Longitudinal epigenetic predictors of amygdala: hippocampus volume ratio

Esther Walton; Charlotte A.M. Cecil; Matthew Suderman; Jingyu Liu; Jessica A. Turner; Vince Calhoun; Stefan Ehrlich; Caroline L. Relton; Edward D. Barker

doi:10.1111/jcpp.12740

Longitudinal epigenetic predictors of amygdala: hippocampus volume ratio

Esther Walton, Charlotte A.M. Cecil, Matthew Suderman, Jingyu Liu, Jessica A. Turner, Vince Calhoun, Stefan Ehrlich, Caroline L. Relton, Edward D. Barker^*

^*Corresponding author for this work

Psychology

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

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Abstract

Background: The ratio between amygdala:hippocampal (AH) volume has been associated with multiple psychiatric problems, including anxiety and aggression. Yet, little is known about its biological underpinnings. Here, we used a methylome-wide approach to test (a) whether DNA methylation in early life (birth, age 7) prospectively associates with total AH volume ratio in early adulthood, and (b) whether significant DNA methylation markers are influenced by prenatal risk factors. Methods: Analyses were based on a subsample (n = 109 males) from the Avon Longitudinal Study of Parents and Children, which included measures of prenatal risk, DNA methylation (Infinium Illumina 450k), T1-weighted brain scans and psychopathology in early adulthood (age 18-21). Amygdala and hippocampus measures were derived using Freesurfer 5.3.0. Methylation markers related to AH volume ratio across time were identified using longitudinal multilevel modeling. Results: Amygdala:hippocampal volume ratio correlated positively with age 18 psychosis-like symptoms (p = .007). Methylation of a probe in the gene SP6 associated longitudinally with (a) higher AH volume ratio (FDR q-value = .01) and (b) higher stressful life events during pregnancy (p = .046). SP6 is expressed in the hippocampus and amygdala and has been implicated in cognitive decline in Alzheimer's disease. The association between SP6 DNA methylation, AH volume ratio and psychopathology was replicated in an independent dataset of 101 patients with schizophrenia and 111 healthy controls. Conclusions: Our findings suggest that epigenetic alterations in genes implicated in neurodevelopment may contribute to a brain-based biomarker of psychopathology.

Original language	English
Journal	Journal of Child Psychology and Psychiatry
Early online date	8 May 2017
DOIs	https://doi.org/10.1111/jcpp.12740
Publication status	Published - Dec 2017

Keywords

Amygdala
Avon Longitudinal Study of Parents and Children
DNA methylation
Hippocampus
Longitudinal
Methylome-wide

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Longitudinal epigenetic predictors of amygdala_WATSON_Accepted 1March2017 GOLD VoR (CC BY)Final published version, 287 KBLicence: CC BY

Cite this

@article{196d327bafe741c5902893ed7856ddfb,

title = "Longitudinal epigenetic predictors of amygdala: hippocampus volume ratio",

abstract = "Background: The ratio between amygdala:hippocampal (AH) volume has been associated with multiple psychiatric problems, including anxiety and aggression. Yet, little is known about its biological underpinnings. Here, we used a methylome-wide approach to test (a) whether DNA methylation in early life (birth, age 7) prospectively associates with total AH volume ratio in early adulthood, and (b) whether significant DNA methylation markers are influenced by prenatal risk factors. Methods: Analyses were based on a subsample (n = 109 males) from the Avon Longitudinal Study of Parents and Children, which included measures of prenatal risk, DNA methylation (Infinium Illumina 450k), T1-weighted brain scans and psychopathology in early adulthood (age 18-21). Amygdala and hippocampus measures were derived using Freesurfer 5.3.0. Methylation markers related to AH volume ratio across time were identified using longitudinal multilevel modeling. Results: Amygdala:hippocampal volume ratio correlated positively with age 18 psychosis-like symptoms (p = .007). Methylation of a probe in the gene SP6 associated longitudinally with (a) higher AH volume ratio (FDR q-value = .01) and (b) higher stressful life events during pregnancy (p = .046). SP6 is expressed in the hippocampus and amygdala and has been implicated in cognitive decline in Alzheimer's disease. The association between SP6 DNA methylation, AH volume ratio and psychopathology was replicated in an independent dataset of 101 patients with schizophrenia and 111 healthy controls. Conclusions: Our findings suggest that epigenetic alterations in genes implicated in neurodevelopment may contribute to a brain-based biomarker of psychopathology.",

keywords = "Amygdala, Avon Longitudinal Study of Parents and Children, DNA methylation, Hippocampus, Longitudinal, Methylome-wide",

author = "Esther Walton and Cecil, {Charlotte A.M.} and Matthew Suderman and Jingyu Liu and Turner, {Jessica A.} and Vince Calhoun and Stefan Ehrlich and Relton, {Caroline L.} and Barker, {Edward D.}",

year = "2017",

month = dec,

doi = "10.1111/jcpp.12740",

language = "English",

journal = "Journal of Child Psychology and Psychiatry",

issn = "0021-9630",

publisher = "Wiley",

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TY - JOUR

T1 - Longitudinal epigenetic predictors of amygdala

T2 - hippocampus volume ratio

AU - Walton, Esther

AU - Cecil, Charlotte A.M.

AU - Suderman, Matthew

AU - Liu, Jingyu

AU - Turner, Jessica A.

AU - Calhoun, Vince

AU - Ehrlich, Stefan

AU - Relton, Caroline L.

AU - Barker, Edward D.

PY - 2017/12

Y1 - 2017/12

N2 - Background: The ratio between amygdala:hippocampal (AH) volume has been associated with multiple psychiatric problems, including anxiety and aggression. Yet, little is known about its biological underpinnings. Here, we used a methylome-wide approach to test (a) whether DNA methylation in early life (birth, age 7) prospectively associates with total AH volume ratio in early adulthood, and (b) whether significant DNA methylation markers are influenced by prenatal risk factors. Methods: Analyses were based on a subsample (n = 109 males) from the Avon Longitudinal Study of Parents and Children, which included measures of prenatal risk, DNA methylation (Infinium Illumina 450k), T1-weighted brain scans and psychopathology in early adulthood (age 18-21). Amygdala and hippocampus measures were derived using Freesurfer 5.3.0. Methylation markers related to AH volume ratio across time were identified using longitudinal multilevel modeling. Results: Amygdala:hippocampal volume ratio correlated positively with age 18 psychosis-like symptoms (p = .007). Methylation of a probe in the gene SP6 associated longitudinally with (a) higher AH volume ratio (FDR q-value = .01) and (b) higher stressful life events during pregnancy (p = .046). SP6 is expressed in the hippocampus and amygdala and has been implicated in cognitive decline in Alzheimer's disease. The association between SP6 DNA methylation, AH volume ratio and psychopathology was replicated in an independent dataset of 101 patients with schizophrenia and 111 healthy controls. Conclusions: Our findings suggest that epigenetic alterations in genes implicated in neurodevelopment may contribute to a brain-based biomarker of psychopathology.

AB - Background: The ratio between amygdala:hippocampal (AH) volume has been associated with multiple psychiatric problems, including anxiety and aggression. Yet, little is known about its biological underpinnings. Here, we used a methylome-wide approach to test (a) whether DNA methylation in early life (birth, age 7) prospectively associates with total AH volume ratio in early adulthood, and (b) whether significant DNA methylation markers are influenced by prenatal risk factors. Methods: Analyses were based on a subsample (n = 109 males) from the Avon Longitudinal Study of Parents and Children, which included measures of prenatal risk, DNA methylation (Infinium Illumina 450k), T1-weighted brain scans and psychopathology in early adulthood (age 18-21). Amygdala and hippocampus measures were derived using Freesurfer 5.3.0. Methylation markers related to AH volume ratio across time were identified using longitudinal multilevel modeling. Results: Amygdala:hippocampal volume ratio correlated positively with age 18 psychosis-like symptoms (p = .007). Methylation of a probe in the gene SP6 associated longitudinally with (a) higher AH volume ratio (FDR q-value = .01) and (b) higher stressful life events during pregnancy (p = .046). SP6 is expressed in the hippocampus and amygdala and has been implicated in cognitive decline in Alzheimer's disease. The association between SP6 DNA methylation, AH volume ratio and psychopathology was replicated in an independent dataset of 101 patients with schizophrenia and 111 healthy controls. Conclusions: Our findings suggest that epigenetic alterations in genes implicated in neurodevelopment may contribute to a brain-based biomarker of psychopathology.

KW - Amygdala

KW - Avon Longitudinal Study of Parents and Children

KW - DNA methylation

KW - Hippocampus

KW - Longitudinal

KW - Methylome-wide

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U2 - 10.1111/jcpp.12740

DO - 10.1111/jcpp.12740

M3 - Article

AN - SCOPUS:85018375518

SN - 0021-9630

JO - Journal of Child Psychology and Psychiatry

JF - Journal of Child Psychology and Psychiatry

ER -

Longitudinal epigenetic predictors of amygdala: hippocampus volume ratio

Abstract

Keywords

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