Genetic and environmental contributions to diagnostic fluctuation in anorexia nervosa and bulimia nervosa.

BACKGROUND: Anorexia nervosa and bulimia nervosa are two severe eating disorders associated with high premature mortality, suicidal risk and serious medical complications. Transition between anorexia nervosa and bulimia nervosa over the illness course and familial co-aggregation of the two eating disorders imply aetiological overlap. However, genetic and environmental liabilities to the overlap are poorly understood. Quantitative genetic research using clinical diagnosis is needed. METHODS: We acquired a clinical diagnosis of anorexia nervosa (prevalence = 0.90%) and bulimia nervosa (prevalence = 0.48%) in a large population-based sample (N = 782 938) of randomly selected full-sisters and maternal half-sisters born in Sweden between 1970 and 2005. Structural equation modelling was applied to quantify heritability of clinically diagnosed anorexia nervosa and bulimia nervosa and the contributions of genetic and environmental effects on their overlap. RESULTS: The heritability of clinically diagnosed anorexia nervosa and bulimia nervosa was estimated at 43% [95% confidence interval (CI) (36-50%)] and 41% (31-52%), respectively, in the study population, with the remaining variance explained by variance in unique environmental effects. We found statistically significant genetic [0.66, 95% CI (0.49-0.82)] and unique environmental correlations [0.55 (0.43-0.66)] between the two clinically diagnosed eating disorders; and their overlap was about equally explained by genetic and unique environmental effects [co-heritability 47% (35-58%)]. CONCLUSIONS: Our study supports shared mechanisms for anorexia nervosa and bulimia nervosa and extends the literature from self-reported behavioural measures to clinical diagnosis. The findings encourage future molecular genetic research on both eating disorders and emphasize clinical vigilance for symptom fluctuation between them.

Factors Associated With Adherence to Methylphenidate Treatment in Adult Patients With Attention-Deficit/Hyperactivity Disorder and Substance Use Disorders.

Adherence to treatment is one of the most consistent factors associated with a favorable addiction treatment outcome. Little is known about factors associated with treatment adherence in individuals affected with comorbid attention-deficit/hyperactivity disorder and substance use disorders (SUD). This study aimed to explore whether treatment-associated factors, such as the prescribing physician's (sub)specialty and methylphenidate (MPH) dose, or patient-related factors, such as sex, age, SUD subtype, and psychiatric comorbidity, were associated with adherence to MPH treatment. Swedish national registers were used to identify adult individuals with prescriptions of MPH and medications specifically used in the treatment of SUD or a diagnosis of SUD and/or coexisting psychiatric diagnoses. Primary outcome measure was days in active MPH treatment in stratified dose groups (≤36 mg, ≥37 mg to ≤54 mg, ≥55 mg to ≤72 mg, ≥73 mg to ≤90 mg, ≥91 mg to ≤108 mg, and ≥109 mg). Lower MPH doses (ie, ≤36 mg day 100) were associated with treatment discontinuation between days 101 and 830 (HR≤36 mg, 1.67; HR37-54mg, 1.37; HR55-72mg, 1.36; HR73-90mg, 1.19; HR≥108mg, 1.09). The results showed a linear trend (P < 0.0001) toward decreased risk of treatment discontinuation along with increase of MPH doses. In conclusion, this study shows that higher MPH doses were associated with long-term treatment adherence in individuals with attention-deficit/hyperactivity disorder and SUD.

Preconception Maternal Bereavement and Infant and Childhood Mortality: A Danish Population-Based Study.

OBJECTIVES: Preconception maternal bereavement may be associated with an increased risk for infant mortality, although these previously reported findings have not been replicated. We sought to examine if the association could be replicated and explore if risk extended into childhood. METHODS: Using a Danish population-based sample of offspring born 1979 to 2009 (N = 1,865,454), we analyzed neonatal (0-28 days), postneonatal infant (29-364 days), and early childhood (1-5 years) mortality after maternal bereavement in the preconception (6-0 months before pregnancy) and prenatal (between conception and birth) periods. Maternal bereavement was defined as death of a first-degree relative of the mother. Analyses were conducted using logistic and log-linear Poisson regressions that were adjusted for offspring, mother, and father sociodemographic and health factors. RESULTS: We identified 6541 (0.004%) neonates, 3538 (0.002%) postneonates, and 2132 (0.001%) children between the ages of 1 and 5 years who died. After adjusting for covariates, bereavement during the preconception period was associated with increased odds of neonatal (adjusted odds ratio = 1.87, 95% confidence interval = 1.53-2.30) and postneonatal infant mortality (adjusted odds ratio = 1.52, 95% confidence interval = 1.15-2.02). Associations were timing specific (6 months before pregnancy only) and consistent across sensitivity analyses. Bereavement during the prenatal period was not consistently associated with increased risk of offspring mortality; however, this may reflect relatively low statistical power. CONCLUSIONS: Results support and extend previous findings linking bereavement during the preconception period with increased odds of early offspring mortality. The period immediately before pregnancy may be a sensitive period with potential etiological implications and ramifications for offspring mortality.