Development and initial evaluation of a clinical prediction model for risk of treatment resistance in first-episode psychosis: Schizophrenia Prediction of Resistance to Treatment (SPIRIT).

Background: A clinical tool to estimate the risk of treatment-resistant schizophrenia (TRS) in people with first-episode psychosis (FEP) would inform early detection of TRS and overcome the delay of up to 5 years in starting TRS medication.

Aims: To develop and evaluate a model that could predict the risk of TRS in routine clinical practice.

Method: We used data from two UK-based FEP cohorts (GAP and AESOP-10) to develop and internally validate a prognostic model that supports identification of patients at high-risk of TRS soon after FEP diagnosis.

The effect of heavy smoking on retirement risk: A mendelian randomisation analysis.

Background And Aims: The extent to which heavy smoking and retirement risk are causally related remains to be determined. To overcome the endogeneity of heavy smoking behaviour, we employed a novel approach by exploiting the genetic predisposition to heavy smoking, as measured with a polygenic risk score (PGS), in a Mendelian Randomisation approach.

Methods: 8164 participants (mean age 68.

The genetic architecture of dog ownership: large-scale genome-wide association study in 97,552 European-ancestry individuals.

Dog ownership has been associated with several complex traits, and there is evidence of genetic influence. We performed a genome-wide association study of dog ownership through a meta-analysis of 31,566 Swedish twins in 5 discovery cohorts and an additional 65,986 European-ancestry individuals in 3 replication cohorts from Sweden, Norway, and the United Kingdom. Association tests with >7.

Long-Term Course of Remission and Recovery in Psychotic Disorders.

Objective: Understanding prognosis is critical to anticipating public health needs and providing care to individuals with psychotic disorders. However, the long-term course of remission and recovery remains unclear. In this study, the most common trajectories of illness course are described for a cohort of individuals followed for 25 years since first admission for psychosis.

Immune-neuroendocrine patterning and response to stress. A latent profile analysis in the English longitudinal study of ageing.

Psychosocial stress exposure can disturb communication signals between the immune, nervous, and endocrine systems that are intended to maintain homeostasis. This dysregulation can provoke a negative feedback loop between each system that has high pathological risk. Here, we explore patterns of immune-neuroendocrine activity and the role of stress.

Polygenic predisposition, sleep duration, and depression: evidence from a prospective population-based cohort.

Suboptimal sleep durations and depression frequently cooccur. Short-sleep and long-sleep are commonly thought of as symptoms of depression, but a growing literature suggests that they may be prodromal. While each represents a process of mutual influence, the directionality between them remains unclear.

Schizophrenia polygenic risk score and type 2 diabetes onset in older adults with no schizophrenia diagnosis.

Objectives: An association between type 2 diabetes (T2DM) and schizophrenia has long been observed, and recent research revealed presence of shared genetic factors. However, epidemiological evidence was inconsistent, some reported insignificant contribution of genetic factors to T2DM-schizophrenia comorbidity. Prior works studied people with schizophrenia, particularly, antipsychotic-naive patients, or those during the first psychotic experience to limit schizophrenia-related environmental factors.

Immune-Neuroendocrine Patterning and Response to Stress. A latent profile analysis in the English Longitudinal Study of Ageing.

Psychosocial stress exposure can disturb communication signals between the immune, nervous, and endocrine systems that are intended to maintain homeostasis. This dysregulation can provoke a negative feedback loop between each system that has high pathological risk. Here, we explore patterns of immune-neuroendocrine activity and the role of stress.

Polygenic Propensity for Longevity, APOE-ε4 Status, Dementia Diagnosis, and Risk for Cause-Specific Mortality: A Large Population-Based Longitudinal Study of Older Adults.

To deepen the understanding of genetic mechanisms influencing mortality risk, we investigated the impact of genetic predisposition to longevity and APOE-ε4, on all-cause mortality and specific causes of mortality. We further investigated the mediating effects of dementia on these relationships. Using data on 7 131 adults aged ≥50 years (mean = 64.

The shared genetic architecture of smoking behaviours and psychiatric disorders: evidence from a population-based longitudinal study in England.

Background: Considering the co-morbidity of major psychiatric disorders and intelligence with smoking, to increase our understanding of why some people take up smoking or continue to smoke, while others stop smoking without progressing to nicotine dependence, we investigated the genetic propensities to psychiatric disorders and intelligence as determinants of smoking initiation, heaviness of smoking and smoking cessation in older adults from the general population.

Results: Having utilised data from the English Longitudinal Study of Ageing (ELSA), our results showed that one standard deviation increase in MDD-PGS was associated with increased odds of being a moderate-heavy smoker (odds ratio [OR] = 1.11, SE = 0.

The role of loneliness in the association between chronic physical illness and depressive symptoms among older adults: A prospective cohort study.

Background: Chronic physical illness increases the risk of subsequent depressive symptoms, but we know little about the mechanisms underlying this association that interventions can target. We investigated whether loneliness might explain associations between chronic illness and subsequent depressive symptoms.

Methods: We used English Longitudinal Study of Ageing data, a prospective cohort of adults over 50.

The interactive association of adverse childhood experiences and polygenic susceptibility with depressive symptoms and chronic inflammation in older adults: a prospective cohort study.

Background: Adverse childhood experiences (ACEs) and genetic liability are important risk factors for depression and inflammation. However, little is known about the gene-environment (G × E) mechanisms underlying their aetiology. For the first time, we tested the independent and interactive associations of ACEs and polygenic scores of major depressive disorder (MDD-PGS) and C-reactive protein (CRP-PGS) with longitudinal trajectories of depression and chronic inflammation in older adults.

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.

Genetic propensity, socioeconomic status, and trajectories of depression over a course of 14 years in older adults.

Depression is one of the leading causes of disability worldwide and is a major contributor to the global burden of disease among older adults. The study aimed to investigate the interplay between socio-economic markers (education and financial resources) and polygenic predisposition influencing individual differences in depressive symptoms and their change over time in older adults, which is of central relevance for preventative strategies. The sample encompassing n = 6202 adults aged ≥50 years old with a follow-up period of 14 years was utilised from the English Longitudinal Study of Ageing.

Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium.

Introduction: Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR.

Methods: We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.

Grip Strength Trajectories and Cognition in English and Chilean Older Adults: A Cross-Cohort Study.

Growing evidence about the link between cognitive and physical decline suggests the early changes in physical functioning as a potential biomarker for cognitive impairment. Thus, we compared grip-strength trajectories over 12-16 years in three groups classified according to their cognitive status (two stable patterns, normal and impaired cognitive performance, and a declining pattern) in two representative UK and Chilean older adult samples. The samples consisted of 7069 UK (ELSA) and 1363 Chilean participants (ALEXANDROS).

Study protocol for the development and internal validation of Schizophrenia Prediction of Resistance to Treatment (SPIRIT): a clinical tool for predicting risk of treatment resistance to antipsychotics in first-episode schizophrenia.

Introduction: Treatment-resistant schizophrenia (TRS) is associated with significant impairment of functioning and high treatment costs. Identification of patients at high risk of TRS at the time of their initial diagnosis may significantly improve clinical outcomes and minimise social and functional disability. We aim to develop a prognostic model for predicting the risk of developing TRS in patients with first-episode schizophrenia and to examine its potential utility and acceptability as a clinical decision tool.

High polygenic predisposition for ADHD and a greater risk of all-cause mortality: a large population-based longitudinal study.

Background: Attention deficit hyperactivity disorder (ADHD) is a highly heritable, neurodevelopmental disorder known to associate with more than double the risk of death compared with people without ADHD. Because most research on ADHD has focused on children and adolescents, among whom death rates are relatively low, the impact of a high polygenic predisposition to ADHD on accelerating mortality risk in older adults is unknown. Thus, the aim of the study was to investigate if a high polygenetic predisposition to ADHD exacerbates the risk of all-cause mortality in older adults from the general population in the UK.

The long-term effects of a polygenetic predisposition to general cognition on healthy cognitive ageing: evidence from the English Longitudinal Study of Ageing.

Background: As an accelerated cognitive decline frequently heralds onset of severe neuropathological disorders, understanding the source of individual differences in withstanding the onslaught of cognitive ageing may highlight how best cognitive abilities may be retained into advanced age.

Methods: Using a population representative sample of 5088 adults aged •50 years from the English Longitudinal Study of Ageing, we investigated relationships of polygenic predisposition to general cognition with a rate of change in cognition during a 10-year follow-up period. Polygenic predisposition was measured with polygenic scores for general cognition (GC-PGS).

Interplay between polygenic propensity for ageing-related traits and the consumption of fruits and vegetables on future dementia diagnosis.

Background: Understanding how polygenic scores for ageing-related traits interact with diet in determining a future dementia including Alzheimer's diagnosis (AD) would increase our understanding of mechanisms underlying dementia onset.

Methods: Using 6784 population representative adults aged ≥50 years from the English Longitudinal Study of Ageing, we employed accelerated failure time survival model to investigate interactions between polygenic scores for AD (AD-PGS), schizophrenia (SZ-PGS) and general cognition (GC-PGS) and the baseline daily fruit and vegetable intake in association with dementia diagnosis during a 10-year follow-up. The baseline sample was obtained from waves 3-4 (2006-2009); follow-up data came from wave 5 (2010-2011) to wave 8 (2016-2017).

Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia.

Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown.