Discovery and replication of cerebral blood flow differences in major depressive disorder

Abstract

Major depressive disorder (MDD) is a serious, heterogeneous disorder accompanied by brain-related changes, many of which are still to be discovered or refined. Arterial spin labeling (ASL) is a neuroimaging technique used to measure cerebral blood flow (CBF; perfusion) to understand brain function and detect differences among groups. CBF differences have been detected in MDD, and may reveal biosignatures of disease-state. The current work aimed to discover and replicate differences in CBF between MDD participants and healthy controls (HC) as part of the EMBARC study. Participants underwent neuroimaging at baseline, prior to starting study medication, to investigate biosignatures in MDD. Relative CBF (rCBF) was calculated and compared between 106 MDD and 36 HC EMBARC participants (whole-brain Discovery); and 58 MDD EMBARC participants and 58 HC from the DLBS study (region-of-interest Replication). Both analyses revealed reduced rCBF in the right parahippocampus, thalamus, fusiform and middle temporal gyri, as well as the left and right insula, for those with MDD relative to HC. Both samples also revealed increased rCBF in MDD relative to HC in both the left and right inferior parietal lobule, including the supramarginal and angular gyri. Cingulate and prefrontal regions did not fully replicate. Lastly, significant associations were detected between rCBF in replicated regions and clinical measures of MDD chronicity. These results (1) provide reliable evidence for ASL in detecting differences in perfusion for multiple brain regions thought to be important in MDD, and (2) highlight the potential role of using perfusion as a biosignature of MDD.

Differences in Cerebral Structure Associated With Depressive Symptoms in the Elderly With Alzheimer’s Disease

“…Although the cognitive impairment was also associated with the insular atrophy, a significant correlation between the insula and depressive symptoms was observed after excluding the effect of the cognitive impairment. The result strongly indicated that the insula is vital in the modulation of emotion, which is consistent with previous research that demonstrated insular structures to be abnormal in patients with depressive disorder (Hayata et al, 2015;Ambrosi et al, 2017;Cooper et al, 2019;Whitton et al, 2019;Xu et al, 2019). The insula, as a vital visceral sensory node, is significantly correlated with somatic symptoms in depressed patients (Zu et al, 2019).…”

Altered Cerebral Blood Flow in Alzheimer's Disease With Depression

“…Our study included moderate dementia with MMSE of about 14 and mild depression with mean HAMD of 13.11, which were different from those studies using SPECT and PET including mild dementia with MMSE ranging from 21 to 24 ( 5 , 6 , 23 , 24 ). Hyperperfusion in the supramarginal gyrus was also observed in AD patients with depression, which could be supported by findings of the increased CBF in the right supramarginal gyrus in patients with major depressive disorder ( 26 , 27 ) and depression in AD ( 1 ). Emotion regulation can cause neurons to activate in the regional brain ( 25 ).…”

Characterizing cerebral hemodynamics across the adult lifespan with arterial spin labeling MRI data from the Human Connectome Project-Aging

“…Due to its quantitative and noninvasive nature, ASL has become a popular approach for studying cerebral hemodynamics in health and also in a range of cerebrovascular ( Donahue et al, 2017 ; Wang et al, 2020 ; Bastos-Leite et al, 2008 ; van Dalen et al, 2016 ; Bahrani et al, 2017 ), neurodegenerative ( Thomas et al, 2019 ; Dolui et al, 2020 ), and psychiatric disorders ( Cooper et al, 2019 ). This rise in popularity over the past decade led to the release of a consensus statement from the Perfusion Study Group of the International Society on Magnetic Resonance in Medicine, which provided guidelines for acquisition and processing of ASL data for clinical use ( Alsop et al, 2015 ).…”