J Psychiatry Neurosci 2015;40(3):197-206
Laura Koenders, MSc*; Marise W.J. Machielsen, MD, MSc*; Floor J. van der Meer, MSc; Angelique C.M. van Gasselt, MSc; Carin J. Meijer, PhD; Wim van den Brink, MD, PhD; Maarten W.J. Koeter, PhD; Matthan W.A. Caan, PhD; Janna Cousijn, PhD; Anouk den Braber, PhD; Dennis van ‘t Ent, PhD; Maaike M. Rive, MD, MSc; Aart H. Schene, MD, PhD; Elsmarieke van de Giessen, MD, PhD; Chaim Huyser, MD, PhD; Bart P. de Kwaasteniet, MD, MSc; Dick J. Veltman, MD, PhD; Lieuwe de Haan, MD, PhD
Background: Schizophrenia is highly comorbid with cannabis use disorders (CUDs), and this comorbidity is associated with an unfavourable course. Early onset or frequent cannabis use may influence brain structure. A key question is whether comorbid CUDs modulate brain morphology alterations associated with schizophrenia.
Methods: We used surface-based analysis to measure the brain volume, cortical thickness and cortical surface area of a priori–defined brain regions (hippocampus, amygdala, thalamus, caudate, putamen, orbitofrontal cortex, anterior cingulate cortex, insula, parahippocampus and fusiform gyrus) in male patients with schizophrenia or related disorders with and without comorbid CUDs and matched healthy controls. Associations between age at onset and frequency of cannabis use with regional grey matter volume were explored.
Results: We included 113 patients with (CUD, n = 80) and without (NCUD, n = 33) CUDs and 84 controls in our study. As expected, patients with schizophrenia (with or without a CUD) had smaller volumes of most brain regions (amygdala, putamen, insula, parahippocampus and fusiform gyrus) than healthy controls, and differences in cortical volume were mainly driven by cortical thinning. Compared with the NCUD group, the CUD group had a larger volume of the putamen, possibly driven by polysubstance use. No associations between age at onset and frequency of use with regional grey matter volumes were found.
Limitations: We were unable to correct for possible confounding effects of smoking or antipsychotic medication.
Conclusion: Patients with psychotic disorders and comorbid CUDs have larger putamen volumes than those without CUDs. Future studies should elaborate whether a large putamen represents a risk factor for the development of CUDs or whether (poly)substance use causes changes in putamen volume.
*Both authors contributed equally to this manuscript and should be referred to as joint first authors.
Submitted Mar. 19, 2014; Revised Sept. 20, 2014; Accepted Sept. 26, 2014; Early-released Dec. 16. 2014
Acknowledgments: The authors thank the patients and healthy controls who participated in this study. This study was funded with grants from ZonMW (grant numbers: 3160007, 91676084, 31160003, 31180002, 31000056, 2812412, 100001002, 100002034), NWO (grant numbers: 90461193, 40007080, 48004004, 40003330), and additional grants from the Amsterdam Brain Imaging Platform, Neuroscience Campus Amsterdam and the Dutch Brain foundation. The processing with FreeSurfer was performed on the Dutch e-Science Grid through the BiG Grid project and COMMIT project “e-Biobanking with imaging for healthcare,” which are funded by the Netherlands Organization for Scientific Research (NWO). The funding agency played no role in the design and conduct of the study; the collection, management, analysis and interpretation of the data; the preparation, review, or approval of the manuscript; or in the decision to submit the manuscript for publication.
Affiliations: Department of Psychiatry (Koenders, Machielsen, Van der Meer, Van Gasselt, Meijer, Van den Brink, Koeter, Cousijn, Rive, Schene, Huyser, De Kwaasteniet, Veltman, de Haan) and Department of Nuclear Medicine (Caan, Van de Giessen), Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, The Netherlands; VU medical center, Amsterdam, The Netherlands (Veltman, Den Braber, Van’t Ent); De Bascule, Academic Center for Child and Adolescent Psychiatry, Amsterdam, The Netherlands (Huyser); Department of Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands (Schene); Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, Nijmegen, the Netherlands (Schene).
Competing interests: None declared.
Contributors: L. Koenders and M. Machielsen had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. L. Koenders, M. Machielsen, C. Meyer and L. de Haan designed the study. L. Koenders, M. Machielsen, A. van Gasselt, M. Caan, J. Cousijn, A. den Braber, D. van ‘t Ent, M. Rive, A. Schene, E. van de Giessen, C. Huyser, B. de Kwaasteniet and D. Veltman acquired the data, which L. Koenders, J Psychiatry Neurosci 2015;40(3) 205 M. Machielsen, F. van der Meer, C. Meyer, W. van den Brink, M. Koeter, M. Caan, J. Cousijn, D. Veltman and L. de Haan analyzed. L. Koenders, M. Machielsen and F. van der Meer wrote the article, which all authors reviewed and approved for publication.
Correspondence to: L. Koenders, AMC, Academic Psychiatric Centre, Meibergdreef 9 1105, AZ Amsterdam, The Netherlands; firstname.lastname@example.org