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Genome-wide analyses reveal DNA methylation in the central nucleus of the amygdala is linked to anxious temperament in young primates

ABSTRACT: We used reduced representation bisulfite sequencing to profiled 5-methylcytosine in the Ce of rhesus monkeys (N = 23) fully phenotyped for anxious temperament (AT) and identified 5,489 CpG sites (1,363 genes) with methylation levels predictive of individual differences in AT (FDR p-value < 0.05), including genes previously implicated in psychiatric-related disorders (e.g. GRIN1, GRM5, HTT, ADCYAP1, and SHANK3).

ORGANISM(S): Macaca mulatta

PROVIDER: GSE58687 | GEO | 2014/12/02

SECONDARY ACCESSION(S): PRJNA253174

REPOSITORIES: GEO

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Project description:Early theorists (Freud and Darwin) speculated that extremely shy children, or those with anxious temperament, were likely to have anxiety problems as adults. More recent studies demonstrate that these children have heightened responses to potentially threatening situations reacting with intense defensive responses that are characterized by behavioral inhibition (BI) (inhibited motor behavior and decreased vocalizations) and physiological arousal. Confirming the earlier impressions, data now demonstrate that children with this disposition are at increased risk to develop anxiety, depression, and comorbid substance abuse. Additional key features of anxious temperament are that it appears at a young age, it is a stable characteristic of individuals, and even in non-threatening environments it is associated with increased psychic anxiety and somatic tension. To understand the neural underpinnings of anxious temperament, we performed imaging studies with 18-fluoro-deoxyglucose (FDG) high-resolution Positron Emission Tomography (PET) in young rhesus monkeys. Rhesus monkeys were used because they provide a well validated model of anxious temperament for studies that cannot be performed in human children. Imaging the same animal in stressful and secure contexts, we examined the relation between regional metabolic brain activity and a trait-like measure of anxious temperament that encompasses measures of BI and pituitary-adrenal reactivity. Regardless of context, results demonstrated a trait-like pattern of brain activity (amygdala, bed nucleus of stria terminalis, hippocampus, and periaqueductal gray) that is predictive of individual phenotypic differences. Importantly, individuals with extreme anxious temperament also displayed increased activity of this circuit when assessed in the security of their home environment. These findings suggest that increased activity of this circuit early in life mediates the childhood temperamental risk to develop anxiety and depression. In addition, the findings provide an explanation for why individuals with anxious temperament have difficulty relaxing in environments that others perceive as non-stressful.

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Genome-wide analyses reveal DNA methylation in the central nucleus of the amygdala is linked to anxious temperament in young primates

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