Association of cannabis, cannabidiol and synthetic cannabinoid use with mental health in UK adolescents.

Background: Cannabis has been associated with poorer mental health, but little is known of the effect of synthetic cannabinoids or cannabidiol (often referred to as CBD).

Aims: To investigate associations of cannabis, synthetic cannabinoids and cannabidiol with mental health in adolescence.

Method: We conducted a cross-sectional analysis with 13- to 14-year-old adolescents across England and Wales in 2019-2020.

Mendelian randomisation studies of Attention Deficit Hyperactivity Disorder.

Background: Observational studies have found Attention Deficit Hyperactivity Disorder (ADHD) to be associated with an increased risk of adverse outcomes as well as with early risk factors; however it is not clear whether these associations reflect causal effects. Alternatives to traditional observational studies are needed to investigate causality: one such design is Mendelian randomization (MR), which uses genetic variants as instrumental variables for the exposure.

Methods: In this review we summarise findings from approximately 50 studies using MR to examine potentially causal associations with ADHD as either an exposure or outcome.

Genetic meta-analysis of levodopa induced dyskinesia in Parkinson's disease.

Importance: Forty percent of Parkinson's disease patients develop levodopa-induced-dyskinesia (LiD) within 4 years of starting levodopa. The genetic basis of LiD remains poorly understood, and there have been few well powered studies.

Objective: To discover common genetic variants in the PD population that increase the probability of developing LiD.

A twin study of genetic and environmental contributions to attention-deficit/hyperactivity disorder over time.

Background: Attention-deficit/hyperactivity disorder (ADHD) is an increasingly commonly diagnosed neurodevelopmental condition. One possibility is that this reflects a genuine increase in the prevalence of ADHD due to secular environmental changes, yet this hypothesis remains untested. We therefore investigated whether the genetic and environmental variance underlying ADHD, and traits of ADHD, has changed over time.

New cases of dementia are rising in elderly populations in Wales, UK.

Dementia is one of the most common diseases in elderly populations, and older populations are one of the fastest growing groups globally. Consequently, the number of people developing and living with dementia is likely to grow. Using longitudinal medical records from Wales, UK between 1999 and 2018, diagnoses of overall dementia and common subtypes were combined with demographic data to assess numbers of new and existing cases per year.

Intellectual disability in the children of the Avon Longitudinal Study of Parents and Children (ALSPAC).

Intellectual disability (ID) describes a neurodevelopmental condition involving impaired cognitive and functional ability. Here, we describe a multisource variable of ID using data from the Avon Longitudinal Study of Parents and Children (ALSPAC).  The multisource indicator variable for ID was derived from i) IQ scores less than 70 measured at age 8 and at age 15, ii) free text fields from parent reported questionnaires, iii) school reported provision of educational services for individuals with a statement of special educational needs for cognitive impairments, iv) from relevant READ codes contained in GP records, iv) international classification of disease diagnoses contained in electronic hospital records and hospital episode statistics and v) recorded interactions with mental health services for ID contained within the mental health services data set.

The network structure of mania symptoms differs between people with and without binge eating.

Objectives: People with bipolar disorder who also report binge eating have increased psychopathology and greater impairment than those without binge eating. Whether this co-occurrence is related to binge eating as a symptom or presents differently across full-syndrome eating disorders with binge eating is unclear.

Methods: We first compared networks of 13 lifetime mania symptoms in 34,226 participants from the United Kingdom's National Institute for Health and Care Research BioResource with (n = 12,104) and without (n = 22,122) lifetime binge eating.

Examining the Relationship Between Trauma, Post-Traumatic Stress Disorder and Psychosis in Patients in a UK Secondary Care Service.

Objective: Traumatic experiences and post-traumatic stress disorder (PTSD) are common in schizophrenia. However, few studies screening for PTSD have established the temporality of PTSD-related traumatic events to psychosis onset. Furthermore, it is unclear how many patients attribute a trauma-based contribution to their psychosis or would find trauma-focused therapy acceptable.

The association between peripheral inflammation, brain glutamate and antipsychotic response in Schizophrenia: Data from the STRATA collaboration.

Glutamate and increased inflammation have been separately implicated in the pathophysiology of schizophrenia and the extent of clinical response to antipsychotic treatment. Despite the mechanistic links between pro-inflammatory and glutamatergic pathways, the relationships between peripheral inflammatory markers and brain glutamate in schizophrenia have not yet been investigated. In this study, we tested the hypothesis that peripheral levels of pro-inflammatory cytokines would be positively associated with brain glutamate levels in schizophrenia.

Lived experiences of depression in autistic children and adolescents: A qualitative study on child and parent perspectives.

Background: Depression is highly prevalent in autistic children and adolescents. Despite this, little is known about the nature of the autistic child's subjective experience of depression and the impact of depression on their lives.

Methods: We therefore conducted a qualitative study using thematic analysis with 7 autistic children and adolescents and their parents to identify common themes and individual differences.

The association between reasons for first using cannabis, later pattern of use, and risk of first-episode psychosis: the EU-GEI case-control study.

Background: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.

Methods: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case-control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.

Secular trends and social inequalities in child behavioural problems across three Brazilian cohort studies (1993, 2004 and 2015).

Aims: Previous epidemiological evidence identified a concerning increase in behavioural problems among young children from 1997 to 2008 in Brazil. However, it is unclear whether behavioural problems have continued to increase, if secular changes vary between sociodemographic groups and what might explain changes over time. We aimed to monitor changes in child behavioural problems over a 22-year period from 1997 to 2019, examine changing social inequalities and explore potential explanations for recent changes in behavioural problems between 2008 and 2019.

The identification and management of people with an at-risk mental state (ARMS) for psychosis in primary and secondary care services: A qualitative interview study.

Aims: Early intervention in people with an at-risk mental state (ARMS) for psychosis can prevent the onset of psychosis. Clinical guidelines recommend that ARMS are referred to triage services, and then to Early Intervention (EI) teams in secondary care for assessment and treatment. However, little is known about how ARMS patients are identified and managed in UK primary and secondary care.

Cognitive performance at first episode of psychosis and the relationship with future treatment resistance: Evidence from an international prospective cohort study.

Background: Antipsychotic treatment resistance affects up to a third of individuals with schizophrenia, with recent research finding systematic biological differences between antipsychotic resistant and responsive patients. Our aim was to determine whether cognitive impairment at first episode significantly differs between future antipsychotic responders and resistant cases.

Methods: Analysis of data from seven international cohorts of first-episode psychosis (FEP) with cognitive data at baseline (N = 683) and follow-up data on antipsychotic treatment response: 605 treatment responsive and 78 treatment resistant cases.

Empirically driven transdiagnostic stages in the development of mood, anxiety and psychotic symptoms in a cohort of youth followed from birth.

Staging models with transdiagnostic validity across mood, psychotic, and anxiety disorders could advance early intervention efforts as well as our understanding of the common underpinnings of such psychopathology. However, there are few well-supported operationalisations for such transdiagnostic models, particularly in community-based samples. We aimed to explore the inter-relationships among mood, psychotic, and anxiety symptom stages, and their common risk factors to develop data-informed transdiagnostic stages.

Investigating young-adult social outcomes of attention deficit hyperactivity disorder.

Objective: Attention Deficit Hyperactivity Disorder (ADHD) is associated with a range of adverse outcomes in adult life. However it is unclear whether the risk pathways to adverse adult outcomes are established during childhood or whether associations are driven by concurrent ADHD symptoms that have persisted to adulthood.

Methods: We examined associations between broadly defined child-limited (remitted) and persistent ADHD (assessed using the ADHD subscale of the Strengths and Difficulties Questionnaire) with social outcomes (low emotional and instrumental support, antisocial behaviour, employment, receipt of state benefits as an indicator of socio-economic disadvantage, homelessness) at age 25 years in a UK longitudinal population sample ALPSAC (the Avon Longitudinal Study of Parents and Children, age 25 data collected between years 2017 and 2018): total N=6439.

Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations.

Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes. This recent study-and most other large-scale human genetics studies-was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear.

Rare coding variants as risk modifiers of the 22q11.2 deletion implicate postnatal cortical development in syndromic schizophrenia.

22q11.2 deletion is one of the strongest known genetic risk factors for schizophrenia. Recent whole-genome sequencing of schizophrenia cases and controls with this deletion provided an unprecedented opportunity to identify risk modifying genetic variants and investigate their contribution to the pathogenesis of schizophrenia in 22q11.

Rare CNVs and phenome-wide profiling highlight brain structural divergence and phenotypical convergence.

Copy number variations (CNVs) are rare genomic deletions and duplications that can affect brain and behaviour. Previous reports of CNV pleiotropy imply that they converge on shared mechanisms at some level of pathway cascades, from genes to large-scale neural circuits to the phenome. However, existing studies have primarily examined single CNV loci in small clinical cohorts.

Polygenic Scores and Onset of Major Mood or Psychotic Disorders Among Offspring of Affected Parents.

Objective: Family history is an established risk factor for mental illness. The authors sought to investigate whether polygenic scores (PGSs) can complement family history to improve identification of risk for major mood and psychotic disorders.

Methods: Eight cohorts were combined to create a sample of 1,884 participants ages 2-36 years, including 1,339 offspring of parents with mood or psychotic disorders, who were prospectively assessed with diagnostic interviews over an average of 5.