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Preclinical atherosclerosis covaries with individual differences in reactivity and functional connectivity of the amygdala.

ABSTRACT: Cardiovascular disease (CVD) is a major source of medical comorbidity for patients with mood and anxiety disorders, and it remains the leading public health burden for the general population in industrialized nations. Indirect neurobiological evidence suggests that preclinical risk for atherosclerosis, the main contributor to CVD, may be conferred by interindividual variation in the functionality of the amygdala, a brain system jointly involved in processing behaviorally salient stimuli and regulating the cardiovascular system.In a neuroimaging study of 36 middle-aged adults (18 women) who were screened for confounding clinical cardiovascular and psychiatric disorders, we examined the direct covariation between a marker of preclinical atherosclerosis, carotid artery intima-media thickness (IMT), and interindividual variation in amygdala reactivity and functional connectivity assessed during the processing of behaviorally salient stimuli (angry and fearful facial expressions).After accounting for traditional CVD risk factors, a thickening of carotid IMT across individuals covaried with greater amygdala reactivity and a more positive functional connectivity between the amygdala and perigenual anterior cingulate cortex, a corticolimbic area also implicated in behavioral salience processing and cardiovascular regulation.Individual differences in amygdala reactivity and functional connectivity may reflect facets of a novel, systems-level neural phenotype conferring risk for atherosclerosis and CVD.

SUBMITTER: Gianaros PJ

PROVIDER: S-EPMC2853713 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Preclinical atherosclerosis covaries with individual differences in reactivity and functional connectivity of the amygdala.

Gianaros Peter J PJ Hariri Ahmad R AR Sheu Lei K LK Muldoon Matthew F MF Sutton-Tyrrell Kim K Manuck Stephen B SB

Biological psychiatry 20081114 11

<h4>Background</h4>Cardiovascular disease (CVD) is a major source of medical comorbidity for patients with mood and anxiety disorders, and it remains the leading public health burden for the general population in industrialized nations. Indirect neurobiological evidence suggests that preclinical risk for atherosclerosis, the main contributor to CVD, may be conferred by interindividual variation in the functionality of the amygdala, a brain system jointly involved in processing behaviorally salie ...[more]

PMID: 19013557

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Project description:Hyperactive amygdala functioning may underlie emotional dysregulation during smoking abstinence and represents one neurobiological target for pharmacological cessation aids. Available pharmacotherapies (e.g., nicotine replacement and varenicline) aid only a subset of individuals with smoking cessation and therefore elucidating the neurobiological impact of these medications is critical to expedite improved interventions. In a fMRI study employing a within-subject, double-blind, placebo-controlled design, we assessed task performance and amygdala functioning during an emotional face matching paradigm following administration of nicotine and varenicline to 24 abstinent smokers and 20 nonsmokers. All participants underwent ~17days of varenicline and placebo pill administration and were scanned, on different days under each condition, wearing a transdermal nicotine or placebo patch. During the amygdala reactivity paradigm, nicotinic acetylcholine receptor (nAChR) stimulation by nicotine and varenicline decreased reaction time (RT) in abstinent smokers but not in nonsmokers. When considering all smokers as a single homogenous group, no drug-induced effects on amygdala reactivity were detected. However, in an exploratory analysis we parsed participants into subgroups according to individual differences in the propensity to demonstrate stable performance augmentation following nAChR stimulation (stable RT-improvers [SI] vs. variable RT-improvers [VI]). Using this exploratory approach, drugs appeared to modulate amygdala reactivity in only one smoker subgroup but not in either nonsmoker subgroup. Specifically, in the SI-smoker cohort abstinence-induced elevated amygdala reactivity was down-regulated by nAChR stimulation. In contrast, varenicline and nicotine did not modulate amygdala functioning in the VI-smoker cohort who displayed moderate levels of amygdala reactivity in the absence of drug administration. These results suggest that pharmacotherapies most robustly dampened amygdala functioning in smokers appearing susceptible to abstinence-induced effects. Such findings provide a step towards fractionating the smoker phenotype by discrete neurobiological characteristics.

Project description:ObjectiveEmotion dysregulation has been suggested to be a potent risk factor for multiple psychiatric conditions. Altered amygdala-prefrontal cortex (PFC) connectivity has been consistently linked to emotion dysregulation. Recent data indicate that amygdala-PFC functional connectivity undergoes a prolonged period of development, with amygdala reactivity during early childhood potentially shaping this unfolding process. Little is known about the relationships between amygdala-PFC functional connectivity, amygdala reactivity, and emotion regulation during early childhood. This information is likely critical for understanding early emotion dysregulation as a transdiagnostic risk factor for psychopathology. The current study examined the relationships between amygdala functional connectivity, amygdala reactivity, and emotion regulation in preschoolers.MethodA total of 66 medication-naive 4- to 6-year-olds participated in a study where resting-state functional magnetic resonance imaging (rs-fMRI) and parent-reported child emotion regulation ability data were collected. fMRI data collected during a face viewing task was also available for 24 children.ResultsRight amygdala-medial PFC (mPFC) functional connectivity was positively associated with child emotion regulation ability and negatively associated with child negative affect and right amygdala reactivity to facial expressions of emotion. Right amygdala-mPFC functional connectivity also statistically mediated the relationship between heightened right amygdala reactivity and elevated child negative affect.ConclusionStudy findings suggest that amygdala-mPFC functional connectivity during early childhood, and its relationships with amygdala reactivity and emotion regulation during this highly sensitive developmental period, may play an important role in early emotional development. These results inform the neurodevelopmental biology of emotion regulation and its potential relationship with risk for psychopathology.

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Preclinical atherosclerosis covaries with individual differences in reactivity and functional connectivity of the amygdala.

Publications

Preclinical atherosclerosis covaries with individual differences in reactivity and functional connectivity of the amygdala.

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