title: Low olfactory bulb volume in first-degree relatives of patients with schizophrenia.
abstract: OBJECTIVE
  There is a substantial genetic contribution to schizophrenia but no way to readily identify individuals at risk. Biological abnormalities reflecting greater genetic vulnerability may be discovered by examining healthy family members of patients with schizophrenia. There is evidence that olfactory impairments are common in patients. The authors previously reported that patients have abnormal olfactory bulbs, assessed by magnetic resonance imaging (MRI). This study examined olfactory bulbs in patients' relatives to determine whether low bulb volume represents an endophenotypic marker of genetic vulnerability.
  
  
  METHODS
  Olfactory psychophysical measures and MRI scans of olfactory bulbs were acquired from 19 healthy first-degree relatives, 20 healthy comparison subjects with similar age and gender distributions, and the 11 patient probands of these relatives. Olfactory bulb volumes were measured by using a reliable region-of-interest procedure.
  
  
  RESULTS
  The patients had impaired ability to detect odors and had lower olfactory bulb volumes than the comparison subjects. Although the family members had normal olfactory ability, they exhibited low right bulb volume. The patients had smaller left, but not right, olfactory bulbs than their own healthy relatives.
  
  
  CONCLUSIONS
  The findings in family members suggest that structural abnormalities of the olfactory system in schizophrenia may partly reflect preexisting genetic vulnerability to illness. Preliminary analyses suggest that right olfactory bulb volume may serve as an endophenotypic marker of genetic vulnerability, while left bulb volume may reflect overt disease among individuals who share genetic vulnerability. Bulb abnormalities in patients are consistent with reports of cellular abnormalities affecting peripheral olfactory receptor neurons.
authors.affiliation: Schizophrenia Research Center, Department of Psychiatry, University of Pennsylvania, USA. turetsky@bbl.med.upenn.edu
authors.forename: Bruce I
authors.initials: BI
authors.lastname: Turetsky
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Moberg
authors.forename: Steven E
authors.initials: SE
authors.lastname: Arnold
authors.forename: Richard L
authors.initials: RL
authors.lastname: Doty
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Gur
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D004056:Differential Threshold / Q000502:physiology; D004192:Discrimination, Psychological / Q000502:physiology; D005190:Family; D005260:Female; D007839:Functional Laterality / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009666:Nose / Q000502:physiology; D009812:Odorants; D000857:Olfaction Disorders / Q000175:diagnosis / Q000235:genetics; D009830:Olfactory Bulb / Q000033:anatomy & histology*; D010641:Phenotype; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis* / Q000235:genetics*; D017603:Signal Detection, Psychological; D012903:Smell / Q000235:genetics / Q000502:physiology