Reduced Intrinsic Connectivity of Amygdala in Adults with Major Depressive Disorder

Abstract

Imaging studies of major depressive disorder (MDD) have demonstrated enhanced resting-state activity of the amygdala as well as exaggerated reactivity to negative emotional stimuli relative to healthy controls (HCs). However, the abnormalities in the intrinsic connectivity of the amygdala in MDD still remain unclear. As the resting-state activity and functional connectivity (RSFC) reflect fundamental brain processes, we compared the RSFC of the amygdala between unmedicated MDD patients and HCs. Seventy-four subjects, 55 adults meeting the DSM-IV criteria for MDD and 19 HCs, underwent a resting-state 3-T functional magnetic resonance imaging scan. An amygdala seed-based low frequency RSFC map for the whole brain was generated for each group. Compared with HCs, MDD patients showed a wide-spread reduction in the intrinsic connectivity of the amygdala with a variety of brain regions involved in emotional processing and regulation, including the ventrolateral prefrontal cortex, insula, caudate, middle and superior temporal regions, occipital cortex, and cerebellum, as well as increased connectivity with the bilateral temporal poles (p < 0.05 corrected). The increase in the intrinsic connectivity of amygdala with the temporal poles was inversely correlated with symptom severity and anxiety scores. Although the directionality of connections between regions cannot be inferred from temporal correlations, the reduced intrinsic connectivity of the amygdala predominantly with regions involved in emotional processing may reflect impaired bottom-up signaling for top-down cortical modulation of limbic regions leading to abnormal affect regulation in MDD.

In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging

“…Resting state fMRI studies also have shown that connectivity in these circuits is altered in generalized anxiety disorder (40), panic disorder (41), and depression (42). Some aspects of these neuronal circuits have also been closely connected with other neurodegenerative tauopathies, e.g., progressive supranuclear palsy, as demonstrated by Gardner et al (43) and further confirmed by direct measurement of PHF-tau accumulation with [F-18]FDDNP PET (19).…”

Neuroanatomical correlates of negative emotionality-related traits: A systematic review and meta-analysis

“…The current meta-analysis extends the previous findings indicating that morphological variability in a core left lateralized cortico-limbic circuit supports NE -related behavioral and functional differences in emotional processing; specifically, the propensity to worry and to ruminate on the negative events, to form persistent associations between emotional stimuli and the reduced ability to adequately regulate emotion is associated an with an increased GM in the left amygdala/PHG, potentially supporting a sustained activation and with lower WM integrity in the left UF and reduced GM in OFC/ACC associated with lower frontal activation. In major depressive disorder one of the most consistent findings is the reduced volume of the left ACC (Drevets et al, 2008); moreover histological changes (Rajkovska et al, 1999, see below) and reduced intrinsic connectivity (Ramasubbu et al, 2014) have been reported predominantly in the left cortico-limbic network (although some inconsistencies exist in the literature). Taken together, these results suggest that NE-related structural differences in the left amygdala/PHG-OFC/ACC circuit are associated to altered emotional processing and regulatory mechanisms and play a more prominent role in the pathophysiology of depression.…”

Altered functional connectivity density in major depressive disorder at rest

“…Functional magnetic resonance imaging (fMRI) has been applied to examine differential activations in certain brain regions between MDD patients and healthy controls (HC), either in the resting state or in a response to a specific task. Resting-state functional connectivity (rs-FC) studies with fMRI data have reported abnormal signal fluctuations in anterior cingulate cortex (ACC) [2], amygdala [3][4][5][6] and orbitofrontal cortex (OFC) [7,8] in MDD individuals.…”