Mina Rydell

Suicide in obsessive–compulsive disorder: a population-based study of 36 788 Swedish patients

The risk of death by suicide in individuals with obsessive–compulsive disorder (OCD) is largely unknown. Previous studies have been small and methodologically flawed. We analyzed data from the Swedish national registers to estimate the risk of suicide in OCD and identify the risk and protective factors associated with suicidal behavior in this group. We used a matched case–cohort design to estimate the risk of deaths by suicide and attempted suicide in individuals diagnosed with OCD, compared with matched general population controls (1:10). Cox regression models were used to study predictors of suicidal behavior. We identified 36 788 OCD patients in the Swedish National Patient Register between 1969 and 2013. Of these, 545 had died by suicide and 4297 had attempted suicide. In unadjusted models, individuals with OCD had an increased risk of both dying by suicide (odds ratio (OR)=9.83 (95% confidence interval (CI), 8.72–11.08)) and attempting suicide (OR=5.45 (95% CI, 5.24–5.67)), compared with matched controls. After adjusting for psychiatric comorbidities, the risk was reduced but remained substantial for both death by suicide and attempted suicide. Within the OCD cohort, a previous suicide attempt was the strongest predictor of death by suicide. Having a comorbid personality or substance use disorder also increased the risk of suicide. Being a woman, higher parental education and having a comorbid anxiety disorder were protective factors. We conclude that patients with OCD are at a substantial risk of suicide. Importantly, this risk remains substantial after adjusting for psychiatric comorbidities. Suicide risk should be carefully monitored in patients with OCD.

Association Between Deliberate Self-harm and Violent Criminality

Importance Individuals who self-harm may have an increased risk of aggression toward others, but this association has been insufficiently investigated. More conclusive evidence may affect assessment, treatment interventions, and clinical guidelines. Objective To investigate the association between nonfatal self-harm and violent crime. Design, Setting, and Participants This population-based longitudinal cohort study, conducted from January 1, 1997, through December 31, 2013, studied all Swedish citizens born between 1982 and 1998 who were 15 years and older (N = 1 850 252). Individuals who emigrated from Sweden before the age of 15 years (n = 104 051) or immigrated to Sweden after the age of 13 years (ie, <2 years before the beginning of the follow-up; n = 22 009) were excluded. Data analysis was performed from April 21, 2016, to June 4, 2016. Exposures Receipt of self-harm–associated clinical care. Main Outcomes and Measures Conviction of a violent crime according to the Swedish penal code. Results The study cohort consisted of 1 850 525 individuals (950 382 males and 900 143 females), and the mean (SD) follow-up time was 8.1 (4.7) years (range, 0-17.0 years; minimum age, 15 years; maximum age, 32 years). During a mean follow-up period of 8.1 years, 55 185 individuals (3.0%) received clinical care for self-harm. The crude hazard ratio was 4.9 (95% CI, 4.8-5.0) for violent crime conviction in exposed individuals compared with the unexposed group. Women who self-harm were at particularly high risk for expressing violent behaviors. After adjustment for relevant psychiatric comorbidities and socioeconomic status, an almost doubled hazard of violent offense remained (hazard ratio, 1.8; 95% CI, 1.8-1.9). Conclusions and Relevance Self-harm is associated with an increased risk of conviction for a violent offense in both sexes. The risk of violence, as well as the risk of suicide and self-harm, should be assessed among offending and self-harming individuals.

Association of Perinatal Risk Factors With Obsessive-Compulsive Disorder: A Population-Based Birth Cohort, Sibling Control Study

Importance Perinatal complications may increase the risk of obsessive-compulsive disorder (OCD). Previous reports were based on small, retrospective, specialist clinic-based studies that were unable to rigorously control for unmeasured environmental and genetic confounding. Objective To prospectively investigate a wide range of potential perinatal risk factors for OCD, controlling for unmeasured factors shared between siblings in the analyses. Design, Setting, and Participants This population-based birth cohort study included all 2 421 284 children from singleton births in Sweden from January 1, 1973, to December 31, 1996, who were followed up through December 31, 2013. From the 1 403 651 families in the cohort, differentially exposed siblings from the 743 885 families with siblings were evaluated; of these, 11 592 families included clusters of full siblings that were discordant for OCD. Analysis of the data was conducted from January, 26, 2015, to September, 5, 2016. Exposures Perinatal data were collected from the Swedish Medical Birth Register and included maternal smoking during pregnancy, labor presentation, obstetric delivery, gestational age (for preterm birth), birth weight, birth weight in relation to gestational age, 5-minute Apgar score, and head circumference. Main Outcomes and Measures Previously validated OCD codes (International Statistical Classification of Diseases and Health Related Problems, Tenth Revision, code F42) in the Swedish National Patient Register. Results Of 2 421 284 individuals included in the cohort, 17 305 persons were diagnosed with OCD. Of these, 7111 were men (41.1%). The mean (SD) age of individuals at first diagnosis of OCD was 23.4 (6.5) years. An increased risk for OCD remained after controlling for shared familial confounders and measured covariates (including sex, year of birth, maternal and paternal age at birth, and parity), for smoking 10 or more cigarettes per day during pregnancy (hazard ratio [HR], 1.27; 95% CI, 1.02-1.58), breech presentation (HR, 1.35; 95% CI, 1.06-1.71), delivery by cesarean section (HR, 1.17; 95% CI, 1.01-1.34), preterm birth (HR, 1.24; 95% CI, 1.07-1.43), birth weight 1501 to 2500 g (HR, 1.30; 95% CI, 1.05-1.62) and 2501 to 3500 g (HR, 1.08; 95% CI, 1.01-1.16), being large for gestational age (HR, 1.23; 95% CI, 1.05-1.45), and Apgar distress scores at 5 minutes (HR, 1.50; 95% CI, 1.07-2.09). Gestational age and birth weight followed inverse dose-response associations, whereby an increasingly higher risk for OCD was noted in children with a shorter gestational age and lower birth weight. We also observed a dose-response association between the number of perinatal events and increased OCD risk, with HRs ranging from 1.11 (95% CI, 1.07-1.15) for 1 event to 1.51 (95% CI, 1.18-1.94) for 5 or more events. Conclusions and Relevance A range of perinatal risk factors is associated with a higher risk for OCD independent of shared familial confounders, suggesting that perinatal risk factors may be in the causal pathway to OCD.

Perinatal risk factors in Tourette’s and chronic tic disorders: a total population sibling comparison study

Adverse perinatal events may increase the risk of Tourette’s and chronic tic disorders (TD/CTD), but previous studies have been unable to control for unmeasured environmental and genetic confounding. We aimed to prospectively investigate potential perinatal risk factors for TD/CTD, taking unmeasured factors shared between full siblings into account. A population-based birth cohort, consisting of all singletons born in Sweden in 1973–2003, was followed until December 2013. A total of 3 026 861 individuals were identified, 5597 of which had a registered TD/CTD diagnosis. We then studied differentially exposed full siblings from 947 942 families; of these, 3563 families included siblings that were discordant for TD/CTD. Perinatal data were collected from the Medical Birth Register and TD/CTD diagnoses were collected from the National Patient Register, using a previously validated algorithm. In the fully adjusted models, impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of TD/CTD, largely independent from shared family confounders and measured covariates. Maternal smoking during pregnancy was associated with risk of TD/CTD in a dose–response manner but the association was no longer statistically significant in the sibling comparison models or after the exclusion of comorbid attention-deficit/hyperactivity disorder. A dose–response relationship between the number of adverse perinatal events and increased risk for TD/CTD was also observed, with hazard ratios ranging from 1.41 (95% confidence interval (CI): 1.33–1.50) for one event to 2.42 (95% CI: 1.65–3.53) for five or more events. These results pave the way for future gene by environment interaction and epigenetic studies in TD/CTD.

Suicide in Tourette’s and Chronic Tic Disorders

BACKGROUND Persons with neuropsychiatric disorders are at increased risk of suicide, but there is little data concerning Tourettes and chronic tic disorders (TD/CTD). We aimed to quantify the risk of suicidal behavior in a large nationwide cohort of patients with TD/CTD, establish the contribution of psychiatric comorbidity to this risk, and identify predictors of suicide. METHODS Using a validated algorithm, we identified 7736 TD/CTD cases in the Swedish National Patient Register during a 44-year period (1969-2013). Using a matched case-cohort design, patients were compared with general population control subjects (1:10 ratio). Risk of suicidal behavior was estimated using conditional logistic regressions. Predictors of suicidal behavior in the TD/CTD cohort were studied using Cox regression models. RESULTS In unadjusted models, TD/CTD patients, compared with control subjects, had an increased risk of both dying by suicide (odds ratio: 4.39; 95% confidence interval [CI]: 2.89-6.67) and attempting suicide (odds ratio: 3.86; 95% CI: 3.50-4.26). After adjusting for psychiatric comorbidities, the risk was reduced but remained substantial. Persistence of tics beyond young adulthood and a previous suicide attempt were the strongest predictors of death by suicide in TD/CTD patients (hazard ratio: 11.39; 95% CI: 3.71-35.02, and hazard ratio: 5.65; 95% CI: 2.21-14.42, respectively). CONCLUSIONS TD/CTD are associated with substantial risk of suicide. Suicidal behavior should be monitored in these patients, particularly in those with persistent tics, history of suicide attempts, and psychiatric comorbidities. Preventive and intervention strategies aimed to reduce the suicidal risk in this group are warranted.

Maternal Smoking in Pregnancy and Offspring Depression:: a cross cohort and negative control study

Previous reports suggest that offspring of mothers who smoke during pregnancy have greater risk of developing depression. However, it is unclear whether this is due to intrauterine effects. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) from the UK (N = 2,869), the Nord-Trøndelag health study (HUNT) from Norway (N = 15,493), the Pelotas 1982 Birth Cohort Study from Brazil (N = 2,626), and the Swedish Sibling Health Cohort (N = 258 sibling pairs), we compared associations of maternal smoking during pregnancy and mother’s partner’s smoking during pregnancy with offspring depression and performed a discordant sibling analysis. In meta-analysis, maternal smoking during pregnancy was associated with higher odds of offspring depression (OR 1.20, 95% CI:1.08,1.34), but mother’s partner’s smoking during pregnancy was not (OR 1.05, 95% CI:0.94,1.17). However, there was only weak statistical evidence that the odds ratios for maternal and mother’s partner’s smoking differed from each other (p = 0.08). There was no clear evidence for an association between maternal smoking during pregnancy and offspring depression in the sibling analysis. Findings do not provide strong support for a causal role of maternal smoking during pregnancy in offspring depression, rather observed associations may reflect residual confounding relating to characteristics of parents who smoke.

Genetic and environmental contributions to the association between ADHD and affective problems in early childhood-A Swedish population-based twin study.

Few twin studies have explored the relative contribution of genetic and environmental factors to the association between attention deficit hyperactivity disorder (ADHD) and affective problems, and no study has focused on preschool children. We used the classical twin design to explore the genetic and environmental overlap between ADHD symptoms and affective problems in preschool children, based on 879 five‐year‐old twin pairs born in Sweden 2004–2005. Questionnaire‐based parent‐ratings were used to measure ADHD symptoms and affective problems. A bivariate twin design was used to decompose variance in ADHD and affective problems into genetic and environmental components, and to test the degree to which these components overlapped across the two traits. Our results showed that there was a significant correlation of 0.34 (95% Confidence Interval [CI] 0.29–0.38) between ADHD and affective problems. This correlation was mostly explained by additive genetic factors (64%, 95%CI 37–93%), and to a lesser extent by shared environmental factors (35%, 95%CI 10–59%). Nonshared environmental factors did not contribute to the correlation between ADHD and affective problems (0%, 95%CI −9 to 10%). These findings show that there is a significant association between ADHD and affective problems in preschool children that is mostly explained by genetic influences. This adds important knowledge about the etiology of both ADHD and affective problems by indicating that these phenotypes are linked from as early as preschool years. This also needs to be taken into consideration when diagnosing young children and clinicians should consider assessing both affective problems and ADHD if one is present.

Maternal smoking during pregnancy and offspring’s tobacco dependence. A study of exposure-discordant sibling pairs

BACKGROUND Prenatal exposure to maternal smoking has previously been linked to tobacco dependence, but confounding from genetic and early-environmental factors is of concern. The aim of this study was to clarify if maternal smoking during pregnancy may affect the onset and manifestations of tobacco dependence after taking such factors into account. METHODS The study is based on a matched cohort of 1538 siblings discordant for prenatal exposure to maternal smoking, who participated in a survey conducted in 2010 in Sweden. Analyses were based on pairs where both siblings had been daily smokers (193 pairs) or snus users (173 pairs) at some time in their life. Participants were 19-27 years old at the time of participation. Outcomes were tobacco dependence measured with the Cigarette Dependence Scale (CDS-12) in smokers and with the adapted Smokeless Tobacco Dependence Scale (STDS-12) in snus users, and previous quit attempts. Exposure to maternal smoking during pregnancy was retrieved from the Swedish Medical Birth Register. RESULTS There was no difference in dependence scores in exposure-discordant siblings (mean difference 0.36 on CDS-12 [95% confidence interval: -1.23 to 1.95] and 0.61 on STDS-12 [95% confidence interval: -1.20 to 2.43]). Neither did the siblings differ with regard to previous quit attempts. CONCLUSIONS Maternal smoking during pregnancy does not appear to influence tobacco dependence in adult offspring. A potential effect of heavy maternal smoking during pregnancy cannot be excluded, but genetic and environmental influences seem to be more influential for the onset of tobacco dependence.

Sex-specific manifestation of genetic risk for attention deficit hyperactivity disorder in the general population

Background Attention deficit hyperactivity disorder (ADHD) is more commonly diagnosed in males than in females. A growing body of research suggests that females with ADHD might be underdiagnosed or receive alternative diagnoses, such as anxiety or depression. Other lines of reasoning suggest that females might be protected from developing ADHD, requiring a higher burden of genetic risk to manifest the disorder. Methods We tested these two hypotheses, using common variant genetic data from two population‐based cohorts. First, we tested whether females and males diagnosed with anxiety or depression differ in terms of their genetic risk for ADHD, assessed as polygenic risk scores (PRS). Second, we tested whether females and males with ADHD differed in ADHD genetic risk burden. We used three different diagnostic definitions: registry‐based clinical diagnoses, screening‐based research diagnoses and algorithm‐based research diagnoses, to investigate possible referral biases. Results In individuals with a registry‐based clinical diagnosis of anxiety or depression, females had higher ADHD PRS than males [OR(CI) = 1.39 (1.12–1.73)] but there was no sex difference for screening‐based [OR(CI) = 1.15 (0.94–1.42)] or algorithm‐based [OR(CI) = 1.04 (0.89–1.21)] diagnoses. There was also no sex difference in ADHD PRS in individuals with ADHD diagnoses that were registry‐based [OR(CI) = 1.04 (0.84–1.30)], screening‐based [OR(CI) = 0.96 (0.85–1.08)] or algorithm‐based [OR(CI) = 1.15 (0.78–1.68)]. Conclusions This study provides genetic evidence that ADHD risk may be more likely to manifest or be diagnosed as anxiety or depression in females than in males. Contrary to some earlier studies, the results do not support increased ADHD genetic risk in females with ADHD as compared to affected males.

Has the attention deficit hyperactivity disorder phenotype become more common in children between 2004 and 2014? Trends over 10 years from a Swedish general population sample

BACKGROUND Studies have reported increases in clinically diagnosed and treated attention deficit hyperactivity disorder (ADHD) during the last decade, but it is unclear if this reflects an increase in the underlying ADHD phenotype. We aimed to clarify if there has been an increase in the prevalence of ADHD-like traits in the general population from 2004 to 2014. METHOD Data were collected from 9-year-old twins (19,271), participating in the population-based Child and Adolescent Twin Study in Sweden between 2004 and 2014. We assessed lifetime ADHD symptoms using the Autism-Tics, ADHD and other Comorbidities inventory. Research proxies for diagnostic-level ADHD and subthreshold ADHD were derived from this scale. We modeled the lifetime prevalence of diagnostic-level and subthreshold ADHD with logistic regression, and assessed mean ADHD scores each year with linear regression. Lifetime prevalence of clinically diagnosed ADHD was retrieved from the National Patient Register and modeled with logistic regression. RESULTS The prevalence of diagnostic-level ADHD based on parent ratings did not differ significantly over time from 2004 to 2014 (OR 1.37; 95% CI: 0.77-2.45; p-value .233). Both subthreshold ADHD and mean ADHD scores increased significantly over time (both p-values <.001). Clinically diagnosed ADHD increased more than fivefold from 2004 to 2014 (OR 5.27, 95% CI: 1.85-14.96). CONCLUSIONS We found no evidence of an increase in ADHD-like traits at the extreme end of the distribution from 2004 to 2014, but small increases in normal and subthreshold variations of ADHD-like traits were observed. This suggests that the increased rates of clinically diagnosed ADHD might reflect changes in diagnostic and treatment practices of ADHD, administrative changes in reporting diagnoses, greater awareness of ADHD, better access to healthcare, or current overdiagnosis, rather than an increase in the ADHD phenotype.