Genetic liability to ADHD and substance use disorders in individuals with ADHD

Aims 1) To investigate whether genetic liability to attention‐deficit/hyperactivity disorder (ADHD), indexed by polygenic risk scores for ADHD (PRS‐ADHD), is associated with substance use disorders (SUD) in individuals with ADHD. 2) To investigate whether other individual‐ or family‐related risk factors for SUD could mediate or confound this association. Design Population‐based cohort study Setting and participants ADHD cases in the iPSYCH sample (a Danish case‐cohort sample of genotyped cases with specific mental disorders), born in Denmark between 1981 and 2003 (N = 13 116). Register‐based information on hospital diagnoses of SUD was available until December 31, 2016. Measurements We estimated odds ratios (ORs) with 95% confidence intervals (CIs) for any SUD as well as for different SUD types (alcohol, cannabis, and other illicit drugs) and severities (use, abuse, and addiction), with effect sizes corresponding to a comparison of the highest PRS‐ADHD decile to the lowest. Findings PRS‐ADHD were associated with any SUD (OR = 1.30, 95% CI: 1.11–1.51). Estimates were similar across different types and severity levels of SUD. Other risk factors for SUD (male sex, age at ADHD diagnosis, comorbid conduct problems, and parental factors including SUD, mental disorders, and socio‐economic status) were independently associated with increased risk of SUD. PRS‐ADHD explained a minor proportion of the variance in SUD (0.2% on the liability scale) compared to the other risk factors. The association between PRS‐ADHD and any SUD was slightly attenuated (OR = 1.21, 95% CI: 1.03–1.41) after adjusting for the other risk factors for SUD. Furthermore, associations were nominally higher in females than in males (ORfemales = 1.59, 95% CI: 1.19–2.12, ORmales = 1.18, 95% CI: 0.98–1.42). Conclusions A higher genetic liability to attention‐deficit/hyperactivity disorder appears to be associated with higher risks of substance use disorders in individuals with attention‐deficit/hyperactivity disorder

Changing neighborhood income deprivation over time, moving in childhood and adult risk of depression

ImportanceComplex biological, socioeconomic and psychological variables combine to cause mental illnesses; with mounting evidence that early-life experiences are related to adulthood mental health. ObjectiveTo determine whether changing neighborhood income deprivation and residential moves during childhood are associated with risk of being diagnosed with depression in adulthood.DesignIndividuals were followed from their 15th birthday until either death, emigration, depression diagnosis, or December 31, 2018. Longitudinal residential location was obtained by linking all individuals to the Danish longitudinal population register. SettingThe whole population cohort of 1,096,916 people born in Denmark, 1981-2001, who resided in the country during the first 15 years of life.Participants35,098 individuals developed depression during follow-up.ExposuresA neighborhood income deprivation index at place of residence for each year of age from 0-15, and a mean income deprivation index for the entire childhood ( aged 0-15).Residential moves were considered by defining ‘stayers’ as individuals who lived in the same Data Zone during their entire childhood, ‘movers’ otherwise.Main Outcomes and MeasuresMultilevel survival analysis determined associations between neighborhood-level income deprivation and incidence rates, after adjustment for individual factors. Results were reported as incidence rate ratios (IRRs). The hypotheses were formulated before data collection. ResultsA total of 1,096,916 (males: 563,864 [51.4%]) individuals were followed from age 15. During follow-up, 35,098 (females: 23,728 [67.6%]) were diagnosed with depression. People from deprived areas during childhood had an increased risk of depression (IRR 1.10, 95% CI: 1.08-1.12). Following full individual-level adjustment the risk was attenuated (IRR of 1.02, 95% CI: 1.01-1.04), indicating an increase of 2% in depression incidence for each standard deviation increase in income deprivation. Moving during childhood, independent of neighborhood deprivation status, was associated with significantly higher rates of depression in adulthood, compared to non-movers, (IRR 1.61, 95% CI: 1.52-1.1.70) for 2 or more moves after full adjustment.Conclusions and Relevance. Rather than just low or changing neighborhood income deprivation trajectories in childhood driving adulthood depression, those individuals with an unsettled home environment in childhood are more likely to develop depression in adulthood. Policies that enable and support settled childhoods should be promoted.Keywords (5):Depression; Social context; Residential mobility; Population registers; Danish longitudinal Deprivation Index <br/

Parental income as a marker for socioeconomic position during childhood and later risk of developing a secondary care-diagnosed mental disorder examined across the full diagnostic spectrum : a national cohort study

Background: Links between parental socioeconomic position during childhood and subsequent risks of developing mental disorders have rarely been examined across the diagnostic spectrum. We conducted a comprehensive analysis of parental income level, including income mobility, during childhood and risks for developing mental disorders diagnosed in secondary care in young adulthood. Methods: National cohort study of persons born in Denmark 1980–2000 (N = 1,051,265). Parental income was measured during birth year and at ages 5, 10 and 15. Follow-up began from 15th birthday until mental disorder diagnosis or 31 December 2016, whichever occurred first. Hazard ratios and cumulative incidence were estimated. Results: A quarter (25.2%; 95% CI 24.8–25.6%) of children born in the lowest income quintile families will have a secondary care-diagnosed mental disorder by age 37, versus 13.5% (13.2–13.9%) of those born in the highest income quintile. Longer time spent living in low-income families was associated with higher risks of developing mental disorders. Associations were strongest for substance misuse and personality disorders and weaker for mood disorders and nxiety/somatoform disorders. An exception was eating disorders, with low parental income being associated with attenuated risk. For all diagnostic categories examined except for eating disorders, downward socioeconomic mobility was linked with higher subsequent risk and upward socioeconomic mobility with lower subsequent risk of developing mental disorders. Conclusions: Except for eating disorders, low parental income during childhood is associated with subsequent increased risk of mental disorders diagnosed in secondary care across the diagnostic spectrum. Early interventions to mitigate the disadvantages linked with low income, and better opportunities for upward socioeconomic mobility could reduce social and mental health inequalities.Peer reviewe

Use of Statins and Risk of Hospitalization With Dementia: A Danish Population-based Case-control Study

Several epidemiological studies have indicated reduced risk of dementia among users of statins. We assessed the risk of hospitalization with dementia associated with use of statins in a population-based case-control study in four Northern Danish counties in the period 1991-2005. We identified 11,039 cases with dementia and 110,340 age- and gender-matched population controls using data from the National Patient Registry, the Danish Psychiatric Central Register and the Civil Registration System. Prescriptions for statins filled before the admission for dementia were identified using population-based prescription databases. We used conditional logistic regression analysis to compute relative risk of hospitalization with dementia associated with use of statins using non-users as reference group. We found an overall reduced risk of hospitalization with dementia among statin users (adjusted odds ratio (OR) 0.67, 95% confidence intervals (CI): 0.60-0.75). The reduced risk associated with statin use remained robust in various subanalyses, however, we found no clear dose-response pattern between the number of filled prescriptions for statin and the risk of hospitalization with dementia. In conclusion, we found a reduced risk of hospitalization with dementia among users of statins, however, whether this association is causal remains to be clarified

Lack of fit with the neighbourhood social environment as a risk factor for psychosis – a national cohort study

BackgroundMany studies report an ethnic density effect whereby psychosis incidence among ethnic minority groups is higher in low co-ethnic density areas. It is unclear whether an equivalent density effect applies with other types of socioeconomic disadvantages.MethodsWe followed a population cohort of 2 million native Danes comprising all those born on 1st January 1965, or later, living in Denmark on their 15th birthday. Socioeconomic disadvantage, based on parents' circumstances at age 15 (low income, manual occupation, single parent and unemployed), was measured alongside neighbourhood prevalence of these indices.ResultsEach indicator was associated with a higher incidence of non-affective psychosis which remained the same, or was slightly reduced, if neighbourhood levels of disadvantage were lower. For example, for individuals from a low-income background there was no difference in incidence for those living in areas where a low-income was least common [incidence rate ratio (IRR) 1.01; 95% confidence interval (CI) 0.93–1.10 v. those in the quintile where a low income was most common. Typically, differences associated with area-level disadvantage were the same whether or not cohort members had a disadvantaged background; for instance, for those from a manual occupation background, incidence was lower in the quintile where this was least v. most common (IRR 0.83; 95% CI 0.71–0.97), as it was for those from a non-manual background (IRR 0.77; 95% CI 0.67–0.87).ConclusionWe found little evidence for group density effects in contrast to previous ethnic density studies. Further research is needed with equivalent investigations in other countries to see if similar patterns are observed

Validation of an algorithm-based definition of treatment resistance in patients with schizophrenia

Large-scale pharmacoepidemiological research on treatment resistance relies on accurate identification of people with treatment-resistant schizophrenia (TRS) based on data that are retrievable from administrative registers. This is usually approached by operationalising clinical treatment guidelines by using prescription and hospital admission information. We examined the accuracy of an algorithm-based definition of TRS based on clozapine prescription and/or meeting algorithm-based eligibility criteria for clozapine against a gold standard definition using case notes. We additionally validated a definition entirely based on clozapine prescription. 139 schizophrenia patients aged 18–65 years were followed for a mean of 5 years after first presentation to psychiatric services in South-London, UK. The diagnostic accuracy of the algorithm-based measure against the gold standard was measured with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). A total of 45 (32.4%) schizophrenia patients met the criteria for the gold standard definition of TRS; applying the algorithm-based definition to the same cohort led to 44 (31.7%) patients fulfilling criteria for TRS with sensitivity, specificity, PPV and NPV of 62.2%, 83.0%, 63.6% and 82.1%, respectively. The definition based on lifetime clozapine prescription had sensitivity, specificity, PPV and NPV of 40.0%, 94.7%, 78.3% and 76.7%, respectively. Although a perfect definition of TRS cannot be derived from available prescription and hospital registers, these results indicate that researchers can confidently use registries to identify individuals with TRS for research and clinical practices