Abstract
Major depressive disorder (MDD) is a leading cause of disability worldwide characterized by altered neuronal activity in brain regions involved in the control of stress and emotion. Although multiple lines of evidence suggest that altered stress-coping mechanisms underlie the etiology of MDD, the homeostatic control of neuronal excitability in MDD at the molecular level is not well established. In this review, we examine past and current evidence implicating dysregulation of the polyamine system as a central factor in the homeostatic response to stress and the etiology of MDD. We discuss the cellular effects of abnormal metabolism of polyamines in the context of their role in sensing and modulation of neuronal, electrical, and synaptic activity. Finally, we discuss evidence supporting an allostatic model of depression based on a chronic elevation in polyamine levels resulting in self-sustained stress response mechanisms maintained by maladaptive homeostatic mechanisms.
Original language | English (US) |
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Pages (from-to) | 80-91 |
Number of pages | 12 |
Journal | Neuroscience and Biobehavioral Reviews |
Volume | 66 |
DOIs | |
State | Published - Jul 1 2016 |
Externally published | Yes |
Keywords
- Excitability
- Homeostasis
- Ion channels
- Major depression
- Neurotransmitter receptors
- Polyamine system
- Suicide
ASJC Scopus subject areas
- Neuropsychology and Physiological Psychology
- Cognitive Neuroscience
- Behavioral Neuroscience