Altered Neurobiological Processing of Unintentional Social Norm Violations: A Multiplex, Multigenerational Functional Magnetic Resonance Imaging Study on Social Anxiety Endophenotypes

Janna Marie Bas-Hoogendam, Henk van Steenbergen, Renaud L. M. Tissier, Nic J. A. van der Wee, P. Michiel Westenberg

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Patients with social anxiety disorder (SAD) fear negative evaluation in social situations. Specifically, previous work indicated that social anxiety is associated with increased medial prefrontal cortex activation in response to unintentional social norm (SN) transgressions, accompanied by increased embarrassment ratings for such SN violations. Here, we used data from the multiplex, multigenerational LFLSAD (Leiden Family Lab study on Social Anxiety Disorder), which involved two generations of families genetically enriched for SAD, and investigated whether these neurobiological and behavioral correlates of unintentional SN processing are SAD endophenotypes. Of four endophenotype criteria, we examined two: first, the cosegregation of these characteristics with social anxiety (SA) within families of SAD probands (criterion 4), and second, the heritability of the candidate endophenotypes (criterion 3). Methods: Participants (n = 110, age range 9.0–61.5 years, eight families) performed the revised Social Norm Processing Task; functional magnetic resonance imaging data and behavioral ratings related to this paradigm were used to examine whether brain activation in response to processing unintentional SN violations and ratings of embarrassment were associated with SA levels. Next, heritability of these measurements was estimated. Results: As expected, voxelwise functional magnetic resonance imaging analyses revealed positive associations between SA levels and brain activation in the medial prefrontal cortex and medial temporal gyrus, superior temporal gyrus, and superior temporal sulcus, and these brain activation levels displayed moderate to moderately high heritability. Furthermore, although SA levels correlated positively with behavioral ratings of embarrassment for SN transgressions, these behavioral characteristics were not heritable. Conclusions: These results show, for the first time, that brain responses in the medial prefrontal cortex and medial temporal gyrus, superior temporal gyrus, and superior temporal sulcus, related to processing unintentional SN violations, provide a neurobiological candidate endophenotype of SAD.
Original languageEnglish
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
DOIs
Publication statusPublished - 1 Jan 2019
Externally publishedYes

Cite this

@article{c8ba3dca132949208408cae50d64453b,
title = "Altered Neurobiological Processing of Unintentional Social Norm Violations: A Multiplex, Multigenerational Functional Magnetic Resonance Imaging Study on Social Anxiety Endophenotypes",
abstract = "Background: Patients with social anxiety disorder (SAD) fear negative evaluation in social situations. Specifically, previous work indicated that social anxiety is associated with increased medial prefrontal cortex activation in response to unintentional social norm (SN) transgressions, accompanied by increased embarrassment ratings for such SN violations. Here, we used data from the multiplex, multigenerational LFLSAD (Leiden Family Lab study on Social Anxiety Disorder), which involved two generations of families genetically enriched for SAD, and investigated whether these neurobiological and behavioral correlates of unintentional SN processing are SAD endophenotypes. Of four endophenotype criteria, we examined two: first, the cosegregation of these characteristics with social anxiety (SA) within families of SAD probands (criterion 4), and second, the heritability of the candidate endophenotypes (criterion 3). Methods: Participants (n = 110, age range 9.0–61.5 years, eight families) performed the revised Social Norm Processing Task; functional magnetic resonance imaging data and behavioral ratings related to this paradigm were used to examine whether brain activation in response to processing unintentional SN violations and ratings of embarrassment were associated with SA levels. Next, heritability of these measurements was estimated. Results: As expected, voxelwise functional magnetic resonance imaging analyses revealed positive associations between SA levels and brain activation in the medial prefrontal cortex and medial temporal gyrus, superior temporal gyrus, and superior temporal sulcus, and these brain activation levels displayed moderate to moderately high heritability. Furthermore, although SA levels correlated positively with behavioral ratings of embarrassment for SN transgressions, these behavioral characteristics were not heritable. Conclusions: These results show, for the first time, that brain responses in the medial prefrontal cortex and medial temporal gyrus, superior temporal gyrus, and superior temporal sulcus, related to processing unintentional SN violations, provide a neurobiological candidate endophenotype of SAD.",
author = "Bas-Hoogendam, {Janna Marie} and {van Steenbergen}, Henk and Tissier, {Renaud L. M.} and {van der Wee}, {Nic J. A.} and Westenberg, {P. Michiel}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.bpsc.2019.03.003",
language = "English",
journal = "Biological Psychiatry: Cognitive Neuroscience and Neuroimaging",
issn = "2451-9022",
publisher = "Elsevier Inc.",

}

Altered Neurobiological Processing of Unintentional Social Norm Violations: A Multiplex, Multigenerational Functional Magnetic Resonance Imaging Study on Social Anxiety Endophenotypes. / Bas-Hoogendam, Janna Marie; van Steenbergen, Henk; Tissier, Renaud L. M.; van der Wee, Nic J. A.; Westenberg, P. Michiel.

In: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 01.01.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Altered Neurobiological Processing of Unintentional Social Norm Violations: A Multiplex, Multigenerational Functional Magnetic Resonance Imaging Study on Social Anxiety Endophenotypes

AU - Bas-Hoogendam, Janna Marie

AU - van Steenbergen, Henk

AU - Tissier, Renaud L. M.

AU - van der Wee, Nic J. A.

AU - Westenberg, P. Michiel

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Patients with social anxiety disorder (SAD) fear negative evaluation in social situations. Specifically, previous work indicated that social anxiety is associated with increased medial prefrontal cortex activation in response to unintentional social norm (SN) transgressions, accompanied by increased embarrassment ratings for such SN violations. Here, we used data from the multiplex, multigenerational LFLSAD (Leiden Family Lab study on Social Anxiety Disorder), which involved two generations of families genetically enriched for SAD, and investigated whether these neurobiological and behavioral correlates of unintentional SN processing are SAD endophenotypes. Of four endophenotype criteria, we examined two: first, the cosegregation of these characteristics with social anxiety (SA) within families of SAD probands (criterion 4), and second, the heritability of the candidate endophenotypes (criterion 3). Methods: Participants (n = 110, age range 9.0–61.5 years, eight families) performed the revised Social Norm Processing Task; functional magnetic resonance imaging data and behavioral ratings related to this paradigm were used to examine whether brain activation in response to processing unintentional SN violations and ratings of embarrassment were associated with SA levels. Next, heritability of these measurements was estimated. Results: As expected, voxelwise functional magnetic resonance imaging analyses revealed positive associations between SA levels and brain activation in the medial prefrontal cortex and medial temporal gyrus, superior temporal gyrus, and superior temporal sulcus, and these brain activation levels displayed moderate to moderately high heritability. Furthermore, although SA levels correlated positively with behavioral ratings of embarrassment for SN transgressions, these behavioral characteristics were not heritable. Conclusions: These results show, for the first time, that brain responses in the medial prefrontal cortex and medial temporal gyrus, superior temporal gyrus, and superior temporal sulcus, related to processing unintentional SN violations, provide a neurobiological candidate endophenotype of SAD.

AB - Background: Patients with social anxiety disorder (SAD) fear negative evaluation in social situations. Specifically, previous work indicated that social anxiety is associated with increased medial prefrontal cortex activation in response to unintentional social norm (SN) transgressions, accompanied by increased embarrassment ratings for such SN violations. Here, we used data from the multiplex, multigenerational LFLSAD (Leiden Family Lab study on Social Anxiety Disorder), which involved two generations of families genetically enriched for SAD, and investigated whether these neurobiological and behavioral correlates of unintentional SN processing are SAD endophenotypes. Of four endophenotype criteria, we examined two: first, the cosegregation of these characteristics with social anxiety (SA) within families of SAD probands (criterion 4), and second, the heritability of the candidate endophenotypes (criterion 3). Methods: Participants (n = 110, age range 9.0–61.5 years, eight families) performed the revised Social Norm Processing Task; functional magnetic resonance imaging data and behavioral ratings related to this paradigm were used to examine whether brain activation in response to processing unintentional SN violations and ratings of embarrassment were associated with SA levels. Next, heritability of these measurements was estimated. Results: As expected, voxelwise functional magnetic resonance imaging analyses revealed positive associations between SA levels and brain activation in the medial prefrontal cortex and medial temporal gyrus, superior temporal gyrus, and superior temporal sulcus, and these brain activation levels displayed moderate to moderately high heritability. Furthermore, although SA levels correlated positively with behavioral ratings of embarrassment for SN transgressions, these behavioral characteristics were not heritable. Conclusions: These results show, for the first time, that brain responses in the medial prefrontal cortex and medial temporal gyrus, superior temporal gyrus, and superior temporal sulcus, related to processing unintentional SN violations, provide a neurobiological candidate endophenotype of SAD.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31031203

U2 - 10.1016/j.bpsc.2019.03.003

DO - 10.1016/j.bpsc.2019.03.003

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SN - 2451-9022

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