In pursuit of neuroimaging biomarkers to guide treatment selection in major depressive disorder: a review of the literature

Abstract

Over the last few decades, neuroimaging techniques have advanced the identification of structural, functional, and neurochemical brain abnormalities that are associated with the increased risk, clinical course, and treatment outcomes of major depressive disorder (MDD). This paper reviews specific neuroimaging abnormalities that, on the basis of early studies, may discriminate between MDD patients who do or do not respond to current therapeutic modalities, such as antidepressants, cognitive behavioral therapy, or novel therapies. Differences in gray matter volume, white matter coherence, brain activity via structural and functional magnetic resonance imaging techniques, and concentrations of specific brain metabolites (as measured with magnetic resonance spectroscopy), are potential biomarkers discussed in this review. Given the heterogeneity of MDD, larger, multisite studies with increased statistical power will be needed to identify more precise imaging biomarkers of treatment response in MDD.

Depressive disorders: Processes leading to neurogeneration and potential novel treatments

“…Studies of MDD patients using magnetic resonance diffusion tensor imaging (DTI) have shown changes indicating altered connectivity in several areas including the left superior longitudinal fasciculus, right caudate, corona radiate, genu of the corpus callusom, posterior thalamic radiations and brain stem (Choi et al, 2015;Han et al, 2017;Lener and Iosifescu, 2015;Liao et al, 2013;Murphy and Frodl, 2011;Sexton et al, 2009;Tymofiyeva et al, 2017). Because of these numerous reports it has been proposed that depression may be a syndrome with a disconnection between prefrontal and limbic areas (Liao et al, 2013).…”

“…Moreover circulating inflammatory and antioxidant markers are associated with changes on MRI and MRS (Frodl and Amico, 2014;Lindqvist et al, 2014;Young et al, 2014). Postmortem neuropathological studies have shown decreased neuronal cell size and quantity, synaptic density and glial cell quantity (Lener and Iosifescu, 2015). Whether these volumetric changes represent a susceptibility to MDD, a result of or compensation to MDD or even a response to treatment is not clearly established at this time.…”

“…In the ACC activation was correlated with greater depression severity on the Hamilton rating scale. Reviews of magnetic resonance spectroscopy (MRS) studies describe a variety of changes in metabolites which have been associated with neuronal death and also abnormalities in neurotransmitter systems in some of the areas identified in MDD by MRI (Frodl and Amico, 2014;Lener and Iosifescu, 2015). Moreover circulating inflammatory and antioxidant markers are associated with changes on MRI and MRS (Frodl and Amico, 2014;Lindqvist et al, 2014;Young et al, 2014).…”

Glutamate and Gamma-Aminobutyric Acid Systems in the Pathophysiology of Major Depression and Antidepressant Response to Ketamine

“…In comparison to healthy subjects, aberrant amino acid neurotransmitter levels measured by 1 H-MRS have been found in individuals with MDD (6, 17–19) and BD (20, 21). Specifically, in MDD patients, Glu and Glx reductions were found in the dorsolateral prefrontal cortex (dlPFC) (22) and other prefrontal cortical (PFC) areas such as the dorso-medial and dorso-anterolateral PFC (23) and anterior cingulate cortex (ACC) (24), with increased levels in the occipital cortex (OCC) (25) to a degree that may be related to duration of illness (26).…”

Cortical abnormalities and association with symptom dimensions across the depressive spectrum

“…Biomarkers based on neuroimaging techniques noninvasively visualize brain abnormalities implicated in MDD and are well-suited to guide the development of novel treatments, assess treatment response, and tailor treatment approaches to biological subtypes of depression (Lener and Iosifescu 2015; Niciu et al 2014). Structural MRI methods using cortical parcellation and morphometic analysis have allowed for the examination of subtle morphometric brain changes (eg., cortical thickness and surface area) (Tu et al 2012; Qiu et al 2014; Han et al 2014) through the application of FreeSurfer (Fischl 2012), voxel-based morphometry (VBM), and voxel-based analysis (VBA) have allowed for the detection of subtle structural abnormalities in MDD within prefrontal, temporal, and limbic areas compared to healthy volunteers (Lorenzetti et al 2009; Kempton et al 2011; Bora et al 2012; Du et al 2012; Lai 2013; Sacher et al 2012).…”