The objectives of this paper were (1) to review recent research on the actions of vitamin D as a steroid derivative with neuroactive properties and (2) to highlight clinical relevance and need for more research. Our methods included review of research from current journals, Medline, and Cochrane Reviews; theoretical discussion. Scientific research has had a justifiably strong emphasis on how vitamin D affects calcium metabolism and bone. This appears to have eclipsed its fundamental actions on several other important systems, including the central nervous system. Vitamin D as a neuroactive compound, a prohormone, is highly active in regulating cell differentiation, proliferation, and peroxidation in a variety of structures, including the brain. Vitamin D insufficiency is not rare. Historically, focus has been on bone metabolism, which appears to have caused research bias and evidence bias, distorting physiological importance. The central nervous system is increasingly recognized as a target organ for vitamin D via its wide-ranging hormonal effects, including the induction of proteins such as nerve growth factor. We need more research on this important neuroactive substance because it may play a role as a relatively safe and inexpensive pharmaceutical in the prevention and treatment of a number of common neuropsychiatric conditions.

Brain injuries are too common. Most people are unaware of the incidence of and horrendous consequences of traumatic brain injury (TBI) and mild traumatic brain injury (MTBI). Research and the advent of sophisticated imaging have led to progression in the understanding of brain pathophysiology following TBI. Seminal evidence from animal and human experiments demonstrate links between TBI and the subsequent onset of premature, psychiatric syndromes and neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Objectives of this summary are, therefore, to instill appreciation regarding the importance of brain injury prevention, diagnosis, and treatment, and to increase awareness regarding the long-term delayed consequences following TBI.

Despite the paucity of human research, basic animal models and clinical data overwhelmingly support the notion that exercise treatment is a major protective factor against neurodegeneration of varied etiologies. The final common pathway of degradation is clearly related to oxidative stress, nitrosative stress, glucocorticoid dysregulation, inflammation and amyloid deposition. We conclude that people prone to chronic distress, brain ischemia, brain trauma, and the aged are at increased risk for neurodegenerative diseases such as Alzheimer's. Exercise training may be a major protective factor but without clinical guidelines, its prescription and success with treatment adherence remain elusive.

It behooves us to research diagnostic methods pertaining to psychoses and affective disorders associated with hypercortisolemic states. Very little research is available, but we must be alert to the possibility that the elderly are more susceptible to cortisol endotoxicosis than the younger adult population. Without accurate diagnosis, we cannot take advantage of existing antiglucocorticoid strategies.