Einfluss von Gen und Umwelt auf die psychische Gesundheit – Der Effekt der Risikovariante CACNA1C rs1006737 und relevanter Schizophrenie Umweltrisikofaktoren auf schizotype Merkmale bei gesunden Probanden
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Philipps-Universität Marburg
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Abstract
In the past few years much research has been done on the aetiology of schi-
zophrenia. Many genes associated with the risk of this disease were found in
genome-wide association studies (GWAS), one of them being CACNA1C (Crad-
dock et al., 2005; Burton et al., 2007; Ferreira et al., 2008; Ripke and Schizo-
phrenia Working Group of the Psychiatric Genomics Consortium, 2014), a gene
encoding for a calcium channel and expressed in the CNS (Soldatov, 1994; Ca-
samassima et al., 2010).
Beside the genetic risk factors for schizophrenia, environmental risk factors
were identified such as: childhood trauma, excessive cannabis use during ado-
lescence, migration, obstetric complications, birth in winter, growing up in an
urban environment, having an older father and traumatic brain injury (van Os
et al., 2008). Several risk factors often appear at the same time giving rise
to the question how these risk factors interact and what their joint impact on
schizophrenia is. Gene-environment studies are being conducted to examine
these questions.
Previous studies have shown that the schizotypy personality trait is associa-
ted with an increased vulnerability for schizophrenia (Linney et al., 2003; Mil-
ler et al., 2002). Schizotypy can be assesd using a questionnaire, which is a
helpful tool for research on schizophrenia, especially for early diagnosis and
assessment of the subclinical state.
The aim of this study was to contribute to the research on the subclinical state
of schizophrenia. The genetic risk factor CACNA1C rs1006737 (A-allele) was
chosen for this purpose and environmental risk factors examined were child-
hood trauma, urbanicity, season of birth and age of father. The aim was to ex-
amine the impact of every individual risk factor on the schizotypal personality
trait and the interaction between CACNA1C rs1006737 and each environmen-
tal risk factor. Here the joint impact of the gene and a specific environmental
risk factor on schizotypal personality trait as a marker of vulnerability for schizophrenia was of specific interest.
Data collection was done from May 2010 to December 2011 as part of the
study „Cultural Neuroscience - neuronal processes, social interaction and con-
flicts“ at the Philipps-University, Department of Psychiatry and Psychotherapy
in Marburg (Lahn), Germany.
In total 102 healthy men (50,5%) between the ages of 19 and 38 and 100
healthy women (49,5%) between the ages of 19 and 32 participated in the
study.
A venous blood sample was taken and the participant was genotyped and clas-
sified into CACNA1C risk allele group AA/AG or CACNA1C non-risk allele group
GG.
The environmental risk factors were assessed using the THQ (trauma history
questionnaire) for childhood trauma and a questionnaire for urbanicity, sea-
son of birth and age of father. The level of schizotypy of each participant was
examined using the SPQ-B (Schizotypal Personality Questionnaire-Brief).
In a first step of statistical analysis, either a t-test or an ANOVA was used to
analyse the main effect of the genetic risk factor CACNA1C rs1006737 as well
as of each individual environmental risk factor on schizotypy. In a second step
of statistical analysis, a two-factor variance analysis was used to examine the
joint effect of the genetic risk factor CACNA1C rs1006737 and each environ-
mental risk factor on schizotypy (gene-environment interaction).
A statistically significant effect of the environmental risk factor childhood trauma on schizotypy (p=0,006) was found. Looking at the gene-environment in-
teraction, two significant interactions were seen: the effect of CACNA1C
rs1006737 and childhood trauma (p=0,040), as well as the effect of CACNA1C
rs1006737 and season of birth (p=0,003) on the schizotypal personality trait.
No significant main effect of the genetic risk allele CACNA1C rs1006737 on
schizotypy (p=0,372) was found. The environmental risk factors urbanicity
(p=0,324), age of father (p=0,544) and season of birth (p=0,308) also sho-
wed no significant main effect on schizotypy. The gene-environment interacti-
on between CACNA1C rs1006737 and the age of the father showed a positiv
trend for the group without the genetic risk (GG) (p=0,087). This is the oppo-
site of the expected direction.
This study showed that childhood trauma leads to an increase of schizotypal
personality trait. From this observation it can be assumed that the risk for schizophrenia is increased by this environmental risk factor. The risk allele itself did not show a main effect on schizotypy, however a significant gene-environment
interaction was found for CACNA1C rs1006737 and childhood trauma. Further-
more, information on the interaction of the risk allele CACNA1C rs1006737 and
individual environmental risk factors was collected. There was a significant in-
teraction and synergistic effect of CACNA1C rs1006737 and season of birth
on schizotypy. These two risk factors do not individually influence the risk for
schizotypy significantly, but when occurring together, they mutually reinforce
each other, resulting in higher levels of schizotypy.
In the context of the vulnerability-stress-model a higher vulnerability for schi
zotypy can be assumed by the occurrence of CACNA1C rs 1006737 A-allele.
Through this mechanism the stressors childhood trauma and season of birth
have a higher impact on schizotypy resulting in a higher risk for schizophrenia.
No significant gene-environment interaction between CACNA1C rs1006737 and
urbanicity could be shown. Neither a main effect between these risk factors,
nor an interaction could be observed. This is an interesting finding as previous
studies have shown a gene-urbanicity interaction (Van Os et al., 2003; van
Os et al., 2004; Weiser et al., 2007; Spauwen et al., 2006b). However these
studies used representative genetic markers and not a specific gene or SNP
as was the case in this study. Based on this sample the risk allele CACNA1C
rs1006737 is not involved in a gene-urbanicity interaction.
It would be interesting to examine the interaction between multiple genetic
and environmental risk factors in further studies. For studies with such inter-
action models and numerous variables, reaching statistical power could be
challenging. It is therefore suggested that multicenter studies should be con-
ducted to prove the stability of the findings of this study. Risk factors that can be proven stable in this context may be used in preventive and therapeutic
measures.
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Dates
Created: 2015Issued: 2016-02-25
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
gene-Environment-Interactionschizophreniaenvironmental risk factorCACNA1C rs1006737
DFG-subjects
SchizophrenieCACNA1C rs1006737UmweltfaktorenGen-Umwelt-Interaktion
DDC-Numbers
610
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Drexler, Rebecca: Einfluss von Gen und Umwelt auf die psychische Gesundheit – Der Effekt der Risikovariante CACNA1C rs1006737 und relevanter Schizophrenie Umweltrisikofaktoren auf schizotype Merkmale bei gesunden Probanden. : Philipps-Universität Marburg 2016-02-25. DOI: https://doi.org/10.17192/z2016.0132.
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This item has been published with the following license: In Copyright