The Experts below are selected from a list of 4326 Experts worldwide ranked by ideXlab platform

Richard P Ebstein - One of the best experts on this subject based on the ideXlab platform.

  • serotonin and early life stress interact to shape brain architecture and Anxious avoidant behavior a tph2 imaging genetics approach
    Psychological Medicine, 2020
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein
    Abstract:

    Background Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2) and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by Anxious Avoidance. Methods The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). Results Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. Conclusions The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment.

  • serotonin and childhood maltreatment interact to shape brain architecture and Anxious avoidant behavior a tph2 imaging genetics approach
    bioRxiv, 2019
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein, Shuxia Yao, Keith M Kendrick
    Abstract:

    Background: Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2), and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by Anxious Avoidance. Methods: The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). Results: Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. Conclusions: The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment. Keywords: amygdala, early life stress, punishment sensitivity, frontal cortex, serotonin

  • gene environment interaction a tph2 polymorphism and early life stress shape brain architecture and Anxious avoidant behavior
    bioRxiv, 2019
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein, Keith M Kendrick
    Abstract:

    Abstract Serotonin regulates developmental and experience-dependent neuroplasticity in limbic-prefrontal systems engaged in emotional reactivity and regulation. Tryptophan hydroxylase 2 (TPH2) regulates central serotonergic biosynthesis rates and transgenic animal models suggest that TPH2-associated changes in serotonergic signaling mediate the impact of early life stress (ELS) shaping a phenotype characterized by Anxious Avoidance. The present study employed an imaging genomics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of ELS on brain structure and function and punishment sensitivity in humans (n = 252). Higher ELS exposure was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. On the phenotype level, the genotype moderated the association between higher ELS exposure and higher punishment sensitivity. In TT carriers, the association between higher ELS exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. The present findings suggest that ELS shapes the neural organization of the thalamic-limbic-prefrontal circuits in interaction with individual variations in TPH2 to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment.

Christian Montag - One of the best experts on this subject based on the ideXlab platform.

  • serotonin and early life stress interact to shape brain architecture and Anxious avoidant behavior a tph2 imaging genetics approach
    Psychological Medicine, 2020
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein
    Abstract:

    Background Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2) and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by Anxious Avoidance. Methods The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). Results Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. Conclusions The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment.

  • serotonin and childhood maltreatment interact to shape brain architecture and Anxious avoidant behavior a tph2 imaging genetics approach
    bioRxiv, 2019
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein, Shuxia Yao, Keith M Kendrick
    Abstract:

    Background: Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2), and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by Anxious Avoidance. Methods: The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). Results: Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. Conclusions: The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment. Keywords: amygdala, early life stress, punishment sensitivity, frontal cortex, serotonin

  • gene environment interaction a tph2 polymorphism and early life stress shape brain architecture and Anxious avoidant behavior
    bioRxiv, 2019
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein, Keith M Kendrick
    Abstract:

    Abstract Serotonin regulates developmental and experience-dependent neuroplasticity in limbic-prefrontal systems engaged in emotional reactivity and regulation. Tryptophan hydroxylase 2 (TPH2) regulates central serotonergic biosynthesis rates and transgenic animal models suggest that TPH2-associated changes in serotonergic signaling mediate the impact of early life stress (ELS) shaping a phenotype characterized by Anxious Avoidance. The present study employed an imaging genomics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of ELS on brain structure and function and punishment sensitivity in humans (n = 252). Higher ELS exposure was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. On the phenotype level, the genotype moderated the association between higher ELS exposure and higher punishment sensitivity. In TT carriers, the association between higher ELS exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. The present findings suggest that ELS shapes the neural organization of the thalamic-limbic-prefrontal circuits in interaction with individual variations in TPH2 to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment.

Dirk Scheele - One of the best experts on this subject based on the ideXlab platform.

  • serotonin and early life stress interact to shape brain architecture and Anxious avoidant behavior a tph2 imaging genetics approach
    Psychological Medicine, 2020
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein
    Abstract:

    Background Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2) and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by Anxious Avoidance. Methods The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). Results Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. Conclusions The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment.

  • serotonin and childhood maltreatment interact to shape brain architecture and Anxious avoidant behavior a tph2 imaging genetics approach
    bioRxiv, 2019
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein, Shuxia Yao, Keith M Kendrick
    Abstract:

    Background: Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2), and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by Anxious Avoidance. Methods: The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). Results: Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. Conclusions: The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment. Keywords: amygdala, early life stress, punishment sensitivity, frontal cortex, serotonin

  • gene environment interaction a tph2 polymorphism and early life stress shape brain architecture and Anxious avoidant behavior
    bioRxiv, 2019
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein, Keith M Kendrick
    Abstract:

    Abstract Serotonin regulates developmental and experience-dependent neuroplasticity in limbic-prefrontal systems engaged in emotional reactivity and regulation. Tryptophan hydroxylase 2 (TPH2) regulates central serotonergic biosynthesis rates and transgenic animal models suggest that TPH2-associated changes in serotonergic signaling mediate the impact of early life stress (ELS) shaping a phenotype characterized by Anxious Avoidance. The present study employed an imaging genomics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of ELS on brain structure and function and punishment sensitivity in humans (n = 252). Higher ELS exposure was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. On the phenotype level, the genotype moderated the association between higher ELS exposure and higher punishment sensitivity. In TT carriers, the association between higher ELS exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. The present findings suggest that ELS shapes the neural organization of the thalamic-limbic-prefrontal circuits in interaction with individual variations in TPH2 to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment.

Congcong Liu - One of the best experts on this subject based on the ideXlab platform.

  • serotonin and early life stress interact to shape brain architecture and Anxious avoidant behavior a tph2 imaging genetics approach
    Psychological Medicine, 2020
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein
    Abstract:

    Background Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2) and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by Anxious Avoidance. Methods The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). Results Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. Conclusions The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment.

  • serotonin and childhood maltreatment interact to shape brain architecture and Anxious avoidant behavior a tph2 imaging genetics approach
    bioRxiv, 2019
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein, Shuxia Yao, Keith M Kendrick
    Abstract:

    Background: Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2), and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by Anxious Avoidance. Methods: The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). Results: Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. Conclusions: The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment. Keywords: amygdala, early life stress, punishment sensitivity, frontal cortex, serotonin

  • gene environment interaction a tph2 polymorphism and early life stress shape brain architecture and Anxious avoidant behavior
    bioRxiv, 2019
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein, Keith M Kendrick
    Abstract:

    Abstract Serotonin regulates developmental and experience-dependent neuroplasticity in limbic-prefrontal systems engaged in emotional reactivity and regulation. Tryptophan hydroxylase 2 (TPH2) regulates central serotonergic biosynthesis rates and transgenic animal models suggest that TPH2-associated changes in serotonergic signaling mediate the impact of early life stress (ELS) shaping a phenotype characterized by Anxious Avoidance. The present study employed an imaging genomics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of ELS on brain structure and function and punishment sensitivity in humans (n = 252). Higher ELS exposure was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. On the phenotype level, the genotype moderated the association between higher ELS exposure and higher punishment sensitivity. In TT carriers, the association between higher ELS exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. The present findings suggest that ELS shapes the neural organization of the thalamic-limbic-prefrontal circuits in interaction with individual variations in TPH2 to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment.

Cornelia Sindermann - One of the best experts on this subject based on the ideXlab platform.

  • serotonin and early life stress interact to shape brain architecture and Anxious avoidant behavior a tph2 imaging genetics approach
    Psychological Medicine, 2020
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein
    Abstract:

    Background Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2) and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by Anxious Avoidance. Methods The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). Results Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. Conclusions The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment.

  • serotonin and childhood maltreatment interact to shape brain architecture and Anxious avoidant behavior a tph2 imaging genetics approach
    bioRxiv, 2019
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein, Shuxia Yao, Keith M Kendrick
    Abstract:

    Background: Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2), and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by Anxious Avoidance. Methods: The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). Results: Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. Conclusions: The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment. Keywords: amygdala, early life stress, punishment sensitivity, frontal cortex, serotonin

  • gene environment interaction a tph2 polymorphism and early life stress shape brain architecture and Anxious avoidant behavior
    bioRxiv, 2019
    Co-Authors: Congcong Liu, Feng Zhou, Xi Yang, Xiaoxiao Zheng, Cornelia Sindermann, Christian Montag, Dirk Scheele, Richard P Ebstein, Keith M Kendrick
    Abstract:

    Abstract Serotonin regulates developmental and experience-dependent neuroplasticity in limbic-prefrontal systems engaged in emotional reactivity and regulation. Tryptophan hydroxylase 2 (TPH2) regulates central serotonergic biosynthesis rates and transgenic animal models suggest that TPH2-associated changes in serotonergic signaling mediate the impact of early life stress (ELS) shaping a phenotype characterized by Anxious Avoidance. The present study employed an imaging genomics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of ELS on brain structure and function and punishment sensitivity in humans (n = 252). Higher ELS exposure was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. On the phenotype level, the genotype moderated the association between higher ELS exposure and higher punishment sensitivity. In TT carriers, the association between higher ELS exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. The present findings suggest that ELS shapes the neural organization of the thalamic-limbic-prefrontal circuits in interaction with individual variations in TPH2 to promote a phenotype characterized by facilitated threat Avoidance, thus promoting early adaptation to an adverse environment.