The effect of inflammation, SARS-CoV-2 infection, age and mental health on serotonin, and kynurenine and catecholamine pathway metabolites.

BACKGROUND: A high prevalence of mental disorders following COVID-19 has been described. It is therefore essential to elucidate underlying biological mechanisms linking SARS-CoV-2 infection and mental health. The kynurenine and catecholamine metabolic pathways are modulated by inflammation and can affect systemic levels of serotonin and dopamine. Their activity may hence link physical disorders with mental health. We investigated factors that affect kynurenine and catecholamine pathway activity in SARS-CoV-2 infection and recovery. METHODS: The cross-sectional SIMMUN (n = 165) and longitudinal INCOV cohort (n = 167, Su et al. 2022) were analyzed. Demographic and clinical characteristic, inflammatory markers, SARS-CoV-2 infection, symptoms of depression and anxiety (HADS), and mental stress (PSS-4) served as explanatory variables. Blood serotonin and markers of kynurenine (kynurenine/tryptophan ratio), and catecholamine pathway activity (dopamine 3-O-sulfate, phenylalanine/tyrosine ratio) were modeled by multi-parameter linear regression. RESULTS: In the SIMMUN cohort, the inflammatory marker neopterin (ß = 0.47 [95% CI: 0.34-0.61]), SARS-CoV-2-positivity (0.42 [0.16-0.68]), mental stress (0.18 [0.055-0.31]), and age (0.26 [0.12-0.39]) were positively associated with the kynurenine/tryptophan ratio. The phenylalanine/tyrosine ratio was lower in SARS-CoV-2-positive than uninfected participants (-0.38 [-0.68 to -0.08]). In the INCOV cohort, markers of inflammation were associated with lower serotonin (IL6: -0.22 [-0.38 to -0.053]) and dopamine 3-O-sulfate levels (interferon-gamma: -0.15 [-0.26 to -0.036]). Serotonin (0.76 [0.34-1.2]) and dopamine 3-O-sulfate levels (0.63 [0.28-0.99]) were higher during recovery than in acute SARS-CoV-2 infection. CONCLUSION: SARS-CoV-2 infection, inflammation, age and mental stress are key independent predictors of kynurenine pathway activity, which may influence serotonin availability. The catecholamine pathway was also affected in SARS-CoV-2 infection. Altered activity of these pathways may contribute to impaired mental health following COVID-19.

Disorders of eating and body image during the menopausal transition: associations with menopausal stage and with menopausal symptomatology.

OBJECTIVE: Recent reports from our laboratory and others suggest that the menopausal transition may represent a window of vulnerability for eating disorders in women. Here, we present new findings regarding this issue. METHODS: We surveyed 230 women aged 40-60 years using an anonymous questionnaire focused on eating-disorder and body-image symptomatology. We then compared groups of respondents based on (a) menopausal stage as assessed by World Health Organization (WHO) criteria and (b) menopausal symptomatology as assessed by the Menopause Rating Scale (MRS). RESULTS: WHO-defined menopausal stage (premenopausal, perimenopausal, and postmenopausal) showed no significant associations with eating and body-image measures. However, MRS scores showed strong associations with most measures of the Eating Disorder Examination Questionnaire, as well as with questions regarding satisfaction with body image. These associations remained little changed even when removing the four psychological items from the MRS score and examining only the association of the MRS somato-vegetative and urogenital items with these outcome variables. DISCUSSION: Our data augment existing evidence that the menopausal transition may be associated with eating and body-image disturbances. However, reported menopausal stage, which is difficult to define reliably, may be less informative than menopausal symptoms as a predictor of disordered eating and associated symptoms. LEVEL OF EVIDENCE: V-descriptive survey study.