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Genetic and Perinatal Determinants of Structural Brain Deficits in Schizophrenia

Genetic and Perinatal Determinants of Structural Brain Deficits in Schizophrenia Abstract • Using a subsample from the Copenhagen schizophrenia high-risk project, we examined the contributions of schizophrenic genetic liability and perinatal complications to computed tomographic (CT) measurements of ventricular enlargement and cortical and cerebellar abnormalities. A factor analysis of six CT measurements yielded two significant factors. One factor reflected multisite neural deficits as evidenced by abnormality of the cerebellar vermis and widening of the sylvian and interhemispheric fissures and cortical sulci. The other factor reflected periventricular damage as evidenced by enlargement of the third and lateral ventricles. Because all of the subjects had schizophrenic mothers, the major source of genetic variation is contributed by the diagnostic status of their fathers. In a stepwise multiple-regression analysis, it was determined that the multisite neural deficits factor was significantly related to genetic risk for schizophrenia (as measured by schizophrenia spectrum illness in the subjects' fathers) but was unrelated to pregnancy or delivery complications or to weight at birth. Periventricular damage was highly and significantly correlated with the number of complications suffered at delivery, but only among subjects with an elevated genetic risk. Although limited by a small sample size, these results suggest that the two types of CT abnormalities in schizophrenia may reflect partially independent processes based on different combinations of genetic and perinatal influences. References 1. Weinberger DR, Wagner RL, Wyatt RJ. Neuropathological studies of schizophrenia: a selective review . Schizophr Bull . 1983;9:193-212.Crossref 2. Gruzelier JH. Central nervous system signs in schizophrenia . In: Frederiks JAM, ed. Handbook of Clinical Neurology, Vol 2: Neurobehavioral Disorders . Amsterdam, the Netherlands: Elsevier Science Publishers; 1985. 3. Heath RG, Franklin DE, Shraberg D. Gross pathology of the cerebellum in patients diagnosed and treated as psychiatric disorders . J Nerv Ment Dis . 1979;167:585-592.Crossref 4. Weinberger DR, Torrey EF, Wyatt RJ. Cerebellar atrophy in chronic schizophrenia . Lancet . 1979;1:718-719.Crossref 5. Lippman S, Manshadi M, Baldwin H, Brasin G, Rice J, Alraheh S. Cerebellar vermis dimensions on computerized tomographic scans of schizophrenia and bipolar patients . Am J Psychiatry . 1982;139:667-668. 6. Golden CJ, Graber B, Coffman J, Berg RA, Newlin DB, Bloch S. Brain density deficits in chronic schizophrenia . Psychiatry Res . 1980;3:179-184.Crossref 7. Weinberger DR, Torrey EF, Neophytides AN, Wyatt RJ. Structural abnormalities in the cerebral cortex of chronic schizophrenic patients . Arch Gen Psychiatry . 1979;36:935-939.Crossref 8. Nasrallah HA, Kuperman S, McCalley-Whitters M, Hamra B. Clinical correlates of sulcal widening in chronic schizophrenia . Psychiatry Res . 1983;10:237-242.Crossref 9. Boronow J, Pickar D, Ninan PT, Roy A, Hommer D, Linnoila M, Paul SM. Atrophy limited to the third ventricle in chronic schizophrenic patients . Arch Gen Psychiatry . 1985;42:266-271.Crossref 10. Okasha A, Madkour O. Cortical and central atrophy in chronic schizophrenia . Acta Psychiatr Scand . 1982;65:29-34.Crossref 11. Kling AS, Kurtz N, Tachiki K, Orzeck A. CT scans in subgroups of chronic schizophrenics . J Psychiatr Res . 1982/1983;17:375-394.Crossref 12. Rieder RO, Mann LS, Weinberger DR, Van Kammen DP, Post RM. Computed tomographic scans in patients with schizophrenia, schizoaffective and bipolar affective disorder . Arch Gen Psychiatry . 1983;40:735-739.Crossref 13. Pfefferbaum A, Zipursky RB, Lim KO. Computerized quantification of cerebral atrophy in schizophrenics. Presented at the American College of Neuropsychopharmacology; December 1986; Washington, DC. 14. Vita A, Sacchetti E, Calzeroni A, Cazzullo CL. Cortical atrophy in schizophrenia: prevalence and associated features . Schizophr Res . In press. 15. DeLisi LE, Goldin LR, Hamovit JR, Maxwell ME, Kurtz D, Gershon ES. A family study of the association of increased ventricular size with schizophrenia . Arch Gen Psychiatry . 1986;43:148-153.Crossref 16. Weinberger DR, DeLisi LE, Neophytides AN, Wyatt RJ. Familial aspects of CT abnormalities in chronic schizophrenic patients . Psychiatry Res . 1981;4:65-71.Crossref 17. Schulsinger F, Parnas J, Peterson ET, Schulsinger H, Teasdale TW, Mednick SA, Moller L, Silverton L. Cerebral ventricular size in the offspring of schizophrenic mothers . Arch Gen Psychiatry . 1984;41:602-606.Crossref 18. Silverton L, Finello K, Mednick SA, Schulsinger F. Low birthweight and ventricular enlargement in a high risk sample . J Abnorm Psychol . 1985;94:402-407.Crossref 19. Lewis SW, Murray RM. Obstetric complications, neurodevelopmental deviance, and risk for schizophrenia . J Psychiatr Res . 1987;21:413-421.Crossref 20. Turner SW, Toone BK, Brett-Jones JR. Computerized tomographic scan changes in early schizophrenia . Psychol Med . 1986;16:219-225.Crossref 21. Pearlson GC, Garbacz DJ, Moberg PJ, Ahn HS, dePaulo JR. Symptomatic, familial, perinatal, and social correlates of CAT changes in schizophrenics and bipolars . J Nerv Ment Dis . 1985;173:42-50.Crossref 22. Mednick SA, Machon RA, Huttunen MO, Bonett D. Adult schizophrenia following prenatal exposure to an influenza epidemic . Arch Gen Psychiatry . 1988;45:189-192.Crossref 23. Huttunen MO, Niskanen P. Prenatal loss of father and psychiatric disorders . Arch Gen Psychiatry . 1978;35:429-431.Crossref 24. Torrey EF, Rawlings R, Waldman IN. Schizophrenic births and viral disease in two states . Schizophr Res . 1988;1:73-77.Crossref 25. Barr CE, Mednick SA. A replication of the second trimester effect in Denmark: a 50 year study of the association between viral infection and schizophrenia. Presented at the Second World Congress on Viruses, Immunity and Mental Health; October 4, 1988; Mont Gabriel, Canada. 26. Jacob H, Beckmann H. Prenatal development disturbances in the limbic allocortex in schizophrenics . J Neural Transm . 1986;65:303-326.Crossref 27. Kovelman JA, Scheibel AB. A neurohistological correlate of schizophrenia . Biol Psychiatry . 1984;19:1601-1621. 28. Bogerts B, Meertz E, Schonfeld-Bausch R. Basal ganglia and limbic system pathology in schizophrenia . Arch Gen Psychiatry . 1985;42:784-791.Crossref 29. Andreasen N, Nasrallah HA, Dunn V, Olson SC, Grove WM, Ehrhardt JC, Coffman JA, Crossett JHW. Structural abnormalities in the frontal system in schizophrenia . Arch Gen Psychiatry . 1986;43:136-144.Crossref 30. Sartorius N. Early manifestations and first contact incidence of schizophrenics in different cultures . Psychol Med . 1986;16:909-928.Crossref 31. Nowakowski RS. Basic concepts of CNS development . Child Dev . 1987;58:568-595.Crossref 32. Rakic P, Sidman RL. Sequence of developmental abnormalities leading to granule cell deficit in cerebellar cortex of weaver mutant mice . J Comp Neurol . 1978;152:103-132.Crossref 33. Cannon TD, Mednick SA, Parnas J. Two pathways to schizophrenia in children at risk . In: Robins L, Rutter M, eds. Straight and Devious Pathways From Childhood to Adulthood . New York, NY: Cambridge University Press. In press. 34. Mednick SA, Machon RA, Huttunen MO. Disturbances of fetal neural development and adult schizophrenia . In: Schulz SC, ed. Schizophrenia: A Scientific Focus . New York, NY: Oxford University Press Inc. 1989:69-77. 35. Brann AW. Factors during neonatal life that influence brain disorders . In Freeman JM, ed. Prenatal and Perinatal Factors Associated With Brain Disorders . Washington, DC: National Institutes of Health; 1985:263-358. 36. Sinha SK, Davies JM, Sims DG, Chiswick ML. Relation between periventricular hemorrhage and ischaemic brain lesions diagnosed by ultrasound in very preterm infants . Lancet . 1985;2:1154-1156.Crossref 37. Lane EA, Albee GW. Comparative birthweights of schizophrenics and their siblings . J Psychol . 1966;64:227-231.Crossref 38. Marcus J, Hans SL, Mednick SA, Schulsinger F, Michelsen N. Neurological dysfunctioning in offspring of schizophrenics in Israel and Denmark: a replication analysis . Arch Gen Psychiatry . 1985;42:753-761.Crossref 39. Mednick SA, Schulsinger F. A longitudinal study of children with a high risk for schizophrenia: a preliminary report . In: Vandenberg S, ed. Methods and Goals in Human Behavior Genetics . Orlando, Fla: Academic Press Inc; 1965:255-296. 40. Schulsinger H. A ten year follow-up of children of schizophrenic mothers: a clinical assessment . Acta Psychiatr Scand . 1976;53:371-386.Crossref 41. Parnas J, Schulsinger F, Teasdale TW, Schulsinger H, Feldman PM, Mednick SA. Perinatal complications and clinical outcome within the schizophrenia spectrum . Br J Psychiatry . 1982;140:416-420.Crossref 42. Weinberger DR, Torrey EF, Neophytides AN, Wyatt RJ. Lateral cerebral ventricular enlargement in chronic schizophrenia . Arch Gen Psychiatry . 1979;36:735-739.Crossref 43. Gottesman II, Shields J. Schizophrenia: The Epigenetic Puzzle . New York, NY: Cambridge University Press; 1982. 44. Parnas J. Mates of schizophrenic mothers: a study of assortative mating from the American-Danish high risk study . Br J Psychiatry . 1985;146:490-497.Crossref 45. Spitzer RL, Endicott J. Schedule for Affective Disorders and Schizophrenia—Lifetime Version . Biometric Research . 3rd ed. New York, NY: New York Psychiatric Institute; 1978. 46. SAS User's Guide. Cary, NC: SAS Institute Inc; 1984. 47. Cliff N. Analyzing Multivariate Data . New York, NY: Harcourt Brace Jovanovich Publishers; 1987. 48. Parnas J, Teasdale TW. Treated versus untreated schizophrenia spectrum cases: a matched paired high risk population study . Acta Psychiatr Scand . 1987;75:44-50.Crossref 49. Bogerts B. Neuropathological abnormalities and their clinical correlates in schizophrenia. Presented at the National Institute of Mental Health Conference Fetal Neural Development and Schizophrenia; May 31, 1988; Washington, DC. 50. Weinberger DR, DeLisi LE, Perman G, Targum S, Wyatt RJ. CT scans in schizophreniform disorder and other acute psychiatric patients . Arch Gen Psychiatry . 1982;39:778-783.Crossref 51. Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia . Arch Gen Psychiatry . 1987;44:660-669.Crossref 52. Sostek AM, Smith YF, Katz KS, Grant EG. Developmental outcome of preterm infants with intraventricular hemorrhage at 1 and 2 years of age . Child Dev . 1987;58:779-786.Crossref 53. Weinberger DR, Cannon-Spoor HE, Potkin SG, Wyatt RJ. Poor premorbid adjustment and CT scan abnormalities in chronic schizophrenia . Am J Psychiatry . 1980;137:1410-1413. 54. Andreasen NC, Olsen SA, Dennert JW, Smith MR. Ventricular enlargement in schizophrenia: relationship to positive and negative symptoms . Am J Psychiatry . 1982;139:297-302. 55. Cannon TD, Fuhrmann M, Mednick SA, Machon RA, Parnas J, Schulsinger F. Third ventricle enlargement and reduced electrodermal responsiveness . Psychophysiology . 1988;25:153-157.Crossref 56. Huber G. Pneumoencephalographische und Psychopathologische Bilder Bei Endogen Psychosen . New York, NY: Springer-Verlag NY Inc; 1957. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Genetic and Perinatal Determinants of Structural Brain Deficits in Schizophrenia

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Publisher
American Medical Association
Copyright
Copyright © 1989 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1989.01810100025005
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Abstract

Abstract • Using a subsample from the Copenhagen schizophrenia high-risk project, we examined the contributions of schizophrenic genetic liability and perinatal complications to computed tomographic (CT) measurements of ventricular enlargement and cortical and cerebellar abnormalities. A factor analysis of six CT measurements yielded two significant factors. One factor reflected multisite neural deficits as evidenced by abnormality of the cerebellar vermis and widening of the sylvian and interhemispheric fissures and cortical sulci. The other factor reflected periventricular damage as evidenced by enlargement of the third and lateral ventricles. Because all of the subjects had schizophrenic mothers, the major source of genetic variation is contributed by the diagnostic status of their fathers. In a stepwise multiple-regression analysis, it was determined that the multisite neural deficits factor was significantly related to genetic risk for schizophrenia (as measured by schizophrenia spectrum illness in the subjects' fathers) but was unrelated to pregnancy or delivery complications or to weight at birth. Periventricular damage was highly and significantly correlated with the number of complications suffered at delivery, but only among subjects with an elevated genetic risk. Although limited by a small sample size, these results suggest that the two types of CT abnormalities in schizophrenia may reflect partially independent processes based on different combinations of genetic and perinatal influences. References 1. Weinberger DR, Wagner RL, Wyatt RJ. Neuropathological studies of schizophrenia: a selective review . Schizophr Bull . 1983;9:193-212.Crossref 2. Gruzelier JH. Central nervous system signs in schizophrenia . In: Frederiks JAM, ed. Handbook of Clinical Neurology, Vol 2: Neurobehavioral Disorders . Amsterdam, the Netherlands: Elsevier Science Publishers; 1985. 3. Heath RG, Franklin DE, Shraberg D. Gross pathology of the cerebellum in patients diagnosed and treated as psychiatric disorders . J Nerv Ment Dis . 1979;167:585-592.Crossref 4. Weinberger DR, Torrey EF, Wyatt RJ. Cerebellar atrophy in chronic schizophrenia . Lancet . 1979;1:718-719.Crossref 5. Lippman S, Manshadi M, Baldwin H, Brasin G, Rice J, Alraheh S. Cerebellar vermis dimensions on computerized tomographic scans of schizophrenia and bipolar patients . Am J Psychiatry . 1982;139:667-668. 6. Golden CJ, Graber B, Coffman J, Berg RA, Newlin DB, Bloch S. Brain density deficits in chronic schizophrenia . Psychiatry Res . 1980;3:179-184.Crossref 7. Weinberger DR, Torrey EF, Neophytides AN, Wyatt RJ. Structural abnormalities in the cerebral cortex of chronic schizophrenic patients . Arch Gen Psychiatry . 1979;36:935-939.Crossref 8. Nasrallah HA, Kuperman S, McCalley-Whitters M, Hamra B. Clinical correlates of sulcal widening in chronic schizophrenia . Psychiatry Res . 1983;10:237-242.Crossref 9. Boronow J, Pickar D, Ninan PT, Roy A, Hommer D, Linnoila M, Paul SM. Atrophy limited to the third ventricle in chronic schizophrenic patients . Arch Gen Psychiatry . 1985;42:266-271.Crossref 10. Okasha A, Madkour O. Cortical and central atrophy in chronic schizophrenia . Acta Psychiatr Scand . 1982;65:29-34.Crossref 11. Kling AS, Kurtz N, Tachiki K, Orzeck A. CT scans in subgroups of chronic schizophrenics . J Psychiatr Res . 1982/1983;17:375-394.Crossref 12. Rieder RO, Mann LS, Weinberger DR, Van Kammen DP, Post RM. Computed tomographic scans in patients with schizophrenia, schizoaffective and bipolar affective disorder . Arch Gen Psychiatry . 1983;40:735-739.Crossref 13. Pfefferbaum A, Zipursky RB, Lim KO. Computerized quantification of cerebral atrophy in schizophrenics. Presented at the American College of Neuropsychopharmacology; December 1986; Washington, DC. 14. Vita A, Sacchetti E, Calzeroni A, Cazzullo CL. Cortical atrophy in schizophrenia: prevalence and associated features . Schizophr Res . In press. 15. DeLisi LE, Goldin LR, Hamovit JR, Maxwell ME, Kurtz D, Gershon ES. A family study of the association of increased ventricular size with schizophrenia . Arch Gen Psychiatry . 1986;43:148-153.Crossref 16. Weinberger DR, DeLisi LE, Neophytides AN, Wyatt RJ. Familial aspects of CT abnormalities in chronic schizophrenic patients . Psychiatry Res . 1981;4:65-71.Crossref 17. Schulsinger F, Parnas J, Peterson ET, Schulsinger H, Teasdale TW, Mednick SA, Moller L, Silverton L. Cerebral ventricular size in the offspring of schizophrenic mothers . Arch Gen Psychiatry . 1984;41:602-606.Crossref 18. Silverton L, Finello K, Mednick SA, Schulsinger F. Low birthweight and ventricular enlargement in a high risk sample . J Abnorm Psychol . 1985;94:402-407.Crossref 19. Lewis SW, Murray RM. Obstetric complications, neurodevelopmental deviance, and risk for schizophrenia . J Psychiatr Res . 1987;21:413-421.Crossref 20. Turner SW, Toone BK, Brett-Jones JR. Computerized tomographic scan changes in early schizophrenia . Psychol Med . 1986;16:219-225.Crossref 21. Pearlson GC, Garbacz DJ, Moberg PJ, Ahn HS, dePaulo JR. Symptomatic, familial, perinatal, and social correlates of CAT changes in schizophrenics and bipolars . J Nerv Ment Dis . 1985;173:42-50.Crossref 22. Mednick SA, Machon RA, Huttunen MO, Bonett D. Adult schizophrenia following prenatal exposure to an influenza epidemic . Arch Gen Psychiatry . 1988;45:189-192.Crossref 23. Huttunen MO, Niskanen P. Prenatal loss of father and psychiatric disorders . Arch Gen Psychiatry . 1978;35:429-431.Crossref 24. Torrey EF, Rawlings R, Waldman IN. Schizophrenic births and viral disease in two states . Schizophr Res . 1988;1:73-77.Crossref 25. Barr CE, Mednick SA. A replication of the second trimester effect in Denmark: a 50 year study of the association between viral infection and schizophrenia. Presented at the Second World Congress on Viruses, Immunity and Mental Health; October 4, 1988; Mont Gabriel, Canada. 26. Jacob H, Beckmann H. Prenatal development disturbances in the limbic allocortex in schizophrenics . J Neural Transm . 1986;65:303-326.Crossref 27. Kovelman JA, Scheibel AB. A neurohistological correlate of schizophrenia . Biol Psychiatry . 1984;19:1601-1621. 28. Bogerts B, Meertz E, Schonfeld-Bausch R. Basal ganglia and limbic system pathology in schizophrenia . Arch Gen Psychiatry . 1985;42:784-791.Crossref 29. Andreasen N, Nasrallah HA, Dunn V, Olson SC, Grove WM, Ehrhardt JC, Coffman JA, Crossett JHW. Structural abnormalities in the frontal system in schizophrenia . Arch Gen Psychiatry . 1986;43:136-144.Crossref 30. Sartorius N. Early manifestations and first contact incidence of schizophrenics in different cultures . Psychol Med . 1986;16:909-928.Crossref 31. Nowakowski RS. Basic concepts of CNS development . Child Dev . 1987;58:568-595.Crossref 32. Rakic P, Sidman RL. Sequence of developmental abnormalities leading to granule cell deficit in cerebellar cortex of weaver mutant mice . J Comp Neurol . 1978;152:103-132.Crossref 33. Cannon TD, Mednick SA, Parnas J. Two pathways to schizophrenia in children at risk . In: Robins L, Rutter M, eds. Straight and Devious Pathways From Childhood to Adulthood . New York, NY: Cambridge University Press. In press. 34. Mednick SA, Machon RA, Huttunen MO. Disturbances of fetal neural development and adult schizophrenia . In: Schulz SC, ed. Schizophrenia: A Scientific Focus . New York, NY: Oxford University Press Inc. 1989:69-77. 35. Brann AW. Factors during neonatal life that influence brain disorders . In Freeman JM, ed. Prenatal and Perinatal Factors Associated With Brain Disorders . Washington, DC: National Institutes of Health; 1985:263-358. 36. Sinha SK, Davies JM, Sims DG, Chiswick ML. Relation between periventricular hemorrhage and ischaemic brain lesions diagnosed by ultrasound in very preterm infants . Lancet . 1985;2:1154-1156.Crossref 37. Lane EA, Albee GW. Comparative birthweights of schizophrenics and their siblings . J Psychol . 1966;64:227-231.Crossref 38. Marcus J, Hans SL, Mednick SA, Schulsinger F, Michelsen N. Neurological dysfunctioning in offspring of schizophrenics in Israel and Denmark: a replication analysis . Arch Gen Psychiatry . 1985;42:753-761.Crossref 39. Mednick SA, Schulsinger F. A longitudinal study of children with a high risk for schizophrenia: a preliminary report . In: Vandenberg S, ed. Methods and Goals in Human Behavior Genetics . Orlando, Fla: Academic Press Inc; 1965:255-296. 40. Schulsinger H. A ten year follow-up of children of schizophrenic mothers: a clinical assessment . Acta Psychiatr Scand . 1976;53:371-386.Crossref 41. Parnas J, Schulsinger F, Teasdale TW, Schulsinger H, Feldman PM, Mednick SA. Perinatal complications and clinical outcome within the schizophrenia spectrum . Br J Psychiatry . 1982;140:416-420.Crossref 42. Weinberger DR, Torrey EF, Neophytides AN, Wyatt RJ. Lateral cerebral ventricular enlargement in chronic schizophrenia . Arch Gen Psychiatry . 1979;36:735-739.Crossref 43. Gottesman II, Shields J. Schizophrenia: The Epigenetic Puzzle . New York, NY: Cambridge University Press; 1982. 44. Parnas J. Mates of schizophrenic mothers: a study of assortative mating from the American-Danish high risk study . Br J Psychiatry . 1985;146:490-497.Crossref 45. Spitzer RL, Endicott J. Schedule for Affective Disorders and Schizophrenia—Lifetime Version . Biometric Research . 3rd ed. New York, NY: New York Psychiatric Institute; 1978. 46. SAS User's Guide. Cary, NC: SAS Institute Inc; 1984. 47. Cliff N. Analyzing Multivariate Data . New York, NY: Harcourt Brace Jovanovich Publishers; 1987. 48. Parnas J, Teasdale TW. Treated versus untreated schizophrenia spectrum cases: a matched paired high risk population study . Acta Psychiatr Scand . 1987;75:44-50.Crossref 49. Bogerts B. Neuropathological abnormalities and their clinical correlates in schizophrenia. Presented at the National Institute of Mental Health Conference Fetal Neural Development and Schizophrenia; May 31, 1988; Washington, DC. 50. Weinberger DR, DeLisi LE, Perman G, Targum S, Wyatt RJ. CT scans in schizophreniform disorder and other acute psychiatric patients . Arch Gen Psychiatry . 1982;39:778-783.Crossref 51. Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia . Arch Gen Psychiatry . 1987;44:660-669.Crossref 52. Sostek AM, Smith YF, Katz KS, Grant EG. Developmental outcome of preterm infants with intraventricular hemorrhage at 1 and 2 years of age . Child Dev . 1987;58:779-786.Crossref 53. Weinberger DR, Cannon-Spoor HE, Potkin SG, Wyatt RJ. Poor premorbid adjustment and CT scan abnormalities in chronic schizophrenia . Am J Psychiatry . 1980;137:1410-1413. 54. Andreasen NC, Olsen SA, Dennert JW, Smith MR. Ventricular enlargement in schizophrenia: relationship to positive and negative symptoms . Am J Psychiatry . 1982;139:297-302. 55. Cannon TD, Fuhrmann M, Mednick SA, Machon RA, Parnas J, Schulsinger F. Third ventricle enlargement and reduced electrodermal responsiveness . Psychophysiology . 1988;25:153-157.Crossref 56. Huber G. Pneumoencephalographische und Psychopathologische Bilder Bei Endogen Psychosen . New York, NY: Springer-Verlag NY Inc; 1957.

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Oct 1, 1989

References