B vitamin polymorphisms and behavior: Evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline

Abstract

The B vitamins folic acid, vitamin B12 and B6 are essential for neuronal function, and severe deficiencies have been linked to increased risk of neurodevelopmental disorders, psychiatric disease and dementia. Polymorphisms of genes involved in B vitamin absorption, metabolism and function, such as methylene tetrahydrofolate reductase (MTHFR), cystathionine β synthase (CβS), transcobalamin 2 receptor (TCN2) and methionine synthase reductase (MTRR), have also been linked to increased incidence of psychiatric and cognitive disorders. However, the effects of these polymorphisms are often quite small and many studies failed to show any meaningful or consistent associations. This review discusses previous findings from clinical studies and highlights gaps in knowledge. Future studies assessing B vitamin-associated polymorphisms must take into account not just traditional demographics, but subjects' overall diet, relevant biomarkers of nutritional status and also analyze related genetic factors that may exacerbate behavioral effects or nutritional status.

Folate Pathway Gene Polymorphisms and Risk of Childhood Brain Tumors: Results from an Australian Case–Control Study

“…The MTRR 66GG variant has been shown to produce up to 4-fold lower enzyme activity by comparison with the wild-type allele (22), suggesting a functional role of this polymorphism in affecting the methionine metabolic pathway as well as a mechanistic link with aberrant methylation levels in cells. In addition, MTRR 66G has also been linked to a number of cognitive disorders in children (23). In the current study, the reduced OR for the GG genotype was observed across family members and subgroup analyses, and, taken together, the data suggest the MTRR 66GG genotype has a protective effect against CBT particularly in situations involving maternal prepregnancy folic acid supplementation.…”

Behavioral experiences as drivers of oligodendrocyte lineage dynamics and myelin plasticity

“…Vitamin D receptors are found throughout the brain in many cell types, including oligodendrocytes (Eyles et al, 2005;Harms et al, 2011), and vitamin D receptor signaling engages in cross-talk with many signaling pathways known to influence oligodendrocyte lineage biology, including MAPK signaling (Deeb et al, 2007). Conversely, vitamin deficiencies have been correlated with demyelination and susceptibility to mood disorders, including schizophrenia, post-traumatic stress disorder, and dementia (De Lau et al, 2009;Malouf et al, 2003;Miller et al, 2005;Mitchell et al, 2014). Here, vitamin supplementation may enhance or preserve cognitive performance, particularly learning and memory, by stimulating calcium related signaling, G protein functions, synaptic transmission, or even clearance of amyloid plaques (Adlard et al, 2005;Ding et al, 2006;Farmer et al, 2004;Soni et al, 2012;Vaynman et al, 2003;J.…”

Severe Mood Lability and Depression in an Adolescent Girl with a Methylenetetrahydrofolate Reductase Gene Mutation

“…Studies have found variable results depending on the population studied, the precise mutation analyzed (C677T or A1298C), and the psychiatric pathology in question (with mood disorders and psychotic disorders being the most widely studied). One prominent theory involves the role of MTHFR and vitamin B-12 in the one carbon transfer pathways (Mitchell 2014). A deficiency in either MTHFR activity or vitamin B-12 availability can lead to elevated homocysteine levels, which has been implicated in amyloid buildup, and damage to neurons via mitochondrial dysfunction, direct DNA damage and initiation of apoptosis (Mitchell 2014).…”

“…One prominent theory involves the role of MTHFR and vitamin B-12 in the one carbon transfer pathways (Mitchell 2014). A deficiency in either MTHFR activity or vitamin B-12 availability can lead to elevated homocysteine levels, which has been implicated in amyloid buildup, and damage to neurons via mitochondrial dysfunction, direct DNA damage and initiation of apoptosis (Mitchell 2014). Dysregulation of the complex methyl donor system can also lead to the buildup of methylmalonic acid, a toxic intermediate metabolite, and low levels of Sadenosylmethionine (SAM), a necessary component of neurotransmitter metabolism (Frankenburg 2007).…”