A new track for understanding the pathogenesis of multiple sclerosis: from the perspective of early developmental deficit caused by the potential 5-HT deficiency in individuals in high-latitude areas.

The association between the prevalence of multiple sclerosis (MS) and latitude gradient indicates the importance of environmental factors in MS susceptibility. Studies on immigrants have shown that the living environment in the first two decades of life determines MS risk, suggesting that early development may be critical for the occurrence of MS in adulthood. The level of 5-hydroxytryptamine (5-HT) in individuals living in high-latitude areas might be decreased because of limited levels of its metabolic precursor, the essential amino acid tryptophan, and superabundant levels of its metabolic product, melatonin, attributable to long duration of darkness in high-latitude areas. Considering the significant loss and damage of myelin observed in many psychiatric disorders with the etiology of 5-HT deficiency, we hypothesize that 5-HT deficiency due to superabundant synthesis of melatonin in individuals living in high-latitude areas may potentially cause the developmental myelin deficit early in life. This developmental deficit may play an important role in triggering MS in adulthood. This is the first proposal of the potential role of early development in the susceptibility to MS, and we suggest monitoring 5-HT levels in both patients with MS and in individuals with high environmental risk, especially children living in high-latitude areas. This will validate our hypothesis and contribute to designing specific preventive strategies that can be applied early in life.