1Neurosci. Lett. 2010 Dec 486: 220-3
TitleMaternal vitamin D deficiency alters the expression of genes involved in dopamine specification in the developing rat mesencephalon.
Abstractschizophrenia is a neurodevelopment disorder that is strongly associated with alterations in dopamine neurotransmission. Common features of animal models of schizophrenia include behavioural, cognitive and/or pharmacological abnormalities reflective of aberrant DA signaling. The aim of this study was to examine the expression of genes important for dopaminergic development and maturation within the embryonic mesencephalon using an epidemiologically-informed animal model of schizophrenia, the developmental vitamin D (DVD) deficient rat model. Two groups of female Sprague-Dawley rats were fed either a diet replete (1000IU/kg) or deplete (0IU/kg) of vitamin D, mated and foetal mesencephalon collected at embryonic day (E) E12 or E15. Using real time-PCR, the DVD-deficient embryos had a significant reduction in factors crucial in specifying dopaminergic phenotype, such as Nurr1 and p57Kip2. No group differences were found for Lmx1b or PTX3. Reductions in these specification factors may alter the ontogeny of DA neurons and may ultimately help to explain the behavioural abnormalities reported in adult offspring from this model.
SCZ Keywordsschizophrenia
2Psychoneuroendocrinology 2012 Dec 37: 1901-11
TitleIncreased level of serum cytokines, chemokines and adipokines in patients with schizophrenia is associated with disease and metabolic syndrome.
AbstractAt present there are strong indications of a shared vulnerability factor for schizophrenia (SZ), diabetes and the metabolic syndrome (metS). In this study we focus on an aberrantly activated monocyte/macrophage system as the shared factor. We measured in SZ patients (n=144), the serum levels of monocyte/macrophage cytokines/chemokines/adipokines CCL2, CCL4, IL-1?, TNF-?, IL-6, PTX3, leptin, adiponectin, PAI-1, OPG and ICAM-1 and compared these levels to healthy controls (HC) (n=138). Using multivariate analysis, we studied the effect of the presence of the disease SZ, the components of the metS including BMI, the levels of lipids (HDL cholesterol and triglycerides (TG)), diabetes (hyperglycemia) and the use of antipsychotic medication, on the serum levels of these immune compounds. We found all measured immune compounds with the exception of PAI-1 and OPG to be elevated in the SZ patient population. Multivariate analysis showed that elevations were linked to gender (ICAM-1, leptin, TNF-? and adiponectin), an increased BMI (leptin, adiponectin), hyperglycemia/diabetes (CCL4, and OPG), reduced HDL-cholesterol or increased levels of TG (adiponectin and PTX3) or the metS (CCL2, leptin and adiponectin). IL-1? and IL-6 were the only immune compounds raised in the serum of patients not affected by any of the included factors. Although many of the immune compounds were found linked to (components of) the metS, the most dominant linkage was found with the disease schizophrenia, confirming earlier reports on increased monocyte/macrophage activation as a key component for understanding the pathogenesis of schizophrenia.
SCZ Keywordsschizophrenia
3J. Nerv. Ment. Dis. 2015 May 203: 319-24
TitlePredictors of the Onset of Schizophrenia in US Military Personnel.
AbstractAlterations in immune response may be an important component in the etiopathogenesis of schizophrenia and bipolar disorder. We examined the associations of pentraxin-3 (PTX3) with the onset of schizophrenia or bipolar disorder. We tested preonset serum specimens from 160 US military service members who were later diagnosed with schizophrenia or bipolar disorder and 160 matched controls without psychiatric disorders. Lower serum levels of PTX3 were predictive of schizophrenia but not of bipolar disorder. Subjects with below-median PTX3 levels had a 3.0 odds ratio (confidence interval, 1.6-5.7) for schizophrenia onset in the multivariable logistic regression model controlling for demographic and military variables. The test for trends was significant (p = 0.002), with the likelihood increasing as the levels of PTX3 decreased. Crude and adjusted categorized levels were not predictive of bipolar disorder. A lower level of inflammatory response indicated by PTX3 might be implicated in developing schizophrenia.
SCZ Keywordsschizophrenia