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Schizophrenia immunology

Dominique Endres, Rick Dersch, Oliver Stich, Armin Buchwald, Evgeniy Perlov, Bernd Feige, Simon Maier, Andreas Riedel, Ludger Tebartz van Elst
INTRODUCTION: Vitamin D has many immunomodulatory, anti-inflammatory, and neuroprotective functions, and previous studies have demonstrated an association between vitamin D deficiency and neuropsychiatric disease. The aim of our study was to analyze the prevalence of vitamin D deficiency in a 1-year cohort of adult inpatients with schizophreniform and autism spectrum syndromes in a naturalistic inpatient setting in Germany. PARTICIPANTS AND METHODS: Our study was comprised of 60 adult schizophreniform and 23 adult high-functioning autism spectrum patients who were hospitalized between January and December of 2015...
2016: Frontiers in Psychiatry
Ana Laura Colín-González, Gabriela Aguilera, Abel Santamaría
The endocannabinoid system (ECS) comprises a complex of receptors, enzymes, and endogenous agonists that are widely distributed in the central nervous system of mammals and participates in a considerable number of neuromodulatory functions, including neurotransmission, immunological control, and cell signaling. In turn, the kynurenine pathway (KP) is the most relevant metabolic route for tryptophan degradation to form the metabolic precursor NAD(+). Recent studies demonstrate that the control exerted by the pharmacological manipulation of the ECS on the glutamatergic system in the brain may offer key information not only on the development of psychiatric disorders like psychosis and schizophrenia-like symptoms, but it also may constitute a solid basis for the development of therapeutic strategies to combat excitotoxic events occurring in neurological disorders like Huntington's disease (HD)...
2016: Advances in Neurobiology
Maria Di Bari, Giovanni Di Pinto, Marcella Reale, Guadalupe Mengod, Ada Maria Tata
Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system (CNS) characterized by leucocytes infiltration, demyelination, axonal degeneration and neuronal death. Although the etiology of MS is still unknown, inflammation and autoimmunity are considered to be key players of the disease. The severe alterations affecting the nervous system contribute to the motor and cognitive disabilities and are in large part dependent on severe inflammatory processes active in both central nervous system and immune system...
August 22, 2016: Central Nervous System Agents in Medicinal Chemistry
Koichi Inoue, Eisuke Sakuma, Hiroyuki Morimoto, Hayato Asai, Yoshinori Koide, Tiandong Leng, Ikuo Wada, Zhi-Gang Xiong, Takatoshi Ueki
Microglia are derived from myelogenous cells and contribute to immunological and inflammatory responses in central nervous system. They play important roles not only in infectious diseases and inflammation after stroke, but also in psychiatric diseases such as schizophrenia. While recent studies suggest the significances of serum- and glucocorticoid-inducible kinases (SGKs) in other immune cells such as macrophages, T cells and dendritic cells, their role in microglia remains unknown. Here we, for the first time, report that SGK1 and SGK3 are expressed in multiple microglial cell lines...
September 9, 2016: Biochemical and Biophysical Research Communications
Jonathan L Hess, Daniel S Tylee, Rahul Barve, Simone de Jong, Roel A Ophoff, Nishantha Kumarasinghe, Paul Tooney, Ulrich Schall, Erin Gardiner, Natalie Jane Beveridge, Rodney J Scott, Surangi Yasawardene, Antionette Perera, Jayan Mendis, Vaughan Carr, Brian Kelly, Murray Cairns, Ming T Tsuang, Stephen J Glatt
The application of microarray technology in schizophrenia research was heralded as paradigm-shifting, as it allowed for high-throughput assessment of cell and tissue function. This technology was widely adopted, initially in studies of postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders...
October 2016: Schizophrenia Research
Maiara Zeni-Graiff, Lucas B Rizzo, Rodrigo B Mansur, Pawan K Maurya, Sumit Sethi, Graccielle R Cunha, Elson Asevedo, Pedro Pan, André Zugman, Ana S Yamagata, Cinthia Higuchi, Rodrigo A Bressan, Ary Gadelha, Elisa Brietzke
BACKGROUND: Immuno-inflammatory imbalances have been documented in schizophrenia, but very little is known about the immunological changes prior to the onset of disease. OBJECTIVE: This work aimed to compare serum levels of pro- and anti-inflammatory cytokines in young subjects at ultra-high risk (UHR) of developing psychosis with age- and sex-matched healthy controls. METHODS: A total of 12 UHR and 16 age- and sex-matched healthy controls (HC) subjects were enrolled in this study...
October 2016: Schizophrenia Research
Pawel Kapelski, Maria Skibinska, Malgorzata Maciukiewicz, Joanna Pawlak, Dorota Zaremba, Joanna Twarowska-Hauser
Schizophrenia is a heterogeneous disorder and its etiology remains incompletely elucidated. Among possible causes, immunological factors have been implicated in its pathogenesis and course. Interleukin-10 (IL10) and it's receptor IL10RA may play an important role for immunological aspects in etiologies of major psychiatric disorders including schizophrenia. The aim of this study was to perform a transmission disequilibrium test (TDT) on a group of 146 schizophrenia trios from the Polish population. Functional polymorphisms from IL10 (rs1800872, rs1800871, rs1800896, rs1800890, and rs6676671) and IL10RA (rs3135932 and rs2229113) genes were analyzed...
August 15, 2016: Journal of Neuroimmunology
Şeref Şimşek, Veli Yıldırım, Abdullah Çim, Savaş Kaya
OBJECTIVE: In this study, it was aimed to understand the underlying possible immunopathogenesis of first episode, early onset schizophrenia (EOS) through profiling the T helper 1 (Th1) cell cytokines TNF-α, IFN-γ, and IL-2, Th2 cell cytokines IL-4 and IL-10, Th17 cell cytokine IL-17A, and inflammatory cytokine IL-6. METHODS: The study included a total of 30 children, admitted to child psychiatry outpatient clinic aged between 10 and 17 years of age, who had not received prior therapy and were diagnosed with psychosis according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) as the patient group, and 26 age- and gender-matched children as the control group...
July 6, 2016: Journal of Child and Adolescent Psychopharmacology
J de Bie, C K Lim, G J Guillemin
Schizophrenia has a clear sexual dimorphism in age of onset and progression. The underlying mechanisms of this dimorphism are not known, but may be found in the interactions of sex hormones with the tryptophan catabolising kynurenine pathway. Schizophrenia is associated with general inflammation and disruption of glutamatergic and dopaminergic signalling. Metabolites of the kynurenine pathway have been shown to be immunomodulatory and have effects on glutamatergic and dopaminergic signalling. This review discusses the currently available literature on sex hormones and their effect on the kynurenine pathway in the context of the glutamatergic, dopaminergic and immunological features of schizophrenia...
October 2016: Neurotoxicity Research
Palle Duun Rohde, Ditte Demontis, Beatriz Castro Dias Cuyabano, Anders D Børglum, Peter Sørensen
Schizophrenia is a psychiatric disorder with large personal and social costs, and understanding the genetic etiology is important. Such knowledge can be obtained by testing the association between a disease phenotype and individual genetic markers; however, such single-marker methods have limited power to detect genetic markers with small effects. Instead, aggregating genetic markers based on biological information might increase the power to identify sets of genetic markers of etiological significance. Several set test methods have been proposed: Here we propose a new set test derived from genomic best linear unbiased prediction (GBLUP), the covariance association test (CVAT)...
August 2016: Genetics
Emilio Fernandez-Egea, Petra E Vértes, Shaun M Flint, Lorinda Turner, Syed Mustafa, Alex Hatton, Kenneth G C Smith, Paul A Lyons, Edward T Bullmore
BACKGROUND: Hypothetically, psychotic disorders could be caused or conditioned by immunological mechanisms. If so, one might expect there to be peripheral immune system phenotypes that are measurable in blood cells as biomarkers of psychotic states. METHODS: We used multi-parameter flow cytometry of venous blood to quantify and determine the activation state of 73 immune cell subsets for 18 patients with chronic schizophrenia (17 treated with clozapine), and 18 healthy volunteers matched for age, sex, BMI and smoking...
2016: PloS One
Jennie G Pouget, Vanessa F Gonçalves, Sarah L Spain, Hilary K Finucane, Soumya Raychaudhuri, James L Kennedy, Jo Knight
There has been intense debate over the immunological basis of schizophrenia, and the potential utility of adjunct immunotherapies. The major histocompatibility complex is consistently the most powerful region of association in genome-wide association studies (GWASs) of schizophrenia and has been interpreted as strong genetic evidence supporting the immune hypothesis. However, global pathway analyses provide inconsistent evidence of immune involvement in schizophrenia, and it remains unclear whether genetic data support an immune etiology per se...
September 2016: Schizophrenia Bulletin
Lekshmy Srinivas, Neetha N Vellichirammal, Ann Mary Alex, Chandrasekharan Nair, Indu V Nair, Moinak Banerjee
BACKGROUND: In schizophrenia, genetic background may provide a substrate for intrinsic maldevelopment of the brain through environmental influences, by recruiting neurotrophic factors and cytokines, to trigger the changes that lead to impaired neuronal functions. Cytokines being the key regulators of immune/inflammatory reactions are also known to influence the dopaminergic, noradrenergic, and serotonergic neurotransmission. Therefore, functional polymorphisms in cytokine genes may result in imbalances in the pro- and anti-inflammatory cytokine production...
2016: Journal of Neuroinflammation
James S Brown
For at least a century, a debate has continued as to whether cancer risk is reduced in schizophrenia. Genetic studies have also suggested the 2 conditions may share protein transcriptional pathways. The author predicted that if the pathophysiology of schizophrenia confers protection from cancer, then the immunology of schizophrenia should reflect a state of tumor suppression, ie, the opposite of tumor escape. To examine this possibility, the author performed a literature search for measurements of cytokines in drug-naïve first episode subjects with schizophrenia for comparison with cytokine expression in tumor escape vs tumor suppression...
May 11, 2016: Schizophrenia Bulletin
Ester Coutinho, Angela Vincent
The immune system's role in the pathophysiology of several neuropsychiatric disorders has been the subject of research for many decades. Despite suggestive evidence from genetic, epidemiologic, and immunologic studies, those findings did not translate into clinical practice. Recent recognition of antibody-mediated central nervous system (CNS) disorders has fueled the search for a subgroup of patients with an antibody-mediated psychiatric illness. This chapter focuses on the current understanding of autoimmune CNS disorders and how they may be relevant to psychiatric disorders, particularly schizophrenia and autism...
2016: Handbook of Clinical Neurology
A F Iznak, E V Iznak, T P Klyushnik, I V Oleichik, L I Abramova, G M Kobel'kov, M A Lozhnikov
OBJECTIVE: to identify a complex of neurobiological parameters informative for the assessment of severity of patient's initial clinical state and for individual prognosis of therapeutic response. MATERIAL AND METHODS: Correlation and regression analyses of clinical scores measured by the PANSS scale, resting EEG spectral parameters and immunological parameters have been performed in 45 patients (mean age 31.3±11.4 years with manic-delusional conditions in attack-like schizophrenia...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
L V Androsova, N V Simashkova, O V Shushpanova, I N Otman, T P Klyushnik
OBJECTIVE: To compare clinical and immunological parameters in children with schizophrenia and to analyze the possibility of using them in the assessment of the pathological process activity. MATERIAL AND METHODS: We examined 62 patients, 39 boys and 23 girls, aged from 4 to 17 years, with childhood-onset schizophrenia. Mental state of the patients was assessed using a psychopathological method and with PANSS and CGI scales. The activity of leukocyte elastase (LE) and alpha(1)-proteinase inhibitor (α1-PI) was measured by spectrophotometric method...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Sajjad Karim, Mohammad A Kamal, Zafar Iqbal, Shakeel A Ansari, Mahmood Rasool, Mohammed H Al-Qahtani, Gazi Damanhouri, Zeenat Mirza
Schizophrenia, a psychological disorder with enormous societal impact, is a result of abnormalities in gene expression and dysregulation of the immune response in the brain. Few studies have been conducted to understand its etiology, however, the exact molecular mechanism largely remains unknown, though some poorly understood theories abound. Present meta-study links the role of central nervous system, immunological system and psychological disorders by using global expression approach and pathway analysis...
2016: CNS & Neurological Disorders Drug Targets
Ladislav Hosák, Jirina Hosakova
The etiology of schizophrenia is complex. The aim of this article is to present a global view of the causes of schizophrenia and their interconnectivity. Recent genetic research into schizophrenia is based on genome-wide association studies, the assessment of DNA copy number variations, and the concept of endophenotypes. A lot of suspected genes have already been identified, mostly relating to neurodevelopment, neuroplasticity, immunology and neuroendocrinology. Gene-environment interactions (G×E) reflect genetic variation in susceptibility to the environment...
December 2015: Neuro Endocrinology Letters
I N Otman, S A Zozulya, Z V Sarmanova, T P Klushnik
Parameters of innate (the leukocyte elastase (LE) and alpha1-proteinase inhibitor (α-1-PI) activity) and adaptive immunity (the level of autoantibodies to neuroantigens nerve growth factor (NGF) and myelin basic protein (MPB)) were studied over time in the blood serum of 107 children with perinatal hypoxic-ischemic encephalopathy; 188 children with autism spectrum disorder; 108 patients with schizophrenia. The correlations between immunological parameters and clinical status assessment in all groups of patients using psychometric scales were analyzed...
July 2015: Patologicheskaia Fiziologiia i èksperimental'naia Terapiia
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