5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression - PubMed (original) (raw)
doi: 10.1038/nn1463. Epub 2005 May 8.
Affiliations
- PMID: 15880108
- DOI: 10.1038/nn1463
5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression
Lukas Pezawas et al. Nat Neurosci. 2005 Jun.
Abstract
Carriers of the short allele of a functional 5' promoter polymorphism of the serotonin transporter gene have increased anxiety-related temperamental traits, increased amygdala reactivity and elevated risk of depression. Here, we used multimodal neuroimaging in a large sample of healthy human subjects to elucidate neural mechanisms underlying this complex genetic association. Morphometrical analyses showed reduced gray matter volume in short-allele carriers in limbic regions critical for processing of negative emotion, particularly perigenual cingulate and amygdala. Functional analysis of those regions during perceptual processing of fearful stimuli demonstrated tight coupling as a feedback circuit implicated in the extinction of negative affect. Short-allele carriers showed relative uncoupling of this circuit. Furthermore, the magnitude of coupling inversely predicted almost 30% of variation in temperamental anxiety. These genotype-related alterations in anatomy and function of an amygdala-cingulate feedback circuit critical for emotion regulation implicate a developmental, systems-level mechanism underlying normal emotional reactivity and genetic susceptibility for depression.
Comment in
- Genetics of psychiatric disorders.
[No authors listed] [No authors listed] Nat Neurosci. 2005 Jun;8(6):693. doi: 10.1038/nn0605-693. Nat Neurosci. 2005. PMID: 15917827 No abstract available. - Blue genes: wiring the brain for depression.
Hamann S. Hamann S. Nat Neurosci. 2005 Jun;8(6):701-3. doi: 10.1038/nn0605-701. Nat Neurosci. 2005. PMID: 15917831 No abstract available.
Similar articles
- Blue genes: wiring the brain for depression.
Hamann S. Hamann S. Nat Neurosci. 2005 Jun;8(6):701-3. doi: 10.1038/nn0605-701. Nat Neurosci. 2005. PMID: 15917831 No abstract available. - A susceptibility gene for affective disorders and the response of the human amygdala.
Hariri AR, Drabant EM, Munoz KE, Kolachana BS, Mattay VS, Egan MF, Weinberger DR. Hariri AR, et al. Arch Gen Psychiatry. 2005 Feb;62(2):146-52. doi: 10.1001/archpsyc.62.2.146. Arch Gen Psychiatry. 2005. PMID: 15699291 - Interaction of the serotonin transporter-linked polymorphic region and environmental adversity: increased amygdala-hypothalamus connectivity as a potential mechanism linking neural and endocrine hyperreactivity.
Alexander N, Klucken T, Koppe G, Osinsky R, Walter B, Vaitl D, Sammer G, Stark R, Hennig J. Alexander N, et al. Biol Psychiatry. 2012 Jul 1;72(1):49-56. doi: 10.1016/j.biopsych.2012.01.030. Epub 2012 Mar 13. Biol Psychiatry. 2012. PMID: 22418015 - Neuroimaging genetics: new perspectives in research on major depression?
Frodl T, Möller HJ, Meisenzahl E. Frodl T, et al. Acta Psychiatr Scand. 2008 Nov;118(5):363-72. doi: 10.1111/j.1600-0447.2008.01225.x. Epub 2008 Jul 14. Acta Psychiatr Scand. 2008. PMID: 18644006 Review. - Imaging genetics: perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing.
Hariri AR, Drabant EM, Weinberger DR. Hariri AR, et al. Biol Psychiatry. 2006 May 15;59(10):888-97. doi: 10.1016/j.biopsych.2005.11.005. Epub 2006 Jan 25. Biol Psychiatry. 2006. PMID: 16442081 Review.
Cited by
- Induction and quantification of prefrontal cortical network plasticity using 5 Hz rTMS and fMRI.
Esslinger C, Schüler N, Sauer C, Gass D, Mier D, Braun U, Ochs E, Schulze TG, Rietschel M, Kirsch P, Meyer-Lindenberg A. Esslinger C, et al. Hum Brain Mapp. 2014 Jan;35(1):140-51. doi: 10.1002/hbm.22165. Epub 2012 Sep 11. Hum Brain Mapp. 2014. PMID: 22965696 Free PMC article. - Nature experience reduces rumination and subgenual prefrontal cortex activation.
Bratman GN, Hamilton JP, Hahn KS, Daily GC, Gross JJ. Bratman GN, et al. Proc Natl Acad Sci U S A. 2015 Jul 14;112(28):8567-72. doi: 10.1073/pnas.1510459112. Epub 2015 Jun 29. Proc Natl Acad Sci U S A. 2015. PMID: 26124129 Free PMC article. - Human amygdala volume is predicted by common DNA variation in the stathmin and serotonin transporter genes.
Stjepanović D, Lorenzetti V, Yücel M, Hawi Z, Bellgrove MA. Stjepanović D, et al. Transl Psychiatry. 2013 Jul 16;3(7):e283. doi: 10.1038/tp.2013.41. Transl Psychiatry. 2013. PMID: 23860484 Free PMC article. - An ecological animal model of subthreshold depression in adolescence: behavioral and resting state 18F-FDG PET imaging characterization.
Accrombessi G, Galineau L, Tauber C, Serrière S, Moyer E, Brizard B, Le Guisquet AM, Surget A, Belzung C. Accrombessi G, et al. Transl Psychiatry. 2022 Sep 1;12(1):356. doi: 10.1038/s41398-022-02119-1. Transl Psychiatry. 2022. PMID: 36050307 Free PMC article. - Genetic and pharmacological manipulations of the serotonergic system in early life: neurodevelopmental underpinnings of autism-related behavior.
Kinast K, Peeters D, Kolk SM, Schubert D, Homberg JR. Kinast K, et al. Front Cell Neurosci. 2013 Jun 12;7:72. doi: 10.3389/fncel.2013.00072. eCollection 2013. Front Cell Neurosci. 2013. PMID: 23781172 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical