Impact of genetic, sociodemographic, and clinical features on antidepressant treatment trajectories in the perinatal period

Pregnant women on antidepressants must balance potential fetal harm with the relapse risk. While various clinical and sociodemographic factors are known to influence treatment decisions, the impact of genetic factors remains unexplored. We conducted a cohort study among 2,316 women with diagnosed affective disorders who had redeemed antidepressant prescriptions six months before pregnancy, identified from the Danish Integrated Psychiatric Research study. We calculated polygenic risk scores (PGSs) for major depression (MDD), bipolar disorder (BD), and schizophrenia (SCZ) using individual-level genetic data and summary statistics from genomewide association studies. We retrieved data on sociodemographic and clinical features from national registers. Applying group-based trajectory modeling, we identified four treatment trajectories across pregnancy and postpartum: Continuers (38.2 %), early discontinuers (22.7 %), late discontinuers (23.8 %), and interrupters (15.3 %). All three PGSs were not associated with treatment trajectories; for instance, the relative risk ratio for continuers versus early discontinuers was 0.93 (95 % CI: 0.81-1.06), 0.98 (0.84-1.13), 1.09 (0.95-1.27) for per 1-SD increase in PGS for MDD, BD, and SCZ, respectively. Sociodemographic factors were generally not associated with treatment trajectories, except for the association between primiparity and continuing antidepressant use. Women who received >= 2 classes or a higher dose of antidepressants had a higher probability of being late discontinuers, interrupters, and continuers. The likelihood of continuing antidepressants or restarting antidepressants postpartum increased with the previous antidepressant treatment duration. Our findings indicate that continued antidepressant use during pregnancy is influenced by the severity of the disease rather than genetic predisposition as measured by PGSs

Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores

Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R(2) increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase

Polygenic risk score, parental socioeconomic status, family history of psychiatric disorders, and the risk for schizophrenia: a Danish population-based study and meta-analysis

IMPORTANCE Schizophrenia has a complex etiology influenced both by genetic and nongenetic factors but disentangling these factors is difficult. OBJECTIVE To estimate (1) how strongly the risk for schizophrenia relates to the mutual effect of the polygenic risk score, parental socioeconomic status, and family history of psychiatric disorders; (2) the fraction of cases that could be prevented if no one was exposed to these factors; (3) whether family background interacts with an individual's genetic liability so that specific subgroups are particularly risk prone; and (4) to what extent a proband's genetic makeup mediates the risk associated with familial background. DESIGN, SETTINGS, AND PARTICIPANTS We conducted a nested case-control study based onDanish population-based registers. The study consisted of 866 patients diagnosed as having schizophrenia between January 1, 1994, and December 31, 2006, and 871 matched control individuals. Genome-wide data and family psychiatric and socioeconomic background information were obtained from neonatal biobanks and national registers. Results from a separate meta-analysis (34 600 cases and 45 968 control individuals) were applied to calculate polygenic risk scores. EXPOSURES Polygenic risk scores, parental socioeconomic status, and family psychiatric history. MAIN OUTCOMES AND MEASURES Odds ratios (ORs), attributable risks, liability R2 values, and proportions mediated. RESULTS Schizophrenia was associated with the polygenic risk score (OR, 8.01; 95%CI, 4.53-14.16 for highest vs lowest decile), socioeconomic status (OR, 8.10; 95%CI, 3.24-20.3 for 6 vs no exposures), and a history of schizophrenia/psychoses (OR, 4.18; 95%CI, 2.57-6.79). The R2 values were 3.4%(95%CI, 2.1-4.6) for the polygenic risk score, 3.1%(95%CI, 1.9-4.3) for parental socioeconomic status, and 3.4%(95%CI, 2.1-4.6) for family history. Socioeconomic status and psychiatric history accounted for 45.8% (95%CI, 36.1-55.5) and 25.8% (95%CI, 21.2-30.5) of cases, respectively. There was an interaction between the polygenic risk score and family history (P = .03). A total of 17.4%(95%CI, 9.1-26.6) of the effect associated with family history of schizophrenia/psychoses was mediated through the polygenic risk score. CONCLUSIONS AND RELEVANCE Schizophrenia was associated with the polygenic risk score, family psychiatric history, and socioeconomic status. Our study demonstrated that family history of schizophrenia/psychoses is partly mediated through the individual's genetic liability

Social inequalities in changes in health-related behaviour among Slovak adolescents aged between 15 and 19: A longitudinal study

<p>Abstract</p> <p>Background</p> <p>Lower socioeconomic position is generally associated with higher rates of smoking and alcohol consumption and lower levels of physical activity. Health-related behaviour is usually established during late childhood and adolescence. The aim of this study is to explore changes in health-related behaviour in a cohort of adolescents aged between 15 and 19, overall and by socioeconomic position.</p> <p>Methods</p> <p>The sample consisted of 844 first-year students (42.8% males, baseline in 1998 – mean age 14.9, follow-up in 2002 – mean age 18.8) from 31 secondary schools located in Kosice, Slovakia. This study focuses on changes in adolescents' smoking, alcohol use, experience with marijuana and lack of physical exercise with regard to their socioeconomic position. Four indicators of socioeconomic position were used – adolescents' current education level and employment status, and the highest education level and highest occupational status of their parents. We first made cross tabulations of HRB with these four indicators, using McNemar's test to assess differences. Next, we used logistic regression to assess adjusted associations, using likelihood ratio tests to assess statistical significance.</p> <p>Results</p> <p>Statistically significant increases were found in all health-related behaviours. Among males, the most obvious socioeconomic gradient was found in smoking, both at age 15 and at 19. Variations in socioeconomic differences in health-related behaviour were more apparent among females. Although at age 15, almost no socioeconomic differences in health-related behaviour were found, at age 19 differences were found for almost all socioeconomic indicators. Among males, only traditional socioeconomic gradients were found (the lower the socioeconomic position, the higher the prevalence of potentially harmful health-related behaviour), while among females reverse socioeconomic gradients were also found.</p> <p>Conclusion</p> <p>We confirmed an increase in unhealthy health-related behaviour during adolescence. This increase was related to socioeconomic position, and was more apparent in females.</p

The association between weekly hours of physical activity and mental health: A three-year follow-up study of 15–16-year-old students in the city of Oslo, Norway

<p>Abstract</p> <p>Background</p> <p>Mental health problems are a worldwide public health burden. The literature concerning the mental health benefits from physical activity among adults has grown. Adolescents are less studied, and especially longitudinal studies are lacking. This paper investigates the associations between weekly hours of physical activity at age 15–16 and mental health three years later.</p> <p>Methods</p> <p>Longitudinal self-reported health survey. The baseline study consisted of participants from the youth section of the Oslo Health Study, carried out in schools in 2000–2001 (<it>n </it>= 3811). The follow-up in 2003–2004 was conducted partly at school and partly through mail. A total of 2489 (1112 boys and 1377 girls) participated in the follow-up. Mental health was measured by the Strengths and Difficulties Questionnaire with an impact supplement. Physical activity was measured by a question on weekly hours of physical activity outside of school, defined as exertion 'to an extent that made you sweat and/or out of breath'. Adjustments were made for well-documented confounders and mental health at baseline.</p> <p>Results</p> <p>In boys, the number of hours spent on physical activity per week at age 15–16 was negatively associated with emotional symptoms [B (95%CI) = -0.09 (-0.15, -0.03)] and peer problems [B (95%CI) = -0.08 (-0.14, -0.03)] at age 18–19 after adjustments. In girls, there were no significant differences in SDQ subscales at age 18–19 according to weekly hours of physical activity at age 15–16 after adjustments. Boys and girls with five to seven hours of physical activity per week at age 15–16 had the lowest mean scores for total difficulties and the lowest percentage with high impact score at age 18–19, but the differences were not statistically significant after adjustments.</p> <p>Conclusion</p> <p>Weekly hours of physical activity at age 15–16 years was weakly associated with mental health at three-year follow-up in boys. Results encourage a search for further knowledge about physical activity as a possible protective factor in relation to mental health problems in adolescence.</p

Parent and child physical activity and sedentary time: Do active parents foster active children?

<p>Abstract</p> <p>Background</p> <p>Physical activity has many positive effects on children's health while TV viewing has been associated with adverse health outcomes. Many children do not meet physical activity recommendations and exceed TV viewing guidelines. Parents are likely to be an important influence on their children's behaviour. There is an absence of information about the associations between parents' and children's physical activity and TV viewing.</p> <p>Methods</p> <p>Year 6 children and their parent were recruited from 40 primary schools. Results are presented for the 340 parent-child dyads with accelerometer data that met a ≥ 3 day inclusion criteria and the 431 parent-child dyads with complete self-reported TV viewing. Over 80% of the dyads with valid TV viewing data included mothers and their child. Mean minutes of moderate to vigorous physical activity (MVPA), minutes of sedentary time per day and counts per minute were assessed by accelerometer. Self-reported hours of TV viewing were coded into 3 groups (< 2 hours per day, 2-4 hours per day and >4 hours per day. Linear and multi-nominal regression models were run by child gender to examine parent-child associations.</p> <p>Results</p> <p>In linear regression models there was an association for the overall sedentary time of girls and their parents (t = 2.04. p = .020) but there was no association between girls' and parents' physical activity. There were no associations between parents' and boys' sedentary or physical activity time. For girls, the risk of watching more than 4 hours of TV per day, (reference = 2 hours of TV per day), was 3.67 times higher if the girl's parent watched 2-4 hours of TV per day (p = 0.037). For boys, the risk of watching more than 4 hours of TV per day, was 10.47 times higher if the boy's parent watched more than 4 hours of TV per day (p = 0.038).</p> <p>Conclusions</p> <p>There are associations in the sedentary time of parents and daughters. Higher parental TV viewing was associated with an increased risk of high levels of TV viewing for both boys and girls. There were no associations between the time that parents and children spend engaged in physical activity.</p

Patterns in sedentary and exercise behaviors and associations with overweight in 9–14-year-old boys and girls - a cross-sectional study.

BACKGROUND: Before starting interventions addressing energy-balance related behaviors, knowledge is needed about the prevalence of sedentary behaviors and low physical exercise, their interrelationships, possible gender differences. Therefore this study aimed to describe gender differences in sedentary and physical exercise behaviors and their association with overweight status in children from nine European countries. Additionally, to identify clusters of children sharing the same pattern regarding sedentary and physical exercise behavior and compare these groups regarding overweight status. METHODS: Cross-sectional study among 11-year-old children in nine countries (n = 12538). Self-administered questionnaires assessed the time spent on TV viewing during dinner and during the day, PC use and on physical exercise. The parents reported children's weight and height. Descriptive statistics, cluster analyses, and logistic regression analyses were used for data analyses. RESULTS: Boys spent more time on sedentary behaviors but also more on physical exercise than girls. High TV viewing and low exercise behavior independently increased the risk of being overweight. Based on the behaviors, five clusters were identified. Among boys, clear associations with being overweight were found, with the most unhealthy behavior pattern having the highest risks of being overweight. Among girls, high TV viewers and high PC users had increased risk of being overweight. In girls sedentary behaviors seemed more important than physical exercise with regard to overweight status. CONCLUSION: Despite selective non-response on BMI and reliance on self-reports, the associations between clusters and overweight in boys were clear, and differences between boys and girls regarding the behaviors and risks for overweight are noteworthy. These differences need to be considered when developing tailored intervention strategies for prevention of overweight