Associations of schizophrenia risk genes ZNF804A and CACNA1C with schizotypy and modulation of attention in healthy subjects

Meller, Tina; Schmitt, Simon; Stein, Frederike; Mosebach, Johannes; Yűksel, Dilara; Zaremba, Dario; Grotegerd, Dominik; Dohm, Katharina; Meinert, Susanne; Förster, Katharina; Redlich, Ronny; Repple, Jonathan; Hahn, Tim; Jansen, Andreas; Andlauer, Till F. M.; Forstner, Andreas J.; Heilmann‐Heimbach, Stefanie; Streit, Fabian; Witt, Stephanie H.; Rietschel, Marcella; Müller‐Myhsok, Bertram; Nöthen, Markus M.; Dannlowski, Udo; Krug, Axel; Kircher, Tilo; Nenadić, Igor

doi:10.1016/j.schres.2019.04.018

Cited by 23 publications

(15 citation statements)

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“…As argued by Debbane and Barrantes-Vidal (2015), prospective longitudinal research to date has focused more on positive symptoms and bypassed the potential predictive role of negative schizotypal traits. This is despite the fact that initial clinical developmental studies have shown that different dimensions of schizotypy interact (Debbane & Barrantes-Vidal, 2015), and that differential correlates of schizotypy factors have been uncovered (Meller et al, 2019). The three sub-dimensions of cognitive-perceptual, interpersonal, and disorganized features are factors that are repeatedly observed in CFAs of positive and negative symptoms of schizophrenia (Tibber et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

The Schizotypal Personality Questionnaire for Children (SPQ-C): Factor Structure, Child Abuse, and Family History of Schizotypy

Raine

Wong

Liu

2020

Schizophrenia Bulletin

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There is a relative dearth of research on features of schizotypal personality in children, in part due to lack of instrumentation. This study tests 5 competing models of the factor structure of the self-report Schizotypal Personality Questionnaire for Children (SPQ-C) and examines its relationship with a family history of schizotypal personality disorder (SPD), child abuse, and stability over time. Hypotheses were tested on 454 11- to 12-year-old schoolchildren and their caregivers. Confirmatory factor analyses supported a 3-factor structure of the SPQ-C (cognitive-perceptual, interpersonal, and disorganized). Test-retest stability was relatively robust over 3 months (r = .67), 6 months (r = .64), and 12 months (r = .55), with acceptable internal reliabilities (r = .84 to .91). Regarding construct validity, children with a biological family history of SPD had higher scores on all 3 factors (d =.51). Abused children had higher schizotypy scores (d = .55). A genetic × environment interaction was observed, with schizotypy highest in those with both a family history of schizotypy and also child abuse. Findings are the first in the child schizotypy field to document a gene × environment interaction and the independence of child abuse from confounding genetic influences. Results support the utility of the SPQ-C in future family and clinical studies of schizotypal personality and provide an avenue for much-needed and neglected research into the early antecedents of child schizotypal personality.

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Section: Discussionmentioning

confidence: 99%

The Schizotypal Personality Questionnaire for Children (SPQ-C): Factor Structure, Child Abuse, and Family History of Schizotypy

Raine

Wong

Liu

2020

Schizophrenia Bulletin

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“…Genotyping and calculation of PGSs Genotyping was conducted using the PsychArray BeadChip, followed by quality control and imputation, as described previously [41,42] (Methods S2). Imputed genetic data were available for n = 1146 discovery-stage and n = 556 replicationstage individuals (Fig.…”

Section: Sample Descriptionmentioning

confidence: 99%

Identification of transdiagnostic psychiatric disorder subtypes using unsupervised learning

Pelin

Ising

Stein

et al. 2021

Neuropsychopharmacol.

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Psychiatric disorders show heterogeneous symptoms and trajectories, with current nosology not accurately reflecting their molecular etiology and the variability and symptomatic overlap within and between diagnostic classes. This heterogeneity impedes timely and targeted treatment. Our study aimed to identify psychiatric patient clusters that share clinical and genetic features and may profit from similar therapies. We used high-dimensional data clustering on deep clinical data to identify transdiagnostic groups in a discovery sample (N = 1250) of healthy controls and patients diagnosed with depression, bipolar disorder, schizophrenia, schizoaffective disorder, and other psychiatric disorders. We observed five diagnostically mixed clusters and ordered them based on severity. The least impaired cluster 0, containing most healthy controls, showed general well-being. Clusters 1–3 differed predominantly regarding levels of maltreatment, depression, daily functioning, and parental bonding. Cluster 4 contained most patients diagnosed with psychotic disorders and exhibited the highest severity in many dimensions, including medication load. Depressed patients were present in all clusters, indicating that we captured different disease stages or subtypes. We replicated all but the smallest cluster 1 in an independent sample (N = 622). Next, we analyzed genetic differences between clusters using polygenic scores (PGS) and the psychiatric family history. These genetic variables differed mainly between clusters 0 and 4 (prediction area under the receiver operating characteristic curve (AUC) = 81%; significant PGS: cross-disorder psychiatric risk, schizophrenia, and educational attainment). Our results confirm that psychiatric disorders consist of heterogeneous subtypes sharing molecular factors and symptoms. The identification of transdiagnostic clusters advances our understanding of the heterogeneity of psychiatric disorders and may support the development of personalized treatments.

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“…The results indicated that: i) the main effect of disease factors revealed that the FA value of the right posterior radiocrown in the SZ group was significantly lower than ------------------------------------------------------------ that in the HC group; ii) the main effect of rs1344706 polymorphism in the ZNF804a gene revealed that the FA value of the right lower occipital east and right upper radiocrown were significantly lower; and iii) the interaction of the same gene polymorphism in the SZ group revealed that the FA value of the patient group was significantly lower than that in the control group, Compared with the AA control group, the FA value in the splenium of the corpus callosum, the body part of the corpus callosum part and the right cingulate tract in the gene carrier group was significantly decreased. The findings of Cui et al (16) suggest that ZNF804A affects the resting-state functional activation by interacting with COMT and may improve our understanding of the neurobiological effects of ZNF804A and its association with schizophrenia (16,37). The FA value of the SZ group was significantly lower than that of HC group.…”

Section: Discussionmentioning

confidence: 97%

“…These findings suggest that the local white matter fiber bundle and other micro structure abnormalities of the radiation crown may be related to the pathological mechanism of SZ, however there was no gene correlation. Research by Meller et al which focused on the relationship between ZNF804 gene polymorphism and Alzheimer's disease did not evaluate the clinical indications of patients, but our study focused more on the correlation between ZNF804 gene and clinical manifestations of schizophrenia disease, such as MRI examination and analysis of the white matter of the head of patients (37). Other studies (5,11,12) revealed that the FA value of the right anterior radiocrown was positively correlated to the age of onset, although no decrease in the FA value of the SZ group compared with the HC group was reported.…”

Section: Allele Frequency (%)mentioning

confidence: 99%

rs1344706 polymorphism of zinc finger protein 804a (ZNF804a) gene related to the integrity of white matter fiber bundle in schizophrenics

et al. 2021

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Genetic factors play an important role in the pathogenesis of schizophrenia (SZ), and the zinc finger protein 804a (ZNF804a) gene has been considered to be a risk gene for schizophrenia. In the present study, the correlation between rs1344706 polymorphism of ZNF804a gene and the integrity of white matter in schizophrenic cases was explored. A total of 60 SZ patients and 100 healthy controls (HC) were included to undergo head MRI. According to the genotyping of rs1344706 in ZNF804a, the subjects in each group were divided into a normal allele and risk allele-carrying group. The imaging data were preprocessed by PANDA software, and thefractional anisotropy (FA) of each subject was calculated. With SPM8 software, age and years of education were considered as covariates, and diagnosis as well as genotype (AA, GG/AG) were considered as intergroup factors. Four groups of FA images were analyzed by two-factor analysis of variance. The FA value of the right posterior radiocrown in the patient group was lower than that in the control group, and the difference was statistically significant. The FA value of the right lower frontal occipital tract and the right upper radiocrown in the G allele carrier group was lower than that in the A allele homozygous group. There was detection of an interaction between the FA value of the splenium of corpus callosum, the body part of the corpus callosum and the right cingulate tract. In the present study, it was demonstrated that the rs1344706 GG/AG genotype of the ZNF804a gene locus in SZ patients suffered from abnormal structure in a specific region of the brain. This finding indicated that the rs1344706 single nucleotide polymorphism of the ZNF804a gene may affect the integrity of the white matter of the brain in SZ patients and may be involved in the pathophysiological mechanism of SZ.

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Associations of schizophrenia risk genes ZNF804A and CACNA1C with schizotypy and modulation of attention in healthy subjects

Cited by 23 publications

References 92 publications

The Schizotypal Personality Questionnaire for Children (SPQ-C): Factor Structure, Child Abuse, and Family History of Schizotypy

The Schizotypal Personality Questionnaire for Children (SPQ-C): Factor Structure, Child Abuse, and Family History of Schizotypy

Identification of transdiagnostic psychiatric disorder subtypes using unsupervised learning

rs1344706 polymorphism of zinc finger protein 804a (ZNF804a) gene related to the integrity of white matter fiber bundle in schizophrenics

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