Altered Cerebellar Functional Connectivity with Intrinsic Connectivity Networks in Adults with Major Depressive Disorder

Abstract

BackgroundNumerous studies have demonstrated the higher-order functions of the cerebellum, including emotion regulation and cognitive processing, and have indicated that the cerebellum should therefore be included in the pathophysiological models of major depressive disorder. The aim of this study was to compare the resting-state functional connectivity of the cerebellum in adults with major depression and healthy controls.MethodsTwenty adults with major depression and 20 gender-, age-, and education-matched controls were investigated using seed-based resting-state functional connectivity magnetic resonance imaging.ResultsCompared with the controls, depressed patients showed significantly increased functional connectivity between the cerebellum and the temporal poles. However, significantly reduced cerebellar functional connectivity was observed in the patient group in relation to both the default-mode network, mainly including the ventromedial prefrontal cortex and the posterior cingulate cortex/precuneus, and the executive control network, mainly including the superior frontal cortex and orbitofrontal cortex. Moreover, the Hamilton Depression Rating Scale score was negatively correlated with the functional connectivity between the bilateral Lobule VIIb and the right superior frontal gyrus in depressed patients.ConclusionsThis study demonstrated increased cerebellar coupling with the temporal poles and reduced coupling with the regions in the default-mode and executive control networks in adults with major depression. These differences between patients and controls could be associated with the emotional disturbances and cognitive control function deficits that accompany major depression. Aberrant cerebellar connectivity during major depression may also imply a substantial role for the cerebellum in the pathophysiological models of depression.

Altered cerebellar–cerebral resting-state functional connectivity reliably identifies major depressive disorder

“…A recent quantitative meta-analysis of a considerable number of functional imaging studies of depressed patients revealed the abnormal activation of the ACC, the prefrontal cortex, the fusiform gyrus, and the temporal gyrus in depressed patients (Fitzgerald et al, 2008). In addition, the involvement of the cerebellum in MDD was confirmed by the findings of morphologic alterations and neural bias of the cerebellum in MDD studies during rest (Alalade et al, 2011;Liu et al, 2012;Zeng et al, 2012) and by task-related fMRI (Chantiluke et al, 2012;Fitzgerald et al, 2008). Although these findings have provided evidence for the dysfunction of the cerebellum in MDD, to our knowledge, the current study is the first to explore altered cerebellar-cerebral functional connectivity patterns to discriminate MDD patients from controls, which could provide a deeper understanding of the role of the cerebellum in the symptoms and deficits associated with MDD from the viewpoint of cerebellar-cerebral circuits.…”

“…Indeed, the cerebellum has been shown to be involved in the pathology of depression by converging evidence. In addition to the structural abnormalities of the cerebellum observed in depression (Allen et al, 1997;Frodl et al, 2010;Lee et al, 2011;Liu et al, 2010;Peng et al, 2011;Soares and Mann, 1997), several functional MRI studies have found irregular activation patterns in the cerebellum, for instance, altered cerebellar-cerebral functional connectivity during the resting state (Alalade et al, 2011;Liu et al, 2012;Zeng et al, 2012) and abnormal cerebellum activation in MDD patients performing cognitive (Chantiluke et al, 2012) and emotional tasks (Fitzgerald et al, 2008;Frodl et al, 2010). Moreover, despite an early, intense dispute, the significant insight that the cerebellum not only subserves the prevailing motor coordination but also some other higher functions, i.e., cognition and emotion control, has achieved strong consensus (Allen et al, 1997;Gao et al, 1996;Konarski et al, 2005;Middleton and Strick, 1994).…”

Abnormal cerebellar volume in acute and remitted major depression

“…Of note, cerebellar area IX has even been suggested to form a major node of this functional network (Habas et al 2009). Available investigations on altered cerebellar-cerebral functional connectivity in depressed patients have yet employed cerebellar seed regions other than area IX (Alalade et , Liu et al 2012, Guo et al 2013, Ma et al 2013. Also, the techniques for imaging data analyses in these investigations relied on conventional segmentation algoriths and did not employ cerebellum-optimized protocols (Guo et al 2013).…”

Combined Metabolomics and Proteomics Analysis of Major Depression in an Animal Model: Perturbed Energy Metabolism in the Chronic Mild Stressed Rat Cerebellum

“…Moreover, emerging evidence has indicated cerebellar abnormalities in MDD; specifically, smaller cerebellar and cerebellar vermal volumes have been found in MDD patients (Beyer and Krishnan, 2002;Shah et al, 1992). Neurobehavioral (Greer et al, 2005;Sweeney et al, 1998) and neuroimaging studies have associated MDD with abnormal cerebellar function (Kimbrell et al, 2002;Liu L. et al, 2012;Liu Z. et al, 2010;Nofzinger et al, 2005). Furthermore, previous findings have also shown cerebellar involvement in the stress response (Ito, 2006;Madtes and King, 1999;Mazzocchi et al, 1999;Sanchez et al, 2000).…”