Mild early‐life stress exaggerates the impact of acute stress on corticolimbic resting‐state functional connectivity

AbstractBackgroundExposure to threat-related early life stress (ELS) has been related to vulnerability for stress-related disorders in adulthood, putatively via disrupted corticolimbic circuits involved in stress response and regulation. However, previous research on ELS has not examined both the intrinsic strength and flexibility of corticolimbic circuits, which may be particularly important for adaptive stress responding, or associations between these dimensions of corticolimbic dysfunction and acute stress response in adulthood.MethodsSeventy unmedicated women varying in history of threat-related ELS completed a functional magnetic resonance imaging scan to evaluate voxelwise static (overall) and dynamic (variability over a series of sliding windows) resting-state functional connectivity (RSFC) of bilateral amygdala. In a separate session and subset of participants (n = 42), measures of salivary cortisol and affect were collected during a social-evaluative stress challenge.ResultsHigher severity of threat-related ELS was related to more strongly negative static RSFC between amygdala and left dorsolateral prefrontal cortex (DLPFC), and elevated dynamic RSFC between amygdala and rostral anterior cingulate cortex (rACC). Static amygdala-DLPFC antagonism mediated the relationship between higher severity of threat-related ELS and blunted cortisol response to stress, but increased dynamic amygdala-rACC connectivity weakened this mediated effect and was related to more positive post-stress mood.ConclusionsThreat-related ELS was associated with RSFC within lateral corticolimbic circuits, which in turn was related to blunted physiological response to acute stress. Notably, increased flexibility between the amygdala and rACC compensated for this static disruption, suggesting that more dynamic medial corticolimbic circuits might be key to restoring healthy stress response.

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Too much, too young? Altered corticolimbic axonal innervation and resting state functional connectivity suggests sex-dependent outcomes in a rat model of early life adversity

10.1101/700666 ◽

2019 ◽

Author(s):

Jennifer A. Honeycutt ◽

Camila Demaestri ◽

Shayna Peterzell ◽

Marisa M. Silveri ◽

Xuezhu Cai ◽

...

Keyword(s):

Functional Connectivity ◽

Resting State ◽

Life Stress ◽

Early Life ◽

Female Rats ◽

Brain Maturation ◽

Resting State Functional Connectivity ◽

Early Maturation ◽

Male And Female Rats ◽

Increased Risk

AbstractAdverse early experiences significantly alter behavioral and neural trajectories via aberrant brain maturation. Children with a history of early life stress (ELS) exhibit maladaptive behaviors and increased risk of mental illness later in life. Evidence in ELS-exposed humans identifies a role of atypical corticolimbic development; specifically, within amygdala-prefrontal cortex (PFC) circuits, and show precocially mature task-based corticolimbic functional connectivity (FC). However, the neurobiological substrates of such ELS-driven developmental changes remain unknown. Here, we identify putative neurobiological changes to determine the timeline of developmental perturbations following ELS in rats. Anterograde axonal tracing from basolateral amygdala (BLA) to pre- and infralimbic (PL, IL) PFC was quantified at postnatal days (PD)28, 38, and 48, along with anxiety-like behavior, in maternally separated (ELS) or control reared (CON) male and female rats. Resting state (rs)FC was assessed at PD28 and PD48 in a separate cohort. We report that ELS-exposed female rats show early maturation of BLA-PFC innervation at PD28, with ELS-related changes in males not appearing until PD38. ELS disrupted the maturation of rsFC from PD28 to PD48 in females, with enduring relationships between early rsFC and later anxiety-like behavior. Only transient ELS-related changes in rsFC were seen in male PL. Together, these data provide evidence that female rats may be more vulnerable to the effects of ELS via precocial BLA-PFC innervation, which may drive altered corticolimbic rsFC. These data also provide evidence that increased BLA-IL rsFC is associated with behavioral resiliency following ELS in female rats, providing mechanistic insight into the underlying etiology of adversity-induced vulnerability and resiliency.

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Translatomic profiling of the acute stress response: It’s a TRAP

10.1101/2020.11.24.392464 ◽

2020 ◽

Author(s):

Lukas von Ziegler ◽

Johannes Bohacek ◽

Pierre-Luc Germain

Keyword(s):

Life Stress ◽

Early Life ◽

Pyramidal Neurons ◽

Acute Stress ◽

Affinity Purification ◽

Early Life Stress ◽

Cell Types ◽

Ca3 Pyramidal Neurons ◽

The Impact ◽

The Brain

AbstractThe impact of stress on gene expression in different cell types of the brain remains poorly characterized. Three pioneering studies have recently used translating ribosome affinity purification followed by RNA sequencing (TRAP-seq) to assess the response to stress in CA3 pyramidal neurons of the hippocampus. The results suggest that acute stress alters the translation of thousands of genes in CA3 pyramidal neurons, and that this response is strongly modulated by factors such as sex, genotype and a history of early life stress. However, our reanalysis of these datasets leads to different conclusions. We confirm that acute stress induces robust translational changes in a small set of genes. However, we found no evidence that either early life stress or sex have an effect on gene translation induced by acute stress. Our findings highlight the need for additional studies with adequate sample sizes and proper methods of analysis to assess the impact of stress across cell types in the brain.

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Faculty Opinions recommendation of [CONFERENCE POSTER]: Towards imaging biomarkers of early life stress: decreased resting state default network connectivity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717097875.792402837 ◽

2012 ◽

Author(s):

Amit Etkin

Keyword(s):

Resting State ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Network Connectivity ◽

Imaging Biomarkers ◽

Default Network

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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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