J Psychiatry Neurosci 2015;40(6):394-400
Jakub Späti, PhD; Justin Chumbley, PhD; Nadja Doerig, PhD; Janis Brakowski, MD; Martin Grosse Holtforth, PhD; Erich Seifritz, MD; Simona Spinelli, PhD
Background: Reduced sensitivity to positive feedback is common in patients with major depressive disorder (MDD). However, findings regarding negative feedback are ambiguous, with both exaggerated and blunted responses being reported. The ventral striatum (VS) plays a major role in processing valenced feedback, and previous imaging studies have shown that the locus of controls (self agency v. external agency) over the outcome influences VS response to feedback. We investigated whether attributing the outcome to one’s own action or to an external agent influences feedback processing in patients with MDD. We hypothesized that depressed participants would be less sensitive to the feedback attribution reflected by an altered VS response to self-attributed gains and losses.
Methods: Using functional MRI and a motion prediction task, we investigated the neural responses to self-attributed (SA) and externally attributed (EA) monetary gains and losses in unmedicated patients with MDD and healthy controls.
Results: We included 21 patients and 25 controls in our study. Consistent with our prediction, healthy controls showed a VS response influenced by feedback valence and attribution, whereas in depressed patients striatal activity was modulated by valence but was insensitive to attribution. This attribution insensitivity led to an altered ventral putamen response for SA – EA losses in patients with MDD compared with healthy controls.
Limitations: Depressed patients with comorbid anxiety disorder were included.
Conclusion: These results suggest an altered assignment of motivational salience to SA losses in patients with MDD. Altered striatal response to SA negative events may reinforce the belief of not being in control of negative outcomes contributing to a cycle of learned helplessness.
Submitted Nov. 10, 2014; Revised Nov. 26, 2014, Jan. 13, 2015; Accepted Feb. 7, 2015; Early-released June 23, 2015.
Acknowledgments: The authors thank Dr. Philipp Stämpfli for his invaluable assistance in study procedures. S. Spinelli is funded by a Swiss National Science Foundation Ambizione Fellowship (grants PZ00P3_126363/1 and PZ00P3_146001/1). J. Chumbley is funded by a grant from FAN of the Zurich University Association (ZUNIV). M. Grosse Holtforth and N. Doerig are funded by a grant from the Swiss National Science Foundation (grant PP00P1-123377/1) and a research grant by the Foundation for Research in Science and the Humanities at the University of Zurich. We acknowledge support by the Clinical Research Priority Program “Molecular Imaging” at the University of Zurich.
Affiliations: From the Department of Psychophysiology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan (Späti); the Laboratory for Social and Neural Systems Research, Department of Economics, University of Zurich, Switzerland (Chumbley); the Institute of Psychology, University of Zurich, Zurich, Switzerland (Doerig, Grosse Holtforth); the Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland (Brakowski, Seifritz); the Department of Psychology, University of Bern, Bern, Switzerland (Grosse Holtforth); the Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland (Spinelli); the Neuroscience Center, University and ETH Zurich, Zurich, Switzerland ( Spinelli); and the Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland ( Seifritz, Spinelli).
Competing interests: None declared.
Contributors: J. Chumbley and S. Spinelli designed the study. J. Späti, N. Doerig and J. Brakowski acquired the data, which J. Chumbley, M. Grosse Holtforth, E. Seifritz and S. Spinelli analyzed. S. Spinelli wrote the article. All authors reviewed and approved it for publication.
Correspondence to: S. Spinelli, Preclinical Laboratory for Translational Research into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, August Forel-Strasse 7, CH-8008 Zurich, Switzerland; firstname.lastname@example.org