Is elevated norepinephrine an etiological factor in some cases of schizophrenia?
A number of hypotheses have been put forth regarding the etiology of schizophrenia, including the dopamine hypothesis, NMDA receptor hypofunction hypothesis, and others. A lesser known theory is that elevated noradrenergic signaling plays a causative role in the disease. This paper briefly re-examines the merits of this hypothesis, including as it relates to some recently published studies. Several lines of evidence are investigated, including: endogenous level studies of norepinephrine (NE); modulation of the disease by noradrenergic drugs; association of the disease with bipolar disorder and hypertension, since these latter two conditions may involve elevated NE transmission; and effects of psychological stress on the disease, since stress can produce elevated release of NE. For many of these lines of evidence, their relationship with prepulse inhibition of startle is examined. A number of these studies support the hypothesis, and several suggest that elevated NE signaling plays a particularly prominent role in the paranoid subtype of schizophrenia. If the hypothesis is correct for some persons, conventional pharmaceutical treatment options, such as use of atypical antipsychotics (which may themselves modulate noradrenergic signaling), may be improved if selective NE transmission modulating agents are added to or even substituted for these conventional drugs.
Department of Psychology, Texas A&M University, College Station, Room 3200 ILSB, TX 77843-4235, USA. Electronic address: pfitz@mbi.mb.jhu.edu.
Paul J
PJ
Fitzgerald
D000316:Adrenergic alpha-Agonists / Q000009:adverse effects / Q000378:metabolism*; D014150:Antipsychotic Agents / Q000009:adverse effects; D001714:Bipolar Disorder / Q000150:complications; D006801:Humans; D006973:Hypertension / Q000150:complications; D009638:Norepinephrine / Q000378:metabolism* / Q000502:physiology; D012559:Schizophrenia / Q000209:etiology* / Q000503:physiopathology; D015398:Signal Transduction; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D014150:Antipsychotic Agents; D009638:Norepinephrine
Clonidine; Desipramine; Guanfacine; Paranoid schizophrenia; Prazosin; Propranolol; Yohimbine