Research report Neural correlates of disbalanced motor control in major depression S. Walther a, ⁎, O. Höfle a , A. Federspiel b , H. Horn a , S. Hügli a , R. Wiest c , W. Strik a , T.J. Müller a a University Hospital of Psychiatry, Bern, Switzerland b Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, Bern, Switzerland c Institute of Diagnostic and Interventional Neuroradiology, University of Bern, Switzerland article info abstract Article history: Received 17 June 2011 Received in revised form 19 August 2011 Accepted 19 August 2011 Available online 17 September 2011 Background: Motor retardation is a common symptom of major depressive disorder (MDD). Despite the existence of various assessment methods, little is known on the pathobiology of motor retardation. We aimed to elucidate aspects of motor control investigating the association of objective motor activity and resting state cerebral blood flow (CBF). Methods: Nineteen control subjects and 20 MDD patients were investigated using arterial spin la- beling (ASL) at 3 T in the morning to quantify resting state CBF. Afterwards wrist actigraphy was recorded for 24 h. CBF, group and activity level (AL) were entered into a whole brain general linear model. Results: MDD patients had reduced AL. Both groups had linear associations of AL and CBF in bilat- eral rostral prefrontal cortex. Groups differed in four clusters associated with motor control. In controls a positive association was found in the left caudal cingulate zone (CCZ) and an inverse association in the right external globus pallidus (GPe). MDD patients had positive associations in the right orbitofrontal cortex and inverse associations in the left supplemental motor area. Limitations: Patients were on antidepressant medication. Conclusions: The pattern of associations between CBF and AL suggest disbalanced motor control in MDD. Findings are in line with the hypothesis of dopamine deficits contributing to motor retardation in MDD. © 2011 Elsevier B.V. All rights reserved. Keywords: Arterial spin labeling Actigraphy Major depression Caudal cingulate zone External globus pallidus Supplemental motor area 1. Introduction Psychomotor retardation is a key symptom in major de- pressive disorder (MDD) (Schrijvers et al., 2008; Sobin and Sackeim, 1997). Furthermore, psychomotor symptoms are thought to have discriminative validity and might predict treatment response (Calugi et al., 2011; Schrijvers et al., 2008; Sobin and Sackeim, 1997). Psychomotor retardation in MDD has been assessed using observation based rating scales, measures of gross motor activity, such as actigraphy, or fine motor performance of different tasks (Hegerl et al., 2005; Pier et al., 2004; Schrijvers et al., 2008; Sobin and Sackeim, 1997). Actigraphy is an easy method of ambulatory behavioral monitoring that has repeatedly demonstrated lower daytime activity in medicated or unmedicated MDD patients (Teicher, 1995; Todder et al., 2009; Volkers et al., 2003). In addition, actigraphy can help to identify neurobiolog- ical correlates of motor behavior (Walther et al., 2010; Walther et al., 2011a, b). Little is known about the neurobiology of motor retardation in major depression. Some findings point to hypodopaminergic states (Martinot et al., 2001; Meyer et al., 2006; Schrijvers et al., 2008; Sobin and Sackeim, 1997) or structural alterations of the basal ganglia circuits (Naismith et al., 2002; Rogers et al., 1998). In fact, motor retardation in MDD shares some aspects of motor disturbances seen in hypodopaminergic basal ganglia disor- ders, such as Parkinson's disease (Caligiuri and Ellwanger, 2000; Rogers et al., 1987, 1998; Sachdev and Aniss, 1994). Clinically rated psychomotor retardation has been associ- ated with decreased resting state cerebral blood flow (CBF) in the dorsolateral prefrontal cortex (DLPFC), orbitofrontal Journal of Affective Disorders 136 (2012) 124–133 ⁎ Corresponding author at: University Hospital of Psychiatry, Bolligenstrasse 111, 3060 Bern, Switzerland. Tel.: +41 31 930 9111; fax: +41 31 930 9404. E-mail address: walther@puk.unibe.ch (S. Walther). 0165-0327/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2011.08.020 Contents lists available at SciVerse ScienceDirect Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad