Prefrontal brain responsiveness to negative stimuli distinguishes familial risk for major depression from acute disorder

Prefrontal brain responsiveness to negative stimuli distinguishes familial risk for major depression from acute disorder


J Psychiatry Neurosci 2017;42(5):343-352

Nils Opel, MD; Ronny Redlich, PhD; Dominik Grotegerd, PhD; Katharina Dohm, MA; Dario Zaremba, MA; Susanne Meinert, MA; Christian Bürger, MA; Leonie Plümpe; Judith Alferink, MD; Walter Heindel, MD; Harald Kugel, PhD; Peter Zwanzger, MD; Volker Arolt, MD, PhD; Udo Dannlowski, MA, MD, PhD


Background: Identifying reliable trait markers of familial risk for major depressive disorder (MDD) is a challenge in translational psychiatric research. In individuals with acute MDD, dysfunctional connectivity patterns of prefrontal areas have been shown repeatedly. However, it has been unclear in which neuronal networks functional alterations in individuals at familial risk for MDD might be present and to what extent they resemble findings previously reported in those with acute MDD.

Methods: We investigated differences in blood oxygen level–dependent (BOLD) response of the medial orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) to aversive stimuli between acute MDD and familial risk for the disorder in healthy first-degree relatives of acutely depressed patients with MDD (HC-FH+), healthy age- and sex-matched controls without any family history of depression (HC-FH–), and acutely depressed patients with MDD with (MDD-FH+) and without a family history of depression (MDD-FH–) during a frequently used emotional face-matching paradigm. Analyses of task-specific network connectivity were conducted in terms of psychophysiological interactions (PPI).

Results: The present analysis included a total of 100 participants: 25 HC-FH+, 25 HC-FH–, 25 MDD-FH+ and 25 MDD-FH–. Patients with MDD exhibited significantly increased activation in the medial OFC to negative stimuli irrespective of familial risk status, whereas healthy participants at familial risk and patients with MDD alike showed significant hypoactivation in the DLPFC compared with healthy participants without familial risk. The PPI analyses revealed significantly enhanced task-specific coupling between the medial OFC and differing cortical areas in individuals with acute MDD and those with familial risk for the disorder.

Limitations: The main limitation of our study is its cross-sectional design.

Conclusion: Whereas hypoactivation during negative emotion processing in the DLPFC appears as a common feature in both healthy high-risk individuals and acutely depressed patients, activation patterns of the medial OFC and its underlying connectivity seem to distinguish familial risk from acute disorder.

Submitted Oct. 3, 2016; Revised Jan. 27, 2017; Accepted Feb. 16, 2017; Early-released June 13, 2017

Acknowledgements: The study was supported by grants of Innovative Medizinische Forschung (IMF) of the Medical Faculty of Münster (DA120309, DA111107 and DA211012 to U. Dannlowski), a research grant of the University Medical Center Giessen and Marburg (UKGM) (7/2013 MR to U. Dannlowski), and grants of the German Research Foundation (DFG; grants FOR 2107, DA1151/5-1 and SFB-TRR58, Project C09 to U. Dannlowski). The authors acknowledge support from the Open Access Publication Fund of the University of Muenster.

Affiliations: From the Department of Psychiatry, University of Münster, Münster, Germany (Opel, Redlich, Grotegerd, Dohm, Zaremba, Meinert, Bürger, Plümpe, Alferink, Arolt, Dannlowski); the Cluster of Excellence EXC 1003, Cells in Motion, University of Münster, Münster, Germany (Alferink); the Department of Clinical Radiology, University of Münster, Münster, Germany (Heindel, Kugel); the kbo-Inn-Salzach-Klinikum, Wasserburg am Inn, Germany (Zwanzger); the Department of Psychiatry, Ludwig-Maximilian-University, Munich, Germany (Zwanzger); and the Department of Psychiatry, University of Marburg, Marburg, Germany (Dannlowski).

Competing interests: None declared.

Contributors: N. Opel, R. Redlich, P. Zwanzger, V. Arolt and U. Dannlowski designed the study. N. Opel, D. Grotegerd, K. Dohm, D. Zaremba, S. Meinert, C. Bürger, L. Plümpe, J. Alferink, W. Heindel and H. Kugel acquired the data, which N. Opel and U. Dannlowski analyzed. N. Opel and U. Dannlowski wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.160198

Correspondence to: U. Dannlowski, Department of Psychiatry, University of Münster, Albert-Schweitzer-Str. 11, 48149 Münster, Germany;