AUTHOR=Kessler Roman , Schmitt Simon , Sauder Torsten , Stein Frederike , Yüksel Dilara , Grotegerd Dominik , Dannlowski Udo , Hahn Tim , Dempfle Astrid , Sommer Jens , Steinsträter Olaf , Nenadic Igor , Kircher Tilo , Jansen Andreas 

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

JOURNAL=Frontiers in Systems Neuroscience

VOLUME=14

YEAR=2020

URL=https://www.frontiersin.org/journals/systems-neuroscience/articles/10.3389/fnsys.2020.00028

DOI=10.3389/fnsys.2020.00028

ISSN=1662-5137

ABSTRACT=<p>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 <italic>FOR2107</italic> cohort (<ext-link ext-link-type="uri" xlink:href="http://www.for2107.de" xmlns:xlink="http://www.w3.org/1999/xlink">www.for2107.de</ext-link>). 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 <italic>genetic risk</italic> if subjects had a first-degree relative with an affective disorder and an <italic>environmental risk</italic> 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 <italic>genetic risk</italic> (i.e., a family history) did not result in changes in amygdala inhibition compared to <italic>no risk</italic> subjects. In contrast, childhood maltreatment as <italic>environmental risk</italic> 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 <italic>environmental</italic><italic>risk</italic> factor for depression, we emphasize the importance of this potential early biomarker.</p>