title: Abnormal auditory N100 amplitude: a heritable endophenotype in first-degree relatives of schizophrenia probands.
abstract: BACKGROUND
  N100 evoked potential amplitude and gating abnormalities have been widely observed in schizophrenia patients. However, previous studies have been inconclusive as to whether similar deficits are present in unaffected family members. The Consortium on the Genetics of Schizophrenia (COGS) is a multisite National Institute of Mental Health (NIMH) initiative examining neurocognitive and neurophysiological measures as endophenotypes for genetic studies of schizophrenia. We report initial results from the COGS dataset of auditory N100 amplitude and gating as candidate endophenotypes.
  
  
  METHODS
  Evoked potential data were acquired from 142 schizophrenia probands, 373 unaffected first-degree relatives, and 221 community comparison subjects (CCS), using an auditory paired-click stimulation paradigm. Amplitude of the N100 response to each click and the click 2/click 1 ratio were dependent variables. Heritability was estimated based on kinships using Solar v.2.1.2. Group differences were examined after subjects were categorized as either "broad" or "narrow," based on the presence (broad) or absence (narrow) of nonpsychotic psychiatric comorbidity.
  
  
  RESULTS
  Heritability estimates were .40 and .29 for click1 and click2 amplitudes and .22 for the ratio. Broad and narrow patients both had impaired click 1 amplitudes. Broad relatives, but not narrow relatives, exhibited similar impairments. There were no group differences for either click 2 amplitude or the gating ratio.
  
  
  CONCLUSIONS
  N100 amplitude is a heritable measure that is abnormal in patients and a subset of relatives for whom psychiatric comorbidity may be a genetically associated phenotype. Auditory N100 gating, although heritable, is less viable as a schizophrenia endophenotype.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. turetsky@upenn.edu
authors.forename: Bruce I
authors.initials: BI
authors.lastname: Turetsky
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Greenwood
authors.forename: Ann
authors.initials: A
authors.lastname: Olincy
authors.forename: Allen D
authors.initials: AD
authors.lastname: Radant
authors.forename: David L
authors.initials: DL
authors.lastname: Braff
authors.forename: Kristin S
authors.initials: KS
authors.lastname: Cadenhead
authors.forename: Dorcas J
authors.initials: DJ
authors.lastname: Dobie
authors.forename: Robert
authors.initials: R
authors.lastname: Freedman
authors.forename: Michael F
authors.initials: MF
authors.lastname: Green
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Gur
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Gur
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Light
authors.forename: James
authors.initials: J
authors.lastname: Mintz
authors.forename: Keith H
authors.initials: KH
authors.lastname: Nuechterlein
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Siever
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Silverman
authors.forename: William S
authors.initials: WS
authors.lastname: Stone
authors.forename: Neal R
authors.initials: NR
authors.lastname: Swerdlow
authors.forename: Debby W
authors.initials: DW
authors.lastname: Tsuang
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.forename: Monica E
authors.initials: ME
authors.lastname: Calkins
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D004569:Electroencephalography / Q000379:methods; D004777:Environment; D005072:Evoked Potentials, Auditory / Q000235:genetics / Q000502:physiology*; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*; D055815:Young Adult