This paper examined whether distinct life-course trajectories of psychological distress from adolescence to midlife were associated with poorer mental health outcomes during the pandemic.

We present a secondary analysis of two nationally representative British birth cohorts, the 1958 National Child Development Study (NCDS) and 1970 British Cohort Study (BCS70). We used latent variable mixture models to identify pre-pandemic longitudinal trajectories of psychological distress and a modified Poisson model with robust standard errors to estimate associations with psychological distress, life satisfaction and loneliness at different points during the pandemic.

Our analysis identified five distinct pre-pandemic trajectories of psychological distress in both cohorts. All trajectories with prior symptoms of psychological distress irrespective of age of onset, severity and chronicity were associated with a greater relative risk of poorer mental health outcomes during the pandemic and the probability of poorer mental health associated with psychological distress trajectories remained fairly constant. The relationship was not fully attenuated when most recent pre-pandemic psychological distress and other midlife factors were controlled for.

Whilst life-course trajectories with any prior symptoms of psychological distress put individuals at greater risk of poor mental health outcomes during the pandemic, those with chronic and more recent occurrences were at highest risk. In addition, prior poor mental health during the adult life-course may mean individuals are less resilient to shocks, such as pandemics. Our findings show the importance of considering heterogeneous mental health trajectories across the life-course in the general population in addition to population average trends.

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.

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).

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.

The new open access scale provides a psychometrically robust assessment of positive cognitions that are strongly connected to psychological well-being.

The utilisation of massed therapy for treating posttraumatic stress disorder (PTSD) is gaining strength, especially prolonged exposure. However, it is unknown whether massed prolonged exposure (MPE) is non-inferior to standard prolonged exposure (SPE) protocols in the long term. The current study aimed to assess whether MPE was non-inferior to SPE at 12 months post-treatment, and to ascertain changes in secondary measure outcomes.

A multi-site non-inferiority randomised controlled trial (RCT) compared SPE with MPE in 12 clinics. The primary outcome was PTSD symptom severity (CAPS-5) at 12 months post-treatment commencement. Secondary outcome measures included symptoms of depression, anxiety, anger, disability, and quality of life at 12 weeks and 12 months post-treatment commencement. Outcome assessors were blinded to treatment allocation. The intention-to-treat sample included 138 Australian military members and veterans and data were analysed for 134 participants (SPE = 71, MPE = 63).

Reductions in PTSD severity were maintained at 12 months and MPE remained non-inferior to SPE. Both treatment groups experienced a reduction in depression, anxiety, anger, and improvements in quality of life at 12 weeks and 12 months post-treatment commencement. Treatment effects for self-reported disability in the SPE group at 12 weeks were not maintained, with neither group registering significant effects at 12 months.

The emergence of massed protocols for PTSD is an important advancement. The current study provides RCT evidence for the longevity of MPE treatment gains at 12 months post-treatment commencement and demonstrated non-inferiority to SPE. Promisingly, both treatments also significantly reduced the severity of comorbid symptoms commonly occurring alongside PTSD.

Patients with remitted psychosis face a dilemma between the wish to discontinue antipsychotics and the risk of relapse. We test if an operationalized guided-dose-reduction algorithm can help reach a lower effective dose without increased risks of relapse.

A 2-year open-label randomized prospective comparative cohort trial from Aug 2017 to Sep 2022. Patients with a history of schizophrenia-related psychotic disorders under stable medications and symptoms were eligible, randomized 2:1 into guided dose reduction group (GDR) v. maintenance treatment group (MT1), together with a group of naturalistic maintenance controls (MT2). We observed if the relapse rates would be different between 3 groups, to what extent the dose could be reduced, and if GDR patients could have improved functioning and quality of life.

A total of 96 patients, comprised 51, 24, and 21 patients in GDR, MT1, and MT2 groups, respectively. During follow-up, 14 patients (14.6%) relapsed, including 6, 4, and 4 from GDR, MT1, and MT2, statistically no difference between groups. In total, 74.5% of GDR patients could stay well under a lower dose, including 18 patients (35.3%) conducting 4 consecutive dose-tapering and staying well after reducing 58.5% of their baseline dose. The GDR group exhibited improved clinical outcomes and endorsed better quality of life.

GDR is a feasible approach as the majority of patients had a chance to taper antipsychotics to certain extents. Still, 25.5% of GDR patients could not successfully decrease any dose, including 11.8% experienced relapse, a risk comparable to their maintenance counterparts.

The study is aimed to identify brain functional connectomes predictive of depressed and elevated mood symptomatology in individuals with bipolar disorder (BD) using the machine learning approach Connectome-based Predictive Modeling (CPM).

Functional magnetic resonance imaging data were obtained from 81 adults with BD while they performed an emotion processing task. CPM with 5000 permutations of leave-one-out cross-validation was applied to identify functional connectomes predictive of depressed and elevated mood symptom scores on the Hamilton Depression and Young Mania rating scales. The predictive ability of the identified connectomes was tested in an independent sample of 43 adults with BD.

CPM predicted the severity of depressed [concordance between actual and predicted values (r = 0.23, pperm (permutation test) = 0.031) and elevated (r = 0.27, pperm = 0.01) mood. Functional connectivity of left dorsolateral prefrontal cortex and supplementary motor area nodes, with inter- and intra-hemispheric connections to other anterior and posterior cortical, limbic, motor, and cerebellar regions, predicted depressed mood severity. Connectivity of left fusiform and right visual association area nodes with inter- and intra-hemispheric connections to the motor, insular, limbic, and posterior cortices predicted elevated mood severity. These networks were predictive of mood symptomatology in the independent sample (r ⩾ 0.45, p = 0.002).

This study identified distributed functional connectomes predictive of depressed and elevated mood severity in BD. Connectomes subserving emotional, cognitive, and psychomotor control predicted depressed mood severity, while those subserving emotional and social perceptual functions predicted elevated mood severity. Identification of these connectome networks may help inform the development of targeted treatments for mood symptoms.

Studies have reported mixed findings regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women and birth outcomes. This study used a quasi-experimental design to account for potential confounding by sociodemographic characteristics.

Data were drawn from 16 prenatal cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) program. Women exposed to the pandemic (delivered between 12 March 2020 and 30 May 2021) (n = 501) were propensity-score matched on maternal age, race and ethnicity, and child assigned sex at birth with 501 women who delivered before 11 March 2020. Participants reported on perceived stress, depressive symptoms, sedentary behavior, and emotional support during pregnancy. Infant gestational age (GA) at birth and birthweight were gathered from medical record abstraction or maternal report.

After adjusting for propensity matching and covariates (maternal education, public assistance, employment status, prepregnancy body mass index), results showed a small effect of pandemic exposure on shorter GA at birth, but no effect on birthweight adjusted for GA. Women who were pregnant during the pandemic reported higher levels of prenatal stress and depressive symptoms, but neither mediated the association between pandemic exposure and GA. Sedentary behavior and emotional support were each associated with prenatal stress and depressive symptoms in opposite directions, but no moderation effects were revealed.

There was no strong evidence for an association between pandemic exposure and adverse birth outcomes. Furthermore, results highlight the importance of reducing maternal sedentary behavior and encouraging emotional support for optimizing maternal health regardless of pandemic conditions.

Postpartum depression (PPD) affects up to one in five mothers and birthing parents, yet as few as 10% access evidence-based treatment. One-day cognitive behavioral therapy (CBT)-based workshops for PPD have the potential to reach large numbers of sufferers and be integrated into stepped models of care.

This randomized controlled trial of 461 mothers and birthing parents in Ontario, Canada with Edinburgh Postnatal Depression Scale (EPDS) scores ⩾10, age ⩾18 years, and an infant <12 months of age compared the effects of a 1-day CBT-based workshop plus treatment as usual (TAU; i.e. care from any provider(s) they wished) to TAU alone at 12-weeks post-intervention on PPD, anxiety, the mother–infant relationship, offspring behavior, health-related quality of life, and cost-effectiveness. Data were collected via REDCap.

Workshops led to meaningful reductions in EPDS scores (m = 15.77 to 11.22; b = −4.6, p < 0.01) and were associated with three times higher odds of a clinically significant decrease in PPD [odds ratio (OR) 3.00, 95% confidence interval (CI) 1.93–4.67]. Anxiety also decreased and participants had three times the odds of clinically significant improvement (OR 3.20, 95% CI 2.03–5.04). Participants reported improvements in mother–infant bonding, infant-focused rejection and anger, and effortful control in their toddlers. The workshop plus TAU achieved similar quality-adjusted life-years at lower costs than TAU alone.

One-day CBT-based workshops for PPD can lead to improvements in depression, anxiety, and the mother–infant relationship and are cost-saving. This intervention could represent a perinatal-specific option that can treat larger numbers of individuals and be integrated into stepped care approaches at reasonable cost.

To clarify, in a national sample, associations between risk for seven psychiatric and substance use disorders and five key transitions in Sweden's public educational system.

Swedish-born individuals (1972–1995, N = 1 997 910) were followed through 12-31-2018, at mean age 34.9. We predicted, from these educational transitions, risk for major depression (MD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), anorexia nervosa (AN), alcohol use disorder (AUD), and drug use disorder (DUD), assessed from Swedish national registers, by Cox regression, censoring individuals with onsets ⩽17. We also predicted risk from the deviation of grades from family-genetic expectations (deviation 1) and from changes in grades from ages 16 to 19 (deviation 2).

We observed four major risk patterns across transitions in our disorders: (i) MD and BD, (ii) OCD and SZ, (iii) AUD and DUD, and (iv) AN. Failing early educational transitions had the greatest impact on risk for OCD and SZ while for other disorders, not progressing from basic to upper high school had the largest effect. Completing vocational v. college-prep upper high school was strongly associated with risk for AUD and DUD, had little relation with MD, OCD, BD, and SZ risk, and was protective for AN. Deviation 1 predicted risk most strongly for SZ, AN, and MD. Deviation 2 predicted risk most strongly for SZ, AUD, and DUD.

The pattern of educational transitions and within family and within person development deviations are strongly and relatively specifically associated with future risk for seven psychiatric and substance-use disorders.

Adolescent internalizing symptoms and trauma exposure have been linked with altered reward learning processes and decreased ventral striatal responses to rewarding cues. Recent computational work on decision-making highlights an important role for prospective representations of the imagined outcomes of different choices. This study tested whether internalizing symptoms and trauma exposure among youth impact the generation of prospective reward representations during decision-making and potentially mediate altered behavioral strategies during reward learning.

Sixty-one adolescent females with varying exposure to interpersonal violence exposure (n = 31 with histories of physical or sexual assault) and severity of internalizing symptoms completed a social reward learning task during fMRI. Multivariate pattern analyses (MVPA) were used to decode neural reward representations at the time of choice.

MVPA demonstrated that rewarding outcomes could accurately be decoded within several large-scale distributed networks (e.g. frontoparietal and striatum networks), that these reward representations were reactivated prospectively at the time of choice in proportion to the expected probability of receiving reward, and that youth with behavioral strategies that favored exploiting high reward options demonstrated greater prospective generation of reward representations. Youth internalizing symptoms, but not trauma exposure characteristics, were negatively associated with both the behavioral strategy of exploiting high reward options as well as the prospective generation of reward representations in the striatum.

These data suggest diminished prospective mental simulation of reward as a mechanism of altered reward learning strategies among youth with internalizing symptoms.

Mindfulness-based cognitive therapy (MBCT) seems a promising intervention for bipolar disorder (BD), but there is a lack of randomised controlled trials (RCT) investigating this. The purpose of this multicentre, evaluator blinded RCT was to investigate the added value of MBCT to treatment as usual (TAU) in BD up to 15 months follow-up (NCT03507647).

A total of 144 participants with BD type I and II were randomised to MBCT + TAU (n = 72) and TAU (n = 72). Primary outcome was current depressive symptoms. Secondary outcomes were current (hypo)manic and anxiety symptoms, recurrence rates, rumination, dampening of positive affect, functional impairment, mindfulness skills, self-compassion, and positive mental health. Potential moderators of treatment outcome were examined.

MBCT + TAU was not more efficacious than TAU in reducing current depressive symptoms at post-treatment (95% CI [−7.0 to 1.8], p = 0.303, d = 0.24) or follow-up (95% CI [−2.2 to 6.3], p = 0.037, d = 0.13). At post-treatment, MBCT + TAU was more effective than TAU in improving mindfulness skills. At follow-up, TAU was more effective than MBCT + TAU in reducing trait anxiety and improving mindfulness skills and positive mental health. Exploratory analysis revealed that participants with higher depressive symptoms and functional impairment at baseline benefitted more from MBCT + TAU than TAU.

In these participants with highly recurrent BD, MBCT may be a treatment option in addition to TAU for those who suffer from moderate to severe levels of depression and functional impairment.

ClinicalTrials.gov, NCT03507647. Registered the 25 April 2018, https://www.clinicaltrials.gov/ct2/show/NCT01126827.

The transition to university and resultant social support network disruption can be detrimental to the mental health of university students. As the need for mental health support is becoming increasingly prevalent in students, identification of factors associated with poorer outcomes is a priority. Changes in social functioning have a bi-directional relationship with mental health, however it is not clear how such measures may be related to effectiveness of psychological treatments.

Growth mixture models were estimated on a sample of 5221 students treated in routine mental health services to identify different trajectories of change in self-rated impairment in social leisure activities and close relationships during the course of treatment. Multinomial regression explored associations between trajectory classes and treatment outcomes.

Five trajectory classes were identified for social leisure activity impairment while three classes were identified for close relationship impairment. In both measures most students remained mildly impaired. Other trajectories included severe impairment with limited improvement, severe impairment with delayed improvement, and, in social leisure activities only, rapid improvement, and deterioration. Trajectories of improvement were associated with positive treatment outcomes while trajectories of worsening or stable severe impairment were associated with negative treatment outcomes.

Changes in social functioning impairment are associated with psychological treatment outcomes in students, suggesting that these changes may be associated with treatment effectiveness as well as recovery experiences. Future research should seek to establish whether a causal link exists to understand whether integrating social support within psychological treatment may bring additional benefit for students.

Identification of genetic risk factors may inform the prevention and treatment of posttraumatic stress disorder (PTSD). This study evaluates the associations of polygenic risk scores (PRS) with patterns of posttraumatic stress symptoms following combat deployment.

US Army soldiers of European ancestry (n = 4900) provided genomic data and ratings of posttraumatic stress symptoms before and after deployment to Afghanistan in 2012. Latent growth mixture modeling was used to model posttraumatic stress symptom trajectories among participants who provided post-deployment data (n = 4353). Multinomial logistic regression models tested independent associations between trajectory membership and PRS for PTSD, major depressive disorder (MDD), schizophrenia, neuroticism, alcohol use disorder, and suicide attempt, controlling for age, sex, ancestry, and exposure to potentially traumatic events, and weighted to account for uncertainty in trajectory classification and missing data.

Participants were classified into low-severity (77.2%), increasing-severity (10.5%), decreasing-severity (8.0%), and high-severity (4.3%) posttraumatic stress symptom trajectories. Standardized PTSD-PRS and MDD-PRS were associated with greater odds of membership in the high-severity v. low-severity trajectory [adjusted odds ratios and 95% confidence intervals, 1.23 (1.06–1.43) and 1.18 (1.02–1.37), respectively] and the increasing-severity v. low-severity trajectory [1.12 (1.01–1.25) and 1.16 (1.04–1.28), respectively]. Additionally, MDD-PRS was associated with greater odds of membership in the decreasing-severity v. low-severity trajectory [1.16 (1.03–1.31)]. No other associations were statistically significant.

Higher polygenic risk for PTSD or MDD is associated with more severe posttraumatic stress symptom trajectories following combat deployment. PRS may help stratify at-risk individuals, enabling more precise targeting of treatment and prevention programs.

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.

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).

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.

Internet-delivered psychological interventions could be a suitable model of accessible supportive care for patients with neurological disorders.

While implicit distraction could ameliorate negative feelings in patients with major depressive disorders (MDD), it remains unclear whether patients could benefit from explicit, voluntary distraction. Meanwhile, though the dorsolateral prefrontal cortex (DLPFC) is established as a crucial brain region involved in attentional control, the causal relationship between the DLPFC and voluntary distraction is unexplored in patients.

Combing explicit distraction and transcranial magnetic stimulation (TMS), this study investigated whether TMS-activated DLPFC facilitates voluntary distraction in MDD patients. Eighty patients diagnosed with current MDD underwent either active (n = 40) or sham (n = 40) TMS sessions, followed by receiving negative social feedback from other patients, during which they were requied to use distraction strategy to down-regulate their painful feelings. Electroencephalogram was recorded during the task.

Both the subjective emotional rating and the amplitude of late positive potential showed that depressed patients successfully down-regulate their negative emotions via voluntary distraction, and the TMS-activated left DLPFC produced a larger benefit of emotion regulation compared to the sham TMS group. Results also revealed that while emotion regulation effect was negatively associated with depressive symptoms in the sham TMS group, this correlation was largely diminished when patients' left DLPFC was activated by TMS during the voluntary distraction.

These findings demonstrated that distraction is valuable for emotion regulation in MDD patients and they could be beneficial in voluntary distraction by activating their left DLPFC using neural modulation techniques. This study has valuable implications for clinical treatement of emotional dysregulation in MDD patients.

Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.

We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.

BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.

We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

The extent to which digital media use by adolescents contributes to poor mental health, or vice-versa, remains unclear. The purpose of the present study is to clarify the strength and direction of associations between adolescent internet use and the development of depression symptoms using a longitudinal modeling approach. We also examine whether associations differ for boys and girls.

Data are drawn from (N = 1547) participants followed for the Quebec longitudinal Study of Child Development (QLSCD 1998–2020). Youth self-reported internet use in terms of the average hours of use per week at the ages of 13, 15, and 17. Youth also self-reported depression symptoms at the same ages.

After testing sex-invariance, random intercepts cross-lagged panel models stratified by sex, revealed that internet use by girls was associated with significant within-person (time-varying) change in depression symptoms. Girl's internet use at age 13 was associated with increased depression symptoms at age 15 (ß = 0.12) and internet use at age 15 increased depression at age 17 (ß = 0.10). For boys, internet use was not associated with significant time varying change in depression symptoms.

The present findings support the hypothesis that internet use by adolescents can represent a significant risk factor for the development of depressive symptoms, particularly in girls.

Slowed information processing speed (IPS) is the core contributor to cognitive impairment in patients with late-life depression (LLD). The hippocampus is an important link between depression and dementia, and it may be involved in IPS slowing in LLD. However, the relationship between a slowed IPS and the dynamic activity and connectivity of hippocampal subregions in patients with LLD remains unclear.

One hundred thirty-four patients with LLD and 89 healthy controls were recruited. Sliding-window analysis was used to assess whole-brain dynamic functional connectivity (dFC), dynamic fractional amplitude of low-frequency fluctuations (dfALFF) and dynamic regional homogeneity (dReHo) for each hippocampal subregion seed.

Cognitive impairment (global cognition, verbal memory, language, visual–spatial skill, executive function and working memory) in patients with LLD was mediated by their slowed IPS. Compared with the controls, patients with LLD exhibited decreased dFC between various hippocampal subregions and the frontal cortex and decreased dReho in the left rostral hippocampus. Additionally, most of the dFCs were negatively associated with the severity of depressive symptoms and were positively associated with various domains of cognitive function. Moreover, the dFC between the left rostral hippocampus and middle frontal gyrus exhibited a partial mediation effect on the relationships between the scores of depressive symptoms and IPS.

Patients with LLD exhibited decreased dFC between the hippocampus and frontal cortex, and the decreased dFC between the left rostral hippocampus and right middle frontal gyrus was involved in the underlying neural substrate of the slowed IPS.

Anorexia nervosa (AN) is a psychiatric disorder associated with marked morbidity. Whilst AN genetic studies could identify novel treatment targets, integration of functional genomics data, including transcriptomics and proteomics, would assist to disentangle correlated signals and reveal causally associated genes.

We used models of genetically imputed expression and splicing from 14 tissues, leveraging mRNA, protein, and mRNA alternative splicing weights to identify genes, proteins, and transcripts, respectively, associated with AN risk. This was accomplished through transcriptome, proteome, and spliceosome-wide association studies, followed by conditional analysis and finemapping to prioritise candidate causal genes.

We uncovered 134 genes for which genetically predicted mRNA expression was associated with AN after multiple-testing correction, as well as four proteins and 16 alternatively spliced transcripts. Conditional analysis of these significantly associated genes on other proximal association signals resulted in 97 genes independently associated with AN. Moreover, probabilistic finemapping further refined these associations and prioritised putative causal genes. The gene WDR6, for which increased genetically predicted mRNA expression was correlated with AN, was strongly supported by both conditional analyses and finemapping. Pathway analysis of genes revealed by finemapping identified the pathway regulation of immune system process (overlapping genes = MST1, TREX1, PRKAR2A, PROS1) as statistically overrepresented.

We leveraged multiomic datasets to genetically prioritise novel risk genes for AN. Multiple-lines of evidence support that WDR6 is associated with AN, whilst other prioritised genes were enriched within immune related pathways, further supporting the role of the immune system in AN.