Neuroimaging markers of cellular function in major depressive disorder: implications for therapeutics, personalized medicine, and prevention.
It is estimated that 15% of all individuals will experience a major depressive episode (MDE) during their lifetime and that treatment response is inadequate in 40% of these cases. To address this, neuroimaging is being used to identify MDE subtypes and mechanisms of onset as well as to optimize target occupancy of novel treatments. Neuroimaging of monoamine oxidase-A (MAO-A) binding; glutamate levels; indexes of 5-HT(2A), 5-HTT, 5-HT(1A), and 5-HT(1B) receptors; levels of dopamine transporters D(1) and D(2); and hippocampal volume are described here. Three themes emerge. First, symptoms such as pessimism, motor retardation, anxiety disorder, and verbal memory deficits best indicate the subtype of depression. Second, measures related to mechanisms of monoamine loss, particularly elevated MAO-A binding in prefrontal and anterior cingulate cortex, are present in MDE and in high-risk states for MDE. Third, clinical trials show a consistent 80% 5-HTT occupancy of selective serotonin reuptake inhibitors at doses sufficient to distinguish from placebo in clinical trials (although in vitro affinities vary 100-fold), thereby supporting the need for further occupancy studies to accelerate therapeutic development.
Mood and Anxiety Division and Research Imaging Centre, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. jeff.meyer@camhpet.ca
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Meyer
D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D055808:Drug Discovery / Q000379:methods; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008959:Models, Neurological; D008995:Monoamine Oxidase / Q000378:metabolism; D059906:Neuroimaging / Q000379:methods / Q000523:psychology* / Q000706:statistics & numerical data; D057285:Precision Medicine / Q000379:methods; D011877:Radionuclide Imaging; D011954:Receptors, Dopamine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D018698:Glutamic Acid; D008995:Monoamine Oxidase; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors