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Neurochemical Imaging and Depressive Behaviours

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Behavioral Neurobiology of Depression and Its Treatment

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 14))

Abstract

Neurochemical imaging is frequently applied to measure markers of pathological change so as to understand mechanisms that create symptoms of major depressive disorder. For example, indices of greater monoamine oxidase A(MAO-A) level, particularly in the prefrontal and anterior cingulate cortex, are associated with depressed mood states, and high-risk states for onset of major depressive episodes. MAO-A metabolises monoamines, and greater metabolism of monoamines occurs when MAO-A is elevated in brain. Lower extracellular serotonin is associated with greater pessimism in humans and chronic serotonin deficiency is associated with upregulation of 5-HT2A (serotonin2A) receptors in cortex. During major depressive episodes when pessimism is more severe, greater 5-HT2A BPND, an index of density occurs in prefrontal and anterior cingulate cortex. These results argue for a mechanism of lowering extracellular serotonin in the prefrontal and anterior cingulate cortex, consequent to elevated MAO-A level. The relationship between elevated 5-HTT BPND and greater pessimism during major depressive episodes suggests that greater 5-HTT density in the context of elevated MAO-A level further contributes to serotonin deficiency in these brain regions. A similar mechanism may explain the association between neuroimaging indices of greater dorsal striatal D2 density, DAT density and symptoms of motor retardation: Greater MAO-A level and relatively greater DAT density lower extracellular dopamine in the dorsal striatum, leading to motor retardation. Indices of greater 5-HT1A density, particularly in the cingulate cortex, have been associated with major depressive disorder, and well as anxiety disorders, suggesting that this abnormality is mechanistically related to presence of anxiety symptoms. To date, abnormalities of Glx a measure reflecting glutamate and glutamine levels have been most strongly associated with presence of major depressive episodes, with greater levels in occipital cortex, and reduced levels in prefrontal cortex. Ultimately, the future for neurochemical imaging is to better understand the mechanisms that predispose toward onset of MDE so as to create biologically informed, novel, methods of prevention, and superior, more symptom-targeted treatments.

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Authors and Affiliations

  1. Department of Psychiatry, University of Toronto, Toronto, Canada

    Jeffrey H. Meyer

  2. Canada Research Chair in Neurochemistry of Depression Head, Neurochemical Imaging Program in Mood Disorders Centre for Addiction and Mental Health Research Imaging Center, Toronto, Canada

    Jeffrey H. Meyer

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  1. Warneford Hospital, Dept. Psychiatry, University of Oxford, Oxford, OX3 7JX, United Kingdom

    Philip J. Cowen

  2. Dept. Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom

    Trevor Sharp

  3. , Dep of Experimental Psychology, University of Oxford, South Parks Road, Oxford, OX1 3UD, United Kingdom

    Jennifer Y. F. Lau

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Meyer, J.H. (2012). Neurochemical Imaging and Depressive Behaviours. In: Cowen, P., Sharp, T., Lau, J. (eds) Behavioral Neurobiology of Depression and Its Treatment. Current Topics in Behavioral Neurosciences, vol 14. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2012_219

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