Equitable access to mental healthcare is a priority for many countries. The National Health Service in England uses a weighted capitation formula to ensure that the geographical distribution of resources reflects need.

To produce a revised formula for estimating local need for secondary mental health, learning disability (intellectual disability) and psychological therapies services for adults in England.

We used demographic records for 43 751 535 adults registered with a primary care practitioner in England linked with service use, ethnicity, physical health diagnoses and type of household, from multiple data-sets. Using linear regression, we estimated the individual cost of care in 2015 as a function of individual- and area-level need and supply variables in 2013 and 2014. We sterilised the effects of the supply variables to obtain individual-need estimates. We aggregated these by general practitioner practice, age and gender to derive weights for the national capitation formula.

Higher costs were associated with: being 30–50 years old, compared with 20–24; being Irish, Black African, Black Caribbean or of mixed ethnicity, compared with White British; having been admitted for specific physical health conditions, including drug poisoning; living alone, in a care home or in a communal environment; and living in areas with a higher percentage of out-of-work benefit recipients and higher prevalence of severe mental illness. Longer distance from a provider was associated with lower cost.

The resulting needs weights were higher in more deprived areas and informed the distribution of some 12% (£9 bn in 2019/20) of the health budget allocated to local organisations for 2019/20 to 2023/24.

The first episode of psychosis is a critical period in the emergence of cardiometabolic risk.

We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis.

This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months.

Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol).

Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.

Individuals with depression often do not respond to medication or psychotherapy. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting overcontrolled personality, common in refractory depression.

To compare RO DBT plus treatment as usual (TAU) for refractory depression with TAU alone (trial registration: ISRCTN 85784627).

RO DBT comprised 29 therapy sessions and 27 skills classes over 6 months. Our completed randomised trial evaluated RO DBT for refractory depression over 18 months in three British secondary care centres. Of 250 adult participants, we randomised 162 (65%) to RO DBT. The primary outcome was the Hamilton Rating Scale for Depression (HRSD), assessed masked and analysed by treatment allocated.

After 7 months, immediately following therapy, RO DBT had significantly reduced depressive symptoms by 5.40 points on the HRSD relative to TAU (95% CI 0.94–9.85). After 12 months (primary end-point), the difference of 2.15 points on the HRSD in favour of RO DBT was not significant (95% CI –2.28 to 6.59); nor was that of 1.69 points on the HRSD at 18 months (95% CI –2.84 to 6.22). Throughout RO DBT participants reported significantly better psychological flexibility and emotional coping than controls. However, they reported eight possible serious adverse reactions compared with none in the control group.

The RO DBT group reported significantly lower HRSD scores than the control group after 7 months, but not thereafter. The imbalance in serious adverse reactions was probably because of the controls' limited opportunities to report these.

Diagnosing eating disorders can be difficult and few people with the disorder receive specialist services despite the associated high morbidity and mortality.

To examine the burden of eating disorders in the population in terms of incidence, comorbidities and survival.

We used linked electronic health records from general practitioner and hospital admissions in Wales, UK within the Secure Anonymised Information Linkage (SAIL) databank to investigate the incidence of new eating disorder diagnoses. We examined the frequency of comorbid diagnoses and prescribed medications in cases and controls in the 2 years before and 3 years after diagnosis, and performed a survival analysis.

A total of 15 558 people were diagnosed with eating disorders between 1990 and 2017. The incidence peaked at 24 per 100 000 people in 2003/04. People with eating disorders showed higher levels of other mental disorders (odds ratio 4.32, 95% CI 4.01–4.66) and external causes of morbidity and mortality (odds ratio 2.92, 95% CI 2.44–3.50). They had greater prescription of central nervous system drugs (odds ratio 3.15, 95% CI 2.97–3.33), gastrointestinal drugs (odds ratio 2.61, 95% CI 2.45–2.79) and dietetic drugs (odds ratio 2.42, 95% CI 2.24–2.62) before diagnosis. These excess diagnoses and prescriptions remained 3 years after diagnosis. Mortality was raised compared with controls for some eating disorders, particularly in females with anorexia nervosa.

Incidence of diagnosed eating disorders is relatively low in the population but there is a major longer term burden in morbidity and mortality to the individual.

Optimal transition from child to adult services involves continuity, joint care, planning meetings and information transfer; commissioners and service providers therefore need data on how many people require that service. Although attention-deficit hyperactivity disorder (ADHD) frequently persists into adulthood, evidence is limited on these transitions.

To estimate the national incidence of young people taking medication for ADHD that require and complete transition, and to describe the proportion that experienced optimal transition.

Surveillance over 12 months using the British Paediatric Surveillance Unit and Child and Adolescent Psychiatry Surveillance System, including baseline notification and follow-up questionnaires.

Questionnaire response was 79% at baseline and 82% at follow-up. For those aged 17–19, incident rate (range adjusted for non-response) of transition need was 202–511 per 100 000 people aged 17–19 per year, with successful transition of 38–96 per 100 000 people aged 17–19 per year. Eligible young people with ADHD were mostly male (77%) with a comorbid condition (62%). Half were referred to specialist adult ADHD and 25% to general adult mental health services; 64% had referral accepted but only 22% attended a first appointment. Only 6% met optimal transition criteria.

As inclusion criteria required participants to be on medication, these estimates represent the lower limit of the transition need. Two critical points were apparent: referral acceptance and first appointment attendance. The low rate of successful transition and limited guideline adherence indicates significant need for commissioners and service providers to improve service transition experiences.

Little is known about the long-term outcome of anorexia nervosa.

To study the 30-year outcome of adolescent-onset anorexia nervosa.

All 4291 individuals born in 1970 and attending eighth grade in 1985 in Gothenburg, Sweden were screened for anorexia nervosa. A total of 24 individuals (age cohort for anorexia nervosa) were pooled with 27 individuals with anorexia nervosa (identified through community screening) who were born in 1969 and 1971–1974. The 51 individuals with anorexia nervosa and 51 school- and gender-matched controls were followed prospectively and examined at mean ages of 16, 21, 24, 32 and 44. Psychiatric disorders, health-related quality of life and general outcome were assessed.

At the 30-year follow-up 96% of participants agreed to participate. There was no mortality. Of the participants, 19% had an eating disorder diagnosis (6% anorexia nervosa, 2% binge-eating disorder, 11% other specified feeding or eating disorder); 38% had other psychiatric diagnoses; and 64% had full eating disorder symptom recovery, i.e. free of all eating disorder criteria for 6 consecutive months. During the elapsed 30 years, participants had an eating disorder for 10 years, on average, and 23% did not receive psychiatric treatment. Good outcome was predicted by later age at onset among individuals with adolescent-onset anorexia nervosa and premorbid perfectionism.

This long-term follow-up study reflects the course of adolescent-onset anorexia nervosa and has shown a favourable outcome regarding mortality and full symptom recovery. However, one in five had a chronic eating disorder.

Maternal exposure to major stressors during pregnancy has been found to increase the risk of neurodevelopmental, cognitive and psychiatric disorders in the offspring. However, the association between prenatal exposure to earthquake and the risk of adult schizophrenia has yet to be examined.

To explore the potential long-term effects of prenatal exposure to maternal stress on the risk of schizophrenia in adulthood, using the Great Tangshan Earthquake in 1976 as a natural experiment.

We obtained data from the Second China National Sample Survey on Disability, and analysed 94 410 Chinese individuals born between 1975 and 1979. We obtained difference-in-differences estimates of the earthquake effects on schizophrenia by exploiting temporal variation in the timing of earthquake exposure across four birth cohorts born between 1975 and 1979, along with geographical variation in earthquake severity at the prefecture level. Schizophrenia was ascertained by psychiatrists using the ICD-10 classification. Earthquake severity was measured by seismic intensity.

Earthquake cohort who experienced prenatal exposure to felt earthquake had higher risk of schizophrenia (odds ratio, 3.38; 95% CI 1.43–8.00) compared with the unexposed reference cohort. After specifying the timing of exposure by the trimester of pregnancy, prenatal exposure to felt earthquake during the first trimester of pregnancy increased the risk of adulthood schizophrenia significantly (odds ratio, 7.45; 95% CI 2.83–19.59).

Prenatal (particularly early pregnancy) exposure to maternal stress after a major disaster substantially affects the mental health of Chinese adults.

Two longitudinal studies have shown that depressive symptoms in women with eating disorders might improve in the antenatal and early postnatal periods. No study has followed up women beyond 8 months postnatal.

To investigate long-term trajectories of depressive symptoms in mothers with lifetime self-reported eating disorders.

Using data from the Avon Longitudinal Study of Parents and Children and multilevel growth curves we modelled trajectories of depressive symptoms from the 18th week of pregnancy to 18 years postnatal in women with lifetime self-reported anorexia nervosa, bulimia nervosa or both anorexia and bulimia nervosa. As sensitivity analyses we also investigated these trajectories using quintiles of a continuous measure of body image in pregnancy.

Of the 9276 women in our main sample, 126 (1.4%) reported a lifetime diagnosis of anorexia nervosa, 153 (1.6%) of bulimia nervosa and 60 (0.6%) of both anorexia and bulimia nervosa. Women with lifetime eating disorders had greater depressive symptoms scores than women with no eating disorders, before and after adjustment for confounders (anorexia nervosa: 2.10, 95% CI 1.36–2.83; bulimia nervosa: 2.28, 95% CI: 1.61–2.94, both anorexia and bulimia nervosa: 2.86, 95% CI 1.81–3.90). We also observed a dose–response association between greater body image and eating concerns in pregnancy and more severe trajectories of depressive symptoms, even after adjusting for lifetime eating disorders which also remained independently associated with greater depressive symptoms.

Women with eating disorders experience persistently greater depressive symptoms across the life-course. More training for practitioners and midwives on how to recognise eating disorders in pregnancy could help to identify depressive symptoms and reduce the long-term burden of disease resulting from this comorbidity.

Studies on neighbourhood characteristics and depression show equivocal results.

This large-scale pooled analysis examines whether urbanisation, socioeconomic, physical and social neighbourhood characteristics are associated with the prevalence and severity of depression.

Cross-sectional design including data are from eight Dutch cohort studies (n= 32 487). Prevalence of depression, either DSM-IV diagnosis of depressive disorder or scoring for moderately severe depression on symptom scales, and continuous depression severity scores were analysed. Neighbourhood characteristics were linked using postal codes and included (a) urbanisation grade, (b) socioeconomic characteristics: socioeconomic status, home value, social security beneficiaries and non-Dutch ancestry, (c) physical characteristics: air pollution, traffic noise and availability of green space and water, and (d) social characteristics: social cohesion and safety. Multilevel regression analyses were adjusted for the individual's age, gender, educational level and income. Cohort-specific estimates were pooled using random-effects analysis.

The pooled analysis showed that higher urbanisation grade (odds ratio (OR) = 1.05, 95% CI 1.01–1.10), lower socioeconomic status (OR = 0.90, 95% CI 0.87–0.95), higher number of social security beneficiaries (OR = 1.12, 95% CI 1.06–1.19), higher percentage of non-Dutch residents (OR = 1.08, 95% CI 1.02–1.14), higher levels of air pollution (OR = 1.07, 95% CI 1.01–1.12), less green space (OR = 0.94, 95% CI 0.88–0.99) and less social safety (OR = 0.92, 95% CI 0.88–0.97) were associated with higher prevalence of depression. All four socioeconomic neighbourhood characteristics and social safety were also consistently associated with continuous depression severity scores.

This large-scale pooled analysis across eight Dutch cohort studies shows that urbanisation and various socioeconomic, physical and social neighbourhood characteristics are associated with depression, indicating that a wide range of environmental aspects may relate to poor mental health.

None.

Self-management is intended to empower individuals in their recovery by providing the skills and confidence they need to take active steps in recognising and managing their own health problems. Evidence supports such interventions in a range of long-term physical health conditions, but a recent systematic synthesis is not available for people with severe mental health problems.

To evaluate the effectiveness of self-management interventions for adults with severe mental illness (SMI).

A systematic review of randomised controlled trials was conducted. A meta-analysis of symptomatic, relapse, recovery, functioning and quality of life outcomes was conducted, using RevMan.

A total of 37 trials were included with 5790 participants. From the meta-analysis, self-management interventions conferred benefits in terms of reducing symptoms and length of admission, and improving functioning and quality of life both at the end of treatment and at follow-up. Overall the effect size was small to medium. The evidence for self-management interventions on readmissions was mixed. However, self-management did have a significant effect compared with control on subjective measures of recovery such as hope and empowerment at follow-up, and self-rated recovery and self-efficacy at both time points.

There is evidence that the provision of self-management interventions alongside standard care improves outcomes for people with SMI. Self-management interventions should form part of the standard package of care provided to people with SMI and should be prioritised in guidelines: research on best methods of implementing such interventions in routine practice is needed.

None.

Mental illnesses may explain vulnerability to develop extremist beliefs that can lead to violent protest and terrorism. Yet there is little evidence.

To investigate the relationship between mental illnesses and extremist beliefs.

Population survey of 618 White British and Pakistani people in England. Extremism was assessed by an established measure of sympathies for violent protest and terrorism (SVPT). Respondents with any positive scores (showing sympathies) were compared with those with all negative scores. We calculated associations between extremist sympathies and ICD-10 diagnoses of depression and dysthymia, and symptoms of anxiety, personality difficulties, autism and post-traumatic stress. Also considered were demographics, life events, social assets, political engagement and criminal convictions.

SVPT were more common in those with major depression with dysthymia (risk ratio 4.07, 95% CI 1.37–12.05, P = 0.01), symptoms of anxiety (risk ratio 1.09, 95% CI 1.03–1.15, P = 0.002) or post-traumatic stress (risk ratio 1.03, 95% CI 1.01–1.05, P = 0.003). At greater risk of SVPT were: young adults (<21 versus ≥21: risk ratio 3.05, 95% CI 1.31–7.06, P = 0.01), White British people (versus Pakistani people: risk ratio 2.24, 95% CI 1.25–4.02, P = 0.007) and those with criminal convictions (risk ratio 2.23, 95% CI 1.01–4.95, P = 0.048). No associations were found with life events, social assets and political engagement.

Depression, dysthymia and symptoms of anxiety and post-traumatic stress are associated with extremist sympathies.

Recent studies suggest psychotic and eating disorders can be comorbid and could have shared genetic liability. However, this comorbidity has been overlooked in the epidemiological literature.

To test whether polygenic risk scores (PRS) for schizophrenia are associated with disordered eating behaviours and body mass index (BMI) in the general population.

Using data from the Avon Longitudinal Study of Parents and Children and random-effects logistic and linear regression models, we investigated the association between PRS for schizophrenia and self-reported disordered eating behaviours (binge eating, purging, fasting and excessive exercise) and BMI at 14, 16 and 18 years.

Of the 6920 children with available genetic data, 4473 (64.6%) and 5069 (73.3%) had at least one disordered eating and one BMI outcome measurement, respectively. An s.d. increase in PRS was associated with greater odds of having binge eating behaviours (odds ratio, 1.36; 95% CI 1.16–1.60) and lower BMI (coefficient, −0.03; 95% CI, −0.06 to −0.01).

Our findings suggest the presence of shared genetic risk between schizophrenia and binge eating behaviours. Intermediate phenotypes such as impaired social cognition and irritability, previously shown to be positively correlated in this sample with schizophrenia PRS, could represent risk factors for both phenotypes. Shared genetic liability between binge eating and schizophrenia could also explain higher rates of metabolic syndrome in individuals with schizophrenia, as binge eating could be a mediator of this association in drug-naïve individuals. The finding of an association between greater PRS and lower BMI, although consistent with existing epidemiological and genetic literature, requires further investigation.

None.

Befriending by volunteers has the potential to reduce the frequent social isolation of patients with schizophrenia and thus improve health outcomes. However, trial-based evidence for its effectiveness is limited.

To conduct a randomised controlled trial of befriending for patients with schizophrenia or related disorders.

Patients were randomised to a befriending programme for 1 year or to receive information about social activities only (trial registration: ISRCTN14021839). Outcomes were assessed masked to allocation at the end of the programme; at 12 months and at a 6-month follow-up. The primary outcome was daily time spent in activities (using the Time Use Survey (TUS)) with intention-to-treat analysis.

A total of 124 patients were randomised (63 intervention, 61 active control) and 92 (74%) were followed up at 1 year. In the intervention group, 49 (78%) met a volunteer at least once and 31 (49%) had more than 12 meetings. At 1 year, mean TUS scores were more than three times higher in both groups with no significant difference between them (adjusted difference 8.9, 95% CI −40.7 to 58.5, P = 0.72). There were no significant differences in quality of life, symptoms or self-esteem. However, patients in the intervention group had significantly more social contacts than those in the control group at the end of the 12-month period. This difference held true at the follow-up 6 months later.

Although no difference was found on the primary outcome, the findings suggest that befriending may have a lasting effect on increasing social contacts. It may be used more widely to reduce the social isolation of patients with schizophrenia.

People with bipolar disorder typically require long-term pharmacological treatment to prevent episodes of depression or mania. However, evidence-based guidelines are often not followed by prescribers and, in some countries, prescribing of lithium is in decline. Polypharmacy is also common in bipolar disorder.

To employ a data linkage approach to describe and evaluate prescribing patterns in bipolar disorder in Scotland between 2009 and 2016.

By linking prescribing data to the electronic Scottish Morbidity Records, we identified a cohort of 23 135 patients with bipolar disorder who were prescribed psychotropic medication between 2009 and 2016. We examined trends in proportions of patients prescribed each of six drug categories. Random effects logistic models examined change in prescribing over years of interest.

The most common form of treatment was antidepressant monotherapy (24.96%), with only 5.90% of patients receiving lithium monotherapy. Prescribing of antipsychotics and anti-epileptics increased from 2009 to 2016 (antipsychotics: odds ratio 1.16, 95% CI 1.15–1.18; anti-epileptics: odds ratio 1.34, 95% CI 1.32–1.36), whereas prescribing of lithium decreased (odds ratio 0.83, 95% CI 0.82–0.85). Prescribing of valproate decreased from 2009–2016 in women, but increased in men (women: odds ratio 0.93, 95% CI 0.90–0.97; men: odds ratio 1.11, 95% CI 1.04–1.18).

Antidepressant monotherapy was the most common form of treatment for bipolar disorder in Scotland and prescribing of lithium has declined between 2009 and 2016. The findings are concerning and represent a gap between treatment guidelines and clinical practice.

None.

Lung cancer risk factors, like tobacco smoking, are highly prevalent in patients with schizophrenia. Whether these patients have a higher risk of lung cancer remains unknown.

We aimed to investigate whether patients with schizophrenia have a higher incidence of lung cancer compared with general population, in a meta-analysis.

Eligible studies were searched from PubMed and EMBASE databases to identify cases of lung cancer in patients with schizophrenia and the general population. This meta-analysis utilised the random-effects model and prediction interval was used to calculate the heterogeneity of these eligible studies. We assessed the quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

There were 12 studies, totalling 496 265 patients, included in this meta-analysis. The data showed that the baseline schizophrenia diagnosis was not associated with any changes in lung cancer incidence in the overall population, with a standardised incidence ratio of 1.11 (95% CI 0.90–1.37; P = 0.31), although there was a significant heterogeneity among these studies (I2 = 94%). Moreover, there was also a substantial between-study variance with wide prediction interval values (0.47–2.64). The data were consistent for both males and females.

Up-to-date evidence from epidemiological studies indicates the lack of certainty about the association between schizophrenia diagnosis and lung cancer incidence.

The past decade has seen the development of services for adults presenting with symptoms of autism spectrum disorder (ASD) in the UK. Compared with children, little is known about the phenotypic and genetic characteristics of these patients.

This e-cohort study aimed to examine the phenotypic and genetic characteristics of a clinically presenting sample of adults diagnosed with ASD by specialist services.

Individuals diagnosed with ASD as adults were recruited by the National Centre for Mental Health and completed self-report questionnaires, interviews and provided DNA; 105 eligible individuals were matched to 76 healthy controls. We investigated demographics, social history and comorbid psychiatric and physical disorders. Samples were genotyped, copy number variants (CNVs) were called and polygenic risk scores were calculated.

Of individuals with ASD, 89.5% had at least one comorbid psychiatric diagnosis, with depression (62.9%) and anxiety (55.2%) being the most common. The ASD group experienced more neurological comorbidities than controls, particularly migraine headache. They were less likely to have married or be in work, and had more alcohol-related problems. There was a significantly higher load of autism common genetic variants in the adult ASD group compared with controls, but there was no difference in the rate of rare CNVs.

This study provides important information about psychiatric comorbidity in adult ASD, which may inform clinical practice and patient counselling. It also suggests that the polygenic load of common ASD-associated variants may be important in conferring risk within the non-intellectually disabled population of adults with ASD.

None.

Excessive use of the internet is increasingly recognised as a global public health concern. Individual studies have reported cognitive impairment in problematic internet use (PIU), but have suffered from various methodological limitations. Confirmation of cognitive deficits in PIU would support the neurobiological plausibility of this disorder.

To conduct a rigorous meta-analysis of cognitive performance in PIU from case–control studies; and to assess the impact of study quality, the main type of online behaviour (for example gaming) and other parameters on the findings.

A systematic literature review was conducted of peer-reviewed case–controlled studies comparing cognition in people with PIU (broadly defined) with that of healthy controls. Findings were extracted and subjected to a meta-analysis where at least four publications existed for a given cognitive domain of interest.

The meta-analysis comprised 2922 participants across 40 studies. Compared with controls, PIU was associated with significant impairment in inhibitory control (Stroop task Hedge's g = 0.53 (s.e. = 0.19–0.87), stop-signal task g = 0.42 (s.e. = 0.17–0.66), go/no-go task g = 0.51 (s.e. = 0.26–0.75)), decision-making (g = 0.49 (s.e. = 0.28–0.70)) and working memory (g = 0.40 (s.e. = 0.20–0.82)). Whether or not gaming was the predominant type of online behaviour did not significantly moderate the observed cognitive effects; nor did age, gender, geographical area of reporting or the presence of comorbidities.

PIU is associated with decrements across a range of neuropsychological domains, irrespective of geographical location, supporting its cross-cultural and biological validity. These findings also suggest a common neurobiological vulnerability across PIU behaviours, including gaming, rather than a dissimilar neurocognitive profile for internet gaming disorder.

S.R.C. consults for Cambridge Cognition and Shire. K.I.’s research activities were supported by Health Education East of England Higher Training Special interest sessions. A.E.G.'s research has been funded by Innovational grant (VIDI-scheme) from ZonMW: (91713354). N.A.F. has received research support from Lundbeck, Glaxo-SmithKline, European College of Neuropsychopharmacology (ECNP), Servier, Cephalon, Astra Zeneca, Medical Research Council (UK), National Institute for Health Research, Wellcome Foundation, University of Hertfordshire, EU (FP7) and Shire. N.A.F. has received honoraria for lectures at scientific meetings from Abbott, Otsuka, Lundbeck, Servier, Astra Zeneca, Jazz pharmaceuticals, Bristol Myers Squibb, UK College of Mental Health Pharmacists and British Association for Psychopharmacology (BAP). N.A.F. has received financial support to attend scientific meetings from RANZCP, Shire, Janssen, Lundbeck, Servier, Novartis, Bristol Myers Squibb, Cephalon, International College of Obsessive-Compulsive Spectrum Disorders, International Society for Behavioral Addiction, CINP, IFMAD, ECNP, BAP, the World Health Organization and the Royal College of Psychiatrists. N.A.F. has received financial royalties for publications from Oxford University Press and payment for editorial duties from Taylor and Francis. J.E.G. reports grants from the National Center for Responsible Gaming, Forest Pharmaceuticals, Takeda, Brainsway, and Roche and others from Oxford Press, Norton, McGraw-Hill and American Psychiatric Publishing outside of the submitted work.

Rare copy number variants (CNVs) are associated with risk of neurodevelopmental disorders characterised by varying degrees of cognitive impairment, including schizophrenia, autism spectrum disorder and intellectual disability. However, the effects of many individual CNVs in carriers without neurodevelopmental disorders are not yet fully understood, and little is known about the effects of reciprocal copy number changes of known pathogenic loci.

We aimed to analyse the effect of CNV carrier status on cognitive performance and measures of occupational and social outcomes in unaffected individuals from the UK Biobank.

We called CNVs in the full UK Biobank sample and analysed data from 420 247 individuals who passed CNV quality control, reported White British or Irish ancestry and were not diagnosed with neurodevelopmental disorders. We analysed 33 pathogenic CNVs, including their reciprocal deletions/duplications, for association with seven cognitive tests and four general measures of functioning: academic qualifications, occupation, household income and Townsend Deprivation Index.

Most CNVs (24 out of 33) were associated with reduced performance on at least one cognitive test or measure of functioning. The changes on the cognitive tests were modest (average reduction of 0.13 s.d.) but varied markedly between CNVs. All 12 schizophrenia-associated CNVs were associated with significant impairments on measures of functioning.

CNVs implicated in neurodevelopmental disorders, including schizophrenia, are associated with cognitive deficits, even among unaffected individuals. These deficits may be subtle but CNV carriers have significant disadvantages in educational attainment and ability to earn income in adult life.

None.