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Brain Networks Implicated in Seasonal Affective Disorder: A Neuroimaging PET Study of the Serotonin Transporter
Background: Seasonal Affective Disorder (SAD) is a subtype of Major Depressive Disorder characterized by seasonally occurring depression that often presents with atypical vegetative symptoms such as hypersomnia and carbohydrate craving. It has recently been shown that unlike healthy people, patients...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682039/ https://www.ncbi.nlm.nih.gov/pubmed/29163018 http://dx.doi.org/10.3389/fnins.2017.00614 |
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author | Nørgaard, Martin Ganz, Melanie Svarer, Claus Fisher, Patrick M. Churchill, Nathan W. Beliveau, Vincent Grady, Cheryl Strother, Stephen C. Knudsen, Gitte M. |
author_facet | Nørgaard, Martin Ganz, Melanie Svarer, Claus Fisher, Patrick M. Churchill, Nathan W. Beliveau, Vincent Grady, Cheryl Strother, Stephen C. Knudsen, Gitte M. |
author_sort | Nørgaard, Martin |
collection | PubMed |
description | Background: Seasonal Affective Disorder (SAD) is a subtype of Major Depressive Disorder characterized by seasonally occurring depression that often presents with atypical vegetative symptoms such as hypersomnia and carbohydrate craving. It has recently been shown that unlike healthy people, patients with SAD fail to globally downregulate their cerebral serotonin transporter (5-HTT) in winter, and that this effect seemed to be particularly pronounced in female S-carriers of the 5-HTTLPR genotype. The purpose of this study was to identify a 5-HTT brain network that accounts for the adaption to the environmental stressor of winter in females with the short 5-HTTLPR genotype, a specific subgroup previously reported to be at increased risk for developing SAD. Methods: Nineteen females, either S' carriers (L(G)- and S-carriers) without SAD (N = 13, mean age 23.6 ± 3.2 year, range 19–28) or S' carriers with SAD (N = 6, mean age 23.7 ± 2.4, range 21–26) were PET-scanned with [(11)C]DASB during both summer and winter seasons (asymptomatic and symptomatic phase, 38 scans in total) in randomized order, defined as a 12-week interval centered on summer or winter solstice. We used a multivariate Partial Least Squares (PLS) approach with NPAIRS split-half cross-validation, to identify and map a whole-brain pattern of 5-HTT levels that distinguished the brains of females without SAD from females suffering from SAD. Results: We identified a pattern of 5-HTT levels, distinguishing females with SAD from those without SAD; it included the right superior frontal gyrus, brainstem, globus pallidus (bilaterally) and the left hippocampus. Across seasons, female S' carriers without SAD showed nominally higher 5-HTT levels in these regions compared to female S' carriers with SAD, but the group difference was only significant in the winter. Female S' carriers with SAD, in turn, displayed robustly increased 5-HTT levels in the ventral striatum (bilaterally), right orbitofrontal cortex, middle frontal gyrus (bilaterally), extending to the left supramarginal gyrus, left precentral gyrus and left postcentral gyrus during winter compared to female S' carriers without SAD. Limitations: The study is preliminary and limited by small sample size in the SAD group (N = 6). Conclusions: These findings provide novel exploratory evidence for a wintertime state-dependent difference in 5-HTT levels that may leave SAD females with the short 5-HTTLPR genotype more vulnerable to persistent stressors like winter. The affected brain regions comprise a distributed set of areas responsive to emotion, voluntary, and planned movement, executive function, and memory. The preliminary findings provide additional insight into the neurobiological components through which the anatomical distribution of serotonergic discrepancies between individuals genetically predisposed to SAD, but with different phenotypic presentations during the environmental stressor of winter, may constitute a potential biomarker for resilience against developing SAD. |
format | Online Article Text |
id | pubmed-5682039 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56820392017-11-21 Brain Networks Implicated in Seasonal Affective Disorder: A Neuroimaging PET Study of the Serotonin Transporter Nørgaard, Martin Ganz, Melanie Svarer, Claus Fisher, Patrick M. Churchill, Nathan W. Beliveau, Vincent Grady, Cheryl Strother, Stephen C. Knudsen, Gitte M. Front Neurosci Neuroscience Background: Seasonal Affective Disorder (SAD) is a subtype of Major Depressive Disorder characterized by seasonally occurring depression that often presents with atypical vegetative symptoms such as hypersomnia and carbohydrate craving. It has recently been shown that unlike healthy people, patients with SAD fail to globally downregulate their cerebral serotonin transporter (5-HTT) in winter, and that this effect seemed to be particularly pronounced in female S-carriers of the 5-HTTLPR genotype. The purpose of this study was to identify a 5-HTT brain network that accounts for the adaption to the environmental stressor of winter in females with the short 5-HTTLPR genotype, a specific subgroup previously reported to be at increased risk for developing SAD. Methods: Nineteen females, either S' carriers (L(G)- and S-carriers) without SAD (N = 13, mean age 23.6 ± 3.2 year, range 19–28) or S' carriers with SAD (N = 6, mean age 23.7 ± 2.4, range 21–26) were PET-scanned with [(11)C]DASB during both summer and winter seasons (asymptomatic and symptomatic phase, 38 scans in total) in randomized order, defined as a 12-week interval centered on summer or winter solstice. We used a multivariate Partial Least Squares (PLS) approach with NPAIRS split-half cross-validation, to identify and map a whole-brain pattern of 5-HTT levels that distinguished the brains of females without SAD from females suffering from SAD. Results: We identified a pattern of 5-HTT levels, distinguishing females with SAD from those without SAD; it included the right superior frontal gyrus, brainstem, globus pallidus (bilaterally) and the left hippocampus. Across seasons, female S' carriers without SAD showed nominally higher 5-HTT levels in these regions compared to female S' carriers with SAD, but the group difference was only significant in the winter. Female S' carriers with SAD, in turn, displayed robustly increased 5-HTT levels in the ventral striatum (bilaterally), right orbitofrontal cortex, middle frontal gyrus (bilaterally), extending to the left supramarginal gyrus, left precentral gyrus and left postcentral gyrus during winter compared to female S' carriers without SAD. Limitations: The study is preliminary and limited by small sample size in the SAD group (N = 6). Conclusions: These findings provide novel exploratory evidence for a wintertime state-dependent difference in 5-HTT levels that may leave SAD females with the short 5-HTTLPR genotype more vulnerable to persistent stressors like winter. The affected brain regions comprise a distributed set of areas responsive to emotion, voluntary, and planned movement, executive function, and memory. The preliminary findings provide additional insight into the neurobiological components through which the anatomical distribution of serotonergic discrepancies between individuals genetically predisposed to SAD, but with different phenotypic presentations during the environmental stressor of winter, may constitute a potential biomarker for resilience against developing SAD. Frontiers Media S.A. 2017-11-03 /pmc/articles/PMC5682039/ /pubmed/29163018 http://dx.doi.org/10.3389/fnins.2017.00614 Text en Copyright © 2017 Nørgaard, Ganz, Svarer, Fisher, Churchill, Beliveau, Grady, Strother and Knudsen. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Nørgaard, Martin Ganz, Melanie Svarer, Claus Fisher, Patrick M. Churchill, Nathan W. Beliveau, Vincent Grady, Cheryl Strother, Stephen C. Knudsen, Gitte M. Brain Networks Implicated in Seasonal Affective Disorder: A Neuroimaging PET Study of the Serotonin Transporter |
title | Brain Networks Implicated in Seasonal Affective Disorder: A Neuroimaging PET Study of the Serotonin Transporter |
title_full | Brain Networks Implicated in Seasonal Affective Disorder: A Neuroimaging PET Study of the Serotonin Transporter |
title_fullStr | Brain Networks Implicated in Seasonal Affective Disorder: A Neuroimaging PET Study of the Serotonin Transporter |
title_full_unstemmed | Brain Networks Implicated in Seasonal Affective Disorder: A Neuroimaging PET Study of the Serotonin Transporter |
title_short | Brain Networks Implicated in Seasonal Affective Disorder: A Neuroimaging PET Study of the Serotonin Transporter |
title_sort | brain networks implicated in seasonal affective disorder: a neuroimaging pet study of the serotonin transporter |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682039/ https://www.ncbi.nlm.nih.gov/pubmed/29163018 http://dx.doi.org/10.3389/fnins.2017.00614 |
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