Homicide rates have fallen markedly in the UK over the past decade. There has been little research on whether homicides by people with mental disorder have contributed to this downward trend. Furthermore, there is limited information on trends in court outcomes for people with mental disorder who commit homicide.

To examine trends in general population homicide and homicide by people with mental disorder, and to explore court outcome.

We conducted a national, consecutive case series of homicide in England and Wales (1997–2015). Data were received from the Home Office Statistics Unit of Home Office Science. Clinical information was obtained from psychiatric reports and mental health services.

There has been a fall in the homicide rate in England and Wales since 2008. Despite this, the relative contribution of mental disorder as a proportion of all homicide has increased. Our findings also showed the inappropriate management of people with serious mental illness convicted of homicide. Of those who committed homicide and were diagnosed with schizophrenia, a third were imprisoned, and there was a marked fall in hospital order referrals. We found this to be linked to substance misuse comorbidity.

The proportional increase in homicide by people with schizophrenia suggests more complex factors may be driving rates, such as substance misuse. Addressing substance misuse comorbidity and maintaining engagement with services may help prevent patient homicide. Despite their complex needs, people with serious mental illness continue to be imprisoned. Improvements in assessment and the timely transfer of prisoners to health services are required.

The efficacy of acetylcholinesterase inhibitors and memantine in the symptomatic treatment of Alzheimer's disease is well-established. Randomised trials have shown them to be associated with a reduction in the rate of cognitive decline.

To investigate the real-world effectiveness of acetylcholinesterase inhibitors and memantine for dementia-causing diseases in the largest UK observational secondary care service data-set to date.

We extracted mentions of relevant medications and cognitive testing (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores) from de-identified patient records from two National Health Service (NHS) trusts. The 10-year changes in cognitive performance were modelled using a combination of generalised additive and linear mixed-effects modelling.

The initial decline in MMSE and MoCA scores occurs approximately 2 years before medication is initiated. Medication prescription stabilises cognitive performance for the ensuing 2–5 months. The effect is boosted in more cognitively impaired cases at the point of medication prescription and attenuated in those taking antipsychotics. Importantly, patients who are switched between agents at least once do not experience any beneficial cognitive effect from pharmacological treatment.

This study presents one of the largest real-world examination of the efficacy of acetylcholinesterase inhibitors and memantine for symptomatic treatment of dementia. We found evidence that 68% of individuals respond to treatment with a period of cognitive stabilisation before continuing their decline at the pre-treatment rate.

During a psychotic episode, patients frequently suffer from severe maladaptive beliefs known as delusions. Despite the abundant literature investigating the simple presence or absence of these beliefs, there exists little detailed knowledge regarding their actual content and severity at the onset of illness.

This study reports on delusions during the initiation of indicated treatment for first-episode psychosis (FEP).

Data were systematically collected from a sample of 636 patients entering a catchment-based early intervention service for FEP. The average severity and frequency of each delusional theme at baseline was reported with the Scale for the Assessment of Positive Symptoms. Delusional severity (globally and per theme) was examined across a number of sociodemographic and clinical variables.

Delusions were present in the vast majority of individuals experiencing onset of FEP (94%), with persecutory (77.7%) being the most common theme. Persecutory delusions remained consistent in severity across diagnoses, but were more severe with older age at onset of FEP. No meaningful differences in delusional severity were observed across gender, affective versus non-affective psychosis, or presence/absence of substance use disorder. Globally, delusion severity was associated with anxiety, but not depression. Delusions commonly referred to as passivity experiences were related to hallucinatory experiences.

This community sample offers a rare clinical lens into the severity and content of delusions in FEP. Although delusional severity was consistent across certain sociodemographic and clinical variables, this was not always the case. Future research should now consider the course of delusion themes over time.

Although attention-deficit hyperactivity disorder (ADHD) is classified as a neurodevelopmental disorder in the latest diagnostic manuals, it shows phenotypic and genetic associations of similar magnitudes across neurodevelopmental, externalising and internalising disorders.

To investigate if ADHD is aetiologically more closely related to neurodevelopmental than externalising or internalising disorder clusters, after accounting for a general psychopathology factor.

Full and maternal half-sibling pairs (N = 774 416), born between 1980 and 1995, were identified from the Swedish Medical Birth and Multi-Generation Registers, and ICD diagnoses were obtained from the Swedish National Patient Register. A higher-order confirmatory factor analytic model was fitted to examine associations between ADHD and a general psychopathology factor, as well as a neurodevelopmental, externalising and internalising subfactor. Quantitative genetic modelling was performed to estimate the extent to which genetic, shared and non-shared environmental effects influenced the associations with ADHD.

ADHD was significantly and strongly associated with all three factors (r = 0.67–0.75). However, after controlling for a general psychopathology factor, only the association between ADHD and the neurodevelopmental-specific factor remained moderately strong (r = 0.43, 95% CI = 0.42–0.45) and was almost entirely influenced by genetic effects. In contrast, the association between ADHD and the externalising-specific factor was smaller (r = 0.25, 95% CI = 0.24–0.27), and largely influenced by non-shared environmental effects. There remained no internalising-specific factor after accounting for a general factor.

Findings suggest that ADHD comorbidity is largely explained by genetically influenced general psychopathology, but the strong link between ADHD and other neurodevelopmental disorders is also substantially driven by unique genetic influences.

The effects of coronavirus disease 2019 (COVID-19) on the population's mental health and well-being are likely to be profound and long lasting.

To investigate the trajectory of mental health and well-being during the first 6 weeks of lockdown in adults in the UK.

A quota survey design and a sampling frame that permitted recruitment of a national sample was employed. Findings for waves 1 (31 March to 9 April 2020), 2 (10 April to 27 April 2020) and 3 (28 April to 11 May 2020) are reported here. A range of mental health factors was assessed: pre-existing mental health problems, suicide attempts and self-harm, suicidal ideation, depression, anxiety, defeat, entrapment, mental well-being and loneliness.

A total of 3077 adults in the UK completed the survey at wave 1. Suicidal ideation increased over time. Symptoms of anxiety, and levels of defeat and entrapment decreased across waves whereas levels of depressive symptoms did not change significantly. Positive well-being also increased. Levels of loneliness did not change significantly over waves. Subgroup analyses showed that women, young people (18–29 years), those from more socially disadvantaged backgrounds and those with pre-existing mental health problems have worse mental health outcomes during the pandemic across most factors.

The mental health and well-being of the UK adult population appears to have been affected in the initial phase of the COVID-19 pandemic. The increasing rates of suicidal thoughts across waves, especially among young adults, are concerning.

In the treatment of psychosis, agitation and aggression in Alzheimer's disease, guidelines emphasise the need to ‘use the lowest possible dose’ of antipsychotic drugs, but provide no information on optimal dosing.

This analysis investigated the pharmacokinetic profiles of risperidone and 9-hydroxy (OH)-risperidone, and how these related to treatment-emergent extrapyramidal side-effects (EPS), using data from The Clinical Antipsychotic Trials of Intervention Effectiveness in Alzheimer's Disease study (Clinicaltrials.gov identifier: NCT00015548).

A statistical model, which described the concentration–time course of risperidone and 9-OH-risperidone, was used to predict peak, trough and average concentrations of risperidone, 9-OH-risperidone and ‘active moiety’ (combined concentrations) (n = 108 participants). Logistic regression was used to investigate the associations of pharmacokinetic biomarkers with EPS. Model-based predictions were used to simulate the dose adjustments needed to avoid EPS.

The model showed an age-related reduction in risperidone clearance (P < 0.0001), reduced renal elimination of 9-OH-risperidone (elimination half-life 27 h), and slower active moiety clearance in 22% of patients, (concentration-to-dose ratio: 20.2 (s.d. = 7.2) v. 7.6 (s.d. = 4.9) ng/mL per mg/day, Mann–Whitney U-test, P < 0.0001). Higher trough 9-OH-risperidone and active moiety concentrations (P < 0.0001) and lower Mini-Mental State Examination (MMSE) scores (P < 0.0001), were associated with EPS. Model-based predictions suggest the optimum dose ranged from 0.25 mg/day (85 years, MMSE of 5), to 1 mg/day (75 years, MMSE of 15), with alternate day dosing required for those with slower drug clearance.

Our findings argue for age- and MMSE-related dose adjustments and suggest that a single measure of the concentration-to-dose ratio could be used to identify those with slower drug clearance.

Generalised anxiety disorder and symptoms are associated with poor physical, emotional and social functioning and frequent primary and acute care visits. We investigated recent temporal trends in anxiety and related mental illness in UK general practice.

The aims of this analysis are to examine temporal changes in recording of generalised anxiety in primary care and initial pharmacologic treatments.

Annual incidence rates of generalised anxiety diagnoses and symptoms were calculated from 795 UK general practices contributing to The Health Improvement Network (THIN) database between 1998 and 2018. Poisson mixed regression was used to account for age, gender and general practitioner practice. Subsequent pharmacologic treatment was examined.

Generalised anxiety recording rates increased in both genders aged 18–24 between 2014 and 2018. For women, the increase was from 17.06 to 23.33/1000 person years at risk (PYAR); for men, 8.59 to 11.65/1000 PYAR. Increases persisted for a composite of anxiety and depression (49.74 to 57.81/1000 PYAR for women; 25.41 to 31.45/1000 PYAR for men). Smaller increases in anxiety were seen in both genders age 25–34 and 35–44. Anxiety rates among older patients remained stable, although a composite of anxiety and depression decreased for older women. About half of drug-naïve patients were prescribed anxiety drugs within 1 year following diagnosis. The most common choice was a selective serotonin reuptake inhibitor. Benzodiazepine prescription rate has fallen steadily.

We observed a substantial increase in general practitioner consulting for generalised anxiety and depression recently, concentrated within younger people and in particular women.

Population studies have suggested that most adults with attention-deficit hyperactivity disorder (ADHD) did not have the disorder in childhood, challenging the neurodevelopmental conceptualisation of ADHD. Arbitrary definitions of age at onset and lack of defined trajectories were accounted for the findings.

The objective of this study was to assess the proportion of individuals presenting with either a neurodevelopmental trajectory or late-onset disorder, and to assess risk factors associated with them.

Data of 4676 individuals from the 1993 Pelotas birth cohort at 11, 15, 18 and 22 years of age were used. Polythetic and latent class mixed model analyses were performed to define ADHD trajectories from childhood to adulthood, and characterise the neurodevelopmental or late-onset courses. Regression models were applied to assess factors associated with different trajectories.

Classical polythetic analyses showed that 67% of those with ADHD at 22 years of age had a neurodevelopmental course of the disorder. Latent class mixed model analysis indicated that 78% of adults with ADHD had a trajectory of persistent symptoms, more common in males. The remaining adults with ADHD had an ascending symptom trajectory that occurred after puberty, with late-onset ADHD associated with female gender and higher IQ.

Both polythetic and latent trajectories analyses provided empirical evidence supporting that the large majority of adults with ADHD had a neurodevelopmental disorder.

The link between schizophrenia and cigarette smoking has been well established through observational studies. However, the cause–effect relationship remains unclear.

We conducted Mendelian randomisation analyses to assess any causal relationship between genetic variants related to four smoking-related traits and the risk of schizophrenia.

We performed a two-sample Mendelian randomisation using summary statistics from genome-wide association studies (GWAS) of smoking-related traits and schizophrenia (7711 cases, 18 327 controls) in East Asian populations. Single nucleotide polymorphisms (SNPs) correlated with smoking behaviours (smoking initiation, smoking cessation, age at smoking initiation and quantity of smoking) were investigated in relation to schizophrenia using the inverse-variance weighted (IVW) method. Further sensitivity analyses, including Mendelian randomisation-Egger (MR-Egger), weighted median estimates and leave-one-out analysis, were used to test the consistency of the results.

The associated SNPs for the four smoking behaviours were not significantly associated with schizophrenia status. Pleiotropy did not inappropriately affect the results.

Cigarette smoking is a complex behaviour in people with schizophrenia. Understanding factors underlying the observed association remains important; however, our findings do not support a causal role of smoking in influencing risk of schizophrenia.

The COVID-19 pandemic and mitigation measures are likely to have a marked effect on mental health. It is important to use longitudinal data to improve inferences.

To quantify the prevalence of depression, anxiety and mental well-being before and during the COVID-19 pandemic. Also, to identify groups at risk of depression and/or anxiety during the pandemic.

Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC) index generation (n = 2850, mean age 28 years) and parent generation (n = 3720, mean age 59 years), and Generation Scotland (n = 4233, mean age 59 years). Depression was measured with the Short Mood and Feelings Questionnaire in ALSPAC and the Patient Health Questionnaire-9 in Generation Scotland. Anxiety and mental well-being were measured with the Generalised Anxiety Disorder Assessment-7 and the Short Warwick Edinburgh Mental Wellbeing Scale.

Depression during the pandemic was similar to pre-pandemic levels in the ALSPAC index generation, but those experiencing anxiety had almost doubled, at 24% (95% CI 23–26%) compared with a pre-pandemic level of 13% (95% CI 12–14%). In both studies, anxiety and depression during the pandemic was greater in younger members, women, those with pre-existing mental/physical health conditions and individuals in socioeconomic adversity, even when controlling for pre-pandemic anxiety and depression.

These results provide evidence for increased anxiety in young people that is coincident with the pandemic. Specific groups are at elevated risk of depression and anxiety during the COVID-19 pandemic. This is important for planning current mental health provisions and for long-term impact beyond this pandemic.

Discrepancies between the National Institute for Health and Care Excellence (NICE) schizophrenia guideline recommendations and current clinical practice in the UK have been reported.

We aim to assess whether it is cost-effective to improve adherence to the NICE schizophrenia guideline recommendations, compared with current practice.

A previously developed whole-disease model for schizophrenia, using the discrete event simulation method, was adapted to assess the cost and health impacts of adherence to the NICE recommendations. Three scenarios to improve adherence to the clinical guidelines were modelled: universal provision of cognitive–behavioural therapy for patients at clinical high risk of psychosis, universal provision of family intervention for patients with first-episode psychosis and prompt provision of clozapine for patients with treatment-resistant schizophrenia. The primary outcomes were lifetime costs and quality-adjusted life-years gained.

The results suggest full adherence to the guideline recommendations would decrease cost and improve quality-adjusted life-years. Based on the NICE willingness-to-pay threshold of £20 000–£30 000 per quality-adjusted life-year gained, prompt provision of clozapine for patients with treatment-resistant schizophrenia results in the greatest net monetary benefit, followed by universal provision of cognitive–behavioural therapy for patients at clinical high risk of psychosis, and universal provision of family intervention for patients with first-episode psychosis.

Our results suggest that adherence to guideline recommendations would decrease cost and improve quality-adjusted life-years. Greater investment is needed to improve guideline adherence and therefore improve patient quality of life and realise potential cost savings.

Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain.

To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies.

We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard.

At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52–77%), specificity 88% (76–95%) and accuracy 76% (68–84%), with positive likelihood ratio 5.3.

It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically.

N.C.J. is the owner of a free application published on the Google Play Store entitled ‘Mood Triggers’. He does not receive any direct or indirect revenue from his ownership of the application (i.e. the application is free, there are no advertisements and the data is only being used for research purposes). C.O. has no conflicts to declare.

Schizophrenia is a highly heritable disorder with undetermined neurobiological causes. Understanding the impact on brain anatomy of carrying genetic risk for the disorder will contribute to uncovering its neurobiological underpinnings.

To examine the effect of rare copy number variants (CNVs) associated with schizophrenia on brain cortical anatomy in a sample of unaffected participants from the UK Biobank.

We used regression analyses to compare cortical thickness and surface area (total and across gyri) between 120 unaffected carriers of rare CNVs associated with schizophrenia and 16 670 participants without any pathogenic CNV. A measure of cortical thickness and surface area covariance across gyri was also compared between groups.

Carrier status was associated with reduced surface area (β = −0.020 mm2, P < 0.001) and less robustly with increased cortical thickness (β = 0.015 mm, P = 0.035), and with increased covariance in thickness (carriers z = 0.31 v. non-carriers z = 0.22, P < 0.0005). Associations were mainly present in frontal and parietal areas and driven by a limited number of rare risk alleles included in our analyses (mainly 15q11.2 deletion for surface area and 16p13.11 duplication for thickness covariance).

Results for surface area conformed with previous clinical findings, supporting surface area reductions as an indicator of genetic liability for schizophrenia. Results for cortical thickness, though, argued against its validity as a potential risk marker. Increased structural thickness covariance across gyri also appears related to risk for schizophrenia. The heterogeneity found across the effects of rare risk alleles suggests potential different neurobiological gateways into schizophrenia's phenotype.

Intellectual and developmental disabilities (IDDs) and psychiatric disorders frequently co-occur. Although each has been associated with negative outcomes, their combined effect has rarely been studied.

To examine the likelihood of five negative health and healthcare outcomes for adults with IDD and mental health/addiction disorders (MHAs), both separately and together. For each outcome, demographic, clinical and system-level factors were also examined.

Linked administrative data-sets were used to identify adults in Ontario, Canada, with IDD and MHA (n = 29 476), IDD-only (n = 35 223) and MHA-only (n = 727 591). Five outcomes (30-day readmission, 30-day repeat ED visit, delayed discharge, long-term care admission and premature mortality) were examined by logistic regression models with generalised estimating equation or survival analyses. For each outcome, crude (disorder groups only) and complete (adding biosocial covariates) models were run using a general population reference group.

The IDD and MHA group had the highest proportions across outcomes for both crude and complete models. They had the highest adjusted ratios for readmissions (aOR 1.93, 95%CI 1.88–1.99), repeat ED visit (aOR 2.00, 95%CI 1.98–2.02) and long-term care admission (aHR 12.19, 95%CI 10.84–13.71). For delayed discharge, the IDD and MHA and IDD-only groups had similar results (aOR 2.00 (95%CI 1.90–2.11) and 2.21 (95%CI 2.07–2.36). For premature mortality, the adjusted ratios were similar for all groups.

Poorer outcomes for adults with IDD, particularly those with MHA, suggest a need for a comprehensive, system-wide approach spanning health, disability and social support.

Epidemiological data on the association between mental disorders and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity are limited.

To evaluate the association between mental disorders and the risk of SARS-CoV-2 infection and severe outcomes following COVID-19.

We performed a cohort study using the Korean COVID-19 patient database based on national health insurance data. Each person with a mental or behavioural disorder (diagnosed during the 6 months prior to their first SARS-CoV-2 test) was matched by age, gender and Charlson Comorbidity Index with up to four people without mental disorders. SARS-CoV-2-positivity risk and the risk of death or severe events (intensive care unit admission, use of mechanical ventilation and acute respiratory distress syndrome) post-infection were calculated using conditional logistic regression analysis.

Among 230 565 people tested for SARS-CoV-2, 33 653 (14.6%) had mental disorders; 928/33 653 (2.76%) tested SARS-CoV-2 positive and 56/928 (6.03%) died. In multivariable analysis using the matched cohort, there was no association between mental disorders and SARS-CoV-2-positivity risk (odds ratio OR = 0.95; 95% CI 0.87–1.04); however, a higher risk was associated with schizophrenia-related disorders (OR = 1.50; 95% CI 1.14–1.99). Among confirmed COVID-19 patients, the mortality risk was significantly higher in patients with than in those without mental disorders (OR = 1.99, 95% CI 1.15–3.43).

Mental disorders are likely contributing factors to mortality following COVID-19. Although the infection risk was not higher for people with mental disorders overall, those with schizophrenia-related disorders were more vulnerable to infection.