Serotonin dysfunction disorders: a behavioral neurochemistry perspective.
The spectrum of efficacy of the serotonin selective reuptake inhibitor (SSRI) antidepressant drugs continues to expand. In fact, no psychiatric syndrome seems to worsen with these agents, and few studies fail to demonstrate clinical improvement in some patients, regardless of any nosologic nicety, such as precise DSM diagnosis. This suggests that the biological rubric of psychopathology is dimensional rather than categorical. New research using in vivo microdialysis shows differences in neurochemistry among SSRIs, wherein fluoxetine blocks reuptake of dopamine and norepinephrine, as well as serotonin, in medial prefrontal cortex, and fluvoxamine has a relatively more selective neurochemical profile. In the animal model of learned helplessness, which is a biobehavioral model for stress-induced anxiety causing depression, the SSRIs including fluvoxamine prevent helplessness. From these and other data, a neurotransmitter balance theory of biopsychopathology is formulated. In this hypothetical construct, dopamine, norepinephrine, and GABA modulate thought, anxiety, and mood, respectively. Serotonin is a stabilizing agent, which assists in returning the mind to its homeostatic setpoint.
Petty
F
F
Veterans Affairs Medical Center, University of Texas Southwestern Medical School, Dallas 75216, USA.
Davis
L L
LL
Kabel
D
D
Kramer
G L
GL
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001008:Anxiety Disorders / Q000188:drug therapy / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D003072:Cognition Disorders / Q000503:physiopathology; D003866:Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D006380:Helplessness, Learned; D006801:Humans; D009638:Norepinephrine / Q000502:physiology; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy / Q000503:physiopathology*; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology / Q000627:therapeutic use; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000928:Antidepressive Agents; D004298:Dopamine; D009638:Norepinephrine; D012701:Serotonin; D018490:Serotonin Agents; D017367:Selective Serotonin Reuptake Inhibitors; D005680:gamma-Aminobutyric Acid