Psychometric schizotypy modulates levodopa effects on lateralized lexical decision performance.

Emergence of psychotic thought has been related to a breakdown in left-hemisphere language dominance. Dopamine (DA) is implicated in both psychotic pathology and modulation of the semantic system. The present study explored whether controlled DA administration modulates basic language functions: (1) in general and/or (2) as a function of schizophrenia-associated thought. Forty healthy men performed a tachistoscopic lexical decision task. Participants' performance was also analyzed as a function of their positive (magical ideation, MI) and negative (physical anhedonia, PHYSAN) schizotypal features. Half of the subjects received 200 mg levodopa, the other half a placebo. Our findings showed that pharmacological treatment per se did not influence task performance, but influenced laterality patterns as a function of participants' schizotypal features. In the placebo, but not in the levodopa group, right hemisphere language contribution increased as a function of increasing MI scores. In the levodopa, but not in the placebo group, superior left hemisphere lexical decision performance was related to increasing PHYSAN scores. The findings from both substance groups suggest that in the healthy brain, a DA agonist restores left-hemispheric dominance for language by reducing right-hemispheric contribution with respect to a positive schizotypal trait and by increasing left-hemispheric specialization with respect to a negative schizotypal trait. We conjecture that the healthy brain compensates through intact neurochemical mechanisms an increased DA concentration, in particular for persons with elevated positive psychotic-like features.

[1]  A. Nieoullon Dopamine and the regulation of cognition and attention , 2002, Progress in Neurobiology.

[2]  S. Faraone,et al.  Correlates of psychosis proneness in relatives of schizophrenic patients. , 1995, Journal of abnormal psychology.

[3]  Richard Coppola,et al.  Effects of Dextroamphetamine on Cognitive Performance and Cortical Activation , 2000, NeuroImage.

[4]  H. Bracha,et al.  Correlation of severity of psychiatric patients' delusions with right hemispatial inattention (left-turning behavior). , 1993, The American journal of psychiatry.

[5]  B Mazoyer,et al.  Altered hemispheric functional dominance during word generation in negative schizophrenia. , 2000, Schizophrenia bulletin.

[6]  M. LeMay,et al.  Abnormalities of the left temporal lobe and thought disorder in schizophrenia. A quantitative magnetic resonance imaging study. , 1992, The New England journal of medicine.

[7]  M. Iyo,et al.  Methamphetamine-related psychiatric symptoms and reduced brain dopamine transporters studied with PET. , 2001, The American journal of psychiatry.

[8]  F. Previc Dopamine and the Origins of Human Intelligence , 1999, Brain and Cognition.

[9]  M. Farah,et al.  Effects of bromocriptine on human subjects depend on working memory capacity , 1997, Neuroreport.

[10]  P. Brugger,et al.  Lateralized Direct and Indirect Semantic Priming Effects in Subjects with Paranormal Experiences and Beliefs , 2001, Psychopathology.

[11]  L. Siever,et al.  L-dopa challenge and relapse in schizophrenia. , 1987, The American journal of psychiatry.

[12]  T. Barnes,et al.  The assessment of psychoses : a practical handbook , 1994 .

[13]  J D Cohen,et al.  A network model of catecholamine effects: gain, signal-to-noise ratio, and behavior. , 1990, Science.

[14]  S. Park Hemispheric asymmetry of spatial working memory deficit in schizophrenia. , 1999, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[15]  Michael P. Maloney,et al.  Hemispheric dysfunction in schizophrenia: Assessment by visual perception tasks , 1979, Psychiatry Research.

[16]  L J Chapman,et al.  Magical ideation as an indicator of schizotypy. , 1983, Journal of consulting and clinical psychology.

[17]  J. Os,et al.  Psychotic symptoms in non-clinical populations and the continuum of psychosis , 2002, Schizophrenia Research.

[18]  G. Fleming,et al.  Dementia Praecox or the Group of the Schizophrenias , 1952 .

[19]  T. Goldberg,et al.  Neuropsychological effects of amphetamine may correlate with personality characteristics. , 1995, Psychopharmacology bulletin.

[20]  T Landis,et al.  The dynamics of cerebral dominance during unilateral limbic seizures. , 1994, Brain : a journal of neurology.

[21]  P. Boyer,et al.  Anhedonia in the Deficit Syndrome of Schizophrenia , 1999, Psychopathology.

[22]  Theodor Landis,et al.  Dissociated hemispheric superiorities for reading stenography vs print , 1985, Neuropsychologia.

[23]  I. Kiss,et al.  Improvement in cognitive functioning in patients with first-episode psychosis during treatment with quetiapine: An interim analysis , 2002, British Journal of Psychiatry.

[24]  Gregor Thut,et al.  Hands, Arms, and Minds: Interactions Between Posture and Thought , 2003, Journal of clinical and experimental neuropsychology.

[25]  R. V. Van Heertum,et al.  Schizophrenia subgroups differing in dichotic listening laterality also differ in neurometabolism and symptomatology. , 2000, The Journal of neuropsychiatry and clinical neurosciences.

[26]  F. Guillem,et al.  Neuropsychological impairments in the syndromes of schizophrenia: A comparison between different dimensional models , 2001, Brain and Cognition.

[27]  L. DeLisi,et al.  Functional asymmetries in schizophrenia and their relationship to cognitive performance , 1996, Psychiatry Research.

[28]  K. Tallent,et al.  Wisconsin Card Sorting Test deficits in schizotypic individuals , 1999, Schizophrenia Research.

[29]  Friedemann Pulvermüller,et al.  Interhemispheric cooperation during word processing: evidence for callosal transfer dysfunction in schizophrenic patients , 2000, Schizophrenia Research.

[30]  P. Goldman-Rakic,et al.  Modulation of memory fields by dopamine Dl receptors in prefrontal cortex , 1995, Nature.

[31]  L. J. Chapman,et al.  Putatively psychosis-prone subjects 10 years later. , 1994, Journal of abnormal psychology.

[32]  Thomas L. Jackson,et al.  Cerebral dominance assessed by object- and color-naming latencies: Sex and familial sinistrality effects , 1979, Brain and Language.

[33]  M. Egan,et al.  Effects of neuroleptic medications on speech disorganization in schizophrenia: biasing associative networks towards meaning , 2000, Psychological Medicine.

[34]  Atsuko Nakagawa Role of Anterior and Posterior Attention Networks in Hemispheric Asymmetries during Lexical Decisions , 1991, Journal of Cognitive Neuroscience.

[35]  W. Ea,et al.  Hemispheric functioning in paranoid and nonparanoid schizophrenia. , 1979 .

[36]  Brigitte Rockstroh,et al.  Reduced interhemispheric transmission in schizophrenia patients: evidence from event-related potentials , 2002, Neuroscience Letters.

[37]  P. Brugger,et al.  Functional Hemispheric Asymmetry and Belief in ESP: Towards a “Neuropsychology of Belief” , 1993, Perceptual and motor skills.

[38]  R. Graves Mouth asymmetry, dichotic ear advantage and tachistoscopic visual field advantage as measures of language lateralization , 1983, Neuropsychologia.

[39]  P. Brugger,et al.  Nonstereotyped Responding in Positive Schizotypy after a Single Dose of Levodopa , 2004, Neuropsychopharmacology.

[40]  E. Stip Happy birthday neuroleptics! 50 years later: la folie du doute , 2002, European Psychiatry.

[41]  M. Beeman,et al.  Complementary Right- and Left-Hemisphere Language Comprehension , 1998 .

[42]  J. Krystal,et al.  Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. , 1998, The American journal of psychiatry.

[43]  J. Rotrosen,et al.  Amphetamine response and relapse risk after depot neuroleptic discontinuation , 2004, Psychopharmacology.

[44]  J. Beaumont,et al.  Brain Disconnection and Schizophrenia , 1973, British Journal of Psychiatry.

[45]  J. Cohen,et al.  Context, cortex, and dopamine: a connectionist approach to behavior and biology in schizophrenia. , 1992, Psychological review.

[46]  M. Spitzer,et al.  A cognitive neuroscience view of schizophrenic thought disorder. , 1997, Schizophrenia bulletin.

[47]  M. Spitzer,et al.  Dopaminergic modulation of semantic network activation , 1996, Neuropsychologia.

[48]  L. J. Chapman,et al.  The measurement of handedness , 1987, Brain and Cognition.

[49]  L. J. Chapman,et al.  Scales for physical and social anhedonia. , 1976, Journal of abnormal psychology.

[50]  P. Goldman-Rakic,et al.  Dopamine D2 receptor mechanisms contribute to age-related cognitive decline: the effects of quinpirole on memory and motor performance in monkeys , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[51]  Magaro Pa,et al.  Information processing and lateralization in schizophrenia. , 1983 .

[52]  Adrian M. Owen,et al.  Methylphenidate Enhances Working Memory by Modulating Discrete Frontal and Parietal Lobe Regions in the Human Brain , 2000, The Journal of Neuroscience.

[53]  L. J. Chapman,et al.  Physical anhedonia, perceptual aberration, and psychosis proneness. , 1980, Schizophrenia bulletin.

[54]  P. Flor-Henry,et al.  Asymmetrical olfactory acuity and neuroleptic treatment in schizophrenia , 2000, Schizophrenia Research.

[55]  T. Crow Schizophrenia as the price that Homo sapiens pays for language: a resolution of the central paradox in the origin of the species , 2000, Brain Research Reviews.

[56]  S. Gershon,et al.  Dopamine and depression , 2005, Journal of Neural Transmission / General Section JNT.

[57]  K. Hugdahl,et al.  Dichotic listening during auditory hallucinations in patients with schizophrenia. , 1994, The American journal of psychiatry.

[58]  M. Hautzinger,et al.  Two-year stability of Psychosis Proneness Scales and their relations to personality disorder traits. , 1999, Journal of personality assessment.

[59]  Curt von Euler,et al.  Brain and Reading , 1989 .

[60]  H. Spohn,et al.  The Effects of Antipsychotic Medication on the Linguistic Ability of Schizophrenics , 1980, Journal of Nervous and Mental Disease.

[61]  D. Janowsky,et al.  Amphetamine psychosis and psychotic symptoms , 1979, Psychopharmacology.

[62]  A. Arnsten,et al.  Catecholamine regulation of the prefrontal cortex , 1997, Journal of psychopharmacology.

[63]  Peter Brugger,et al.  Magical ideation modulates spatial behavior. , 2003, The Journal of neuropsychiatry and clinical neurosciences.

[64]  A. Burns Textbook of Geriatric Neuropsychiatry (2nd edn) , 2001, British Journal of Psychiatry.

[65]  Giuseppe Esposito,et al.  Dextroamphetamine Enhances “Neural Network-Specific” Physiological Signals: A Positron-Emission Tomography rCBF Study , 1996, The Journal of Neuroscience.

[66]  R. Kahn,et al.  Language lateralization in female patients with schizophrenia: an fMRI study , 2003, Schizophrenia Research.

[67]  P. Flor-Henry,et al.  Neuroleptics reverse attention asymmetries in schizophrenic patients , 1989, Biological Psychiatry.

[68]  Theodor Landis,et al.  Hemispheric dissociation in judging semantic relations: Complementarity for close and distant associates , 1992, Brain and Language.

[69]  Asymmetrical hand force persistence and neuroleptic treatment in schizophrenia , 2001, Journal of the International Neuropsychological Society.

[70]  Ron Kikinis,et al.  Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study , 2001, Psychiatry Research: Neuroimaging.

[71]  R. Gur,et al.  Left hemisphere dysfunction and left hemisphere overactivation in schizophrenia. , 1978, Journal of abnormal psychology.

[72]  K. Jorga,et al.  COMT Inhibition by Tolcapone Further Improves Levodopa Pharmacokinetics when Combined with a Dual-Release Formulation of Levodopa/Benserazide , 1999, European Neurology.

[73]  Jules Davidoff,et al.  The dual brain D. Frank Benson and Eran Zaidel (eds.), (Guilford Press, New York, 1985) pp. 430, £34 , 1987, Biological Psychology.

[74]  E. Zaidel Hemispheric Independence and Interaction in Word Recognition , 1989 .

[75]  P. Brugger,et al.  Creative, paranormal, and delusional thought: a consequence of right hemisphere semantic activation? , 1998, Neuropsychiatry, neuropsychology, and behavioral neurology.

[76]  Pierre Flor-Henry,et al.  Hemisphere asymmetries of function in psychopathology , 1979 .

[77]  J. Cronly-Dillon,et al.  Vision and visual dysfunction. , 1994, Journal of cognitive neuroscience.

[78]  S. Kosslyn,et al.  Bridging psychology and biology. The analysis of individuals in groups. , 2002, The American psychologist.

[79]  K. Davis,et al.  Dopamine in schizophrenia: a review and reconceptualization. , 1991, The American journal of psychiatry.

[80]  M. Mishkin,et al.  Word recognition as a function of retinal locus. , 1952, Journal of experimental psychology.

[81]  T. Robbins,et al.  Chemical neuromodulation of frontal-executive functions in humans and other animals , 2000, Experimental Brain Research.

[82]  E. Granholm,et al.  Positive and negative schizotypal symptoms relate to different aspects of crossover reaction time task performance , 1998, Psychiatry Research.

[83]  Tom Dening,et al.  Textbook of Geriatric Neuropsychiatry , 1996 .

[84]  G. Alexander,et al.  Cortical blood flow and negative symptoms in schizophrenia. , 1996, Neuropsychobiology.

[85]  M. Hautzinger,et al.  Zur psychometrischen Erfassung von Schizotypie: Methodische Überprüfung und erste Validierung von zwei Skalen zur Erfassung von Risikomerkmalen , 1991 .

[86]  H. Bracha,et al.  Medicated chronic schizophrenic patients do not demonstrate left turning asymmetry. , 1997, Neuropsychobiology.

[87]  David B. Boles,et al.  Hemispheric Interaction in Visual Field Asymmetry , 1983, Cortex.

[88]  David Caplan,et al.  The measure of laterality , 1975, Neuropsychologia.

[89]  R. Kahn,et al.  Language lateralization in schizophrenia, an fMRI study , 2001, Schizophrenia Research.

[90]  J. Cronly-Dillon,et al.  Visual Agnosias and Other Disturbances of Visual Perception and Cognition , 1991 .

[91]  M. Laruelle,et al.  Dopamine as the wind of the psychotic fire: new evidence from brain imaging studies , 1999, Journal of psychopharmacology.

[92]  G. Lenzi,et al.  Bromocriptine and speech therapy in non-fluent chronic aphasia after stroke , 2000, Neurological Sciences.

[93]  Dietrich Lehmann,et al.  Brain electric correlates of strong belief in paranormal phenomena: intracerebral EEG source and regional Omega complexity analyses , 2000, Psychiatry Research: Neuroimaging.

[94]  L. J. Chapman,et al.  Magical ideation and social anhedonia as predictors of psychosis proneness: a partial replication. , 1997, Journal of abnormal psychology.

[95]  M. Corballis,et al.  Ambidexterity and magical ideation , 2002, Laterality.

[96]  P. Maruff,et al.  Asymmetries in the covert orienting of visual spatial attention in schizophrenia , 1995, Neuropsychologia.

[97]  H. Sauer,et al.  Gender differences in D2 dopamine receptor binding in drug-naive patients with schizophrenia: an [123I]iodobenzamide single photon emission computed tomography study , 1997, Psychiatry Research: Neuroimaging.

[98]  M. Alpert,et al.  Medication Effects on Referent Communication in Schizophrenic Patients: An Evaluation with a Structured Task , 1994, Brain and Language.

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

[100]  B. Rockstroh,et al.  Topography of the auditory P300 in schizotypal personality , 1999, Biological Psychiatry.