The cerebellum plays an important role in depression. Cerebro-cerebellar circuits have been found to show aberrance in bipolar disorder (BD) and major depressive disorder (MDD). However, whether the cerebro-cerebellar connectivity contributes equally to the pathologic mechanisms of BD and MDD remains unknown. We recruited 33 patients with MDD, 32 patients with BD, and 43 healthy controls (HC). We selected six seed regions (three per hemisphere) in the cerebrum, corresponding to the affective, cognitive control, and default mode networks, to establish cerebro-cerebellar functional connectivity maps. Relative to the HC, both the BD and MDD patients exhibited weaker negative connectivity between the right subgenual anterior cingulate cortex and the cerebellar vermis IV_V (p = 0.03, p = 0.001) and weaker positive connectivity between the left precuneus and the left cerebellar lobule IX (p = 0.043, p = 0.000). Moreover, the MDD patients showed weaker positive connectivity in the left precuneus-left cerebellar lobule IX circuit than the BD patients (p = 0.049). In addition, the BD patients showed weaker positive connectivity in the right dorsolateral prefrontal cortex-left cerebellar lobule Crus Ι circuit compared to the HC (p = 0.002) or the MDD patients (p = 0.013). Receiver operating characteristic curves analyses showed that the altered cerebro-cerebellar connectivities could be used to distinguish the patients from the HC with relatively high accuracy. Our findings suggested that differences in connectivity of cerebro-cerebellar circuits, which are involved in affective or cognitive functioning, significantly contributed to BD and MDD.
Disturbed hypothalamus-pituitary-adrenal axis function, which leads to excessive and prolonged hypercortisolemia, is a core feature of major depressive disorder (MDD). However, the relationships between depression, brain structure and function, and cortisol levels are unclear. The current study examined the whole-brain functional connectivity pattern of patients with MDD and evaluated the association between functional connectivity and serum cortisol levels in MDD. A total of 93 unmedicated patients with MDD and 139 healthy control subjects underwent resting-state functional magnetic resonance imaging. Voxel-wise whole-brain connectivity was analyzed by using a graph theory approach: functional connectivity strength (FCS). A seed-based resting-state functional connectivity analysis was further performed to investigate abnormal functional connectivity patterns of those regions with changed FCS. Morning blood samples were drawn for cortisol measurements in some subjects (including 53 MDD patients and 30 controls). The MDD patients had a significantly lower FCS in the left posterior lobes of the cerebellum (mainly lobule Crus II) (p < 0.05, TFCE corrected). The seed-based functional connectivity analysis revealed decreased functional connectivity between the left posterior cerebellum and the left medial orbitofrontal cortex (OFC) (p < 0.05, TFCE corrected). Moreover, the functional connectivity between the left posterior cerebellum and the left medial OFC were significantly positively correlated with the serum cortisol levels in MDD patients. Our results suggest that cerebellar dysconnectivity, in particular distributed cerebellar-OFC functional connectivity, may be associated with serum cortisol levels in MDD patients.
Purpose To investigate the whole-brain intrinsic functional connectivity patterns of patients with bipolar disorder (BD). Materials and Methods This prospective study was approved by the research ethics committee, and all participants provided informed consent. Thirty-seven patients with nonmedicated BD II depression and 37 healthy control participants underwent resting-state functional magnetic resonance (MR) imaging. Whole-brain connectivity was analyzed by using a graph theory approach: functional connectivity strength (FCS). Clinical state was assessed by using the 24-item Hamilton Depression Rating Scale and the Young Mania Rating Scale. Two-sample t test and nonparametric correlation analysis were used. Results Compared with healthy control participants, patients with BD II showed decreased FCS in the default mode network (ie, the bilateral medial prefrontal cortex, bilateral middle temporal gyrus, left precuneus, and right posterior cingulate cortex), right supramarginal gyrus and angular gyrus, right superior frontal gyrus, and right superior parietal gyrus and increased FCS in the bilateral temporal pole (including the parahippocampal gyrus and amygdale), left anterior cingulate cortex, left superior temporal gyrus, right lingual gyrus, and left anterior lobe of the cerebellum (P < .05; AlphaSim corrected). Conclusion These results suggest that patients with BD have disrupted intrinsic functional connectivity mainly in the default mode network and limbic system, which might be associated with the pathophysiologic structure of BD. (©) RSNA, 2016.
Depression in the context of bipolar disorder (BD) is often misdiagnosed as unipolar depression (UD), leading to mistreatment and poor clinical outcomes. However, little is known about the similarities and differences in cerebellum between BD and UD. Patients with BD (n=35) and UD (n=30) during a depressive episode as well as 40 healthy controls underwent diffusional kurtosis imaging (DKI) and three dimensional arterial spin labeling (3D ASL). The DKI parameters including mean kurtosis (MK), axial kurtosis (Ka), radial kurtosis (Kr),fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da) and radial diffusivity (Dr) and 3D ASL parameters (i.e. cerebral blood flow) was measured by using regions-of-interest (ROIs) analysis in the superior cerebellar peduncles (SCP), middle cerebellar peduncles (MCP) and dentate nuclei (DN) of cerebellum. Patients with UD exhibited significant differences from controls for DKI measures in bilateral SCP and MCP and cerebral blood flow (CBF) in bilateral SCP and left DN. Patients with BD exhibited significant differences from controls for DKI measures in the right MCP and left DN and CBF in the left DN. Patients with UD showed significantly lower MD values compared with patients with BD in the right SCP. Correlation analysis showed there were negative correlations between illness duration and MD and Dr values in the right SCP in UD. This study was cross-sectional and the sample size was not large. Parts of the patients included were under medication prior to MRI scanning. Our findings provide new evidence of microstructural changes in cerebellum in BD and UD. The two disorders may have overlaps in microstructural abnormality in MCP and DN during the depressive period. Microstructural abnormality in SCP may be a key neurobiological feature of UD.
Depression in the context of bipolar disorder (BD) is often misdiagnosed as unipolar depression (UD), leading to mistreatment and poor clinical outcomes. However, little is known about the similarities and differences in interhemispheric functional connectivity between BD and UD. Patients with bipolar II disorder (n = 36) and UD (n = 32) during a depressive episode as well as 40 healthy controls underwent resting-state functional magnetic resonance imaging. The functional connectivity between any pair of symmetric interhemispheric voxels (i.e., functional homotopy) was measured by voxel-mirrored homotopic connectivity (VMHC). The three groups showed significant VMHC differences in the posterior cingulate cortex (PCC), fusiform and lingual gyrus, anterior lobe of the cerebellum (CeAL), and posterior lobe of the cerebellum (CePL). In the BD group, the VMHC decreases in the fusiform/lingual gyrus, CeAL, and CePL were shown relative to controls. In the UD group, the VMHC decreases in the PCC, fusiform/lingual gyrus, and CePL were shown relative to controls. No regions of increased VMHC were detected in either patient group. There was no significant difference in the VMHC values in any brain region between the BD group and the UD group. Depressive episodes in BD and UD have similar impairments of interhemispheric coordination, which might imply an overlap in the neuropathology of depression.
Several recent studies have reported a strong association between the cerebellar structural and functional abnormalities and psychiatric disorders. However, there are no studies to investigate possible changes in cerebellar functional connectivity in bipolar disorder. This study aimed to examine the whole-brain functional connectivity pattern of patients with remitted bipolar disorder II, in particular in the cerebellum. A total of 25 patients with remitted bipolar disorder II and 25 controls underwent resting-state functional magnetic resonance imaging and neuropsychological tests. Voxel-wise whole-brain connectivity was analyzed using a graph theory approach: functional connectivity strength. A seed-based resting-state functional connectivity analysis was further performed to investigate abnormal functional connectivity pattern of those regions with changed functional connectivity strength. Remitted bipolar disorder II patients had significantly decreased functional connectivity strength in the bilateral posterior lobes of cerebellum (mainly lobules VIIb/VIIIa). The seed-based functional connectivity analyses revealed decreased functional connectivity between the right posterior cerebellum and the default mode network (i.e. right posterior cingulate cortex/precuneus and right superior temporal gyrus), bilateral hippocampus, right putamen, left paracentral lobule and bilateral posterior cerebellum and decreased functional connectivity between the left posterior cerebellum and the right inferior parietal lobule and bilateral posterior cerebellum in patients with remitted bipolar disorder II. Our results suggest that cerebellar dysconnectivity, in particular distributed cerebellar-cerebral functional connectivity, might be associated with the pathogenesis of bipolar disorder.
Identifying brain differences and similarities between bipolar disorder (BD) and major depressive disorder (MDD) is necessary for increasing our understanding of the pathophysiology and for developing more effective treatments. However, the features of whole-brain intrinsic functional connectivity underlying BD and MDD have not been directly compared. We collected resting-state fMRI data from 48 BD patients, 48 MDD patients, and 51 healthy subjects. We constructed voxel-wise whole-brain functional networks and computed regional functional connectivity strength (FCS) using graph-theory and further divided the regional FCS into long-range FCS (lFCS) and short-range FCS (sFCS). Relative to the controls, both the BD and MDD patients showed decreased sFCS in the bilateral precuneus. In addition, the BD patients showed increased and the MDD patients showed decreased lFCS and sFCS in the bilateral cerebellum. The BD patients also showed increased lFCS in the right middle temporal gyrus and increased sFCS in the bilateral thalamus compared to either the MDD patients or the controls. These findings suggest that BD and MDD may have some shared as well as a greater number of specific impairments in their functional connectivity patterns, providing new evidence for the pathophysiology of BD and MDD at the large-scale whole brain connectivity level.