Novel Schizophrenia Risk Gene TCF4 Influences Verbal Learning and Memory Functioning in Schizophrenia Patients

Lennertz, Leonhard; Rujescu, Dan; Wagner, Michael; Frommann, Ingo; Schulze-Rauschenbach, Svenja; Schuhmacher, Anna; Landsberg, Martin W.; Franke, Petra; Möller, Hans‐Jürgen; Wölwer, Wolfgang; Gäebel, Wolfgang; Häfner, Heinz; Maier, Wolfgang; Mößner, Rainald

doi:10.1159/000317844

Cited by 44 publications

(36 citation statements)

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“…The assessed cognitive functions attention and vigilance, working memory, processing speed, visuo-motor speed and set-shifting, and verbal fluency were all unaffected by rs9960767 in both groups (unpublished data). Of note, although TCF4 mutations are clearly related to severely disrupted intellectual functions, no effect of the rs9960767 polymorphism on verbal intelligence or any other neuropsychological function was evident in our sample [21].…”

Section: Tcf4 and Cognitive Endophenotypes Of Schizophreniacontrasting

confidence: 59%

“…Partly based on these findings, we sought to examine the role of the common TCF4 schizophrenia risk variant rs9960767 on verbal memory in a sample of schizophrenia patients [21]. Impaired verbal memory is among the most prominent cognitive deficits of schizophrenia [10].…”

Section: Tcf4 and Cognitive Endophenotypes Of Schizophreniamentioning

confidence: 99%

“…In our study [21], we investigated a sample of 401 schizophrenia patients, all of whom were genotyped for the rs9960767 variant and completed a neuropsychological verbal memory test. Verbal memory was assessed using the Rey Auditory Verbal Memory Test (RAVLT, [17]).…”

Section: Tcf4 and Cognitive Endophenotypes Of Schizophreniamentioning

confidence: 99%

“…The schizophrenia patients were admitted to hospital due to an exacerbation of psychotic symptoms. TCF4 rs9960767 was genotyped as described previously [21]. We assessed the improvement of the PANSS scale and subscales during neuroleptic treatment over four weeks.…”

Section: Pharmacogenetics Of Tcf4mentioning

confidence: 99%

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Impact of TCF4 on the genetics of schizophrenia

Lennertz

Quednow

Benninghoff

et al. 2011

Eur Arch Psychiatry Clin Neurosci

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Mutations of the transcription factor 4 (TCF4) gene cause mental retardation with or without associated facial dysmorphisms and intermittent hyperventilation. Subsequently, a polymorphism of TCF4 was shown in a genome-wide association study to slightly increase the risk of schizophrenia. We have further analysed the impact of this TCF4 variant rs9960767 on early information processing and cognitive functions in schizophrenia patients. We have shown in a sample of 401 schizophrenia patients that TCF4 influences verbal memory in the Rey Auditory Verbal Learning Test. Contrary to expectations, carriers of the schizophrenia-associated allele showed better recognition, thus indicating that while TCF4 influences verbal memory, the TCF4-mediated schizophrenia risk is not determined by the influence of TCF4 on verbal memory. TCF4 does not impact on various other cognitive functions belonging to the domains of attention and executive functions. Moreover, in a pharmacogenetic approach, TCF4 does not modulate the improvement of positive or negative schizophrenia symptoms during treatment with antipsychotics. Finally, we have assessed a key electrophysiological endophenotype of schizophrenia, sensorimotor gating. As measured by prepulse inhibition, the schizophrenia risk allele C of TCF4 rs9960767 reduces sensorimotor gating. This indicates that TCF4 influences key mechanisms of information processing, which may contribute to the pathogenesis of schizophrenia.

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Section: Tcf4 and Cognitive Endophenotypes Of Schizophreniacontrasting

confidence: 59%

Section: Tcf4 and Cognitive Endophenotypes Of Schizophreniamentioning

confidence: 99%

Section: Tcf4 and Cognitive Endophenotypes Of Schizophreniamentioning

confidence: 99%

Section: Pharmacogenetics Of Tcf4mentioning

confidence: 99%

See 2 more Smart Citations

Impact of TCF4 on the genetics of schizophrenia

Lennertz

Quednow

Benninghoff

et al. 2011

Eur Arch Psychiatry Clin Neurosci

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“…Human haploinsufficiency of TCF4 may result in severe cognitive deficiency (ie, mental retardation) in patients with Pitt-Hopkins syndrome (Pitt and Hopkins, 1978) or Angelman syndrome (Takano et al, 2010). However, the role of the TCF4 gene in cognitive deficiency in SCZ patients has seldom been studied (for exceptions, see Lennertz et al (2011); Quednow et al (2011)). …”

Section: Introductionmentioning

confidence: 99%

Associations between TCF4 Gene Polymorphism and Cognitive Functions in Schizophrenia Patients and Healthy Controls

Zhu

Liu

et al. 2012

Neuropsychopharmacol

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The SNP rs2958182 was reported to be significantly associated with schizophrenia (SCZ) in Han Chinese. This study examined this SNP's associations with cognitive functions in 580 SCZ patients and 498 controls. Cognitive functions were assessed using the Wechsler Adult Intelligence Scale-Revised (WAIS-RC), the Attention Network Task (ANT), the Stroop task, the dot pattern expectancy (DPX), task and the N-back working memory task. Results showed significant or marginally significant interaction effects between genotype and diagnosis status on IQ (P ¼ 0.011) and attention-related tasks (ie, the forward digit span of WAIS-RC, P ¼ 0.005; the ANT conflict effect; P ¼ 0.020, and its ratios over mean reaction time (RT), P ¼ 0.036; the Stroop conflict effect, P ¼ 0.032, and its ratios over mean RT, P ¼ 0.062; and the DPX task's error rate under the BX condition, Po0.001, and the error rate of BX minus the error rate of AY (BX À AY), P ¼ 0.002). There were no such interaction effects on the measures of working memory (all P-values 40.05). Further analysis of the significant genotype-by-diagnosis interactions showed that the risk (T) allele was associated with better performance on cognitive tasks in patients but with worse performance in controls. These results seem to indicate that the association between this SNP and selected cognitive functions may be of an inverted U-shaped pattern. Future research is needed to replicate these results and to explore the biochemical mechanisms behind this association.

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Polymorphisms of the TCF4 gene are associated with the risk of schizophrenia in the Han Chinese

Chen

Wang

et al. 2016

American J of Med Genetics Pt B

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Schizophrenia (SCZ) is a complex and severe mental disorder with highly heritability (80%). Several large genome-wide association studies have identified that the transcription factor 4 (TCF4) polymorphisms were strongly associated with SCZ. Therefore, the present study was to replicate the potential relationships between the TCF4 polymorphisms and SCZ. Furthermore, the study also investigated whether other variants were associated with SCZ in the Han Chinese. We conducted a case-control study including 499 patients and 500 healthy controls. Five SNPs were successfully genotyped and evaluated the association with SCZ by using χ test and genetic model analysis. We found that the genotype "AG" of rs9320010 and "GA" of rs7235757 decreased SCZ risk (OR = 0.70, 95%CI = 0.50-0.99, P = 0.041; OR = 0.69, 95%CI = 0.49-0.97, P = 0.034, respectively). In the genetic model analysis, we also observed that the allele "A" of rs9320010 and "G" of rs7235757 were inversely related with the risk of SCZ in the dominant model (OR = 0.72, 95%CI = 0.52-0.98, P = 0.039; OR = 0.69, 95%CI = 0.50-0.96, P = 0.025, respectively). Further interaction and stratification analysis suggested that rs1452787 was notably correlated with increased SCZ risk in males (OR = 2.77, 95%CI = 1.43-5.35, P = 0.002). Our study indicated that rs9320010, rs7235757, and rs1452787 were prominently associated with SCZ. Further studies are required to verify our findings and focus on determining the biological functions of the SNPs. © 2016 Wiley Periodicals, Inc.

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Novel Schizophrenia Risk Gene TCF4 Influences Verbal Learning and Memory Functioning in Schizophrenia Patients

Abstract: mediate recall or total verbal learning. Conclusion: VDM function is influenced by the TCF4 gene in schizophrenia patients. However, the elevated risk for schizophrenia is not conferred by TCF4-mediated VDM impairment.

Cited by 44 publications

References 70 publications

Impact of TCF4 on the genetics of schizophrenia

Impact of TCF4 on the genetics of schizophrenia

Associations between TCF4 Gene Polymorphism and Cognitive Functions in Schizophrenia Patients and Healthy Controls

Polymorphisms of the TCF4 gene are associated with the risk of schizophrenia in the Han Chinese

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