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Whole-cortex mapping of common genetic influences on depression and a social deficits dimension
Social processes are associated with depression, particularly understanding and responding to others, deficits in which can manifest as callousness/unemotionality (CU). Thus, CU may reflect some of the genetic risk to depression. Further, this vulnerability likely reflects the neurological substrate...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856353/ https://www.ncbi.nlm.nih.gov/pubmed/31727881 http://dx.doi.org/10.1038/s41398-019-0611-6 |
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author | Hatoum, Alexander S. Reineberg, Andrew E. Smolker, Harry R. Hewitt, John K. Friedman, Naomi P. |
author_facet | Hatoum, Alexander S. Reineberg, Andrew E. Smolker, Harry R. Hewitt, John K. Friedman, Naomi P. |
author_sort | Hatoum, Alexander S. |
collection | PubMed |
description | Social processes are associated with depression, particularly understanding and responding to others, deficits in which can manifest as callousness/unemotionality (CU). Thus, CU may reflect some of the genetic risk to depression. Further, this vulnerability likely reflects the neurological substrates of depression, presenting biomarkers to capture genetic vulnerability of depression severity. However, heritability varies within brain regions, so a high-resolution genetic perspective is needed. We developed a toolbox that maps genetic and environmental associations between brain and behavior at high resolution. We used this toolbox to estimate brain areas that are genetically associated with both depressive symptoms and CU in a sample of 258 same-sex twin pairs from the Colorado Longitudinal Twin Study (LTS). We then overlapped the two maps to generate coordinates that allow for tests of downstream effects of genes influencing our clusters. Genetic variance influencing cortical thickness in the right dorsal lateral prefrontal cortex (DLFPC) sulci and gyri, ventral posterior cingulate cortex (PCC), pre-somatic motor cortex (PreSMA), medial precuneus, left occipital-temporal junction (OTJ), parietal–temporal junction (PTJ), ventral somatosensory cortex (vSMA), and medial and lateral precuneus were genetically associated with both depression and CU. Split-half replication found support for both DLPFC clusters. Meta-analytic term search identified “theory of mind”, “inhibit”, and “pain” as likely functions. Gene and transcript mapping/enrichment analyses implicated calcium channels. CU reflects genetic vulnerability to depression that likely involves executive and social functioning in a distributed process across the cortex. This approach works to unify neuroimaging, neuroinformatics, and genetics to discover pathways to psychiatric vulnerability. |
format | Online Article Text |
id | pubmed-6856353 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68563532019-11-21 Whole-cortex mapping of common genetic influences on depression and a social deficits dimension Hatoum, Alexander S. Reineberg, Andrew E. Smolker, Harry R. Hewitt, John K. Friedman, Naomi P. Transl Psychiatry Article Social processes are associated with depression, particularly understanding and responding to others, deficits in which can manifest as callousness/unemotionality (CU). Thus, CU may reflect some of the genetic risk to depression. Further, this vulnerability likely reflects the neurological substrates of depression, presenting biomarkers to capture genetic vulnerability of depression severity. However, heritability varies within brain regions, so a high-resolution genetic perspective is needed. We developed a toolbox that maps genetic and environmental associations between brain and behavior at high resolution. We used this toolbox to estimate brain areas that are genetically associated with both depressive symptoms and CU in a sample of 258 same-sex twin pairs from the Colorado Longitudinal Twin Study (LTS). We then overlapped the two maps to generate coordinates that allow for tests of downstream effects of genes influencing our clusters. Genetic variance influencing cortical thickness in the right dorsal lateral prefrontal cortex (DLFPC) sulci and gyri, ventral posterior cingulate cortex (PCC), pre-somatic motor cortex (PreSMA), medial precuneus, left occipital-temporal junction (OTJ), parietal–temporal junction (PTJ), ventral somatosensory cortex (vSMA), and medial and lateral precuneus were genetically associated with both depression and CU. Split-half replication found support for both DLPFC clusters. Meta-analytic term search identified “theory of mind”, “inhibit”, and “pain” as likely functions. Gene and transcript mapping/enrichment analyses implicated calcium channels. CU reflects genetic vulnerability to depression that likely involves executive and social functioning in a distributed process across the cortex. This approach works to unify neuroimaging, neuroinformatics, and genetics to discover pathways to psychiatric vulnerability. Nature Publishing Group UK 2019-11-14 /pmc/articles/PMC6856353/ /pubmed/31727881 http://dx.doi.org/10.1038/s41398-019-0611-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Hatoum, Alexander S. Reineberg, Andrew E. Smolker, Harry R. Hewitt, John K. Friedman, Naomi P. Whole-cortex mapping of common genetic influences on depression and a social deficits dimension |
title | Whole-cortex mapping of common genetic influences on depression and a social deficits dimension |
title_full | Whole-cortex mapping of common genetic influences on depression and a social deficits dimension |
title_fullStr | Whole-cortex mapping of common genetic influences on depression and a social deficits dimension |
title_full_unstemmed | Whole-cortex mapping of common genetic influences on depression and a social deficits dimension |
title_short | Whole-cortex mapping of common genetic influences on depression and a social deficits dimension |
title_sort | whole-cortex mapping of common genetic influences on depression and a social deficits dimension |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856353/ https://www.ncbi.nlm.nih.gov/pubmed/31727881 http://dx.doi.org/10.1038/s41398-019-0611-6 |
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