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Krishnamurthy, Divya; Harris, Laura W.; Levin, Yishai; Koutroukides, Theodoros A.; Rahmoune, Hassan; Pietsch, Sandra; Vanattou-Saifoudine, Natacha; Leweke, F. Markus; Guest, Paul C.; Bahn, Sabine
doi: 10.3109/15622975.2011.601759pmid: 22248022
AbstractObjectives. To identify a molecular profile for schizophrenia using post-mortem pituitaries from schizophrenia and control subjects. Methods. Molecular profiling analysis of pituitaries from schizophrenia (n = 14) and control (n = 15) subjects was carried out using a combination of liquid chromatography tandem mass spectrometry (LC-MSE), multiplex analyte profiling (MAP), two-dimensional difference gel electrophoresis (2D-DIGE) and Western blot analysis. Results. This led to identification of differentially expressed molecules in schizophrenia patients including hypothalamic–pituitary–adrenal axis-associated constituents such as cortisol, pro-adrenocorticotropic hormone, arginine vasopressin precursor, agouti-related protein, growth hormone, prolactin and secretagogin, as well as molecules associated with lipid transport and metabolism such as apolipoproteins A1, A2, C3 and H. Altered levels of secretagogin in serum from a cohort of living first onset schizophrenia patients were also detected, suggesting disease association and illustrating the potential for translating some components of this molecular profile to serum-based assays. Conclusions. Future studies on the molecules identified here may lead to new insights into schizophrenia pathophysiology and pave the way for translation of novel diagnostics for use in a clinical setting.
Wilmsdorff, Martina Von; Blaich, Carolin; Zink, Mathias; Treutlein, Jens; Bauer, Manfred; Schulze, Thomas; Schneider-Axmann, Thomas; Gruber, Oliver; Rietschel, Marcella; Schmitt, Andrea; Falkai, Peter
Montag, Christiane; Brockmann, Eva-Maria; Bayerl, Martin; Rujescu, Dan; Müller, Daniel J.; Gallinat, Jürgen
doi: 10.3109/15622975.2012.677547pmid: 22651577
AbstractObjectives. Dysfunctions of the “social brain” belong to the core features of schizophrenia. The neurohormone oxytocin (OXT), mediated through its specific receptor (OXTR), is involved in the regulation of social behaviour and social cognition. Previous research has suggested a role of OXT system genes in disorders of social reciprocity. Preliminary evidence points to an association of peripheral OXT levels as well as OXT and OXTR gene polymorphisms with psychotic symptoms and treatment response in schizophrenia. This study aims to determine a possible contribution of OXT and OXTR genetic variations to schizophrenia susceptibility. Methods. Using n = 406 individuals diagnosed with schizophrenia according to DSM-IV and n = 406 healthy controls matched for age and gender in a case–control design, two single nucleotide polymorphisms (SNPs) within the OXT gene (rs2740204, rs2740210) and four SNPs within the OXTR gene (rs53576, rs237880, rs237885, rs237902) that were previously investigated in other studies were genotyped. Results. Chi2-testing suggested significant associations of OXTR SNPs rs53576(A > G) (P = 0.008) and rs237885(T > G) (P = 0.025) with a diagnosis of schizophrenia. Post-hoc ANCOVA revealed significant associations of OXTR SNPs rs53576 with general psychopathology and rs237902 with negative symptom scores in schizophrenic patients. Conclusions. Our findings support hypotheses about an involvement of oxytocinergic gene variants in schizophrenia vulnerability and warrant independent replication.
Okusaga, Olaoluwa; Yolken, Robert H.; Langenberg, Patricia; Sleemi, Aamar; Kelly, Deanna L.; Vaswani, Dipika; Giegling, Ina; Hartmann, Annette M.; Konte, Bettina; Friedl, MARION; Mohyuddin, Farooq; Groer, Maureen W.; Rujescu, Dan; Postolache, Teodor T.
Toma, Claudio; Hervás, Amaia; Balmaña, Noemí; Salgado, Marta; Maristany, Marta; Vilella, Elisabet; Aguilera, Francisco; Orejuela, Carmen; Cuscó, Ivon; Gallastegui, Fátima; Pérez-Jurado, Luis Alberto; Caballero-Andaluz, Rafaela; Diego-Otero, Yolanda de; Guzmán-Alvarez, Guadalupe;
Abdallah, Morsi W.; Larsen, Nanna; Grove, Jakob; Nørgaard-Pedersen, Bent; Thorsen, Poul; Mortensen, Erik L.; Hougaard, David M.
doi: 10.3109/15622975.2011.639803pmid: 22175527
AbstractObjectives. The aim of the study was to analyze cytokine profiles in amniotic fluid (AF) samples of children developing autism spectrum disorders (ASD) and controls, adjusting for maternal autoimmune disorders and maternal infections during pregnancy. Methods. AF samples of 331 ASD cases and 698 controls were analyzed for inflammatory cytokines using Luminex xMAP technology utilizing a historic birth cohort. Clinical data were retrieved from nationwide registers, and case-control differences in AF cytokine levels were assessed using chi-square tests, logistic and tobit regression models. Results. Overall, individuals with ASD had significantly elevated AF levels of TNF-α and TNF-β compared to controls. Analyzing individuals diagnosed only with ICD-10 codes yielded significantly elevated levels of IL-4, IL-10, TNF-α and TNF-β in ASD patients. Restricting analysis to infantile autism cases showed significantly elevated levels of IL-4, TNF-α and TNF-β compared to controls with no psychiatric comorbidities. Elevated levels of IL-6 and IL-5 were found in individuals with other childhood psychiatric disorders (OCPD) when compared to controls with no psychiatric comorbidities. Conclusions. AF samples of individuals with ASD or OCPD showed differential cytokine profiles compared to frequency-matched controls. Further studies to examine the specificity of the reported cytokine profiles in ASD and OCPD are required.
Lieb, Martin; Palm, Ulrich; Chiang, Sonnig; Laubender, Rüdiger P.; Nothdurfter, Caroline; Sarubin, Nina; Mokhtari-Nejad, Rabee; Koller, Gabriele; Soyka, Michael
doi: 10.3109/15622975.2013.812239pmid: 24020866
Showing 1 to 8 of 8 Articles
AbstractObjectives. The glutamatergic hypothesis of schizophrenia proposes alterations of excitatory amino acid transporters (solute carrier family, SLCs) expression and cerebellar dysfunctions. The influence of the neuregulin-1 (NRG1) risk genotype or effects of antipsychotics on expression of EAATs are unknown. Methods. We compared post-mortem samples from the cerebellar hemispheres and vermis of 10 schizophrenia patients with nine normal subjects by investigating gene expression of SLC1A3, SLC1A1 and SLC1A6 by in-situ hybridization. We further assessed the allelic composition regarding the polymorphism rs35753505 (SNP8NRG221533) near the NRG1 gene. To control for effects due to antipsychotic treatment, we chronically treated rats with the antipsychotics haloperidol or clozapine and assessed gene expression of SLCs. Results. Schizophrenia patients showed increased expression of SLC1A3 in the molecular layer of the vermis. Individuals carrying at least one C allele of rs35753505 (SNP8NRG221533) showed decreased expression of SLC1A6 in the molecular layer of both hemispheres, compared to individuals homozygous for the T allele. The animal model revealed suppression of SLC1A6 by clozapine. Conclusions. Increased SLC1A3 expression indicates facilitated transport and may result in reduced glutamate neurotransmission. Decreased SLC1A6 expression in NRG1 risk variant may be an adaptive effect to restore glutamate signalling, but treatment effects cannot be excluded.
doi: 10.3109/15622975.2012.747699pmid: 23282016
AbstractObjectives. We aimed to replicate, in a larger sample and in a different geographical location, the previously reported elevation of anti-gliadin IgG antibodies in schizophrenia. Methods. A total of 950 adults with schizophrenia (severity assessed by PANSS) and 1000 healthy controls were recruited in the Munich metropolitan area. Anti-gliadin IgG antibodies were analyzed with ELISA. χ2-tests and logistic regression were used to analyze the association of schizophrenia with elevated anti-gliadin IgG. A multivariable general linear model was used to compare anti-gliadin IgG levels between patients and controls. Results. The odds ratio of having elevated anti-gliadin IgG antibodies in the schizophrenia group was 2.13 (95% CI 1.57 to 2.91, p < 0.0001). Mean anti-gliadin IgG levels were higher in schizophrenia patients (0.81 ± 0.79 vs. 0.52 ± 0.56, t = 9.529, df = 1,697, p < 0.0001) and the difference persisted after adjusting for potential confounders. Conclusions. Our study, limited by its cross sectional design, confirmed an association between anti-gliadin IgG antibodies and schizophrenia. Replication in longitudinal studies, clinical trials of gluten free diet and mechanistic investigation could lead to novel treatment targets, preventive and therapeutic considerations in schizophrenia.
doi: 10.3109/15622975.2011.602719pmid: 22397633
AbstractObjectives. Neurotransmitter systems and neurotrophic factors can be considered strong candidates for autism spectrum disorder (ASD). The serotoninergic and dopaminergic systems are involved in neurotransmission, brain maturation and cortical organization, while neurotrophic factors (NTFs) participate in neurodevelopment, neuronal survival and synapses formation. We aimed to test the contribution of these candidate pathways to autism through a case–control association study of genes selected both for their role in central nervous system functions and for pathophysiological evidences. Methods. The study sample consisted of 326 unrelated autistic patients and 350 gender-matched controls from Spain. We genotyped 369 tagSNPs to perform a case-control association study of 37 candidate genes. Results. A significant association was obtained between the DDC gene and autism in the single-marker analysis (rs6592961, P = 0.00047). Haplotype-based analysis pinpointed a four-marker combination in this gene associated with the disorder (rs2329340C–rs2044859T–rs6592961A–rs11761683T, P = 4.988e-05). No significant results were obtained for the remaining genes after applying multiple testing corrections. However, the rs167771 marker in DRD3, associated with ASD in a previous study, displayed a nominal association in our analysis (P = 0.023). Conclusions. Our data suggest that common allelic variants in the DDC gene may be involved in autism susceptibility.
AbstractObjectives: Animal and clinical studies implicated opioid dysfunction in the pathogenesis of alcohol abuse and dependence. The π-opioid antagonist naltrexone reduces craving, eventually modulated by hypothalamic–pituitary–adrenal axis. Altered cortisol response to opioid receptor blockade not only in alcohol dependent persons, but also in persons with a family history of alcohol dependency was reported. Methods: Twenty patients with alcohol dependence who had undergone detoxification were recruited. Naloxone (3.2 mg/70 kg body weight) having a very similar receptor profile to naltrexone and placebo were administered in cross-over fashion on two separate days 48 h apart. Mood and craving was assessed with well-established instruments (Alcohol Craving Questionnaire (ACQ), Profile of Mood Scale (POMS)). Both patients and raters were blind to all treatments. Twelve patients were first treated with naloxone, eight were first treated with placebo. Results: No significant differences were found between the placebo and naloxone groups according to ACQ and POMS. Cortisol levels were significantly higher in naloxone group. Conclusions: We could not replicate the result, that blocking of the endogenous opioid system leads to reduced craving in alcohol-dependent individuals, while increase of cortisol after naloxone challenge is the expected biological effect of opioid receptor blockade on the hypothalamic–pituitary–adrenal (HPA) axis.