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Genetics of generalized anxiety disorder and related traits
Open accessAbstract
This review serves as a systematic guide to the genetics of generalized anxiety disorder (GAD) and further focuses on anxiety-relevant endophenotypes, such as pathological worry fear of uncertainty, and neuroticism. We inspect clinical genetic evidence for the familialityl heritability of GAD and cross-disorder phenotypes based on family and twin studies. Recent advances of linkage studies, genome-wide association studies, and candidate gene studies (eg, 5-HTT, 5-HT1A, MAOA, BDNF) are outlined. Functional and structural neuroimaging and neurophysiological readouts relating to peripheral stress markers and psychophysiology are further integrated, building a multilevel disease framework. We explore etiologic factors in gene-environment interaction approaches investigating childhood trauma, environmental adversity, and stressful life events in relation to selected candidate genes (5-HTT, NPSR1, COMT, MAOA, CRHR1, RGS2), Additionally, the pharmacogenetics of selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor treatment are summarized (5-HTT, 5-HT2A, COMT, CRHR1). Finally, GAD and trait anxiety research challenges and perspectives in the field of genetics, including epigenetics, are discussed.
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“Monozygotic twins 123-126 and first-degree relatives (depending on the number of probands) 127-130 also have an increased likelihood of developing these disorders.”
From Preventive psychiatry: a blueprint for improving the mental health of young people (2021) · cites this paper as [129]
In the citing paper
“clinical genetics have been able to identify various susceptibility genes, including the 5-HT transporter 5-HTT, 5-HT 1A receptor, monoamine oxidase A, catechol-O-methyltransferase, phosphodiesterase 4B and the brain-derived neurotrophic factor (BDNF) gene, involved in specific anxiety-relevant phenotypes and/or in in the aetiology and maintenance of pathological anxiety in a non-specific or disor”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Gottschalk & Domschke, 2017
In the citing paper
“altered DNA methylation patterns in GAD (Gottschalk & Domschke, 2017), PD (Iurato et al., 2017) or adolescents with anxiety disorder (Bortoluzzi et al., 2018) have been found.”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Gottschalk & Domschke, 2017
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Metadata
- Authors
- Gottschalk, M. G., & Domschke, K.
- Affiliations
- Universitätsklinikum Würzburg (DE)
- University of Freiburg (DE)
- Corresponding author
- Domschke, Katharina
- Venue
- Dialogues in Clinical Neuroscience
- Publisher
- Informa UK Limited
- Published
- 2017-06-30
- Volume
- 19
- Issue
- 2
- Pages
- 159-168
- ISSN
- 1294-8322 (ISSN-L)
- 1958-5969
- PMC
- PMC5573560
- OpenAlex
- W2923926520
- Cited by
- 194
- References
- 67
- Citations by year
- 2026: 8 · 2025: 28 · 2024: 25 · 2023: 38 · 2022: 25 · 2021: 23 · 2020: 23 · 2019: 18 · 2018: 6
- FWCI
- 16.63
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- Locations
- Dialogues in Clinical Neuroscience (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (TRR‐58, SFB TRR 58)
- Bundesministerium für Bildung und Forschung (01EE1402A)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- generalized anxiety disorder, endophenotypes, pathological worry, fear of uncertainty, neuroticism, heritability, familial aggregation, twin studies, family studies, linkage analysis, genome-wide association study, candidate genes, serotonin transporter, monoamine oxidase A, brain-derived neurotrophic factor, stress response, psychophysiology, gene-environment interaction, childhood trauma, life events, pharmacogenetics, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, epigenetics, trait anxiety
- MeSH terms
- Anxiety, Anxiety Disorders, Humans, Norepinephrine, Phenotype, Selective Serotonin Reuptake Inhibitors, Genome-Wide Association Study, Gene-Environment Interaction, Neuroimaging
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