Sex Differences in Tryptophan Metabolism: A Systematic Review Focused on Neuropsychiatric Disorders

Abstract

Tryptophan (Tryp) is an essential amino acid and the precursor of several neuroactive compounds within the central nervous system (CNS). Tryp metabolism, the common denominator linking serotonin (5-HT) dysfunctions and neuroinflammation, is involved in several neuropsychiatric conditions, including neurological, neurodevelopmental, neurodegenerative, and psychiatric diseases. Interestingly, most of those conditions occur and progress in a sex-specific manner. Here, we explore the most relevant observations about the influence of biological sex on Tryp metabolism and its possible relation to neuropsychiatric diseases. Consistent evidence suggests that women have a higher susceptibility than men to suffer serotoninergic alterations due to changes in the levels of its precursor Tryp. Indeed, female sex bias in neuropsychiatric diseases is involved in a reduced availability of this amino acid pool and 5-HT synthesis. These changes in Tryp metabolism could lead to sexual dimorphism on the prevalence and severity of some neuropsychiatric disorders. This review identifies gaps in the current state of the art, thus suggesting future research directions. Specifically, there is a need for further research on the impact of diet and sex steroids, both involved in this molecular mechanism as they have been poorly addressed for this topic.

Novel Technologies Targeting the Rehabilitation of Neurological Disorders

“…We need to study metabolic changes in the brain tissue of stroke rats in the future to further demonstrate the role of metabolism, such as tryptophan, in the development of stroke. Studies have shown known sex differences in tryptophan metabolism in healthy adults or rats, with females having higher tryptophan metabolism or tryptophan utilization than males (Leskanicova et al, 2020;Cai et al, 2021;Pais et al, 2023), which may limit the translation of our study. Finally, we will invest in further studies in the future to determine whether tryptophan metabolism in female rats versus patients in the clinical setting has the same results as noted in this study.…”

Host–Microbiome Interactions: Tryptophan Metabolism and Aromatic Hydrocarbon Receptors after Traumatic Brain Injury

“…However, studies on tryptophan metabolism in the context of acute and chronic inflammatory responses after TBI are still limited, focusing mainly on preclinical studies. There are no studies on sex and other factors that may contribute to abnormal tryptophan metabolism in TBI [ 137 ] . Furthermore, studies probing the inflammatory mechanisms of tryptophan metabolism subsequent to TBI are largely absent.…”

Sex-Dependent Effects of Chronic Restraint Stress on Mood-Related Behaviours and Neurochemistry in Mice

“…Previous studies of chronic RS found decreased TPH2 and increased IDO and MAO-A in male rodents [ 23 ]; however, sex differences have not yet been investigated in the context of chronic stress, to our knowledge. This is of importance, given female rodents are known to have higher levels of tryptophan and serotonin in both the brain and the circulation compared with males [ 35 ]. Indeed, the present study found higher levels of TPH2 in the PFC in female controls, suggesting higher basal levels of serotonin; however, TPH2 in the hippocampus as well as IDO and MAO-A in both the PFC and the hippocampus were unaffected by sex or chronic RS.…”