Molecular, Functional, and Structural Imaging of Major Depressive Disorder

Abstract

Major depressive disorder (MDD) is a significant cause of morbidity and mortality worldwide, correlating with genetic susceptibility and environmental risk factors. Molecular, functional, and structural imaging approaches have been increasingly used to detect neurobiological changes, analyze neurochemical correlates, and parse pathophysiological mechanisms underlying MDD. We reviewed recent neuroimaging publications on MDD in terms of molecular, functional, and structural alterations as detected mainly by magnetic resonance imaging (MRI) and positron emission tomography. Altered structure and function of brain regions involved in the cognitive control of affective state have been demonstrated. An abnormal default mode network, as revealed by resting-state functional MRI, is likely associated with aberrant metabolic and serotonergic function revealed by radionuclide imaging. Further multi-modal investigations are essential to clarify the characteristics of the cortical network and serotonergic system associated with behavioral and genetic variations in MDD.

Keywords: Functional connectivity; Magnetic resonance imaging; Major depressive disorder; Molecular imaging; Positron emission tomography; Serotonin.

Fig. 1

The publication trend of neuroimaging articles using PET, MRI, and/or multi-modal imaging approaches in MDD from 2006 to 2015. a Publication trend of articles using PET/SPECT, MRI and multi-modal imaging with PET/SPECT and MRI. b Publication trend of studies investigating functional and structural alterations using various MRI approaches. c Publication trend of articles using PET or SPECT in investigating serotonergic system or others

Fig. 2

Left regions with cortical thickness differences between MDD patients and healthy controls; significant cortical thickening in right rostral middle frontal gyrus and right supramarginal gyrus (red). Right scatterplots showing a negative correlation between cortical thickness in the right rostral middle frontal gyrus and right supramarginal gyrus and HDRS scores (right) [31]. (reprint permission was obtained from both the publisher and the corresponding author)

Fig. 3

Left connectivity maps from dorsal nexus to all the regions in the brain. Pictured are the lateral and medial surface functional connectivity of the left hemisphere for both healthy controls (a, b) and MDD patients (c, d). Significantly increased functional connectivity for MDD is evident. Right comparison of MDD and control groups for mean resting-state connectivity between the dorsal nexus and the combined regions in dorsal lateral prefrontal cortex, precuneus, and subgenual anterior cingulate cortex (P < 0.01) [71]. (reprint permission was obtained from both the publisher and the corresponding author)

Fig. 4

Resting ¹⁸F-FDG PET imaging in MDD patients with psychodynamic psychotherapy. a A significant positive correlation between pretreatment HDRS and regional cerebral glucose metabolism was identified in three clusters in and adjacent to the right posterior insula (yellow; P < 0.05, corrected for whole-brain volume). b Pretreatment regional cerebral glucose metabolism in the right precuneus was significantly higher in completers compared with non-completers (yellow; P < 0.05, corrected for whole-brain volume). c In all patients, pretreatment glucose metabolism in the right precuneus significantly and positively correlated with psychological mindedness (ρ = 0.70; P = 0.002) [102]. (reprint permission was obtained from both the publisher and the corresponding author)

Fig. 5

Inverse correlation between HDRS score and midbrain SERT BP_ND. It manifested an inverse correlation between HDRS and midbrain SERT BP_ND. SERT, serotonin transporter; BP_ND, binding potential of non-displaceable region [120]. (reprint permission was obtained from both the publisher and the corresponding author)

Fig. 6

The SERT BP_ND ratio between PFC and midbrain in depressed suicide, depressed non-suicide patients, and healthy controls. The ratio was significantly higher in the depressed suicide group than in both the depressed non-suicide patients and healthy controls (P < 0.01). Bars represent mean values. SERT, serotonin transporter; BP_ND, binding potential of non-displaceable region; PFC, prefrontal cortex [120]. (reprint permission was obtained from both the publisher and the corresponding author)