Abstract
Schizophrenia is a complex disease with multifactorial etiology. The schizophrenia phenotype has been traditionally defined by chronic psychosis and functional deterioration. However, the boundary of the phenotype is likely to be more extensive than the one defined by chronic psychosis. This is highlighted by the findings of subtle, schizophrenialike deficits in the nonschizophrenic, first-degree relatives of schizophrenic patients. Subtle clinical signs and symptoms, cognitive impairment particularly in attention and memory, and neurophysiologic deficits such as in sensory gating and smooth-pursuit eye movements all define aspects of the schizophrenia phenotype.
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References and Recommended Reading
Kendler KS, Diehl SR:The genetics of schizophrenia: a current, genetic-epidemiologic perspective. Schizophr Bull 1993, 19:261–285.
Carpenter WT Jr, Buchanan RW: Schizophrenia. N Engl J Med 1994, 330:681–690.
Kraepelin E: Dementia praecox and paraphrenia. Huntington NY: Krieger; 1919.
Bleuler M: Demential Praecox or the Group of Schizophrenias. New York: International Universities Press; 1950.
Ciompi L, Muller C: Lifestyle and age of schizophrenics. A catamnestic long-term study into old age [in German]. Monogr Gesamtgeb Psychiatr Psychiatry Ser 1976, 1:1–242.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, edn 3, revised. Washington, DC, American Psychiatric Press; 1987.
Carpenter WT, Arango C, Buchanan RW, Kirkpatrick B: Deficit psychopathology and a paradigm shift in schizophrenia research. Biol Psychiatry 1999, 46:352–360. In this article, the authors summarize findings from recent studies of deficit syndrome psychopathology to address heterogeneity.
Liddle PF: The symptoms of chronic schizophrenia: a re-examination of the positive-negative dichotomy. Br J Psychiatry 1987, 151:145–151.
Kay SR, Sevy S: Pyramidical model of schizophrenia. Schizophr Bull 1990, 16:537–545.
Barnes TR, Liddle PF: Evidence for the validity of negative symptoms. Mod Prob Pharmacopsychiatry 1990, 24:43–72.
Lenzenweger MF, Dworkin RH, Wethington E: Examining the underlying structure of schizophrenic phenomenology: evidence for a three-process model. Schizophr Bull 1991, 17:515–524.
Kirkpatrick B, Castle D, Murray RM, Carpenter WT Jr: Risk factors for the deficit syndrome of schizophrenia. Schizophr Bull 2000, 26:233–242.
Ross DE, Kirkpatrick B, Karkowski LM, Straub RE, et al.: Sibling correlation of deficit syndrome in the Irish study of high-density schizophrenia families. Am J Psychiatry 2000, 157:1071–1076.
Kopelowicz A, Zarate R, Tripodis K, et al.: Differential efficacy of olanzapine for deficit and nondeficit negative symptoms in schizophrenia. Am J Psychiatry 2000, 157:987993.
Buchanan RW, Breier A, Kirkpatrick B, et al.: Structural abnormalities in deficit and nondeficit schizophrenia. Am J Psychiatry 1993, 150:59–65.
Tamminga CA, Thaker GK, Buchanan R, et al.: Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome. Arch Gen Psychiatry 1992, 49:522–530.
Buchanan RW, Strauss ME, Kirkpatrick B, et al.: Neuropsychological impairments in deficit vs nondeficit forms of schizophrenia. Arch Gen Psychiatry 1994, 51:804–811.
Ross DE, Thaker GK, Buchanan RW, et al.: Association of abnormal smooth pursuit eye movements with the deficit syndrome in schizophrenic patients. Am J Psychiatry 1996, 153:1158–1165.
Meehl PE: Schizotaxia, schizotypy and schizophrenia. Amer Psychologist 1962, 17:827–383.
Kety S: Schizophrenic illness in the families of schizophrenic adoptees: findings from the Danish national sample. Schizophr Bull 1988, 14:217–222.
Lowing PA, Mirsky AF, Pereira R: The inheritance of schizophrenia spectrum disorders: a reanalysis of the Danish adoptee study data. Am J Psychiatry 1983, 140:1167–1171.
Baron M, Gruen R, Asnis L, Kane J: Familial relatedness of schizophrenia and schizotypal states. Am J Psychiatry 1983, 140:1437–1442.
Baron M, Gruen R, Asnis L, Lord S: Familial transmission of schizotypal and borderline personality disorders. Am J Psychiatry 1985, 142:927–934.
Frangos E, Athanassenas G, Tsitourides S, et al.: Prevalence of DSM III schizophrenia among the first-degree relatives of schizophrenic probands. Acta Psychiatrica Scand 1985, 72:382–386.
Kendler KS: A twin study of individuals with both schizophrenia and alcoholism. Br J Psychiatry 1985, 147:48–53.
Kendler KS: Diagnostic approaches to schizotypal personality disorder: a historical perspective. Schizophr Bull 1985, 11:538–553.
Kendler KS, McGuire M, Gruenberg AM, Walsh D: Schizotypal symptoms and signs in the Roscommon Family Study. Their factor structure and familial relationship with psychotic and affective disorders. Arch Gen Psychiatry 1995, 52:296–303.
Varma SL, Sharma I: Psychiatric morbidity in the first-degree relatives of schizophrenic patients. Br J Psychiatry 1993, 162:672–678.
Thaker GK, Cassady S, Adami H, et al.: Eye movements in spectrum personality disorders: comparison of community subjects and relatives of schizophrenic patients. Am J Psychiatry 1996, 153:362–368.
Thaker GK, Ross DE, Cassady SL, et al.: Smooth pursuit eye movements to extraretinal motion signals: deficits in relatives of patients with schizophrenia. Arch Gen Psychiatry 1998, 55:830–836.
Coryell W, Zimmerman M: The heritability of schizophrenia and schizoaffective disorder. A family study. Arch Gen Psychiatry 1988, 45:323–327.
Squires-Wheeler E, Skodol AE, Friedman D, et al.: The specificity of DSM-III schizotypal personality traits. Psychol Med 1988, 18:757–765.
Squires-Wheeler E, Skodol AE, Bassett A, Erlenmeyer-Kimling L: DSM-III-R schizotypal personality traits in offspring of schizophrenic disorder, affective disorder, and normal control parents. J Psychiatr Res 1989, 23:229–239.
Squires-Wheeler E, Skodol AE, Erlenmeyer-Kimling L: The assessment of schizotypal features over two points in time. Schizophr Res 1991, 6:75–85.
Lyons MJ, Toomey R, Faraone SV, Tsuang MT: Comparison of schizotypal relatives of schizophrenic versus affective probands. Am J Med Genet 1994, 54:279–285.
Reiss AL, Hagerman RJ, Vinogradov S, et al.: Psychiatric disability in female carriers of the fragile X chromosome. Arch Gen Psychiatry 1988, 45:25–30.
Sobesky WE, Hull CE, Hagerman RJ: Symptoms of schizotypal personality disorder in fragile X women. J Am Acad Child Adolesc Psychiatry 1994, 33:247–255.
Battaglia M, Gasperini M, Sciuto G, et al.: Psychiatric disorders in the families of schizotypal subjects. Schizophr Bull 1991, 17:659–668.
Soloff PH, Millward JW: Psychiatric disorders in the families of borderline patients. Arch Gen Psychiatry 1983, 40:37–44.
Kendler KS, Gruenberg AM: An independent analysis of the Danish Adoption Study of Schizophrenia. VI. The relationship between psychiatric disorders as defined by DSM-III in the relatives and adoptees. Arch Gen Psychiatry 1984, 41:555–564.
Baron M, Gruen R, Rainer JD, et al.: A family study of schizophrenic and normal control probands: implications for the spectrum concept of schizophrenia. Am J Psychiatry 1985, 142:447–455.
Schulz PM, Schulz SC, Goldberg SC, et al.: Diagnoses of the relatives of schizotypal outpatients. J Nerv Ment Dis 1986, 174:457–463.
Siever LJ, Silverman JM, Horvath TB, et al.: Increased morbid risk for schizophrenia-related disorders in relatives of schizotypal personality disordered patients. Arch Gen Psychiatry 1990, 47:634–640.
Thaker GK, Adami H, Moran M, et al.: Psychiatric illnesses in families of subjects with schizophrenia-spectrum personality disorders: high morbidity risks for unspecified functional psychoses and schizophrenia. Am J Psychiatry 1993, 150:66–71.
Chapman LJ, Chapman JP: Problems in the measurement of cognitive deficit. Psychol Bull 1973, 79:380–385.
Goldberg TE, Weinberger DR, Berman KF, et al.: Further evidence for dementia of the prefrontal type in schizophrenia? A controlled study of teaching the Wisconsin Card Sorting Test. Arch Gen Psychiatry 1987, 44:1008–1014.
Nuechterlein KH, Dawson ME, Gitlin M, et al.: Developmental processes in schizophrenic disorders: longitudinal studies of vulnerability and stress. Schizophr Bull 1992, 18:387–425.
Saykin AJ, Gur RC, Gur RE, et al.: Neuropsychological function in schizophrenia. Selective impairment in memory and learning. Arch Gen Psychiatry 1991, 48:618–624.
Gold JM, Hermann BP, Randolph C, et al.: Schizophrenia and temporal lobe epilepsy. A neuropsychological analysis. Arch Gen Psychiatry 1994, 51:265–272.
Goldman-Rakic PS: Working memory dysfunction in schizophrenia. J Neuropsychiatry Clin Neurosci 1994, 6:348–357.
Asarnow RF, Granholm E, Sherman T: Span of apprehension in schizophrenia. In Handbook of Schizophrenia: Neuropsychology, Psychophysiology, and Information Processing. Edited by Steinhauer SR, Gruzelier JH, Zubin J. Amsterdan: Elsevier; 1991:335–370.
Balogh DW, Merritt RD: Susceptibility to type A backward pattern masking among hypothetically psychosis-prone college students. J Abnorm Psychol 1985, 94:377–383.
Braff DL: Impaired speed of information processing in nonmedicated schizotypal patients. Schizophr Bull 1981, 7:499–508.
Cornblatt BA, Winters L, Erlenmeyer-Kimling L: Attentional markers of schizophrenia: evidence from the New York high risk study. Schizophrenia:Scientific progress. Edited by Schultz SC, Tamminga CA. New York: Oxford University Press; 1989.
Green MF, Nuechterlein KH, Breitmeyer B: Backward masking performance in unaffected siblings of schizophrenic patients. Evidence for a vulnerability indicator. Arch Gen Psychiatry 1997, 54:465–472.
Nuechterlein KH: Signal detection in vigilance tasks and behavioral attributes among offspring of schizophrenic mothers and among hyperactive children. J Abnorm Psychol 1983, 92:4–28.
Park S, Holzman PS, Goldman-Rakic PS: Spatial working memory deficits in the relatives of schizophrenic patients. Arch Gen Psychiatry 1995, 52:821–828.
Cannon TD, Mednick SA, Parnas J, et al.: Developmental brain abnormalities in the offspring of schizophrenic mothers. II. Structural brain characteristics of schizophrenia and schizotypal personality disorder. Arch Gen Psychiatry 1994, 51:955–962.
Faraone SV, Kremen WS, Lyons MJ, et al.: Diagnostic accuracy and linkage analysis: how useful are schizophrenia spectrum phenotypes? Am J Psychiatry 1995, 152:1286–1290.
Faraone SV, Seidman LJ, Kremen WS, et al.: Neuropsychological functioning among the nonpsychotic relatives of schizophrenic patients: a diagnostic efficiency analysis. J Abnorm Psychol 1995, 104:286–304.
Barnes GR, Asselman PT: The mechanism of prediction in human smooth pursuit eye movements. J Physiol 1991, 439:439–461.
Holzman PS: Recent studies of psychophysiology in schizophrenia. Schizophr Bull 1987, 13:49–75.
Clementz BA, Sweeney JA: Is eye movement dysfunction a biological marker for schizophrenia? A methodological review. Psychol Bull 1990, 108:77–92.
Holzman PS, Solomon CM, Levin S, Waternaux CS: Pursuit eye movement dysfunctions in schizophrenia. Family evidence for specificity. Arch Gen Psychiatry 1984, 41:136–139.
Blackwood DH, St Clair DM, Muir WJ, Duffy JC: Auditory P300 and eye tracking dysfunction in schizophrenic pedigrees. Arch Gen Psychiatry 1991, 48:899–909.
Iacono WG, Moreau M, Beiser M, et al.: Smooth-pursuit eye tracking in first-episode psychotic patients and their relatives. J Abnorm Psychol 1992, 101:104–116.
Keefe RS, Silverman JM, Mohs RC, et al.: Eye tracking, attention, and schizotypal symptoms in nonpsychotic relatives of patients with schizophrenia. Arch Gen Psychiatry 1997, 54:169–176.
Clementz BA, Sweeney JA, Hirt M, et al.: Pursuit gain and saccadic intrusions in first-degree relatives of probands with schizophrenia. J Abnorm Psychol 1990, 99:327–335.
Whicker L, Abel LA, Dell’Osso LF: Smooth pursuit eye movements in the parents of schizophrenics. Neuroophthalmology 1985, 5:1–8.
Arolt V, Lencer R, Nolte A, et al.: Eye tracking dysfunction in families with multiple cases of schizophrenia. Eur Arch Psychiatry Clin Neurosci 1996, 246:175–181.
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.
Newsome WT, Wurtz RH, Dursteler MR, Mikami A: Deficits in visual motion processing following ibotenic acid lesions of the middle temporal visual area of the macaque monkey. J Neurosci 1985, 5:825–840.
Gellman RS, Carl JR: Motion processing for saccadic eye movements in humans. Exper Brain Res 1991, 84:660–667.
Chen Y, Nakayama K, Levy DL, et al.: Psychophysical isolation of a motion-processing deficit in schizophrenics and their relatives and its association with impaired smooth pursuit. Proc Natl Acad Sci U S A 1999, 96:4724–4729.
Sweeney JA, Clementz BA, Haas GL, et al.: Eye tracking dysfunction in schizophrenia: characterization of component eye movement abnormalities, diagnostic specificity, and the role of attention. J Abnorm Psychol 1994, 103:222–230.
Thaker GK, Ross DE, Buchanan RW, et al.: Smooth pursuit eye movements to extraretinal motion signals: deficits in patients with schizophrenia. Psychiatry Res 1999, 88:209–219.
Fukushima J, Fukushima K, Chiba T, et al.: Disturbances of voluntary control of saccadic eye movements in schizophrenic patients. Biol Psychiatry 1988, 23:670–677.
Crawford TJ, Sharma T, Puri BK, et al.: Saccadic eye movements in families multiply affected with schizophrenia: the Maudsley Family Study. Am J Psychiatry 1998, 155:1703–1710.
Clementz BA, McDowell JE, Zisook S: Saccadic system functioning among schizophrenia patients and their first-degree biological relatives. J Abnorm Psychol 1994, 103:277–287.
Katsanis J, Kortenkamp S, Iacono WG, Grove WM: Antisaccade performance in patients with schizophrenia and affective disorder. J Abnorm Psychol 1997, 106:468–472.
McDowell JE, Myles-Worsley M, Coon H, et al.: Measuring liability for schizophrenia using optimized antisaccade stimulus parameters. Psychophysiology 1999, 36:138–141.
Thaker GK, Ross DE, Gold JM, Blaxton TA: Model of smooth pursuit eye movement function in schizophrenia. Schizophr Res 1999, 36:267–267.
Pfefferbaum A, Wenegrat BG, Ford JM, et al.: Clinical application of the P3 component of event-related potentials. II. Dementia, depression and schizophrenia. Electroencephalogr Clin Neurophysiol 1984, 59:104–124.
Blackwood DH, St Clair DM, Muir WJ, Duffy JC: Auditory P300 and eye tracking dysfunction in schizophrenic pedigrees. Arch Gen Psychiatry 1991, 48:899–909.
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.
Braff DL: Information processing and attention dysfunctions in schizophrenia. Schizophr Bull 1993, 19:233–259.
Freedman R, Adler LE, Gerhardt GA, et al.: Neurobiological studies of sensory gating in schizophrenia. Schizophr Bull 1987, 13:669–678.
Freedman R, Coon H, Myles-Worsley M, et al.: Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proc Natl Acad Sci U S A 1997, 94:587–592.
Freeman R, Adler LE, Leonard S: Alternative phenotypes for the complex genetics of schizophrenia. Biol Psychiatry 1999, 45:551–558. The authors review the concept of alternate phenotype with a focus on neuropsychologic markers.
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Thaker, G.K. Defining the schizophrenia phenotype. Curr Psychiatry Rep 2, 398–403 (2000). https://doi.org/10.1007/s11920-000-0022-6
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DOI: https://doi.org/10.1007/s11920-000-0022-6