Cortical interneurons, immune factors and oxidative stress as early targets for schizophrenia.
Schizophrenia is a common disorder in which strong genetic predisposition is combined with environmental factors. Despite the widely recognized developmental nature of the disease, symptoms do not emerge until late adolescence. Current therapeutic approaches are therefore employed too late, as brain alterations may have been present earlier than symptom onset. Here I review the developmental trajectory of the cortical circuits responsible for excitation-inhibition balance, which are at the center of current pathophysiological views, and propose that oxidative stress in cortical interneurons may be a final common pathway by which several different etiological factors can yield the cortical dysfunction characteristic of schizophrenia. If this scenario is correct, redox modulators may be beneficial for the disease. It is critical that the developmental trajectories of the factors yielding oxidative stress are taken into account for those approaches to succeed.
Department of Anatomy, University of Maryland School of Medicine, 20 Penn St., Room S-251, Baltimore, MD 21201, USA. podon002@umaryland.edu
Patricio
P
O'Donnell
D000293:Adolescent; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D061345:Early Medical Intervention; D006801:Humans; D007155:Immunologic Factors / Q000502:physiology; D007395:Interneurons / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D017397:Prefrontal Cortex / Q000254:growth & development / Q000503:physiopathology; D051381:Rats; D018079:Receptors, GABA / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology
D000975:Antioxidants; D007155:Immunologic Factors; D018079:Receptors, GABA