Smooth Pursuit Performance in Families With Multiple Occurrence of Schizophrenia and Nonpsychotic Families Rebekka Lencer, Carsten P. Malchow, Katja Krecker, Achim Nolte, Marlene Pinnow, Susanne Zimmerman v. Siefart, Eberhard Schwinger, and Volker Arolt Background: Eye tracking dysfunction (ETD) has been put forward as a trait marker for biological susceptibility to schizophrenia with the hope of identifying a link to specific cerebral lesions. Methods: Eye movements were recorded using infrared oculography in 8 families (67 members) showing multiple occurrence of schizophrenia and in 9 nonpsychotic fami- lies (80 members). Triangle wave stimuli at 15°/s and 30°/s were used and gains (eye velocity/target velocity), rates and amplitudes of different saccade categories (catch-up, back-up, anticipatory saccades, and square- wave-jerks) were determined. Results: In the relatives, the same deficit in maintenance of smooth pursuit performance was found as was seen in the schizophrenic patients. This deficit, which was not observed in the nonpsychotic families, consisted of lower gains for leftward as compared to rightward pursuit. This was emphasized most clearly at 30°/s and was associated with an excess of catch-up saccades in the schizophrenic patients, whereas in the relatives a tendency to exhibit more and larger anticipatory saccades was observed. Conclusions: The results confirm the hypothesis that eye-tracking dysfunction is a phenotypic marker for ge- netic liability to schizophrenia. Neurophysiologically, a cerebral dysfunction which includes one or more of the oculomotor centers can be assumed in subjects who carry a genetic susceptibility to schizophrenia. Biol Psychiatry 1999;45:694 –703 © 1999 Society of Biological Psychia- try Key Words: Smooth pursuit, gain, saccades, schizophre- nia multiplex families, nonpsychotic families Introduction R ecent research on schizophrenia has used molecular genetic analysis to reveal the underlying genetic mechanisms and to attempt an identification of the gene loci believed to be involved in conveying susceptibility to schizophrenia (Cloninger 1997). One of the major prob- lems is that it is difficult 1) to define the borders of the various schizophrenia spectrum disorders; and 2) to iden- tify those individuals who carry the genetic trait without suffering from the disease (Levinson et al 1991). Eye tracking dysfunction (ETD) has been put forward as one of the most promising biologic, ie phenotypic trait markers for genetic liability to schizophrenia (Holzman 1989; Grove et al 1992), although Litman et al 1997 recently were sceptical of the use of ETD for identifying putative gene carriers among at-risk relatives. However, our group has found evidence for a significant linkage of ETD to markers on chromosome 6p23-21 in families showing multiple occurrences of schizophrenia (Arolt et al 1996a). Specific methods of assessment such as gain analysis (the ratio of the velocity of the smooth pursuit component of eye movement to target velocity) and high resolution techniques (e.g., infra-red oculography), have been adopted from neuroophthalmologic research. These have been introduced into schizophrenia research (Abel et al 1991) with the hope of finding a link to specific lesions within oculomotor centers, such as the frontal eye field (FEF), the middle temporal visual area (MT), the medial superior temporal visual area (MST), or the supplementary motor area (SMA), which might be responsible for ocu- lomotor deficits in schizophrenic patients. Those saccades which occur during smooth pursuit eye movements can be classified either as catch-up saccades (CUS), back-up saccades (BUS), anticipatory saccades (AS), or square wave jerks (SWJ). The most frequent subtype both in normals and schizophrenic patients is CUS, followed in order of frequency by AS, BUS, and SWJ. There is convincing evidence that in schizophrenic patients, the From the Department of Psychiatry (RL, KK, AN, MP, SZvS, CPM) and the Institute of Human Genetics (ES) of the University of Luebeck School of Medicine, Luebeck, and the Department of Psychiatry of the Westfaelische Wilhelms-University (VA), Muenster, Germany. Address reprint requests to Rebekka Lencer, MD, Klinik fu ¨r Psychiatrie, Mediz- inische Universita ¨t zu Lu ¨beck, Ratzeburger Allee 160, 23538 Lu ¨beck, Ger- many. Received March 9, 1998; revised September 1, 1998; accepted September 2, 1998. © 1999 Society of Biological Psychiatry 0006-3223/99/$19.00 PII S0006-3223(98)0245-5