Targets of polyamine dysregulation in major depression and suicide: Activity-dependent feedback, excitability, and neurotransmission.
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.
Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92627, USA.
Agenor
A
Limon
Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92627, USA.
Firoza
F
Mamdani
Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92627, USA.
Brooke E
BE
Hjelm
Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92627, USA.
Marquis P
MP
Vawter
Functional Genomics Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92627, USA. Electronic address: psequeir@uci.edu.
Adolfo
A
Sequeira
D001921:Brain; D003865:Major Depressive Disorder; D006801:Humans; D011073:Polyamines; D013405:Suicide; D009435:Synaptic Transmission
D011073:Polyamines
Excitability; Homeostasis; Ion channels; Major depression; Neurotransmitter receptors; Polyamine system; Suicide