Trends in Neurosciences
ReviewVitamin D in Synaptic Plasticity, Cognitive Function, and Neuropsychiatric Illness
Section snippets
Vitamin D and Cognition
Vitamin D deficiency affects nearly a billion people worldwide [1]. In addition to its established roles in causing rickets and osteomalacia, the convergence of in vitro animal and epidemiological research points to vitamin D deficiency as a candidate modifiable risk factor for a range of neuropsychiatric and neurological diseases [1]. While definitive links remain to be substantiated, vitamin D deficiency has been associated with vulnerability to various disorders including schizophrenia [2],
Physiological Roles of Vitamin D in the Body and Brain
Vitamin D is a group of fat-soluble secosteroids that play important roles in the human body [7]. The two major forms of vitamin D are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). While both cholecalciferol and ergocalciferol can be obtained through dietary sources, vitamin D3 is typically obtained through the synthesis of cholecalciferol in the skin from 7-dehydrocholesterol by UV radiation [8]. Cholecalciferol enters the circulation and is transported by the vitamin D binding
Effect of Vitamin D Deficiency in Healthy Adults
Meta-analyses and systematic reviews have shown that vitamin D deficiency is associated with cognitive difficulties in healthy adults 20, 21, 22. Furthermore, observational studies have shown a relationship between low vitamin D status and cognitive decline in elderly adults 23, 24, 25, 26, 27, 28. Llewellyn and colleagues [23] have suggested that vitamin D deficiency is associated with an increased risk of cognitive impairment in the elderly population. Other work also supports this finding,
Vitamin D Deficiency and Schizophrenia
Schizophrenia is a group of neuropsychiatric disorders characterised by positive symptoms (hallucinations and delusions), negative symptoms (depression, impaired motivation, and affective flattening), and global cognitive deficits (impairments in attention, memory, disorganised thinking, and executive functioning). The development of schizophrenia is complex, driven by genetic risks interacting with multiple vulnerability factors [42]. Vitamin D deficiency has been identified as a plausible
Vitamin D and Synaptic Plasticity
Synaptic plasticity refers to the ability to generate new synapses, eliminate synapses, and alter the electrophysiological, molecular, and structural properties of existing synapses in response to experience. Synaptic plasticity is thought to be one of the key processes mediating learning and memory [56]. Rapidly evolving research implicates vitamin D in the process of long-term potentiation (LTP); a widely recognised mechanism of synaptic plasticity and an essential element in information
PNNs and Schizophrenia
Recent evidence suggests that PNNs are involved in the pathophysiology of schizophrenia (for reviews, see 114, 115). Observational studies have shown in a number of human post-mortem brain studies that there is a disease-specific reduction in the density of PNNs as well as altered expression of genes that regulate PNNs and ECM in key brain structures associated with schizophrenia, including the amygdala, olfactory epithelium, entorhinal cortex, superior temporal cortex, and prefrontal cortex 116
PNNs and Vitamin D: Is There a Link?
Mounting evidence indicates that deficiency of vitamin D is associated with increased MMP-9 production 135, 136. For instance, Moradi and colleagues [136] investigated the association of serum levels of vitamin D and MMPs in patients with coronary artery disease (CAD). They found that there was a significant inverse correlation between MMP-9 concentrations and serum vitamin D levels in patients with CAD, such that the patients with low levels of vitamin D had high levels of circulating MMP-9.
Concluding Remarks and Future Directions
In this review we have attempted to delineate the contribution of vitamin D to brain physiology, and the possible mechanisms linking vitamin D deficiency to cognitive deficits, including those observed in neuropsychiatric disorders, with a focus on schizophrenia. Evidence suggests that vitamin D deficiency may affect synaptic plasticity, leading to a decline in cognition. An emerging concept is that vitamin D deficiency may weaken the integrity of PNNs through modulation of MMPs, thereby
Acknowledgements
This work was supported by the National Health and Medical Research Council grant APP1070081 to T.B. and a University of Queensland PhD Scholarship to P.M. The funding bodies had no role in the writing of the manuscript, and in the decision to submit the article for publication. We thank Dr Nick Valmas for preparing the illustrations. The authors have no conflicts of interest to declare.
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