Vitamin B6 deficiency could lead to cognitive impairments, study finds

Vitamin B6 deficiency enhances the noradrenergic system, leading to behavioral deficits, according to a new study published in the journal Translational Psychiatry.

Schizophrenia is a heterogeneous psychiatric disorder characterized by positive symptoms such as hallucinations and delusions, negative symptoms such as apathy and lack of emotion, and cognitive impairment. The researchers reported that vitamin B6 pyridoxal levels in peripheral blood of a subpopulation of patients with schizophrenia is significantly lower than that of healthy controls.

More than 35 percent of patients with schizophrenia have low levels of vitamin B6. Additionally, vitamin B6 was inversely proportional to severity score on the positive and negative symptom scale (PANSS), suggesting that deficiency might contribute to the development of schizophrenia symptoms.

A recent review has shown the decreased vitamin B6 in patients with schizophrenia as the most convincing evidence in peripheral biomarkers for major mental disorders. Previous research found high-dose vitamin B6, pyridoxamine, was effective in alleviating psychotic symptoms, particularly the PANSS negative and general subscales, in a subset of patients with schizophrenia. Although a link between lower vitamin B6 levels and schizophrenia is widely hypothesized, the mechanism behind this remains poorly understood, the researchers said.

Vitamin B6 is not synthesized de novo in humans but is primarily obtained from foods. For the study, to clarify the relationship between vitamin B6 deficiency and schizophrenia, the researchers generated vitamin B6-deficient mice through feeding with a vitamin B6-lacking diet as a mouse model for the subpopulation of schizophrenia patients with VB6 deficiency. After feeding for four weeks, plasma vitamin B6 levels in vitamin B6-deficient mice decreased to 3 percent of that in control mice. The vitamin B6 deficient mice showed social deficits and cognitive impairment. Furthermore, the vitamin B6-deficient mice showed a marked increase in 3-methoxy-4-hydroxyphenylglycol (MHPG) in the brain, suggesting enhanced NA metabolism in vitamin B6-deficient mice.

The researchers confirmed the increased NA release in the prefrontal cortex and the striatum of vitamin B6-deficient mice through in vivo microdialysis. These findings suggest that the activities of NAergic neuronal systems are enhanced in vitamin B6-deficient mice.

Furthermore, vitamin B6 supplementation directly into the brain using an osmotic pump ameliorated the hyperactivation of the NAergic system and behavioral abnormalities. indicating that the enhanced NA turnover and the behavioral deficits shown in the vitamin B6-deficient mice are attributed to vitamin B6 deficiency in the central nervous system. In addition, the ?2A adrenergic receptor agonist guanfacine also improved the hyperactivated NAergic system in the frontal cortex and behavioral disorders. These results show that the behavioral deficits in vitamin B6-deficient mice may be caused by an enhancement of NAergic signaling, the researchers said.