Research reportNeural correlates of disbalanced motor control in major depression
Introduction
Psychomotor retardation is a key symptom in major depressive 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 neurobiological correlates of motor behavior (Walther et al., 2010, Walther et al., 2011a, Walther et al., 2011b).
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 disorders, such as Parkinson's disease (Caligiuri and Ellwanger, 2000, Rogers et al., 1987, Rogers et al., 1998, Sachdev and Aniss, 1994).
Clinically rated psychomotor retardation has been associated with decreased resting state cerebral blood flow (CBF) in the dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC) (Bench et al., 1993, Mayberg et al., 1994, Narita et al., 2004, Videbech et al., 2002). Likewise, longer reaction times were associated with reduced CBF increase in the striatum during a simple motor task (Hickie et al., 1999). However, previous work on resting state CBF was restricted to region of interest analyses (ROI) with low spatial resolution using positron emission tomography (PET) or single photon emission tomography (SPECT). Improved spatial resolution during CBF quantification is now possible using magnetic resonance imaging (MRI) based arterial spin labeling (ASL), a non-invasive method free from external contrast agents (Wong et al., 1997) that has been applied in major depression before (Chen et al., 2011, Lui et al., 2009).
The aim of the present study was to investigate neural mechanisms involved in motor control in MDD to elucidate the pathobiology of motor retardation. We chose a clinically relevant behavioral marker such as gross motor activity and a relatively simple marker of baseline neural activity, i.e. resting state CBF. Therefore, we applied perfusion MRI at rest and actigraphy on the same day in order to elucidate the association of gross motor activity and resting state CBF in medicated patients with MDD. We hypothesized that patients with MDD would demonstrate reduced motor activity. In addition, we assumed that regional resting state CBF in key motor brain regions would correlate with motor activity. Further, we hypothesized that the associations between motor performance and CBF would differ between MDD patients and healthy subjects.
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Participants
In total, 20 inpatients and outpatients with MDD according to DSM-IV were recruited at the University Hospital of Psychiatry, Bern, Switzerland. In addition, 19 healthy control subjects were recruited, matched for age, gender and education. Diagnoses were ascertained in semi-structured interviews. Patients were further screened with the structured clinical interview for DSM-IV part 2 (SCID-II) to exclude patients with comorbid personality disorders. The unified Parkinson's disease rating scale
Results
The activity level (AL) differed between groups during the day, but not during sleep (see Table 1). Patients had lower AL values. In addition, patients had longer estimated sleep duration (ESD) (see Table 1). To test, whether sleep variables such as duration and quality of sleep had an effect on AL between the groups, a stepwise linear regression analysis was computed for AL with PSQI, ESD and group as regressors. Only the factor group remained in the model (R2 = 0.252, F = 12.5, p = 0.001) was group
Discussion
This is the first study investigating the association of CBF and objective motor activity in MDD. The main finding was that resting state CBF in prefrontal and motor areas in the morning was predictive of motor activity during the rest of the day. Thus, resting state neural activity was linked to behavioral outcome in the direct future. In MDD patients as well as in healthy controls CBF had a positive linear association with AL in bilateral rostral prefrontal cortex (BA 10). In addition, a
Role of the funding source
There was no funding.
Conflict of interest
Dr. Horn has received speaker's fees from Eli-Lilly, Bristol-Myers-Squibb, Lundbeck, Boehringer-Ingelheim and Vifor. Prof. Strik received speaker's fees from/is advisory board member of Eli-Lilly, Pfizer and Lundbeck. Dr. Müller has received research support from Eli-Lilly, speaker's fees from AstraZeneca, Bristol-Myers-Squibb, Janssen-Cilag, Eli-Lilly, Pfizer, Sanofi-Aventis, Glaxo-Smith-Kline, Desitin-Pharma and Vifor. Dr. Müller is advisory board member of Eli-Lilly, Janssen-Cillag, and
Acknowledgments
None.
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