Digital interventions for promoting relaxation are increasingly popular, yet few combine multiple sensory modalities. This study evaluated the effectiveness of a fully digital relaxation program combining hypnotherapy with aromatherapy and explored whether the scent can induce a conditioned relaxation effect.

In this four-arm randomized controlled trial (N = 504), participants were assigned to one of four groups for a 4-week intervention: (a) combined (hypnotherapy + aromatherapy), (b) hypnotherapy-only, (c) aromatherapy-only, or (d) control (minimal intervention pause). Sessions were self-guided and delivered online every 2 days. The primary outcome was subjective calmness, assessed via the calmness–restlessness subscale of the Multidimensional Mood Questionnaire. Secondary outcomes included perceived stress (PSS-10) and well-being (WHO-5). A fifth week with aromatherapy-only exposure was conducted in the combined and aromatherapy-only groups to test for conditioning.

At post-intervention, both hypnotherapy-involved groups reported significant greater calmness than controls. The combined group showed a mean difference of β = 2.08 (95% CI: 0.50–3.65, p = 0.010, d = 0.38), while the hypnotherapy-only group showed β = 1.80 (95% CI: 0.24–3.37, p = 0.024, d = 0.33). Both effects were consistent across intention-to-treat and per-protocol analyses. Within-group improvements in calmness were also observed across all groups. No significant differences emerged from the conditioning test in week 5.

Digital hypnotherapy improved relaxation, with modest added benefit from aromatherapy. The results support the use of multisensory digital tools to enhance subjective calmness. However, no evidence for conditioned effects of the scent was observed under the current conditions.

Childhood trauma is common in functional motor disorder (FMD), but it is unclear whether specific trauma dimensions are differentially linked to symptom burden, and whether depression, anxiety, or multimorbidity can mediate these associations.

We conducted a cross-sectional case–control study including 322 patients with clinically definite FMD and 215 neurologically healthy controls, balanced with respect to age and sex. Six outcomes – motor symptom severity, cognitive complaints, depression, anxiety, fatigue, and pain – were jointly modeled using Bayesian multivariate regression with Childhood Trauma Questionnaire subscales as predictors. Bayesian structural equation modeling tested mediation by depression, anxiety, and multimorbidity.

In FMD, emotional abuse was the most consistent trauma correlate, associated with higher depression (β = 0.37, 95% CrI 0.22–0.51), anxiety (β = 0.32, 95% CrI 0.16–0.47), cognitive complaints (β = 0.27, 95% CrI 0.11–0.42), fatigue (β = 0.17, 95% CrI 0.03–0.32), and motor symptom severity (β = 0.15, 95% CrI 0.04–0.25). Mediation analyses indicated that affective symptoms fully accounted for trauma–symptom associations (indirect effect β = 0.42, 95% CrI 0.27–0.56). Multimorbidity was associated with more severe affective symptoms (β = 0.24, 95% CrI 0.12–0.37) and FMD symptoms (β = 0.24, 95% CrI 0.07–0.42) but did not mediate trauma–symptom relationships.

Emotional abuse is a key developmental risk factor for FMD, with its effects on symptom severity mediated by depression and anxiety. Multimorbidity increases symptom burden but is not a primary pathway linking trauma to FMD. Findings support routine trauma and affective symptom screening in FMD and targeted psychotherapeutic interventions.

Exposure to major life stressors and aberrant brain functioning have been related to anxiety and depression in adolescence. However, whether these associations differ based on the specific characteristics of the stressors and/or brain functional networks remains unclear.

In a longitudinal sample of adolescents enriched for anxiety and depressive disorders, we examined cumulative lifetime stressor frequency and severity of five stressor characteristics: physical danger, interpersonal loss, humiliation, entrapment, and role change/disruption. Anxiety and depression symptoms were assessed at three time points: baseline, 6-month, and 12-month follow-ups. Linear mixed-effect models tested if lifetime frequency and severity of these stressor characteristics were associated with anxiety and depression symptoms across the three time points. We also identified whole-brain resting-state functional connectivity (RSFC) features linked to the predictive stressor characteristics and examined their associations with anxiety and depression symptoms across time.

Controlling for all other stressor characteristics and covariates, lifetime frequency and severity of humiliation and entrapment predicted greater anxiety and depression symptoms across the three time points. After additionally accounting for co-occurring depression and anxiety symptoms, only entrapment frequency and severity remained significant. More negative RSFC between the frontoparietal network and the left cerebellum were linked to greater entrapment severity at baseline, and associated with greater anxiety and depression symptoms across time.

Our study highlights lifetime exposures to humiliation and entrapment as central stressor characteristics linked to adolescent internalizing symptoms. Our results also suggest that frontoparietal–left cerebellar connectivity may be a stress-sensitive marker of adolescent internalizing problems over time.

Increasing evidences show that inflammation might be involved in bipolar disorder (BD), but the association between abnormal brain function and inflammation in BD is still unclear. In this study, we tried to explore the disrupted brain functional network topology, peripheral inflammatory cytokine levels, and their correlations in unmedicated bipolar II depression (BDII-D).

In this study, 65 individuals with unmedicated BDII-D and 50 healthy controls (HCs) underwent resting-state magnetic resonance imaging scans. Graph theory analysis was performed to investigate the topological properties of the whole-brain functional connectome at both global and nodal levels. Besides, serum levels of 17 inflammatory cytokines were measured in both BDII-D and HCs. Correlations between topological properties, clinical variables, and peripheral inflammatory cytokine levels in BDII-D were calculated.

Compared with HCs, at the global level, BDII-D showed significantly higher $ \lambda $, decreased $ \gamma $, $ \sigma $, Eglo, and Eloc; at the nodal level, BDII-D showed decreased Enodal in the right olfactory cortex, left pallidum, and vermis. Besides, BDII-D showed higher levels of interleukin-8 (IL-8), interleukin-10 (IL-10), and granulocyte colony-stimulating factor (G-CSF) compared with the HCs. In BDII-D, $ \gamma $ and $ \sigma $ were significantly negatively correlated with the Hamilton Depression Rating Scale (HDRS) scores and number of episodes. Also, IL-8 level showed significant negative correlation with $ \gamma $, $ \sigma $, and Enodal of the left pallidum in BDII-D.

Reduced information segregation and integration, and lower nodal efficiency in the left pallidum were associated with proinflammatory cytokine IL-8 level and might contribute to severe depressive symptoms in unmedicated BDII-D.

Parental violent offending and offspring suicidal behavior are associated, but a deeper understanding of the risk within this population is needed to best identify and support those most in need. This study examined the risk of suicidal behavior among offspring of parents with violent convictions, primarily aiming to identify high-risk subgroups.

The study included 2,956,465 individuals born in Sweden 1977–2010, and their parents. Data were obtained from nationwide registers available until the end of 2020. The authors examined the risk of suicidal behavior among offspring with none, one, or both parents with violent convictions by offspring’s age 10, and further investigated the risk among exposed offspring by parental psychiatric disorders, child–parent coresiding, and other factors. Children-of-siblings analyses were conducted to better understand the nature of the association.

There were 254,793 (8.6%) and 11,777 (0.4%) offspring with one or both parents with violent convictions. Absolute risk of suicidal behavior was highest among those with both parents convicted; 14.3% (95% CI, 13.0–15.7) of male and 16.6% (95% CI, 15.3–18.0) of female offspring engaged in suicidal behavior by age 30, compared to 4%–4.5% of offspring of parents without convictions. The more adversities accumulated in families with parental offending, the higher the cumulative incidence of suicidal behavior. Genetic factors partly accounted for the association.

Offspring of parents with violent convictions are a group at high risk of suicidal behavior in need of early identification, multiagency coordination, and measures to reduce the risk of self-harm and suicide.

The triglyceride–glucose (TyG) index, a surrogate marker for insulin resistance, has been associated with depressive symptoms, but findings are inconsistent and predominantly based on cross-sectional studies. This study investigated whether the TyG index is associated with incident depression independent of genetic predisposition and explored potential risk factors underlying this association.

A total of 335,586 UK Biobank participants without baseline depression were included. Incident depression cases were extracted by linking electronic health records. Polygenic risk scores quantified genetic predisposition. Cox proportional hazards models examined the associations. We further evaluated the contribution of socioeconomic status (education, employment, and Townsend Deprivation Index), lifestyle factors (smoking, alcohol consumption, physical activity, and sleep duration), biological indicators (body mass index and total cholesterol), and health conditions (hypertension, diabetes, and cardiovascular disease). No preregistered protocol was used.

During a mean follow-up of 13.1 years, 14,096 (4.2%) individuals developed depression. Compared with the lowest TyG quartile (Q1), the fully adjusted hazard ratios (95% confidence intervals) for Q2, Q3, and Q4 were 1.051 (1.000–1.104), 1.078 (1.025–1.134), and 1.144 (1.086–1.206), respectively (P for trend <0.001). Per standard deviation increment in the TyG index was associated with a 5.9% (3.9%–7.8%) higher risk of depression. Individuals with both high TyG levels and high genetic predisposition had the highest risk, although no significant interaction was observed. All adjusted risk factors appeared to attenuate 63.9% of the association.

A higher TyG index was associated with increased risk of incident depression, independent of genetic predisposition.

While clinical research on psychedelics often reports mild and transient side effects, broader survey studies indicate that a subset of users experiences lasting adverse mental health effects. This study investigated whether some of these meet diagnostic criteria for post-traumatic stress disorder (PTSD).

A cross-sectional online survey (N = 243) was conducted with individuals reporting distressing psychedelic experiences with effects persisting beyond the acute phase (convenience sampling). It assessed characteristics of the acute experience, post-traumatic stress, post-traumatic growth, and coping strategies.

A total of 31.3% of participants met the DSM-5 criteria for PTSD as measured by self-report measures. PTSD symptom severity was strongly associated with characteristics of the acute experience. Avoidance-related experiences significantly predicted greater PTSD symptoms, while acceptance-related experiences were linked to lower symptom severity. Post-traumatic growth was unrelated to the intensity of the challenging experience or avoidance but positively predicted by acceptance-related experiences. Post-psychedelic help-seeking behavior was common: most consulted online resources or spoke with friends and family, though psychotherapy was rated the most helpful intervention.

Findings provide the first systematic evidence that difficult psychedelic experiences can be associated with later PTSD symptoms and highlight the critical role of acute psychological processes in shaping long-term outcomes. Since the survey targeted individuals with highly challenging acute experiences, the data do not allow the extrapolation of prevalence estimates to the broader population of psychedelic users. As psychedelic use expands beyond clinical settings, access to trauma-informed care and targeted integration support will be essential to minimize harm and support recovery.

Child maltreatment is strongly linked to depression, yet comparisons across maltreatment forms have been inconsistent. Prior meta-analyses mostly used single-level models and combined studies assessing different subsets of maltreatment forms, introducing statistical dependence and between-samples confounds that can distort cross-form comparisons.

We synthesized data from 12 eligible meta-analytic reviews (those assessing at least emotional, physical, and sexual abuse, and providing effect size data), extracting 563 effect sizes from 217 depression risk studies and 501 effect sizes from 157 depression severity studies. Meta-analyses used two-level random-effects multilevel models, accounting for within-study dependence. Initial analyses compared all abuse forms plus emotional and physical neglect. Subsequent analyses compared just abuse forms either from samples assessing all three (‘complete-abuse’ samples) or only one or two (‘incomplete-abuse’ samples), which addressed between-samples confounds.

Effect sizes for different maltreatment forms were strongly correlated within studies (median rs ≈ .46–.48), confirming statistical dependence. Across all analytic layers, emotional abuse showed the strongest association with depression, and sexual abuse the weakest. In complete-abuse studies – the most internally comparable designs – a clear hierarchy emerged: emotional abuse > physical abuse > sexual abuse for both risk and severity. Incomplete-abuse studies obscured these differences.

By modeling effect size dependence and reducing between-samples confounds, this study provides clearer evidence that emotional maltreatment – particularly emotional abuse – is most strongly linked to depression. These findings underscore the need for greater clinical and prevention focus on emotional forms of maltreatment.

Transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) is poorly managed, with discontinuity of care commonplace, leading to poorer outcomes, while evidence-based interventions to improve transition are scarce. This study is a secondary analysis of the MILESTONE trial, aiming to determine whether managed transition increases the proportion of young people who appropriately transition from CAMHS to AMHS.

The MILESTONE trial was a multicenter, two-arm, cluster-randomized controlled trial across eight countries at 40 CAMHS sites to compare usual care (UC) to managed transition (MT). MT consisted of training, identification, and assessment of transition readiness and appropriateness. Eligible participants were receiving CAMHS care, IQ ⩾ 70 and within 1 year of their service transition boundary. CAMHS sites were randomized 2:1 between UC and MT. The main outcome was whether participants were receiving care from AMHS at 15 months follow up.

The MILESTONE study included 793 participants, 552 receiving UC and 241 receiving MT. In the MT group, 24.9% transitioned to AMHS at 15 months compared to 14.2% in the UC group (p = 0.002), and appropriate transitions (in those with a need for transition at baseline or ongoing clinical need at 15 months) were 32.3% in the MT group compared to 16.4% in the UC group (p < 0.001).

A higher proportion of the MT group transitioned to AMHS at 15 months, and there was a higher proportion of appropriate transitions compared to UC. Clinicians and services should consider the incorporation of MT into routine clinical care.

The individual effects of genetic factors and adverse childhood experiences (ACEs) on risk of psychosis, including schizophrenia (SCZ) and bipolar disorder (BIP), have been widely acknowledged, but their interaction effects on individual psychopathological symptoms remain unclear.

Based on data from 163,704 individuals in the UK Biobank, we investigated the joint effects of polygenic risk scores (PRSs) of SCZ and BIP and ACEs on psychopathology. ACEs status and 55 psychopathological symptoms from seven domains were measured retrospectively using an online mental health questionnaire in 2016. Recent genome-wide association studies for SCZ and BIP were combined with genotype data to generate PRSs. Logistic regression analyses were then conducted to explore univariate and joint main effects of PRSs and ACEs on psychopathological symptoms, as well as their additive and multiplicative interaction effects.

The interaction mechanisms for PRSs and ACEs varied across symptom domains: additive interactions were observed on the depression (RERIBIP-ACEs = 0.20–0.25), anxiety (RERISCZ-ACEs = 0.20; RERIBIP-ACEs = 0.22–0.26), help-seeking (RERISCZ-ACEs = 0.24; RERIBIP-ACEs = 0.23), and cognition domains (RERISCZ-ACEs = −0.23 to -0.17), whereas multiplicative interactions were only detected on the psychotic (betaSCZ-ACEs = −0.543; betaBIP-ACEs = −0.181), mania (betaBIP-ACEs = −0.195), self-harm or suicide (betaSCZ-ACEs = −0.118), and cognitive domains (betaSCZ-ACEs = −0.204 to −0.157).

The interplay mechanisms for genetic liability to SCZ and BIP and ACEs vary across symptom domains. This study reveals heterogeneity in gene–ACEs interaction mechanisms underlying psychosis and may provide personalized guidance for psychological care after ACEs.

Working memory (WM) impairment is a core cognitive deficit in schizophrenia, associated with dysfunction of large-scale brain networks, particularly the triple-network system comprising the default mode, frontoparietal, and salience networks. Given the role of environmental risks like childhood trauma (CT) in cognitive deficits, we investigated whether trauma relates to altered triple-network flexibility and WM in schizophrenia.

We enrolled 190 patients with schizophrenia (SZ) and 117 healthy controls (HCs). Among them, 162 SZ and 99 HCs underwent n-back task-based functional magnetic resonance imaging. We computed temporal variability (TV) in the triple-network connectivity, defining ΔTV as the change between 0-back and 2-back conditions. Subgroup comparisons of ΔTV were conducted within each group based on trauma status. Associations of ΔTV with WM performance and clinical symptoms were examined in SZ, followed by mediation analyses testing whether ΔTV mediates the relationship between trauma and WM.

Among HCs, individuals with childhood trauma showed reduced ΔTV across triple-network connections, whereas no such differences appeared in SZ. In SZ, greater ΔTV within the frontoparietal network (FPN) was correlated with lower positive symptom severity (r = −0.211, p-fdr = 0.046) and better n-back target accuracy (r = 0.303, p-fdr = 0.002). Furthermore, ΔTV within the FPN partially mediated the association between trauma and n-back accuracy.

Our findings highlight the central role of FPN flexibility in mediating childhood trauma’s effect on working memory in schizophrenia. This outlines a key pathway through which an early environmental risk (trauma) translates into cognitive and clinical manifestations in schizophrenia.

Mental stress-induced myocardial ischemia (MSIMI) is common in women with angina with no obstructive coronary artery disease (ANOCA) and is associated with adverse cardiovascular outcomes. Interleukin-6 (IL-6), a central mediator of chronic inflammation, predicts future cardiovascular risk, but its relationship with MSIMI remains unclear.

Eighty women with ANOCA underwent 13N-ammonia positron emission tomography/computed tomography to assess myocardial perfusion and myocardial blood flow (MBF) at rest, during mental stress, and during adenosine-induced stress. Resting inflammatory biomarkers were measured, and multivariable logistic and linear regression models were used to evaluate associations with mental stress-induced perfusion defects. Proteomic profiling was performed in a selected subset to explore potential underlying mechanisms.

Mental stress induced significantly greater myocardial perfusion defects in MSIMI+ patients. Resting IL-6 levels were significantly higher in MSIMI+ patients (3.20 versus 1.80 pg/mL, p = 0.024). Although baseline CRP, hsCRP, and complement C3 levels were also higher in MSIMI+ patients, only resting IL-6 remained independently associated with both the presence of MSIMI and the severity of mental stress-induced myocardial perfusion defects after adjustment for demographic, clinical, and psychosocial factors, and resting MBF. Proteomic analyses demonstrated enrichment of innate immune–hemostatic pathways and mitochondrial oxidative phosphorylation in MSIMI+ patients with high IL-6 levels.

Elevated resting IL-6 is independently associated with the presence and severity of MSIMI in women with ANOCA. These findings suggest that IL-6 may serve as a biomarker of MSIMI and support IL-6-related inflammation as a key pathophysiological pathway underlying MSIMI, with potential implications for targeted therapeutic strategies.

Altered stress responses are closely linked to mental disorders, but the role of brain structure in acute cortisol responses to psychosocial stress remains underexplored, particularly in healthy individuals. Previous studies, with predominantly small samples, primarily focused on selected limbic regions and functional measures. Thus, this study investigates associations between brain structure and cortisol responses to psychosocial stress, exploring if hypothalamic–pituitary–adrenal axis reactivity can be predicted from brain morphology.

Our study included 291 subjects (157 females, 18–62 years) and consisted of two parts. First, a confirmatory analysis examined associations between specific cortical surface area, thickness, and subcortical volume with stress-induced cortisol increases using Permutation Analysis of Linear Models (PALM). Second, we conducted an exploratory whole-brain vertex-wise analysis, followed by out-of-sample prediction of cortisol increases from structural measures.

We found consistent negative associations between cingulate cortex (CC) sub-structures and acute cortisol increases. In PALM- and whole-brain analysis, a smaller surface area of the left rostral and caudal anterior cingulate cortex (cACC), posterior cingulate cortex, and right cACC were associated with higher cortisol stress responses, particularly in males. The left cACC surface area emerged as the most promising predictor in machine learning analyses. Additionally, other fronto-limbic structures were also associated with or predictive of acute cortisol reactivity.

Our findings demonstrate that cortical and subcortical structural measures, particularly smaller surface areas of the CC, predict acute hormonal stress responses. Notably, the left cACC emerged as the most consistent predictor, emphasizing its important role in stress reactivity.

Postnatal depression (PND) can disrupt maternal communication during early interactions, affecting infant socioemotional development. Singing is a natural form of caregiver–infant communication and a promising intervention to enhance maternal well-being and bonding. However, its effects on observed communication and perceived attachment in clinical PND populations remain underexplored.

Within the Scaling-Up Health-Arts Programs: Postnatal Depression trial, 199 mothers with PND were randomized 2:1 to a 10-week group singing intervention (Breathe Melodies for Mums) or a non-singing community activity. One hundred participants (singing = 70; control = 30) completed video-recorded interactions at baseline, week 10, and week 36. Maternal speech was coded using the Parental Cognitive Attributions and Mentalization Scale (PCAMS) for mentalization, affective tone, and attentional focus. Perceived maternal attachment was assessed separately via self-report using the Maternal Postnatal Attachment Scale.

At week 10, singing mothers showed greater improvement in communication with their infants than controls, with about 1.7-fold higher proportions of mentalizing comments (p = 0.01), 1.4-fold more infant-focused speech (p < 0.001), 2.4-fold less parent-focused speech (p < 0.001), and fivefold less negative speech (p < 0.001). These effects were maintained at week 36. Perceived attachment improved significantly across both groups (p < 0.001), but only singing mothers showed further gains from week 10 to week 36 (p = 0.02), indicating continued strengthening of attachment perceptions.

Group singing enhanced maternal communication and perceived attachment in mothers with PND. Findings support community-based, arts-informed interventions as accessible approaches to strengthen early relational health and complement perinatal mental healthcare.

Inflammation has been implicated in psychosis, but its role in individuals at clinical (CHR) and genetic (GHR) high-risk remains unclear. We therefore conducted a network meta-analysis (NMA) to compare circulating cytokine levels across CHR, GHR, and healthy control (HC) groups.

We systematically searched multiple databases up to February 2025, extracting cytokine levels (plasma/serum) from CHR, GHR, and HC groups. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were estimated using random-effects models. Given that no direct head-to-head comparisons between CHR and GHR were available, indirect comparisons were performed through the common comparator (HC). The transitivity assumption was assessed by comparing key study and participant characteristics across comparisons.

Thirty studies were included (CHR: 1601, GHR: 675, HC: 1980). NMA estimates indicated higher IL-6 levels in CHR compared with GHR, while IL-6 and IL-1β levels were lower in GHR compared with HC. In pairwise subgroup analyses, CHR converters showed higher IL-13 levels than non-converters. The evidence network was sparse and star-shaped, with all CHR–GHR estimates relying exclusively on indirect comparisons.

This study represents the first NMA to synthesize cytokine alterations in individuals at high risk for psychosis using indirect evidence. Elevated IL-6 in CHR individuals suggests immune activation, whereas reduced IL-6 in GHR may reflect a distinct immune profile. Increased IL-13 levels in converters highlight potential involvement of Th2-related pathways during transition to psychosis. However, the sparse nature of the evidence network necessitates cautious interpretation of the findings, and larger, standardized multi-center studies are required for confirmation.