A dynamic relation between whole-brain white matter microstructural integrity and anxiety symptoms in preadolescent females with pathological anxiety
Abstract Pathological anxiety typically emerges during preadolescence and has been linked to alterations in white matter (WM) pathways. Because myelination is critical for efficient neuronal communication, characterizing associations between WM microstructure and symptoms may provide insights into p...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-02-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-022-01827-y |
| _version_ | 1819274842350813184 |
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| author | Nakul Aggarwal Lisa E. Williams Do P. M. Tromp Daniel S. Pine Ned H. Kalin |
| author_facet | Nakul Aggarwal Lisa E. Williams Do P. M. Tromp Daniel S. Pine Ned H. Kalin |
| author_sort | Nakul Aggarwal |
| collection | DOAJ |
| description | Abstract Pathological anxiety typically emerges during preadolescence and has been linked to alterations in white matter (WM) pathways. Because myelination is critical for efficient neuronal communication, characterizing associations between WM microstructure and symptoms may provide insights into pathophysiological mechanisms associated with childhood pathological anxiety. This longitudinal study examined 182 girls enrolled between the ages of 9–11 that were treatment-naïve at study entry: healthy controls (n = 49), subthreshold-anxiety disorders (AD) (n = 82), or meeting DSM-5 criteria for generalized, social, and/or separation ADs (n = 51), as determined through structured clinical interview. Anxiety severity was assessed with the Clinical Global Impression Scale and Screen for Child Anxiety and Related Emotional Disorders (SCARED). Participants (n = 182) underwent clinical, behavioral, and diffusion tensor imaging (DTI) assessments at study entry, and those with pathological anxiety (subthreshold-AD and AD, n = 133) were followed longitudinally for up to 3 additional years. Cross-sectional ANCOVAs (182 scans) examining control, subthreshold-AD, and AD participants found no significant relations between anxiety and DTI measurements. However, in longitudinal analyses of girls with pathological anxiety (343 scans), linear mixed-effects models demonstrated that increases in anxiety symptoms (SCARED scores) were associated with reductions in whole-brain fractional anisotropy, independent of age (Std. β (95% CI) = −0.06 (−0.09 to −0.03), F(1, 46.24) = 11.90, P = 0.001). Using a longitudinal approach, this study identified a dynamic, within-participant relation between whole-brain WM microstructural integrity and anxiety in girls with pathological anxiety. Given the importance of WM microstructure in modulating neural communication, this finding suggests the possibility that WM development could be a viable target in the treatment of anxiety-related psychopathology. |
| first_indexed | 2024-12-23T23:14:51Z |
| format | Article |
| id | doaj.art-5c0847d872f64aeb873f95f68675caea |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-12-23T23:14:51Z |
| publishDate | 2022-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-5c0847d872f64aeb873f95f68675caea2022-12-21T17:26:31ZengNature Publishing GroupTranslational Psychiatry2158-31882022-02-0112111110.1038/s41398-022-01827-yA dynamic relation between whole-brain white matter microstructural integrity and anxiety symptoms in preadolescent females with pathological anxietyNakul Aggarwal0Lisa E. Williams1Do P. M. Tromp2Daniel S. Pine3Ned H. Kalin4Department of Psychiatry, University of Wisconsin-MadisonDepartment of Psychiatry, University of Wisconsin-MadisonDepartment of Psychiatry, University of Wisconsin-MadisonSection on Developmental and Affective Neuroscience, National Institute of Mental HealthDepartment of Psychiatry, University of Wisconsin-MadisonAbstract Pathological anxiety typically emerges during preadolescence and has been linked to alterations in white matter (WM) pathways. Because myelination is critical for efficient neuronal communication, characterizing associations between WM microstructure and symptoms may provide insights into pathophysiological mechanisms associated with childhood pathological anxiety. This longitudinal study examined 182 girls enrolled between the ages of 9–11 that were treatment-naïve at study entry: healthy controls (n = 49), subthreshold-anxiety disorders (AD) (n = 82), or meeting DSM-5 criteria for generalized, social, and/or separation ADs (n = 51), as determined through structured clinical interview. Anxiety severity was assessed with the Clinical Global Impression Scale and Screen for Child Anxiety and Related Emotional Disorders (SCARED). Participants (n = 182) underwent clinical, behavioral, and diffusion tensor imaging (DTI) assessments at study entry, and those with pathological anxiety (subthreshold-AD and AD, n = 133) were followed longitudinally for up to 3 additional years. Cross-sectional ANCOVAs (182 scans) examining control, subthreshold-AD, and AD participants found no significant relations between anxiety and DTI measurements. However, in longitudinal analyses of girls with pathological anxiety (343 scans), linear mixed-effects models demonstrated that increases in anxiety symptoms (SCARED scores) were associated with reductions in whole-brain fractional anisotropy, independent of age (Std. β (95% CI) = −0.06 (−0.09 to −0.03), F(1, 46.24) = 11.90, P = 0.001). Using a longitudinal approach, this study identified a dynamic, within-participant relation between whole-brain WM microstructural integrity and anxiety in girls with pathological anxiety. Given the importance of WM microstructure in modulating neural communication, this finding suggests the possibility that WM development could be a viable target in the treatment of anxiety-related psychopathology.https://doi.org/10.1038/s41398-022-01827-y |
| spellingShingle | Nakul Aggarwal Lisa E. Williams Do P. M. Tromp Daniel S. Pine Ned H. Kalin A dynamic relation between whole-brain white matter microstructural integrity and anxiety symptoms in preadolescent females with pathological anxiety Translational Psychiatry |
| title | A dynamic relation between whole-brain white matter microstructural integrity and anxiety symptoms in preadolescent females with pathological anxiety |
| title_full | A dynamic relation between whole-brain white matter microstructural integrity and anxiety symptoms in preadolescent females with pathological anxiety |
| title_fullStr | A dynamic relation between whole-brain white matter microstructural integrity and anxiety symptoms in preadolescent females with pathological anxiety |
| title_full_unstemmed | A dynamic relation between whole-brain white matter microstructural integrity and anxiety symptoms in preadolescent females with pathological anxiety |
| title_short | A dynamic relation between whole-brain white matter microstructural integrity and anxiety symptoms in preadolescent females with pathological anxiety |
| title_sort | dynamic relation between whole brain white matter microstructural integrity and anxiety symptoms in preadolescent females with pathological anxiety |
| url | https://doi.org/10.1038/s41398-022-01827-y |
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