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Linkage and association study of schizophrenia and DNA-markers on chromosome 9q
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arousal, interpreted within a framework of a possibly genetically based neurointegrative disorder. The present study evaluated wakefulness and arousal patterns in neonates born to women with schizophrenic (n=20), schizo-affective (n= 12), affective (n = 19) and unspecified functional (n = 4) psychoses, as well as in 70 demographically similar controls. Wakefulness/arousal was assessed per Prechtl's 6-point scale 36 times during the course of a standardized neurological examination performed blindly by an experienced pediatric neurologist on the offspring's 3rd-4th day after birth. While offspring in all groups typically became increasingly aroused during the course of the examination, only the offspring of schizophrenics showed significantly reduced wakefulness-arousal during the initial stages of the examination (as compared with controls). Only among the offspring of schizophrenics was reduced wakefulnessarousal also associated with neurological abnormality on the total examination and with nontypical sensitivity to stimulation. These findings suggest not only that deviation in wakefulness and arousal is differentially characteristic of a subgroup of newborn offspring of schizophrenics but also that such deviations may represent part of a more generalized pattern of neurological abnormality in offspring at increased genetic risk for schizophrenia.
LINKAGE AND ASSOCIATION STUDY OF SCHIZOPHRENIA AND DNA-MARKERS ON CHROMOSOME 9q K. Meszaros*, E. Lenzinger, U. Willinger, A.M. Heiden, E. Miller Reiter, E. Resinger, V. Pfersmann, T. Stompe, K. Fuchs, E. Shimada, H.R. C h a u d h r y , W. Sieghart, R. Strobl, H.N. A s c h a u e r
University Hospital for Psychiatry, Department of General Psychiatry, A-1090 Vienna, Austria Disturbances in dopamine and norepinephrine neurotransmitter systems may play a major role in the pathogenesis of schizophrenia. Dopamine-beta-hydroxylase (DBH) is the enzyme that catalyses the metabolism of dopamine to norepinephrine in neurons. The aim of this study was to test a candidate gene region for schizophrenia on chromosome 9q (DBH; 9q34.3) for linkage and for association with the illness. We ascertained a sample of 34 families (more than 200 individuals) with multiple cases of schizophrenia and schizophrenia-related disorders. In addition 64 unrelated patients with schizophrenia and matched controls were sampled. Standardized diagnostic instruments were used (e.g. SADS-LA, OPCRIT) and a DSM III-R consensus diagnosis was made. In our study we did not find a linkage or association of DBH with schizophrenia. Therefore a strong influence of DBH in the pathogenesis of schizophrenia and related disorders could not be established. Supported by FWF 7639 and ESF-MNMI.
FAMILIAL
AGGREGATION
AND ATTENTIONAL
OF MEMORY
DEFICITS
IN
SCHIZOPHRENIA S.O. Moldin*, J.W. Newcomer, J.S. Richter, D.C. Boyd
Department of Psychiatry, Washington U. Medical School, St. Louis, MO 63110, USA Added power for the genetic analysis of schizophrenia may be afforded through the study of traits correlated with liability to illness. We searched for such traits by giving the Continuous Performance Test-IP Version, California Verbal Learning Test, and Wechsler Memory Scale-Revised (WMS-R) to schizophrenic probands (SZ; n = 24), their nonpsychotic first-degree relatives (SZREL; n = 54), bipolar probands (BP; n = 40), and their nonpsychotic first-degree relatives (BPREL; n=22). Subjects were diagnosed according to DSM-III-R criteria after being given the Diagnostic Interview for Genetic Studies. There were no significant 1Q differences for SZ vs BP or SZREL vs BPREL comparisons, and no relative met DSM-III-R substance abuse/ dependence criteria within the last three years. A clear pattern of differential deficits was found in SZs and SZRELs but not in BPs or BPRELs. Memory performance was worse in SZs vs BPs, as well as in SZRELs vs BPRELs (p < 0.05). Attentional performance on verbal and spatial tasks was worse in SZs vs BPs, as well as in SZRELs vs BPRELs (p<0.05). While attentional and memory deficits occurred in schizophrenia and bipolar disorder, they aggregated in relatives of schizophrenic probands only. Implications for genetic studies of schizophrenia are discussed.
LONGITUDINAL COURSE OF PSYCHOMETRIC DEVIANCE IN OFFSPRING OF SCHIZOPHRENIC PROBANDS: EVIDENCE FROM THE NEW YORK HIGH-RISK PROJECT S.O. Moldin*, I.I. G o t t e s m a n , L. Erlenmeyer-Kimling
Department of Psychiatry, Washington ~Z Medical School, St. Louis, MO 63110, USA Evidence from family, twin, and adoption studies supports the involvement of genetic factors in the etiology of schizophrenia. However, a specific major gene or multiple genes of lesser effect have not yet been identified in segregation and linkage analysis. Identification of etiologic factors may be enhanced if biobehavioral deficits correlated with liability to schizophrenia are identified. Here, we focus on psychometric deficits as a potential indicator of liability to schizophrenia in two samples of offspring of schizophrenic, mood-disordered, and psychiatrically normal parents in the New York High-Risk Project, a longitudinal, prospective study following these offspring from childhood to adulthood. We relate MMPI data collected in adolescence and again in adulthood to lifetime diagnoses based on the Schedule for Affective Disorders and Schizophrenia-
arousal, interpreted within a framework of a possibly genetically based neurointegrative disorder. The present study evaluated wakefulness and arousal patterns in neonates born to women with schizophrenic (n=20), schizo-affective (n= 12), affective (n = 19) and unspecified functional (n = 4) psychoses, as well as in 70 demographically similar controls. Wakefulness/arousal was assessed per Prechtl's 6-point scale 36 times during the course of a standardized neurological examination performed blindly by an experienced pediatric neurologist on the offspring's 3rd-4th day after birth. While offspring in all groups typically became increasingly aroused during the course of the examination, only the offspring of schizophrenics showed significantly reduced wakefulness-arousal during the initial stages of the examination (as compared with controls). Only among the offspring of schizophrenics was reduced wakefulnessarousal also associated with neurological abnormality on the total examination and with nontypical sensitivity to stimulation. These findings suggest not only that deviation in wakefulness and arousal is differentially characteristic of a subgroup of newborn offspring of schizophrenics but also that such deviations may represent part of a more generalized pattern of neurological abnormality in offspring at increased genetic risk for schizophrenia.
LINKAGE AND ASSOCIATION STUDY OF SCHIZOPHRENIA AND DNA-MARKERS ON CHROMOSOME 9q K. Meszaros*, E. Lenzinger, U. Willinger, A.M. Heiden, E. Miller Reiter, E. Resinger, V. Pfersmann, T. Stompe, K. Fuchs, E. Shimada, H.R. C h a u d h r y , W. Sieghart, R. Strobl, H.N. A s c h a u e r
University Hospital for Psychiatry, Department of General Psychiatry, A-1090 Vienna, Austria Disturbances in dopamine and norepinephrine neurotransmitter systems may play a major role in the pathogenesis of schizophrenia. Dopamine-beta-hydroxylase (DBH) is the enzyme that catalyses the metabolism of dopamine to norepinephrine in neurons. The aim of this study was to test a candidate gene region for schizophrenia on chromosome 9q (DBH; 9q34.3) for linkage and for association with the illness. We ascertained a sample of 34 families (more than 200 individuals) with multiple cases of schizophrenia and schizophrenia-related disorders. In addition 64 unrelated patients with schizophrenia and matched controls were sampled. Standardized diagnostic instruments were used (e.g. SADS-LA, OPCRIT) and a DSM III-R consensus diagnosis was made. In our study we did not find a linkage or association of DBH with schizophrenia. Therefore a strong influence of DBH in the pathogenesis of schizophrenia and related disorders could not be established. Supported by FWF 7639 and ESF-MNMI.
FAMILIAL
AGGREGATION
AND ATTENTIONAL
OF MEMORY
DEFICITS
IN
SCHIZOPHRENIA S.O. Moldin*, J.W. Newcomer, J.S. Richter, D.C. Boyd
Department of Psychiatry, Washington U. Medical School, St. Louis, MO 63110, USA Added power for the genetic analysis of schizophrenia may be afforded through the study of traits correlated with liability to illness. We searched for such traits by giving the Continuous Performance Test-IP Version, California Verbal Learning Test, and Wechsler Memory Scale-Revised (WMS-R) to schizophrenic probands (SZ; n = 24), their nonpsychotic first-degree relatives (SZREL; n = 54), bipolar probands (BP; n = 40), and their nonpsychotic first-degree relatives (BPREL; n=22). Subjects were diagnosed according to DSM-III-R criteria after being given the Diagnostic Interview for Genetic Studies. There were no significant 1Q differences for SZ vs BP or SZREL vs BPREL comparisons, and no relative met DSM-III-R substance abuse/ dependence criteria within the last three years. A clear pattern of differential deficits was found in SZs and SZRELs but not in BPs or BPRELs. Memory performance was worse in SZs vs BPs, as well as in SZRELs vs BPRELs (p < 0.05). Attentional performance on verbal and spatial tasks was worse in SZs vs BPs, as well as in SZRELs vs BPRELs (p<0.05). While attentional and memory deficits occurred in schizophrenia and bipolar disorder, they aggregated in relatives of schizophrenic probands only. Implications for genetic studies of schizophrenia are discussed.
LONGITUDINAL COURSE OF PSYCHOMETRIC DEVIANCE IN OFFSPRING OF SCHIZOPHRENIC PROBANDS: EVIDENCE FROM THE NEW YORK HIGH-RISK PROJECT S.O. Moldin*, I.I. G o t t e s m a n , L. Erlenmeyer-Kimling
Department of Psychiatry, Washington ~Z Medical School, St. Louis, MO 63110, USA Evidence from family, twin, and adoption studies supports the involvement of genetic factors in the etiology of schizophrenia. However, a specific major gene or multiple genes of lesser effect have not yet been identified in segregation and linkage analysis. Identification of etiologic factors may be enhanced if biobehavioral deficits correlated with liability to schizophrenia are identified. Here, we focus on psychometric deficits as a potential indicator of liability to schizophrenia in two samples of offspring of schizophrenic, mood-disordered, and psychiatrically normal parents in the New York High-Risk Project, a longitudinal, prospective study following these offspring from childhood to adulthood. We relate MMPI data collected in adolescence and again in adulthood to lifetime diagnoses based on the Schedule for Affective Disorders and Schizophrenia-