92 proteins reached false discovery rate (FDR) 5% significance after adjustment. Vascular endothelial growth factor A, C-C motif chemokine ligand, CD5, interleukin 12B, fibroblast growth factor-23, and monocyte chemoattractant protein-1 emerged as top proteins associated with risk of NDDs. The sparse partial least squares approach identified 34 proteins associated with any NDD, and 39 with ADHD with predominantly inattentive presentation. There were no associations with EF after FDR correction. Conclusions and relevance: The maternal inflammatory proteome during pregnancy was associated with NDDs risks in offspring at age 10 years. Further research is warranted to elucidate the specific pathways involving these proteins during pregnancy that could be targeted with prevention strategies to reduce risk of NDDs in children.

Objective: To examine the associations of serotonergic antidepressant exposure during pregnancy with the risk of depression and anxiety disorders in offspring. Method: The Mayo Clinic Rochester Epidemiology Project medical records-linkage system was used to study offspring born to mothers who were prescribed a selective serotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor (S/NRI users, n = 837) during pregnancy (1997-2010). Cox regression models were used to calculate hazard ratios to examine associations of S/NRIs with diagnosed depression and anxiety, defined based on a review of medical records by 2 board-certified psychiatrists, vs no maternal antidepressant use during pregnancy (nonusers, n = 863) and maternal antidepressant use in the year prior to pregnancy (former users, n = 399) as control groups. Results: After all adjustments for covariates, children born to S/NRI users during pregnancy did not differ in onset of depression or anxiety from the children of nonusers (adjusted hazard ratio = 1.00, 95% CI [0.74, 1.85]) or former users (adjusted hazard ratio = 0.94, 95% CI [0.69, 1.27]). These associations were similar when exposure was limited only to selective serotonin reuptake inhibitors. Conclusion: The results suggest that higher rates of childhood and adolescent depression or anxiety conditioned on maternal S/NRI use in pregnancy are more likely to be driven by maternal depression or underlying propensity for depression rather than direct pharmacological effects of in utero S/NRI exposure.

Background: Nutraceuticals have been taken as an alternative and add-on treatment for depressive disorders. Direct comparisons between different nutraceuticals and between nutraceuticals and placebo or antidepressants are limited. Thus, it is unclear which nutraceuticals are the most efficacious. Methods: We conducted a network meta-analysis to estimate the comparative efficacy and tolerability of nutraceuticals for the treatment of depressive disorder in adults. The primary outcome was the change in depressive symptoms, as measured by the standard mean difference (SMD). Secondary outcomes included response rate, remission rate, and anxiety. Tolerability was defined as all-cause discontinuation and adverse events. Frequentist random-effect NMA was conducted. Results: Hundred and ninety-two trials involving 17,437 patients and 44 nutraceuticals were eligible for inclusion. Adjunctive nutraceuticals consistently showed better efficacy than antidepressants (ADT) alone in outcomes including SMD, remission, and response. Notable combinations were Eicosapentaenoic acid + Docosahexaenoic Acid plus ADT (EPA + DHA + ADT) (SMD 1.04, 95% confidence interval 0.64-1.44), S-Adenosyl Methionine (SAMe) + ADT (0.99, 0.31-1.68), curcumin + ADT (1.03, 0.55-1.51), Zinc + ADT (1.59, 0.63-2.55), tryptophan + ADT (1.24, 0.32-2.16), and folate + ADT (0.64, 0.17-1.10). Additionally, four nutraceutical monotherapies demonstrated superior efficacy compared to ADT: EPA + DHA (0.6, 0.32-0.88), SAMe (0.52, 0.18-0.87), curcumin (0.62, -0.17 to 1.40) and saffron (0.69, 0.34-1.04). It is noted that EPA + DHA, SAMe, and curcumin showed strong performance as either monotherapies or adjuncts to ADT. Most nutraceuticals showed comparable tolerability to placebo. Conclusions: This extensive systematic review and NMA of nutraceuticals for treating depressive disorders indicated a number of nutraceuticals that could offer benefits, either as adjuncts or monotherapies.

While antipsychotic maintenance treatment effectively prevents relapse after a first psychotic episode, many remitted antipsychotic users wish to reduce or discontinue their medication, due to side effects, long-term health concerns, stigma, or the desire to regain autonomy. Current guidelines suggest gradual tapering, but what the optimal speed of this tapering should be, especially in patients who remitted from a first psychotic episode, remains unclear. Furthermore, D2 receptor affinity of the antipsychotic drug may also affect relapse risk. This study examined relapse risk and time to relapse, within the first 18 months after remission from a first psychotic episode, in 227 individuals who tapered antipsychotic medication. Relapse was defined dichotomously using consensus criteria based on the Positive and Negative Syndrome Scale, hospitalization for psychosis, or explicit clinical judgement of the treating psychiatrist. Tapering speed (in olanzapine equivalents mg/day) was calculated as the difference of antipsychotic dose between the start and the end of tapering, divided by the number of days in between. Antipsychotics were classified into partial D2 agonists, or antagonists with low or high D2 affinity. Logistic and Cox proportional hazards regression analyses were controlled for age, sex, cannabis use, and duration of first psychotic episode, as well as for differences in clinical and sociodemographic characteristics between the three drug D2 affinity groups using inverse probability of treatment weighting. During the follow-up period, 45.8% (N=104) of participants experienced a relapse after tapering. The average tapering speed was 10 mg olanzapine equivalents over 75 days, with an average tapering duration of 124 days (range: 6-334 days). Logistic regression analysis showed that the tapering speed did not predict the risk of relapse (z=0.989, p=0.323). Compared with users of high D2 affinity antagonists (N=57), patients using low D2 affinity antagonists (N=116) and partial D2 agonists (N=54) had a lower risk of relapse (respectively, z=-2.104; odds ratio, OR=0.48, p=0.035; and z=-2.278, OR=0.44, p=0.023). Users of high D2 affinity antagonists had a shorter time between the end of tapering and relapse (mean: 280 days) than low D2 affinity antagonist users (mean: 351 days, p=0.027) and partial D2 agonist users (mean: 357 days, p=0.040). Thus, D2 receptor affinity of the antipsychotic was more important than tapering speed in predicting psychotic relapse risk in individuals remitted from a first psychotic episode. Users of high D2 affinity antipsychotics had an about twice higher risk of relapse than users of other types of antipsychotics. This higher risk of relapse after tapering should be regarded as a relevant factor when selecting an antipsychotic drug for people with a first psychotic episode. For patients using strong D2 antagonists after remission from a first psychotic episode, extra monitoring during tapering is required.

Although clozapine is the most effective medication for treatment-resistant schizophrenia, response is inadequate in over half of people with that condition. There is limited guidance available on effective clozapine augmentation strategies. We studied the comparative effectiveness of specific doses of oral olanzapine, quetiapine, risperidone and aripiprazole augmentation of clozapine treatment on the risk of hospitalization due to a psychotic episode, as a marker for severe relapse, among patients with schizophrenia or schizoaffective disorder. In this population-based study, patients with one of those diagnoses receiving clozapine were identified from Finnish (years 1995-2017, N=14,053) and Swedish (years 2006-2021, N=8,743) nationwide registers. The risk of hospitalization due to a psychotic episode associated with periods of antipsychotic augmentation of clozapine treatment vs. same-dose clozapine monotherapy was assessed by a within-individual design, using each individual as his/her own control to eliminate selection bias, and analyzed with stratified Cox models. The two national cohorts were first analyzed separately; then results were combined using a random-effect meta-analysis. Secondary outcomes were somatic hospitalization, and hospitalization for psychosis or a somatic cause. The only augmentation associated with a significantly decreased risk of hospitalization due to psychosis in both countries was medium-dose (9 to <16.5 mg/day) aripiprazole combined with high-dose (≥330 mg/day) clozapine, and this combination was associated with the best outcome in the meta-analysis (adjusted hazard ratio, aHR=0.68, 95% CI: 0.62-0.75, p<0.0001). Among patients using medium-dose (180 to <330 mg/day) clozapine, medium-dose aripiprazole augmentation was the only treatment more effective than clozapine monotherapy after Bonferroni correction (aHR=0.79, 95% CI: 0.70-0.91, p=0.0006). The use of all high-dose augmentations was associated with an increased risk of hospitalization due to psychosis. Only aripiprazole augmentations were associated with a decreased risk of hospitalization for psychosis or a somatic cause, and the lowest risk was observed for medium-dose aripiprazole plus high-dose clozapine (aHR=0.70, 95% CI: 0.58-0.84, p=0.0001). This meta-analysis of two nationwide cohorts, totaling almost 23,000 patients using clozapine, indicates that medium-dose aripiprazole augmentation of clozapine treatment is associated with a 20-30% decreased risk of severe relapse compared with clozapine monotherapy within the same individuals, while augmentation with higher doses of aripiprazole (as well as with high doses of all other antipsychotics) is associated with an increased relapse risk.

Real-world studies provide valuable insights into long-term outcomes across diverse populations. Here, we contextualise recent findings on the association between antipsychotic use and breast cancer risk in women with schizophrenia. We discuss clinical implications and the strengths and limitations of real-world studies in psychiatry. We conclude with future perspectives.

Background: Aripiprazole, a prolactin-sparing antipsychotic, is considered relatively safe during pregnancy and has a better metabolic profile compared to other antipsychotics. However, its impact on lactation has not been adequately studied. This study aimed to assess the relationship between aripiprazole use during pregnancy and the postpartum period with lactation outcomes. Methods: Clinical charts of women attending perinatal psychiatry services between January 2016 and December 2021 were reviewed for details of aripiprazole prescription, clinical information, and lactation outcomes. Lactation failure was defined as the total absence of milk flow or secretion of minimal amounts for at least 7 days. Results: Among the 398 women attending perinatal psychiatry services, 60 were prescribed aripiprazole during pregnancy, with lactation data available for 35 women who continued the drug during the postpartum period. The mean age of women in years was 29 (±4.4) years. The most common diagnosis for aripiprazole prescription was schizophrenia (60%). Approximately 54.2% of the women were primiparous. Of the 35 women with available lactation data, 26 (74%) experienced complete lactation failure, and 4 (11%) had insufficient milk production while on aripiprazole. The mean dose of aripiprazole was 16.4 mg/day, with a mean duration of use of 20 months. Conclusions: In this study, most women who continued aripiprazole through pregnancy and postpartum experienced either lactation failure or insufficient milk production. It is important to discuss lactation issues associated with the use of aripiprazole with women during pregnancy and the postpartum period.

Background: Electroconvulsive therapy (ECT) is the most effective treatment of major depression, but autobiographical memory loss may limit its use. Despite previous attempts to synthesise the literature, the nature of autobiographical memory loss after ECT is still debated. Aims: To provide an overview of the effect of ECT on autobiographical memory in patients with depression and explore whether the effect is temporary or permanent. Furthermore, we wanted to analyse if ECT parameters or clinical information are associated with this effect. Method: PubMed, EMBASE, PsycINFO and Web of Science databases were searched on 26 January 2024. We included longitudinal studies measuring autobiographical memory before and after ECT in patients with depression compared to patients with depression receiving other treatment or healthy controls. Synthesis approach was a meta-analysis. PROSPERO ID: CRD42021267901. Results: Nine studies were included (432 patients, 173 controls). At post-ECT, we found that ECT patients had larger autobiographical memory loss than controls (standardised mean difference (SMD) = 0.55; 95% CI = 0.35-0.75). Right unilateral (RUL) ECT entailed a small effect on autobiographical memory (SMD = 0.32; 95% CI = 0.06-0.57), while bilateral ECT yielded a large effect (SMD = 0.82; 95% CI = 0.49-1.15). Higher age was associated with smaller effect. Autobiographical memory was stable at long-term follow-up. Conclusions: The studies suggest that ECT causes autobiographical memory loss in patients with depression. Results also suggest that lost memories are not regained. Furthermore, results support that RUL ECT is less detrimental to autobiographical memory. Strangely, a higher age might mitigate the autobiographical memory loss. Our findings are limited by studies being mainly observational and generally consisting of small sample sizes. Future studies should prioritise long-term follow-up assessments of autobiographical memory.

Background: Selective serotonin reuptake inhibitors (SSRIs) are the preferred pharmacological treatment for obsessive-compulsive disorder (OCD). However, insufficient response is common and it remains unclear whether specific patient-level factors influence the likelihood of treatment response. Aims: To determine the efficacy and acceptability of SSRIs in adult OCD, and to identify patient-level modifiers of efficacy. Methods: We conducted an individual patient data meta-analysis (IPDMA) of industry-sponsored short-term, randomised, placebo-controlled SSRI trials submitted for approval to the Dutch regulatory agency to obtain marketing approval for treating OCD in adults. We performed a two-stage meta-analysis, using crude data of available trials. The primary outcome was the difference in Yale-Brown Obsessive-Compulsive Scale (YBOCS) change between active treatment and placebo. Secondary outcomes were differences in response (defined as the odds ratio of ≥35% YBOCS point reduction) and acceptability (defined as the odds ratio for all-cause discontinuation). We examined the modifying effect of baseline characteristics: age, gender, illness severity, depressive symptoms, weight, illness duration and history of antidepressant use. Results: After excluding three trials because of missing data, we analysed results from 11 trials (79% of all submitted trials, n = 2372). The trial duration ranged from 10 to 13 weeks. Mean difference of SSRIs relative to placebo was 2.65 YBOCS points (95% CI 1.85-3.46, p < 0.0001), equalling a small effect size (0.33 Hedges' g). The odds ratio for response was 2.21 in favour of active treatment (95% CI 1.72-2.83, p < 0.0001), with a number needed to treat of seven. Patient characteristics did not modify symptom change or response. Acceptability was comparable for SSRIs and placebo. Conclusions: Our IPDMA showed that SSRIs are well accepted and superior to placebo for treating OCD. The effects are modest and independent of baseline patient characteristics.

Background: Anhedonia is a core diagnostic symptom of major depressive disorder (MDD). Post hoc analyses evaluated cariprazine plus antidepressant treatment (ADT) in patients with MDD and moderate-to-severe anhedonia. Methods: Data were analyzed from a positive phase 3, randomized, fixed-dose (1.5 or 3 mg/d), double-blind, placebo-controlled, parallel-group cariprazine study (NCT03738215). Post hoc outcomes (e.g., change from baseline to week 6 in MADRS total score, MADRS anhedonia subscale score, MADRS anhedonia subscale item scores including item 8 [inability to feel]) were assessed in 2 anhedonia patient subgroups (baseline MADRS anhedonia subscale score ≥ 18; baseline MADRS anhedonia item 8 score ≥ 4) using a mixed-effects model for repeated measures. Results: Most patients met subgroup inclusion criteria (anhedonia subscale score ≥ 18 = 584 [77.8 %]; anhedonia item 8 score ≥ 4 = 508 [67.6 %]). LSMDs in change from baseline were statistically significant in favor of adjunctive cariprazine versus adjunctive placebo in the MADRS anhedonia subscale score ≥ 18 subgroup (MADRS total score: 1.5 mg/d = -3.4, p = .0006; 3 mg/d = -2.1, p = .0358; anhedonia subscale score: 1.5 mg/d = -2.1, p = .0010; 3 mg/d = -1.26, p = .0399) and in the anhedonia item 8 score ≥ 4 subgroup for adjunctive cariprazine 1.5 mg/d (MADRS total score: -3.2, p = .0037; anhedonia subscale score: -1.9, p = .0066). Significant differences were seen for adjunctive cariprazine versus adjunctive placebo on several anhedonia subscale single items, including anhedonia item 8 for the 1.5 mg/d dose. Limitation: Post hoc analysis. Conclusion: In patients with MDD and moderate-to-severe anhedonia, adjunctive cariprazine improved symptoms of general depression and anhedonia, suggesting a potential benefit for patients with this clinically significant symptom.

Context: High-frequency (HF) transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is widely used in Major Depressive Episode (MDE). Optimization of its efficacy with a neuro-navigation system has been proposed based on a small randomized controlled trial (RCT) supporting a large effect. Method: This evaluator- and patient-blind, multicenter RCT assessed the superiority in terms of efficacy of 10 HF rTMS sessions of the left DLPFC targeted with MRI based neuro-navigation versus similar sessions targeted by the standard 5 cm technique. The study was conducted between January 2013 and April 2017, at 4 hospitals centers in France where both in- and out- patients with MDE were included. Randomization was computer-generated (1:1), with allocation concealment implemented within the e-CRF. The main outcome measure was the percentage of responders 44 days (D44) after the rTMS session. Secondary outcomes were percentage of remitters, Beck Depression Inventory and psychomotor retardation assessed with Salpêtrière retardation rating scale (SRRS) for depression at D14 and D44. The results are presented along with their 95% confidence intervals. Results: 105 patients were randomized and 92 were evaluable with respectively 45 patients in the neuronavigation group and 47 in the standard group. A treatment response was observed for 14 (31.8%) of 44 patients analyzed in the intervention group, and for 16 (35.6%) of 45 patients analyzed in the control group with no statistical difference (relative risk 0.89; 95% confidence interval, [0.50;1.61]). No difference was evidenced for secondary outcomes at D44 whether it concerns remission at D44 (relative risk, 0.82; 95% CI, 0.36 to 1.88), or BDI results (difference in means, 0,01; 95% CI, -3.06 to 3.26), or SRRS results (difference in means, 0.11; 95% CI, -2.42 to 5.02). Similar results were observed at D14. Rates of adverse events were similar in both groups with 23 (47.9%) and 1 (2.1%) of adverse events and serious adverse events in the neuro-navigation group versus 20 (40.8%) and 0 (0%) in the standard group. Discussion: This study failed to reproduce previous findings supporting the use of neuro-navigation system to optimize rTMS efficacy. Limitations of this study includes a small sample size and a number of rTMS sessions that may appear substandard in 2025.

Since the COVID-19 pandemic, there has been an exponential rise in mental health crises among youth, particularly with depressive symptoms.1 More than 1 in 5 children and adolescents worldwide experience depressive symptoms or meet criteria for major depressive disorder,2 highlighting a critical public health challenge. Although physical activity has long been considered a protective factor against depression, most published research has relied on cross-sectional or short-term studies. This editorial will review and contextualize the recent study by Steinsbekk and colleagues,3 which provides crucial insights into the dynamic relationship between physical activity and depressive symptoms by leveraging objective measures and a longitudinal, within-person analytical approach from childhood through adolescence.

American conservatives tend to rate their mental health more positively than their liberal counterparts. One explanation for this finding is that conservatives may be more likely to justify existing inequalities in society, leading to a palliative effect on their mental health that does not happen for liberals. Conservatives also score higher on personality and attitude measures, such as religiosity, marital status, and patriotism, which are associated with better mental health. We examine whether this ideological mental health gap holds for a different facet of well-being that is closely related to mental health. Further, we suggest that the ideological mental health gap may have more to do with a stigmatized reaction to the term "mental health" which has become increasingly politicized in the US context since its introduction to literature in the early 20th century. First, we examine whether the conservative-liberal divide in self-assessments of mental health remains once we control for a wide variety of demographics, socioeconomic factors, and recent life experiences. We find that accounting for these alternative explanations reduces the gap by about 40%, but that ideology remains a strong predictor of mental health self-reports. Second, we conducted an experiment where we randomly assigned whether people were asked to evaluate their mental health or their overall mood. While conservatives report much higher mental health ratings, asking instead about overall mood eliminated the gap between liberals and conservatives. One explanation is that rather than a genuine mental health divide, conservatives may inflate their mental health ratings when asked, due to stigma surrounding the term. Another possibility is that ideological differences persist for some aspects of mental well-being, but not others.