Early life stress combined with serotonin 3A receptor and brain-derived neurotrophic factor valine 66 to methionine genotypes impacts emotional brain and arousal correlates of risk for depression

Justine M. Gatt, Charles Nemeroff, Peter R. Schofield, Robert H. Paul, C. Richard Clark, Evian Gordon, Leanne M. Williams

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Background Depression will be the second largest burden of disease by 2020. Developing new tools for identifying risk and ultimately prevention of depression relies on elucidating the integrative relationships between susceptibility markers from gene-stress interactions and how they impact emotional brain and arousal systems. They have largely been studied in isolation. Methods We examined how genetic (brain-derived neurotrophic factor [BDNF] valine 66 to methionine [Val66Met] and serotonin receptor gene 3A [HTR3A]) and early life stress susceptibility factors interact in predicting electroencephalogram (EEG) asymmetry, emotion-elicited heart rate, and self-reported negativity bias, each correlates of risk for depression. Caucasian volunteers (n = 363) were derived from the Brain Resource International Database, via the Brain Research And Integrative Neuroscience Network. Results Individuals with both BDNF methionine and HTR3A CC risk genotypes and early life stressors demonstrated a profile of elevated emotion-elicited heart rate and right frontal hyper-activation with right parietotemporal hypoactivation in EEG asymmetry. Elevations in heart rate were a moderator of negativity bias. Conclusions The findings provide new evidence that these gene-stress susceptibility factors contribute to a brain-arousal profile indicative of risk for depression. They are a step toward identifying biological markers for detecting risk before overt symptoms. It would be valuable for future studies to examine comorbidity and specificity issues; for instance, whether these gene-stress factors contribute in different ways to the partially distinct EEG asymmetry profiles found with anxiety.

Original languageEnglish
Pages (from-to)818-824
Number of pages7
JournalBiological Psychiatry
Volume68
Issue number9
DOIs
StatePublished - Nov 1 2010

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Serotonin Receptors
Brain-Derived Neurotrophic Factor
Valine
Arousal
Psychological Stress
Methionine
Genotype
Depression
Brain
Electroencephalography
Heart Rate
Genes
Emotions
Neurosciences
Comorbidity
Volunteers
Anxiety
Biomarkers
Databases
Research

Keywords

  • Arousal
  • brain imaging
  • Brain Research And Integrative Neuroscience Network (BRAINnet)
  • brain-derived neurotrophic factor (BDNF) Val66Met polymorphism
  • depression
  • early life stress
  • emotion regulation
  • serotonin 3A receptor HTR3A polymorphism

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Early life stress combined with serotonin 3A receptor and brain-derived neurotrophic factor valine 66 to methionine genotypes impacts emotional brain and arousal correlates of risk for depression. / Gatt, Justine M.; Nemeroff, Charles; Schofield, Peter R.; Paul, Robert H.; Clark, C. Richard; Gordon, Evian; Williams, Leanne M.

In: Biological Psychiatry, Vol. 68, No. 9, 01.11.2010, p. 818-824.

Research output: Contribution to journalArticle

Gatt, Justine M. ; Nemeroff, Charles ; Schofield, Peter R. ; Paul, Robert H. ; Clark, C. Richard ; Gordon, Evian ; Williams, Leanne M. / Early life stress combined with serotonin 3A receptor and brain-derived neurotrophic factor valine 66 to methionine genotypes impacts emotional brain and arousal correlates of risk for depression. In: Biological Psychiatry. 2010 ; Vol. 68, No. 9. pp. 818-824.
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AB - Background Depression will be the second largest burden of disease by 2020. Developing new tools for identifying risk and ultimately prevention of depression relies on elucidating the integrative relationships between susceptibility markers from gene-stress interactions and how they impact emotional brain and arousal systems. They have largely been studied in isolation. Methods We examined how genetic (brain-derived neurotrophic factor [BDNF] valine 66 to methionine [Val66Met] and serotonin receptor gene 3A [HTR3A]) and early life stress susceptibility factors interact in predicting electroencephalogram (EEG) asymmetry, emotion-elicited heart rate, and self-reported negativity bias, each correlates of risk for depression. Caucasian volunteers (n = 363) were derived from the Brain Resource International Database, via the Brain Research And Integrative Neuroscience Network. Results Individuals with both BDNF methionine and HTR3A CC risk genotypes and early life stressors demonstrated a profile of elevated emotion-elicited heart rate and right frontal hyper-activation with right parietotemporal hypoactivation in EEG asymmetry. Elevations in heart rate were a moderator of negativity bias. Conclusions The findings provide new evidence that these gene-stress susceptibility factors contribute to a brain-arousal profile indicative of risk for depression. They are a step toward identifying biological markers for detecting risk before overt symptoms. It would be valuable for future studies to examine comorbidity and specificity issues; for instance, whether these gene-stress factors contribute in different ways to the partially distinct EEG asymmetry profiles found with anxiety.

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