Post by Lincoln Tracy
What's the science?
Major depressive disorder (MDD) is a common mood disorder that is believed to be associated with changes in the brain. Researchers have used magnetic resonance imaging (MRI) techniques to identify brain-related biomarkers for other conditions such as Alzheimer’s disease. However, brain-related biomarkers have not yet been identified for use in the diagnosis or treatment of MDD. One noninvasive neuroimaging technique used to measure brain function is arterial spin labelling (ASL). In ASL a magnetic pulse labels blood before it enters the brain. The amount of labelled blood in each region of the brain can then be quantified; greater blood flow is typically indicative of greater activity in that brain region. This week in Molecular Psychiatry, Cooper and colleagues used ASL as part of a randomized, double-blind, placebo-controlled trial aiming to find brain-related biomarkers for the diagnosis and treatment of MDD.
How did they do it?
The authors recruited 200 individuals with MDD as well as 98 non-depressed individuals (to act as controls) as part of a clinical trial. All participants underwent a baseline MRI scan with an ASL sequence prior to starting their allocated treatment for the trial. The baseline MRI and ASL data was split into Discovery-Replication subgroups. The ASL-derived cerebral blood flow (CBF) data from the Discovery group was used in an exploratory manner to identify brain regions where CBF differed between MDD and non-depressed individuals. The Replication group was then used to independently confirm these CBF differences. The blood flow in regions where CBF differences replicated were then correlated with clinical features of MDD (e.g., length of illness, number of MDD episodes, age of MDD onset) to explore potential relationships between CBF and clinical features.
What did they find?
The Discovery sample showed that there were differences in CBF between the MDD and control participants. The MDD participants had lower CBF compared to the control participants in five brain clusters, and greater CBF compared to the control participants in five brain clusters. Using the regions of interest (ROIs) from the Discovery sample, the Replication sample confirmed three clusters where CBF was lower in individuals with MDD compared to the control participants—the cerebellum and midbrain regions, the right middle temporal gyrus, and the left insula. The Replication sample also confirmed three clusters where CBF was greater in individuals with MDD compared to the control participants—the left anterior prefrontal and dorsolateral cortices, the right inferior parietal lobule, and the left inferior parietal lobule. The CBF of several replicated ROIs were correlated with the clinical features of MDD. For example, the decreased CBF within the left insula negatively correlated with the length of illness. That is, a longer length of illness in individuals with MDD was associated with lower perfusion within the left insula.
What's the impact?
This study is the first to discover and provide unbiased confirmation of CBF differences in a large population of individuals with MDD. These are important and exciting findings for this field of research as there has previously been a lack of discovery-replication work. These findings suggest that CBF could serve as a potential marker for the long-term effects of MDD and may also serve as a potential mediator of responses to treatment. These findings also have implications for future studies aimed at developing CBF as a biomarker for the diagnosis and treatment of MDD and other clinical populations.
Cooper et al. Discovery and replication of cerebral blood flow differences in major depressive disorder. Molecular Psychiatry (2019).Access the original scientific publication here.