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Pathophysiology of depression: the concept of synaptic plasticity

Published online by Cambridge University Press:  16 April 2020

R.S. Duman*
Affiliation:
Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, NewHaven, CT, USA
*
*Corresponding author: 34 Park Street, New Haven, CT 06508, USA. E-mail address: ronald.duman@yale.edu (R.S. Duman).
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Summary

Neuronal plasticity or remodeling is most often discussed with regard to cellular and behavioral models of learning and memory. However, neuronal plasticity is a fundamental process by which the brain acquires information and makes the appropriate adaptive responses in future-related settings. Dysfunction of these fundamental processes could thereby contribute to the pathophysiology of mood disorders, and recovery could occur by induction of the appropriate plasticity or remodeling. These possibilities are supported by preclinical and clinical studies demonstrating that there are structural alterations that occur in response to stress and in patients with mood disorders. Moreover, antidepressant treatment may oppose these effects by regulation of signal transduction and gene expression pathways linked to neuronal plasticity. These findings comprise a novel conceptual framework for future studies of the etiology of mood disorders and for the development of novel therapeutic interventions.

Type
Research Article
Copyright
Copyright Éditions scientifiques et médicales Elsevier SAS 2002

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Footnotes

To be presented at ECNP Barcelona, 5-9 October 2002, during the symposium “A new pharmacology of depression: the concept of synaptic plasticity.”

References

Chen, AHShirayama, YShin, KHNeve, RLDuman, RSExpression of the cAMP response element binding protein (CREB) in hippocampus produces antidepressant effect. Biol Psychiatry 2001;49:753762.CrossRefGoogle ScholarPubMed
Dowlatshahi, DMacQueen, GMWang, JFYoung, LTIncreased temporal cortex CREB concentrations and antidepressant treatment in major depression. Lancet 1998;352:17541755.Google ScholarPubMed
Drevets, WNeuroimaging studies of mood disorders. Biol Psychiatry 2000;48:813829.CrossRefGoogle ScholarPubMed
Duman, RSHeninger, GRNestler, EJA molecular and cellular theory of depression. Arch Gen Psychiatry 1997;54:597606.CrossRefGoogle ScholarPubMed
Duman, RSMalberg, JNakagawa, SD'Sa, CNeuronal plasticity and survival in mood disorders. Biol Psychiatry 2000;48:732739.CrossRefGoogle ScholarPubMed
Gould, EPanapat, PRydel, THastings, NRegulation of hippocampal neurogenesis in adulthood. Biol Psychiatry 2000;48:715720.CrossRefGoogle ScholarPubMed
Malberg, JEEisch, AJNestler, EJDuman, RSChronic antidepressant treatment increases neurogenesis in adult hippocampus. J Neurosci 2000;20:91049110.CrossRefGoogle Scholar
Malberg, JEEisch, AJNestler, EJDuman, RSEffects of antidepressant treatment and learned helplessness training on hippocampal neurogenesis in adult rat. Abstr Soc Neurosci 2000;26.Google Scholar
Manji, HMoore, GJChen, GClinical and preclinical evidence for the neurotrophic effects of mood stabilizers: implications for the pathophysiology and treatment of manic-depressive illness. Biol Psychiatry 2000;48:740754.CrossRefGoogle ScholarPubMed
McEwen, BEffects of adverse experiences for brain structure and function. Biol Psychiatry 2000;48:721731.CrossRefGoogle ScholarPubMed
Rajkowska, GPostmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry 2000;48:766777.CrossRefGoogle ScholarPubMed
Sheline, YSanghavi, MMintun, MAGado, MH3D MRI studies of neuroatomic changes in unipolar major depression: the role of stress and medical comorbidity. Biol Psychiatry 2000;48:791800.CrossRefGoogle ScholarPubMed
Shirayama, YChen, ACHDuman, RSAntidepressant-like effects of BDNF and NT-3 in behavioral models of depression. Abstr Soc Neurosci 2000;26.Google Scholar
Siuciak, JALewis, DRWiegand, SJLindsay, RAntidepressant-like effect of brain derived neurotrophic factor (BDNF). Pharmacol Biochem Behav 1996;56:131137.CrossRefGoogle Scholar
Smith, MAMakino, SKvetnansky, RPost, RMStress alters the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 1995;15:17681777.CrossRefGoogle Scholar
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