Psychological Medicine[JOURNAL]
Sun
200 papers
Why does FND mainly affect women? A consideration of gender imbalance in neuropsychiatric disease.
Bradlow R, Von Der Weid L, Zwickl S … +2 more , Cheung A, Kanaan R
Psychol Med · 2026 Apr · PMID 41969052 · Full text
BACKGROUND: Functional neurological disorder (FND) is a common and disabling neuropsychiatric condition in which women comprise approximately 75% of cases. This paper examines whether the gender imbalance seen in FND is...
BACKGROUND: Functional neurological disorder (FND) is a common and disabling neuropsychiatric condition in which women comprise approximately 75% of cases. This paper examines whether the gender imbalance seen in FND is unique among neurological and psychiatric conditions and explores the biological, psychological, and social contributors to this disparity. METHODS: A narrative review was conducted using MEDLINE, PsycINFO, and Web of Science. Gender ratios were compared across depression, anxiety, post-traumatic stress disorder, schizophrenia, eating disorders, Parkinson's disease, and multiple sclerosis. Evidence regarding sex hormones, early life trauma, gender-based social determinants, and diagnostic biases were synthesized thematically. RESULTS: Amongst the psychiatric and neurological conditions reviewed, FND shows a pronounced female predominance (approximately 3:1), placing it amongst the most gender imbalanced disorders in our sample, with only eating disorders showing a larger female predominance. Biological factors (particularly the influence of estrogen and progesterone on stress reactivity, neuronal excitability, and agency), may heighten female vulnerability. Social determinants (increased exposure to trauma, socioeconomic inequality, and gender norms) further contribute to this risk. FND shares clinical and demographic similarities with other internalizing disorders and conditions linked to dissociation and trauma. The literature suggests FND emerges from a bidirectional interaction between gonadal hormones and psychosocial stressors. CONCLUSIONS: The marked gender imbalance in FND arises from the interplay of biological vulnerability and gendered social adversity. Understanding these intersecting influences is essential for reducing stigma and guiding future research, diagnosis, and treatment. The findings support the need for a gender-sensitive, biopsychosocial approach to FND care, and investigation.
Cost-utility and cost-effectiveness of SELFIE, a transdiagnostic ecological momentary intervention for improving self-esteem in youth aged 12-26 years exposed to childhood adversity: Findings from a multicenter randomized controlled trial.
Boonstra A, Daemen M, Osstyn S … +19 more , Handels R, Drost R, Postma MR, Hoes-van der Meulen I, Volbragt N, Nieman D, Delespaul P, van der Pluijm M, Breedvelt JJF, van der Gaag M, Lindauer R, Boehnke J, van den Berg D, de Haan L, Evers S, Smit F, Bockting C, van Amelsvoort T, Reininghaus U
Psychol Med · 2026 Apr · PMID 41969051 · Full text
BACKGROUND: A novel transdiagnostic blended Ecological Momentary Intervention (EMI) for improving self-esteem in youth who experienced childhood adversity has shown beneficial effects. However, evidence on the cost-effec...
BACKGROUND: A novel transdiagnostic blended Ecological Momentary Intervention (EMI) for improving self-esteem in youth who experienced childhood adversity has shown beneficial effects. However, evidence on the cost-effectiveness of SELFIE and EMIs overall is lacking. METHODS: In this RCT-based economic evaluation, participants aged 12-26 years with low self-esteem (<26 on the Rosenberg Self-Esteem Scale [RSES]) and experienced childhood adversity were recruited from specialized mental health services and the general population and randomly allocated to CAU (control condition) or CAU + SELFIE (experimental condition). The Trimbos/iMTA Questionnaire for Costs Associated with Psychiatric Illness (TiC-P), the RSES, and EQ-5D-5L were assessed at baseline, post-intervention, and 6-, 18-, and 24-month follow-up. Incremental cost-effectiveness (ICER) and cost-utility (ICUR) ratios, and acceptability curves, were generated. Sensitivity and subgroup analyses assessed robustness. RESULTS: From a societal perspective, the ICER presented €1,219 per improved point of self-esteem, and the ICUR presented €53,986 per QALY gained. The probability of cost-effectiveness was 26% at a willingness-to-pay (WTP) threshold of €20,000/QALY and 49% at €50,000/QALY. At €50,000/QALY, the probability of cost-effectiveness was 77% from a healthcare perspective (ICUR €15,671/QALY gained) and 87% for participants recruited from specialized mental health services (ICUR €-14,567/QALY gained). CONCLUSIONS: At the societal level, the SELFIE intervention exceeded the WTP threshold. Tests for robustness showed higher probabilities of cost-effectiveness from a healthcare perspective, likely reflecting the absence of educational productivity loss costs in the societal perspective, and in youth recruited from specialized mental health services. The innovative field of blended EMIs yields encouraging first results, urging more cost-effectiveness research.
Elevated C-reactive protein is associated with suicide attempts in youth with bipolar disorder.
Desai D, Dimick MK, Kennedy KG … +3 more , Sultan AA, Mio M, Goldstein BI
Psychol Med · 2026 Apr · PMID 41969048 · Full text
BACKGROUND: C-reactive protein (CRP) has been studied in relation to bipolar disorder (BD) and suicidality independently. Although suicide risk is elevated in youth with BD, little is known about the association of CRP w...
BACKGROUND: C-reactive protein (CRP) has been studied in relation to bipolar disorder (BD) and suicidality independently. Although suicide risk is elevated in youth with BD, little is known about the association of CRP with suicidality in this population. METHODS: 211 youth participated, including 23 BD with lifetime suicide attempts (BD), 45 BD with lifetime non-suicidal self-injury (NSSI; BD), 39 BD without lifetime suicide attempt or NSSI (BD), and 104 healthy controls (HC). Suicide attempts and NSSI were assessed systematically. Fasting blood samples yielded CRP levels. Primary analyses controlled for age, sex, and body mass index percentile. RESULTS: CRP levels differed across groups ( = 3.40, = 0.02, = 0.05). In post hoc analyses, CRP levels were significantly higher among BD (3.44 ± 6.42 mg/L) vs HC (0.81 ± 0.90 mg/L; < 0.01) and BD (1.42 ± 3.31 mg/L; = 0.01) groups; however, no difference was seen with the BD group (1.83 ± 2.22 mg/L; ). Between-group differences in CRP levels persisted in independent sensitivity analyses controlling for current mood symptoms, lifetime mania score, lifetime smoking, and medications, but not with lifetime depression score. CONCLUSIONS: Suicide attempts among youth with BD are associated with elevated CRP. Given accessibility of CRP testing, the present findings have potential clinical implications. Larger, longitudinal studies with repeated measures are needed to examine time-varying associations between CRP and suicide risk among youth with BD.
Interventions to prevent antipsychotic-induced weight gain and metabolic complications in individuals with a first-episode psychosis and minimal antipsychotic exposure: a systematic review and meta-analysis.
O'Mahony BW, Burke T, Hamill R … +6 more , Gannon L, Perry BI, Siskind D, Pawełczyk T, O'Shea D, O'Donoghue B
Psychol Med · 2026 Apr · PMID 41958303 · Full text
BACKGROUND: Rapid weight gain commonly occurs following the onset of first-episode psychosis (FEP), leading to cardiometabolic disease. Most weight gain in FEP occurs in the first 3 months of treatment, offering a critic...
BACKGROUND: Rapid weight gain commonly occurs following the onset of first-episode psychosis (FEP), leading to cardiometabolic disease. Most weight gain in FEP occurs in the first 3 months of treatment, offering a critical window for prevention. Despite this, most studies aiming to prevent antipsychotic-induced weight gain include people with chronic illness or people who have had lengthy exposure to antipsychotic medication. We aimed to synthesize and analyze the literature on interventions aimed at preventing antipsychotic-induced weight gain. METHODS: We conducted a systematic review in PsycInfo, MEDLINE, CINAHL, and EMBASE of studies that examined the effectiveness of interventions in preventing antipsychotic-induced weight gain in FEP. We examined their effect on weight gain and a range of cardiometabolic markers. RESULTS: We screened 2,092 articles, 13 of which were eligible. Behavioral interventions, all three of which consisted of a multidisciplinary team approach, resulted in a mean of 3.05 kg less weight gain than treatment-as-usual (95% CI 1.36 kg to 4.73 kg). Pharmacological interventions displayed marked clinical and statistical heterogeneity, with each of the seven trials in adults using a different pharmacological intervention. Few studies collected comprehensive data on metabolic health. Only two pharmacological studies, and five studies in total, have been published since 2010. CONCLUSIONS: Despite the importance of preventing weight gain in FEP, there have been few recent studies investigating this topic. Our results indicate that multidisciplinary team interventions are effective in preventing weight gain in FEP and should be offered to all patients.
Prevalence of internalizing disorders, symptoms, and traits across age using advanced nonlinear models - ERRATUM.
van Loo HM, Beijers L, Wieling M … +3 more , de Jong TR, Schoevers RA, Kendler KS
Psychol Med · 2026 Apr · PMID 41958302 · Full text
Abstract loading — click title to view on PubMed.
Inflammatory cytokine alterations in genetic and clinical high risk groups of psychosis: a systematic review and network meta-analysis.
Huang H, Sun Y, Yin J … +5 more , An S, Liu M, Gong Q, Chen Y, Deng H
Psychol Med · 2026 Apr · PMID 41958296 · Full text
BACKGROUND: 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 circul...
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Causal relationships between somatic movement, brain structures, and mental well-being: A multi-stage Mendelian randomization study.
Guo L, Shen Y, Wen J … +6 more , An K, Zhang D, Zhao X, Zhang W, Zhu J, Qian Y
Psychol Med · 2026 Apr · PMID 41958291 · Full text
BACKGROUND: While the relationships between somatic movement, mental well-being, and brain health have been well established, the causal nature and underlying mechanisms of such associations remain incompletely understoo...
BACKGROUND: While the relationships between somatic movement, mental well-being, and brain health have been well established, the causal nature and underlying mechanisms of such associations remain incompletely understood. METHODS: By applying multi-stage Mendelian randomization to multi-source summary data derived from genome-wide association studies, we examined the causal effects of 4 somatic movement measures on 2 mental well-being indices and 13 types of brain structures, followed by testing the mediating roles of brain structures in accounting for the causal associations between somatic movement and mental well-being. RESULTS: Two-sample Mendelian randomization revealed that more physical activity was causally associated with greater mental well-being (life satisfaction and positive affect), while more sedentary behavior (longer leisure screen time and more sedentary behavior at work) with lower mental well-being. With respect to brain structures, sedentary behavior was causally linked to decreased volume, surface area, and local gyrification index in distributed cortical regions. Remarkably, decreased surface area of the piriform cortex was found to mediate the causal associations between sedentary behavior and lower mental well-being. CONCLUSIONS: Our findings not only complement and extend earlier reports on the associations of somatic movement with mental well-being and brain health by further resolving the causality but also help elucidate the neural mechanisms by which sedentary behavior adversely affects mental well-being.
Linking brain structure to stress reactivity: cingulate surface area predicts acute cortisol responses.
Serin E, Schill LS, Bärtl C … +9 more , Giglberger M, Konzok J, Peter HL, Speicher N, Kreuzpointner L, Kudielka BM, Wüst S, Walter H, Henze GI
Psychol Med · 2026 Apr · PMID 41943954 · Full text
BACKGROUND: 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....
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Joint effects of childhood adversity and genetic risk for psychosis on psychopathology in the UK Biobank.
Lu ZA, Ploner A, Bergen SE
Psychol Med · 2026 Apr · PMID 41943949 · Full text
BACKGROUND: 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 inte...
BACKGROUND: 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. METHODS: 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. RESULTS: The interaction mechanisms for PRSs and ACEs varied across symptom domains: additive interactions were observed on the depression (RERI = 0.20-0.25), anxiety (RERI = 0.20; RERI = 0.22-0.26), help-seeking (RERI = 0.24; RERI = 0.23), and cognition domains (RERI = -0.23 to -0.17), whereas multiplicative interactions were only detected on the psychotic (beta = -0.543; beta = -0.181), mania (beta = -0.195), self-harm or suicide (beta = -0.118), and cognitive domains (beta = -0.204 to -0.157). CONCLUSIONS: 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.
Maternal communication and attachment following a group singing intervention for postnatal depression: findings from the SHAPER-PND trial.
Rebecchini L, Bind RH, Estevao C … +15 more , Hazelgrove K, Priestley K, Laijawala R, Sangha S, Sethna V, Woods AJ, Crane N, Manoharan M, Burton A, Dye H, Osborn T, Greenwood L, Fancourt D, Pariante CM, Dazzan P
Psychol Med · 2026 Apr · PMID 41943945 · Full text
BACKGROUND: 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 promisin...
BACKGROUND: 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. METHODS: 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. RESULTS: 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 ( = 0.01), 1.4-fold more infant-focused speech ( < 0.001), 2.4-fold less parent-focused speech ( < 0.001), and fivefold less negative speech ( < 0.001). These effects were maintained at week 36. Perceived attachment improved significantly across both groups ( < 0.001), but only singing mothers showed further gains from week 10 to week 36 ( = 0.02), indicating continued strengthening of attachment perceptions. CONCLUSIONS: 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.
Sleep diary-derived parameters and sleep measures mediate the efficacy of transdiagnostic sleep and circadian intervention for depression.
Poon CY, Ho FY, Lo HK … +4 more , Yeung WF, Chung KF, Chan CS, Harvey A
Psychol Med · 2026 Apr · PMID 41943940 · Full text
The present study aimed to explore sleep diary-derived parameters and sleep measures as mediators of the effects of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TSC) on psychological outcomes. A...
The present study aimed to explore sleep diary-derived parameters and sleep measures as mediators of the effects of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TSC) on psychological outcomes. A secondary analysis of a two-arm randomized controlled trial of a group-based TSC for major depressive disorder was conducted. The participants included 152 adults (mean age = 34.0; 79.6% female) who were randomized into either the TSC or care-as-usual group. Mediation analysis indicated that reduction in insomnia symptom severity (standardized indirect effects: -0.06 to -0.17), sleep disturbance (-0.04 to -0.22), and sleep-related impairment (-0.04 to -0.17) was significantly mediated by sleep diary-derived sleep parameters. The treatment effects on depressive symptoms (standardized indirect effects: -0.05 to -0.10), anxiety symptoms (-0.04 to -0.07), fatigue (-0.05 to -0.09), functional impairment (-0.06 to -0.09), and quality of life (0.04 to 0.08) were sequentially mediated by sleep parameters and insomnia symptom severity. However, the severity of insomnia symptoms alone (magnitudes of standardized indirect effects: 0.09-0.17) but not sleep parameters alone (0.00-0.07) mediated the treatment effects on psychological outcomes, indicating that sleep parameters need to influence subjective sleep measures to sequentially affect psychological outcomes. These results underscore the critical roles of subjective sleep measures in clinical improvements within a sleep-targeted intervention.
Dynamic frontoparietal flexibility and cognitive dysfunction in schizophrenia: disentangling the roles of symptom burden and childhood trauma.
Huang D, Liu Z, Tan W … +8 more , Sopodenkiewicz M, Liu X, Yang J, Wang F, Huang W, Yang J, Long Y, Palaniyappan L
Psychol Med · 2026 Apr · PMID 41943939 · Full text
BACKGROUND: 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, fron...
BACKGROUND: 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. METHODS: We enrolled 190 patients with schizophrenia (SZ) and 117 healthy controls (HCs). Among them, 162 SZ and 99 HCs underwent -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. RESULTS: 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 ( = -0.211, -fdr = 0.046) and better -back target accuracy ( = 0.303, -fdr = 0.002). Furthermore, ΔTV within the FPN partially mediated the association between trauma and -back accuracy. CONCLUSIONS: 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.
Interpreting cross-sectional comparisons of menopausal status and brain outcomes.
Keye C
Psychol Med · 2026 Apr · PMID 41943931 · Full text
Abstract loading — click title to view on PubMed.
Dose-dependent association between elevated resting IL-6 levels and severity of mental stress-induced myocardial perfusion defects.
Yin H, Chang J, Jia M … +15 more , Jiang C, Wang Y, Liu F, Bai B, Liu Y, Liu Q, Wang H, Huang J, Xue D, Jin N, Cheng L, Liu J, Wang S, Ma H, Geng Q
Psychol Med · 2026 Apr · PMID 41943927 · Full text
BACKGROUND: 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...
BACKGROUND: 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. METHODS: Eighty women with ANOCA underwent N-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. RESULTS: 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, = 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. CONCLUSIONS: 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.
Associations between five forms of child maltreatment and depression: a multilevel meta-analytic comparison.
Rind B, Rieger G
Psychol Med · 2026 Apr · PMID 41940550 · Full text
BACKGROUND: 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 differ...
BACKGROUND: 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. METHODS: 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. RESULTS: Effect sizes for different maltreatment forms were strongly correlated within studies (median s ≈ .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. CONCLUSIONS: 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.
The effect of managed transition on the proportion of young people transitioning from CAMHS to AMHS: Analysis of the Milestone Cluster Randomised Clinical Trial.
Rowland T, Winsper C, Morroni D … +18 more , Appleton R, Tuomainen H, Dieleman GC, Franić T, de Girolamo G, Madan J, Maras A, McNicholas F, Paul M, Purper-Ouakil D, Santosh P, Schulze UM, Street C, Tremmery S, Verhulst F, Wolke D, Singh SP, MILESTONE Transition Consortium
Psychol Med · 2026 Apr · PMID 41940539 · Full text
BACKGROUND: 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...
BACKGROUND: 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. METHODS: 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. RESULTS: 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 ( = 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 ( < 0.001). CONCLUSIONS: 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.
Post-traumatic stress disorder symptoms following psychedelic use: a naturalistic survey study.
Evens R, Uyar A, Gosslau E … +4 more , Dambeck F, Repantis D, Wolff M, Lueken U
Psychol Med · 2026 Apr · PMID 41919323 · Full text
BACKGROUND: 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 inve...
BACKGROUND: 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). METHODS: A cross-sectional online survey ( = 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. RESULTS: 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. DISCUSSION: 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.
Parental violent offending and offspring suicidal behavior: a nationwide register-based study.
Järvinen A, Fazel S, Kuja-Halkola R … +6 more , Brikell I, Chang Z, D'Onofrio BM, Larsson H, Lichtenstein P, Latvala A
Psychol Med · 2026 Apr · PMID 41919313 · Full text
BACKGROUND: 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 e...
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Triglyceride-glucose index, genetic predisposition, and incident depression: a prospective cohort study from the UK Biobank.
Hu W, Liu TS, Shen ZZ … +3 more , Tian G, Jia CX, Liu BP
Psychol Med · 2026 Apr · PMID 41918219 · Full text
BACKGROUND: 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....
BACKGROUND: 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. METHODS: 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. RESULTS: 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 ( 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. CONCLUSIONS: A higher TyG index was associated with increased risk of incident depression, independent of genetic predisposition.
Life experiences of humiliation, entrapment, and frontoparietal-cerebellar connectivity predict adolescent anxiety and depression symptoms.
Qu YL, Chopra S, Qu S … +8 more , Cocuzza CV, Labache L, Bauer CCC, Morfini F, Whitfield-Gabrieli S, Slavich GM, Joormann J, Holmes AJ
Psychol Med · 2026 Mar · PMID 41909935 · Full text
BACKGROUND: 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...
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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