England's primary care service for psychological therapy (Improving Access to Psychological Therapies [IAPT]) treats anxiety and depression, with a target recovery rate of 50%. Identifying the characteristics of patients who achieve recovery may assist in optimizing future treatment. This naturalistic cohort study investigated pre-therapy characteristics as predictors of recovery and improvement after IAPT therapy.

In a cohort of patients attending an IAPT service in South London, we recruited 263 participants and conducted a baseline interview to gather extensive pre-therapy characteristics. Bayesian prediction models and variable selection were used to identify baseline variables prognostic of good clinical outcomes. Recovery (primary outcome) was defined using (IAPT) service-defined score thresholds for both depression (Patient Health Questionnaire [PHQ-9]) and anxiety (Generalized Anxiety Disorder [GAD-7]). Depression and anxiety outcomes were also evaluated as standalone (PHQ-9/GAD-7) scores after therapy. Prediction model performance metrics were estimated using cross-validation.

Predictor variables explained 26% (recovery), 37% (depression), and 31% (anxiety) of the variance in outcomes, respectively. Variables prognostic of recovery were lower pre-treatment depression severity and not meeting criteria for obsessive compulsive disorder. Post-therapy depression and anxiety severity scores were predicted by lower symptom severity and higher ratings of health-related quality of life (EuroQol questionnaire [EQ5D]) at baseline.

Almost a third of the variance in clinical outcomes was explained by pre-treatment symptom severity scores. These constructs benefit from being rapidly accessible in healthcare services. If replicated in external samples, the early identification of patients who are less likely to recover may facilitate earlier triage to alternative interventions.

Childhood adversity has been associated with increased peripheral inflammation in adulthood. However, not all individuals who experience early adversity develop these inflammatory outcomes. Separately, there is also a link between various internalizing emotional distress conditions (e.g. depression, anxiety, and fear) and inflammation in adulthood. It is possible the combination of adult emotional distress and past childhood adversity may be uniquely important for explaining psychopathology-related immune dysfunction at midlife.

Using data from the Midlife in the United States (MIDUS) study (n = 1255), we examined whether internalizing, defined as past 12-month emotional distress symptomatology and trait neuroticism, moderated associations between childhood adversity and heightened inflammation in adulthood. Using latent variable modeling, we examined whether transdiagnostic or disorder-specific features of emotional distress better predicted inflammation.

We observed that childhood adversity only predicted adult inflammation when participants also reported adult internalizing emotional distress. Furthermore, this moderation effect was specific to the transdiagnostic factor of emotional distress rather than the disorder-specific features.

We discuss the possibility that adult internalizing symptoms and trait neuroticism together may signal the presence of temporally stable vulnerabilities that amplify the impact of childhood adversity on midlife immune alterations. The study highlights the importance of identifying emotional distress in individuals who have experienced childhood adversity to address long-term immune outcomes and enhance overall health.

Prior studies suggest that childhood maltreatment is associated with altered hippocampal volume. However, longitudinal studies are currently scarce, making it difficult to determine how alterations in hippocampal volume evolve over time. The current study examined the relationship between childhood maltreatment and hippocampal volumetric development across childhood and adolescence in a community sample.

In this longitudinal study, a community sample of 795 participants underwent brain magnetic resonance imaging (MRI) in three waves spanning ages 6–21 years. Childhood maltreatment was assessed using parent-report and children´s self-report at baseline (6–12 years old). Mixed models were used to examine the relationship between childhood maltreatment and hippocampal volume across time.

The quadratic term of age was significantly associated with both right and left hippocampal volume development. High exposure to childhood maltreatment was associated with reduced offset of right hippocampal volume and persistent reduced volume throughout adolescence.

Critically, the relationship between childhood maltreatment and reduced right hippocampal volume remained significant after adjusting for the presence of any depressive disorder during late childhood and adolescence and hippocampal volume polygenic risk scores. Time-by-CM and Sex-by-CM interactions were not statistically significant.

The present study showed that childhood maltreatment is associated with persistent reduction of hippocampal volume in children and adolescents, even after adjusting for the presence of major depressive disorder and genetic determinants of hippocampal structure.

At a time of increased demand for specialist mental health services, a more nuanced understanding of how adolescents navigate systems of care and support is essential. We mapped ‘networks of care’ to explore patterns of mental health help-seeking alongside the perceived helpfulness of support accessed.

We examined data from 23 927 adolescents aged 11–18 years who participated in the 2023 OxWell Student Survey, an English school-based, repeated cross-sectional survey of mental health and wellbeing. Students self-reported past-year access to 18 types of support across informal (e.g. friends and family), semi-formal (e.g. school and charities), and formal (e.g. health and social care) domains, alongside how helpful they found the support. We used a network approach to explore interconnections between sources of support accessed and perceived helpfulness.

One in four (27.0%, 6449/23927) adolescents reported past-year access to mental health support, of which 56.7% (3658/6449) reported accessing multiple types. Informal networks were the most commonly accessed (23.1%, 5523/23927), followed by semi-formal (9.7%, 2317/23927) and formal (6.8%, 1623/23927) supports. Informal sources had high acceptability, with around 80–90% reporting them as helpful, whereas child and adolescent mental health services (CAMHS), helplines, and online supports were perceived to be the least helpful. The networks also identified groups who might not be optimally served by current systems, including gender diverse adolescents and adolescents who found mental health support from their parents unhelpful.

Adolescents are accessing mental health support across informal, semi-formal, and formal sources of care. Services can no longer be developed, delivered, or evaluated in isolation from these networks.

Loneliness has become a major public health issue of the recent decades due to its severe impact on health and mortality. Little is known about the relation between loneliness and social anxiety. This study aimed (1) to explore levels of loneliness and social anxiety in the general population, and (2) to assess whether and how loneliness affects symptoms of social anxiety and vice versa over a period of five years.

The study combined data from the baseline assessment and the five-year follow-up of the population-based Gutenberg Health Study. Data of N = 15 010 participants at baseline (Mage = 55.01, s.d.age = 11.10) were analyzed. Multiple regression analyses with loneliness and symptoms of social anxiety at follow-up including sociodemographic, physical illnesses, and mental health indicators at baseline were used to test relevant covariates. Effects of loneliness on symptoms of social anxiety over five years and vice versa were analyzed by autoregressive cross-lagged structural equation models.

At baseline, 1076 participants (7.41%) showed symptoms of social anxiety and 1537 (10.48%) participants reported feelings of loneliness. Controlling for relevant covariates, symptoms of social anxiety had a small significant effect on loneliness five years later (standardized estimate of 0.164, p < 0.001). Vice versa, there was no significant effect of loneliness on symptoms of social anxiety taking relevant covariates into account.

Findings provided evidence that symptoms of social anxiety are predictive for loneliness. Thus, prevention and intervention efforts for loneliness need to address symptoms of social anxiety.

Both childhood adversity (CA) and first-episode psychosis (FEP) have been linked to alterations in cortical thickness (CT). The interactive effects between different types of CAs and FEP on CT remain understudied.

One-hundred sixteen individuals with FEP (mean age = 23.8 ± 6.9 years, 34% females, 80.2% non-affective FEP) and 98 healthy controls (HCs) (mean age = 24.4 ± 6.2 years, 43% females) reported the presence/absence of CA <17 years using an adapted version of the Childhood Experience of Care and Abuse (CECA.Q) and the Retrospective Bullying Questionnaire (RBQ) and underwent magnetic resonance imaging (MRI) scans. Correlation analyses were used to assess associations between brain maps of CA and FEP effects. General linear models (GLMs) were performed to assess the interaction effects of CA and FEP on CT.

Eighty-three individuals with FEP and 83 HCs reported exposure to at least one CA. CT alterations in FEP were similar to those found in participants exposed to separation from parents, bullying, parental discord, household poverty, and sexual abuse (r = 0.50 to 0.25). Exposure to neglect (β = −0.24, 95% CI [−0.37 to −0.12], p = 0.016) and overall maltreatment (β = −0.13, 95% CI [−0.20 to −0.06], p = 0.043) were associated with cortical thinning in the right medial orbitofrontal region.

Cortical alterations in individuals with FEP are similar to those observed in the context of socio-environmental adversity. Neglect and maltreatment may contribute to CT reductions in FEP. Our findings provide new insights into the specific neurobiological effects of CA in early psychosis.

Motivated behaviors vary widely across individuals and are controlled by a range of environmental and intrinsic factors. However, due to a lack of objective measures, the role of intrinsic v. extrinsic control of motivation in psychiatric disorders remains poorly understood.

We developed a novel multi-factorial behavioral task that separates the distinct contributions of intrinsic v. extrinsic control, and determines their influence on motivation and outcome sensitivity in a range of contextual environments. We deployed this task in two independent cohorts (final in-person N = 181 and final online N = 258), including individuals with and without depression and anxiety disorders.

There was a significant interaction between group (controls, depression, anxiety) and control-condition (extrinsic, intrinsic) on motivation where participants with depression showed lower extrinsic motivation and participants with anxiety showed higher extrinsic motivation compared to controls, while intrinsic motivation was broadly similar across the groups. There was also a significant group-by-valence (rewards, losses) interaction, where participants with major depressive disorder showed lower motivation to avoid losses, but participants with anxiety showed higher motivation to avoid losses. Finally, there was a double-dissociation with anhedonic symptoms whereby anticipatory anhedonia was associated with reduced extrinsic motivation, whereas consummatory anhedonia was associated with lower sensitivity to outcomes that modulated intrinsic behavior. These findings were robustly replicated in the second independent cohort.

Together this work demonstrates the effects of intrinsic and extrinsic control on altering motivation and outcome sensitivity, and shows how depression, anhedonia, and anxiety may influence these biases.

The relationship between adolescent alcohol use and emotional problems remains unclear and contradictory. These inconsistencies may in part be due to differences in the measurement and operationalization of alcohol use and emotional problems across studies, as well as confounder selection and missing data decisions. This study explores the associations between common specifications of adolescent alcohol use and emotional problems in a large sample of adolescents.

A multiverse analysis (also known as specification curve analysis or vibration of effects) was done with 7680 unique model specifications in a large longitudinal sample of 6639 Australian adolescents (aged ~14.7–15.7, 2021–2022).

While alcohol use and emotional problems nearly universally co-occurred in minimally adjusted cross-sectional models (98–99%), the operationalization of emotional problems, temporality of prospective relationships, and choice of confounders substantially impacted findings. Emotional problems appeared to predict later alcohol use more-so than the reverse, depression-focused measures yielded more consistent associations with alcohol use than anxiety-focused measures, and certain confounders (i.e. conduct, ADHD, smoking) explained most of the associations between adolescent alcohol use and emotional problems. Missing data decisions and whether outcomes were modelled continuously v. dichotomously had minimal impact on findings.

While adolescent alcohol use and emotional problems commonly co-occur, inconsistencies in the magnitude, direction, and significance of effects are closely tied to researcher decisions that are often made arbitrarily.

Stigma of mental health conditions hinders recovery and well-being. The Honest, Open, Proud (HOP) program shows promise in reducing stigma but there is uncertainty about the feasibility of a randomized trial to evaluate a peer-delivered, individual adaptation of HOP for psychosis (Let's Talk).

A multi-site, Prospective Randomized Open Blinded Evaluation (PROBE) design, feasibility randomised controlled trial (RCT) comparing the peer-delivered intervention (Let's Talk) to treatment as usual (TAU). Follow-up was 2.5 and 6 months. Randomization was via a web-based system, with permuted blocks of random size. Up to 10 sessions of the intervention over 10 weeks were offered. The primary outcome was feasibility data (recruitment, retention, intervention attendance). Primary outcomes were analyzed by intention to treat. Safety outcomes were reported by as treated status. The study was prospectively registered: https://doi.org/10.1186/ISRCTN17197043.

149 patients were referred to the study and 70 were recruited. 35 were randomly assigned to intervention + TAU and 35 to TAU. Recruitment was 93% of the target sample size. Retention rate was high (81% at 2.5 months primary endpoint), and intervention attendance rate was high (83%). 21% of 33 patients in Let's talk + TAU had an adverse event and 16% of 37 patients in TAU. One serious adverse event (pre-randomization) was partially related and expected.

This is the first trial to show that it is feasible and safe to conduct a RCT of HOP adapted for people with psychosis and individual delivery. An adequately powered trial is required to provide robust evidence.

The identification of predictors of treatment response is crucial for improving treatment outcome for children with anxiety disorders. Machine learning methods provide opportunities to identify combinations of factors that contribute to risk prediction models.

A machine learning approach was applied to predict anxiety disorder remission in a large sample of 2114 anxious youth (5–18 years). Potential predictors included demographic, clinical, parental, and treatment variables with data obtained pre-treatment, post-treatment, and at least one follow-up.

All machine learning models performed similarly for remission outcomes, with AUC between 0.67 and 0.69. There was significant alignment between the factors that contributed to the models predicting two target outcomes: remission of all anxiety disorders and the primary anxiety disorder. Children who were older, had multiple anxiety disorders, comorbid depression, comorbid externalising disorders, received group treatment and therapy delivered by a more experienced therapist, and who had a parent with higher anxiety and depression symptoms, were more likely than other children to still meet criteria for anxiety disorders at the completion of therapy. In both models, the absence of a social anxiety disorder and being treated by a therapist with less experience contributed to the model predicting a higher likelihood of remission.

These findings underscore the utility of prediction models that may indicate which children are more likely to remit or are more at risk of non-remission following CBT for childhood anxiety.

Accumulating evidence suggests that rapid eye movement sleep (REM) supports the consolidation of extinction memory. REM is disrupted in posttraumatic stress disorder (PTSD), and REM abnormalities after traumatic events increase the risk of developing PTSD. Therefore, it was hypothesized that abnormal REM in trauma-exposed individuals may pave the way for PTSD by interfering with the processing of extinction memory. In addition, PTSD patients display reduced vagal activity. Vagal activity contributes to the strengthening of memories, including fear extinction memory, and recent studies show that the role of vagus in memory processing extends to memory consolidation during sleep. Therefore, it is plausible that reduced vagal activity during sleep in trauma-exposed individuals may be an additional mechanism that impairs extinction memory consolidation. However, to date, the contribution of sleep vagal activity to the consolidation of extinction memory or any emotional memory has not been investigated.

Trauma-exposed individuals (n = 113) underwent a 2-day fear conditioning and extinction protocol. Conditioning and extinction learning phases were followed by extinction recall 24 h later. The association of extinction recall with REM characteristics and REM vagal activity (indexed as heart rate variability) during the intervening consolidation night was examined.

Consistent with our hypotheses, REM disruption was associated with poorer physiological and explicit extinction memory. Furthermore, higher vagal activity during REM was associated with better explicit extinction memory, and physiological extinction memory in males.

These findings support the notion that abnormal REM, including reduced REM vagal activity, may contribute to PTSD by impairing the consolidation of extinction memory.

Among those with common mental health disorders (e.g. mood, anxiety, and stress disorders), comorbidity of substance and other addictive disorders is prevalent. To simplify the seemingly complex relationships underlying such comorbidity, methods that include multiple measures to distill which specific addictions are uniquely associated with specific mental health disorders rather than due to the co-occurrence of other related addictions or mental health disorders can be used.

In a general population sample of Jewish adults in Israel (N = 4002), network analysis methods were used to create partial correlation networks of continuous measures of problematic substance (non-medical use of alcohol, tobacco, cannabis, and prescription sedatives, stimulants, and opioid painkillers) and behavioral (gambling, electronic gaming, sexual behavior, pornography, internet, social media, and smartphone) addictions and common mental health problems (depression, anxiety, and post-traumatic stress disorder [PTSD]), adjusted for all variables in the model.

Strongest associations were observed within these clusters: (1) PTSD, anxiety, and depression; (2) problematic substance use and gambling; (3) technology-based addictive behaviors; and (4) problematic sexual behavior and pornography. In terms of comorbidity, the strongest unique associations were observed for PTSD and problematic technology-based behaviors (social media, smartphone), and sedatives and stimulants use; depression and problematic technology-based behaviors (gaming, internet) and sedatives and cannabis use; and anxiety and problematic smartphone use.

Network analysis isolated unique relationships underlying the observed comorbidity between common mental health problems and addictions, such as associations between mental health problems and technology-based behaviors, which is informative for more focused interventions.

Dialectical behavior therapy (DBT) is a specialized treatment that has a growing evidence base for binge-spectrum eating disorders. However, cost and workforce capacity limit wide-scale uptake of DBT since it involves over 20 in-person sessions with a trained professional (and six sessions for guided self-help format). Interventions translated for delivery through modern technology offer a solution to increase the accessibility of evidence-based treatments. We developed the first DBT-specific skills training smartphone application (Resilience: eDBT) for binge-spectrum eating disorders and evaluated its efficacy in a randomized clinical trial.

Participants reporting recurrent binge eating were randomized to Resilience (n = 287) or a waitlist (n = 289). Primary outcomes were objective binge eating episodes and global levels of eating disorder psychopathology. Secondary outcomes were behavioral and cognitive symptoms, psychological distress, and the hypothesized processes of change (mindfulness, emotion regulation, and distress tolerance).

Intention-to-treat analyses showed that the intervention group reported greater reductions in objective binge eating episodes (incidence rate ratio = 0.69) and eating disorder psychopathology (d = −0.68) than the waitlist at 6 weeks. Significant group differences favoring the intervention group were also observed on secondary outcomes, except for subjective binge eating, psychological distress, and distress tolerance. Primary symptoms showed further improvements from 6 to 12 weeks. However, dropout rate was high (48%) among the intervention group, and engagement decreased over the study period.

A novel, low-intensity DBT skills training app can effectively reduce symptoms of eating disorders. Scalable apps like these may increase the accessibility of evidence-based treatments.

The association between heatwave and heat-related outcomes in people with mental health conditions with and without psychotropics was unclear.

We identified people with severe mental illness (SMI) and depression, respectively, using Japanese claim data of Ibaraki prefecture during 1/1/2014–31/12/2021. We conducted self-controlled case series to estimate the incidence rate ratio (IRR) of heat-related illness, myocardial infarction and delirium, respectively, during 5-day pre-heatwave, heatwave, and 5-day post-heatwave periods v. all other periods (baseline) within an individual, stratified by periods prescribed psychotropics and periods not prescribed psychotropics, respectively.

Among people with SMI, heatwave was associated with an increased rate of heat-related illness v. baseline, with no evidence of a difference in the IRRs between those prescribed v. not prescribed antipsychotics (IRR: 1.48 [95% CI 1.40–1.56]; 1.45 [95% CI 1.35–1.56] respectively, p interaction: 0.53). Among people with depression, heatwave was similarly associated with heat-related illness, with no evidence of a difference in the IRRs between those prescribed v. not prescribed antidepressants (IRR: 1.54 [95% CI 1.46–1.64]; 1.64 [95% CI 1.57–1.71] respectively, p interaction: 0.33). Smaller increased rates of heat-related illness were also observed in pre- and post-heatwave periods, v. baseline in both cohorts. There was weak evidence of an increased risk of MI and delirium associated with heatwave v. baseline.

We showed an increased risk of heat-related illness, myocardial infarction and delirium associated with heatwave in people with mental health conditions regardless of whether being prescribed psychotropics. Risks of heat-related illness, myocardial infarction and delirium associated with heatwave might not be factors to influence decisions about the routine use of psychotropics.

Markers of inflammation and cannabis exposure are associated with an increased risk of mental disorders. In the current study, we investigated associations between cannabis use and biomarkers of inflammation.

Utilizing a sample of 914 participants from the Avon Longitudinal Study of Parents and Children, we investigated whether interleukin-6 (IL-6), tumor necrosis factor α (TNFα), C-reactive protein (CRP), and soluble urokinase plasminogen activator receptor (suPAR) measured at age 24 were associated with past year daily cannabis use, less frequent cannabis use, and no past year cannabis use. We adjusted for a number of covariates including sociodemographic measures, body mass index, childhood trauma, and tobacco smoking. We found evidence of a strong association between daily or near daily cannabis use and suPAR.

We did not find any associations between less frequent cannabis use and suPAR. We did not find evidence of an association between IL-6, TNFα or CRP, and cannabis use.

Our finding that frequent cannabis use is strongly associated with suPAR, a biomarker of systemic chronic inflammation implicated in neurodevelopmental and neurodegenerative processes is novel. These findings may provide valuable insights into biological mechanisms by which cannabis affects the brain and impacts the risk of serious mental disorders.

Psychostimulants and nonstimulants have partially overlapping pharmacological targets on attention-deficit/hyperactivity disorder (ADHD), but whether their neuroimaging underpinnings differ is elusive. We aimed to identify overlapping and medication-specific brain functional mechanisms of psychostimulants and nonstimulants on ADHD.

After a systematic literature search and database construction, the imputed maps of separate and pooled neuropharmacological mechanisms were meta-analyzed by Seed-based d Mapping toolbox, followed by large-scale network analysis to uncover potential coactivation patterns and meta-regression analysis to examine the modulatory effects of age and sex.

Twenty-eight whole-brain task-based functional MRI studies (396 cases in the medication group and 459 cases in the control group) were included. Possible normalization effects of stimulant and nonstimulant administration converged on increased activation patterns of the left supplementary motor area (Z = 1.21, p < 0.0001, central executive network). Stimulants, relative to nonstimulants, increased brain activations in the left amygdala (Z = 1.30, p = 0.0006), middle cingulate gyrus (Z = 1.22, p = 0.0008), and superior frontal gyrus (Z = 1.27, p = 0.0006), which are within the ventral attention network. Neurodevelopmental trajectories emerged in activation patterns of the right supplementary motor area and left amygdala, with the left amygdala also presenting a sex-related difference.

Convergence in the left supplementary motor area may delineate novel therapeutic targets for effective interventions, and distinct neural substrates could account for different therapeutic responses to stimulants and nonstimulants.