Darryl W Eyles

University of Queensland , Brisbane, Queensland, Australia

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Publications (164)421.25 Total impact

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    ABSTRACT: Cytokines and vitamin D both have a role in modulating the immune system, and are also potentially useful biomarkers in mental illnesses such as major depressive disorder (MDD) and schizophrenia. Studying the variability of cytokines and vitamin D in a healthy population sample may add to understanding the association between these biomarkers and mental illness. To assess genetic and environmental contributions to variation in circulating levels of cytokines and vitamin D (25-hydroxy vitamin D: 25(OH)D3), we analyzed data from a healthy adolescent twin cohort (mean age 16.2 years; standard deviation 0.25). Plasma cytokine measures were available for 400 individuals (85 MZ, 115 DZ pairs), dried blood spot sample vitamin D measures were available for 378 individuals (70 MZ, 118 DZ pairs). Heritability estimates were moderate but significant for the cytokines transforming growth factor-β1 (TGF-β1), 0.57 (95% CI 0.26-0.80) and tumor necrosis factor-receptor type 1 (TNFR1), 0.50 (95% CI 0.11-0.63) respectively. Measures of 25(OH)D3 were within normal range and heritability was estimated to be high (0.86, 95% CI 0.61-0.94). Assays of other cytokines did not generate meaningful results. These potential biomarkers may be useful in mental illness, with further research warranted in larger sample sizes. They may be particularly important in adolescents with mental illness where diagnostic uncertainty poses a significant clinical challenge.
    Twin research and human genetics : the official journal of the International Society for Twin Studies. 12/2014;
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    ABSTRACT: Animal models confirm that low vitamin D during development is associated with changes in adult brain outcomes.•Animal models of adult vitamin D deficiency are associated with subtle changes in behaviour and brain neurochemistry.•Low vitamin D status may exacerbate the progression of brain disorders (a ‘two-hit’ model).•The links between vitamin D status and L-type voltage gated channels warrants closer scrutiny.
    The Journal of Steroid Biochemistry and Molecular Biology. 11/2014;
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    ABSTRACT: MicroRNAs (miRNAs) play a pivotal role in coordinating messenger RNA (mRNA) transcription and stability in almost all known biological processes, including the development of the central nervous system. Despite our broad understanding of their involvement, we still have a very sparse understanding of specifically how miRNA contribute to the strict regional and temporal regulation of brain development. Accordingly, in the current study we have examined the contribution of miRNA in the developing rat telencephalon and mesencephalon from just after neural tube closure till birth using a genome-wide microarray strategy.
    BMC Genomics 09/2014; 15(1):777. · 4.40 Impact Factor
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    ABSTRACT: Repeated exposure to psychostimulants that either increase dopamine (DA) release or target N-methyl-D-aspartate (NMDA) receptors can induce behavioural sensitisation, a phenomenon that may be important for the processes of addiction and even psychosis. A critical component of behavioural sensitisation is an increase in DA release within mesocorticolimbic circuits. In particular, sensitisation to amphetamine leads to increased DA release within well-known sub-cortical brain regions and also regulatory regions such as prefrontal cortex (PFC). However, it is unknown how DA release within the PFC of animals is altered by sensitisation to NMDA receptor antagonists.
    Psychopharmacology 07/2014; · 4.06 Impact Factor
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    ABSTRACT: Context: Recognition that vitamin D might be associated with many chronic diseases has led to large-scale epidemiological and clinical studies. Dried blood spots (DBS) are a useful resource for these studies. Consequently, accurate, efficient and inexpensive assays to quantify 25-hydroxyvitamin D (25OHD) in DBS are required. Objective: This study evaluated the validity and reliability of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for measuring 25OHD in archived DBS, and compared measurements of 25OHD in DBS with those in plasma. Design and Participants: Sixty two participants in the Melbourne Collaborative Cohort Study who had plasma and matching DBS stored since study entry in the early 1990s were randomly selected for a study calibrating 25OHD concentrations in DBS with plasma. As part of a study of vitamin D and mortality, cancer and diabetes, we also assessed the reliability of measurements from DBS using 500 replicates placed randomly within 31 batches run over 15 months. Outcome measure: 25OHD concentrations measured by LC-MS/MS. Results: There was good agreement between measurements of 25OHD from DBS and plasma; R(2) = 0.73 from a regression of plasma concentration on DBS concentration. The within-batch and between-batch intra-class correlations from the 500 replicate measurements were 0.82 (95% CI: 0.80, 0.85) and 0.73 (95% CI: 0.68, 0.78), respectively. Conclusions: Measuring 25OHD in DBS is a valid and reliable alternative to measuring 25OHD in sera or plasma. A simple calibration model was developed to convert measurements from DBS to equivalent plasma measurements, thus enabling comparisons against clinical reference ranges and with studies using sera or plasma samples.
    The Journal of clinical endocrinology and metabolism. 06/2014;
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    ABSTRACT: Developmental vitamin D (DVD) deficiency has been proposed as a risk factor for schizophrenia. DVD-deficient rats show selective cognitive deficits and novelty-induced hyperlocomotion and enhanced locomotor responses from acute treatment with psychomimetic drugs, such as amphetamine and MK-801. Here we aimed to examine the effect of a drug from a different class of psychomimetic/psychoactive compounds, Δ-tetrahydrocannabinol (THC), on tasks of relevance to the cognitive and positive symptoms of schizophrenia. The aim of this study was to investigate whether DVD deficiency modulates the behavioural effects of THC on tests of delay-dependent memory, sensorimotor gating and locomotion. Adult control and DVD-deficient rats were injected with THC (0, 0.3, 0.6, 1.25, 2.5 mg/kg) 15 min before a delay match to sample (DMTS) task using variable delays (0-24 s). A separate group of rats was injected with either 2.5 mg/kg THC or vehicle before tests of either prepulse inhibition (PPI) of the acoustic startle response or in the open field. Control and DVD-deficient rats showed a similar dose-dependent impairment in performance on the DMTS. The greatest impairment was observed at 2.5 mg/kg for all delays (0-24 s). DVD-deficient rats showed THC-induced enhancement of PPI, which was not observed in control rats. There was no effect of maternal diet on acoustic startle response or locomotor responses in the open field. This study reports the novel findings that DVD-deficient rats were more sensitive to the acute effects of THC on PPI. It appears that prenatal vitamin D deficiency has long-term effects on sensitivity to the behavioural effects of cannabinoids.
    Behavioural pharmacology 06/2014; 25(3):236-44. · 2.85 Impact Factor
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    Darryl W. Eyles, Pei-Yun Liu, Peter Josh, Xiaoying Cui
    Neuroscience 03/2014; · 3.12 Impact Factor
  • 2014 Meeting of the Australasian Neuroscience Society; 01/2014
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    D.W. Eyles, P.Y. Liu, P. Josh, X. Cui
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    ABSTRACT: Apart from its role in regulating calcium there is growing evidence that vitamin D is a neuroactive steroid capable of regulating multiple pathways important for both brain development and mature brain function. Vitamin D induces its genomic effects through its nuclear receptor the vitamin D receptor (VDR). Although there is abundant evidence for this receptor’s presence in the mammalian brain from studies employing immunohistochemistry, Western blot or quantitative RNA studies there remains some dispute regarding the validity of these studies. In this study we provide unambiguous confirmation for the VDR in adult rodent brain using proteomic techniques. However Western blot experiments show that compared to more classic target organs such as the gut and kidney, VDR expression is quantitatively lower in the brain. In addition we have examined VDR subcellular distribution in the gut, kidney and brain from both embryonic and adult tissues. We show that in all embryonic tissues VDR distribution is mostly nuclear, however by adulthood it appears that at least in the gut and kidney, VDR presence in the plasma membrane is more prominent perhaps reflecting some change in VDR function with the maturation of these tissues. Finally the subcellular distribution of VDR in the embryo did not appear to be altered by vitamin D deficiency indicating that perhaps there are other mechanisms at play in vivo to stabilize this receptor in the absence of its ligand.
    Neuroscience 01/2014; 268:1–9. · 3.12 Impact Factor
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    American Journal of Clinical Nutrition 03/2013; · 6.50 Impact Factor
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    ABSTRACT: During foetal development, calcium requirements are met as a consequence of maternal adaptations independent of vitamin D status. In contrast, after birth, dependency on vitamin D appears necessary for calcium metabolism and skeletal health. We used a rodent model (Sprague-Dawley rats), to determine if maternal vitamin D deficiency during pregnancy had a deleterious effect on bone structure at birth. Vitamin D deplete females were maintained under deplete conditions until birth of the pups, whereupon all dams were fed a vitamin D replete diet. Offspring were harvested at birth, and 140 days of age. Bones were analyzed using micro-computed tomography and strength tested to study differences in bone structure, density and strength and subjected to elemental analysis using plasma mass spectrometry to determine strontium, barium and calcium contents. Offspring from deplete mothers displayed altered trabecular parameters in the femur at birth and 140 days of age. In addition, at 140 days of age there was evidence of premature mineralization of the secondary ossification centre of the femoral head. Elemental analysis showed increased strontium uptake in the femur of the developmentally vitamin D-deficient offspring. Vitamin D depletion during development in the offspring may have a long-lasting effect, despite repletion of vitamin D from birth. This may have consequences for human health given the low vitamin D levels seen during pregnancy and current lifestyle of sun avoidance due to the risk of skin cancer.
    Journal of Developmental Origins of Health and Disease 02/2013; 4(1):49-55. · 1.21 Impact Factor
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    ABSTRACT: There is growing evidence that vitamin D is a neuroactive steroid capable of regulating multiple pathways important for both brain development and mature brain function. In particular, there is evidence from rodent models that prenatal vitamin D deficiency alters the development of dopaminergic pathways and this disruption is associated with altered behavior and neurochemistry in the adult brain. Although the presence of the vitamin D receptor (VDR) has been noted in the human substantia nigra, there is a lack of direct evidence showing that VDR is present in dopaminergic cells. Here we confirm that the VDR is present in the nucleus of tyrosine hydroxylase (TH)-positive neurons in both the human and rat substantia nigra, and it emerges early in development in the rat, between embryonic day 12 (E12) and E15. Consistent evidence based on immunohistochemistry, real-time PCR and western blot confirmed a pattern of increasing VDR expression in the rat midbrain until weaning. The nuclear expression of VDR in TH-positive neurons during critical periods of brain development suggests that alterations in early life vitamin D status may influence the orderly development of dopaminergic neurons.
    Neuroscience 01/2013; 236:77–87. · 3.12 Impact Factor
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    ABSTRACT: It has been observed that certain developmental environmental risk factors for schizophrenia when modeled in rodents alter the trajectory of dopaminergic development, leading to persistent behavioural changes in adults. This has recently been articulated as the "dopamine ontogeny hypothesis of schizophrenia". To test one aspect of this hypothesis, namely that transient dopaminergic effects during development modulate attention-like behavior and arousal in adults, we turned to a small-brain model, Drosophila melanogaster. By applying genetic tools allowing transient activation or silencing of dopaminergic neurons in the fly brain, we investigated whether a critical window exists during development when altered dopamine (DA) activity levels could lead to impairments in arousal states in adult animals. We found that increased activity in dopaminergic neurons in later stages of development significantly increased visual responsiveness and locomotion, especially in adult males. This misallocation of visual salience and hyperactivity mimicked the effect of acute methamphetamine feeding to adult flies, suggesting up-regulated DA signaling could result from developmental manipulations. Finally, brain recordings revealed significantly reduced gamma-band activity in adult animals exposed to the transient developmental insult. Together, these data support the idea that transient alterations in DA signaling during development can permanently alter behavior in adults, and that a reductionist model such as Drosophila can be used to investigate potential mechanisms underlying complex cognitive disorders such as schizophrenia.
    Translational psychiatry. 01/2013; 2:e2026.
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    ABSTRACT: Schizophrenia is a heterogeneous group of disorders with unknown etiology. Although abnormalities in multiple neurotransmitter systems have been linked to schizophrenia, alterations in dopamine (DA) neurotransmission remain central to the treatment of this disorder. Given that schizophrenia is considered a neurodevelopmental disorder we have hypothesized that abnormal DA signaling in the adult patient may result from altered DA signaling during fetal brain development. Environmental and genetic risk factors can be modeled in rodents to allow for the investigation of early neurodevelopmental pathogenesis that may lead to clues into the etiology of schizophrenia. To address this we created an animal model of one such risk factor, developmental vitamin D (DVD) deficiency. DVD-deficient adult rats display an altered behavioral profile in response to DA releasing and blocking agents that are reminiscent of that seen in schizophrenia patients. Furthermore, developmental studies revealed that DVD deficiency also altered cell proliferation, apoptosis, and neurotransmission across the embryonic brain. In particular, DVD deficiency reduces the expression of crucial dopaminergic specification factors and alters DA metabolism in the developing brain. We speculate such alterations in fetal brain development may change the trajectory of DA neuron ontogeny to induce the behavioral abnormalities observed in adult offspring. The widespread evidence that both dopaminergic and structural changes are present in people who develop schizophrenia prior to onset also suggest that early alterations in development are central to the disease. Taken together, early alterations in DA ontogeny may represent a core feature in the pathology of schizophrenia. Such a mechanism could bring together evidence from multiple risk factors and genetic vulnerabilities to form a convergent pathway in disease pathophysiology.
    Frontiers in Cellular Neuroscience 01/2013; 7:111. · 4.47 Impact Factor
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    ABSTRACT: Vitamin D deficiency is common in the adult population, and this has been linked to depression and cognitive outcomes in clinical populations. The aim of this study was to investigate the effects of adult vitamin D (AVD) deficiency on behavioural tasks of relevance to neuropsychiatric disorders in male Sprague-Dawley rats. Ten-week old male Sprague-Dawley rats were fed a control or vitamin D deficient diet for 6 weeks prior to, and during behavioural testing. We first examined a range of behavioural domains including locomotion, exploration, anxiety, social behaviour, learned helplessness, sensorimotor gating, and nociception. We then assessed locomotor response to the psychomimetic drugs, amphetamine and MK-801. Attention and vigilance were assessed using the 5 choice serial reaction time task (5C-SRT) and the 5 choice continuous performance task (5C-CPT) and, in a separate cohort, working memory was assessed using the delay match to sample (DMTS) task. We also examined excitatory and inhibitory neurotransmitters in prefrontal cortex and striatum. AVD-deficient rats were deficient in vitamin D3 (<10 nM) and had normal calcium and phosphate levels after 8-10 weeks on the diet. Overall, AVD deficiency was not associated with an altered phenotype across the range of behavioural domains tested. On the 5C-SRT AVD-deficient rats made more premature responses and more head entries during longer inter-trial intervals (ITI) than control rats. On the 5C-CPT AVD-deficient rats took longer to make false alarm (FA) responses than control rats. AVD-deficient rats had increases in baseline GABA levels and the ratio of DOPAC/HVA within the striatum. AVD-deficient rats exhibited no major impairments in any of the behavioural domains tested. Impairments in premature responses in AVD-deficient rats may indicate that these animals have specific alterations in striatal systems governing compulsive or reward-seeking behaviour.
    PLoS ONE 01/2013; 8(8):e71593. · 3.53 Impact Factor
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    ABSTRACT: Evidence from epidemiological studies suggest that low levels of vitamin D during early life alter brain development and may increase the risk of various adverse health outcomes, including schizophrenia. The aim of this experiment was to examine the effect of developmental vitamin D (DVD) deficiency on attentional processing using the 5-choice serial reaction time task (5C-SRT) and the 5-choice continuous performance test (5C-CPT), which specifically assesses sustained attention and vigilance in rodents. DVD-deficient and control rats were exposed to a series of target and non-target trials within each operant testing session. A number of measures were recorded including hit, miss, false alarm and correct rejection, as well as premature and perseverative responses. Performance on 5C-CPT was also assessed after administration of the atypical antipsychotic, clozapine. The adult offspring of DVD-deficient rats had higher levels of impulsivity, as demonstrated by a significant increase in premature responses. On the 5C-SRT and target trials of the 5C-CPT, accuracy was not significantly affected by prenatal diet; however DVD-deficient rats made 50% fewer correct rejections compared to controls on non-target trials of the 5C-CPT. Thus, control rats were able to discriminate between target and non-target trials, whereas DVD-deficient rats were unable to make this discrimination. Clozapine reduced the occurrence of false alarms in DVD-deficient rats to a level comparable to control values. Taken together these data suggest DVD-deficient rats have increased impulsivity as well as a lack of inhibitory control, and these features may be informative in terms of modeling the cognitive deficits observed in schizophrenia.
    Behavioural brain research 12/2012; · 3.22 Impact Factor
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    ABSTRACT: Epidemiological evidence suggests that low levels of vitamin D may predispose people to develop depression and cognitive impairment. While rodent studies have demonstrated that prenatal vitamin D deficiency is associated with altered brain development, there is a lack of research examining adult vitamin D (AVD) deficiency. The aim of this study was to examine the impact of AVD deficiency on behaviour and brain function in the mouse. Ten-week old male C57BL/6J and BALB/c mice were fed a control or vitamin D deficient diet for 10 weeks prior to, and during behavioural testing. We assessed a broad range of behavioural domains, excitatory and inhibitory neurotransmission in brain tissue, and, in separate groups of mice, locomotor response to D-amphetamine and MK-801. Overall, AVD deficiency resulted in hyperlocomotion in a novel open field and reduced GAD65/67 levels in brain tissue. AVD-deficient BALB/c mice had altered behaviour on the elevated plus maze, altered responses to heat, sound and shock, and decreased levels of glutamate and glutamine, and increased levels of GABA and glycine. By contrast C57BL/6 mice had a more subtle phenotype with no further behavioural changes but significant elevations in serine, homovanillic acid and 5-hydroxyindoleacetic acid. Although the behavioural phenotype of AVD did not seem to model a specific disorder, the overall reduction in GAD65/67 levels associated with AVD deficiency may be relevant to a number of neuropsychiatric conditions. This is the first study to show an association between AVD deficiency and prominent changes in behaviour and brain neurochemistry in the mouse.
    Behavioural brain research 12/2012; · 3.22 Impact Factor
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    ABSTRACT: Although a number of factors have been proposed to explain the increase in food allergy during the last decade, the possibility that vitamin D status may play a pathogenic role has received recent attention. To determine whether lower levels of neonatal 25-hydroxyvitamin D (25[OH]D) would be observed in children with peanut allergy compared with in population controls. The concentration of 25(OH)D was measured from neonatal dried blood samples by liquid chromatography tandem mass spectrometry. Levels were compared between children with IgE-mediated peanut allergy younger than 72 months assessed during 2008-2011 in a specialist referral clinic in the Australian Capital Territory and population births matched by sex, birth date, and birth location. Odds ratios were calculated for the matched pairs across quintiles of 25(OH)D. Neonatal 25(OH)D levels ranged from 8 to 180 nmol/L (median, 66 nmol/L; interquartile range, 46-93 nmol/L); only 4 children (3%) had levels less than 25 nmol/L, and 24 (20.9%) had levels greater than 100 nmol/L. No significant association was found between socioeconomic or clinical factors and 25(OH)D levels. Compared with the reference group (50-74.9 nmol/L), levels of 75 to 99.9 nmol/L were associated with lower risk of peanut allergy (P = .02). No further reduction was found at levels of 100 nmol/L or higher, and the risk of peanut allergy at levels less than 50 nmol/L was not significantly different from the reference group. The relationship between neonatal 25(OH)D level and childhood peanut allergy was nonlinear, with slightly higher levels (75-99.9 nmol/L) associated with lower risk than those in the reference group (50-74.9 nmol/L). Vitamin D status may be one of many potential factors contributing to childhood peanut allergy pathogenesis.
    Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 11/2012; 109(5):324-8. · 3.45 Impact Factor
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    ABSTRACT: The neurodevelopmental hypothesis of schizophrenia suggests that the disruption of early brain development increases the risk of later developing schizophrenia. This hypothesis focuses attention on critical periods of early brain development. From an epidemiologic perspective, various prenatal and perinatal risk factors have been linked to schizophrenia, including exposures related to infection, nutrition, and obstetric complications. From a genetic perspective, candidate genes have also been linked to altered brain development. In recent decades evidence from neuropathology has provided support for the neurodevelopmental hypothesis. Animal models involving early life exposures have been linked to changes in these same brain systems, providing convergent evidence for this long-standing hypothesis.
    The Psychiatric clinics of North America 09/2012; 35(3):571-84. · 1.87 Impact Factor

Publication Stats

3k Citations
421.25 Total Impact Points

Institutions

  • 1989–2014
    • University of Queensland 
      • • Queensland Brain Institute
      • • Queensland Centre for Mental Health Research (QCMHR)
      • • Perinatal Research Centre
      • • Queensland Centre for Schizophrenia Research
      • • School of Biomedical Sciences
      • • School of Medicine
      • • Department of Medicine
      Brisbane, Queensland, Australia
  • 2013
    • University of California, San Diego
      • Department of Medicine
      San Diego, CA, United States
  • 2012
    • Aix-Marseille Université
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2011
    • University of Wollongong
      • Centre for Translational Neuroscience (CTN)
      Wollongong, New South Wales, Australia
  • 2004–2006
    • Griffith University
      • Eskitis Institute for Drug Discovery
      Southport, Queensland, Australia
  • 1994
    • Princess Alexandra Hospital (Queensland Health)
      • Division of Medicine
      Brisbane, Queensland, Australia