Physiology of schizophrenia, bipolar disorder, and schizoaffective disorder.
OBJECTIVE
Endophenotypes have been proposed to identify the genetic and biological substrates of complex disorders. Three physiological inhibitory endophenotypes of large effect size in schizophrenia include suppression of P50 auditory evoked responses, inhibition of leading (small anticipatory) saccades during smooth pursuit eye movements, and cancellation of reflexive saccades in the antisaccade eye movement task. The aim of this study was to determine if the pattern of endophenotype abnormalities within individuals with schizophrenia differed from that within individuals with bipolar disorder. A second aim was to determine whether subjects with schizoaffective disorder, bipolar type, were neurophysiologically more similar to subjects with schizophrenia or subjects with bipolar disorder.


METHODS
Endophenotypes were recorded for subjects diagnosed with schizophrenia (N=29), bipolar disorder (DSM-IV-TR) (N=40), and schizoaffective disorder, bipolar type (N=18). Data from normal comparison subjects were used to establish normal performance.


RESULTS
Logistic regression determined that P50 ratio and frequency of leading saccades identified subjects with schizophrenia and bipolar disorder with a sensitivity of 95% and a specificity of 83%. The schizoaffective disorder group was split, with six subjects physiologically classified as schizophrenia-like and 12 subjects as bipolar-like. Those classified as schizophrenia-like were significantly younger at illness onset and had higher symptom ratings.


CONCLUSIONS
A composite endophenotype of P50 ratio and frequency of leading saccades is consistent with the current clinical nosology of schizophrenia and bipolar disorder and parses patients with schizoaffective disorder, bipolar type, into two subgroups.
Department of Psychiatry, University of Colorado at Denver and Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA. laura.martin@uchsc.edu
Laura F
LF
Martin
Mei-Hua
MH
Hall
Randal G
RG
Ross
Gary
G
Zerbe
Robert
R
Freedman
Ann
A
Olincy
D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015415:Biomarkers; D001714:Bipolar Disorder / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D003937:Diagnosis, Differential; D005072:Evoked Potentials, Auditory / Q000502:physiology*; D005260:Female; D006801:Humans; D007266:Inhibition, Psychological; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011618:Psychotic Disorders / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D011698:Pursuit, Smooth / Q000502:physiology*; D012372:ROC Curve; D012438:Saccades / Q000502:physiology*; D012559:Schizophrenia / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D012565:Schizophrenic Psychology; D012680:Sensitivity and Specificity; D013647:Task Performance and Analysis
D015415:Biomarkers