Elementary phenotypes in the neurobiological and genetic study of schizophrenia.
This review describes the strategy of using elementary phenotypes for neurobiological and genetic linkage studies of schizophrenia. The review concentrates on practical aspects of selecting the phenotype and then understanding the confounds in its measurement and interpretation. Examples from the authors' studies of deficits in P50 inhibition and smooth pursuit eye movement dysfunction are presented. These two phenotypes share considerable similarity in their neurobiology, including a similar response to nicotine. They also appear to co-segregate with the genetic risk for schizophrenia as autosomal co-dominant phenotypes. Although most schizophrenic patients inherit these abnormalities unilinealy, i.e., from one parent, apparent bilineal inheritance produces a more severe illness, observed clinically as childhood-onset schizophrenia. The initial study showing linkage of the P50 deficit to the chromosome 15q14 locus of the alpha 7-nicotinic acetylcholine receptor is an example of the potential usefulness of these phenotypes for combined genetic and neurobiological study of schizophrenia.
Department of Psychiatry, University of Colorado Health Sciences Center, Denver 80262, USA.
L E
LE
Adler
R
R
Freedman
R G
RG
Ross
A
A
Olincy
M C
MC
Waldo
D001288:Attention / Q000502:physiology; D001921:Brain / Q000002:abnormalities*; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005072:Evoked Potentials, Auditory; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D009538:Nicotine / Q000493:pharmacokinetics; D010641:Phenotype; D011950:Receptors, Cholinergic / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects; D012307:Risk Factors; D012438:Saccades / Q000187:drug effects; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D009538:Nicotine