title: P50 amplitude reduction: a nicotinic receptor-mediated deficit in first-degree relatives of schizophrenia patients.
abstract: BACKGROUND
  Impaired P50 gating is a putative index of genetically mediated nicotinic dysfunction in schizophrenia. However, assessment is confounded, in patients, by differential effects of smoking, symptoms, and treatment.
  
  
  OBJECTIVE
  This double-blind placebo-controlled study was designed to tease apart the relationships among P50, acute and chronic nicotine exposure, and familial risk.
  
  
  RESULTS
  Experiment 1: To assess the putative effects of genetic vulnerability without other confounds, 14 unaffected relatives of schizophrenia patients and 15 controls, all nonsmokers, were tested with/without 7 mg transdermal nicotine. Family members had reduced P50 amplitude to an initial auditory stimulus, but normal P50 gating. Nicotine decreased P50 amplitude in controls; family members had a mixed response: eight decreased and six increased P50 amplitude with nicotine. Experiment 2: To assess chronic nicotine use and short-term withdrawal as a model of nicotinic dysfunction, 26 healthy smokers (14 abstinent for >12 h) received 21 mg transdermal nicotine. Chronic nicotine use, alone, did not alter P50 amplitude or gating. Short-term withdrawal resulted in decreased P50 amplitude, with no effect on P50 gating. Nicotine increased P50 amplitude in abstinent smokers and decreased it in nonabstinent smokers.
  
  
  CONCLUSIONS
  Familial vulnerability to schizophrenia reduces P50 amplitude. Nicotinic modulation of this deficit mirrors the effect of nicotine during smoking abstinence and suggests an "inverted-U" relationship between P50 amplitude and endogenous nicotinic activity. P50 amplitude may, therefore, be a sensitive marker of nicotinic dysfunction in individuals with familial risk for schizophrenia, which is mediated through mechanisms (e.g., α₄β₂ receptors) that are distinct from those (e.g., α₇ receptors) that mediate P50 gating.
authors: Department of Psychiatry, University of Pennsylvania, 10th Floor, Gates Building, 3400 Spruce Street, Philadelphia, PA 19104, USA. turetsky@upenn.edu
authors: Bruce I
authors: BI
authors: Turetsky
authors: Gersham
authors: G
authors: Dent
authors: Judith
authors: J
authors: Jaeger
authors: Stephen R
authors: SR
authors: Zukin
mesh_terms: D000293:Adolescent; D000328:Adult; D005072:Evoked Potentials, Auditory / Q000187:drug effects / Q000502:physiology*; D005190:Family / Q000523:psychology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000523:psychology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*; D012559:Schizophrenia / Q000235:genetics*; D055139:Sensory Gating / Q000187:drug effects / Q000502:physiology; D012907:Smoking / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology
chemical_list: D011978:Receptors, Nicotinic; D009538:Nicotine