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Riboflavin also plays a role in thyroxine metabolism, and its deficiency may contribute to mental illness, because riboflavin activates vitamin B6, leading to lower thyroxine levels, reduced hypothalamic serotonin synthesis, and decreased levels of S-adenosylmethionine (SAMe), because of disrupting the folate-methylation pathways involved in SAMe synthesis, all of which are associated with antidepressant effects, consequently, low levels of these compounds may cause depression ( Figure 4 ) (48, 49)