Comparison of outcomes for patients with and without a serious mental illness presenting to hospital for chronic obstruction pulmonary disease: retrospective observational study using administrative data.

Background: There are few data on the profile of those with serious mental illness (SMI) admitted to hospital for physical health reasons.

Aims: To compare outcomes for patients with and without an SMI admitted to hospital in England where the primary reason for admission was chronic obstructive pulmonary disease (COPD).

Method: This was a retrospective, observational analysis of the English Hospital Episodes Statistics data-set for the period from 1 April 2018 to 31 March 2019, for patients aged 18-74 years with COPD as the dominant reason for admission.

Schizophrenia polygenic risk score influence on white matter microstructure.

Schizophrenia (SZ) and bipolar disorder (BD) are highly heritable, share symptomatology, and have a polygenic architecture. The impact of recent polygenic risk scores (PRS) for psychosis, which combine multiple genome-wide associated risk variations, should be assessed on heritable brain phenotypes also previously associated with the illnesses, for a better understanding of the pathways to disease. We have recently reported on the current SZ PRS's ability to predict 1st episode of psychosis case-control status and general cognition.

Structured lifestyle education to support weight loss for people with schizophrenia, schizoaffective disorder and first episode psychosis: the STEPWISE RCT.

Background: Obesity is twice as common in people with schizophrenia as in the general population. The National Institute for Health and Care Excellence guidance recommends that people with psychosis or schizophrenia, especially those taking antipsychotics, be offered a healthy eating and physical activity programme by their mental health care provider. There is insufficient evidence to inform how these lifestyle services should be commissioned.

Structured lifestyle education for people with schizophrenia, schizoaffective disorder and first-episode psychosis (STEPWISE): randomised controlled trial.

Background: Obesity is a major challenge for people with schizophrenia.AimsWe assessed whether STEPWISE, a theory-based, group structured lifestyle education programme could support weight reduction in people with schizophrenia.

Method: In this randomised controlled trial (study registration: ISRCTN19447796), we recruited adults with schizophrenia, schizoaffective disorder or first-episode psychosis from ten mental health organisations in England.

The effect of psychosis associated CACNA1C, and its epistasis with ZNF804A, on brain function.

CACNA1C-rs1006737 and ZNF804A-rs1344706 polymorphisms are among the most robustly associated with schizophrenia (SCZ) and bipolar disorder (BD), and recently with brain phenotypes. As these patients show abnormal verbal fluency (VF) and related brain activation, we asked whether the latter was affected by these polymorphisms (alone and in interaction)-to better understand how they might induce risk. We recently reported effects on functional VF-related (for ZNF804A-rs1344706) and structural (for both) connectivity.

Effects of risk for bipolar disorder on brain function: A twin and family study.

Bipolar disorder (BPD) is associated with altered regional brain function during the performance of cognitive tasks. The relative contribution of genetic and environmental risk factors for BPD to these changes has not yet been quantified. We sought to address this issue in a functional neuroimaging study of people who varied in their risk for BPD.

STEPWISE - STructured lifestyle Education for People WIth SchizophrEnia: a study protocol for a randomised controlled trial.

Background: People with schizophrenia are two to three times more likely to be overweight than the general population. The UK National Institute of Health and Care Excellence (NICE) recommends an annual physical health review with signposting to, or provision of, a lifestyle programme to address weight concerns and obesity. The purpose of this randomised controlled trial is to assess whether a group-based structured education programme can help people with schizophrenia to lose weight.

Services for people with complex psychosis: towards a new understanding.

This paper describes the need for commissioners and service providers to consider the development of a whole-system approach to providing rehabilitation services for patients with complex psychosis, in the context of the current economic pressures and emergence of a competitive market in this area of mental health. The practical and organisational arrangements for the management of risk with such services are described, taking into account the varying provision of rehabilitation services across the UK and considering how these can be developed against the care clustering system and interfaces with other mental health services.

New insights into the endophenotypic status of cognition in bipolar disorder: genetic modelling study of twins and siblings.

Background: Twin studies have lacked statistical power to apply advanced genetic modelling techniques to the search for cognitive endophenotypes for bipolar disorder.

Aims: To quantify the shared genetic variability between bipolar disorder and cognitive measures.

Method: Structural equation modelling was performed on cognitive data collected from 331 twins/siblings of varying genetic relatedness, disease status and concordance for bipolar disorder.

Heritability of the limbic networks.

Individual differences in cognitive ability and social behaviour are influenced by the variability in the structure and function of the limbic system. A strong heritability of the limbic cortex has been previously reported, but little is known about how genetic factors influence specific limbic networks. We used diffusion tensor imaging tractography to investigate heritability of different limbic tracts in 52 monozygotic and 34 dizygotic healthy adult twins.

Age-Related Differences and Heritability of the Perisylvian Language Networks.

Unlabelled: Acquisition of language skills depends on the progressive maturation of specialized brain networks that are usually lateralized in adult population. However, how genetic and environmental factors relate to the age-related differences in lateralization of these language pathways is still not known. We recruited 101 healthy right-handed subjects aged 9-40 years to investigate age-related differences in the anatomy of perisylvian language pathways and 86 adult twins (52 monozygotic and 34 dizygotic) to understand how heritability factors influence language anatomy.

Interaction between effects of genes coding for dopamine and glutamate transmission on striatal and parahippocampal function.

The genes for the dopamine transporter (DAT) and the D-Amino acid oxidase activator (DAOA or G72) have been independently implicated in the risk for schizophrenia and in bipolar disorder and/or their related intermediate phenotypes. DAT and G72 respectively modulate central dopamine and glutamate transmission, the two systems most robustly implicated in these disorders. Contemporary studies have demonstrated that elevated dopamine function is associated with glutamatergic dysfunction in psychotic disorders.

Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder.

Studies of the major psychoses, schizophrenia (SZ) and bipolar disorder (BD), have traditionally focused on genetic and environmental risk factors, although more recent work has highlighted an additional role for epigenetic processes in mediating susceptibility. Since monozygotic (MZ) twins share a common DNA sequence, their study represents an ideal design for investigating the contribution of epigenetic factors to disease etiology. We performed a genome-wide analysis of DNA methylation on peripheral blood DNA samples obtained from a unique sample of MZ twin pairs discordant for major psychosis.

The genetic and environmental influences of event-related gamma oscillations on bipolar disorder.

Objectives: Gamma oscillations have been proposed to play an important role in neural information coding. There have been a limited number of electrophysiology studies in evoked gamma band responses (GBRs) in bipolar disorder (BPD). It is also unclear whether GBR deficits, if present, are potential endophenotypes for BPD as little is known about the heritability of GBRs.

Effect of D-amino acid oxidase activator (DAOA; G72) on brain function during verbal fluency.

Background: The D-Amino acid oxidase activator (G72 or DAOA) is believed to play a key role in the regulation of central glutamatergic transmission which is seen to be altered in psychosis. It is thought to regulate D-amino acid oxidase (DAO), which metabolizes D-serine, a co-agonist of NMDA-type glutamate receptors and to be involved in dendritic arborization. Linkage, genetic association and expression studies have implicated the G72 gene in both schizophrenia and bipolar disorder.

Twin study of illness history variables in psychosis.

Background: Genetic factors are important in the aetiology of psychotic disorders, but it is unclear how far they influence aspects of illness history within psychoses.

Aims: To investigate the extent, and type of familial aggregation for a range of illness history variables in psychosis.

Methods: Two-hundred-and-twenty-four proband-wise twin pairs (106 monozygotic, 118 same-sex dizygotic), where probands had psychosis, were ascertained from the Maudsley Twin Register in London.

Neural response to specific components of fearful faces in healthy and schizophrenic adults.

Perception of fearful faces is associated with functional activation of cortico-limbic structures, which has been found altered in individuals with psychiatric disorders such as schizophrenia, autism and major depression. The objective of this study was to isolate the brain response to the features of standardized fearful faces by incorporating principal component analysis (PCA) into the analysis of neuroimaging data of healthy volunteers and individuals with schizophrenia. At the first stage, the visual characteristics of morphed fearful facial expressions (FEEST, Young et al.

Increased inferior frontal activation during word generation: a marker of genetic risk for schizophrenia but not bipolar disorder?

During verbal-fluency tasks, impairments in performance and functional abnormalities in the inferior frontal cortex have been observed in both schizophrenia patients and their unaffected relatives. We sought to examine whether such functional abnormalities are a specific marker of genetic vulnerability to schizophrenia. We studied a sample of 132 subjects, comprising 39 patients with schizophrenia, 10 unaffected monozygotic (MZ) cotwins of schizophrenia probands, 28 patients with bipolar disorder, 7 unaffected MZ cotwins of bipolar disorder probands and 48 healthy controls.

Stroop-test interference in bipolar disorder.

We analysed Stroop (neuropsychological screening test) measures of response inhibition in 18 twin pairs discordant for bipolar I disorder compared with 17 healthy control pairs, as well as 40 singletons with bipolar disorder with psychotic features and a family history of psychosis, 46 of their first-degree relatives without bipolar disorder or psychosis and 48 controls. In both studies, individuals with bipolar disorder showed Stroop deficits and their first-degree relatives showed intact performance. In the twin patients, an interference score was associated with depressive symptoms.

Opposite effects of catechol-O-methyltransferase Val158Met on cortical function in healthy subjects and patients with schizophrenia.

Background: Catechol-O-methyltransferase (COMT) is essential for dopamine metabolism in the brain, and normal variation in the COMT Val158Met polymorphism can influence regional brain function during cognitive tasks. How this is affected when central dopamine function is perturbed is unclear. We addressed this by comparing the effects of COMT Val158Met genotype on cortical activation during a task of executive functions in healthy and schizophrenic subjects.

The effects of neuregulin1 on brain function in controls and patients with schizophrenia and bipolar disorder.

Recent studies have identified neuregulin1 as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders. The present investigation examined the impact of neuregulin1 genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers.

Further evidence for shared genetic effects between psychotic bipolar disorder and P50 suppression: a combined twin and family study.

P50 suppression deficit has been reported in patients with psychotic bipolar disorder. In our previous report on twin pairs concordant and discordant for bipolar disorder, we found significant genetic overlap between bipolar disorder and P50 sensory gating. However, the sample size in that study was relatively small.

Differential methylation of the X-chromosome is a possible source of discordance for bipolar disorder female monozygotic twins.

Monozygotic (MZ) twins may be subject to epigenetic modifications that could result in different patterns of gene expression. Several lines of evidence suggest that epigenetic factors may underlie mental disorders such as bipolar disorder (BD) and schizophrenia (SZ). One important epigenetic modification, of relevance to female MZ twins, is X-chromosome inactivation.

Genetic overlap between bipolar illness and event-related potentials.

Background: Electrophysiological endophenotypes are far less explored in bipolar disorder as compared to schizophrenia. No previous twin study of event-related potentials (ERPs) in bipolar illness has been reported. This study uses a twin design and advanced genetic model fitting analyses aiming to (1) assess and quantify the relationship of a range of ERP components with bipolar disorder with psychotic features, and (2) examine the source of the relationship (due to genetic or environmental factors).

Meta-analysis of magnetic resonance imaging brain morphometry studies in bipolar disorder.

Background: Several studies assessing volumetric measurements of regional brain structure in bipolar disorder have been published in recent years, but their results have been inconsistent. Our aim was to complete a meta-analysis of regional morphometry in bipolar disorder as assessed using magnetic resonance imaging (MRI).

Methods: We conducted a systematic literature search of MRI studies of bipolar disorder and identified studies which reported volume measurements in a selected number of regions.