본문 바로가기
KERD
논문KCI 등재

A Disrupted-in-Schizophrenia 1 Gene Variant is Associated with Clinical Symptomatology in Patients with First-Episode Psychosis

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류정신과학

초록

Objective DISC1 gene is one of the main candidate genes for schizophrenia since it has been associated to the illness in several populations. Moreover, variations in several DISC1 polymorphisms, and in particular Ser704Cys SNP, have been associated in schizophrenic patients to structural and functional modifications in two brain areas (pre-frontal cortex and hippocampus) that play a central role in the genesis of psychotic symptoms. This study tested the association between Ser704Cys DISC1 polymorphism and the clinical onset of psychosis. Methods Two hundred and thirteen Caucasian drug-naïve patients experiencing a first episode of non-affective psychosis were genotyped for rs821616 (Ser704Cys) SNP of the DISC1 gene. The clinical severity of the illness was assessed using SAPS and SANS scales. Other clinical and socio-demographic variables were recorded to rule out possible confounding effects. Results Patients homozygous for the Ser allele of the Ser704Cys DISC1 SNP had significantly (p<0.05) higher rates at the positive symptoms dimension (SAPS-SANS scales) and hallucinations item, compared to Cys carriers. Conclusion DISC1 gene variations may modulate the clinical severity of the psychosis at the onset of the disorder.

Abstract

Objective DISC1 gene is one of the main candidate genes for schizophrenia since it has been associated to the illness in several populations. Moreover, variations in several DISC1 polymorphisms, and in particular Ser704Cys SNP, have been associated in schizophrenic patients to structural and functional modifications in two brain areas (pre-frontal cortex and hippocampus) that play a central role in the genesis of psychotic symptoms. This study tested the association between Ser704Cys DISC1 polymorphism and the clinical onset of psychosis. Methods Two hundred and thirteen Caucasian drug-naïve patients experiencing a first episode of non-affective psychosis were genotyped for rs821616 (Ser704Cys) SNP of the DISC1 gene. The clinical severity of the illness was assessed using SAPS and SANS scales. Other clinical and socio-demographic variables were recorded to rule out possible confounding effects. Results Patients homozygous for the Ser allele of the Ser704Cys DISC1 SNP had significantly (p<0.05) higher rates at the positive symptoms dimension (SAPS-SANS scales) and hallucinations item, compared to Cys carriers. Conclusion DISC1 gene variations may modulate the clinical severity of the psychosis at the onset of the disorder.

참고문헌 (42)

  1. St Clair D, "Association within a family of a balanced autosomal translocation with major mental illness", Lancet, 336, pp.13~16 (1990)
  2. Chen QY, "Case-control association study of Disrupted-in-Schizophrenia-1(DISC1) gene and schizophrenia in the Chinese population", J Psychiatr Res, 41, pp.428~434 (2007)
  3. Hashimoto R, "Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signalling", Hum Mol Genet, 15, pp.3024~3033 (2006)
  4. Liu YL, "A single nucleotide polymorphism fine mapping study of chromosome 1q42.1 reveals the vulnerability genes for schizophrenia, GNPAT and DISC1:Association with impairment of sustained attention", Biol Psychiatry, 60, pp.554~562 (2006)
  5. Hennah W, "A haplotype within the DISC1 gene is associated with visual memory functions in families with a high density of schizophrenia", Mol Psychiatry, 10, pp.1097~1103 (2005)
  6. Zhang X, "Association study of the DISC1", TRAX locus with schizophrenia in a Japanese population, 2005, pp.79, 175~180
  7. Callicott JH, "Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia", P Natl Acad Sci U S A, 102, pp.8627~8632 (2005)
  8. Ekelund J, "Replication of 1q42 linkage in Finnish schizophrenia pedigrees", Mol Psychiatry, 9, pp.1037~1041 (2004)
  9. Kockelkorn TT, "Association study of polymorphisms in the 5’ upstream region of human DISC1 gene with schizophrenia", Neurosci Lett, 368, pp.41~45 (2004)
  10. Hodgkinson CA, "Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder", Am J Hum Genet, 75, pp.862~872 (2004)
  11. Hennah W, "Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects", Hum Mol Genet, 12, pp.3151~3159 (2003)
  12. Ekelund J, "Chromosome 1 loci in Finnish schizophrenia families", Hum Mol Genet, 10, pp.1611~1617 (2001)
  13. Hennah W, "The DISC1 pathway modulates expression of neurodevelopmental, synaptogenic and sensory perception genes", PLoS ONE, 4, pp.e4906~ (2009)
  14. Mackie S, "Role of DISC1 in neural development and schizophrenia", Curr Opin Neurobiol, 17, pp.95~102 (2007)
  15. Di Giorgio A, "Association of the Ser704Cys DISC1 polymorphism with human hippocampal formation gray matter and function during memory encoding", Eur J Neurosci, 28, pp.2129~2136 (2008)
  16. Prata DP, "Effect of disrupted-in-schizophrenia-1 on pre-frontal cortical function", Mol Psychiatry, 13, pp.915~917 (2008)
  17. Palo OM, "Association of distinct allelic haplotypes of DISC1 with psychotic and bipolar spectrum disorders and with underlying cognitive impairments", Hum Mol Genet, 16, pp.2517~2528 (2007)
  18. Cannon TD, "Association of DISC1", TRAX haplotypes with schizophrenia, reduced prefrontal gray matter, and impaired short- and long-term memory, 2005, pp.62, 1205~1213
  19. Burdick KE, "DISC1 and neurocognitive function in schizophrenia", Neuroreport, 16, pp.1399~1402 (2005)
  20. Thomson PA, "Deary IJ. Association between genotype at an exonic SNP in DISC1 and normal cognitive aging", Neurosci Lett, 389, pp.41~45 (2005)
  21. Gasperoni TL, "Genetic linkage and association between chromosome 1q and working memory function in schizophrenia", Am J Med Genet B Neuropsychiatr Genet, 116, pp.8~16 (2003)
  22. Mata I, "Additive effect of NRG1 and DISC1genes on lateral ventricle enlargement in first episode schizophrenia", Neuroimage, 53, pp.1016~1022 (2010)
  23. Tomppo L, "Association of variants in DISC1 with psychosis-related traits in a large population cohort", Arch Gen Psychiatry, 66, pp.134~141 (2009)
  24. Szeszko PR, "DISC1 is associated with prefrontal cortical gray matter and positive symptoms in schizophrenia", Biol Psychol, 79, pp.103~110 (2008)
  25. DeRosse P, "Disrupted in schizophrenia 1 genotype and positive symptoms in schizophrenia", Biol Psychiatry, 61, pp.1208~1210 (2007)
  26. Crespo-Facorro B, "A practical clinical trial comparing haloperidol, risperidone, and olanzapine for the acute treatment of first-episode non-affective psychosis", J Clin Psychiatry, 67, pp.1511~1521 (2006)
  27. Andreasen NC, "Scale for the Assessment of Positive Symptoms (SAPS)" (1984), University of Iowa
  28. Andreasen NC, "Scale for the Assessment of Negative Symptoms (SANS)" (1983), University of Iowa
  29. Grube BS, "Meta-analysis of symptom factors in schizophrenia", Schizophr Res, 31, pp.113~120 (1998)
  30. Flaum M, "Symptom dimensions and brain morphology in schizophrenia and related psychotic disorders", J Psychiatr Res, 29, pp.261~276 (1995)
  31. Mouaffak F, "Association of Disrupted in Schizophrenia 1 (DISC1) missense variants with ultra-resistant schizophrenia", Pharmacogenomics J, 11, pp.267~273 (2011)
  32. Chubb JE, "The DISC locus in psychiatric illness", Mol Psychiatry, 13, pp.36~64 (2008)
  33. Camargo LM, "Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia", Mol Psychiatry, 12, pp.74~86 (2007)
  34. Millar JK, "Yeast two-hybrid screens implicate DISC1 in brain development and function", Biochem Biophys Res Commun, 311, pp.1019~1025 (2003)
  35. Sawa A, "Schizophrenia: neural mechanisms for novel therapies", Mol Med, 9, pp.3~9 (2003)
  36. Wang Q, "How has DISC1 enabled drug discovery?", Mol Cell Neurosci, 37, pp.187~195 (2008)
  37. Millar JK, "DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signalling", Science, 310, pp.1187~1191 (2005)
  38. Lipska BK, "Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs", Hum Mol Genet, 15, pp.1245~1258 (2006)
  39. Howes OD, "The dopamine hypothesis of schizophrenia: version III-the final common pathway", Schizophr Bull, 35, pp.549~562 (2009)
  40. Abi-Dargham A, "The Dopamine Hypothesis of Schizophrenia", Schizophrenia Research Forum 2005 (2005)
  41. Soares DC, "DISC1: Structure, Function, and Therapeutic Potential for Major Mental Illness", ACS Chem Neurosci, 2, pp.609~632 (2011)
  42. Takahashi T, "The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain morphology in schizophrenia", Psychiatry Res, 172, pp.128~135 (2009)

관련 논문AI추천

Disrupted-in-Schizophrenia-1 SNPs and Susceptibility to Schizophrenia: Evidence from MalaysiaAbdullah Kartini, Abdul Razak Tariq, A. Talib Norlelawati, Kuzaifah Norsidah, Musa Ramli, Wan Taib Wan Rohani대한신경정신의학회 · PSYCHIATRY INVESTIGATION2015 · 제12권 제1호Neurophyisological and Neurocognitive Endophenotypes for Schizophrenia Genetics Research주연호대한신경정신의학회 · PSYCHIATRY INVESTIGATION2008 · 제5권 제4호Gender-specific Associations of the Brain-derived Neurotrophic Factor Val66Met Polymorphism with Neurocognitive and Clinical Features in Schizophrenia강희주, 김선영, 김성완, 김재민, 배경열, 신일선, 윤진상, 이주연대한정신약물학회 · Clinical Psychopharmacology and Neuroscience2016 · 제14권 제3호Methylome-wide Association Study of Patients with Recent-onset PsychosisBong Ju Lee, Fatima Zahra Rami, Jung-Jin Kim, Ling Li, Maryam Karamikheirabad, Shi Hyun Kang, Sung-Wan Kim, Yan-Hong Piao, Yin Cui, Young-Chul Chung대한정신약물학회 · Clinical Psychopharmacology and Neuroscience2022 · 제20권 제3호Association between FAT Gene and Schizophrenia in the Korean Population전태연, 정영은대한정신약물학회 · Clinical Psychopharmacology and Neuroscience2013 · 제11권 제2호A Review of Brain-derived Neurotrophic Factor as a Candidate Biomarker in SchizophreniaJimmy Lee, Milawaty Nurjono, Siow-Ann Chong대한정신약물학회 · Clinical Psychopharmacology and Neuroscience2012 · 제10권 제2호

이 간행물의 다른 논문 (4건)