Affect-Modulated Startle: Interactive Influence of Catechol-O-Methyltransferase Val158Met Genotype and Childhood Trauma

Benedikt Klauke; Bernward Winter; Agnes Gajewska; Peter Zwanzger; Andreas Reif; Martin J. Herrmann; Andrea Dlugos; Bodo Warrings; Christian Jacob; Andreas Muehlberger; Volker Arolt; Paul Pauli; Juergen Deckert; Katharina Domschke

doi:10.1371/journal.pone.0039709

Affect-Modulated Startle: Interactive Influence of Catechol-O-Methyltransferase Val158Met Genotype and Childhood Trauma

Benedikt Klauke^*, Bernward Winter, Agnes Gajewska, Peter Zwanzger, Andreas Reif, Martin J. Herrmann, Andrea Dlugos, Bodo Warrings, Christian Jacob, Andreas Muehlberger, Volker Arolt, Paul Pauli, Juergen Deckert, Katharina Domschke

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system--partly conferred by catechol-O-methyltransferase (COMT) gene variation--for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.

Original language	English
Article number	e39709
Journal	PLOS ONE
Volume	7
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0039709
Publication status	Published - 22 Jun 2012

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Klauke, B., Winter, B., Gajewska, A., Zwanzger, P., Reif, A., Herrmann, M. J., Dlugos, A., Warrings, B., Jacob, C., Muehlberger, A., Arolt, V., Pauli, P., Deckert, J., & Domschke, K. (2012). Affect-Modulated Startle: Interactive Influence of Catechol-O-Methyltransferase Val158Met Genotype and Childhood Trauma. PLOS ONE, 7(6), Article e39709. https://doi.org/10.1371/journal.pone.0039709

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title = "Affect-Modulated Startle: Interactive Influence of Catechol-O-Methyltransferase Val158Met Genotype and Childhood Trauma",

abstract = "The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system--partly conferred by catechol-O-methyltransferase (COMT) gene variation--for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.",

author = "Benedikt Klauke and Bernward Winter and Agnes Gajewska and Peter Zwanzger and Andreas Reif and Herrmann, {Martin J.} and Andrea Dlugos and Bodo Warrings and Christian Jacob and Andreas Muehlberger and Volker Arolt and Paul Pauli and Juergen Deckert and Katharina Domschke",

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Klauke, B, Winter, B, Gajewska, A, Zwanzger, P, Reif, A, Herrmann, MJ, Dlugos, A, Warrings, B, Jacob, C, Muehlberger, A, Arolt, V, Pauli, P, Deckert, J & Domschke, K 2012, 'Affect-Modulated Startle: Interactive Influence of Catechol-O-Methyltransferase Val158Met Genotype and Childhood Trauma', PLOS ONE, vol. 7, no. 6, e39709. https://doi.org/10.1371/journal.pone.0039709

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AU - Klauke, Benedikt

AU - Winter, Bernward

AU - Gajewska, Agnes

AU - Zwanzger, Peter

AU - Reif, Andreas

AU - Herrmann, Martin J.

AU - Dlugos, Andrea

AU - Warrings, Bodo

AU - Jacob, Christian

AU - Muehlberger, Andreas

AU - Arolt, Volker

AU - Pauli, Paul

AU - Deckert, Juergen

AU - Domschke, Katharina

PY - 2012/6/22

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N2 - The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system--partly conferred by catechol-O-methyltransferase (COMT) gene variation--for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.

AB - The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system--partly conferred by catechol-O-methyltransferase (COMT) gene variation--for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.

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DO - 10.1371/journal.pone.0039709

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SN - 1932-6203

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