- Email: [email protected]
Early performance in subjects at high risk of developing schizophrenia
85
Conclusions: These palatal abnormalities were common amongst the psychoses, and were not specific for diagnosis. They may all share a common developmental mechanism. Further analysis and the collection of control data are underway.
A . 118. I N F O R M A T I V E MORPHOGENETIC VARIANTS IN SCHIZOPHRENIA AND BIPOLAR AFFECTIVE DISORDER M. Trixler, T. T6nyi, Gy. Csfibi
Department of Psychiatry, Univ. Med School of P~cs, 7623 P6~, Hungary
Psvchiatric Epidemiology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands" Objective: Are dermatoglyphic abnormalities, considered as markers of neurodevelopmental disturbances, specific to schizophrenia? Methods: Total a-b ridge count (TABRC), ridge dissociations (RD) and abnormal palmar flexion creases (APFC) were examined blind to case-control status in a group of 81 healthy controls and 90 individuals with functional psychosis (43 patients with schizophrenia and 47 with other psychosis). Logistic regression was used to calculate the corresponding adjusted odds ratio (OR). We also investigated interactions with sex. Results: Functional psychosis showed a significant excess of RD (OR =2.75; 95%CI = 1.35-5.61) and APFC (2.15; 1.104.21) compared to controls. Although TABRC was lower in the group with functional psychosis (OR=0.96; 0.93-0.99), this effect appeared to be restricted to the group of patients with schizophrenia (OR=0.94; 0.90-0.98). The effect of RD appeared to be largely confined to males (men: 4.12; 1.76 9.63; women: 0.82; 0.18 3.67). Conclusions: Dermatoglyphic abnormalities are associated with functional psychosis, especially in males, and do not seem to be specific to schizophrenia. Our findings add further evidence to a shared neurodevelopmental disturbance in at least a subgroup of functional psychotic disorders.
Objectives: The authors evaluated the prevalence of informative morphogenetic variants (IMVs) reflecting prenatal errors of morphogenesis in schizophrenia and in bipolar disorder. Method: Taking into consideration the criticism of the Waldrop scale, which was widely used until recently to define the presence of informative morphogenetic variants - - continuing their earlier study 1 - - the authors examined 56 IMVs in 30 schizophrenic, in 30 bipolar patients and in 30 matched control subjects. Results: The cumulative IMV prevalence was significantly higher among the patients with schizophrenia as in normal controls (p<0.001), and compared to bipolar patients, too (p<0.001). Yet the bipolar group had a significantly greater number of IMVs compared to the controls (p < 0.001 ). Patients with schizophrenia had significantly higher rates of four minor malformations (furrowed tongue, flat occiput, fiat forehead, primitive shape of ears) and of one phenogenetic variant (wide distance between toes 1 and 2). While compared to bipolar patients schizophrenics had significantly higher rates of two minor maltbrmations (fiat forehead, primitive shape of ears). In bipolar patients only furrowed tongue was significantly more common than in controls. Conclusion: The results support the 'early' neurodevelopmental model of schizophrenia and bipolar affective disorder, which emphasizes a fixed lesion with prenatal exposure.
A . 120. E A R L Y P E R F O R M A N C E IN SUBJECTS AT HIGH RISK OF DEVELOPING SCHIZOPHRENIA
Reference
E.C. Johnstone, E. G r a n t , A. Hodges, D.G.C. Owens
1. Trix]er M., Tenyi T., Csfibi Gy., Szab6 G., M6hes K. Informative Morphogenetic Variants in Patients with Schizophrenia and Alcohol-Dependent Patients: Beyond the Waldrop Scale. Am J Psychiatry, 1997, 154, 691-693.
University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh EHIO 5HF, Scotland
A. 119. D E R M A T O G L Y P H I C ABNORMALITIES IN PSYCHOSIS: CONTROL STUDY
A CASE-
F. N a v a r r o - M a t e u * , A. Micol*, D. Barcia*, J. van Os*
*Departamento de Salud Mental, Consejeria de Sanidad, Avda, Ronda de Levante, 11, 4aplanta, 30008-Murcia, Spain "/"Corresponding author: Section Social Psychiatry and
References 1. Van Os J., Fafianas L., Cannon M., MacDonald A., Murray R. Dermatoglyphic abnormalities in Psychosis: a twin study. Biol Psychiatry, 1997: 41: 624-626. 2. Guti6rrez B., van Os J., Guillamat R., Campillo M., Fafianas L. Congenital dermatoglyphic malformations in severe bipolar disorder. Psychiatry Research, 1998; 78: 133-140.
Background: Children destined to develop schizophrenia have been found to have some educational and behaviour differences in comparison with their peers who will remain well (e.g. Done et al.). This study examines premorbid performance in the subjects of the Edinburgh High Risk Study, which at present concerns 162 assessed subjects at enhanced risk of schizophrenia because they have at least two affected close relatives, 36 matched well controls and 37 matched first episode schizophrenics. Methods: All subjects were assessed at entry and the high risk and control subjects assessed every 18 months thereafter. Assessments concerned school performance, educational attain-
86
ments, psychiatric and psychological difficulties in childhood, social work involvement and police involvement. High risk and control groups were compared and within the high risk group those with and without psychotic parents at home were compared. Results: There were small, sometimes significant differences between the high risk subjects and controls in terms of school problems, educational and employment attainment and police involvement. Differences in terms of psychiatric and psychological problems and social services involvement were substantiated. The enhanced social services involvement, but not any of the other difficulties, could be attributed to the presence of a schizophrenic parent. Conclusion: The enhanced social work contact of high risk subjects is due to parental illness but their difficulties in education/employment and psychiatric/psychological problems are likely to result from neurodevelopmental disorder.
Reference Done J. et al. (1994). Br Med J 309:699 703.
B. Retroviral A.121. HOMO SAPIENS SPECIFIC ENDOGENOUS RETRO-ELEMENTS AS POTENTIAL PATHOGENS IN PSYCHOSIS R. Wadekar, H.S. Kim, T.J. Crow
POWIC, University Department of Psvchiato', The Warnefi)rd Hospital. OxJbrd 0)(3 7JX, UK The hypothesis that the predisposing gene has the structure of a retrovirus or retrotransposon (Crow, 1984) explains some aspects of psychosis (e.g. episodicity). With a combination of a PCR search based upon known sequences and phylogenetic analysis of these sequences in Homo sapiens and hominoid primates we have identified three classes of element that have been subject to recent change in the course of primate evolution and that include members that are specific to the human genome: (1) the SINE-R.C2 element that has been associated with Fukuyama-type muscular dystrophy, and long terminal repeat (LTR) structures associated with the human endogenous retroviruses (HERVs) in the (2) HERV-W, and (3) HERV-K classes. Each of these classes has the capacity to activate adjacent genes and includes members that have been subject to recent transposition in the human genome. We have investigated elements in these classes that are present within the region of Xq21.3/Yp region of homology that was generated by a transposition from the X to the Y chromosome that occurred after the separation of the chimpanzee and Homo sapiens lineages. This is a candidate region for a gene for cerebral asymmetry and psychosis, and these retro-elements are candidate genes.
ReJerences Crow T.J. (1984) Brit J Psychiat, 145:243 253. Kim H. S. et al. (1999) SINE-R.C2 (a Homo sapiens specific
retroposon) is homologous to cDNA from post-mortem brain in schizophrenia and to two loci in the Xq21.3/Yp block linked to handedness and psychosis. Amer J Med Genet (Neuropsychiat Genet) - - in press.
A . 122. D I F F E R E N T I A L RNA EXPRESSION IN A CELL LINE COCULTURED WITH CSF OF A SCHIZOPHRENIC PATIENT D. Hinze-Selch 1, F. Yee, L. Jones-Brando, S. B a c h m a n n , J. Schroeder, E.F. Torrey, R. Yolken
1The Stanley Division of Developmental Neurovirology, Johns Hopkins Hospital. 600 N. Wolfe St., Blalock 1105, Baltimore, MD 21287. USA Endogenous retroviruses have been postulated to play a role in the pathogenesis of schizophrenia. We investigated the transcription of RNA in the new world monkey NZP-60 cell line (ATCC: CRL-1924) which, after being cocultured with cerebrospinal fluid obtained from an individual with recent onset schizophrenia (S-CSF), contained retroviral particles as visualized by electron microscopy. This cell line was selected since new world monkeys are not endogenously infected with the human endogenous retroviruses (HERV)-W, HERV-K, ERV-9, and other endogenous retrovirnses implicated in schizophrenia. We are employing the technique of differential display polymerase chain reaction (PCR) in order to characterize the RNA transcription of cells inoculated with S-CSF. We serially passaged S-CSF inoculated NZP-60 cells 9 times in parallel with mock infected cells. RNA was extracted, converted to cDNA, and amplified using a series of differential display primers (Delta Differential Display TM kit by Clontech). Initial analysis has identified a number of amplified products that are differentially expressed in S-CSF and mock inoculated cells. The nucleotide and predicted amino acid sequence and analysis of these differentially expressed products are ongoing. These studies may identify viral and cellular RNA transcripts which are involved in the etiology and pathogenesis of schizophrenia.
A . 123. E N D O G E N O U S RETROVIRUSES AND SCHIZOPHRENIA -- A SOLUTION THE NATURE/NURTURE DILEMMA?
TO
R.H. Yolken, H. Karlsson, E.F. Torrey
Johns Hopkins University, Stanley Division of Developmental Neurovirology, 600 N. Wolfe St., Blalock 1104, Baltimore, MD 21287-4933. USA Endogenous retroviruses (ERs) are components of the genome that share sequence homology with infectious retroviruses. ERs can be inherited in a Mendelian fashion; however, the elements can also become activated and retrotranspose into heterologous areas of the genome. Activation can be induced
Conclusions: These palatal abnormalities were common amongst the psychoses, and were not specific for diagnosis. They may all share a common developmental mechanism. Further analysis and the collection of control data are underway.
A . 118. I N F O R M A T I V E MORPHOGENETIC VARIANTS IN SCHIZOPHRENIA AND BIPOLAR AFFECTIVE DISORDER M. Trixler, T. T6nyi, Gy. Csfibi
Department of Psychiatry, Univ. Med School of P~cs, 7623 P6~, Hungary
Psvchiatric Epidemiology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands" Objective: Are dermatoglyphic abnormalities, considered as markers of neurodevelopmental disturbances, specific to schizophrenia? Methods: Total a-b ridge count (TABRC), ridge dissociations (RD) and abnormal palmar flexion creases (APFC) were examined blind to case-control status in a group of 81 healthy controls and 90 individuals with functional psychosis (43 patients with schizophrenia and 47 with other psychosis). Logistic regression was used to calculate the corresponding adjusted odds ratio (OR). We also investigated interactions with sex. Results: Functional psychosis showed a significant excess of RD (OR =2.75; 95%CI = 1.35-5.61) and APFC (2.15; 1.104.21) compared to controls. Although TABRC was lower in the group with functional psychosis (OR=0.96; 0.93-0.99), this effect appeared to be restricted to the group of patients with schizophrenia (OR=0.94; 0.90-0.98). The effect of RD appeared to be largely confined to males (men: 4.12; 1.76 9.63; women: 0.82; 0.18 3.67). Conclusions: Dermatoglyphic abnormalities are associated with functional psychosis, especially in males, and do not seem to be specific to schizophrenia. Our findings add further evidence to a shared neurodevelopmental disturbance in at least a subgroup of functional psychotic disorders.
Objectives: The authors evaluated the prevalence of informative morphogenetic variants (IMVs) reflecting prenatal errors of morphogenesis in schizophrenia and in bipolar disorder. Method: Taking into consideration the criticism of the Waldrop scale, which was widely used until recently to define the presence of informative morphogenetic variants - - continuing their earlier study 1 - - the authors examined 56 IMVs in 30 schizophrenic, in 30 bipolar patients and in 30 matched control subjects. Results: The cumulative IMV prevalence was significantly higher among the patients with schizophrenia as in normal controls (p<0.001), and compared to bipolar patients, too (p<0.001). Yet the bipolar group had a significantly greater number of IMVs compared to the controls (p < 0.001 ). Patients with schizophrenia had significantly higher rates of four minor malformations (furrowed tongue, flat occiput, fiat forehead, primitive shape of ears) and of one phenogenetic variant (wide distance between toes 1 and 2). While compared to bipolar patients schizophrenics had significantly higher rates of two minor maltbrmations (fiat forehead, primitive shape of ears). In bipolar patients only furrowed tongue was significantly more common than in controls. Conclusion: The results support the 'early' neurodevelopmental model of schizophrenia and bipolar affective disorder, which emphasizes a fixed lesion with prenatal exposure.
A . 120. E A R L Y P E R F O R M A N C E IN SUBJECTS AT HIGH RISK OF DEVELOPING SCHIZOPHRENIA
Reference
E.C. Johnstone, E. G r a n t , A. Hodges, D.G.C. Owens
1. Trix]er M., Tenyi T., Csfibi Gy., Szab6 G., M6hes K. Informative Morphogenetic Variants in Patients with Schizophrenia and Alcohol-Dependent Patients: Beyond the Waldrop Scale. Am J Psychiatry, 1997, 154, 691-693.
University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh EHIO 5HF, Scotland
A. 119. D E R M A T O G L Y P H I C ABNORMALITIES IN PSYCHOSIS: CONTROL STUDY
A CASE-
F. N a v a r r o - M a t e u * , A. Micol*, D. Barcia*, J. van Os*
*Departamento de Salud Mental, Consejeria de Sanidad, Avda, Ronda de Levante, 11, 4aplanta, 30008-Murcia, Spain "/"Corresponding author: Section Social Psychiatry and
References 1. Van Os J., Fafianas L., Cannon M., MacDonald A., Murray R. Dermatoglyphic abnormalities in Psychosis: a twin study. Biol Psychiatry, 1997: 41: 624-626. 2. Guti6rrez B., van Os J., Guillamat R., Campillo M., Fafianas L. Congenital dermatoglyphic malformations in severe bipolar disorder. Psychiatry Research, 1998; 78: 133-140.
Background: Children destined to develop schizophrenia have been found to have some educational and behaviour differences in comparison with their peers who will remain well (e.g. Done et al.). This study examines premorbid performance in the subjects of the Edinburgh High Risk Study, which at present concerns 162 assessed subjects at enhanced risk of schizophrenia because they have at least two affected close relatives, 36 matched well controls and 37 matched first episode schizophrenics. Methods: All subjects were assessed at entry and the high risk and control subjects assessed every 18 months thereafter. Assessments concerned school performance, educational attain-
86
ments, psychiatric and psychological difficulties in childhood, social work involvement and police involvement. High risk and control groups were compared and within the high risk group those with and without psychotic parents at home were compared. Results: There were small, sometimes significant differences between the high risk subjects and controls in terms of school problems, educational and employment attainment and police involvement. Differences in terms of psychiatric and psychological problems and social services involvement were substantiated. The enhanced social services involvement, but not any of the other difficulties, could be attributed to the presence of a schizophrenic parent. Conclusion: The enhanced social work contact of high risk subjects is due to parental illness but their difficulties in education/employment and psychiatric/psychological problems are likely to result from neurodevelopmental disorder.
Reference Done J. et al. (1994). Br Med J 309:699 703.
B. Retroviral A.121. HOMO SAPIENS SPECIFIC ENDOGENOUS RETRO-ELEMENTS AS POTENTIAL PATHOGENS IN PSYCHOSIS R. Wadekar, H.S. Kim, T.J. Crow
POWIC, University Department of Psvchiato', The Warnefi)rd Hospital. OxJbrd 0)(3 7JX, UK The hypothesis that the predisposing gene has the structure of a retrovirus or retrotransposon (Crow, 1984) explains some aspects of psychosis (e.g. episodicity). With a combination of a PCR search based upon known sequences and phylogenetic analysis of these sequences in Homo sapiens and hominoid primates we have identified three classes of element that have been subject to recent change in the course of primate evolution and that include members that are specific to the human genome: (1) the SINE-R.C2 element that has been associated with Fukuyama-type muscular dystrophy, and long terminal repeat (LTR) structures associated with the human endogenous retroviruses (HERVs) in the (2) HERV-W, and (3) HERV-K classes. Each of these classes has the capacity to activate adjacent genes and includes members that have been subject to recent transposition in the human genome. We have investigated elements in these classes that are present within the region of Xq21.3/Yp region of homology that was generated by a transposition from the X to the Y chromosome that occurred after the separation of the chimpanzee and Homo sapiens lineages. This is a candidate region for a gene for cerebral asymmetry and psychosis, and these retro-elements are candidate genes.
ReJerences Crow T.J. (1984) Brit J Psychiat, 145:243 253. Kim H. S. et al. (1999) SINE-R.C2 (a Homo sapiens specific
retroposon) is homologous to cDNA from post-mortem brain in schizophrenia and to two loci in the Xq21.3/Yp block linked to handedness and psychosis. Amer J Med Genet (Neuropsychiat Genet) - - in press.
A . 122. D I F F E R E N T I A L RNA EXPRESSION IN A CELL LINE COCULTURED WITH CSF OF A SCHIZOPHRENIC PATIENT D. Hinze-Selch 1, F. Yee, L. Jones-Brando, S. B a c h m a n n , J. Schroeder, E.F. Torrey, R. Yolken
1The Stanley Division of Developmental Neurovirology, Johns Hopkins Hospital. 600 N. Wolfe St., Blalock 1105, Baltimore, MD 21287. USA Endogenous retroviruses have been postulated to play a role in the pathogenesis of schizophrenia. We investigated the transcription of RNA in the new world monkey NZP-60 cell line (ATCC: CRL-1924) which, after being cocultured with cerebrospinal fluid obtained from an individual with recent onset schizophrenia (S-CSF), contained retroviral particles as visualized by electron microscopy. This cell line was selected since new world monkeys are not endogenously infected with the human endogenous retroviruses (HERV)-W, HERV-K, ERV-9, and other endogenous retrovirnses implicated in schizophrenia. We are employing the technique of differential display polymerase chain reaction (PCR) in order to characterize the RNA transcription of cells inoculated with S-CSF. We serially passaged S-CSF inoculated NZP-60 cells 9 times in parallel with mock infected cells. RNA was extracted, converted to cDNA, and amplified using a series of differential display primers (Delta Differential Display TM kit by Clontech). Initial analysis has identified a number of amplified products that are differentially expressed in S-CSF and mock inoculated cells. The nucleotide and predicted amino acid sequence and analysis of these differentially expressed products are ongoing. These studies may identify viral and cellular RNA transcripts which are involved in the etiology and pathogenesis of schizophrenia.
A . 123. E N D O G E N O U S RETROVIRUSES AND SCHIZOPHRENIA -- A SOLUTION THE NATURE/NURTURE DILEMMA?
TO
R.H. Yolken, H. Karlsson, E.F. Torrey
Johns Hopkins University, Stanley Division of Developmental Neurovirology, 600 N. Wolfe St., Blalock 1104, Baltimore, MD 21287-4933. USA Endogenous retroviruses (ERs) are components of the genome that share sequence homology with infectious retroviruses. ERs can be inherited in a Mendelian fashion; however, the elements can also become activated and retrotranspose into heterologous areas of the genome. Activation can be induced