Human Endogenous Retroviruses (HERVs) in Anorexia Nervosa: Uncovering Potential Hidden Markers of Psychopathology and Clinical Presentation.

Background: Anorexia Nervosa (AN) is an eating disorder characterized by fear of gaining weight and distorted body image, leading to food intake restriction. HERVs are remnants of ancient retroviral infections that have become integrated into the human genome, influencing gene expression. They participate to physiological processes and are implicated in inflammatory, autoimmune and neuropsychiatric disorders. Objectives: The initial objective of this study was to explore the transcription levels of pol genes of HERV-H, -K, and -W families, of env genes of SYN1, SYN2 and MSRV, and of TRIM28/SETDB1 in blood of AN patients. The second aim was to correlate their expression with AN clinical and psychopathological traits. Our hypothesis supporting the implication of HERVs in AN originates from the shared features between AN and other diseases for which altered HERV expression has already been documented. Materials and methods: 0.5 cc of blood were collected during inpatient or DH stay at the Division of Child and Adolescent Neuropsychiatry at OIRM. Each participant received a set of psychometric tests: TCI, EDI-2, SCL-90, ASQ, TAS, PBI, FAD, BDI and NPI. HERVs transcription levels were assessed through RT-PCR. Mann-Whitney was used to compare transcription levels between AN patients and healthy controls (HCs). Pearson’s correlation, Mann-Whitney and multivariate regression were used to link HERV expression to the clinical and psychopathological traits. P-values < 0.05 were considered statistically significant. Results: 37 female adolescents with median age 14.95 years were involved. 20 were inpatients and 17 were treated in the DH. All were of the restrictor subtype with median age onset 13 and median age at admission 14. All patients showed at least one comorbidity among major depression, polarized anxiety disorder, obsessive-compulsive disorder or post-traumatic stress disorder. 31 patients received pharmacological therapy with at least one among SSRI, benzodiazepines or atypical antipsychotics. One patient presented bingeing, 3 with vomiting and 1 with laxatives’ misuse. AN patients showed significantly higher transcription of HERV‐H-pol, HERV‐K-pol, and lower levels of HERV-W-pol compared to HCs. mRNA levels of MRSV and SETDB1 were significantly decreased and increased in AN as compared with HCs, respectively. SYN1, SYN2 and TRIM28 were comparable between the two groups. Positive correlations were obtained between care regimen and HERV-W-pol, SYN2 and MSRV, supported by Mann-Whitney. In support of this, HERV-K-pol and MSRV were found to positively correlate with age and weight at admission. These findings hint at potential novel markers for AN severity. About psychopathology, multivariate regressions point at statistically significant links between age and paternal care with HERV-W-pol. Persistence, ascetism and entitlement are statistically significantly linked with SETDB1. More correlations were seen between HERVs and other clinical and psychopathological traits, but research is necessary to elucidate the veracity of results. Conclusions: Our study demonstrated altered expression of HERVs and related genes in AN, supporting their potential role in influencing clinical and psychopathological traits of the disorder, and its severity. Further research is needed to validate our results and explore the mechanisms through which they might impact AN, potentially leading to novel diagnostic and therapeutic approaches and improving prognosis.