Physiological Indicators of the Schizophrenia Phenotype

Robert Freedman, Randal G. Ross, and Lawrence E. Adler



1. Abel L, Ziegler A. Smooth pursuit eye movements in schizophrenics—What constitutes quantitative assessment? Biol Psychiatry 1988;24:747-761.

2. Adler LE, Hoffer LD, Griffith J, Waldo MC, Freedman R. Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics. Biol Psychiatry 1992;32:607-616.

3. Adler LE, Hoffer LD, Wiser A, Freedman R. Normalization of auditory physiology by cigarette smoking in schizophrenic patients. Am J Psychiatry 1993;150:1856-1861.

4. Adler LE, Hoffer LD, Nagamoto HT, Waldo MC, Kisley M, Griffith JM. Yohimbine impairs P50 auditory sensory gating in normal subjects. Neuropsychopharmacology. 1994;10:249-257.

5. Adler LE, Pang K, Gerhardt G, Rose GM. Modulation of the gating of auditory evoked potentials by norepinephrine: pharmacological evidence obtained using a selective neurotoxin. Biol Psychiatry 1988;24:179-190.

6. Adler LE, Pachtman E, Franks RD, Pecevich M, Waldo MC, Freedman R. Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. Biol Psychiatry 1982;17:639-654.

7. Adler LE, Gerhardt GA, Franks R, et al. Sensory physiology and catecholamines in schizophrenia and mania. Psychiatry Res 1990;31:297-309.

8. Adler LE, Waldo MC, Tatcher A, Cawthra E, Baker N, Freedman R. Lack of relationship of auditory gating defects to negative symptoms in schizophrenia. Schizophr Res 1990;3:131-138.

9. Arolt V, Lencer R, Nolte A, et al. Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease. Am J Med Genet 1996;67:564-579.

10. Barta PE, Pearlson GD, Powers RE, Richards SS, Tune LE. Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia. Am J Psychiatry 1990;147:1257-1262.

11. Bickford-Wimer PC, Nagamoto H, Johnson R, et al. Auditory sensory gating in hippocampal neurons: a model system in the rat. Biol Psychiatry 1990;27:183-192.

12. Blackwood DHR, St Clair DM, Muir WJ, Duffy JC. Auditory P300 and eye tracking dysfunction in schizophrenic pedigrees. Arch Gen Psychiatry 1991;48:899-909.

13. Boutros NN, Zouridakis G, Overall J. Replication and extension of P50 findings in schizophrenia. Clin Electroencephalog 1991;22:40-45.

14. Braff DL, Grillon C, Geyer MA. Gating and habituation of the startle reflex in schizophrenic patients. Arch Gen Psychiatry 1992;49:206-215.

15. Braff, D, Stone C, Callaway E, Geyer M, Glick I, Bali L. Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 1978;15:339-343.

16. Brecher M, Begleiter H. Event-related brain potentials to high-incentive stimuli in drug-naïve schizophrenic patients. Biol Psychiatry 1983;18:661-674.

17. Butler RW, Braff DL, Rausch JL, Jenkins MA, Sprock J, Geyer MA. Physiological evidence of exaggerated startle response in a subgroup of Vietnam veterans with combat-related PTSD. Am J Psychiatry 1990;147:1308-1312.

18. Cadenhead KS, Geyer MA, Braff DL. Impaired startle prepulse inhibition and habituation in patients with schizotypal personality disorder. Am J Psychiatry 1993;150:1862-1867.

19. Cardenas VA, Gerson J, Fein G. The reliability of P50 suppression as measured by the conditioning/testing ratio is vastly improved by dipole modeling. Biol Psychiatry 1993;33:335-344.

20. Cardenas VA, Yingling CD, Jewett D, Fein G. A multichannel, model-free method for estimation of event-related potential amplitudes and its comparison with dipole source localization. J Med EngTechnol 1995;19:88-98.

21. Churchland PS. Neurophilosophy. Cambridge: MIT Press, 1986.

22. Clementz BA, Geyer MA, Braff DL. P50 suppression among schizophrenic and normal comparison subjects: a methodological analysis. Biol Psychiatry 1997; 41:1035-1044.

23. Clementz BA, Grove WM, Iacono WG, Sweeney JA. Smooth-pursuit eye movement dysfunction and liability for schizophrenia: Implications for genetic modeling. J Abnorm Psychol 1992;101:117-129.

24. Clementz BA, Iacono WG, Grove WM. The construct validity of root-mean-square error for quantifying smooth-pursuit eye tracking abnormalities in schizophrenia. Biol Psychiatry 1996;39:448-450.

25. Clementz BA, McDowell JE, Zisook S. Saccadic system functioning among schizophrenic patients and their first-degree relatives. J Abnorm Psychol 1994;103:277-287.

26. Clementz BA, Reid SA, McDowell JE, Cadenhead KS. Abnormality of smooth pursuit eye movement initiation: Specificity to the schizophrenia spectrum? Psychophysiology 1995;32:130-134.

27. Couch RH, Cox JC. Photographic study of ocular movements in mental disease. Arch Neurol Psychiatry 1934;34:556-578.

28. Crawford TJ, Haeger B, Kennard C, Reveley MA, Henderson L. Saccadic abnormalities in psychotic patients. II. The role of neuroleptic treatment. Psychol Med 1995;25:473-483.

29. Cullum CM, Harris JG, Waldo MC, et al. Neurophysiological and neuropsychological evidence of attentional dysfunction in schizophrenia. Schizophr Res 1993;10:131-141.

30. Davis M, Mansbach RS, Swerdlow NR, Campeau S, Braff DL, Geyer MA. Apomorphine disrupts the inhibition of acoustic startle induced by weak prepulses in rats. Psychopharmacology 1990;102:1-4.

31. De Amicis LA, Wagstaff DA, Cromwell RL. Reaction time crossover as a marker of schizophrenia and of higher functioning. J Nerv Ment Dis 1986;174:177-179.

32. Diefendorf AR, Dodge R. An experimental study of the ocular reaction on the insane from photographic records. Brain 1908;31:451-489.

33. Eccles JC. The inhibitory pathways of the central nervous system. Springfield: Thomas,1969.

34. Erwin RJ, Mawhinney HM, Gur RC, Gur RE. Midlatency evoked responses in schizophrenia. Biol Psychiatry 1991;30:430-442.

35. Freedman R, Adler LE, Waldo MC, Pachtman E, Franks RD. Neurophysiological evidence for a defect in inhibitory pathways in schizophrenia: comparison of medicated and drug-free patients. Biol Psychiatry 1983;18:537-551.

36. Freedman R, Adler LE, Myles-Worsley M, et al. Inhibitory gating of an evoked response to repeated auditory stimuli in schizophrenic and normal subjects: human recordings, computer simulation, and an animal model. Arch Gen Psychiatry 1996;53:1114-1121.

37. Freedman R, Coon H, Myles-Worsley M, et al. Linkage of a neurophysiological trait in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci USA 1997;94:587-592.

38. Friedman L, Jesberger JA, Meltzer HY. Effect of typical antipsychotic medication and clozapine on smooth pursuit performance in patients with schizophrenia. Psychiatry Res 1992;41:25-36.

39. Fukushima J, Morita N, Fukusima K, Chiba T, Tanaka S, Yamashita I. Voluntary control of saccadic eye movements in patients with schizophrenia and affective disorders. J Psychiatr Res 1990;41:9-24.

40. Fukushima J, Fukusima K, Morita N, Yamashita I. Further analysis of the control of voluntary saccadic eye movements in schizophrenic patients. Biol Psychiatry 1990;28:943-958.

41. Graham FK. The more or less startling effects of weak prestimuli. Psychophysiology 1975;12:238-248.

42. Green MF. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 1996;153:321-330.

43. Grove WM, Clementz BA, Iacono WG, Katsanis J. Smooth pursuit ocular motor dysfunction in schizophrenia: evidence for a major gene. Am J Psychiatry 1992;149:1362-1368.

44. Hegerl U, Juckel G, Muller-Schubert A, Petzcker A, Gaebel W. Schizophrenics with small P300: a subgroup with a neurodevelopmental disturbance and a high risk for tardive dyskinesia? Acta Psychiatr Scand 1995;91:120-125.

45. Hershman K, Freedman R, Bickford PC. GABAB antagonists diminish the inhibitory gating of auditory response in the rat hippocampus. Neurosci Lett 1993;190:133-136.

46. Holzman PS. The use of eye movement dysfunctions in exploring the genetic transmission of schizophrenia. Eur Arch Psychiatr Neurol Sci 1989;239:43-48.

47. Holzman PS, Kringlen E, Levy DL, Proctor LR, Haberman SJ, Yasillo NJ. Abnormal-pursuit eye movements in schizophrenia. Arch Gen Psychiatry 1977;34:802-831.

48. Holzman PS, Kringlen E, Levy DL, Haberman SJ. Deviant eye tracking in twins discordant for schizophrenia. Arch Gen Psychiatry 1980;37:627-631.

49. Holzman PS, Kringlen E, Matthysse S, et al. A single dominant gene can account for eye tracking dysfunction and schizophrenia in offspring of discordant twins. Arch Gen Psychiatry 1988;45:641-647.

50. Holzman PS, Proctor LR, Hughes DW. Eye tracking patterns in schizophrenia. Science 1973;181:179-181.

51. Hommer DW, Radant AD, Peng C. Oculomotor delayed response tasks in schizophrenia: evidence for prefrontal cortex dysfunction. Soc Neurosci Abstr 1991;17:354.

52. Iacono, WG. Eye movement abnormalities in schizophrenic and affective disorders. In: Johnston CW, Pirozzozo FJ, eds. Neuropsychology of eye movements. Hillsdale, New Jersey: Lawrence Erlbaum Associates, Inc.,1988;31-64.

53. Iacono WG, Moreau M, Beiser M, Fleming JAE, Lin TY. Smooth-pursuit eye tracking in first-episode psychotic patients and their relatives. J Abnorm Psychol 1992;101:104-116.

54. Javitt DC, Doneshka P, Grochowski S, Ritter, W. Impaired mismatch negativity generation reflects widespread dysfunction of working memory in schizophrenia. Arch Gen Psychiatry 1995;52:550-558.

55. Jin Y, Potkin SG, Wu J, Dang C, Sandman C. Single-trial P50 in normal and schizophrenic subjects. Biol Psychiatry 1994;35:631.

56. Johnson M, Adler LE. Transient impairment in P50 auditory sensory gating induced by a cold pressor test. Biol Psychiatry 1993;33:380-387.

57. Judd LJ, McAdams L, Budnick B, Braff DL. Sensory gating deficits in schizophrenia: new results. Am J Psychiatry 1992;149:488-493.

58. Kathmann N, Engel RR. Sensory gating in normal subjects and schizophrenic patients: A failure to find strong P50 suppression in normal subjects. Biol Psychiatry 1990;27:1216-1226.

59. Keefe RSE, Siever LJ, Mohs RC, et al. Eye tracking, schizophrenic symptoms, and schizotypal personality disorder. Eur Arch Psychiatr Neurol Sci 1989;239:39-42.

60. Klein C, Andersen B. On the influence of smoking upon smooth pursuit eye movements of schizophrenics and normal controls. J Psychophysiol 1991;5:361-369.

60a. Knight R. Contribution of human hippocompal region to novelty detection. Nature 383: 256-9,1996

61. Knott VJ, Kerr C, Hooper C, Lusk-Mikkelsen S. Cigarette smoking and event-related brain electrical potential (ERP) topographies associated with attentional-distractive processes. In: Domino EF, ed. Brain imaging of nicotine and tobacco smoking. Ann Arbor: NPP Books, 1995;191-221.

62. Lamberti SJ, Schwarzkopf SB, Smith DA, Crilly J, Martin R. Diminished P50 suppression in schizophrenic patents. Biol Psychiatry 1993;33:117A.

63. Leonard S, Adams C, Breese C, et al. Nicotine receptor function in schizophrenia. Schizophr Bull 1996;22:431-445.

64. Levy DL, Holzman PS, Matthysse S, Mendell NR. Eye tracking dysfunction and schizophrenia: A critical perspective. Schizophr Res 1993;19:461-536.

65. Litman RE, Hommer DW, Radant A, Clem T, Pickar D. Quantitative effects of typical and atypical neuroleptics on smooth pursuit eye tracking in schizophrenia. Schizophr Res 1994;12:107-120.

66. Luntz-Leybman V, Bickford P, Freedman R. Cholinergic gating of response to auditory stimuli in rat hippocampus. Brain Res 1992;587:130-136.

67. Makert A, Flechtner M. Saccadic reaction times in acute and remitted schizophrenics. Eur Arch Psychiatr Neurol Sci 1989;239:33-38.

68. McCarley RW, Shenton M, O'Donnell BF, et al. Auditory P300 abnormalities and left posterior superior temporal gyrus reduction in schizophrenia. Arch Gen Psychiatry 1993;50:190-197.

69. McEvoy JP, Rose JE, Levin ED, VanderZwaag C, McGee M. Clozapine decreases drive to smoke. Schizophr Res 1994;11:104.

70. Meehl PE. Schizotaxia, schizotype, schizophrenia. Am Psychol 1962;17:827-838.

71. Miller C, Freedman R. Medial septal neuron activity in relation to an auditory sensory gating paradigm. Neuroscience 1993;55:373-380.

72. Miller CL, Freedman R. The activity of hippocampal interneurons and pyramidal cells during the response of the hippocampus to repeated stimuli. Neuroscience 1995;69:371-381.

73. Morstyn R, Duffy FH, McCarley RW. Altered P300 topography in schizophrenia. Arch Gen Psychiatry 1983;40:729-734.

74. Mukundan CR. Middle latency components of evoked responses in schizophrenic patients. Biol Psychiatry 1986;21:1097-1100.

75. Nagamoto HT, Adler LE, Hea RA, Griffith JM, McRae K, Freedman R. Gating of auditory P50 in schizophrenics: unique effects of clozapine. Biol Psychiatry 1996;40:181-188.

76. O'Donnell BF, Faux SF, McCarley RW, et al. Increased rate of P300 latency prolongation with age in schizophrenia. Arch Gen Psychiatry 1995;52:544-549.

77. O'Driscoll GA, Alpert NM, Matthysse SW, Levy DL, Rauch SL, Holzman, PS. Functional neuroanatomy of antisaccade movements investigated with positron emission tomography. Proc Natl Acad Sci USA 1995;92:925-929.

78. Olincy A, Ross RG, Young DA, Roath M, Freedman R. Smooth pursuit eye movements and cigarette smoking in schizophrenia. Soc Neurosci Abstr 1995;21:1264.

79. Olincy A, Ross RG, Leonard S, Freedman R. Linkage analysis of small anticipatory saccades in schizophrenia to a chromosome 15 locus. Biol Psychiatry 1997; in press.

80. Park S, Holzman P, Goldman-Rakic P. Spatial working memory deficits in the relatives of schizophrenic patients. Arch Gen Psychiatry 1995;52:821-828.

81. Penn DL, Mueser KT, Spaulding W, Hope DA, Reed D. Information processing and social competence in chronic schizophrenia. Schizophr Bull 1995;21:268-281.

82. Pfefferbaum A, Ford JM, White PM, Roth WT. P3 in schizophrenia is affected by stimulus modality, response requirements, medication status and negative symptoms. Arch Gen Psychiatry 1989;46:1035-1044.

83. Pierrot-Deseilligny C. Saccade and smooth-pursuit impairment after cerebral hemispheric lesions. Eur Neurol 1994;34:121-134.

84. Radant AD, Hommer DW. A quantitative analysis of saccades and smooth pursuit during visual pursuit tracking: A comparison of schizophrenics with normals and substance abusing controls. Schizophr Res 1992;6:225-235.

85. Richardson RT, De Long MR. A reappraisal of the functions of the nucleus basalis of Meynert. Trends Neurosci 1988;11:264-267.

86. Rosenberg DR, Sweeney JA, Squires-Wheeler E, Keshavan MS, Cornblatt BA, Erlenmeyer-Kimling L. Eye tracking dysfunction in offspring from the New York High Risk Project: diagnostic specificity and the role of attention. Psychiatry Res 1997; 66: 121-130.

87. Ross DE, Thaker GK, Holcomb HH, Cascella NG, Medoff DR, Tamminga CA. Abnormal smooth pursuit eye movements in schizophrenic patients are associated with cerebral glucose metabolism in oculomotor regions. Psychiatry Res 1995;58:53-67.

88. Ross RG, Harris JC, Olincy A, Radant A, Adler LE, Freedman R. Smooth pursuit eye movements in parents of probands with schizophrenia: an obligate carrier approach. Soc Neurosci Abstr 1994;20:1262.

89. Ross RG, Hommer D, Radant A, Roath M, Freedman R. Early expression of smooth-pursuit eye movement abnormalities in children of schizophrenic parents. J Am Acad Child Adolesc Psychiatry 1996;35:941-949.

90. Roth WT, Cannon E. Some features of the auditory evoked response in schizophrenia. Arch Gen Psychiatry 1972;27:466-471.

91. Roth WT, Horvath TB, Pfefferbaum A, Kopell BS. Event-related potentials in schizophrenic patients. Electroencephalog Clin Neurophysiol 1980;48:127-139.

92. Schreiber H, Rothmeier J, Becker W, et al. Comparative assessment of saccadic eye movements, psychomotor and cognitive performance in schizophrenics, their first-degree relatives, and control subjects. Acta Psychiatr Scand 1995;91:195-201.

93. Schwarzkopf SB, Lamberti JS, Smith DA. Concurrent assessment of acoustic startle and auditory P50 evoked potential measures of sensory inhibition. Biol Psychiatry 1993;33:815-828.

94. Sereno AB, Holzman PS. Antisaccades and smooth pursuit eye movements in schizophrenia. Biol Psychiatry 1995;37:394-401.

95. Sham PC, Morton NE, Muir WJ, et al. Segregation analysis of complex phenotypes: an application to schizophrenia and auditory P300 latency. Psychiatr Genet 1994;4:29-38.

96. Siegel C, Waldo M, Mizner G, Adler LE, Freedman R. Deficits in sensory gating in schizophrenic patients and their relatives. Evidence obtained with auditory evoked responses. Arch Gen Psychiatry 1984;41:607-612.

97. Siever LJ, Coursey RD, Alterman IS, Buchsbaum M, Murphy DL. Impaired smooth pursuit eye movement: Vulnerability marker for schizotypal personality disorder in a normal volunteer population. Am J Psychiatry 1984;141:1560-1566.

98. Siever LJ, Coursey RD, Alterman IS, et al. Clinical, psychophysiological, and neurological characteristics of volunteers with impaired smooth pursuit eye movements. Biol Psychiatry 1989;26:35-51.

99. Siever LJ, Keefe R, Bernstein DP, et al. Eye tracking impairment in clinically identified patients with schizotypal personality disorder. Am J Psychiatry 1990;147:740-745.

100. Smith DA, Boutros NN, Schwarzkopf SB. Reliability of P50 auditory event-related potential indices of sensory gating. Psychophysiology 1994;31:495-502.

101. Squires-Wheeler E, Friedman D, Skodol AE, Erlenmeyer-Kimling L. A longitudinal study relating P3 amplitude to schizophrenia spectrum personality disorders and to global personality functioning. Biol Psychiatry 1993;33:774-785.

102. Straub RE, McLean CJ, O'Neill FE, et al. A potential susceptibility locus for schizophrenia on chromosome 6p24-22: evidence for genetic heterogeneity. Nature Genet 1995;11:284-293.

103. Straumanis JJ, Shagass C, Romer RA. Influence of antipsychotic and antidepressant drugs on evoked potential correlates of psychosis. Biol Psychiatry 1982;17:1101-1122.

104. Swerdlow NR, Auerbach P, Monroe SM, Hartson H, Geyer MA, Braff DL. Men are more inhibited than women by weak prepulses. Biol Psychiatry 1993;34:253-260.

105. Swerdlow NR, Benbow CH, Zisook S, Geyer MA, Braff DL. A preliminary assessment of sensorimotor gating in patients with obsessive compulsive disorder. Biol Psychiatry 1993;33:298-301.

106. Swerdlow NR, Braff DL, Taaid N, Geyer MA. Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients. Arch Gen Psychiatry 1994;51:139-154.

107. Swerdlow NR, Filion D, Geyer MA, Braff DL. "Normal" personality correlates of sensorimotor, cognitive, and visuospatial gating. Biol Psychiatry 1995;37:286-299.

108. Thaker GK, Cassady S, Adami H, Moran M, Ross DE. Eye movements in spectrum personality disorders: comparison of community subjects and relatives of schizophrenic patients. Am J Psychiatry 1996;153:362-368.

109. Venables P. Input dysfunction in schizophrenia. Prog Exp Pers Res 1964;1:1-47.

110. Vinogradov S, Solomon S, Ober BA, Biggins CA, Shenaut GK, Fein G. Do semantic priming effects correlate with sensory gating in schizophrenia? Biol Psychiatry 1996;39:821-824.

111. Waldo MC, Carey G, Myles-Worsley M, et al. Codistribution of a sensory gating deficit and schizophrenia in multi-affected families. Psychiatry Res 1991;39:257-268.

112. Waldo MC, Cawthra E, Adler LE, et al. Auditory sensory gating, hippocampal volume, and catecholamine metabolism in schizophrenics and their siblings. Schizophr Res 1994;12:93-106.

113. Waldo MC, Gerhardt G, Baker N, Drebing C, Adler L, Freedman R. Auditory sensory gating and catecholamine metabolism in schizophrenic and normal subjects. Psychiatry Res 1992;44:21-32.

114. Ward PB, Catts SV, McConaghy N. P300 and conceptual loosening in normals: an event-related potential correlate of "thought disorder?" Biol Psychiatry 1992;31:650-660.

115. Ward PB, Hoffer LD, Liebert BJ, Catts SV, O'Donnell M, Adler LE. Replication of a P50 auditory gating deficit in Australian patients with schizophrenia. Psychiatry Res 1996;64:121-135.

116. Whicker L, Abel L, Dell'Osso L. Smooth pursuit eye movements in the parents of schizophrenics. Neuroophthalmology 1985;5:1-8.

Back to Chapter

published 2000