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Background: We compared dissociative seizure specific cognitive behavior therapy (DS-CBT) plus standardized medical care (SMC) to SMC alone in a randomized controlled trial. DS-CBT resulted in better outcomes on several secondary trial outcome measures at the 12-month follow-up point. The purpose of this paper is to evaluate putative treatment mechanisms. Methods: We carried out a secondary mediation analysis of the CODES trial. 368 participants were recruited from the National Health Service in secondary / tertiary care in England, Scotland, and Wales. Sixteen mediation hypotheses corresponding to combinations of important trial outcomes and putative mediators were assessed. Twelve-month trial outcomes considered were final-month seizure frequency, Work and Social Adjustment Scale (WSAS), and the SF-12v2, a quality-of-life measure providing physical (PCS) and mental component summary (MCS) scores. Mediators chosen for analysis at six months (broadly corresponding to completion of DS-CBT) included: (a) beliefs about emotions, (b) a measure of avoidance behavior, (c) anxiety and (d) depression. Results: All putative mediator variables except beliefs about emotions were found to be improved by DS-CBT. We found evidence for DS-CBT effect mediation for the outcome variables dissociative seizures (DS), WSAS and SF-12v2 MCS scores by improvements in target variables avoidance behavior, anxiety, and depression. The only variable to mediate the DS-CBT effect on the SF-12v2 PCS score was avoidance behavior. Conclusions: Our findings largely confirmed the logic model underlying the development of CBT for patients with DS. Interventions could be additionally developed to specifically address beliefs about emotions to assess whether it improves outcomes. [ABSTRACT FROM AUTHOR]

Background: The purpose of this paper is to identify the trajectory of conduct and emotional problems for young people within the general population at four time points (between 9 years 7 months and 16 years 6 months), investigate their relationship with hyperactive/inattentive traits and explore the moderating effect of autistic social traits (ASTs). Methods: Data from 9305 individuals involved in The Avon Longitudinal Study of Parents and Children (ALSPAC) study were included. Conduct and emotional problems and hyperactive/inattentive traits were measured by the Strengths and Difficulties Questionnaire. ASTs were assessed using the Social Communication Disorder Checklist. Individual trajectories for conduct and emotional problems were identified via growth curve modelling. Hyperactive/inattentive traits were included within the growth curve model as a time-varying covariate to determine their effect on these outcomes. Finally, participants were split into two groups (below and above clinical threshold ASTs Groups) and multi-group invariance testing was conducted on the data to identify the moderating effect of ASTs on the relationship between hyperactive/inattentive traits and outcomes (i.e. conduct and emotional problems). Results: Hyperactive/inattentive traits were associated with higher rates of conduct and emotional problems for both boys and girls. The presence of ASTs moderated these relationships for boys, but not for girls, by increasing the risk of boys with hyperactive/inattentive traits developing greater conduct and emotional problems. Conclusions: These findings underscore the importance of identifying hyperactive/inattentive traits and ASTs in young people and addressing the increased risk of conduct and emotional problems. Research and clinical implications are explored. [ABSTRACT FROM AUTHOR]

Background: More knowledge about positive outcomes for people with first-episode psychosis (FEP) is needed. An FEP 10-year follow-up study investigated the rate of personal recovery, emotional wellbeing, and clinical recovery in the total sample and between psychotic bipolar spectrum disorders (BD) and schizophrenia spectrum disorders (SZ); and how these positive outcomes overlap. Methods: FEP participants (n = 128) were re-assessed with structured clinical interviews at 10-year follow-up. Personal recovery was self-rated with the Questionnaire about the Process of Recovery-15-item scale (total score ⩾45). Emotional wellbeing was self-rated with the Life Satisfaction Scale (score ⩾5) and the Temporal Experience of Pleasure Scale (total score ⩾72). Clinical recovery was clinician-rated symptom-remission and adequate functioning (duration minimum 1 year). Results: In FEP, rates of personal recovery (50.8%), life satisfaction (60.9%), and pleasure (57.5%) were higher than clinical recovery (33.6%). Despite lower rates of clinical recovery in SZ compared to BD, they had equal rates of personal recovery and emotional wellbeing. Personal recovery overlapped more with emotional wellbeing than with clinical recovery (χ2). Each participant was assigned to one of eight possible outcome groups depending on the combination of positive outcomes fulfilled. The eight groups collapsed into three equal-sized main outcome groups: 33.6% clinical recovery with personal recovery and/or emotional wellbeing; 34.4% personal recovery and/or emotional wellbeing only; and 32.0% none. Conclusions: In FEP, 68% had minimum one positive outcome after 10 years, suggesting a good life with psychosis. This knowledge must be shared to instill hope and underlines that subjective and objective positive outcomes must be assessed and targeted in treatment. [ABSTRACT FROM AUTHOR]

Background: Prenatal and perinatal complications are established risk factors for psychotic disorder, but far less is known about these measures and psychotic experiences (PEs). We investigated the longitudinal effect of prenatal risk factors (maternal behavior, medication complications) and perinatal risk factors (birth weight, medical complications) on frequency of PEs. We also examined the cumulative risk of prenatal/perinatal risk factors, and differences between transient PE, persistent PE, and controls. Methods: The Adolescent Brain Cognitive Development study is a large child cohort (age 9–10 at baseline; n = 11 872 with PE data). PEs were measured longitudinally using the Prodromal Questionnaire-Brief, Child version, and included only if reported as distressing. Mixed-effects models were used for analysis, controlling for random effects, and a substantial number of fixed-effects covariates. Results: Urinary tract infection (β = 0.11, 95% confidence interval [CI] 0.03–0.19) and severe anemia (β = 0.18, 95% CI 0.07–0.29) increased frequency of distressing PEs in childhood. Number of prenatal complications increased frequency of PEs (β = 0.03, 95% CI 0.01–0.06) and risk of persistent PEs (odds ratio [OR] = 1.08, 95% CI 1.01–1.15). Maternal smoking was associated with an increased frequency of PEs (β = 0.11, 95% CI 0.04–0.18) and persistent PEs (OR = 1.31, 95% CI 1.04–1.66). Maternal substance use was a risk factor for a 48% increased risk of persistent PEs (OR = 1.48, 95% CI 1.08–2.01). Perinatal complications showed no effect on PEs. Conclusions: This study provides evidence that certain prenatal medical complications (severe nausea, severe anemia), cumulative number of prenatal medical complications, and maternal behaviors (smoking during pregnancy), increased frequency of distressing PEs in childhood. Maternal smoking and substance use, as well as cumulative number of prenatal complications increased risk of persistent PEs. [ABSTRACT FROM AUTHOR]

Background: Depression is characterized by abnormalities in emotional processing, but the specific drivers of such emotional abnormalities are unknown. Computational work indicates that both surprising outcomes (prediction errors; PEs) and outcomes (values) themselves drive emotional responses, but neither has been consistently linked to affective disturbances in depression. As a result, the computational mechanisms driving emotional abnormalities in depression remain unknown. Methods: Here, in 687 individuals, one-third of whom qualify as depressed via a standard self-report measure (the PHQ-9), we use high-stakes, naturalistic events – the reveal of midterm exam grades – to test whether individuals with heightened depression display a specific reduction in emotional response to positive PEs. Results: Using Bayesian mixed effects models, we find that individuals with heightened depression do not affectively benefit from surprising, good outcomes – that is, they display reduced affective responses to positive PEs. These results were highly specific: effects were not observed to negative PEs, value signals (grades), and were not related to generalized anxiety. This suggests that the computational drivers of abnormalities in emotion in depression may be specifically due to positive PE-based emotional responding. Conclusions: Affective abnormalities are core depression symptoms, but the computational mechanisms underlying such differences are unknown. This work suggests that blunted affective reactions to positive PEs are likely mechanistic drivers of emotional dysregulation in depression. [ABSTRACT FROM AUTHOR]

Background: Adolescence is a key developmental period for the emergence of psychopathology. Reward-related brain activity increases across adolescence and has been identified as a potential neurobiological mechanism of risk for different forms of psychopathology. The reward positivity (RewP) is an event-related potential component that indexes reward system activation and has been associated with both concurrent and family history of psychopathology. However, it is unclear whether the RewP is also associated with higher-order psychopathology subfactors and whether this relationship is present across different types of reward. Methods: In a sample of 193 adolescent females and a biological parent, the present study examined the association between adolescent and parental psychopathology subfactors and adolescent RewP to monetary and social reward. Results: Results indicated that the adolescent and parental distress subfactors were negatively associated with the adolescent domain-general RewP. The adolescent and parental positive mood subfactors were negatively associated with the adolescent domain-general and domain-specific monetary RewP, respectively. Conversely, the adolescent and parental fear/obsessions subfactors were positively associated with the adolescent domain-general RewP. The associations between parental and adolescent psychopathology subfactors and the adolescent RewP were independent of each other. Conclusions: The RewP in adolescent females is associated with both concurrent and parental psychopathology symptoms, suggesting that it indexes both severity and risk for higher-order subfactors. [ABSTRACT FROM AUTHOR]

Background: Little is known about when youth may be at greatest risk for attempting suicide, which is critically important information for the parents, caregivers, and professionals who care for youth at risk. This study used adolescent and parent reports, and a case-crossover, within-subject design to identify 24-hour warning signs (WS) for suicide attempts. Methods: Adolescents (N = 1094, ages 13 to 18) with one or more suicide risk factors were enrolled and invited to complete bi-weekly, 8–10 item text message surveys for 18 months. Adolescents who reported a suicide attempt (survey item) were invited to participate in an interview regarding their thoughts, feelings/emotions, and behaviors/events during the 24-hours prior to their attempt (case period) and a prior 24-hour period (control period). Their parents participated in an interview regarding the adolescents' behaviors/events during these same periods. Adolescent or adolescent and parent interviews were completed for 105 adolescents (81.9% female; 66.7% White, 19.0% Black, 14.3% other). Results: Both parent and adolescent reports of suicidal communications and withdrawal from social and other activities differentiated case and control periods. Adolescent reports also identified feelings (self-hate, emotional pain, rush of feelings, lower levels of rage toward others), cognitions (suicidal rumination, perceived burdensomeness, anger/hostility), and serious conflict with parents as WS in multi-variable models. Conclusions: This study identified 24-hour WS in the domains of cognitions, feelings, and behaviors/events, providing an evidence base for the dissemination of information about signs of proximal risk for adolescent suicide attempts. [ABSTRACT FROM AUTHOR]

Background: Twice weekly sessions of cognitive behavioral therapy (CBT) and interpersonal psychotherapy (IPT) for major depressive disorder (MDD) lead to less drop-out and quicker and better response compared to once weekly sessions at posttreatment, but it is unclear whether these effects hold over the long run. Aims: Compare the effects of twice weekly v. weekly sessions of CBT and IPT for depression up to 24 months since the start of treatment. Methods: Using a 2 × 2 factorial design, this multicentre study randomized 200 adults with MDD to once or twice weekly sessions of CBT or IPT over 16–24 weeks, up to a maximum of 20 sessions. Main outcome measures were depression severity, measured with the Beck Depression Inventory-II and the Longitudinal Interval Follow-up Evaluation. Intention-to-treat analyses were conducted. Results: Compared with patients who received once weekly sessions, patients who received twice weekly sessions showed a significant decrease in depressive symptoms up through month 9, but this effect was no longer apparent at month 24. Patients who received CBT showed a significantly larger decrease in depressive symptoms up to month 24 compared to patients who received IPT, but the between-group effect size at month 24 was small. No differential effects between session frequencies or treatment modalities were found in response or relapse rates. Conclusions: Although a higher session frequency leads to better outcomes in the acute phase of treatment, the difference in depression severity dissipated over time and there was no significant difference in relapse. [ABSTRACT FROM AUTHOR]

Background.Depression and anxiety persist within and across diagnostic boundaries. The manner in which common v. disorder-specific genetic and environmental influences operate across development to maintain internalizing disorders and their co-morbidity is unclear. This paper investigates the stability and change of etiological influences on depression, panic, generalized, separation and social anxiety symptoms, and their co-occurrence, across adolescence and young adulthood.Method.A total of 2619 twins/siblings prospectively reported symptoms of depression and anxiety at mean ages 15, 17 and 20 years.Results.Each symptom scale showed a similar pattern of moderate continuity across development, largely underpinned by genetic stability. New genetic influences contributing to change in the developmental course of the symptoms emerged at each time point. All symptom scales correlated moderately with one another over time. Genetic influences, both stable and time-specific, overlapped considerably between the scales. Non-shared environmental influences were largely time- and symptom-specific, but some contributed moderately to the stability of depression and anxiety symptom scales. These stable, longitudinal environmental influences were highly correlated between the symptoms.Conclusions.The results highlight both stable and dynamic etiology of depression and anxiety symptom scales. They provide preliminary evidence that stable as well as newly emerging genes contribute to the co-morbidity between depression and anxiety across adolescence and young adulthood. Conversely, environmental influences are largely time-specific and contribute to change in symptoms over time. The results inform molecular genetics research and transdiagnostic treatment and prevention approaches. [ABSTRACT FROM PUBLISHER]

Background. Routine mood screening is recommended after stroke. However, clinicians report difficulty selecting appropriate tools from the wide range available. We aimed to systematically review the psychometric properties and clinical utility of mood screening tools for stroke survivors. Method. Electronic databases (AMED, EMBASE, CINAHL, Medline and PsycINFO) were searched to identify studies assessing the sensitivity and specificity of mood screening tools. Tools that demonstrated at least 80% sensitivity and 60% specificity with stroke survivors with identifiable cut-off scores indicating major and/or any mood disorder in at least one study were selected and clinical utility was assessed. Those with high clinical utility (against predefined criteria) were selected for recommendation. Results. Thirty papers examining 27 screening tools were identified and 16 tools met the psychometric and clinical utility criteria: 10 were verbal self-report tools, four were observational and two incorporated visual prompts for those with communication problems. Only the Stroke Aphasic Depression Questionnaire -Hospital version (SADQ-H) met all the psychometric and utility criteria. The nine-item Patient Health Questionnaire (PHQ-9) can detect major depression and the 15-item Geriatric Depression Scale (GDS-15) can identify milder symptoms; both are feasible to use in clinical practice. The Hospital Anxiety and Depression Scale (HADS) was the only tool able to identify anxiety accurately, but clinical utility was mixed. Conclusions. Valid and clinically feasible mood screening tools for stroke have been identified but methodological inconsistency prevented recommendations about the optimal cut-off scores. [ABSTRACT FROM AUTHOR]

Background: Tightly connected symptom networks have previously been linked to treatment resistance, but most findings come from small-sample studies comparing single responder v. non-responder networks. We aimed to estimate the association between baseline network connectivity and treatment response in a large sample and benchmark its prognostic value against baseline symptom severity and variance. Methods: N = 40 518 patients receiving treatment for depression in routine care in England from 2015–2020 were analysed. Cross-sectional networks were constructed using the Patient Health Questionnaire-9 (PHQ-9) for responders and non-responders (N = 20 259 each). To conduct parametric tests investigating the contribution of PHQ-9 sum score mean and variance to connectivity differences, networks were constructed for 160 independent subsamples of responders and non-responders (80 each, n = 250 per sample). Results: The baseline non-responder network was more connected than responders (3.15 v. 2.70, S = 0.44, p < 0.001), but effects were small, requiring n = 750 per group to have 85% power. Parametric analyses revealed baseline network connectivity, PHQ-9 sum score mean, and PHQ-9 sum score variance were correlated (r = 0.20–0.58, all p < 0.001). Both PHQ-9 sum score mean (β = −1.79, s.e. = 0.07, p < 0.001), and PHQ-9 sum score variance (β = −1.67, s.e. = 0.09, p < 0.001) had larger effect sizes for predicting response than connectivity (β = −1.35, s.e. = 0.12, p < 0.001). The association between connectivity and response disappeared when PHQ-9 sum score variance was accounted for (β = −0.28, s.e. = 0.19, p = 0.14). We replicated these results in patients completing longer treatment (8–12 weeks, N = 22 952) and using anxiety symptom networks (N = 70 620). Conclusions: The association between baseline network connectivity and treatment response may be largely due to differences in baseline score variance. [ABSTRACT FROM AUTHOR]

Background: Understanding the interplay between psychosocial factors and polygenic risk scores (PRS) may help elucidate the biopsychosocial etiology of high alcohol consumption (HAC). This study examined the psychosocial moderators of HAC, determined by polygenic risk in a 10-year longitudinal study of US military veterans. We hypothesized that positive psychosocial traits (e.g. social support, personality traits, optimism, gratitude) may buffer risk of HAC in veterans with greater polygenic liability for alcohol consumption (AC). Methods: Data were analyzed from 1323 European-American US veterans who participated in the National Health and Resilience in Veterans Study, a 10-year, nationally representative longitudinal study of US military veterans. PRS reflecting genome-wide risk for AC (AUDIT-C) was derived from a Million Veteran Program genome-wide association study (N = 200 680). Results: Among the total sample, 328 (weighted 24.8%) had persistent HAC, 131 (weighted 9.9%) had new-onset HAC, 44 (weighted 3.3%) had remitted HAC, and 820 (weighted 62.0%) had no/low AC over the 10-year study period. AUDIT-C PRS was positively associated with persistent HAC relative to no/low AC [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI) = 1.23–1.67] and remitted HAC (RRR = 1.63, 95% CI = 1.07–2.50). Among veterans with higher AUDIT-C PRS, greater baseline levels of agreeableness and greater dispositional gratitude were inversely associated with persistent HAC. Conclusions: AUDIT-C PRS was prospectively associated with persistent HAC over a 10-year period, and agreeableness and dispositional gratitude moderated this association. Clinical interventions designed to target these modifiable psychological traits may help mitigate risk of persistent HAC in veterans with greater polygenic liability for persistent HAC. [ABSTRACT FROM AUTHOR]

Background: Nonsuicidal self-injury (NSSI) is prevalent in adolescent clinical samples. There is evidence that NSSI can be treated effectively but data on individual treatment outcomes is limited. The goal of this study was to examine response, remission, exacerbation, and relapse rates over one and two years, respectively, among a clinical sample of adolescents with NSSI. Furthermore, we aimed to identify clinically relevant predictors of NSSI trajectories. Methods: The sample consists of n = 203 adolescents (12–17 y., 94% female) from a specialized outpatient clinic for risk-taking and self-harming behavior with NSSI on at least five days in the six months before first assessment. Assessments were completed at baseline and one (FU1) and two (FU2) years later using structured clinical interviews and self-report questionnaires. Results: At FU1, 75% reported a reduction in NSSI frequency by at least 50% (treatment response); among those, one third (25% of the entire sample) achieved a remission (0 NSSI); an exacerbation (⩾50% more NSSI) was observed in 11% of patients. Of those in remission, 41% relapsed one year later. Predictors of non-response or non-remission were inpatient treatment and depressive symptoms. Adolescents with lower NSSI frequency at baseline had a higher risk of exacerbation. Due to limited sample size at FU2 no prediction model for relapse was established. Conclusions: While most adolescents presenting with NSSI achieved significant improvement, more attention should be paid to the rather low rates of full remission. Prediction and early detection of individuals who deteriorate during or relapse after treatment is critical. [ABSTRACT FROM AUTHOR]

Background: Prior research has identified altered brain structure and function in individuals at risk for self-directed violence thoughts and behaviors. However, these studies have largely utilized healthy controls and findings have been inconsistent. Thus, this study examined differences in resting-state functional network connectivity among individuals with lifetime suicide attempt(s) v. lifetime self-directed violence thoughts alone. Methods: Using data from the UK Biobank, this study utilized a series of linear regressions to compare individuals with lifetime suicide attempt(s) (n = 566) v. lifetime self-directed violence thoughts alone (n = 3447) on within- and between- network resting-state functional connectivity subnetworks. Results: There were no significant between-group differences for between-network, within-network, or whole-brain functional connectivity after adjusting for age, sex, ethnicity, and body mass index and performing statistical corrections for multiple comparisons. Resting-state network measures may not differentiate between individuals with lifetime suicide attempt(s) and lifetime self-directed violence thoughts alone. Conclusions: Null findings diverge from results reported in smaller neuroimaging studies of suicide risk, but are consistent with null findings in other large-scale studies and meta-analyses. Strengths of the study include its large sample size and stringent control group. Future research on a wider array of imaging, genetic, and psychosocial risk factors can clarify relative contributions of individual and combined variables to suicide risk and inform scientific understanding of ideation-to-action framework. [ABSTRACT FROM AUTHOR]

Background: Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis. Methods: Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0–11 years), and late (12–17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use. Results: The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord. Conclusions: Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse. [ABSTRACT FROM AUTHOR]

Background: Developing, elaborating, and consolidating positive views of the self is a plausible route to increased psychological well-being. We set out to provide an assessment of positive self-beliefs that could be used in research and clinical practice. Methods: A non-probability online survey was conducted with 2500 UK adults, quota sampled to match the population for age, gender, ethnicity, income, and region. Exploratory factor analysis of a 94-item pool – generated with guidance from people with lived experience of mental health difficulties – was conducted to develop the Oxford Positive Self Scale (OxPos). The item pool was further reduced using regularised structural equation modelling (SEM) before confirmatory factor analysis. Optimal cut-off scores were developed using receiver operating characteristic curves. Additional validations were carried out with two further general population cohorts (n = 1399; n = 1693). Results: A 24-item scale was developed with an excellent model fit [robust χ2 = 995.676; df = 246; CFI = 0.956; TLI = 0.951; RMSEA = 0.049 (0.047, 0.052); SRMR = 0.031]. The scale comprises four factors: mastery; strength; enjoyment; and character. SEM indicated that the scale explains 68.6% of variance in psychological well-being. The OxPos score was negatively correlated with depression (r = −0.49), anxious avoidance (r = −0.34), paranoia (r = −0.23), hallucinations (r = −0.20), and negative self-beliefs (r = −0.50), and positively correlated with psychological well-being (r = 0.79), self-esteem (r = 0.67), and positive social comparison (r = 0.72). Internal reliability and test–retest reliability were excellent. Cut-offs by age and gender were generated. A short-form was developed, explaining 96% of the full-scale variance. Conclusions: The new open access scale provides a psychometrically robust assessment of positive cognitions that are strongly connected to psychological well-being. [ABSTRACT FROM AUTHOR]

Background: Little has been done to comprehensively study the relationships between multiple well-being constructs at a time. Even less is known about whether child maltreatment and major depressive disorder (MDD) impact different well-being constructs. This study aims to examine whether maltreated or depressed individuals have specific impacts on well-being structures. Methods: Data analyzed were from the Montreal South-West Longitudinal Catchment Area Study (N = 1380). The potential confounding of age and sex was controlled by propensity score matching. We used network analysis to assess the impact of maltreatment and MDD on well-being. The centrality of nodes was estimated with the 'strength' index and a case-dropping bootstrap procedure was used to test network stability. Differences in the structure and connectivity of networks between different studied groups were also examined. Results: Autonomy and daily life and social relations were the most central nodes for the MDD and maltreated groups [MDD group: strength coefficient (SC) autonomy = 1.50; SCdaily life and social relations = 1.34; maltreated group: SCautonomy = 1.69; SCdaily life and social relations = 1.55]. Both maltreatment and MDD groups had statistical differences in terms of the global strength of interconnectivity in their networks. Network invariance differed between with and without MDD groups indicating different structures of their networks. The non-maltreatment and MDD group had the highest level of overall connectivity. Conclusions: We discovered distinct connectivity patterns of well-being outcomes in maltreatment and MDD groups. The identified core constructs could serve as potential targets to maximize the effectiveness of clinical management of MDD and also advance prevention to minimize the sequelae of maltreatment. [ABSTRACT FROM AUTHOR]

Background: Mental health and functional difficulties are highly comorbid across neurological disorders, but supportive care options are limited. This randomised controlled trial assessed the efficacy of a novel transdiagnostic internet-delivered psychological intervention for adults with neurological disorders. Methods: 221 participants with a confirmed diagnosis of epilepsy, multiple sclerosis, Parkinson's disease, or an acquired brain injury were allocated to either an immediate treatment group (n = 115) or treatment-as-usual waitlist control (n = 106). The intervention, the Wellbeing Neuro Course, was delivered online via the eCentreClinic website. The Course includes six lessons, based on cognitive behavioural therapy, delivered over 10 weeks with support from a psychologist via email and telephone. Primary outcomes were symptoms of depression (PHQ-9), anxiety (GAD-7) and disability (WHODAS 2.0). Results: 215 participants commenced the trial (treatment n = 111; control n = 104) and were included in intention-to-treat analysis. At post-treatment, we observed significant between-group differences in depression (PHQ-9; difference = 3.07 [95% CI 2.04–4.11], g = 0.62), anxiety (GAD-7; difference = 1.87 [0.92–2.81], g = 0.41) and disability (WHODAS 2.0 difference = 3.08 [1.09–5.06], g = 0.31), that favoured treatment (all ps < 0.001). Treatment-related effects were maintained at 3-month follow-up. Findings were achieved with minimal clinician time (average of 95.7 min [s.d. = 59.3] per participant), highlighting the public health potential of this approach to care. No adverse treatment events were reported. Conclusions: Internet-delivered psychological interventions could be a suitable model of accessible supportive care for patients with neurological disorders. [ABSTRACT FROM AUTHOR]

Background: Enhanced post-awakening cortisol may serve as a biological marker for individuals with major depressive disorder. However, studies comparing post-awakening cortisol between patients with major depressive disorder (MDD) and healthy controls have produced conflicting findings. The aim of this study was to investigate whether this inconsistency could be due to the effects of childhood trauma. Methods: A total of N = 112 patients with MDD and healthy controls were divided into four groups according to the presence of childhood trauma. Saliva samples were collected at awakening and 15, 30, 45, and 60 min later. The total cortisol output and the cortisol awakening response (CAR) were calculated. Results: The total post-awakening cortisol output was significantly higher in patients with MDD as compared to healthy controls, but only in those individuals reporting childhood trauma. The four groups did not differ regarding the CAR. Conclusions: Elevated post-awakening cortisol in MDD may be confined to those with a history of early life stress. Tailoring and/or augmenting of currently available treatments may be required to meet the specific needs of this population. [ABSTRACT FROM AUTHOR]

Background: Access to evidence-based psychological treatment is a challenge worldwide. We assessed the effectiveness of a fully automated aviophobia smartphone app treatment delivered in combination with a $5 virtual reality (VR) viewer. Methods: In total, 153 participants from the Dutch general population with aviophobia symptoms and smartphone access were randomized in a single-blind randomized controlled trial to either an automated VR cognitive behavior therapy (VR-CBT) app treatment condition (n = 77) or a wait-list control condition (n = 76). The VR-CBT app was delivered over a 6-week period in the participants' natural environment. Online self-report assessments were completed at baseline, post-treatment, at 3-month and at 12-month follow-up. The primary outcome measure was the Flight Anxiety Situations Questionnaire (FAS). Analyses were based on intent-to-treat. Results: A significant reduction of aviophobia symptoms at post-test for the VR-CBT app compared with the control condition [ p < 0.001; d = 0. 98 (95% CI 0.65–1.32)] was demonstrated. The dropout rate was 21%. Results were maintained at 3-month follow-up [within-group d = 1.14 (95% CI 0.46–1.81)] and at 12-month follow-up [within-group d = 1.12 (95% CI 0.46–1.79)]. Six participants reported adverse effects of cyber sickness symptoms. Conclusions: This study is the first to show that fully automated mobile VR-CBT therapy delivered in a natural setting can maintain long-term effectiveness in reducing aviophobia symptoms. In doing so, it offers an accessible and scalable evidence-based treatment solution that can be applied globally at a fraction of the cost of current treatment alternatives. [ABSTRACT FROM AUTHOR]

Background: Child maltreatment (CM) and migrant status are independently associated with psychosis. We examined prevalence of CM by migrant status and tested whether migrant status moderated the association between CM and first-episode psychosis (FEP). We further explored whether differences in CM exposure contributed to variations in the incidence rates of FEP by migrant status. Methods: We included FEP patients aged 18–64 years in 14 European sites and recruited controls representative of the local populations. Migrant status was operationalized according to generation (first/further) and region of origin (Western/non-Western countries). The reference population was composed by individuals of host country's ethnicity. CM was assessed with Childhood Trauma Questionnaire. Prevalence ratios of CM were estimated using Poisson regression. We examined the moderation effect of migrant status on the odds of FEP by CM fitting adjusted logistic regressions with interaction terms. Finally, we calculated the population attributable fractions (PAFs) for CM by migrant status. Results: We examined 849 FEP cases and 1142 controls. CM prevalence was higher among migrants, their descendants and migrants of non-Western heritage. Migrant status, classified by generation (likelihood test ratio:χ2 = 11.3, p = 0.004) or by region of origin (likelihood test ratio:χ2 = 11.4, p = 0.003), attenuated the association between CM and FEP. PAFs for CM were higher among all migrant groups compared with the reference populations. Conclusions: The higher exposure to CM, despite a smaller effect on the odds of FEP, accounted for a greater proportion of incident FEP cases among migrants. Policies aimed at reducing CM should consider the increased vulnerability of specific subpopulations. [ABSTRACT FROM AUTHOR]

Background: The scale of the global mental health burden indicates the inadequacy not only of current treatment options, but also the pace of the standard treatment development process. The 'leapfrog' trial design is a newly-developed simple Bayesian adaptive trial design with potential to accelerate treatment development. A first leapfrog trial was conducted to provide a demonstration and test feasibility, applying the method to a low-intensity internet-delivered intervention targeting anhedonia. Methods: At the start of this online, single-blind leapfrog trial, participants self-reporting depression were randomized to an initial control arm comprising four weeks of weekly questionnaires, or one of two versions of a four-week cognitive training intervention, imagery cognitive bias modification (imagery CBM). Intervention arms were compared to control on an ongoing basis via sequential Bayesian analyses, based on a primary outcome of anhedonia at post-intervention. Results were used to eliminate and replace arms, or to promote them to become the control condition based on pre-specified Bayes factor and sample size thresholds. Two further intervention arms (variants of imagery CBM) were added into the trial as it progressed. Results: N = 188 participants were randomized across the five trial arms. The leapfrog methodology was successfully implemented to identify a 'winning' version of the imagery CBM, i.e. the version most successful in reducing anhedonia, following sequential elimination of the other arms. Conclusions: The study demonstrates feasibility of the leapfrog design and provides a foundation for its adoption as a method to accelerate treatment development in mental health. Registration: clinicaltrials.gov, NCT04791137. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether the enhancing contact model (ECM) intervention is effective in reducing family caregiving burden and improving hope and quality of life (QOL) among family caregivers of persons with schizophrenia (FCPWS). Methods: We conducted a cluster randomized controlled trial in FCPWS in eight rural townships in Xinjin, Chengdu, China. In total, 253 FCPWS were randomly allocated to the ECM, psychoeducational family intervention (PFI), or treatment as usual (TAU) group. FCPWS in three groups were assessed caregiving burden, QOL and state of hope at baseline (T0), post-intervention (T1), 3-month (T2), and 9-month (T3) follow-up, respectively. Results: Compared with participants in the TAU group, participants in the ECM group had statistically significantly lower caregiving burden scores both at T1 and T2 (p = 0.0059 and 0.0257, respectively). Compared with participants in the TAU group, participants in the PFI group had statistically significantly higher QOL scores in T1 (p = 0.0406), while participants in the ECM group had statistically significantly higher QOL scores in T3 (p = 0.0240). Participants in both ECM and PFI groups had statistically significantly higher hope scores than those in the TAU group at T1 (p = 0.0160 and 0.0486, respectively). Conclusions: This is the first study to explore the effectiveness of ECM on reducing family caregiving burden and improving hope and QOL in rural China. The results indicate the ECM intervention, a comprehensive and multifaceted intervention, is more effective than the PFI in various aspects of mental wellbeing among FCPWS. Future research needs to confirm ECM's effectiveness in various population. [ABSTRACT FROM AUTHOR]

Background: Post-traumatic growth (PTG) is a positive psychological consequence of trauma. The aims of this study were to investigate whether combat injury was associated with deployment-related PTG in a cohort of UK military personnel who were deployed to Afghanistan, and whether post-traumatic stress disorder (PTSD), depression and pain mediate this relationship. Methods: 521 physically injured (n = 138 amputation; n = 383 non-amputation injury) and 514 frequency-matched uninjured personnel completed questionnaires including the deployment-related Post-Traumatic Growth Inventory (DPTGI). DPTGI scores were categorised into tertiles of: no/low (score 0–20), moderate (score 21–34) or a large (35–63) degree of deployment-related PTG. Analysis was completed using generalised structural equation modelling. Results: A large degree of PTG was reported by 28.0% (n = 140) of the uninjured group, 36.9% (n = 196) of the overall injured group, 45.4% (n = 62) of amputee and 34.1% (n = 134) of the non-amputee injured subgroups. Combat injury had a direct effect on reporting a large degree of PTG [Relative risk ratio (RRR) 1.59 (95% confidence interval (CI) 1.17–2.17)] compared to sustaining no injury. Amputation injuries also had a significant direct effect [RRR 2.18 (95% CI 1.24–3.75)], but non-amputation injuries did not [RRR 1.35 (95% CI 0.92–1.93)]. PTSD, depression and pain partially mediate this relationship, though mediation differed depending on the injury subtype. PTSD had a curvilinear relationship with PTG, whilst depression had a negative association and pain had a positive association. Conclusions: Combat injury, in particular injury resulting in traumatic amputation, is associated with reporting a large degree of PTG. [ABSTRACT FROM AUTHOR]

Background: Stress is associated with binge eating and emotional eating (EE) cross-sectionally. However, few studies have examined stress longitudinally, limiting understanding of how within-person fluctuations in stress influence EE over time and whether stress is a risk factor or consequence of EE. Additionally, little is known regarding how the biological stress response relates to EE. Methods: We used an intensive, longitudinal design to examine between-person and within-person effects of major life stress, daily stress, and cortisol on EE in a population-based sample of women (N = 477; ages 15–30; M = 21.8; s.d. = 3.0) from the Michigan State University Twin Registry. Participants reported past year major life stress, then provided daily ratings of EE and stress for 49 consecutive days. Hair cortisol concentration (HCC) was collected as a longitudinal biological stress measure. Results: Women reported greater EE when they experienced greater mean stress across days (between-person effects) or greater stress relative to their own average on a given day (within-person effects). Daily stress was more strongly associated with EE than major life stress. However, the impact of daily stress on EE was amplified in women with greater past year major life stress. Finally, participants with lower HCC had increased EE. Conclusions: Findings confirm longitudinal associations between stress and EE in women, and highlight the importance of within-person shifts in stress in EE risk. Results also highlight HCC as a novel biological stress measure that is significantly associated with EE and may overcome limitations of prior physiological stress response indicators. [ABSTRACT FROM AUTHOR]

Background: Lifetime trajectories of mental ill-health are often established during adolescence. Effective interventions to prevent the emergence of mental health problems are needed. In the current study we assessed the efficacy of the cognitive behavioural therapy (CBT)-informed Climate Schools universal eHealth preventive mental health programme, relative to a control. We also explored whether the intervention had differential effects on students with varying degrees of social connectedness. Method: We evaluated the efficacy of the Climate Schools mental health programme (19 participating schools; average age at baseline was 13.6) v. a control group (18 participating schools; average age at baseline was 13.5) which formed part of a large cluster randomised controlled trial in Australian schools. Measures of internalising problems, depression and anxiety were collected at baseline, immediately following the intervention and at 6-, 12- and 18-months post intervention. Immediately following the intervention, 2539 students provided data on at least one outcome of interest (2065 students at 18 months post intervention). Results: Compared to controls, we found evidence that the standalone mental health intervention improved knowledge of mental health, however there was no evidence that the intervention improved other mental health outcomes, relative to a control. Student's social connectedness did not influence intervention outcomes. Conclusion: These results are consistent with recent findings that universal school-based, CBT-informed, preventive interventions for mental health have limited efficacy in improving symptoms of anxiety and depression when delivered alone. We highlight the potential for combined intervention approaches, and more targeted interventions, to better improve mental health outcomes. [ABSTRACT FROM AUTHOR]

Background: Childhood maltreatment (CM) represents a potent risk factor for major depressive disorder (MDD), including poorer treatment response. Altered resting-state connectivity in the fronto-limbic system has been reported in maltreated individuals. However, previous results in smaller samples differ largely regarding localization and direction of effects. Methods: We included healthy and depressed samples [ n = 624 participants with MDD; n = 701 healthy control (HC) participants] that underwent resting-state functional MRI measurements and provided retrospective self-reports of maltreatment using the Childhood Trauma Questionnaire. A-priori defined regions of interest [ROI; amygdala, hippocampus, anterior cingulate cortex (ACC)] were used to calculate seed-to-voxel connectivities. Results: No significant associations between maltreatment and resting-state connectivity of any ROI were found across MDD and HC participants and no interaction effect with diagnosis became significant. Investigating MDD patients only yielded maltreatment-associated increased connectivity between the amygdala and dorsolateral frontal areas [ p FDR < 0.001; η 2partial = 0.050; 95%-CI (0.023–0.085)]. This effect was robust across various sensitivity analyses and was associated with concurrent and previous symptom severity. Particularly strong amygdala-frontal associations with maltreatment were observed in acutely depressed individuals [ n = 264; p FDR < 0.001; η 2partial = 0.091; 95%-CI (0.038–0.166)). Weaker evidence – not surviving correction for multiple ROI analyses – was found for altered supracallosal ACC connectivity in HC individuals associated with maltreatment. Conclusions: The majority of previous resting-state connectivity correlates of CM could not be replicated in this large-scale study. The strongest evidence was found for clinically relevant maltreatment associations with altered adult amygdala-dorsolateral frontal connectivity in depression. Future studies should explore the relevance of this pathway for a maltreated subgroup of MDD patients. [ABSTRACT FROM AUTHOR]

Background: Research has shown a strong relationship between hallucinations and suicidal behaviour in general population samples. Whether hallucinations also index suicidal behaviour risk in groups at elevated risk of suicidal behaviour, namely in individuals with a sexual assault history, remains to be seen. Aims: We assessed whether hallucinations were markers of risk for suicidal behaviour among individuals with a sexual assault history. Methods: Using the cross-sectional 2007 (N = 7403) and 2014 (N = 7546) Adult Psychiatric Morbidity Surveys, we assessed for an interaction between sexual assault and hallucinations in terms of the odds of suicide attempt, as well as directly comparing the prevalence of suicide attempt in individuals with a sexual assault history with v. without hallucinations. Results: Individuals with a sexual assault history had increased odds of hallucinations and suicide attempt compared to individuals without a sexual assault history in both samples. There was a significant interaction between sexual assault and hallucinations in terms of the odds of suicide attempt. In total, 14–19% of individuals with a sexual assault history who did not report hallucinations had one or more suicide attempt. This increased to 33–52% of individuals with a sexual assault history who did report hallucinations (2007, aOR = 2.85, 1.71–4.75; 2014, aOR = 4.52, 2.78–7.35). Conclusions: Hallucinations are a risk marker for suicide attempt even among individuals with an elevated risk of suicidal behaviour, specifically individuals with a sexual assault history. This finding highlights the clinical significance of hallucinations with regard to suicidal behaviour risk, even among high-risk populations. [ABSTRACT FROM AUTHOR]

Background: Automated virtual reality therapies are being developed to increase access to psychological interventions. We assessed the experience with one such therapy of patients diagnosed with psychosis, including satisfaction, side effects, and positive experiences of access to the technology. We tested whether side effects affected therapy. Methods: In a clinical trial 122 patients diagnosed with psychosis completed baseline measures of psychiatric symptoms, received gameChange VR therapy, and then completed a satisfaction questionnaire, the Oxford-VR Side Effects Checklist, and outcome measures. Results: 79 (65.8%) patients were very satisfied with VR therapy, 37 (30.8%) were mostly satisfied, 3 (2.5%) were indifferent/mildly dissatisfied, and 1 (0.8%) person was quite dissatisfied. The most common side effects were: difficulties concentrating because of thinking about what might be happening in the room (n = 17, 14.2%); lasting headache (n = 10, 8.3%); and the headset causing feelings of panic (n = 9, 7.4%). Side effects formed three factors: difficulties concentrating when wearing a headset, feelings of panic using VR, and worries following VR. The occurrence of side effects was not associated with number of VR sessions, therapy outcomes, or psychiatric symptoms. Difficulties concentrating in VR were associated with slightly lower satisfaction. VR therapy provision and engagement made patients feel: proud (n = 99, 81.8%); valued (n = 97, 80.2%); and optimistic (n = 96, 79.3%). Conclusions: Patients with psychosis were generally very positive towards the VR therapy, valued having the opportunity to try the technology, and experienced few adverse effects. Side effects did not significantly impact VR therapy. Patient experience of VR is likely to facilitate widespread adoption. [ABSTRACT FROM AUTHOR]

Background: Depression, the most frequent and harmful mental disorder, has been associated with specific somatic diseases as the leading cause of death. The purposes of this prospective study were to predict incident chronic diseases based on baseline depressive symptoms and to test sex-dependent effects. Methods: In a representative German community sample of over 12 000 participants, baseline depressive symptoms (assessed using the Patient Health Questionnaire-9) were tested as a predictor of new onset of cardiovascular disease (CVD), chronic obstructive lung disease, diabetes, cancer, and migraine at 5-year follow-up. To study disease incidence, we created subsamples for each chronic disease by excluding participants who already had the respective disease at baseline. Potential confounders were included in logistic regression models and sex-specific analyses were performed. Results: Controlling for demographic characteristics and loneliness, in men and women, baseline depressive symptoms were predictive of CVD, chronic obstructive lung disease, diabetes, and migraine, but not of cancer. When we additionally adjusted for metabolic and lifestyle risk factors, there was an 8% increase of chronic obstructive lung disease and migraine per point of depressive symptoms. There was a trend for CVD (4%; p = 0.053). Sex-sensitive analyses revealed trends for the relevance of depressive symptoms for CVD in men (p = 0.065), and for diabetes in women (p = 0.077). Conclusions: These findings underscore the need to implement screening for depression in the treatment of major somatic illnesses. At the same time, depressed patients should be screened for metabolic and lifestyle risk factors and for somatic diseases and offered lifestyle interventions. [ABSTRACT FROM AUTHOR]

Background: Persecutory fears build on feelings of vulnerability that arise from negative views of the self. Body image concerns have the potential to be a powerful driver of feelings of vulnerability. Body image concerns are likely raised in patients with psychosis given the frequent weight gain. We examined for the first-time body esteem – the self-evaluation of appearance – in relation to symptom and psychological correlates in patients with current persecutory delusions. Methods: One-hundred and fifteen patients with persecutory delusions in the context of non-affective psychosis completed assessments of body image, self-esteem, body mass index (BMI), psychiatric symptoms and well-being. Body esteem was also assessed in 200 individuals from the general population. Results: Levels of body esteem were much lower in patients with psychosis than non-clinical controls (d = 1.2, p < 0.001). In patients, body esteem was lower in women than men, and in the overweight or obese BMI categories than the normal weight range. Body image concerns were associated with higher levels of depression (r = − 0.55, p < 0.001), negative self-beliefs (r = −0.52, p < 0.001), paranoia (r = −0.25, p = 0.006) and hallucinations (r = −0.21, p = 0.025). Body image concerns were associated with lower levels of psychological wellbeing (r = 0.41, p < 0.001), positive self-beliefs (r = 0.40, p < 0.001), quality of life (r = 0.23, p = 0.015) and overall health (r = 0.31, p = 0.001). Conclusions: Patients with current persecutory delusions have low body esteem. Body image concerns are associated with poorer physical and mental health, including more severe psychotic experiences. Improving body image for patients with psychosis is a plausible target of intervention, with the potential to result in a wide range of benefits. [ABSTRACT FROM AUTHOR]

Background: Data suggest poorer bereavement outcomes for lesbian, gay and bisexual people, but this has not been estimated in population-based research. This study compared bereavement outcomes for partners of same-gender and different-gender decedents. Methods: In this population-based, cross-sectional survey of people bereaved of a civil partner or spouse 6–10 months previously, we used adjusted logistic and linear regression to investigate outcomes of interest: (1) positive screen on Inventory of Complicated Grief (ICG), (2) positive screen on General Health Questionnaire (GHQ), (3) grief intensity (ICG) and (4) psychiatric symptoms (GHQ-12). Results: Among 233 same-gender partners and 329 of different-gender partners, 66.1% [95% confidence interval (CI) 60.0–72.2] and 59.2% [95% CI (53.9–64.6)] respectively screened positive for complicated grief on the ICG, whilst 76.0% [95% CI (70.5–81.5)] and 69.3% [95% CI (64.3–74.3)] respectively screened positive on the GHQ-12. Same-gender bereaved partners were not significantly more likely to screen positive for complicated grief than different-gender partners [adjusted odds ratio (aOR) 1.56, 95% CI (0.98–2.47)], p = 0.059, but same-gender bereaved partners were significantly more likely to screen for psychiatric caseness [aOR 1.67 (1.02, 2.71) p = 0.043]. We similarly found no significant association of partner gender with grief intensity [ B = 1.86, 95% CI (−0.91to 4.63), p = 0.188], but significantly greater psychological distress for same-gender partners [ B = 1.54, 95% CI (−0.69–2.40), p < 0.001]. Conclusions: Same-gender bereaved partners report significantly more psychological distress. In view of their poorer sub-clinical mental health, clinical and bereavement services should refine screening processes to identify those at risk of poor mental health outcomes. [ABSTRACT FROM AUTHOR]

Background: The Discrimination and Stigma Scale (DISC) is a patient-reported outcome measure which assesses experiences of discrimination among persons with a mental illness globally. Methods: This study evaluated whether the psychometric properties of a short-form version, DISC-Ultra Short (DISCUS) (11-item), could be replicated in a sample of people with a wide range of mental disorders from 21 sites in 15 countries/territories, across six global regions. The frequency of experienced discrimination was reported. Scaling assumptions (confirmatory factor analysis, inter-item and item-total correlations), reliability (internal consistency) and validity (convergent validity, known groups method) were investigated in each region, and by diagnosis group. Results: 1195 people participated. The most frequently reported experiences of discrimination were being shunned or avoided at work (48.7%) and discrimination in making or keeping friends (47.2%). Confirmatory factor analysis supported a unidimensional model across all six regions and five diagnosis groups. Convergent validity was confirmed in the total sample and within all regions [ Internalised Stigma of Mental Illness (ISMI-10): 0.28–0.67, stopping self: 0.54–0.72, stigma consciousness: −0.32–0.57], as was internal consistency reliability (α = 0.74–0.84). Known groups validity was established in the global sample with levels of experienced discrimination significantly higher for those experiencing higher depression [Patient Health Questionnaire (PHQ)-2: p < 0.001], lower mental wellbeing [Warwick-Edinburgh Well-being Scale (WEMWBS): p < 0.001], higher suicidal ideation [Beck Hopelessness Scale (BHS)-4: p < 0.001] and higher risk of suicidal behaviour [Suicidal Ideation Attributes Scale (SIDAS): p < 0.001]. Conclusions: The DISCUS is a reliable and valid unidimensional measure of experienced discrimination for use in global settings with similar properties to the longer DISC. It offers a brief assessment of experienced discrimination for use in clinical and research settings. [ABSTRACT FROM AUTHOR]

Background: Subthreshold depression (sD) negatively impacts well-being and psychosocial function and is more prevalent compared with major depressive disorder (MDD). However, as adults with sD are less likely to seek face-to-face intervention, internet-based cognitive-behavioral therapy (ICBT) may overcome barriers of accessibility to psychotherapy. Although several trials explored the efficacy of ICBT for sD, the results remain inconsistent. This study evaluated whether ICBT is effective in reducing depressive symptoms among Chinese adults with sD. Methods: A randomized controlled trial was performed. The participants were randomly assigned to 5 weeks of ICBT, group-based face-to-face cognitive-behavioral therapy (CBT), or a waiting list (WL). Assessments were conducted at baseline, post-intervention and at a 6-month follow-up. The primary outcome measured depressive symptoms using the Center for Epidemiological Studies Depression Scale (CES-D). Outcomes were analyzed using a mixed-effects model to assess the effects of ICBT. Results: ICBT participants reported greater reductions on all the outcomes compared to the WL group at post-intervention. The ICBT group showed larger improvement on the Patient Health Questionnaire-9 (PHQ-9) at post-intervention (d = 0.12) and at follow-up (d = 0.10), and with CES-D at post-intervention (d = 0.06), compared to the CBT group. Conclusions: ICBT is effective in reducing depressive symptoms among Chinese adults with sD, and improvements in outcomes were sustained at a 6-month follow-up. Considering the low rates of face-to-face psychotherapy, our findings highlight the considerable potential and implications for the Chinese government to promote the use of ICBT for sD in China. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) pandemic might affect mental health. Data from population-representative panel surveys with multiple waves including pre-COVID data investigating risk and protective factors are still rare. Methods: In a stratified random sample of the German household population (n = 6684), we conducted survey-weighted multiple linear regressions to determine the association of various psychological risk and protective factors assessed between 2015 and 2020 with changes in psychological distress [(PD; measured via Patient Health Questionnaire for Depression and Anxiety (PHQ-4)] from pre-pandemic (average of 2016 and 2019) to peri-pandemic (both 2020 and 2021) time points. Control analyses on PD change between two pre-pandemic time points (2016 and 2019) were conducted. Regularized regressions were computed to inform on which factors were statistically most influential in the multicollinear setting. Results: PHQ-4 scores in 2020 (M = 2.45) and 2021 (M = 2.21) were elevated compared to 2019 (M = 1.79). Several risk factors (catastrophizing, neuroticism, and asking for instrumental support) and protective factors (perceived stress recovery, positive reappraisal, and optimism) were identified for the peri-pandemic outcomes. Control analyses revealed that in pre-pandemic times, neuroticism and optimism were predominantly related to PD changes. Regularized regression mostly confirmed the results and highlighted perceived stress recovery as most consistent influential protective factor across peri-pandemic outcomes. Conclusions: We identified several psychological risk and protective factors related to PD outcomes during the COVID-19 pandemic. A comparison of pre-pandemic data stresses the relevance of longitudinal assessments to potentially reconcile contradictory findings. Implications and suggestions for targeted prevention and intervention programs during highly stressful times such as pandemics are discussed. [ABSTRACT FROM AUTHOR]

Background: Childhood maltreatment (CM) exerts various long-lasting psychological and biological changes in affected individuals, with inflammation being an interconnecting element. Besides chronic low-grade inflammation, CM might also affect the energy production of cells by altering the function and density of mitochondria, i.e. the body's main energy suppliers. Here, we compared mitochondrial respiration and density in intact peripheral blood mononuclear cells (PBMC), from women with and without CM between two time points, i.e. at the highly inflammatory phase within 1 week after parturition (t 0) and again after 1 year (t 2). Methods: CM exposure was assessed with the Childhood Trauma Questionnaire. Whole blood was collected from n = 52 healthy women within the study 'My Childhood – Your Childhood' at both time points to isolate and cryopreserve PBMC. Thawed PBMC were used to measure mitochondrial respiration and density by high-resolution respirometry followed by spectrophotometric analyses of citrate-synthase activity. Results: Over time, quantitative respiratory parameters increased, while qualitative flux control ratios decreased, independently of CM. Women with CM showed higher mitochondrial respiration and density at t 0, but not at t 2. We found significant CM group × time interaction effects for ATP-turnover -related respiration and mitochondrial density. Conclusions: This is the first study to longitudinally investigate mitochondrial bioenergetics in postpartum women with and without CM. Our results indicate that CM-related mitochondrial alterations reflect allostatic load, probably due to higher inflammatory states during parturition, which normalize later. However, later inflammatory states might moderate the vulnerability for a second-hit on the level of mitochondrial bioenergetics, at least in immune cells. [ABSTRACT FROM AUTHOR]

Background: Alterations in heart rate (HR) may provide new information about physiological signatures of depression severity. This 2-year study in individuals with a history of recurrent major depressive disorder (MDD) explored the intra-individual variations in HR parameters and their relationship with depression severity. Methods: Data from 510 participants (Number of observations of the HR parameters = 6666) were collected from three centres in the Netherlands, Spain, and the UK, as a part of the remote assessment of disease and relapse-MDD study. We analysed the relationship between depression severity, assessed every 2 weeks with the Patient Health Questionnaire-8, with HR parameters in the week before the assessment, such as HR features during all day, resting periods during the day and at night, and activity periods during the day evaluated with a wrist-worn Fitbit device. Linear mixed models were used with random intercepts for participants and countries. Covariates included in the models were age, sex, BMI, smoking and alcohol consumption, antidepressant use and co-morbidities with other medical health conditions. Results: Decreases in HR variation during resting periods during the day were related with an increased severity of depression both in univariate and multivariate analyses. Mean HR during resting at night was higher in participants with more severe depressive symptoms. Conclusions: Our findings demonstrate that alterations in resting HR during all day and night are associated with depression severity. These findings may provide an early warning of worsening depression symptoms which could allow clinicians to take responsive treatment measures promptly. [ABSTRACT FROM AUTHOR]

Background: Many individuals with posttraumatic stress disorder (PTSD) have limited access to first-line treatments, warranting the development of remotely-delivered treatments. Attention bias modification (ABM), targeting perturbed threat-related attentional patterns, shows promise when delivered in-person. However, previous studies found ABM to be ineffective when delivered remotely. Randomized clinical trials usually applied two variations of ABM: ABM away from threat or attention control training (ACT) balancing attention between threat-related and neutral stimuli. We tested remotely-delivered ACT/ABM with tighter supervision and video-based interactions that resemble in-clinic protocols. We expected to replicate the results of in-clinic trials, in which ACT outperformed ABM for PTSD. Methods: In this double-blinded, parallel-group randomized controlled trial, 60 patients diagnosed with PTSD were randomized (ABM n = 30; ACT n = 30). Patients performed eight bi-weekly remotely-delivered supervised ABM/ACT sessions. Symptoms were assessed pre- and post-treatment with Clinician-Administered PTSD Scale 5 (CAPS-5) severity score and PTSD diagnosis as the primary outcomes. Current depressive episode, current anxiety-related comorbidity, and time elapsed since the trauma were examined as potential moderators of treatment outcome. Results: Significant decrease in CAPS-5 severity scores and PTSD diagnosis was observed following both ACT and ABM with no between-group difference. Patients without depression or whose trauma occurred more recently had greater symptom reduction in the ACT than the ABM group. Conclusions: Contrary to our expectation, symptoms decreased similarly following ACT and ABM. Moderator analyses suggest advantage for ACT in non-depressed patients and patients whose trauma occurred more recently. Further refinements in remotely-delivered ABM/ACT may be needed. [ABSTRACT FROM AUTHOR]

Abstract Background: Chronic muscle diseases (MD) are progressive and cause wasting and weakness in muscles and are associated with reduced quality of life (QoL). The ACTMuS trial examined whether Acceptance and Commitment Therapy (ACT) as an adjunct to usual care improved QoL for such patients as compared to usual care alone. Methods: This two-arm, randomised, multicentre, parallel design recruited 155 patients with MD (Hospital and Depression Scale ⩾ 8 for depression or ⩾ 8 for anxiety and Montreal Cognitive Assessment ⩾ 21/30). Participants were randomised, using random block sizes, to one of two groups: standard medical care (SMC) (n = 78) or to ACT in addition to SMC (n = 77), and were followed up to 9 weeks. The primary outcome was QoL, assessed by the Individualised Neuromuscular Quality of Life Questionnaire (INQoL), the average of five subscales, at 9-weeks. Trial registration was NCT02810028. Results: 138 people (89.0%) were followed up at 9-weeks. At all three time points, the adjusted group difference favoured the intervention group and was significant with moderate to large effect sizes. Secondary outcomes (mood, functional impairment, aspects of psychological flexibility) also showed significant differences between groups at week 9. Conclusions: ACT in addition to usual care was effective in improving QoL and other psychological and social outcomes in patients with MD. A 6 month follow up will determine the extent to which gains are maintained. [ABSTRACT FROM AUTHOR]

Background: Despite a wide range of proposed risk factors and theoretical models, prediction of eating disorder (ED) onset remains poor. This study undertook the first comparison of two machine learning (ML) approaches [penalised logistic regression (LASSO), and prediction rule ensembles (PREs)] to conventional logistic regression (LR) models to enhance prediction of ED onset and differential ED diagnoses from a range of putative risk factors. Method: Data were part of a European Project and comprised 1402 participants, 642 ED patients [52% with anorexia nervosa (AN) and 40% with bulimia nervosa (BN)] and 760 controls. The Cross-Cultural Risk Factor Questionnaire, which assesses retrospectively a range of sociocultural and psychological ED risk factors occurring before the age of 12 years (46 predictors in total), was used. Results: All three statistical approaches had satisfactory model accuracy, with an average area under the curve (AUC) of 86% for predicting ED onset and 70% for predicting AN v. BN. Predictive performance was greatest for the two regression methods (LR and LASSO), although the PRE technique relied on fewer predictors with comparable accuracy. The individual risk factors differed depending on the outcome classification (EDs v. non-EDs and AN v. BN). Conclusions: Even though the conventional LR performed comparably to the ML approaches in terms of predictive accuracy, the ML methods produced more parsimonious predictive models. ML approaches offer a viable way to modify screening practices for ED risk that balance accuracy against participant burden. [ABSTRACT FROM AUTHOR]

Background: Personality traits may predict antidepressant discontinuation and response. However, previous studies were rather small, only explored a few personality traits and did not include adverse drug effects nor the interdependency between antidepressant discontinuation patterns and response. Methods: GENDEP included 589 patients with unipolar moderate-severe depression treated with escitalopram or nortriptyline for 12 weeks. Seven personality dimensions were measured using the self-reported 240-item Temperament and Character Inventory-Revised (TCI-R). We applied Cox proportional models to study discontinuation patterns, logistic and linear regression to investigate response and remission after 8 and 12 weeks, and mixed-effects linear models regarding time-varying treatment response and adverse drug reactions. Results: Low harm avoidance, low cooperativeness, high self-transcendence and high novelty seeking were associated with higher risks for antidepressant discontinuation, independent of depressed mood, adverse drug reactions, drug, sex and age. Regression analyses showed that higher novelty seeking and cooperativeness scores were associated with a greater likelihood of response and remission after 8 and 12 weeks, respectively, but we found no correlations with response in the mixed-effects models. Only high harm avoidance was associated with more self-reported adverse effects. Conclusions: This study, representing the largest investigation between several personality traits and response to two different antidepressants, suggests that correlations between personality traits and antidepressant treatment response may be confounded by differential rates of discontinuation. Future trials on personality in the treatment of depression need to consider this interdependency and study whether interventions aiming at improving compliance for some personality types may improve response to antidepressants. [ABSTRACT FROM AUTHOR]

Background: Suppression of the rostral anterior cingulate cortex (rACC) has shown promise as a prognostic biomarker for depression. We aimed to use machine learning to characterise its ability to predict depression remission. Methods: Data were obtained from 81 15- to 25-year-olds with a major depressive disorder who had participated in the YoDA-C trial, in which they had been randomised to receive cognitive behavioural therapy plus either fluoxetine or placebo. Prior to commencing treatment patients performed a functional magnetic resonance imaging (fMRI) task to assess rACC suppression. Support vector machines were trained on the fMRI data using nested cross-validation, and were similarly trained on clinical data. We further tested our fMRI model on data from the YoDA-A trial, in which participants had completed the same fMRI paradigm. Results: Thirty-six of 81 (44%) participants in the YoDA-C trial achieved remission. Our fMRI model was able to predict remission status (AUC = 0.777 [95% confidence interval (CI) 0.638–0.916], balanced accuracy = 67%, negative predictive value = 74%, p < 0.0001). Clinical models failed to predict remission status at better than chance levels. Testing the model on the alternative YoDA-A dataset confirmed its ability to predict remission (AUC = 0.776, balanced accuracy = 64%, negative predictive value = 70%, p < 0.0001). Conclusions: We confirm that rACC activity acts as a prognostic biomarker for depression. The machine learning model can identify patients who are likely to have difficult-to-treat depression, which might direct the earlier provision of enhanced support and more intensive therapies. [ABSTRACT FROM AUTHOR]

Background: A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. Methods: We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS − ORexposure − ORPRS + 1] with adjustment for potential confounders. Results: There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) −1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI −6.25 to 20.88). Conclusions: Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates. [ABSTRACT FROM AUTHOR]

Background: Psychological models of posttraumatic stress disorder (PTSD) and prolonged grief disorder (PGD) make predictions about the role of unhelpful coping strategies in maintaining difficulties by blocking self-correction of negative appraisals and memory integration following stressful life events like bereavement. However, few studies have tested these predictions directly. Method: We used counterfactually based causal mediation to assess whether unhelpful coping strategies mediated the relationship between (1) loss-related memory characteristics and/or (2) negative grief-related appraisals and symptoms of PGD, PTSD and depression using a three-wave longitudinal sample (N = 275). Appraisals and memory characteristics were measured at time point 1, unhelpful coping strategies at T2, and symptom variables at T3. Additionally, multiple mediation analyses within a structural equation modelling (SEM) framework assessed which types of coping strategies differentially mediated symptoms of PGD, PTSD and depression. Results: Coping strategies mediated the relationship between negative appraisals and memory characteristics and symptoms of PGD, PTSD and depression after adjusting for demographics and loss characteristics. Sensitivity analyses suggested that these results were most robust for PGD, followed by PTSD and then depression. Multiple mediation analyses suggested that all four subscales (avoidance, proximity seeking, loss rumination and injustice rumination) individually mediated the effect of memory characteristics and appraisals on PGD. Conclusions: These results suggest that core predictions of the cognitive model for PTSD and the cognitive behavioural model of PGD are useful in predicting symptoms of post-loss mental health problems in the first 12–18 months after loss. Targeting unhelpful coping strategies is likely to reduce symptoms of PGD, PTSD and depression. [ABSTRACT FROM AUTHOR]

Background: Although mental wellbeing has been linked with positive health outcomes, including longevity and improved emotional and cognitive functioning, studies examining the underlying neural mechanisms of both subjective and psychological wellbeing have been sparse. We assessed whether both forms of wellbeing are associated with neural activity engaged during positive and negative emotion processing and the extent to which this association is driven by genetics or environment. Methods: We assessed mental wellbeing in 230 healthy adult monozygotic and dizygotic twins using a previously validated questionnaire (COMPAS-W) and undertook functional magnetic resonance imaging during a facial emotion viewing task. We used linear mixed models to analyse the association between COMPAS-W scores and emotion-elicited neural activation. Univariate twin modelling was used to evaluate heritability of each brain region. Multivariate twin modelling was used to compare twin pairs to assess the contributions of genetic and environmental factors to this association. Results: Higher levels of wellbeing were associated with greater neural activity in the dorsolateral prefrontal cortex, localised in the right inferior frontal gyrus (IFG), in response to positive emotional expressions of happiness. Univariate twin modelling showed activity in the IFG to have 20% heritability. Multivariate twin modelling suggested that the association between wellbeing and positive emotion-elicited neural activity was driven by common variance from unique environment (r = 0.208) rather than shared genetics. Conclusions: Higher mental wellbeing may have a basis in greater engagement of prefrontal neural regions in response to positive emotion, and this association may be modifiable by unique life experiences. [ABSTRACT FROM AUTHOR]

Background: For a century, psychedelics have been investigated as models of psychosis for demonstrating phenomenological similarities with psychotic experiences and as therapeutic models for treating depression, anxiety, and substance use disorders. This study sought to explore this paradoxical relationship connecting key parameters of the psychotic experience, psychotherapy, and psychedelic experience. Methods: In a randomized, double-blind, placebo-controlled, crossover design, 24 healthy volunteers received 50 μg d-lysergic acid diethylamide (LSD) or inactive placebo. Psychotic experience was assessed by aberrant salience (Aberrant Salience Inventory, ASI), therapeutic potential by suggestibility (Creative Imagination Scale, CIS) and mindfulness (Five Facet Mindfulness Questionnaire, FFMQ; Mindful Attention Awareness Scale, MAAS; Experiences Questionnaire, EQ), and psychedelic experience by four questionnaires (Altered State of Consciousness Questionnaire, ASC; Mystical Experiences Questionnaire, MEQ; Challenging Experiences Questionnaire, CEQ; Ego-Dissolution Inventory, EDI). Relationships between LSD-induced effects were examined. Results: LSD induced psychedelic experiences, including alteration of consciousness, mystical experiences, ego-dissolution, and mildly challenging experiences, increased aberrant salience and suggestibility, but not mindfulness. LSD-induced aberrant salience correlated highly with complex imagery, mystical experiences, and ego-dissolution. LSD-induced suggestibility correlated with no other effects. Individual mindfulness changes correlated with aspects of aberrant salience and psychedelic experience. Conclusions: The LSD state resembles a psychotic experience and offers a tool for healing. The link between psychosis model and therapeutic model seems to lie in mystical experiences. The results point to the importance of meaning attribution for the LSD psychosis model and indicate that psychedelic-assisted therapy might benefit from therapeutic suggestions fostering mystical experiences. [ABSTRACT FROM AUTHOR]

Background: Unpaid carers who look after another member of their household (home-carers) have poorer mental health than the general population. The first COVID-19 national lockdown led to an increasing reliance on home-carers and we investigate the short- and longer-term impacts of lockdown on their mental health. Methods: Data from 9737 adult participants (aged 16+) from the UK Household Longitudinal Study (Understanding Society) were used to explore changes in 12-item General Health Questionnaire (GHQ-12) score between (a) pre-pandemic (2019) and early lockdowns (April 2020) and (b) early and later (July 2020) lockdowns. Results: GHQ-12 scores among home-carers were higher pre-lockdown and increased more than for non-carers from 2019 to April 2020 with further increases for home-carers compared with non-carers between April and July. Compared with respondents caring for a spouse/partner, those caring for a child under 18 had a particularly marked increase in GHQ-12 score between 2019 and April, as did those caring for someone with a learning disability. Home-carers of children under 18 improved from April to July while those caring for adult children saw a marked worsening of their mental health. Home-carers with greater care burden saw larger increases in GHQ-12 score from 2019 to April and from April to July, and increases through both periods were greater for home-carers who had formal help prior to lockdown but then lost it. Conclusions: The mental health of home-carers deteriorated more during lockdown than non-carers. Policies that reinstate support for them and their care-recipients will benefit the health of both vulnerable groups. [ABSTRACT FROM AUTHOR]

Background: Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure. Methods: We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry. Results: (i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains 'emotional neglect' and 'emotional abuse' were most predictive for CHR and ROP, while in ROD 'physical abuse' and 'sexual abuse' were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found. Conclusions: These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Anxiety disorders are highly prevalent with an early age of onset. Understanding the aetiology of disorder emergence and recovery is important for establishing preventative measures and optimising treatment. Experimental approaches can serve as a useful model for disorder and recovery relevant processes. One such model is fear conditioning. We conducted a remote fear conditioning paradigm in monozygotic and dizygotic twins to determine the degree and extent of overlap between genetic and environmental influences on fear acquisition and extinction. Methods: In total, 1937 twins aged 22–25 years, including 538 complete pairs from the Twins Early Development Study took part in a fear conditioning experiment delivered remotely via the Fear Learning and Anxiety Response (FLARe) smartphone app. In the fear acquisition phase, participants were exposed to two neutral shape stimuli, one of which was repeatedly paired with a loud aversive noise, while the other was never paired with anything aversive. In the extinction phase, the shapes were repeatedly presented again, this time without the aversive noise. Outcomes were participant ratings of how much they expected the aversive noise to occur when they saw either shape, throughout each phase. Results: Twin analyses indicated a significant contribution of genetic effects to the initial acquisition and consolidation of fear, and the extinction of fear (15, 30 and 15%, respectively) with the remainder of variance due to the non-shared environment. Multivariate analyses revealed that the development of fear and fear extinction show moderate genetic overlap (genetic correlations 0.4–0.5). Conclusions: Fear acquisition and extinction are heritable, and share some, but not all of the same genetic influences. [ABSTRACT FROM AUTHOR]

Background: Intake of omega-3 polyunsaturated fatty acids (PUFAs) has favorable effects, including reducing violent and aggressive behaviors, but its association with infant maltreatment is unknown. We therefore tested the hypothesis that maternal intake of omega-3 PUFAs is associated with a lower risk of infant maltreatment. Methods: Participants were 92 191 mothers involved in the ongoing Japan Environment and Children's Study. Omega-3 PUFA intake during pregnancy was measured using a food frequency questionnaire. Infant maltreatment was assessed using a self-reported questionnaire administered at 1 and 6 months postpartum. Results: Analysis using the lowest quintile of intake as a reference revealed that the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for cases of 'hitting' decreased as quintiles increased, with values for the second to fifth quintiles of 0.93 (95% CI 0.77–1.13), 0.79 (95% CI 0.64–0.97), 0.78 (95% CI 0.64–0.96), and 0.72 (95% CI 0.59–0.89), respectively. Adjusted ORs (95% CIs) for 'shaking very hard' at 6 months were 0.87 (0.73–1.04), 0.81 (0.67–0.97), 0.73 (0.61–0.89), and 0.78 (0.65–0.94), respectively. Adjusted ORs for 'leaving alone at home' for the second to fifth quintiles were 0.92 (0.87–0.98), 0.91 (0.86–0.97), 0.94 (0.88–0.99), and 0.85 (0.80–0.90), respectively. Conclusions: Higher maternal intake of omega-3 PUFAs during pregnancy was associated with fewer cases of hitting and violent shaking and leaving the child alone at home, implying a lower risk of infant maltreatment. Our results indicate the potential applicability of omega-3 PUFAs in reducing infant maltreatment. [ABSTRACT FROM AUTHOR]