People with anorexia nervosa may be more likely to be early risers, a genetic association study suggested.

Looking at nearly 17,000 cases with this eating disorder, genetic liability for anorexia nervosa was associated with a more morning chronotype — or a preference for the morning (β=0.039, 95% CI 0.006-0.072, P=0.02), Hassan Dashti, PhD, RD, of Massachusetts General Hospital in Boston, and colleagues found.

The same was true when looking at the other direction of this link, they wrote in JAMA Network Open. The researchers found that having a genetic liability for morning chronotype was associated with increased risk of anorexia nervosa (β=0.178, 95% CI 0.042-0.315, P=0.01).

“Our study indicates anorexia nervosa is uniquely morning based, which is surprising as no other psychiatric disorder we are aware of has yet been morning-associated,” Dashti told MedPage Today.

While the effect size of both associations would be considered small, the researchers suggested several clinical implications.

“Sleep is not often considered when treating patients living with anorexia nervosa or other eating disorders,” Dashti explained to MedPage Today. “Our study highlights the importance of asking about sleep timing and sleep quality, as sleep possibly impacts eating disorder symptoms.”

The findings lend themselves to investigating whether circadian and sleep-based interventions might be effective in the treatment or prevention of anorexia nervosa in randomized controlled trials, Dashti noted.

“For example, bright light therapy in the evening or addressing insomnia might be part of a clinicians’ treatment toolbox for anorexia nervosa,” he suggested. “This research indicates a possible circadian and sleep basis to anorexia nervosa, opening research into circadian mechanism-based possible treatments for the disorder.”

Finding new anorexia treatments is urgent as current ones are “limited, with relapse rates of up to 52%,” said Dashti.

“No mechanism-based treatment for anorexia nervosa currently exists, as the cause of the disease is still unclear,” he pointed out. “Treatments are limited to behavioral therapy and the use of medications created for the treatment of other disorders, such as depression or anxiety. With anorexia nervosa having the second highest mortality rate of psychiatric diseases, more research is desperately needed into new prevention strategies and treatments.”

Other than a morning chronotype, genetic liability for anorexia nervosa wasn’t significantly linked with other circadian and sleep traits, like daytime napping, daytime sleepiness, insomnia, or sleep duration. Likewise, genetic liabilities for sleep traits beyond morning chronotype and insomnia weren’t linked with anorexia. However, the researchers found in a sensitivity analysis that there may have been some bias due to horizontal pleiotropy with this insomnia link.

Genome data for the analysis came from the Eating Disorders Working Group of the Psychiatric Genomics Consortium, which included 16,992 anorexia cases and 55,525 controls. Upwards of 88% of cases were female, but half to two-thirds of controls were also female. Anorexia nervosa was defined as a lifetime diagnosis from hospital or register records, structured clinical interviews, and online questionnaires based on standardized criteria like the Diagnostic and Statistical Manual of Mental Disorders or ICD codes.

The research team also looked at data in the Mass General Brigham Biobank, which contained 47,082 adult patients of European ancestry with genetic data. Around 54% of this cohort was female, and the average age was 60.4. A polygenic risk score for anorexia was calculated for each patient in this cohort and associations were tested with prevalent sleep disorders derived from electronic health records.

Here, each additional standard deviation in the anorexia nervosa polygenic risk score was tied with 10% higher odds for organic or persistent insomnia (OR 1.10, 95% CI 1.03-1.17), even after controlling for lifestyle factors. Links with other sleep disorders including sleep apnea and restless legs syndrome weren’t significant.

These findings were somewhat surprising, Dashti said, explaining how they seem to contradict previous observational data suggesting that people with anorexia nervosa tend toward later chronotypes with later bed and wake times. “This likely is due to evening-based psychiatric disorders, like depression and anxiety, being very common among those living with anorexia nervosa,” he noted. “Observational studies are confounded by the presence of other common evening-based disorders, obscuring the relationship between anorexia nervosa and chronotype.”

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