Communication and Coordination in a VA Rapid Rehousing and Homelessness Prevention Program: A Qualitative Study.

Negative emotional states and mental health challenges such as depression, anxiety and stress have high prevalence, resulting in great societal and economic cost [–], and a high proportion of cases go untreated []. Existing drug treatments are not effective for many patients, with a recent analysis of data from over 70,000 clinical trial participants finding that only 15% of patients experience a substantial benefit beyond placebo []. This suggests a need to develop alternative or adjunctive interventions that avoid the drawbacks of existing treatments, which include side effects and social stigma in the case of psychotropic medications, and the difficulty of rolling treatment out at a sufficient scale in the case of talking therapies such as cognitive behavioural therapy and counselling [–]. One potential intervention for depression, anxiety and stress is high‐dose vitamin B6, which performs a crucial coenzyme role in the synthesis of multiple neurotransmitters in the brain. It has long been known that the active form of vitamin B6, pyridoxal‐5′‐phosphate (PLP), acts as a cofactor for enzymes involved in the biosynthesis of gamma‐aminobutyric acid (GABA), serotonin and dopamine, all of which are central to mood regulation and stress response []. If, under normal physiological conditions, the proportion of the relevant enzymes that are not bound to PLP and, therefore, are inactive is significant, then increasing PLP concentration has potential to increase the proportion of active enzyme that is bound to PLP, consequently altering neurotransmitter concentrations. In the case of glutamate decarboxylase (GAD), the enzyme that converts glutamate to GABA, a high proportion of the enzyme exists in the unbound form is well established [, ]. Turning to aromatic L‐amino acid decarboxylase (AADC), which converts L‐DOPA to dopamine and 5‐hydroxytryptophan to serotonin, one study using rats estimated that 22% of AADC in the brain exists in the unbound form, and established that saturating a tissue extract with PLP converted all of this to the active bound form []. Proof of concept for the proposal that high dose vitamin B6 alters neurotransmitter levels and that this has relevant behavioural consequences is provided by animal models. In one study, rats were fed either a vitamin B6‐deficient diet or a high vitamin B6 diet, and the brains of the latter group were found to contain higher GABA and lower glutamate []. While this difference might be explained either by the effect of vitamin B6 deficiency, or of intake exceeding normal dietary levels, or by both of those, a recent study in mice confirmed that exceeding normal dietary levels increases GABA and reduces glutamate []. Furthermore, at the behavioural level, anxious behaviour was reduced, and an ‘n’ shaped dose response curve for both this and the effect on GABA/glutamate was established. Turning to serotonin and depression, a recent mouse model of depression revealed an antidepressant effect of vitamin B6, as well as increased serotonin, which was comparable to fluoxetine []. Interestingly, the effective dose was lower than the dose previously found to be effective for anxiety by the same group []. Turning to rhesus monkeys, a positron emission tomography study found that intravenous infusion with vitamin B6 increased activity of AADC, resulting in 20% increase in the rate of serotonin formation in the corpus striatum, but with noteworthy variation between individual monkeys [].