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Vitamin D Deficiency And Risk Of Mental Conditions Sample Essay

Vitamin D Deficiency And Risk Of Mental Conditions Sample Essay


Vitamin D is a versatile neurosteroid molecule that is intricately involved in brain function of the developing, adult and senescent brain (Groves et al. 2014). The presence of Vitamin D’s (VD) active form has been implicated in neurotransmission modulation, the production and regulation of neurotrophic factors and neuroprotection (Groves et al. 2016). VD involvement in these processes is via both genomic and non-genomic pathways. Given the diverse array of VD functions, it is unsurprising that VD deficiency has been implicated as a risk factor in numerous mental conditions (MC) including Schizophrenia Disorder (SD), Alzheimer’s Disease (AD) and Autism Spectrum Disorder (ASD), (Groves et al. 2014). Mechanisms by which VD deficiency increases risk of developing MC is an active area of research, the existing knowledge of which will be explored below. Vitamin D within the Central Nervous System (CNS)Vitamin D has multiple receptors distributed throughout the human brain. Vitamin D Deficiency And Risk Of Mental Conditions Sample Essay

One such nuclear receptor (VDR) is densely expressed in regions of cell proliferation and differentiation in the developing brain, suggesting VD has an important role in the regulation of neurotrophic factors (Landel et al 2017). Neurotrophic factors involve the production of growth factors, axonal growth, cell differentiation, solidification of dopaminergic and glutamatergic pathways, and apoptosis (Groves et al. 2014). Thereby, a lack of VD may result in non-conventional neurotrophic growth factor expression which would implicate the above components of CNS development. Vitamin D also regulates calcium homeostasis, the maintenance of which is crucial in preserving calcium’s role in neurotransmitter release and uptake (Eyles et al. 2013). Excess calcium leads to over-amplification of signalling, often resulting in neural damage. Conversely, calcium deficits lead to diminished signal transmission and thus loss of cell signalling. Vitamin D Deficiency And Risk Of Mental Conditions Sample Essay

One way VD regulates this is by acting on long lasting voltage dependent calcium channels to globally amplify or dampen neuronal signals, thus protecting against neurotoxicity and premature signal depletion (Harms et al. 2011).

Symptoms of Neurological Disorders Associated with VD Deficiency

Schizophrenia Disorder is an enigmatical group of psychotic illnesses, of which no diagnostic biomarkers have been identified. Although not a diagnostic biomarker, anatomical studies have identified SD patients on average have enlarged lateral ventricles and a reduction in volume of the temporal lobe in comparison to non-SD controls (McCarley et al. 1999). Research points to the unlikelihood of a single cause for SD, but a complex set of risk factors that alter one’s susceptibility. One such factor is developmental vitamin D deficiency, or DVD (Kellett et al. 1978). Autism Spectrum Disorder is a broad term encompassing a large spectrum of neurodevelopmental disorders and symptoms. Both genetic and environmental risk factors are implicated in ASD prevalence (Abrahams and Geschwind 2008).Vitamin D Deficiency And Risk Of Mental Conditions Sample Essay

An inverse association between childhood ASD expression and circulating levels of 25(OH)D3 (VD) has been identified (Mazahery et al. 2016). Alzheimer’s Disease is a neurodegenerative condition with both genetic and sporadic forms. It is characterised anatomically by the build-up of beta amyloid plaques, tau tangles and cortical degradation (Serrano-Pozo et al. 2011). It has been demonstrated that the regulation of calcium homeostasis by VD is inhibited by beta amyloid, exposing neurons to neurotoxic calcium levels (Gezen-Ak et al. 2014). It is important to note that VD deficiency does not have causal links with MC, nor is it the sole risk factor. It is more accurate to think of VD deficiency as one of many risk factors at play which acts and interacts with a collection of other risk factors, all of which increase or decrease the polygenic risk of neurological disorders ensuing.Vitamin D Deficiency And Risk Of Mental Conditions Sample Essay

QBI’s Burne Laboratory

Queensland Brain Institute’s Developmental Neurobiology research group focuses largely on VD deficiency during development (DVD) and the implications deficiency has on the progression of mental conditions (MC). It is led by behavioural neuroscientist, Associate Professor Thomas Burne. Animal models are used extensively so as to limit confounding variables that would be innate in many other experimental frameworks (such as with neurological illness in-patients). With collaborators, this group is at the forefront of research surrounding DVD deficiency as a risk factor for MC. One such study identified a correlation between neonatal vitamin D deficiency and heightened risk of Schizophrenia within a population based sample (McGrath et al. 2010). This furthers the original 1978 observance that Schizophrenic patients have a disproportionate number of winter month birthdays (Kellett et al. 1978).Vitamin D Deficiency And Risk Of Mental Conditions Sample Essay


The group further hypothesised that optimal neonatal vitamin D levels may reduce the prevalence of SD within the sampled population by 43. 6% (McGrath et al. 2010). This is a powerful finding as it strengthens the likelihood of DVD deficiencies involvement as a contributing risk factor throughout development. SD has an estimated cost of US$60 billion per capita in the USA alone (Chong et al. 2016). From the results of this study, implementation of simple strategies that raise awareness of VD deficiency have the potential to significantly reduce the contribution of DVD deficiency as a risk factor for SD. Multiple experiments have explored connections between DVD deficiency and MC by holding mouse models at a deficient VD levels prior to mating until the birth of offspring. Analysis of the ensuing DVD deficient progeny have found that mice from deficient origin typically had reduced apoptosis, enlarged lateral ventricles, altered neurogenesis and increased cellular proliferation (Cui et al. 2007; Eyles et al. 2003; Ko et al. 2004). Alterations in neurotransmitter pathways, synaptic plasticity, calcium binding proteins, attentional processing and learning was also highlighted (which is consistent with previous studies). This is significant as it links vitamin D to symptoms of multiple neurological disorders.Vitamin D Deficiency And Risk Of Mental Conditions Sample Essay

For example, enlarged lateral ventricles has found to be an anatomical feature of SD (McCarley et al. 1999). That this effect was observed in a DVD deficient animal model, while controlling for external factors (such as stabilising and monitoring calcium levels), points to VD as a significant risk factor for SD. Furthermore, differential brain structuring is linked to varied dopaminergic and glutaminergic signalling cascades, which in turn affects GABA (inhibitory) and glutamate (excitatory) neurotransmitter signalling (Kesby et al. 2017). This is yet another association where VD interacts with calcium (among other things), acting as a transcription factor for the synthesis and activation of neurotransmitters (Groves et al. 2016). A 2017 paper addressed DVD deficiency as a risk factor in ASD. Results from this population study supported mid-gestational DVD deficiency as a risk factor in ASD (Vinkhuyzen et al. 2017).Vitamin D Deficiency And Risk Of Mental Conditions Sample Essay

An opposing conclusion was drawn during an experiment with mouse models, which concluded that DVD deficiency is not enough in itself to generate ASD in offspring (Langguth et al. 2018). This highlights the role of DVD deficiency as one risk factor which acts in concert with many other factors to alter the overall polygenic risk of an individual expressing a multitude of MC. It may also support a critical windows hypothesis that will be discussed below. It is also plausible that DVD or VD deficiency doesn’t directly implicate phenotypic expression of MC, but instead VD deficiency is itself a downstream effect from another mechanism which alters the polygenic risk of developing conditions. The wide stretching implications of DVD deficiency is perplexing. Where SD typically has subtle anatomical markers but no neuronal death, AD has distinct tau tangles and amyloid plaques (McCarley et al. 1999; Serrano-Pozo et al. 2011). While AD onset is typically in later life, ASD is usually first diagnosed in early childhood (Serrano-Pozo et al. 2011; Abrahams and Geschwind 2008).Vitamin D Deficiency And Risk Of Mental Conditions Sample Essay

How could all of these widely variant conditions have a common risk factor? The answer may lie in critical windows during gestation. Critical windows are periods of brain development, during which signals are expected to be released and received in order for the brain to wire up ‘typically’ (Selevan et al. 2000). Wiring in a DVD deficient mouse may occur at a later stage in the critical window than a non-deficient mouse. This time lapse may result in a synapse-to dendrite connection occurring at an atypical location. This would have implications for subsequent downstream signals (see Figure 1). Such an effect would help to rationalise VD associations in such a large multitude of MC that each have varied phenotypic expressions. Burne’s lab also explores the implications of adult VD (AVD) deficiency as it pertains to the expression of MC. The group experimentation with mice models which found an association between AVD deficiency and altered neurotransmission, among other neurochemical changes. It was the first study to show this association (Groves et al. 2013).Vitamin D Deficiency And Risk Of Mental Conditions Sample Essay

Future Work

Experiments testing critical windows hypotheses are imprecise due to the time taken for depletion and repletion of VD. Adding to this difficulty is the intricate association VD has with calcium. However, the effects of VD deficiency during late gestational windows may be measurable at various degrees of deficiency. Despite these challenges, the Burne laboratory as undertaken multiple successful experiments illustrating the effect of DVD and AVD on MC expression. Going forward, analysis of whether VD favours its genomic or non-genomic pathways in deficient states (and if VD operates preferentially at all) may be beneficial in achieving the overarching goal which is to determine the mechanism by which DVD deficiency acts as a risk factor for MC. It may also enable reduction of the prevalence of multiple mental illnesses. Vitamin D Deficiency And Risk Of Mental Conditions Sample Essay

Furthermore, exploration of the developmental mechanisms in which VD deficiency is associated with MC would facilitate in understanding AVD deficiency’s effect on the adult brain. Whether optimal AVD intake is effective in stopping the progression or even reversing the effects of mental illnesses has the potential to be translated into a treatment for listed MC. These are goals the Burne laboratory is constantly working towards. Vitamin D Deficiency And Risk Of Mental Conditions Sample Essay


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