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Personalized polyunsaturated fatty acids as a potential adjunctive treatment for anorexia nervosa.

ABSTRACT: Anorexia nervosa (AN) is a complex psychiatric disorder with high morbidity and mortality rates. While many individuals make full recoveries, up to a third of patients develop a chronic, treatment-resistant form of the illness that leads to a premature death in 15-20% of those affected. There have been few advances in treatment, both in terms of psychological or pharmacologic treatment over the last 30 years. Food aversion is commonly cited by patients with AN as a barrier to normalizing eating and weight. Our group has a keen interest in examining factors that might allow this to be addressed, thus improving treatment outcomes through personalized dietary plans or nutritional supplementation related to underlying genetic status. We demonstrated that polyunsaturated fatty acids (PUFAs)-derived bioactive lipids (eicosanoids) are implicated in not only the risk of AN, but also with its comorbid psychopathology. Of interest, the differential postprandial omega 6-derived eicosanoid shift observed in AN highlights the possibility that the metabolism of PUFAs is an important mechanism underlying the profound food version, contributing to pathological food restriction in AN. A concise knowledge of the relationships among PUFAs, eicosanoids, and AN clinical course and psychopathology could be the key to developing personalized nutritional rehabilitative treatments for those suffering from AN. This paper provides a comprehensive overview of the literature on PUFAs in AN. We also selectively reviewed the clinical benefits PUFA treatments exert in other psychiatric diseases, on weight and appetite regulation, and for resolution of inflammation, all of which are relevant in the disease course and outcome of AN. We propose that personalized PUFA formulation be developed and tested as a novel adjunctive treatment for patients with AN. We hypothesize that with personalized PUFA formulation, food aversion and anxiety about eating will decrease while mood, dietary behavior, and weight restoration will improve in AN, leading to improvements in the overall treatment outcome.

SUBMITTER: Shih PB

PROVIDER: S-EPMC5792652 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Personalized polyunsaturated fatty acids as a potential adjunctive treatment for anorexia nervosa.

Shih P Betty PB Morisseau Christophe C Le Thu T Woodside Blake B German J Bruce JB

Prostaglandins & other lipid mediators 20170902

Anorexia nervosa (AN) is a complex psychiatric disorder with high morbidity and mortality rates. While many individuals make full recoveries, up to a third of patients develop a chronic, treatment-resistant form of the illness that leads to a premature death in 15-20% of those affected. There have been few advances in treatment, both in terms of psychological or pharmacologic treatment over the last 30 years. Food aversion is commonly cited by patients with AN as a barrier to normalizing eating ...[more]

PMID: 28873340

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Project description:BackgroundAnorexia Nervosa (AN) is a serious mental illness characterized by emaciation, an intense fear of gaining weight despite being underweight, and distorted body image. Few treatments reverse the core symptoms in AN such as profound aversion to food and food avoidance. Consequently, AN has a chronic and relapsing course and the highest mortality rate of any psychiatric illness. A more complete understanding of the disease pathogenesis is needed in order to develop better treatments and improve AN outcome. The pathogenesis and psychopathophysiology of AN can be better elucidated by combining longitudinal phenotyping with multiple "omics" techniques, including genomics, proteomics, lipidomics, and metabolomics.DesignThis paper summarizes the key findings of a series of interrelated studies including new experimental data and previously published data, and describes our current initiatives and future directions.ResultsExon sequencing data was analyzed in 1205 AN and 1948 controls. Targeted metabolomics, lipidomics, and proteomics data were collected in two independent convenience samples consisting of 75 subjects with eating disorders and 61 sex- and age-matched healthy controls. Study participants were female and the mean age was 22.9 (4.9 [SD]) years. Epoxide hydrolase 2 (EPHX2) genetic variations were significantly associated with AN risk, and epoxide hydrolase (sEH) activity was elevated in AN compared to controls. The polyunsaturated fatty acids (PUFAs) and eicosanoids data revealed that cytochrome P450 pathway was implicated in AN, and AN displayed a dysregulated postprandial metabolism of PUFAs and sEH-dependent eicosanoids.Implication and current initiativesCollectively, our data suggest that dietary factors may contribute to the burden of EPHX2-associated AN susceptibility and affect disease outcome. We are implementing new investigations using a longitudinal study design in order to validate and develop an EPHX2 multi-omics biomarker system. We will test whether sEH-associated postprandial metabolism increases AN risk and affects treatment outcome through an ω-6 rich breakfast challenge. Participants will include 100 ill AN patients, 100 recovered AN patients, and 100 age- and race-matched healthy women. These data will allow us to investigate 1) how genetic and dietary factors independently and synergistically contribute to AN risk and progression, and 2) if clinical severity and treatment response in AN are affected by sEH activity and eicosanoid dysregulation. Results of our study will 1) identify clinically relevant biomarkers, 2) unravel mechanistic functions of sEH, and 3) delineate contributory roles of dietary PUFAs and cytochrome P450 pathway eicosanoids for the purpose of developing novel AN treatments and improving disease prognosis.

Project description:UnlabelledResearch on treatments in anorexia nervosa (AN) is scarce. Although most of the therapeutic programs used in 'real world practice' in AN treatment resort to multidisciplinary approaches, they have rarely been evaluated.ObjectiveTo compare two multidimensional post-hospitalization outpatients treatment programs for adolescents with severe AN: Treatment as Usual (TAU) versus this treatment plus family therapy (TAU+FT).MethodSixty female AN adolescents, aged 13 to 19 years, were included in a randomized parallel controlled trial conducted from 1999 to 2002 for the recruitment, and until 2004 for the 18 months follow-up. Allocation to one of the two treatment groups (30 in each arm) was randomised. The TAU program included sessions for the patient alone as well as sessions with a psychiatrist for the patient and her parents. The TAU+FT program was identical to the usual one but also included family therapy sessions targeting intra-familial dynamics, but not eating disorder symptoms. The main Outcome Measure was the Morgan and Russell outcome category (Good or Intermediate versus Poor outcome). Secondary outcome indicators included AN symptoms or their consequences (eating symptoms, body mass index, amenorrhea, number of hospitalizations in the course of follow-up, social adjustment). The evaluators, but not participants, were blind to randomization.ResultsAt 18 months follow-up, we found a significant group effect for the Morgan and Russell outcome category in favor of the program with family therapy (Intention-to-treat: TAU+FT :12/30 (40%); TAU : 5/29 (17.2%) p?=?0.05; Per Protocol analysis: respectively 12/26 (46.2%); 4/27 (14.8%), p?=?0.01). Similar group effects were observed in terms of achievement of a healthy weight (i.e., BMI?10(th) percentile) and menstrual status.ConclusionsAdding family therapy sessions, focusing on intra-familial dynamics rather than eating symptomatology, to a multidimensional program improves treatment effectiveness in girls with severe AN.Trial registrationControlled-trials.com ISRCTN71142875.

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Personalized polyunsaturated fatty acids as a potential adjunctive treatment for anorexia nervosa.

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Personalized polyunsaturated fatty acids as a potential adjunctive treatment for anorexia nervosa.

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