Abstract
The neuroimaging literature of Major Depressive Disorder (MDD) has grown substantially over the last several decades, facilitating great advances in the identification of specific brain regions, neurotransmitter systems and networks associated with depressive illness. Despite this progress, fundamental questions remain about the pathophysiology and etiology of MDD. More importantly, this body of work has yet to directly influence clinical practice. It has long been a goal for the fields of clinical psychology and psychiatry to have a means of making objective diagnoses of mental disorders. Frustratingly little movement has been achieved on this front, however, and the 'gold-standard’ of diagnostic validity and reliability remains expert consensus. In light of this challenge, the focus of the current review is to provide a critical summary of key findings from different neuroimaging approaches in MDD research, including structural, functional and neurochemical imaging studies. Following this summary, we discuss some of the current conceptual obstacles to better understanding the pathophysiology of depression, and conclude with recommendations for future neuroimaging research.
Highlights
The neuroimaging literature of Major Depressive Disorder (MDD) has exploded in recent years, with the current pace of research including over 250 new articles listed each year in PubMed alone
A substantial majority of these studies have been focused on identifying putative biological and neural variables that differentiate individuals with MDD from psychiatrically healthy controls. This program of research has been successful in demonstrating a large number of abnormalities in MDD samples, including alterations across measures of brain structure and function; endocrine, immune and neurotransmitter systems; and large-scale network organization
Fundamental questions remain about the pathophysiology and etiology of MDD as well as the strengths and pitfalls of neuroimaging methodologies in attempting to answer them
Summary
The neuroimaging literature of Major Depressive Disorder (MDD) has exploded in recent years, with the current pace of research including over 250 new articles listed each year in PubMed alone. Duloxetine reduced connectivity within resting-state and task-positive networks, [90], and boosted ventral striatal responses during a reward task [91], while the NET-selective agent reboxetine increased thalamic dorsolateral prefrontal responsivity to emotional pictures [92,93] While these studies provide promising leads, insufficient functional or molecular imaging work of NE function in the context of MDD is available, despite significant evidence for its role in the disorder [94]. An increasing number of researchers have called for a better understanding of specific circuits that may mediate transdiagnostic symptom expression [144,145] While much of this discussion has rightly emphasized the importance of animal models [146,147], the final section presents several conceptual and methodological approaches to clinical imaging studies that we feel may aid in the identification of circuits rather than regions. Clinical imaging studies can contribute to circuit-based analysis through a focus on network-based analytical techniques, such as functional connectivity, multi-modal imaging methods, the use of within-subject pharmacological challenge designs, and greater sensitivity to potential discrepancies between ‘believing self ’ and ‘experiencing self ’ that may mask important distinctions in the relationships between subjective report and neuroimaging data
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