Myelination of the brain in major depressive disorder : an in vivo magnetic resonance imaging study - Sacchet, Matthew Daniel; Gotlib, Ian H; Wagner, Anthony David; Gross, James; Knutson, Brian; Malenka, Robert C; Stanford University, Neurosciences Program (2016)
Major depressive disorder (MDD) is a debilitating psychiatric condition and a leading contributor to the global burden of disease. Characterizing MDD-related abnormalities in neurobiological processes will inform more comprehensive etiological frameworks of MDD that will facilitate the development of more targeted approaches to the prevention and identification of, and intervention for, this disorder. In this context, one promising biological target is myelin, a specialized biological tissue and fundamental facilitator of neuronal communication. Myelin ensheaths axons and facilitates saltatory conduction of electrical signaling in the nervous system. Postmortem studies of brains of depressed individuals, and non-human animal, genetic, and neuroimaging studies suggest that abnormalities in myelin are associated with MDD. Growing evidence suggests that neural activity and myelin influence each other to support an effective nervous system, and that stress-related neuroinflammation may result in the degradation of myelin in MDD. Brain regions implicated in this research, and in MDD more generally, include the nucleus accumbens (NAcc) and the dorsolateral prefrontal cortex (DLPFC), core regions involved in reward and cognitive control processes, respectively. Recent developments in quantitative magnetic resonance imaging (qMRI) allow for improved assessment of myelin content at the whole brain level, in vivo, in humans through the measure of R1. In this study we used qMRI to measure R1 to examine whether the brains and, in particular, the NAcc and DLPFC, of individuals diagnosed with MDD are characterized by reductions in myelin content compared to individuals without a history of psychiatric disorder (i.e., healthy controls [CTLs]). We found that the MDD group had lower levels of myelin than did the CTL group at the whole brain level and in the NAcc. Furthermore, myelin content of the DLPFC was reduced in MDD participants who had experienced a greater number of depressive episodes compared to both MDD participants who had experienced fewer depressive episodes and participants in the CTL group. Taken together, these results offer new evidence that MDD is characterized by reduced myelin content of the brain and in the NAcc in particular, and that the chronicity of MDD is associated with reduced myelin in the DLPFC. While further research is needed to elucidate the role of myelin in influencing affective, cognitive, behavioral, and clinical aspects of MDD, the current study provides important evidence that a fundamental property of brain composition, myelin, is altered in this disorder.
Submitted to the Program in Neurosciences.
Thesis (Ph.D.)--Stanford University, 2016.
Rights: (c) Copyright 2016 by Matthew Daniel Sacchet
Keywords: theses