Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation.

Abstract Childhood adversity appears to sensitize youth to stress, increasing depression risk following stressful life events occurring throughout the lifespan. Some evidence suggests hypothalamic–pituitary–adrenal (HPA) axis-related and serotonergic genetic variation moderates this effect, in a “gene-by-environment-by-environment” interaction (G × E × E). However, prior research has tested single genetic variants, limiting power. The current study uses a multilocus genetic profile score (MGPS) approach to capture polygenic risk relevant to HPA axis and serotonergic functioning. Adolescents (N = 241, Mage = 15.90) completed contextual-threat-based interviews assessing childhood adversity and acute life events, and diagnostic interviews assessing depression. Established MGPSs indexed genetic variation linked to HPA axis (10 single nucleotide polymorphisms [SNPs]) and serotonergic (five SNPs) functioning. Results showed significant MGPS × Childhood Adversity × Recent Life Stress interactions predicting depression for both HPA axis and serotonergic MGPSs, with both risk scores predicting stronger Childhood Adversity × Recent Stress interactions. Serotonergic genetic risk specifically predicted sensitization to major interpersonal stressors. The serotonergic MGPS G × E × E was re-tested in an independent replication sample of early adolescent girls, with comparable results. Findings support the notion that genetic variation linked to these two neurobiological symptoms alters stress sensitization, and that gene-by-environment (G × E) interactions may be qualified by environmental exposures occurring at different points in development.

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Maternal Depression, Child Temperament, and Early-Life Stress Predict Never-Depressed Preadolescents’ Functional Connectivity During a Negative-Mood Induction

Clinical Psychological Science ◽

10.1177/21677026211016419 ◽

2021 ◽

pp. 216770262110164

Author(s):

Pan Liu ◽

Matthew R. J. Vandermeer ◽

Ola Mohamed Ali ◽

Andrew R. Daoust ◽

Marc F. Joanisse ◽

...

Keyword(s):

Prefrontal Cortex ◽

Functional Connectivity ◽

Maternal Depression ◽

Life Stress ◽

Early Life ◽

Negative Emotion ◽

Negative Mood ◽

Emotion Processing ◽

Early Life Stress ◽

Cingulate Cortex

Understanding the development of depression can inform etiology and prevention/intervention. Maternal depression and maladaptive patterns of temperament (e.g., low positive emotionality [PE] or high negative emotionality, especially sadness) are known to predict depression. Although it is unclear how these risks cause depression, altered functional connectivity (FC) during negative-emotion processing may play an important role. We investigated whether maternal depression and age-3 emotionality predicted FC during negative mood reactivity in never-depressed preadolescents and whether these relationships were augmented by early-life stress. Maternal depression predicted decreased medial prefrontal cortex (mPFC)–amygdala and mPFC–insula FC but increased mPFC–posterior cingulate cortex (PCC) FC. PE predicted increased dorsolateral prefrontal cortex–amygdala FC, whereas sadness predicted increased PCC-based FC in insula, orbitofrontal cortex, and anterior cingulate cortex (ACC). Sadness was more strongly associated with PCC–insula and PCC–ACC FC as early stress increased. Findings indicate that early depression risks may be mediated by FC underlying negative-emotion processing.

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The effects of early life stress on neurobehavioral development in children and adolescents: Mediation by the HPA axis

Psychoneuroendocrinology ◽

10.1016/j.psyneuen.2015.07.393 ◽

2015 ◽

Vol 61 ◽

pp. 3 ◽

Cited By ~ 5

Author(s):

Megan R. Gunnar

Keyword(s):

Children And Adolescents ◽

Hpa Axis ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Neurobehavioral Development

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Thinking and Feeling

Clinical Psychological Science ◽

10.1177/2167702616654688 ◽

2016 ◽

Vol 5 (1) ◽

pp. 150-157 ◽

Cited By ~ 16

Author(s):

Matthew A. Scult ◽

Annchen R. Knodt ◽

Johnna R. Swartz ◽

Bartholomew D. Brigidi ◽

Ahmad R. Hariri

Keyword(s):

Emotion Regulation ◽

Prefrontal Cortex ◽

Everyday Life ◽

Executive Control ◽

Life Stress ◽

Dorsolateral Prefrontal Cortex ◽

Cognitive Reappraisal ◽

Dorsolateral Prefrontal ◽

Clinical Diagnoses ◽

Math Problems

Calculating math problems from memory may seem unrelated to everyday processing of emotions, but they have more in common than one might think. Prior research highlights the importance of the dorsolateral prefrontal cortex (dlPFC) in executive control, intentional emotion regulation, and experience of dysfunctional mood and anxiety. Although it has been hypothesized that emotion regulation may be related to “cold” (i.e., not emotion-related) executive control, this assertion has not been tested. We address this gap by providing evidence that greater dlPFC activity during cold executive control is associated with increased use of cognitive reappraisal to regulate emotions in everyday life. We then demonstrate that in the presence of increased life stress, increased dlPFC activity is associated with lower mood and anxiety symptoms and clinical diagnoses. Collectively, our results encourage ongoing efforts to understand prefrontal executive control as a possible intervention target for improving emotion regulation in mood and anxiety disorders.

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Poster #M195 THE INTERACTION BETWEEN CNR1 GENETIC VARIATION AND CANNABIS EXPOSURE PREDICTS PREFRONTAL FUNCTIONAL CONNECTIVITY AND BEHAVIOR DURING WORKING MEMORY

Schizophrenia Research ◽

10.1016/s0920-9964(14)70745-5 ◽

2014 ◽

Vol 153 ◽

pp. S261

Author(s):

Marco Colizzi ◽

Leonardo Fazio ◽

Laura Ferranti ◽

Annamaria Porcelli ◽

Rita Masellis ◽

...

Keyword(s):

Working Memory ◽

Genetic Variation ◽

Functional Connectivity ◽

And Behavior

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Neural responses during down-regulation of negative emotion in patients with recently diagnosed bipolar disorder and their unaffected relatives

Psychological Medicine ◽

10.1017/s0033291721002737 ◽

2021 ◽

pp. 1-12

Author(s):

Hanne Lie Kjærstad ◽

Julian Macoveanu ◽

Gitte Moos Knudsen ◽

Sophia Frangou ◽

K. Luan Phan ◽

...

Keyword(s):

Bipolar Disorder ◽

Emotion Regulation ◽

Functional Connectivity ◽

Neural Activity ◽

Negative Emotion ◽

Negative Emotions ◽

Imaging Study ◽

Neural Responses ◽

Functional Magnetic Resonance ◽

Down Regulation

Abstract Background Aberrant emotion regulation has been posited as a putative endophenotype of bipolar disorder (BD). We therefore aimed to compare the neural responses during voluntary down-regulation of negative emotions in a large functional magnetic resonance imaging study of BD, patients' unaffected first-degree relatives (URs), and healthy controls (HCs). Methods We compared neural activity and fronto-limbic functional connectivity during emotion regulation in response to aversive v. neutral pictures in patients recently diagnosed with BD (n = 78) in full/partial remission, their URs (n = 35), and HCs (n = 56). Results Patients showed hypo-activity in the left dorsomedial, dorsolateral, and ventrolateral prefrontal cortex (DMPFC and DLPFC) during emotion regulation while viewing aversive pictures compared to HCs, with URs displaying intermediate neural activity in these regions. There were no significant differences between patients with BD and HCs in functional connectivity from the amygdala during emotion regulation. However, exploratory analysis indicated that URs displayed more negative amygdala–DMPFC coupling compared with HCs and more negative amygdala-cingulate DLPFC coupling compared to patients with BD. At a behavioral level, patients and their URs were less able to dampen negative emotions in response aversive pictures. Conclusions The findings point to deficient recruitment of prefrontal resources and more negative fronto-amygdala coupling as neural markers of impaired emotion regulation in recently diagnosed remitted patients with BD and their URs, respectively.

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