Abstract
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/m2, 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.
Highlights
As the strongest single indicator of individual schizophrenia risk, family history of schizophrenia is associated with higher treatment resistance (Kowalec et al, 2019; Mortensen et al, 1999), as well as greater risk for several psychiatric disorders (DeVylder & Lukens, 2013), including eating disorders (EDs)
Low body mass index (BMI) is one of the diagnostic criteria for anorexia nervosa (AN) (American Psychiatric Association, 2000), and both AN and schizophrenia are negatively genetically correlated with BMI (Bulik-Sullivan et al, 2015; Duncan et al, 2017; Ikeda et al, 2018; Watson et al, 2019)
The study population comprised 12 424 individuals with AN and 20 716 individuals with other EDs (OED) identified from the Swedish national registers with a total follow-up of 230 323 person-years for AN and 395 585 person-years for OED
Summary
As the strongest single indicator of individual schizophrenia risk, family history of schizophrenia is associated with higher treatment resistance (Kowalec et al, 2019; Mortensen et al, 1999), as well as greater risk for several psychiatric disorders (DeVylder & Lukens, 2013), including eating disorders (EDs). Individuals with schizophrenia commonly have obesity (Vancampfort et al, 2016), possibly due to side effects of antipsychotic medications (De Hert, Detraux, van Winkel, Yu, & Correll, 2011; Malan-Muller et al, 2016) It is, unclear whether a family history of schizophrenia might influence BMI in individuals with EDs. 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 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). 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
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