The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain morphology in schizophrenia

Takahashi, Tsutomu; Suzuki, Michio; Tsunoda, Masahiko; Maeno, Norikazu; Kawasaki, Yasuhiro; Zhou, Shiyu; Hagino, Hirofumi; Niu, Lisha; Tsuneki, Hiroshi; Kobayashi, Soushi; Sasaoka, Toshiyasu; Seto, Hikaru; Kurachi, Masayoshi; Ozaki, Norio

doi:10.1016/j.pscychresns.2009.01.005

Cited by 45 publications

(35 citation statements)

References 53 publications

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“…Groups did not differ in genotype distribution (c 2 (6) ¼ 3.36, p ¼ 0.76). We compared Cys-carriers (Cys/Cys-and Cys/Ser-genotypes) with Ser-homozygotes, based on the small amount of Cys-homozygotes and in agreement with the literature (Hashimoto et al, 2006;Callicott et al, 2005;Di Giorgio et al, 2008;Prata et al, 2008;Brauns et al, 2011;Takahashi et al, 2009). …”

Section: Genotypingmentioning

confidence: 59%

“…Supportive of this suggestion, in healthy people, the Cys-allele of the Ser704Cys SNP has been associated with less hippocampal activation during working memory (WM) and more hippocampal activation during episodic memory (Callicott et al, 2005), and with less activation of the dorsolateral prefrontal cortex (DLPFC) during both memory (Di Giorgio et al, 2008) and executive functioning . Moreover, smaller hippocampus (Di Giorgio et al, 2008) and anterior cingulate cortex (ACC) volume (Hashimoto et al, 2006) have been demonstrated in Cys-carriers, whereas larger DLPFC volume has been observed (Brauns et al, 2011;Takahashi et al, 2009). These observations suggest that DISC1-genotype is involved in functioning and structure of hippocampal, ACC and prefrontal regions.…”

Section: Introductionmentioning

confidence: 90%

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DISC1 gene and affective psychopathology: A combined structural and functional MRI study

Opmeer

Tol

Kortekaas

et al. 2015

Journal of Psychiatric Research

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The gene Disrupted-In-Schizophrenia-1 (DISC1) has been indicated as a determinant of psychopathology, including affective disorders, and shown to influence prefrontal cortex (PFC) and hippocampus functioning, regions of major interest for affective disorders. We aimed to investigate whether DISC1 differentially modulates brain function during executive and memory processing, and morphology in regions relevant for depression and anxiety disorders (affective disorders). 128 participants, with (n = 103) and without (controls; n = 25) affective disorders underwent genotyping for Ser704Cys (with Cys-allele considered as risk-allele) and structural and functional (f) Magnetic Resonance Imaging (MRI) during visuospatial planning and emotional episodic memory tasks. For both voxel-based morphometry and fMRI analyses, we investigated the effect of genotype in controls and explored genotypeXdiagnosis interactions. Results are reported at p < 0.05 FWE small volume corrected. In controls, Cys-carriers showed smaller bilateral (para)hippocampal volumes compared with Ser-homozygotes, and lower activation in the anterior cingulate cortex (ACC) and dorsolateral PFC during visuospatial planning. In anxiety patients, Cys-carriers showed larger (para)hippocampal volumes and more ACC activation during visuospatial planning. In depressive patients, no effect of genotype was observed and overall, no effect of genotype on episodic memory processing was detected. We demonstrated that Ser704Cys-genotype influences (para)hippocampal structure and functioning the dorsal PFC during executive planning, most prominently in unaffected controls. Results suggest that presence of psychopathology moderates Ser704Cys effects.

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Section: Genotypingmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 90%

DISC1 gene and affective psychopathology: A combined structural and functional MRI study

Opmeer

Tol

Kortekaas

et al. 2015

Journal of Psychiatric Research

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“…Several groups have found SNPs or other lesions in the DISC1 gene, and several linkage studies have associated the DISC1 locus with schizophrenia in cohorts that are not enriched for the DISC1 translocation (Callicott et al, 2005;Chakirova et al, 2011;Eastwood et al, 2010;Szeszko et al, 2008;Takahashi et al, 2009) (reviewed by Roberts (2007)). The DISC1 protein has multiple functions that likely underlie cognitive function.…”

Section: Data From Disc1 Postmortem Studiesmentioning

confidence: 99%

Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

McCullumsmith

Hammond

Shan

et al. 2013

Neuropsychopharmacol

108

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We propose that postmortem tissue is an underutilized substrate that may be used to translate genetic and/or preclinical studies, particularly for neuropsychiatric illnesses with complex etiologies. Postmortem brain tissues from subjects with schizophrenia have been extensively studied, and thus serve as a useful vehicle for illustrating the challenges associated with this biological substrate. Schizophrenia is likely caused by a combination of genetic risk and environmental factors that combine to create a disease phenotype that is typically not apparent until late adolescence. The complexity of this illness creates challenges for hypothesis testing aimed at understanding the pathophysiology of the illness, as postmortem brain tissues collected from individuals with schizophrenia reflect neuroplastic changes from a lifetime of severe mental illness, as well as treatment with antipsychotic medications. While there are significant challenges with studying postmortem brain, such as the postmortem interval, it confers a translational element that is difficult to recapitulate in animal models. On the other hand, data derived from animal models typically provide specific mechanistic and behavioral measures that cannot be generated using human subjects. Convergence of these two approaches has led to important insights for understanding molecular deficits and their causes in this illness. In this review, we discuss the problem of schizophrenia, review the common challenges related to postmortem studies, discuss the application of biochemical approaches to this substrate, and present examples of postmortem schizophrenia studies that illustrate the role of the postmortem approach for generating important new leads for understanding the pathophysiology of severe mental illness.

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“…We cannot, nevertheless, preclude a role of this polymorphism in treatment response given its reported involvement in structural and functional brain alterations, 29,52 as well as its suggested relevance to the effect of antipsychotics on brain morphology. 52 Overall, our results suggest a potential role of DISC1 variants, and especially of the rs3738401 polymorphism in a subset of patients suffering from URS. As mentioned above, rs3738401 is included in the haplotype HEP3, previously associated with cognitive dimensions in schizophrenia.…”

Section: Association Of Disc1 Missense Variants With Ursmentioning

confidence: 95%

Association of Disrupted in Schizophrenia 1 (DISC1) missense variants with ultra-resistant schizophrenia

et al. 2010

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The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain morphology in schizophrenia

Cited by 45 publications

References 53 publications

DISC1 gene and affective psychopathology: A combined structural and functional MRI study

DISC1 gene and affective psychopathology: A combined structural and functional MRI study

Postmortem Brain: An Underutilized Substrate for Studying Severe Mental Illness

Association of Disrupted in Schizophrenia 1 (DISC1) missense variants with ultra-resistant schizophrenia

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