Reducing sampling errors in constructing genetic selection indices

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Interconnected or disconnected? Promotion of mental health and prevention of mental disorder in the digital age

To date there have been few peer-reviewed studies on the feasibility, acceptability and effectiveness of digital technologies for mental health promotion and disorder prevention. Any evaluation of these evolving technologies is complicated by a lack of understanding about the specific risks and possible benefits of the many forms of internet use on mental health. To adequately meet the mental health needs of today's society, psychiatry must engage in rigorous assessment of the impact of digital technologies

Long-term outcomes and the effects of maintenance treatments in bipolar disorder

Objectives To determine 1) mortality and morbidity in people with bipolar disorder, and 2) the impact of maintenance medication on relapse/reoccurrence and adverse events. Methods Objective 1: I conducted a meta-analysis of studies examining mortality in bipolar disorder populations. I then carried out a cohort study in United Kingdom primary care electronic health records to understand rates of mortality and morbidity in bipolar disorder relative to the general population. Objective 2: I completed a network meta-analysis of the efficacy of maintenance mood stabiliser medications (lithium, valproate, olanzapine and quetiapine) in preventing relapse. I then carried out a series of cohort studies in primary care electronic health records. These studies examined 1) the effectiveness and tolerability of these medications, 2) the rates of renal, endocrine, hepatic and metabolic adverse events, and 3) the rates of self-harm, accidental injury and suicide. Propensity score methods were used to address issues of confounding. Results Objective 1: All-cause and cause specific mortality was elevated in people with bipolar disorder (summary standardised mortality ratio 2.05; 95% CI 1.89 to 2.23). In a cohort of 17,341 with bipolar disorder, mortality rates increased from the mid-2000s relative to the general population (hazard ratio increased by 0.14 per year; 95% CI 0.10 to 0.19). Objective 2: Trials comparing lithium, valproate, olanzapine, quetiapine and placebo did not show superiority of one drug. In the electronic health records cohort studies individuals prescribed lithium went for longer before treatment failure (for example valproate had hazard ratio 1.20; 95% CI 1.10 to 1.32 compared with lithium), had increased mild (but not severe) renal failure (hazard ratio for valproate: 0.56; 95% CI 0.45 to 0.69 compared with lithium), hypo- and hyperthyroidism and hypercalcemia rates. However, they had lower rates of clinically significant weight gain (hazard ratio for >15% weight gain with valproate: 1.62; 95% CI 1.31 to 2.01 compared with lithium) and there was no difference in hepatotoxicity, cardiovascular events or diabetes mellitus rates. Additionally, people taking lithium had lower self-harm (hazard ratio for alternatives: 1.51; 95% CI 1.21 to 1.88 compared to lithium) and accidental injury rates. Conclusions Bipolar disorder is associated with increased mortality and morbidity, and the mortality gap with the general population has widened in recent years. Despite limited trial evidence, lithium appears to offer the best opportunity for mood stabilisation. Lithium is associated with increased renal and endocrine dysfunction, but these risks are offset by the potential of more frequent weight gain with alternative drugs. Furthermore, lithium may be associated with specific anti-suicidal effects. These risk and benefits should be considered when individual treatment decisions are made

Curiosity killed the cat: no evidence of an association between cat ownership and psychotic symptoms at ages 13 and 18 years in a UK general population

Congenital or early life infection with Toxoplasma gondii has been implicated in schizophrenia aetiology. Childhood cat ownership has been hypothesized as an intermediary marker of T. gondii infection and, by proxy, as a risk factor for later psychosis. Evidence supporting this hypothesis is, however, limited. We used birth cohort data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to investigate whether cat ownership in pregnancy and childhood (ages 4 and 10 years) was associated with psychotic experiences (PEs) in early (age 13, N = 6705) and late (age 18, N = 4676) adolescence, rated from semi-structured interviews. We used logistic regression to examine associations between cat ownership and PEs, adjusting for several sociodemographic and socioeconomic factors, household characteristics and dog ownership. Missing data were handled via multiple imputation. Cat ownership during pregnancy was not associated with PEs at age 13 years [adjusted odds ratio (OR) 1.15, 95% confidence interval (CI) 0.97–1.35] or 18 years (OR 1.08, 95% CI 0.86–1.35). Initial univariable evidence that cat ownership at ages 4 and 10 years was associated with PEs at age 13 years did not persist after multivariable adjustment (4 years: OR 1.18, 95% CI 0.94–1.48; 10 years: OR 1.12, 95% CI 0.92–1.36). There was no evidence that childhood cat ownership was associated with PEs at age 18 years. While pregnant women should continue to avoid handling soiled cat litter, given possible T. gondii exposure, our study strongly indicates that cat ownership in pregnancy or early childhood does not confer an increased risk of later adolescent PEs

Cancer rates and mortality in people with severe mental illness: Further evidence of lack of parity

Background: Severe mental illness (SMI) is associated with poorer physical health, however the relationship between SMI and cancer is complex and previous study findings are inconsistent. Low incidence of cancer in those with SMI has been attributed to premature mortality, though evidence for this is lacking. We aimed to investigate the relationship between SMI and cancer incidence and mortality, and to assess the effect of premature mortality on cancer incidence rates. / Methods: In this UK-wide matched cohort study using primary care records we calculated incidence and mortality rates of all-cancer, and bowel, lung, breast or prostate cancer, in patients with SMI, compared to matched patients without SMI. We used competing risks regression to account for mortality from other causes. / Findings: 69,632 patients had an SMI diagnosis. The rate of all-cancer diagnoses was reduced in those with SMI (Hazard ratio (HR):0·95; 95%CI 0·93–0·98) compared to those without SMI, and particularly in those with schizophrenia (HR:0·82; 95%CI 0·77–0·88) compared to those without SMI. When accounting for the competing risk of premature mortality, incidence remained lower only in patients with schizophrenia. All-cause mortality after cancer was increased in the SMI group, and cancer-specific mortality was increased in those with schizophrenia (hazard ratio: 1.96; 95%CI 1.57–2.44). / Interpretation: Patients with schizophrenia have lower rates of cancer diagnosis but higher all-cause and cancer-specific mortality rates following diagnosis compared to those without SMI. Premature mortality does not explain these differences, suggesting the findings reflect barriers to cancer diagnosis and treatment, which need to be identified and addressed

Individual and area-level risk factors for suicidal ideation and attempt in people with severe depression

INTRODUCTION: Previous research has identified several risk factors that are strongly associated with suicidal behavior in patients with severe depression. However, the effects of area-level characteristics on suicidal ideation and attempt in this population remain unclear. METHODS: The Clinical Record Interactive Search (CRIS) database was used to identify 2587 patients with severe depression who received secondary mental health services from the Camden & Islington NHS Foundation Trust. Stepwise multivariable logistic regression models were used to examine associations between socio-demographic characteristics, clinical variables, area-level measures, and suicidal ideation and attempt as separate outcomes. RESULTS: Both suicidal ideation and attempts were common among this cohort of severely depressed individuals (70.5% and 37.7%, respectively). While several individual socio-demographic and clinical characteristics were associated with both outcomes, particularly past psychiatric admission (suicidal ideation: adjusted OR=2.86, 95% CI: 2.26-3.62; suicide attempt: adjusted OR=4.00, 95% CI: 3.30-4.89), neither social deprivation nor ethnic density (measured at the area-level) was associated with risk for either outcome. LIMITATIONS: Data were not collected specifically for research purposes and hence information on some potential confounders was not available. Additionally, information was restricted to individuals who accessed secondary mental health services in a defined catchment area and period. The study therefore does not take into account individuals who did not access mental health services. CONCLUSIONS: The variation in risk for suicidal ideation and attempt among severely depressed individuals is explained by differences in individual socio-demographic and clinical characteristics, most notably past psychiatric admission and substance misuse, and not by area-level measures

Association Between Childhood Visual Acuity and Late Adolescent Psychotic Experiences: A Prospective Birth Cohort Study

A cross-sectional association between visual impairment and psychosis exists, but longitudinal evidence from children and young people is limited. We investigated whether childhood visual acuity was associated with subsequent psychotic experiences. Our sample was 6686 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC). We investigated whether our primary exposures, best corrected visual acuity at ages 7 and 11, were associated with psychotic experiences at ages 17 and 24. We also tested whether the following exposures at ages 7 and 11 were associated with subsequent psychotic experiences: requiring glasses, presence of any visual impairment, and between-eye visual acuity difference; and at age 7: strabismus, measures of binocular vision, history of eye patch, near vision impairment, and abnormal saccadic or pursuit eye movements. Analyses used multilevel models before and after adjusting for confounders. Odds of psychotic experiences increased with each 0.1-point deterioration in visual acuity score at age 11 (adjusted odds ratio [AOR] 1.23; 95% confidence interval [CI] 1.06–1.42), and at age 7 (AOR 1.18; 95% CI 1.00–1.40). Wearing glasses and visual impairment at age 11 were associated with psychotic experiences (AOR 1.63; 95% CI 1.21–2.19; AOR 1.64; 95% CI 1.23–2.19, respectively). There was no evidence of an association with other visual exposures. Visual acuity impairment in childhood is associated with psychotic experiences in late adolescence. Future research should aim to elucidate the nature of this association

Air Pollution (Particulate Matter) Exposure and Associations with Depression, Anxiety, Bipolar, Psychosis and Suicide Risk: A Systematic Review and Meta-Analysis

BACKGROUND: Particulate air pollution's physical health effects are well known, but associations between particulate matter (PM) exposure and mental illness have not yet been established. However, there is increasing interest in emerging evidence supporting a possible etiological link. OBJECTIVES: This systematic review aims to provide a comprehensive overview and synthesis of the epidemiological literature to date by investigating quantitative associations between PM and multiple adverse mental health outcomes (depression, anxiety, bipolar disorder, psychosis, or suicide). METHODS: We undertook a systematic review and meta-analysis. We searched Medline, PsycINFO, and EMBASE from January 1974 to September 2017 for English-language human observational studies reporting quantitative associations between exposure to PM 6   months ) PM 2.5 exposure and depression ( n = 5 studies), the pooled odds ratio was 1.102 per 10 - μ g / m 3 PM 2.5 increase (95% CI: 1.023, 1.189; I 2 = 0.00 % ). Two of the included studies investigating associations between long-term PM 2.5 exposure and anxiety also reported statistically significant positive associations, and we found a statistically significant association between short-term PM 10 exposure and suicide in meta-analysis at a 0-2 d cumulative exposure lag. DISCUSSION: Our findings support the hypothesis of an association between long-term PM 2.5 exposure and depression, as well as supporting hypotheses of possible associations between long-term PM 2.5 exposure and anxiety and between short-term PM 10 exposure and suicide. The limited literature and methodological challenges in this field, including heterogeneous outcome definitions, exposure assessment, and residual confounding, suggest further high-quality studies are warranted to investigate potentially causal associations between air pollution and poor mental health

Doxycycline exposure during adolescence and future risk of non-affective psychosis and bipolar disorder: a total population cohort study

Doxycycline has been hypothesized to prevent development of severe mental illness (SMI) through the suppression of microglia, especially if administered during the intense synaptic pruning period of adolescence. However, results from register studies on potential benefits differ considerably. The aim of the present study was to determine whether doxycycline exposure during adolescence is associated with reduced SMI risk, and to investigate if a direct and specific causality is plausible. This is a Swedish national population register-based cohort study of all individuals born from 1993 to 1997, followed from the age of 13 until end of study at the end of 2016. The primary exposure was cumulative doxycycline prescription ≥3000 mg and outcomes were first diagnosis of non-affective psychosis (F20–F29) and first diagnosis of bipolar disorder (F30–F31). Causal effects were explored through Cox regressions with relevant covariates and secondary analyses of multilevel exposure and comparison to other antibiotics. We found no association between doxycycline exposure and risk of subsequent non-affective psychosis (adjusted hazard ratio (HR) 1.15, 95% CI 0.73–1.81, p = 0.541) and an increased risk of subsequent bipolar disorder (adjusted HR 1.95, 95% CI 1.49–2.55, p < 0.001). We do not believe the association between doxycycline and bipolar disorder is causal as similar associations were observed for other common antibiotics