Reframing anorexia nervosa as a metabo-psychiatric disorder

Abstract

Anorexia nervosa (AN) is a serious and often fatal illness. Despite decades of research, investigators have failed to adequately advance our understanding of the biological aspects of AN that could inform the development of effective interventions. Genome-wide association studies are revealing the important role of metabolic factors in AN, and studies of the gastrointestinal tract are shedding light on disruptions in enteric microbial communities and anomalies in gut morphology. In this opinion piece, we review the state of the science through the lens of the clinical presentation of illness. We project how the integration of rigorous science in genomics and microbiology, in collaboration with experienced clinicians, has the potential to markedly enhance treatment outcome via precision interventions. Shifting paradigms in understanding and treating ANAN rests squarely on the psyche-soma border; however, etiological theories and treatments have historically focused on psychological, family, and societal factors. A conceptual shift is underway. The latest genome-wide association study (GWAS; see Glossary) for AN [1] suggested reconceptualizing AN as a 'metabo-psychiatric disorder'. In addition to identifying eight significantly associated genomic loci, a rich panel of genetic correlations underscored the role of psychiatric, anthropometric, and metabolic factors in the etiology of this highly lethal disease.

The impact of anorexia nervosa and BMI polygenic risk on childhood growth: a 20-year longitudinal population-based study

“…In a recent study, we reported a negative genetic correlation between body fat percentage and AN, which was significantly more pronounced in women than in men (women SNP-r g = −0.44, SE = 0.04; men SNP-r g = −0.26; SE = 0.04) [35]. The negative association between the AN-PGS and the BMD trajectory is consistent with the established literature that AN is phenotypically associated with BMD; AN has marked and severe adverse effects on bone metabolism [3,36]. The negative association between the AN-PGS and BMD was only found in female participants.…”

The impact of anorexia nervosa and BMI polygenic risk on childhood growth: A 20-year longitudinal population-based study

“…37 The negative association between the AN PGS and the BMD trajectory is consistent with the established literature that AN is phenotypically associated with BMD; AN has marked and severe adverse effects on bone metabolism. 3,38 The negative association between the AN PGS and BMD was found only in female participants. The observed sex-specific effects of the AN PGS suggest that a specific set of common genetic variants may be differentially active in women and may increase the liability for AN.…”

Are the Effects of Malnutrition on the Gut Microbiota–Brain Axis the Core Pathologies of Anorexia Nervosa?

“…However, the interactions within the gut microbiota and in the GMB axis in humans seem to be extremely complex, and it will probably be challenging to test these hypotheses. However, clinical data indicate that new interventions and new models that reliably lead to sustained weight gain and psychological recovery are needed [ 27 , 118 ]. Although dropout from treatment, rates of relapse, and SE-AN are unacceptably high, the results from some treatments indicate that a lasting cure is possible for many patients with AN [ 3 ].…”