Neurocognitive deficits in the (putative) prodrome and first episode of psychosis

OBJECTIVE International research programs have contributed to the creation of operationally defined criteria to identify individuals at risk for schizophrenia. Although there has been substantial progress in the prospective study of the schizophrenia prodrome, the utility of current diagnostic criteria remains questionable because of the relatively low base rates of incident psychoses, the high false-positive rate and ethical concerns regarding the treatment of individuals at risk. The identification of brain based neurocognitive vulnerability markers for schizophrenia may contribute to the development of an at risk algorithm with greater predictive accuracy. METHODS Forty subjects at risk (AR) for schizophrenia, 15 in their first episode (FE) of schizophrenia, and 36 healthy comparison (HC) subjects were administered a neurocognitive battery that assessed the domains of processing speed, working memory, verbal episodic memory, executive functioning and general intelligence. RESULTS At baseline, AR subjects showed neurocognitive deficits across all domains compared to HC subjects that were less severe than those observed in the FE sample. In preliminary analyses, AR subjects who later converted to psychosis (N=5) had greater neurocognitive impairment at baseline evaluation compared to those individuals who remained "at risk" at follow-up. CONCLUSIONS Neurocognitive deficits may be important in the pathogenesis of early psychosis and could help to define individuals at greatest risk for schizophrenia. Continued research in larger cohorts is needed to test the validity of this neurocognitive profile and its utility as a vulnerability marker.

[1]  G. Thaker,et al.  Saccadic eye movement abnormalities in relatives of patients with schizophrenia , 2000, Schizophrenia Research.

[2]  J. Rapoport,et al.  Mapping adolescent brain change reveals dynamic wave of accelerated gray matter loss in very early-onset schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[3]  R. McCarley,et al.  Neuropsychological dysfunction in schizotypal personality disorder: A profile analysis , 1997, Biological Psychiatry.

[4]  John Suckling,et al.  For personal use. Only reproduce with permission from The Lancet Publishing Group. Kidney transplantation with rabbit antithymocyte globulin induction and sirolimus monotherapy , 2002 .

[5]  D L Braff,et al.  Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits. , 2000, The American journal of psychiatry.

[6]  N C Andreasen,et al.  The family history method using diagnostic criteria. Reliability and validity. , 1977, Archives of general psychiatry.

[7]  Aysenil Belger,et al.  Imaging frontostriatal function in ultra-high-risk, early, and chronic schizophrenia during executive processing. , 2005, Archives of general psychiatry.

[8]  Konstantine K. Zakzanis,et al.  Neurocognitive Deficit in Schizophrenia: A Quantitative Review of the Evidence , 1998 .

[9]  K. Cadenhead,et al.  How does studying schizotypal personality disorder inform us about the prodrome of schizophrenia? , 2005, Current psychiatry reports.

[10]  L. Siever,et al.  The pathophysiology of schizophrenia disorders: perspectives from the spectrum. , 2004, The American journal of psychiatry.

[11]  R. Benedict,et al.  Practice effects during repeated administrations of memory tests with and without alternate forms. , 1998, Journal of clinical and experimental neuropsychology.

[12]  D R Medoff,et al.  Smooth pursuit eye movements to extraretinal motion signals: deficits in relatives of patients with schizophrenia. , 1998, Archives of general psychiatry.

[13]  R. Heaton,et al.  Correlation of neuropsychological and MRI findings in chronic/progressive multiple sclerosis , 1988, Neurology.

[14]  R. Berecz,et al.  Cognitive functions in prepsychotic patients , 2005, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[15]  C. Pantelis,et al.  Spatial working memory ability is a marker of risk-for-psychosis , 2003, Psychological Medicine.

[16]  U. Gschwandtner,et al.  Neuropsychological and neurophysiological findings in individuals suspected to be at risk for schizophrenia: preliminary results from the Basel early detection of psychosis study – Früherkennung von Psychosen (FEPSY) , 2003, Acta psychiatrica Scandinavica.

[17]  T. McGlashan,et al.  Neuropsychological status of subjects at high risk for a first episode of psychosis , 2004, Schizophrenia Research.

[18]  J. Klosterkötter,et al.  Subjective and objective neuropsychological abnormalities in a psychosis prodrome clinic , 2002, British Journal of Psychiatry.

[19]  Godfrey D Pearlson,et al.  Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. , 2003, Schizophrenia bulletin.

[20]  S. Lawrie,et al.  Neuropsychological change in young people at high risk for schizophrenia: results from the first two neuropsychological assessments of the Edinburgh High Risk Study , 2000, Psychological Medicine.

[21]  Jos Twisk,et al.  Attrition in longitudinal studies. How to deal with missing data. , 2002, Journal of clinical epidemiology.

[22]  C. Pantelis,et al.  Generalized and specific cognitive performance in clinical high-risk cohorts: a review highlighting potential vulnerability markers for psychosis. , 2005, Schizophrenia bulletin.

[23]  J. Lieberman,et al.  Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates. , 2000, The American journal of psychiatry.

[24]  H. Meltzer,et al.  The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. , 1999, Schizophrenia bulletin.

[25]  T. McGlashan Psychosis treatment prior to psychosis onset: ethical issues , 2001, Schizophrenia Research.

[26]  S. Wood,et al.  Sustained attention in young people at high risk of psychosis does not predict transition to psychosis , 2005, Schizophrenia Research.

[27]  D. Braff,et al.  Cognitive functions in schizotypal personality disorder , 1999, Schizophrenia Research.

[28]  T. Goldberg,et al.  Genetic risk of neuropsychological impairment in schizophrenia: a study of monozygotic twins discordant and concordant for the disorder , 1995, Schizophrenia Research.

[29]  Michael F. Green,et al.  The neurocognitive effects of aripiprazole: an open-label comparison with olanzapine , 2006, Psychopharmacology.

[30]  C. Pantelis,et al.  Impairment of olfactory identification ability in individuals at ultra-high risk for psychosis who later develop schizophrenia. , 2003, The American journal of psychiatry.

[31]  K. Cadenhead,et al.  Risk and protection in prodromal schizophrenia: ethical implications for clinical practice and future research. , 2005, Schizophrenia bulletin.

[32]  R. C. Hall,et al.  The modified global assessment of functioning scale: addendum. , 1995, Psychosomatics.

[33]  B. Cornblatt,et al.  Update of high-risk research: 1987-1997 , 1997 .

[34]  D. Malaspina,et al.  Prodromal interventions for schizophrenia vulnerability: the risks of being “at risk” , 2005, Schizophrenia Research.

[35]  Ron Dumont,et al.  Wechsler Memory Scale–Third Edition , 2008 .

[36]  P. Holzman,et al.  Antisaccades and smooth pursuit eye tracking and schizotypy. , 1998, Archives of general psychiatry.

[37]  M. Geyer,et al.  The Influence of Schizotypy Traits on Prepulse Inhibition in Young Healthy Controls , 2004, Journal of psychopharmacology.

[38]  C. Pantelis,et al.  Memory impairments identified in people at ultra-high risk for psychosis who later develop first-episode psychosis. , 2005, The American journal of psychiatry.

[39]  Diana O. Perkins,et al.  A longitudinal study of neurocognitive function in individuals at-risk for psychosis , 2006, Schizophrenia Research.

[40]  A. Yung,et al.  Ethics and early intervention in psychosis: keeping up the pace and staying in step , 2001, Schizophrenia Research.

[41]  P. Fletcher,et al.  A putative animal model of the “prodromal” state of schizophrenia , 2005, Biological Psychiatry.

[42]  T. Lencz,et al.  Generalized and Specific Neurocognitive Deficits in Prodromal Schizophrenia , 2006, Biological Psychiatry.

[43]  I. Tendolkar,et al.  Impaired mismatch negativity generation in prodromal subjects and patients with schizophrenia , 2005, Schizophrenia Research.

[44]  E. Johnstone,et al.  Neuropsychological assessment of young people at high genetic risk for developing schizophrenia compared with controls: preliminary findings of the Edinburgh High Risk Study (EHRS) , 1999, Psychological Medicine.

[45]  A. R. Jonckheere,et al.  A DISTRIBUTION-FREE k-SAMPLE TEST AGAINST ORDERED ALTERNATIVES , 1954 .

[46]  R. Freedman,et al.  P50 sensory gating in adolescents from a pacific island isolate with elevated risk for schizophrenia , 2004, Biological Psychiatry.

[47]  Todd Lencz,et al.  The schizophrenia prodrome: treatment and high-risk perspectives , 2002, Schizophrenia Research.