J Psychiatry Neurosci 2015;40(6):412-421
Nenad Vasic, MD; Nadine D. Wolf, MD; Georg Grön, PhD; Zrinka Sosic-Vasic, PhD; Bernhard J. Connemann, MD; Fabio Sambataro, MD, PhD; Anna von Strombeck; Dirk Lang; Stefanie Otte, PhD; Manuela Dudek, MD; Robert C. Wolf, MD
Background: Abnormal regional cerebral blood flow (rCBF) and grey matter volume have been frequently reported in patients with major depressive disorder (MDD). However, it is unclear to what extent structural and functional change co-occurs in patients with MDD and whether markers of neural activity, such as rCBF, can be predicted by structural change.
Methods: Using MRI, we investigated resting-state rCBF and brain structure in patients with MDD and healthy controls between July 2008 and January 2013. We acquired perfusion images obtained with continuous arterial spin labelling, used voxel-based morphometry to assess grey matter volume and integrated biological parametric mapping analyses to investigate the impact of brain atrophy on rCBF.
Results: We included 43 patients and 29 controls in our study. Frontotemporal grey matter volume was reduced in patients compared with controls. In patients, rCBF was reduced in the anterior cingulate and bilateral parahippocampal areas and increased in frontoparietal and striatal regions. These abnormalities were confirmed by analyses with brain volume as a covariate. In patients with MDD there were significant negative correlations between the extent of depressive symptoms and bilateral parahippocampal rCBF. We found a positive correlation between depressive symptoms and rCBF for right middle frontal cortical blood flow.
Limitations: Medication use in patients has to be considered as a limitation of our study.
Conclusion: Our data suggest that while changes of cerebral blood flow and brain volume co-occur in patients with MDD, structural change is not sufficient to explain altered neural activity in patients at rest. Abnormal brain structure and function in patients with MDD appear to reflect distinct levels of neuropathology.
Submitted Aug. 29, 2014; Revised Dec. 2, 2014; Accepted Jan. 13, 2015; Early-released June 30, 2015.
Acknowledgements: The authors thank all patients for their time and interest in this study and Kathrin Brändle for excellent technical support.
Affiliations: Department of Forensic Psychiatry and Psychotherapy, University of Ulm, Germany (Vasic, Dudeck, Otte); Department of Psychiatry and Psychotherapy III, University of Ulm, Germany ( Vasic, Grön, Sosic-Vasic, Connemann, Von Strombeck, Lang); Department of Psychiatry, Psychotherapy and Psychosomatics, Saarland University, Homburg, Germany (N. Wolf, R. Wolf); Brain Center for Motor and Social Cognition@UniPR, Istituto Italiano di Tecnologia, Parma, Italy (Sambataro); Clinic for Psychosomatic Medicine and Psychotherapy, University of Ulm, Germany (Lang).
Competing interests: N. Vasic and M. Dudek declare symposium support from Lilly, Janssen-Cilag, Trommsdorf and Lundbeck. N. Vasic also declares receiving speaker fees from Otsuka and Lundbeck and consulting fees from Servier. F. Sambataro is a full-time employee of Hoffman-La Roche Ltd. in Basel, Switzerland. R. Wolf declares receiving speaker fees from Lundbeck and Otsuka and consulting fees from Trommsdorff. No other competing interests declared.
Contributors: N. Vasic, N. Wolf, B. Connermann and R. Wolf designed the study. N. Vasic, N. Wolf, Z. Sosic-Vasic, A. von Shrombeck, D. Lang and R. Wolf acquired the data, which N. Vasic, N. Wolf, G. Grön, Z. Sosic-Vasic, F. Sambataro, D. Lang, S. Otte, M. Dudek and R. Wolf analyzed. N. Vasic, G. Grön, Z. Sosic-Vasic, S. Otte, M. Dudek and R. Wolf wrote the article, which all authors reviewed and approve for publication.
Correspondence to: N. Vasic, Department of Forensic Psychiatry and Psychotherapy, University of Ulm, District Hospital Guenzburg, Ludwig-Heilmeyer-Str. 2, 89312 Guenzburg, Germany; firstname.lastname@example.org