Dataset Information

Long-Term Neuroanatomical Consequences of Childhood Maltreatment: Reduced Amygdala Inhibition by Medial Prefrontal Cortex.

ABSTRACT: Similar to patients with Major depressive disorder (MDD), healthy subjects at risk for depression show hyperactivation of the amygdala as a response to negative emotional expressions. The medial prefrontal cortex is responsible for amygdala control. Analyzing a large cohort of healthy subjects, we aimed to delineate malfunction in amygdala regulation by the medial prefrontal cortex in subjects at increased risk for depression, i.e., with a family history of affective disorders or a personal history of childhood maltreatment. We included a total of 342 healthy subjects from the FOR2107 cohort (www.for2107.de). An emotional face-matching task was used to identify the medial prefrontal cortex and right amygdala. Dynamic Causal Modeling (DCM) was conducted and neural coupling parameters were obtained for healthy controls with and without particular risk factors for depression. We assigned a genetic risk if subjects had a first-degree relative with an affective disorder and an environmental risk if subjects experienced childhood maltreatment. We then compared amygdala inhibition during emotion processing between groups. Amygdala inhibition by the medial prefrontal cortex was present in subjects without those two risk factors, as indicated by negative model parameter estimates. Having a genetic risk (i.e., a family history) did not result in changes in amygdala inhibition compared to no risk subjects. In contrast, childhood maltreatment as environmental risk has led to a significant reduction of amygdala inhibition by the medial prefrontal cortex. We propose a mechanistic explanation for the amygdala hyperactivity in subjects with particular risk for depression, in particular childhood maltreatment, caused by a malfunctioned amygdala downregulation via the medial prefrontal cortex. As childhood maltreatment is a major environmental risk factor for depression, we emphasize the importance of this potential early biomarker.

SUBMITTER: Kessler R

PROVIDER: S-EPMC7283497 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Long-Term Neuroanatomical Consequences of Childhood Maltreatment: Reduced Amygdala Inhibition by Medial Prefrontal Cortex.

Kessler Roman R Schmitt Simon S Sauder Torsten T Stein Frederike F Yüksel Dilara D Grotegerd Dominik D Dannlowski Udo U Hahn Tim T Dempfle Astrid A Sommer Jens J Steinsträter Olaf O Nenadic Igor I Kircher Tilo T Jansen Andreas A

Frontiers in systems neuroscience 20200603

Similar to patients with Major depressive disorder (MDD), healthy subjects at risk for depression show hyperactivation of the amygdala as a response to negative emotional expressions. The medial prefrontal cortex is responsible for amygdala control. Analyzing a large cohort of healthy subjects, we aimed to delineate malfunction in amygdala regulation by the medial prefrontal cortex in subjects at increased risk for depression, i.e., with a family history of affective disorders or a personal hist ...[more]

PMID: 32581732

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Project description:Altered functional connectivity (FC) between the medial prefrontal cortex (mPFC) and amygdala is widely implicated as a neural mechanism explaining risk for psychopathology among those exposed to early life trauma. Nonetheless, contemporary neuroimaging research has shifted toward large-scale network models of brain function, and it is not clear how this common bi-nodal finding fits into larger-scale network models. Here, using dynamic functional connectivity (DFC) approaches combined with large-scale network analyses, the larger role of bi-nodal FC between mPFC and amygdala among a sample of adolescent girls is investigated. The sample was comprised of 30 healthy control girls and 26 girls exposed to either physical or sexual assault who underwent a resting-state scan during 3T MRI. DFC using a sliding window approach was used to create weighted, undirected, graphs from the resting-state data following parcellation with a 215 regions-of-interest (ROI) atlas. Using a priori ROI, the predicted finding of lessor FC between mPFC and amygdala as a function of early life trauma was replicated in this sample. By contrast, early life trauma was associated with greater large-scale network modularity. Using a dynamic FC approach, it is also demonstrated that within-subject variability in this bi-nodal FC closely tracks within-subject fluctuations in large-scale network patterns, including connectivity between a limbic and default mode network (in which the amygdala and mPFC nodes belong, respectively) as well as overall modular organization. These results suggest that bi-nodal FC, such as amygdala-mPFC FC, may generally reflect larger-scale network patterns. Future research is necessary to understand whether these associations between nodal FC and large-scale network organization better reflect top-down processes (larger-scale network organization drives bi-nodal FC) or bottom-up processes (bi-nodal FC drives larger-scale network organization) and the related impact of early life trauma.

Dataset Information

Long-Term Neuroanatomical Consequences of Childhood Maltreatment: Reduced Amygdala Inhibition by Medial Prefrontal Cortex.

Publications

Long-Term Neuroanatomical Consequences of Childhood Maltreatment: Reduced Amygdala Inhibition by Medial Prefrontal Cortex.

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