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A neurobiological framework of separation anxiety and related phenotypes

A neurobiological framework of separation anxiety and related phenotypes
A neurobiological framework of separation anxiety and related phenotypes

In the DSM-5, separation anxiety disorder (SAD) is newly classified in the chapter on anxiety, renewing research efforts into its etiology. In this narrative review, we summarize the current literature on the genetic, endocrine, physiological, neural and neuropsychological underpinnings of SAD per se, SAD in the context of panic disorder, separation anxiety symptoms, and related intermediate phenotypes. SAD aggregates in families and has a heritability of ~43%. Variants in the oxytocin receptor, serotonin transporter, opioid receptor µ1, dopamine D4 receptor and translocator protein genes have all been associated with SAD. Dysregulation of the hypothalamus-pituitary-adrenal axis, dysfunctional cortico-limbic interaction and biased cognitive processing seem to constitute further neurobiological markers of separation anxiety. Hypersensitivity to carbon dioxide appears to be an endophenotype shared by SAD, panic disorder and anxiety sensitivity. The identification of biological risk markers and its multi-level integration hold great promise regarding the prediction of SAD risk, maintenance and course, and in the future may allow for the selection of indicated preventive and innovative, personalized therapeutic interventions.

Anxiety disorders, CO2 sensitivity, Genetics, Molecular, Panic disorder, Separation anxiety
0924-977X
45-57
Schiele, Miriam A.
3ed65c71-24c9-44ba-a32d-33d630901959
Bandelow, Borwin
2fbbae21-629e-4d76-b5d0-7dff1282d64d
Baldwin, David S.
1beaa192-0ef1-4914-897a-3a49fc2ed15e
Pini, Stefano
d2917a4b-e216-404e-aaff-1c9f5ecb202d
Domschke, Katharina
7c6913b2-7906-4a9e-b3ee-003437dce668
Schiele, Miriam A.
3ed65c71-24c9-44ba-a32d-33d630901959
Bandelow, Borwin
2fbbae21-629e-4d76-b5d0-7dff1282d64d
Baldwin, David S.
1beaa192-0ef1-4914-897a-3a49fc2ed15e
Pini, Stefano
d2917a4b-e216-404e-aaff-1c9f5ecb202d
Domschke, Katharina
7c6913b2-7906-4a9e-b3ee-003437dce668

Schiele, Miriam A., Bandelow, Borwin, Baldwin, David S., Pini, Stefano and Domschke, Katharina (2020) A neurobiological framework of separation anxiety and related phenotypes. European Neuropsychopharmacology, 33, 45-57. (doi:10.1016/j.euroneuro.2020.01.009).

Record type: Review

Abstract

In the DSM-5, separation anxiety disorder (SAD) is newly classified in the chapter on anxiety, renewing research efforts into its etiology. In this narrative review, we summarize the current literature on the genetic, endocrine, physiological, neural and neuropsychological underpinnings of SAD per se, SAD in the context of panic disorder, separation anxiety symptoms, and related intermediate phenotypes. SAD aggregates in families and has a heritability of ~43%. Variants in the oxytocin receptor, serotonin transporter, opioid receptor µ1, dopamine D4 receptor and translocator protein genes have all been associated with SAD. Dysregulation of the hypothalamus-pituitary-adrenal axis, dysfunctional cortico-limbic interaction and biased cognitive processing seem to constitute further neurobiological markers of separation anxiety. Hypersensitivity to carbon dioxide appears to be an endophenotype shared by SAD, panic disorder and anxiety sensitivity. The identification of biological risk markers and its multi-level integration hold great promise regarding the prediction of SAD risk, maintenance and course, and in the future may allow for the selection of indicated preventive and innovative, personalized therapeutic interventions.

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ENP-19-215_revised manuscript_clean_final - Accepted Manuscript
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Accepted/In Press date: 22 January 2020
e-pub ahead of print date: 8 February 2020
Published date: March 2020
Keywords: Anxiety disorders, CO2 sensitivity, Genetics, Molecular, Panic disorder, Separation anxiety

Identifiers

Local EPrints ID: 438497
URI: http://eprints.soton.ac.uk/id/eprint/438497
ISSN: 0924-977X
PURE UUID: 4f97e592-0142-402f-aeeb-489adc537e2f
ORCID for David S. Baldwin: ORCID iD orcid.org/0000-0003-3343-0907

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Date deposited: 11 Mar 2020 17:31
Last modified: 18 Mar 2024 05:26

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Contributors

Author: Miriam A. Schiele
Author: Borwin Bandelow
Author: Stefano Pini
Author: Katharina Domschke

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