A linkage study of schizophrenia with DNA markers from chromosome 8p21-p22 in 25 multiplex families.
ABSTRACT Two recent genome-wide searches for linkage (Lasseter et al., 1994; Moises et al., 1995) suggested that a susceptibility gene for schizophrenia might be located at chromosome 8p21-p22. We attempted to replicate these findings by performing a linkage study of schizophrenia with four DNA markers from this region using 25 multiply affected families. Neither the lod score method nor non-prametric extended sib-pair analysis yielded any evidence for linkage, even under the assumption of locus heterogeneity. We conclude that there is unlikely to be a major gene in the 8p21-p22 region which confers susceptibility to schizophrenia in our set of families. However we cannot exclude the possibility of a major gene present in other families, or of a susceptibility gene with a moderate but widespread effect which we cannot detect.
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ABSTRACT: Positive linkage of schizophrenia to chromosome 8p22-21 loci had been reported in the Caucasian samples. This study was designed to replicate this finding by using eleven microsatellite markers on chromosome 8p22-21 in 52 Taiwanese schizophrenic families with at least two affected siblings. Two phenotype models (narrow: DSM-IV schizophrenia only; and broad: including schizophrenia, schizoaffective, and other non-affective psychotic disorders) were used to define the disease phenotype. Maximum non-parametric linkage scores (NPL score) of 2.45 (P = 0.008) and 1.89 (P = 0.02) were obtained for the marker D8S1222 under the broad and narrow models, respectively. Positive linkage was found across about a 4-cM region. The marker D8S1222 was about 400 kbp distal to the exon 1 of glial growth factor 2 (GGF2), an isoform of Neuregulin 1 gene (NRG1), which has been highly suggested to be a candidate gene for schizophrenia. The results provide suggestive linkage evidence of schizophrenia to loci near NRG1 on chromosome 8p21 in an ethnically distinct Taiwanese sample. Further exploration of the candidate gene and nearby chromosome regions is warranted.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 05/2005; 134B(1):79-83. · 3.23 Impact Factor
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ABSTRACT: A converging body of evidence implicates the gamma-aminobutyric acid (GABA) neurotransmitter system in the pathogenesis of schizophrenia. The authors review neuroscience literature and clinical studies investigating the role of the GABA system in the pathophysiology of schizophrenia. First, a background on the GABA system is provided, including GABA pharmacology and neuroanatomy of GABAergic neurons. Results from basic science schizophrenia animal models and human studies are reviewed. The role of GABA in cognitive dysfunction in schizophrenia is then presented, followed by a discussion of GABAergic compounds used in monotherapy or adjunctively in clinical schizophrenia studies. In basic studies, reductions in GABAergic neuronal density and abnormalities in receptors and reuptake sites have been identified in several cortical and subcortical GABA systems. A model has been developed suggesting GABA's role (including GABA-dopamine interactions) in schizophrenia. In several clinical studies, the use of adjunctive GABA agonists was associated with greater improvement in core schizophrenia symptoms. Alterations in the GABA neurotransmitter system are found in clinical and basic neuroscience schizophrenia studies as well as animal models and may be involved in the pathophysiology of schizophrenia. The interaction of GABA with other well-characterized neurotransmitter abnormalities remains to be understood. Future studies should elucidate the potential therapeutic role for GABA ligands in schizophrenia treatment.Journal of Clinical Psychopharmacology 01/2004; 23(6):601-40. · 3.51 Impact Factor
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ABSTRACT: Trigonelline (N-methyl-3-carboxypyridinium inner salt, TRG) forms with squaric acid (H2SQ) and water three complexes with TRG:H2SQ:H2O ratios of 3:3:1 (1), 2:2:1 (2) and anhydrous 1:1 (3), which stoichiometry depends on the solvent used for recrystallization. Their structures have been determined by X-ray diffraction, DFT calculations and characterized by FTIR and NMR spectroscopy. Crystals 1 contain three hydrogen-bonded TRG–H2SQ complexes and one water molecule in the asymmetric unit of triclinic space group P1¯. Crystals 2 are monoclinic P21/c space group and contain two hydrogen-bonded TRG–H2SQ complexes and one water molecule. In complexes 1 and 2 water molecule play a role of proton-donors and proton-acceptors in hydrogen bonds. Crystal 3, obtained from 98% ethanol belongs to the monoclinic P21/n space group and has one TRG–H2SQ complex in the asymmetric unit. In the structures of 1–3 complexes there are several short asymmetric OH···O hydrogen bonds (2.428(1)–2.542(1)Å). FTIR spectra are dominated by a broad and intense absorption in the 1600–400cm−1 region, typical of such short hydrogen bonds. The structures of hydrate 2a and anhydrous 3a have been optimized at the B3LYP/6-31G(d,p) level of theory.Journal of Molecular Structure 01/2012; · 1.40 Impact Factor