Unitary models A newer alternative, the unitary model, draws from the tradition of Bleuler (1911/1950), who attempted to identify what he considered to be the single fundamental abnormality in schizophrenia. Bleuler defined the fundamental symptoms of schizophrenia as those caused by a ‘loosening of associations’, which were present in all patients, tended to occur only in schizophrenia and therefore were pathognomonic of the illness. Thus, the unitary model stresses that there is a single unifying construct which explains the heterogeneity of the phenotype of schizophrenia. This model proposes that schizophrenia has one fundamental problem in a basic cognitive process. One recent unitary model suggests that the fundamental deficit is a disruption of the fluid co-ordination of mental activity, called ‘cognitive dysmetria’ (Andreasen et al. 1996, 1998, 1999; Andreasen 1997, 1999). Synchrony refers to the normal fluid processing of information required during thought and speech, and ‘dysmetria of thought’ (Schmahmann 1991) or ‘cognitive dysmetria’ conveys its disturbance. This disruption would manifest itself in cognition, emotion and behaviour. Thus, the phenotype is defined by a unitary cognitive abnormality (cognitive dysmetria), which leads to the varied symptoms experienced by patients. This abnormality, not the symptoms, should be used to define the phenotype of the illness. According to this unitary model, schizophrenia is a neurodevelopmental and cognitive disorder with an aetiology reflecting the interaction of genetics and environment and a pathophysiology consisting of the resultant abnormalities of brain development (which continues into early adulthood).  Similar to the ‘multiple hit’ model of cancer, the unitary model suggests that the development of schizophrenia results from multiple aetiological factors leading to a shared pathophysiology and neurobiology in all people with schizophrenia. These complications in brain development from conception to early adulthood lead to disruptions in anatomic and functional connectivity, resulting in neural ‘misconnections’ expressed as ‘cognitive dysmetria’ and ultimately manifested as symptoms such as flattened affect, avolition, disorganized thought, hallucinations or delusions. Several other theories have also attempted to explain the symptoms of schizophrenia via impairment in a single underlying cognitive process. These are the theories of willed action (Frith 1992),  working memory (Goldman-Rakic 1994)  and information processing and attention (Braff 1993). Frith proposed that the general mechanism underlying the symptoms in schizophrenia is a disorder of consciousness or self-awareness, impairing one’s ability to think with ‘metarepresentations’  (higher order abstract concepts which are representations of mental states) (Frith 1992). The impairment in self-awareness is the basis for three features of schizophrenia. 1  A disorder of willed action which leads to an inability to generate spontaneous or willed acts, resulting in poverty of action, perseveration or inappropriate action. 2  A disorder in self-monitoring. An inability to monitor willed intentions may lead to delusions of control, auditory hallucinations or thought insertion. 3  A disorder in monitoring the intentions of others, which leads to delusions of reference or paranoid delusions. Goldman-Rakic (1994)  suggested that another cognitive operation, working memory, may be disrupted in schizophrenia, leading to behavioural disorganization and certain positive and negative symptoms. Working memory is defined as a memory system in which items are held ‘on-line’ while needed and then discarded after use. There is evidence that the prefrontal cortex is involved in the organization and processing of this transitory memory system. Dysfunction in one or more components of working memory could result in the diverse symptoms of schizophrenia. Alogia would result from impaired information retrieval. The inability to hold a concept in mind may lead to thought disorder.  A failure to reference internal or external stimuli against established memories may lead to misrepresentations of causality,  resulting in delusions and hallucinations. Thus, the prefrontal cortex and its circuitry may be disrupted in schizophrenia, leading to impairments in working memory which surface as some of the positive symptoms and negative symptoms. Braff (1993) hypothesized that patients with schizophrenia may have a fundamental deficit in information processing and attention. Patients are unsuccessful in allocating attentional resources to relevant tasks while inhibiting attention towards irrelevant stimuli. Subjectively, they may report trouble ‘focusing’ and feeling overwhelmed by external stimuli. On a wide variety of experimental paradigms to assess information processing and attention (such as prepulse inhibition, P50 gating, ocular motor function, continuous performance task and event-related potentials), patients with schizophrenia are less able to process information rapidly and efficiently,  particularly in the context of distractions, high processing loads and multiple tasks. R.L.M. Fuller, S.K. Schultz and N.C. Andreasen
References

• Addington, J. & Addington, D. (1991) Positive and negative symptoms of schizophrenia: their course and relationship over time. Schizophrenia Research 5, 51 - 59.
• Alda, M., Zvolsky, P. & Dvorakova, M. (1991) Study of chronic schizophrenics with positive and negative family histories of psychosis. Acta Psychiatrica Scandinavica 83, 334 - 337.
• American Psychiatric Association (1980) Diagnostic and Statistical Manual of Mental Disorders (DSM-III), 3rd edn. American Psychiatric Association, Washington DC.
• Andreasen, N.C. (1979a) Affective flattening and the criteria for schizophrenia. American Journal of Psychiatry 136, 944 - 947.
• Andreasen, N.C. (1979b) Thought, language, and communication disorders. I. Clinical assessment, definition of terms, and evaluation of their reliability. Archives of General Psychiatry 36, 1315 - 1321.
• Andreasen, N.C. (1979c) Thought, language, and communication
• disorders. II. Diagnostic significance. Archives of General Psychiatry 36, 1325 - 1330.
• Andreasen, N.C. (1983) The Scale for the Assessment of Negative Symptoms (SANS). University of Iowa, Iowa City, IA.
• Andreasen, N.C. (1984) The Scale for the Assessment of Positive Symptoms (SAPS). University of Iowa, Iowa City, IA.
• Andreasen, N.C. (1985) Positive vs. negative schizophrenia: a critical evaluation. Schizophrenia Bulletin 11, 380 - 389.
• Andreasen, N.C. (1997) Linking mind and brain in the study of mental illnesses: a project for a scientific psychopathology. Science 275, 1586 - 1593.
• Andreasen, N.C. (1999) A unitary model of schizophrenia: Bleuler's 'fragmented phrene' as schizencephaly. Archives of General Psychiatry 56, 781 - 787.
• Andreasen, N.C. & Grove, W.M. (1986) Evaluation of positive and negative symptoms in schizophrenia. Psychiatrie and Psychobiologie 1, 108 - 121.
• Andreasen, N.C. & Olsen, S. (1982) Negative versus positive schizophrenia: definition and validation. Archives of General Psychiatry 39, 789 - 794.
• Andreasen, N.C., Olsen, S.A., Smith, M.R., Dennert, J.W. & Smith, M.R. (1982) Ventricular enlargement in schizophrenia: definition and prevalence. American Journal of Psychiatry 139, 297 - 302.
• Andreasen, N.C., Ehrhardt, J.C., Swayze, V.W. II et al. (1990) Magnetic resonance imaging of the brain in schizophrenia: the pathophysiologic significance of structural abnormalities. Archives of General Psychiatry 47, 35 - 44.
• Andreasen, N.C., Flaum, M., Arndt, S. et al. (1991) Positive and negative symptoms: assessment and validity. Negative Versus Positive Schizophrenia (eds A. Marneros, N.C. Andreasen & M.T. Tsuang), pp. 28 - 51. Springer-Verlag Berlin, Heidelberg.
• Andreasen, N.C., Rezai, K., Alliger, R. et al. (1992) Hypofrontality in neuroleptic-naive and in patients with chronic schizophrenia: assessment with xenon-133 single-photon emission computed tomography and the Tower of London. Archives of General Psychiatry 49, 943 - 958.
• Andreasen, N.C., Flashman, L., Flaum, M. et al. (1994) Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging. Journal of the American Medical Association 272, 1763 - 1769.
• Andreasen, N.C., O'Leary, D.S., Cizadlo, T. et al. (1996) Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal - thalamic - cerebellar circuitry. Procedures of the National Academy of Sciences of the USA 93, 9985 - 9990.
• Andreasen, N.C., Paradiso, S. & O'Leary, D.S. (1998) 'Cognitive dysmetria' as an integrative theory of schizophrenia: a dysfunction in cortical - subcortical - cerebellar circuitry? Schizophrenia Bulletin 24 (2), 203 - 218.
• Andreasen, N.C., Nopoulos, P., O'Leary, D.S. et al. (1999) Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms. Biological Psychiatry 46, 908 - 920.
• Arndt, S., Alliger, R.J. & Andreasen, N.C. (1991) The distinction of positive and negative symptoms: the failure of a two-dimensional model. British Journal of Psychiatry 158, 317 - 322.
• Arndt, S., Andreasen, N.C., Flaum, M., Miller, D. & Nopoulos, P. (1995) A longitudinal study of symptom dimensions in schizophrenia: prediction and patterns of change. Archives of General Psychiatry 52 (5), 352 - 360.
• Barnes, T.R., Hutton, S.B., Chapman, M.J. et al. (2000) West London first-episode study of schizophrenia: clinical correlates of duration of untreated psychosis. British Journal of Psychiatry 177 (3), 207 - 211.
• Barta, P.E., Pearlson, G.D. & Powers, R.E. (1990) Auditory hallucinations and smaller superior temporal gyrus volume in schizophrenia. American Journal of Psychiatry 147, 1457 - 1462.
• Barta, P.E., Powers, R.E., Aylward, E.H. et al. (1997) Quantitative MRI volume changes in late onset schizophrenia and Alzheimer's disease compared to normal controls. Psychiatry Research 68, 65 - 75.
• Biehl, H., Maurer, K. & Schubart, C. (1986) Prediction of outcome and utilization of medical services in a prospective study of first onset schizophrenics: results of a prospective 5-year follow-up study. European Archives of Psychiatry and Neurological Sciences 236, 139 - 147.
• Bilder, R.M., Mukherjee, S. & Rieder, R.O. (1985) Symptomatic and neuropsychological components of defect states. Schizophrenia Bulletin 11, 409 - 491.
• Bleuler, E. (1911/1950) Dementia Praecox or the Group of Schizophrenias. Translated by J. Zinkin. International Universities Press, New York.
• Braff, D.L. (1989) Sensory input deficits and negative symptoms in schizophrenic patients. American Journal of Psychiatry 146, 1006 - 1011.
• Braff, D.L. (1993) Information processing and attention dysfunctions in schizophrenia. Schizophrenia Bulletin 19, 233 - 259.
• Breier, A., Wolkowitz, O.M., Doran, A.R. et al. (1987) Neuroleptic responsivity of negative and positive symptoms in schizophrenia. American Journal of Psychiatry 144 (12), 1549 - 1555.
• Breier, A., Schreiber, J. & Dyer, J. (1991) National Institute of Mental Health longitudinal study of chronic schizophrenia: prognosis and predictors of outcome. Archives of General Psychiatry 48, 239 - 246.
• Brown, K. & White, T. (1992) Syndromes of chronic schizophrenia and some clinical correlates. British Journal of Psychiatry 161, 317 - 322.
• Buchsbaum, M.S., Yang, S., Hazlett, E. et al. (1997) Ventricular volume and asymmetry in schizotypal personality disorder and schizophrenia assessed with magnetic resonance imaging. Schizophrenia Research 27, 45 - 53.
• Carpenter, W.T. & Kirkpatrick, B. (1988) The heterogeneity of the longterm course of schizophrenia. Schizophrenia Bulletin 14, 645 - 659.
• Carpenter, W.T., Strauss, J.S. & Bartko, J.J. (1985) On the heterogeneity of schizophrenia. In: Controversies in Schizophrenia (ed. M. Alpert), pp. 25 - 37. Guildford Press, New York.
• Cohen, M.B., Lake, R.R., Graham, L.S. et al. (1989) Quantitative iodine-123 IMP imaging of brain perfusion in schizophrenia. Journal of Nuclear Medicine 30 (10), 1616 - 1620.
• Cornblatt, B.A., Lenzenweger, M.F. & Dworkin, R.H. (1985) Positive and negative schizophrenic symptoms: attention and information processing. Schizophrenia Bulletin 11, 397 - 407.
• Craig, T.J., Bromet Fennig, E.J., Tanenberg-Karant, S., Lavelle, M. & Galambos, J. (2000) Is there an association between duration of untreated psychosis and 24-month clinical outcome in a first-admission series? American Journal of Psychiatry 157, 60 - 66.
• Crow, T.J. (1980) Molecular pathology of schizophrenia: more than one disease process? British Medical Journal 280, 66 - 68.
• Crow, T.J., Corsellis, J.A.N., Cross, A.J. et al. (1981) The search for changes underlying the type II syndrome. In: Biological Psychiatry (eds C. Perris, G. Struwe & B. Jansson), pp. 727 - 731. Elsevier North-Holland Biomedical Press, Amsterdam,
• Cuesta, M. & Peralta, V. (1995) Cognitive disorders in the positive, negative and disordered syndromes of schizophrenia. Psychiatry Research 58, 227 - 235.
• Dewan, M.J., Pandurangi, A.K., Lee, S.H. et al. (1983) Central brain morphology in chronic schizophrenic patients: a controlled CT study. Biological Psychiatry 18 (10), 1133 - 1140.
• Dworkin, R.H., Lenzenweger, M.F. & Moldin, S.O. (1988) A multidimensional approach to the genetics of schizophrenia. American Journal of Psychiatry 145, 1077 - 1083.
• Endicott, J. & Spitzer, R.L. (1978) A diagnostic interview: the Schedule for Affective Disorders and Schizophrenia (SADS). Archives of General Psychiatry 35, 837 - 844.
• Fenton, W.S. & McGlashan, T.H. (1987) Sustained remission in drugfree schizophrenic patients. American Journal of Psychiatry 144, 1306 - 1309.
• Fenton, W.S. & McGlashan, T.H. (1992) Testing systems for assessment of negative symptoms in schizophrenia. Archives of General Psychiatry 49, 179 - 184.
• Freedman, R. (1998) Basic and clinical approaches to the genetics of deficits in schizophrenia. Biological Psychiatry 43 (Suppl. 8), 3.
• Friston, K.J., Liddle, P.F., Frith, C.D., Hirsch, S.R. & Frackowiak, R.S. (1992) The left medial temporal region and schizophrenia: a PET study. Brain 115 (2), 367 - 382.
• Frith, C.D. (1992) The Cognitive Neuropsychology of Schizophrenia. Lawrence Erlbaum, East Sussex.
• Frith, C.D., Friston, K., Liddle, P.F. & Frackowiak, R.S. (1991) Willed action and the prefrontal cortex in man: a study with PET. Proceedings of the Royal Society of London 244, 241 - 246.
• Gaebel, W., Ulrich, G. & Frick, K. (1987) Visuomotor performance of schizophrenic patients and normal controls in a picture viewing task. Biological Psychiatry 22 (10), 1227 - 1237.
• Goldman-Rakic, P.S. (1994) Working memory dysfunction in schizophrenia. Journal of Neuropsychiatry and Clinical Neuroscience 64, 348 - 357.
• Gur, R.E., Mozley, D., Resnick, S.M. et al. (1991) Relations among clinical scales in schizophrenia. American Journal of Psychiatry 148, 472 - 478.
• Ho, B.-C., Andreasen, N.C., Flaum, M., Nopoulos, P. & Miller, D. (2000) Untreated initial psychosis: its relation to quality of life and symptom remission in first-episode schizophrenia. American Journal of Psychiatry 157, 808 - 815.
• Hull, J.W., Smith, T.E., Anthony, D.T. et al. (1997) Patterns of symptom change: a longitudinal analysis. Schizophrenia Research 24, 17 - 18.
• Inoue, K., Nakajima, T. & Kato, N. (1986) A longitudinal study of schizophrenia in adolescence. I. The 1- to 3-year outcome. Japanese Journal of Psychiatry and Neurology 40, 143 - 151.
• Jackson, J.H. (1931) Selected Writings. Hodder and Stoughton, London.
• Jernigan, T.L., Sargent, T. III, Pfefferbaum, A., Kusubov, N. & Stahl,
• S.M. (1985) 18Fluorodeoxyglucose PET in schizophrenia. Psychiatry Research 16 (4), 317 - 329.
• Johnstone, E.C., Crow, T.J., Frith, C.D., Husband, J. & Kreel, L. (1976)
• Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet 2, 924 - 926.
• Johnstone, E., Frith, C. & Gold, A. (1979) The outcome of severe acute schizophrenic illnesses after 1 year. British Journal of Psychiatry 134, 28 - 33.
• Johnstone, E.C., Owens, D.G.C. & Frith, C.D. (1986) The relative stability of positive and negative features in chronic schizophrenia. British Journal of Psychiatry 150, 60 - 64.
• Kay, S.R., Opler, L.A. & Fiszbein, A. (1986) Significance of positive and negative symptoms in chronic schizophrenia. British Journal of Psychiatry 149, 439 - 448.
• Keefe, R., Mohs, R. & Losonczy, M. (1987) Characteristics of very poor outcome schizophrenia. American Journal of Psychiatry 144, 889 - 895.
• Keilp, J.G., Sweeney, J.A., Jacobsen, P. et al. (1988) Cognitive impairment in schizophrenia: specific regions to ventricular size and negative symptomatology. Biological Psychiatry 24, 47 - 55.
• Kendler, K., Myers, J., O'Neill, A. et al. (2000) Clinical features of schizophrenia and linkage to chromosomes 5q, 6p, 8p, and 10p in the Irish study of high-density schizophrenia families. American Journal of Psychiatry 157 (3), 402 - 408.
• Knight, R.A., Roff, J.D., Barnet, J. & Moss, J.L. (1979) Concurrent and predictive validity of thought disorder and affectivity: a 22-year follow-up of acute schizophrenia. Journal of Abnormal Psychology 88, 1 - 12.
• Knights, A. & Hirsch, S.R. (1981) 'Revealed' depression and drug treatment for schizophrenia. Archives of General Psychiatry 38, 806 - 811.
• Kolakowska, T., Williams, A.O. & Ardern, M. (1985) Schizophrenia with good and poor outcome. I. Early clinical features, response to neuroleptics and signs of organic dysfunction. British Journal of Psychiatry 146, 229 - 239.
• Kraepelin, E. (1919) Dementia Praecox and Paraphrenia. Translated by R.M. Barkley. E. & S. Livingstone, Edinburgh.
• Kulhara, P., Kota, S.K. & Joseph, S. (1986) Positive and negative subtypes of schizophrenia: a study from India. Acta Psychiatrica Scandinavica 74, 353 - 359.
• Liddle, P. (1987a) Schizophrenia symptoms, cognitive performance and neurological dysfunction. Psychological Medicine 17, 49 - 57.
• Liddle, P. (1987b) The symptoms of chronic schizophrenia: a reexamination of the positive - negative dichotomy. British Journal of Psychiatry 151, 145 - 151.
• Liddle, P. & Morris, D. (1991) Schizophrenic syndromes and frontal lobe performance. British Journal of Psychiatry 158, 340 - 345.
• Liddle, P., Friston, K.J. & Frith, C.D. (1992) Cerebral blood flow and mental processes in schizophrenia. Journal of the Royal Society of Medicine 85, 224 - 226.
• Lindenmayer, J.P., Kay, S.R. & Friedman, C. (1986) Negative and positive schizophrenic syndromes after the acute phase: a prospective follow-up. Comprehensive Psychiatry 27, 276 - 286.
• Lo, W.H. & Lo, T. (1977) A 10-year follow-up study of Chinese schizophrenics in Hong Kong. British Journal of Psychiatry 131, 63 - 66.
• McGuffin, P. & Owen, M. (1991) The molecular genetics of schizophrenia: an overview and forward view. European Archives of Psychiatry and Clinical Neuroscience 240, 169 - 173.
• Malaspina, D., Goetz, R.R., Yale, S. et al. (2000) Relation of familial schizophrenia to negative symptoms but not to the deficit syndrome. American Journal of Psychiatry 157, 994 - 1003.
• Marneros, A., Deister, A. & Rohde, A. (1991) Stability of diagnoses in affective, schizoaffective and schizophrenic disorders: cross-sectional versus longitudinal diagnosis. European Archives of Psychiatry and Clinical Neuroscience 241, 1870 - 1192.
• Merriam, A.E., Kay, S.R. & Opler, L.A. (1990) Neurological signs and the positive - negative dimension in schizophrenia. Biological Psychiatry 28, 181 - 192.
• Miller, D.D., Arndt, S.V. & Andreasen, N.C. (1993) Alogia, attentional impairment, and inappropriate affect: their status in the dimensions of schizophrenia. Comprehensive Psychiatry 34, 221 - 226.
• Minas, I.H., Stuart, G.W., Klimidis, S. et al. (1992) Positive and negative symptoms in the psychoses: multidimensional scaling of SAPS and SANS items. Schizophrenia Research 8, 143 - 156.
• Munk-Jorgensen, P. & Mortensen, P.B. (1989) Schizophrenia: a 13-year follow-up - diagnostic and psychopathological aspects. Acta Psychiatrica Scandinavica 79, 391 - 399.
• Nelson, M.D., Saykin, A.J., Flashman, L.A. & Riordan, H.J. (1998) Hippocampal reduction in schizophrenia as assessed by magnetic resonance imaging: a meta-analytic study. Archives of General Psychiatry 55 (5), 433 - 440.
• O'Leary, D., Flaum, M., Kesler, M. et al. (2000) Cognitive correlates of the negative, disorganized, and psychotic symptom dimensions of schizophrenia. Journal of Neuropsychiatry and Clinical Neurosciences 12, 4 - 15.
• Pearlson, G.D., Garbacz, D.J. & Moberg, P.J. (1985) Symptomatic, familial, perinatal, and social correlates of computerized axial tomography (CAT) changes in schizophrenics and bipolars. Journal of Nervous and Mental Disorders 173, 42 - 50.
• Pfohl, B. & Winokur, G. (1982) The evolution of symptoms in institutionalized hebephrenic/catatonic schizophrenics. British Journal of Psychiatry 141, 567 - 572.
• Pogue-Geile, M.F. & Harrow, M. (1984) Negative and positive symptoms in schizophrenia and depression: a follow up. Schizophrenia Bulletin 10, 371 - 387.
• Pogue-Geile, M.F. & Harrow, M. (1985) Negative symptoms in schizophrenia: their longitudinal course and prognostic importance. Schizophrenia Bulletin 11, 427 - 439.
• Portas, C.M., Goldstein, J.M., Shenton, M.E. et al. (1998) Volumetric evaluation of the thalamus in schizophrenic male patients using MRI. Biological Psychiatry 43 (9), 649 - 659.
• Post, R.M., DeLisi, L.E., Holcomb, H.H. et al. (1987) Glucose utilization in the temporal cortex of affectively ill patients: positron emission tomography. Biological Psychiatry 22 (5), 545 - 553.
• Reynolds, J. (1858) On the pathology of convulsions, with special reference to those of children. Liverpool Medico-chirurgie Journal 2, 1 - 14.
• Reynolds, J. (1861) Epilepsy: its Symptoms, Treatment and Relation to Other Chronic Convulsive Diseases, Vol. 2. John Churchill, London.
• Roff, J.D. & Knight, R. (1978) A schizophrenia checklist: reliability without stability, concurrent without predictive validity. Psychological Report 43, 791 - 794.
• Schmahmann, J. (1991) An emerging concept: the cerebellar contribution to higher function. Archives of Neurology 48, 1178 - 1187.
• Schneider, K. (1959) Clinical Psychopathology. Translated by M.W. Hamilton. Grune & Stratton, New York.
• Schroeder, J., Buchsbaum, M.S., Siegel, B.V., Geider, F.J. & Niethammer, R. (1995) Structural and functional correlates of subsyndromes in chronic schizophrenia. Psychopathology 28, 38 - 45.
• Scully, P.J., Coakley, G., Kinsella, A. & Waddington, J.L. (1997)
• Psychopathology, executive (frontal) and general cognitive impairment in relation to duration of initially untreated versus subsequently treated psychosis in chronic schizophrenia. Psychological Medicine 27, 1303 - 1310.
• Shenton, M., Kikinis, R. & Jolesz, F. (1992) Abnormalities of the left temporal lobe and thought disorder in schizophrenia: a quantitative magnetic resonance imaging study. New England Journal of Medicine 327, 604 - 612.
• Siris, S.G. (1991) Diagnosis of secondary depression in schizophrenia: implications for DSM-IV. Schizophrenia Bulletin 17, 75 - 98.
• Spitzer, R., Endicott, J. & Robins, E. (1978) Research Diagnostic Criteria (RDC) for a Selected Group of Functional Disorders, Biometrics Research, 3rd edn. New York State Psychiatric Institute, New York.
• Stephens, J.H. (1978) Long-term prognosis and follow-up in schizophrenia. Schizophrenia Bulletin 4, 25 - 47.
• Strauss, J. & Carpenter, W.T. (1974) Characteristic symptoms and outcome in schizophrenia. Archives of General Psychiatry 30, 429 - 434.
• Tamminga, C.A., Thaker, G.K., Buchanan, R.W. et al. (1992)
• Limbic-system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alternations with deficit syndrome. Archives of General Psychiatry 49, 522 - 530.
• Vaillant, G. (1978) A 10-year followup of remitting schizophrenics. Schizophrenia Bulletin 4, 78 - 85.
• Volkow, N.D., Wolf, A.P., Van Gelder, P. et al. (1987) Phenomenological correlates of metabolic activity in 18 patients with chronic schizophrenia. American Journal of Psychiatry 144 (2), 151 - 158.
• Waddington, J.L., Youssef, H.A. & Kinsella, A. (1995) Sequential cross-sectional and 10-year prospective study of severe negative symptoms in relation to duration of initially untreated psychosis in chronic schizophrenia. Psychological Medicine 25, 849 - 857.
• Wassink, T., Flaum, M., Nopolous, P. & Andreasen, N. (1999) Prevalence of depressive symptoms early in the course of schizophrenia. American Journal of Psychiatry 156, 315 - 316.
• Weinberger, D.R., Bigelow, L.B., Kleinman, J.E. et al. (1980) Cerebral ventricular enlargement in chronic schizophrenia: an association with poor response to treatment. Archives of General Psychiatry 37, 11 - 13.
• Wing, J.K. (1970) A standard form of psychiatric Present State Examinations (PSE): a method for standardizing the classification of symptoms. In: Psychiatric Epidemiology (eds E.H. Hare & J.K. Wing). Oxford University Press, London.
• Wolkin, A., Sanfilipo, M., Wolf, A.P. et al. (1992) Negative symptoms and hypofrontality in chronic schizophrenia. Archives of General Psychiatry 49 (12), 959 - 965.
• Wyatt, R.J., Green, M.F. & Tuma, A.H. (1997) Long-term morbidity associated with delayed treatment of first admission schizophrenic patients: a re-analysis of the Camarillo State Hospital data. Psychological Medicine 27, 261 - 268.