Neurotransmitter, peptide and cytokine processes in relation to depressive disorder: comorbidity between depression and neurodegenerative disorders.
Given the array of biological changes induced by stressors, it is not surprising that these experiences may provoke a variety of illnesses. Among others things, stressors promote functional changes of neuropeptide and classical neurotransmitter systems. The peptidergic changes, for instance, include alterations of corticotropin releasing hormone, arginine vasopressin, and bombesin-like peptides at specific brain sites. Similarly some of the neurotransmitter systems influenced by stressors include GABAergic and monoamine functioning. Variations of these processes may limit neurogenesis (and dysregulation of growth factors such as BDNF) and influence cellular viability (through NFkappaB and MAP kinase pathways). As well, stressors activate the inflammatory immune system, notably the release of signaling molecules (cytokines), which may provoke many of the same neuropeptide (and other neurotransmitter) changes. By virtue of their actions on neuronal functioning, inflammatory processes may influence stress-related illness, such as depression, and may be a common denominator for the comorbidity that exists between depression and neurological conditions, including Parkinson's and Alzheimer's diseases, as well as cardiovascular-related pathology. The present report provides an overview of biological endophenotypes associated with stressors that are thought to be related to major depressive disorder and related comorbid conditions. The view is taken that synergy between stressors and inflammatory factors may promote pathological outcomes through their actions on neuropeptides and several neurotransmitters. As well, stressful events may result in the sensitization of neurochemical and cytokine processes, so that later re-exposure to these stimuli may promote rapid and exaggerated responses that favor illness recurrence.
Anisman
Hymie
H
Institute of Neuroscience, Carleton University, Ottawa, Ontario K1S 5B6, Canada. hanisman@ccs.carleton.ca
Merali
Zul
Z
Hayley
Shawn
S
D000818:Animals; D015897:Comorbidity; D016207:Cytokines / Q000378:metabolism*; D003866:Depressive Disorder / Q000453:epidemiology / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000453:epidemiology / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*
D016207:Cytokines; D018377:Neurotransmitter Agents; D010455:Peptides