Cogprints

Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy

Oades, R.D. and Rao, M.L. and Bender, S. and Sartory, G. and Müller, B.W. (2000) Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy. [Journal (Paginated)]

Full text available as:

[img] PDF
942Kb

Abstract

Introduction: Patients with schizophrenia are widely reported to show impairments of attention and neuropsychological performance, but the extent to which this is attributable to medication and dopamine (DA) function remains largely unexplored. Methods: We describe here the putative influence of 1) the dose of antipsychotic medication (chlorpromazine equivalents, CPZ), 2) the antipsychotic serum concentration (neuroleptic units in terms of butyrophenone displacement from animal neostriatum) and 3) the approximated DA D2-receptor occupancy in the brain (based on regression curves from 11 studies published for 5 neuroleptics) - - on conditioned blocking (CB) measures of attention and performance on a neuropsycholog-ical battery. We studied 108 patients with schizophrenia with 62 healthy controls. Results: 1) Antipsychotic serum concentration and D2-occupancy were higher in patients with a paranoid vs. non-paranoid diagnosis, and in female vs. male patients (independent of symptom severity). 2) Controlling for D2-occupancy removed the difference between high CB in paranoid and impaired low CB measures of selective attention in nonparanoid patients. 3) Similar partial correlations for antipsychotic drug dose and serum levels of DA D2-blocking activity with performance on the trail-making and picture completion tests (negative) and the block-design test (positive) showed the functional importance of DA-related activity. 4) High estimates of D2-occupancy were related to impaired verbal fluency - but - were associated with improved recall of stories, especially in paranoid patients. 5) Non-dopaminergic aspects of medication (i.e. CPZ-dependent but not D2-occupancy-associated) impaired verbal recall in males (left-hemisphere function) and non-verbal performance in females (reflecting right hemisphere function). Conclusions: This first study of its kind tentatively imputes a role for DA D2-related activity in left frontal (e.g. CB and verbal fluency) and temporal lobe functions (verbal recall), as well as in some non-verbal abilities mediated more in the right hemisphere of patients with schizophrenia

Item Type:Journal (Paginated)
Keywords:schizophrenia, paranoid, nonparanoid, disorganized, thought disorder, ideas of reference, gender, conitioned blocking, attention, neuropsychology, trail-making, Stroop, verbal fluency, Mooney faces, memory, block design, picture completion, logical memories, visual reproduction, neuroleptic, dopamine, DA, D2, receptor, occupancy, haloperidol, olanzapine, clozapine, serum, chlorpromazine,antipsychotic, dose laterality, frontal lobe, temporal lobe
Subjects:Neuroscience > Neurochemistry
Neuroscience > Neuropharmacology
Neuroscience > Neuropsychology
Neuroscience > Neuropsychiatry
Psychology > Psychobiology
ID Code:1843
Deposited By: OADES, Robert D.
Deposited On:27 Oct 2001
Last Modified:11 Mar 2011 08:54

References in Article

Select the SEEK icon to attempt to find the referenced article. If it does not appear to be in cogprints you will be forwarded to the paracite service. Poorly formated references will probably not work.

Aleman A, Hijman R, de Haan, EHF, Kahn RS (1999). Memory impairment in schizophrenia: a meta-analysis. Am J Psychiatry 156:1358-1366.

American Psychiatric Association. (1994). Diagnostic and Statistical Manual of Mental Disorders (4th ed.,). Washington, DC.

Amin F, Silverman JM, Siever LJ, Smith CJ, Knott PJ, Davis KL (1999). Genetic antecedents of dopamine dysfunction in schizophrenia. Biol Psychiat 45:1143-1150.

Andreasen NC, Olsen S (1982). Negative versus positive schizophrenia: definition and validation. Arch Gen Psychiatry 39:789-794.

Bagli M, Süverküp R, Quadflied E, Höflich G, Kasper S, Möller H-J, Lange M, Barleger U, Rao ML (1999). Pharmacokinetic-, pharmacodynamic-modeling of tolerance to the prolactin secreting effect of chlorprothixene of the different modes of drug administration. J Pharmacol exp Ther 291:547-554.

Batra A (2000). Tabakabhängigkeit und Raucherentwöhnung bei psychiatrischen Patienten. Fortschr Neurol Psychiatrie 68:80-92.

Bender S, Schall U, Wolstein J, Grzella I, Zerbin D, Oades RD (1999). A topographic event-related potential follow-up study on ‘prepulse inhibition’ in first and second episode schizophrenia. Psychiat Res Neuroimaging 90:41-53.

Bender S, Müller BW, Oades RD, Sartory G (2000). Conditioned blocking and schizophrenia: a replication and study of the role of symptoms, age, onset-age of psychosis and illness-duration. Schizophr Res in press.

Benkert O, Hippius H (1986). Psychiatrische Pharmakotherapie (4th ed.). Springer-Verlag, Heidelberg.

Benton AL, Hamsher K (1989). Multilingual Aphasia Examination. AJA Associates, Iowa City, IA

Bilder RM, Turkel E, Lipschutz-Broch L, Lieberman JA (1992) Antipsychotic medication effects on neuropsychological functions. Psychopharmacol Bull 28:353-366.

Brauns H, Haun D, Steinmann S (1997). The construction of an internationally comparable classification by class. Erwerbsstatistische Besonderheiten am Beispiel von Labour Force Surveys der Bundesrepublik Deutschland, Frankreichs, Großbritanniens und Ungarns. Arbeitspapiere Arbeitsbereich 1/22, Mannheim Center for European Social Research (MZES), Mannheim.

Brebion G, Amador X, Smith MJ, Malaspina D, Sharif Z, Gorman J (1999). Opposite links of positive and negative symptomatology with memory errors in schizophrenia. Psychiat Res 88:15-24.

Di Paolo T (1994). Modulation of brain dopamine transmission by sex steroids. Rev Neurosci 5:27-42.

Farde L, Wiesel FA, Nordström AL, Sedvall G (1989). D1- and D2 dopamine receptor occupancy during treatment with flupenthixol conventional and atypical neuroleptics. Psychopharmacology 99:s28-s31.

Farde L, Nordström AL, Wiesel FA, Pauli S, Halldin C, Sedvall G (1992). Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Arch Gen Psychiatry, 49:538-544.

Gilbertson MW, Yao JK, Van Kammen DP (1994). Memory and plasma HVA changes in schizophrenia: are they episode markers ? Biol Psychiatry 35:203-206.

Gray NS, Pickering AD, Hemsley DR, Dawling S, Gray JA (1992). Abolition of latent inhibition by a single 5 mg dose of d-amphetamine in man. Psychopharmacology 107:425-430

Gray NS, Pilowsky LS, Gray JA, Kerwin RW (1995). Latent inhibition in drug-naive schizophrenics: relationship to duration of illness and dopamine D2 binding using SPET. Schizophr Res 17:95-107.

Gray NS, Pickering AD, Gray JA, Jones SH, Abrahams SH, Hemsley DR, (1997). Kamin blocking is not disrupted by amphetamine in human subjects. J Psychopharmacology 11:301-311.

Gurden H, Tassin J-P, Jay TM (1999). Integrity of the mesocortical dopaminergic system is necessary for complete expression of in vivo hippocampal-prefrontal cortex long-term potentiation. Neuroscience 94:1019-1027.

Hess EJ, Bracha S, Kleinman J. Creese I (1987). Dopamine receptor sub-type imbalance in schizophrenia. Life Sci 40:1487-1497.

Kamin LJ (1969). Predictability, surprise. Attention and conditioning. In R. Church & B. Campbell (Eds.), Punishment and Aversive Behavior. Appleton-Century-Crofts, New York NY, pp. 279-296.

Kapur S, Zipursky RB, Remington G, Jones C, DaSilva J, Wilson AA,Houle S (1998). 5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation. Am J Psychiatry, 155:921-928

Kane JM, 1996. Drug therapy: Schizophrenia. New England Journal of Medicine 334, 34-41

Kay SR, Opler LA, Fizbein A (1992). The Positive and Negative Syndrome Scale (PANSS). Manual. Multi-Health Systems, Toronto.

Knable MB, Heinz A, Raedler T, Weinberger DR (1997). Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels. Psychiat Res 75:91-101.

Lansdell H (1970). Relation of extent of temporal removals to closure and visuomotor factors. Percept Motor Skills 31:491-498.

Laruelle M, Abi-Dargham A, Gil R, Kegeles L, Innis R (1999). Increased dopamine transmission in schizophrenia: relationship to illness phases. Biol Psychiatry 46:56-72.

Lavalaye J, Linszen DH, Booij J, Reneman L, Gersons BPR, van Royen EA (1999). Dopamine D2 receptor occupancy by olanzapine or risperidone in young patients with schizophrenia. Psychiat Res Neuroimaging 92:33-44.

Li B-M, Mao Z-M, Wang M, Mei Z-T (1999). Alpha-2 adrenergic modulation of prefrontal cortical neuronal activity related to spatial working memory in monkeys. Neuropsychopharmacology 21:601-610.

Meltzer HY, McGurk SR (1999). The effects of clozapine, risperidone and olanzapine on cognitive function in schizophrenia. Schizophr Bull 25:233-255.

Mooney CM, Ferguson GA (1951). A new closure test. Canad J Psychology 5:129-133.

Nordström AL, Farde L, Nyberg S, Karlsson P, Halldin C, Sedvall G (1995). D1, D2 and 5-HT2 receptor occupancy in relation to clozapine serum concentration: a PET study of schizophrenic patients. Am J Psychiatry, 152:1444-1449.

Nordström AL, Nyberg S, Olsson H, Farde L (1998). Positron emission tomography finding of a high striatal D2 receptor occupancy in olanzapine-treated patients. Arch Gen Psychiatry 55:283-284.

Nyberg S, Farde L, Halldin C (1997). Delayed normalization of central D2 dopamine receptor availability after discontinuation of haloperidol decanoate. Arch Gen Psychiatry, 54:953-958.

Nyberg S, Eriksson B, Oxenstierna G, Halldin C, Farde L (1999). Suggested minimal effective dose of risperidone based on PET-measured D2 and 5-HT2A receptor occupancy in schizophrenic patients. Am J Psychiatry, 156:869-875.

Oades RD, Röpcke B, Eggers C (1994). Monoamine activity reflected in urine of young patients with obsessive compulsive disorder, psychosis with and without reality distortion and healthy subjects: an explorative analysis. J neural Transm 96:143-159.

Oades RD, Röpcke B, Schepker R (1996a). A test of conditioned blocking and its development in childhood and adolescence: relationship to personality and monoamine metabolism. Dev Neuropsychology 12:207-230.

Oades RD, Zimmermann B, Eggers C (1996b). Conditioned blocking in patients with paranoid, non-paranoid psychosis or obsessive compulsive disorder: associations with symptoms, personality and monoamine metabolism. J Psychiatr Res 30:369-390.

Oades RD, Rivet J-M, Taghzouti K, Kharouby M, Simon H, Le Moal M (1987). Catecholamines and conditioned blocking: effects of ventral tegmental, septal and frontal 6-hydroxydopamine lesions in rats. Brain Res 406;136-146.

Oades RD, Heeper C, Czwenk A, Eisenbeis I, Fierro L, Dolberg A, Müller B (2000). What neuropsycological signs are associated with the presence or absence of conditioned blocking in schizophrenia ? Schizophr Res 41:291

Oldfield RC (1971). The assessment and analysis of handedness: the Edinburgh Inventory. Neuropsychologia 9:97-113.

Pickar D, Su TP, Weinberger DR, Coppola R, Malhotra AK, Knable MB, Lee KS, Gorey J, Bartko JJ, Breier A, Hsiao J (1996). Individual variation in D2 dopamine receptor occupancy in clozapine-treated patients. Am J Psychiatry, 153:1571-1578.

Raedler TJ, Knable MB, Lafargue T, Urbina RA, Egan MF, Pickar D, Weinberger DR (1999). In vivo determination of striatal dopamine D2 receptor occupancy in patients treated with olanzapine. Psychiat Res, 90:81-90.

Rao ML (1986). Modification of the radioreceptor assay technique for estimation of serum neuroleptic drug levels leads to improved precision and sensitivity. Psychopharmacology 90:548-553.

Raven JC (1976). Raven-Matrizen-Test: Advanced Progressive Matrices. German language manual. H. Kratzmeier and R. Horn (Eds.). Beltz-Verlag, Stuttgart

Reitan RM (1958). The validity of the Trail Making Test as an indicator of organic brain damage. Percept Motor Skills 8:271-276.

Remington G, Kapur S, Zipursky R (1998). The relationship between risperidone plasma levels and dopamine D2 occupancy: a positron emission tomographic study. J Clin Psychopharmacology 18:82-82.

Rey M-J, Schulz P, Costa C, Dick P Tissot R, (1989). Guidelines for the dosage of neuroleptics. 1: Chlorpromazine equivalents of orally administered neuroleptics. Int Clin Psychopharmacology 4:95-104

Schulz, P., Rey, M-J., Dick, P. & Tissot, R., 1989. Guidelines for the dosage of neuroleptics. II: Changing from daily oral to long-acting injectable neuroleptics. Int Clin Psychopharmacology 4:105-114.

Seeman P (1997). Neurobiology of dopamine receptors, neuroleptics and schizophrenia. Biol Psychiatry 42: 198-199s

Seeman P, Kapur S (1997). Clozapine occupies high levels of dopamine D2 receptors. Life Sci 60:207-216

Simpson GM, Angus JWS (1970). A rating scale for extrapyramidal side-effects. Acta Psychiatr Scand. supplement 212:1-19.

Spohn HE, Strauss ME (1989). Relation of neuroleptic and anticholinergic medication to cognitive functions in schizophrenia. J Abnorm Psychol 98:367-380.

Straube ER, Oades RD (1992). Schizophrenia: Empirical Research and Findings. San Diego: Academic Press.

Tauscher J, Küfferle B, Asenbaum S, Fischer P, Pezawas L, Barnas C, Tauscher-Wisniewski S, Brücke T, Kasper S (1999). In vivo 123 I IBZM SPECT imaging of striatal dopamine-2 receptor occupancy in schizophrenic patients treated with olanzapine in comparison to clozapine and haloperidol. Psychopharmacology 141:175-181.

Wechsler D (1981). Wechsler Adult Intelligence Scale-revised (WAIS-R). The Psychological Corporation, New York, NY.

Wechsler D (1987). The Wechsler Memory Scale-Revised. The Psychological Corporation, Harcourt Brace Jovanovich, San Antonio, TX.

Wiesel FA, Farde L, Nordström AL, Sedvall G (1990). Die Bedeutung der D1- und D2-Dopaminrezeptor-Blockade für die antipsychotische Wirkung von Neuroleptika. Eine PET-Studie an schizophrenen Patienten. In Müller-Oerlinghausen B, Möller HJ, Rüther E (eds.). Thioxanthene in der Neuroleptika-Behandlung. Springer-Verlag, New York, 13-24.

Williams LM, Gordon E (2000). “Masked” span of apprehension in schizophrenic subgroups. Cog Neuropsychiatry 5:37-52.

Metadata

Repository Staff Only: item control page

Cogprints is powered by EPrints 3 which is developed by the School of Electronics and Computer Science at the University of Southampton. More information and software credits.