Brain structure alterations in depression: Psychoradiological evidence

Abstract

Depression is the leading cause of disability around the world, but little is known about its pathology. Currently, the diagnosis of depression is made based on clinical manifestations, with little objective evidence. Magnetic resonance imaging (MRI) has been used to investigate the pathological changes in brain anatomy associated with this disorder. MRI can identify structural alterations in depressive patients in vivo, which could make considerable contributions to clinical diagnosis and treatment. Numerous studies that focused on gray and white matter have found significant brain region alterations in major depressive disorder patients, such as in the frontal lobe, hippocampus, temporal lobe, thalamus, striatum, and amygdala. The results are inconsistent and controversial because of the different demographic and clinical characteristics. However, some regions overlapped; thus, we think that there may be a "hub" in MDD and that an impairment in these regions contributes to disease severity. Brain connections contain both structural connections and functional connections, which reflect disease from a different view and support that MDD may be caused by the interaction of multiple brain regions. According to previous reports, significant circuits include the frontal-subcortical circuit, the suicide circuit, and the reward circuit. As has been recognized, the pathophysiology of major depressive disorder is complex and changeable. The current review focuses on the significant alterations in the gray and white matter of patients with the depressive disorder to generate a better understanding of the circuits. Moreover, identifying the nuances of depressive disorder and finding a biomarker will make a significant contribution to the guidance of clinical diagnosis and treatment.

Keywords: Psychoradiology, diffusion MRI; magnetic resonance imaging; major depressive disorder; structure MRI.

Figure 1

Structural network hubs of the human brain. Structural brain hubs were identified by diffusion tensor imaging, and the nodes normalized to an intramodular degree higher than 1 were defined as hubs.14, 21 ACG, anterior cingulate and paracingulate gyri; CAL, calcarine fissure and surrounding cortex; HIP, hippocampus; INS, insula; L, left; MOG, middle occipital gyrus; MTG, middle temporal gyrus; PCUN, precuneus; PUT, putamen; R, right; SOG, superior occipital gyrus; SPG, superior parietal gyrus; SFGdor, dorsolateral part of the superior frontal gyrus; SFGmed, medial part of the superior frontal gyrus; THA, thalamus

Figure 2

Prefrontal circuit. The striatum, thalamus, and prefrontal cortex constitute the prefrontal‐ subcortical circuit (A). The dorsolateral prefrontal circuit (B) originates in the dorsolateral prefrontal cortex, which projects to the dorsolateral caudate. Then, fibers track through the direct or indirect pathway to the lateral dorsomedial globus pallidus and the substantia nigra. The globus pallidus and the substantia nigra then project to the ventral anterior and medial dorsal thalamus.86 The thalamus collects all the information and sends it back to the dorsolateral prefrontal cortex; the orbitofrontal prefrontal circuit (C) originates in the inferolateral prefrontal cortex. The OFC fibers project to the ventromedial caudate. Then, the caudate outputs fibers through the direct and indirect pathways to the medial dorsomedial globus pallidus and the substantia nigra. The pallidum and the substantia nigra have connections with the ventral anterior and medial dorsal thalamic nuclei. All information will ultimately return to the orbitofrontal cortex; the anterior cingulate‐prefrontal circuit (D) begins in the ACC, and the fibers project to the ventral striatum and the substantia nigra. The striatum outputs to the medial dorsal thalamus. Finally, the thalamus sends all the information back to the ACC. ACC, anterior cingulate cortex; DLPFC, dorsolateral prefrontal cortex; GPs, globus pallidus; mid, middle; OFC, orbitofrontal prefrontal cortex; SN, substantia nigra; THA, thalamus

Figure 3

Two pathways from the caudate to the thalamus. The prefrontal‐subcortical circuit originates from the prefrontal cortex and outputs fibers projecting to the striatum. Directly, the striatum transmits information through GABAergic neurons and projects to the globus pallidus. Indirectly, the striatum projects to the globus pallidus. The subthalamic nucleus receives information from the cortex via glutamatergic neurons and from the globus pallidus via GABAergic neurons, which then output through glutamatergic neurons to the globus pallidus. All information ultimately returns to the prefrontal cortex. ACC, anterior cingulate cortex; DLPFC, dorsolateral prefrontal cortex; GABA, gamma‐aminobutyric acid; Glu, glutamatergic; GPs, globus pallidum; OFC, orbitofrontal prefrontal cortex; SN, substantia nigra; THA, thalamus

Figure 4

Suicide circuit. MDD patients who committed suicide were found to have abnormal connections among the left anterior limb of the internal capsule, the left middle frontal cortex, the orbital prefrontal cortex, and the left thalamus. IC, internal capsule; L, left; MDD, major depressive disorder; MFC, middle frontal cortex; OFC, orbitofrontal prefrontal cortex; THA, thalamus