Cortico-limbic connectivity in MAOA-L carriers is vulnerable to acute tryptophan depletion

Patrick Eisner, Martin Klasen, Dhana Wolf, Klaus Zerres, Thomas Eggermann, Albrecht Eisert, Mikhail Zvyagintsev, Pegah Sarkheil, Krystyna A. Mathiak, Florian Zepf, Klaus Mathiak

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    Abstract

    Introduction: A gene–environment interaction between expression genotypes of the monoamine oxidase A (MAOA) and adverse childhood experience increases the risk of antisocial behavior. However, the neural underpinnings of this interaction remain uninvestigated. A cortico-limbic circuit involving the prefrontal cortex (PFC) and the amygdala is central to the suppression of aggressive impulses and is modulated by serotonin (5-HT). MAOA genotypes may modulate the vulnerability of this circuit and increase the risk for emotion regulation deficits after specific life events. Acute tryptophan depletion (ATD) challenges 5-HT regulation and may identify vulnerable neuronal circuits, contributing to the gene–environment interaction. Methods: Functional magnetic resonance imaging measured the resting-state state activity in 64 healthy males in a double-blind, placebo-controlled study. Cortical maps of amygdala correlation identified the impact of ATD and its interaction with low- (MAOA-L) and high-expression variants (MAOA-H) of MAOA on cortico-limbic connectivity. Results: Across all Regions of Interest (ROIs) exhibiting an ATD effect on cortico-limbic connectivity, MAOA-L carriers were more susceptible to ATD than MAOA-H carriers. In particular, the MAOA-L group exhibited a larger reduction of amygdala connectivity with the right prefrontal cortex and a larger increase of amygdala connectivity with the insula and dorsal PCC. Conclusion: MAOA-L carriers were more susceptable to a central 5-HT challenge in cortico-limbic networks. Such vulnerability of the cortical serotonergic system may contribute to the emergence of antisocial behavior after systemic challenges, observed as gene–environment interaction. Hum Brain Mapp 38:1622–1635, 2017.

    Original languageEnglish
    Pages (from-to)1622-1635
    Number of pages14
    JournalHuman Brain Mapping
    Volume38
    Issue number3
    DOIs
    Publication statusPublished - 1 Mar 2017

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    Monoamine Oxidase
    Tryptophan
    Serotonin
    Amygdala
    Prefrontal Cortex
    Genotype
    Risk-Taking
    Emotions
    Placebos
    Magnetic Resonance Imaging
    Brain

    Cite this

    Eisner, P., Klasen, M., Wolf, D., Zerres, K., Eggermann, T., Eisert, A., ... Mathiak, K. (2017). Cortico-limbic connectivity in MAOA-L carriers is vulnerable to acute tryptophan depletion. Human Brain Mapping, 38(3), 1622-1635. https://doi.org/10.1002/hbm.23475
    Eisner, Patrick ; Klasen, Martin ; Wolf, Dhana ; Zerres, Klaus ; Eggermann, Thomas ; Eisert, Albrecht ; Zvyagintsev, Mikhail ; Sarkheil, Pegah ; Mathiak, Krystyna A. ; Zepf, Florian ; Mathiak, Klaus. / Cortico-limbic connectivity in MAOA-L carriers is vulnerable to acute tryptophan depletion. In: Human Brain Mapping. 2017 ; Vol. 38, No. 3. pp. 1622-1635.
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    title = "Cortico-limbic connectivity in MAOA-L carriers is vulnerable to acute tryptophan depletion",
    abstract = "Introduction: A gene–environment interaction between expression genotypes of the monoamine oxidase A (MAOA) and adverse childhood experience increases the risk of antisocial behavior. However, the neural underpinnings of this interaction remain uninvestigated. A cortico-limbic circuit involving the prefrontal cortex (PFC) and the amygdala is central to the suppression of aggressive impulses and is modulated by serotonin (5-HT). MAOA genotypes may modulate the vulnerability of this circuit and increase the risk for emotion regulation deficits after specific life events. Acute tryptophan depletion (ATD) challenges 5-HT regulation and may identify vulnerable neuronal circuits, contributing to the gene–environment interaction. Methods: Functional magnetic resonance imaging measured the resting-state state activity in 64 healthy males in a double-blind, placebo-controlled study. Cortical maps of amygdala correlation identified the impact of ATD and its interaction with low- (MAOA-L) and high-expression variants (MAOA-H) of MAOA on cortico-limbic connectivity. Results: Across all Regions of Interest (ROIs) exhibiting an ATD effect on cortico-limbic connectivity, MAOA-L carriers were more susceptible to ATD than MAOA-H carriers. In particular, the MAOA-L group exhibited a larger reduction of amygdala connectivity with the right prefrontal cortex and a larger increase of amygdala connectivity with the insula and dorsal PCC. Conclusion: MAOA-L carriers were more susceptable to a central 5-HT challenge in cortico-limbic networks. Such vulnerability of the cortical serotonergic system may contribute to the emergence of antisocial behavior after systemic challenges, observed as gene–environment interaction. Hum Brain Mapp 38:1622–1635, 2017.",
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    author = "Patrick Eisner and Martin Klasen and Dhana Wolf and Klaus Zerres and Thomas Eggermann and Albrecht Eisert and Mikhail Zvyagintsev and Pegah Sarkheil and Mathiak, {Krystyna A.} and Florian Zepf and Klaus Mathiak",
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    Eisner, P, Klasen, M, Wolf, D, Zerres, K, Eggermann, T, Eisert, A, Zvyagintsev, M, Sarkheil, P, Mathiak, KA, Zepf, F & Mathiak, K 2017, 'Cortico-limbic connectivity in MAOA-L carriers is vulnerable to acute tryptophan depletion' Human Brain Mapping, vol. 38, no. 3, pp. 1622-1635. https://doi.org/10.1002/hbm.23475

    Cortico-limbic connectivity in MAOA-L carriers is vulnerable to acute tryptophan depletion. / Eisner, Patrick; Klasen, Martin; Wolf, Dhana; Zerres, Klaus; Eggermann, Thomas; Eisert, Albrecht; Zvyagintsev, Mikhail; Sarkheil, Pegah; Mathiak, Krystyna A.; Zepf, Florian; Mathiak, Klaus.

    In: Human Brain Mapping, Vol. 38, No. 3, 01.03.2017, p. 1622-1635.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Cortico-limbic connectivity in MAOA-L carriers is vulnerable to acute tryptophan depletion

    AU - Eisner, Patrick

    AU - Klasen, Martin

    AU - Wolf, Dhana

    AU - Zerres, Klaus

    AU - Eggermann, Thomas

    AU - Eisert, Albrecht

    AU - Zvyagintsev, Mikhail

    AU - Sarkheil, Pegah

    AU - Mathiak, Krystyna A.

    AU - Zepf, Florian

    AU - Mathiak, Klaus

    PY - 2017/3/1

    Y1 - 2017/3/1

    N2 - Introduction: A gene–environment interaction between expression genotypes of the monoamine oxidase A (MAOA) and adverse childhood experience increases the risk of antisocial behavior. However, the neural underpinnings of this interaction remain uninvestigated. A cortico-limbic circuit involving the prefrontal cortex (PFC) and the amygdala is central to the suppression of aggressive impulses and is modulated by serotonin (5-HT). MAOA genotypes may modulate the vulnerability of this circuit and increase the risk for emotion regulation deficits after specific life events. Acute tryptophan depletion (ATD) challenges 5-HT regulation and may identify vulnerable neuronal circuits, contributing to the gene–environment interaction. Methods: Functional magnetic resonance imaging measured the resting-state state activity in 64 healthy males in a double-blind, placebo-controlled study. Cortical maps of amygdala correlation identified the impact of ATD and its interaction with low- (MAOA-L) and high-expression variants (MAOA-H) of MAOA on cortico-limbic connectivity. Results: Across all Regions of Interest (ROIs) exhibiting an ATD effect on cortico-limbic connectivity, MAOA-L carriers were more susceptible to ATD than MAOA-H carriers. In particular, the MAOA-L group exhibited a larger reduction of amygdala connectivity with the right prefrontal cortex and a larger increase of amygdala connectivity with the insula and dorsal PCC. Conclusion: MAOA-L carriers were more susceptable to a central 5-HT challenge in cortico-limbic networks. Such vulnerability of the cortical serotonergic system may contribute to the emergence of antisocial behavior after systemic challenges, observed as gene–environment interaction. Hum Brain Mapp 38:1622–1635, 2017.

    AB - Introduction: A gene–environment interaction between expression genotypes of the monoamine oxidase A (MAOA) and adverse childhood experience increases the risk of antisocial behavior. However, the neural underpinnings of this interaction remain uninvestigated. A cortico-limbic circuit involving the prefrontal cortex (PFC) and the amygdala is central to the suppression of aggressive impulses and is modulated by serotonin (5-HT). MAOA genotypes may modulate the vulnerability of this circuit and increase the risk for emotion regulation deficits after specific life events. Acute tryptophan depletion (ATD) challenges 5-HT regulation and may identify vulnerable neuronal circuits, contributing to the gene–environment interaction. Methods: Functional magnetic resonance imaging measured the resting-state state activity in 64 healthy males in a double-blind, placebo-controlled study. Cortical maps of amygdala correlation identified the impact of ATD and its interaction with low- (MAOA-L) and high-expression variants (MAOA-H) of MAOA on cortico-limbic connectivity. Results: Across all Regions of Interest (ROIs) exhibiting an ATD effect on cortico-limbic connectivity, MAOA-L carriers were more susceptible to ATD than MAOA-H carriers. In particular, the MAOA-L group exhibited a larger reduction of amygdala connectivity with the right prefrontal cortex and a larger increase of amygdala connectivity with the insula and dorsal PCC. Conclusion: MAOA-L carriers were more susceptable to a central 5-HT challenge in cortico-limbic networks. Such vulnerability of the cortical serotonergic system may contribute to the emergence of antisocial behavior after systemic challenges, observed as gene–environment interaction. Hum Brain Mapp 38:1622–1635, 2017.

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    KW - amygdala

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    Eisner P, Klasen M, Wolf D, Zerres K, Eggermann T, Eisert A et al. Cortico-limbic connectivity in MAOA-L carriers is vulnerable to acute tryptophan depletion. Human Brain Mapping. 2017 Mar 1;38(3):1622-1635. https://doi.org/10.1002/hbm.23475