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

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

doi:10.3389/fnsys.2020.00028

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

Front Syst Neurosci. 2020 Jun 3:14:28. doi: 10.3389/fnsys.2020.00028. eCollection 2020.

Authors

Roman Kessler^{1

2}, Simon Schmitt^{1

2}, Torsten Sauder^{1

3}, Frederike Stein^{1

2}, Dilara Yüksel^{1

2}, Dominik Grotegerd⁴, Udo Dannlowski⁴, Tim Hahn⁴, Astrid Dempfle⁵, Jens Sommer^{2

6}, Olaf Steinsträter^{2

6}, Igor Nenadic^{1

2}, Tilo Kircher^{1

2}, Andreas Jansen^{1

2

6}

Affiliations

¹ Department of Psychiatry and Psychotherapy, Department of Medicine, University of Marburg, Marburg, Germany.
² Centre for Mind, Brain and Behavior (CMBB), University of Marburg and Justus Liebig University Giessen, Marburg, Germany.
³ Department of Neurology, Bayreuth Clinic, Klinikum Bayreuth GmbH, Bayreuth, Germany.
⁴ Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany.
⁵ Institute of Medical Informatics and Statistics, Kiel University, Kiel, Germany.
⁶ Core-Unit Brainimaging, Faculty of Medicine, University of Marburg, Marburg, Germany.

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.

Keywords: childhood maltreatment; connectivity; dynamic causal modeling; emotion processing; fMRI; major depression.