Genetic predispositions and psychopathological processes associated with obesity, ADHD, and depression may be biomarkers for vulnerability towards eating disorders in adolescence and therefore could help achieve early and differential diagnoses, researchers found in a longitudinal cohort study published in JAMA Network Open.

The researchers used data from 1623 adolescents of European descent (829 girls with a mean age of 14.5 years (standard deviation (SD): 0.4 years)) from IMAGEN, a multicenter prospective longitudinal population study of adolescents aged 14 years, who reported any disordered eating behaviors (DEB) at baseline (2010), follow-up 1 (2012) or follow-up 2 (2015) or screened negative for the Development and Well-Being Assessment (DAWBA) section P screening eating disorder questions at each corresponding age who had complete cases, and therefore were referred to as healthy controls and having no DEBs.

The researchers used the DAWBA, the Eating Disorder Examination questionnaire, the European School Survey Project on Alcohol and Other Drugs, the Alcohol Use Disorders Identification Test, the Neuroticism-Extraversion Openness Five-Factor Inventory and the Strengths and Difficulties Questionnaire to assess the participants’ body mass index (BMI), distress about eating pattern and body shape, mental health symptoms, conduct and peer relationship problems, prosocial behavior, probability of current or future mental health disorders, substance use behaviors, and personality variables at each stage.

They also conducted polygenetic risk score (PRS) analyses of 1975 cases and 502 single-nucleotide variations with alternative bases at nucleotide 160 and generated PRS for neuroticism (depressed affect and worry), BMI and ADHD symptoms based on summary statistics from large-scale genome-wide association studies on these traits.


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The researchers used DEBs as time-varying estimators and logistic and linear regression models controlling for sex and study site to estimate and investigate the prospective associations, correlates, and outcomes of DEBs.

They found that 1509 of the participants had DEB information at 14 years, 1317 at 16 years and 853 at 19 years. Of the “developers,” the participants who reported DEBs at 16 or 19 years of age, but not at 14 years, 127 were classified as “binge-eating developers,” 207 as “purge developers,” and 86 as “dieting developers.”

Future binge eating (OR, 2.18; 95% CI, 1.37-3.45) and future purging (OR, 2.59; 95% CI, 1.69-3.95) were associated with self-harm and conduct problems (future binge eating: OR, 1.41; 95% CI, 1.17-1.69; future purging: OR, 1.42; 95% CI, 1.20-1.68). Future binge eating was specifically associated with high levels of neuroticism at age 14 (OR, 1.04; 95% CI, .010-1.06) and future purging with conduct disorder (OR, 2.73; 95% CI, 1.47-5.09) plus drug use (OR, 2.91; 95% CI, 1.78-4.74), alcohol misuse (OR, 1.31, 95% CI, 1.10-1.54) and low agreeableness (OR, .95; 95% CI, .092-.097). Low agreeableness (OR, .81; 95% CI, .072-.092) and high conduct problems (OR, 1.32; 95% CI, 1.15-1.46) at age 14 both were associated with overweight status at 14 years. Conduct problems at 14 years were associated with future overweight status of individuals who had normal weights at 14 years (OR, 1.31; 95% CI, 1.02-1.71).

The BMI PRS (5.15% (P <.01) of the variance in BMI at 14 years) was associated with purging (at 14 years: OR, 1.34; lower bound 95% CI, 1.12, at 16 years; OR, 1.32; lower bound 95% CI, 1.14) and dieting (at 14 years: OR, 1.27; lower bound 95% CI, 1.08; at 16 years: OR, 1.38; lower bound 95% CI, 1.17).

The ADHD PRS (1.11% of the variance of ADHD symptoms at 14 years) was associated with purging (at 16 years: OR, 1.25; lower bound 95% CI, 1.08; at 19 years: OR, 1.23; lower bound 95% CI, 1.06). Finally, the full-scale neuroticism PRS (1.64% of the variance in neuroticism at 14 years, was associated with binge eating (at 14 years: OR, 1.32; lower bound 95% CI, 1.11; at 16 years: OR, 1.24; lower bound 95% CI, 1.06).

The researchers found through mediation analyses that BMI mediated the associations between BMI PRS and dieting (indirect effect, 0.23; 95% CI, 0.17-0.32; 83.2% mediated) and purging (indirect effect, 0.14; 95% CI, 0.08-0.20; 41% mediated) at 14 years, neuroticism partially mediated the effects of the neuroticism PRS on binge eating at 14 years (indirect effect, 0.057; 95% CI, 0.04-0.11; 23.9% mediated), but did not find evidence of mediation by ADHD symptoms on associations between ADHD PRS and purging at 16 (indirect effect, 0.034; 95% CI, -0.012 to 0.065).

They found that dieting at 14 years was associated with future depression symptoms (OR, 2.53; 95% CI, 1.56-4.10), generalized anxiety (OR, 2.27; 95% CI, 1.14-4.51), deliberate self-harm (OR, 2.10; 95% CI, 1.51-4.24), emotional problems (OR, 1.24; 95% CI, 1.08-1.43) and smoking (OR, 2.16; 95% CI, 1.36-3.48). Purging at 14 years was associated with future depression (OR, 2.87; 95% CI, 1.69-5.01) and anxiety (OR, 2.48; 95% CI, 1.49-4.12).

Limitations of the study included a low number of boys who reported DEBs, the researchers said.

Disclosure: Multiple authors declared affiliations with and financial support from industry, and the study received funding from several sources. Please see the original reference for a full list of authors’ disclosures.

Reference

Robinson L, Zhang Z, Jia T, et al. Association of genetic and phenotypic assessments with onset of disordered eating behaviors and comorbid mental health problems among adolescents. JAMA Netw Open. Published online December 2, 2020. doi:10.1001/jamanetworkopen.2020.26874