title: An excitatory synapse hypothesis of depression.
abstract: Depression is a common cause of mortality and morbidity, but the biological bases of the deficits in emotional and cognitive processing remain incompletely understood. Current antidepressant therapies are effective in only some patients and act slowly. Here, we propose an excitatory synapse hypothesis of depression in which chronic stress and genetic susceptibility cause changes in the strength of subsets of glutamatergic synapses at multiple locations, including the prefrontal cortex (PFC), hippocampus, and nucleus accumbens (NAc), leading to a dysfunction of corticomesolimbic reward circuitry that underlies many of the symptoms of depression. This hypothesis accounts for current depression treatments and suggests an updated framework for the development of better therapeutic compounds.
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA; Department of Psychiatry, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA; Programs in Neuroscience and Membrane Biology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA. Electronic address: sthom003@umaryland.edu.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Thompson
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA; Programs in Neuroscience and Membrane Biology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Angy J
authors.initials: AJ
authors.lastname: Kallarackal
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA; Programs in Neuroscience and Membrane Biology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA; Medical Scientist Training Program, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Kvarta
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA; Programs in Neuroscience and Membrane Biology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Van Dyke
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA.
authors.forename: Tara A
authors.initials: TA
authors.lastname: LeGates
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, MD 21201, USA; Department of Physiology, Southern Illinois University, Carbondale, IL 62901, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Cai
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D003863:Depression / Q000188:drug therapy / Q000473:pathology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
chemical_list: D000928:Antidepressive Agents
keywords: glutamate; hippocampus; ketamine; nucleus accumbens; reward; stress