Familial co-aggregation studies of eating disorders (EDs) and schizophrenia reveal shared genetic and environment factors, yet their etiological and clinical relationship remains unclear. We evaluate ...the influence of schizophrenia family history on clinical outcomes of EDs.
We conducted a cohort evaluation of the association between family history of schizophrenia and ED clinical features, psychiatric comorbidities, and somatic and mental health burden in individuals born in Sweden 1977-2003 with anorexia nervosa (AN) or other EDs (OED: bulimia nervosa, binge-eating disorder, and ED not otherwise specified).
Of 12 424 individuals with AN and 20 716 individuals with OED, 599 (4.8%) and 1118 (5.4%), respectively, had a family history of schizophrenia (in up to third-degree relatives). Among individuals with AN, schizophrenia in first-degree relatives was significantly associated with increased comorbid attention-deficit/hyperactivity disorder (ADHD) HR(95% CI) 2.26 (1.27-3.99), substance abuse disorder (SUD) HR (95% CI) 1.93 (1.25-2.98), and anxiety disorders HR (95% CI) 1.47 (1.08-2.01), but higher lowest illness-associated body mass index (BMI) 1.14 kg/m
, 95% CI (0.19-2.10). Schizophrenia in any relative (up to third-degree) in AN was significantly associated with higher somatic and mental health burden, but lower ED psychopathology scores -0.29, 95% CI (-0.54 to -0.04). Schizophrenia in first-degree relatives in individuals with OED was significantly associated with increased comorbid ADHD, obsessive-compulsive disorder, SUD, anxiety disorders, somatic and mental health burden, and suicide attempts.
We observed different patterns of ED-related outcomes, psychiatric comorbidity, and illness burden in individuals with EDs with and without family histories of schizophrenia and provide new insights into the diverse manifestations of EDs.
Background
Sleep disorders in youth have been associated with increased risks of injury, including suicidal behavior. This study investigated whether melatonin, which is the most common medication ...for sleep disturbances in youth in Sweden, is associated with a decreased risk of injury.
Methods
This population‐based cohort study included 25,575 youths who initiated melatonin treatment between ages 6 and 18. Poisson regression was used to estimate rate of injuries in the year prior to and following melatonin treatment initiation. A within‐individual design was used to estimate relative risks by comparing injury risk in the last unmedicated month with injury risks in the 12 months after medication initiation. Analyses were stratified by sex, injury type, psychiatric comorbidities and age at melatonin‐treatment initiation.
Results
While body injuries, falls and transport accident rates were comparable in the year before and after melatonin‐treatment initiation, the risk of self‐harm was highest in the months immediately prior to medication, and decreased thereafter. This was particularly prominent among adolescents with depression and/or anxiety, with females displaying greater absolute risks than males. Compared to the last unmedicated month, the 12 months post medication initiation had decreased relative risks for self‐harm, with an IRR 95% CI in the month following melatonin‐treatment initiation of 0.46 0.27–0.76 among adolescent females with psychiatric disorders, after excluding antidepressant users.
Conclusions
Decreased risk of intentional self‐harm was observed following melatonin‐treatment initiation among females with depression and anxiety, suggesting that sleep interventions could be considered in an effort to reduce risk of self‐harm in this population.
A growing body of literature recognizes associations between eating disorders (EDs) and schizophrenia and suggests that familial liability to schizophrenia in individuals with anorexia nervosa (AN) ...reveals distinct patterns of clinical outcomes. To further investigate the influence of schizophrenia genetic liability among individuals with EDs, we evaluated the associations between schizophrenia polygenic risk scores (PRS) and clinical presentations of individuals with EDs including their overall health condition and ED-related symptoms. Using data from two previous studies of the genetics of EDs comprising 3,573 Anorexia Nervosa Genetics Initiative (ANGI) cases and 696 Binge Eating Genetics Initiative (BEGIN) cases born after 1973 and linked to the Swedish National Patient Register, we examined the association of schizophrenia PRS on ED clinical features, psychiatric comorbidities, and somatic and mental health burden. Among ANGI cases, higher schizophrenia PRS was statistically significantly associated with higher risk of major depressive disorder (MDD) measured by hazard ratio (HR) with 95% confidence interval (CI) (HR 95% CI: 1.07 1.02, 1.13) and substance abuse disorder (SUD) (HR 95% CI: 1.14 1.03, 1.25) after applying multiple testing correction. Additionally, higher schizophrenia PRS was associated with decreased clinical impairment assessment scores (-0.56, 95% CI: -1.04, -0.08) at the conventional significance level (p < 0.05). Further, in BEGIN cases, higher schizophrenia PRS was statistically significantly associated with earlier age at first ED symptom (-0.35 year, 95% CI: -0.64, -0.06), higher ED symptom scores (0.16, 95% CI: 0.04, 0.29), higher risk of MDD (HR 95% CI: 1.18 1.04, 1.34) and SUD (HR 95% CI: 1.36 1.07, 1.73). Similar, but attenuated, patterns held in the subgroup of exclusively AN vs other eating disorder (OED) cases. These results suggest a similar pattern of influence of schizophrenia PRS for AN and OED cases in terms of psychiatric comorbidities, but a different pattern in terms of ED-related clinical features. The disparity of the effect of schizophrenia PRS on AN vs OED merits further investigation.
Eating disorders and schizophrenia are both moderately to highly heritable and share significant genetic risk despite distinct diagnostic criteria. Large-scale family studies on the co-aggregation of ...these disorders are lacking. Thus, we aimed to estimate the co-occurrence and familial co-aggregation of these disorders within the entire Swedish and Danish population. The proband cohort consisted of individuals born in Sweden (1977-2003) and Denmark (1984-2006) and still residing in their respective country at age six (N
= 2,535,191, N
= 1,382,367). Probands were linked to their biological parents, siblings, grandparents, uncles/aunts, and cousins. Diagnoses for anorexia nervosa (AN) and other eating disorders (OED: bulimia nervosa, binge-eating disorder, and eating disorder not otherwise specified) for probands and schizophrenia diagnoses for both probands and relatives were obtained. The likelihood of having schizophrenia in those with AN or OED and their relatives was compared with individuals without eating disorder diagnoses and their relatives. Probands with AN or OED were more likely to have schizophrenia than probands without these disorders. All relatives of probands with AN or OED (except parents and uncles/aunts of probands with AN) were at increased risk of schizophrenia. In general, the magnitude of odds ratios attenuated with decreasing genetic relatedness. These results suggest familial liability contributes to the association between eating disorders and schizophrenia. Clinicians should be mindful of this comorbid and co-aggregation pattern as it may influence case conceptualization and treatment decisions.
Since psychiatric disorders have genetic architectures dominated by common variants of small effects, successful elucidation in psychiatric genetics necessitates large sample sizes. Collaboration and ...unconventional ascertainment methods are required to fulfill this need. Electronic health records have been increasingly seen as holding great potential for research, although they often pose substantial technical, legal and ethical challenges. Universal health care and national‐scale registers with comprehensive medical, developmental, demographic, and geographic information make the Nordic countries ideal for psychiatric genetic epidemiology. The Genomic Aggregation Project in Sweden is gathering genetic data from subjects with and without complex genetic diseases in a single location for standardized processing and use in a wide variety of scientific investigations. Thirty groups with >160 K genotyped samples have joined GAPS. Although GAPS is general across medicine, many psychiatric disorders are represented within GAPS, and initial studies will focus on major depressive disorder. Through in‐depth genetic investigations, the genes and pathways that will be identified can be leveraged for predictive and drug‐development purposes. Sweden offers exceptional possibilities for psychiatric genetics, and GAPS aims to harness the wealth of available information for research to improve human health.
Numerous genome-wide association studies (GWAS) of schizophrenia have been published in the past 6 years, with a number of key reports published in the last year. The studies have evolved in scale ...from small individual samples to large collaborative endeavors. This review aims to critically assess whether the results have improved as the sample size and scale of genetic association studies have grown.
Genomic genotyping and increasing sample sizes for schizophrenia association studies have led to parallel increases in the number of risk genes discovered with high statistical confidence. Nearly 20 genes or loci have surpassed the genome-wide significance threshold (P = 5 × 10) in a single study, and several have been replicated in more than one GWAS.
Identifying the genetic underpinnings of complex diseases offers insight into the etiological mechanisms leading to manifestation of the disease. New and more effective treatments for schizophrenia are desperately needed, and the ability to target the relevant biological processes grows with our understanding of the genes involved. As the size of GWAS samples has increased, more genes have been identified with high confidence that have begun to provide insight into the etiological and pathophysiological foundations of this disorder.
Prior studies report increased risk of schizophrenia (SCZ) in migrants relative to the native-born population; however, few have investigated bipolar disorder (BD) and migrant characteristics which ...may influence risk. We aimed to examine the risk of SCZ and BD in migrants and their children relative to those of Swedish ancestry, and whether risk varied by age at migration, region of origin, sex, and parental migrant status.
We conducted a nested case-control study using 5539 SCZ cases and 20,577 BD cases diagnosed 1988–2013, individually matched to five population-based controls by birth year and sex. Conditional logistic regression was used to evaluate the risk of SCZ and BD by migrant status, region of origin and age at migration, with models stratified by sex.
First-generation migrants had increased risk of SCZ and decreased risk of BD. There was a distinct pattern of risk for SCZ by age at migration. Childhood migrants from all regions had increased risk of SCZ, particularly those from Africa. In contrast, risk for BD declined with age at migration, with increased risk only in Nordic child migrants. SCZ and BD diagnoses were decreased in adult migrants, elevated in second-generation migrants (with risk differing by number of migrant parents and greater for those with migrant fathers) and higher in male migrants (vs. female).
Age at migration, sex, and region of origin affect risk of SCZ and BD. Further research is required to determine how migration-related factors influence disease etiology and the receipt of these diagnoses.
To assess the association and familial coaggregation between early-onset type 2 diabetes (diagnosed before age 45 years) and mood, anxiety, and stress-related disorders and estimate the contribution ...of genetic and environmental factors to their co-occurrence.
This population-based cohort study included individuals born in Sweden during 1968-1998, from whom pairs of full siblings, half-siblings, and cousins were identified. Information on diagnoses of early-onset type 2 diabetes and mood (including unipolar depression and bipolar disorder), anxiety, and stress-related disorders was obtained from the National Patient Register. Logistic and Cox regression models were used to assess the phenotypic association and familial coaggregation between type 2 diabetes and psychiatric disorders. Quantitative genetic modeling was conducted in full and maternal half-sibling pairs to estimate the relative contributions of genetic and environmental factors to the association.
Among a total of 3,061,192 individuals, 7,896 (0.3%) were diagnosed with early-onset type 2 diabetes. These individuals had higher risks of any diagnosis (odds ratio OR 3.62 95% CI 3.44, 3.80) and specific diagnosis of unipolar depression (3.97 3.75, 4.22), bipolar disorder (4.17 3.68, 4.73), anxiety (3.76 3.54, 3.99), and stress-related disorders (3.35 3.11, 3.61). Relatives of individuals with early-onset type 2 diabetes also had higher overall risks of the examined psychiatric disorders (ORs 1.03-1.57). These associations are largely explained by genetic factors (51-78%), with the rest explained by nonshared environmental factors.
Our findings highlight the burden of mood, anxiety, and stress-related disorders in early-onset type 2 diabetes and demonstrate that shared familial liability may contribute to their co-occurrence, suggesting that in the future research investigators should aim to identify shared risk factors and ultimately refine preventive and intervention strategies.
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