Polymorphisms in schizophrenia candidate gene UFD1L may contribute to cognitive deficits

Ota, Vanessa Kiyomi; Berberian, Arthur de Almeida; Gadelha, Ary; Santoro, Marcos; Ottoni, Gustavo L.; Matsuzaka, Camila T.; Mari, Jair J.; Melaragno, Maria Isabel; Lara, Diogo R.; Smith, Marı́lia de Arruda Cardoso; Belangero, Síntia Iole; Bressan, Rodrigo A.

doi:10.1016/j.psychres.2013.03.035

Cited by 5 publications

(5 citation statements)

References 33 publications

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“…UFD1L SNP, rs5992403, has been associated with schizophrenia (De Luca et al 2001), with earlyonset of the disorder (Ota et al 2010) and with a defi cit in the set-shifting task (which represents a defi cit in fundamental dimensions of cognition in schizophrenia) (Ota et al 2013). Moreover, its genomic region (22q11.2) is deleted in DiGeorge syndrome, which is considered one of the main genetic risk factors, beside monozygotic twins, for schizophrenia ( ∼ 25% displays psychotic symptoms in early adulthood) (Bassett et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Gene expression analysis in blood of ultra-high risk subjects compared to first-episode of psychosis patients and controls

Santoro

Gadelha

Ota

et al. 2015

The World Journal of Biological Psychiatry

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These genes are directly related to neurodevelopmental processes and have been associated to schizophrenia. Recent findings described that DISC1 overexpression can disrupt MBP expression, thus, we think that these alterations in UHR individuals could be associated with a common process. UFD1L showed a different pattern of expression only for UHR group, suggesting that they can be under an acute endoplasmatic reticulum stress, demanding elevated levels of Ufd1. Further studies can improve knowledge on disease progression and putative targets to preventive strategies.

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Section: Discussionmentioning

confidence: 99%

Gene expression analysis in blood of ultra-high risk subjects compared to first-episode of psychosis patients and controls

Santoro

Gadelha

Ota

et al. 2015

The World Journal of Biological Psychiatry

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“…Neuroimaging data from healthy individuals support the unity/diversity model in that the updating mechanism appears to mainly recruit areas in the lateral prefrontal cortex,12 that switching between mental sets is thought to depend on the medial prefrontal cortex,13 and that inhibition tasks mainly activate the orbitofrontal cortex 14. In schizophrenia, some of these skills present consistent evidence of impairment,15 -17 association with diagnostic gene candidates,18,19 association with peripheral levels of chemokines, brain-derived neurotrophic factor (BDNF) and oxidative markers,20 and potentially available homologous animal models 21…”

Section: Introductionmentioning

confidence: 84%

Component mechanisms of executive function in schizophrenia and their contribution to functional outcomes

Berberian

Gadelha

Dias

et al. 2019

Braz. J. Psychiatry

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Objective:In schizophrenia, scores reflecting deficits in different cognitive processes are strongly correlated, making it difficult to establish a solid relationship between different cognitive mechanisms and other features of this disorder. The objective of this study was to explore whether three frequently postulated executive functions (updating, shifting, and inhibition) could be compared between groups and considered independently in terms of their respective roles in functional outcome.Methods:This study relied on confirmatory factor analysis of schizophrenia patients (n=141) and healthy controls (n=119). The main analyses examined the degree to which three executive functions (updating, set-shifting, and inhibition) could be separated in schizophrenia and compared this model among groups. Structural equation modeling analysis was also performed to examine the extent to which executive function components contribute to functional outcome in schizophrenia.Results:Multiple-group confirmatory factor analysis with unconstrained model parameters indicated that the full three-factor model may fit the data in both groups (χ2 = 61.48, degrees of freedom = 34, p < 0.001, comparative fit index = 0.95; standardized root mean square residual = 0.037; root mean square error of approximation = 0.04; Akaike’s information criteria = 169.49; normed fit index = 0.90), although there was also a good data fit for the patient group with a two-factor model. In the patient group, structural equation modeling suggested that shifting and (principally) updating were associated with the general measure of functional outcome (regression path coefficients: 0.34, p < 0.005; 0.39, p < 0.005, respectively), although when combined the mechanisms fail to contribute.Conclusion:This data suggests that the factor structure may be similar but not identical between groups, and both updating and shifting may play an important role in functional outcome in schizophrenia.

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“…Moreover, UFD1L gene expression was reported to be upregulated in the blood cells of ultra-high-risk subjects (Santoro et al, 2015). As for a role in cognition, only one study reported that rs5992403 AA genotype carriers had higher preservation error scores in the Wisconsin Card Sorting test (Ota et al, 2013). CDC45 , the human homolog of a yeast cell cycle protein, is located in a genomic region telomeric and adjacent to UFD1L (McKie et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Association of genetic variants at 22q11.2 chromosomal region with cognitive performance in Japanese patients with schizophrenia

Akiyama

Saito

Saitô

et al. 2019

Schizophrenia Research: Cognition

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22q11.2 heterozygous multigene deletions confer an increased risk of schizophrenia with marked impairment of cognition. We explored whether genes on 22q11.2 are associated with cognitive performance in patients with idiopathic schizophrenia. A total of 240 schizophrenia patients and 240 healthy controls underwent the Japanese-language version of the Brief Assessment of Cognition in Schizophrenia (BACS) and were genotyped for 115 tag single-nucleotide polymorphisms (tag SNPs) at the 22q11.2 region using the golden gate assay (Illumina®). Associations between z-scores of the BACS cognitive domains and SNPs and haplotypes were analyzed using linear regression in PLINK 1.07. An additional set of 149 patients with bipolar disorder were included for cognitive assessment and selected SNPs were genotyped using real-time PCR. Patients with schizophrenia and bipolar disorder showed qualitatively comparable profiles of cognitive impairment across BACS subdomains, as revealed by significant correlation between the two groups in the resulting cognitive effect sizes relative to controls. rs4819522 ( TBX1 ) and rs2238769 ( UFD1L ) were significantly and nominally associated, respectively, with symbol coding in patients with schizophrenia. Haplotype analyses revealed that haplotypes containing the A allele at rs4819522 and G allele at rs2238769 showed significant negative associations with symbol coding in patients with schizophrenia. There was no effect of any haplotypes on cognition in patients with bipolar disorder. Our results have implications for the understanding of the role of haplotypes of UFD1L and TBX1 genes associated with symbol coding in patients with schizophrenia. Further replication studies in a cohort of newly diagnosed patients and other ethnicities are warranted.

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Polymorphisms in schizophrenia candidate gene UFD1L may contribute to cognitive deficits

Cited by 5 publications

References 33 publications

Gene expression analysis in blood of ultra-high risk subjects compared to first-episode of psychosis patients and controls

Gene expression analysis in blood of ultra-high risk subjects compared to first-episode of psychosis patients and controls

Component mechanisms of executive function in schizophrenia and their contribution to functional outcomes

Association of genetic variants at 22q11.2 chromosomal region with cognitive performance in Japanese patients with schizophrenia

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