title: Frontal D2/3 Receptor Availability in Schizophrenia Patients Before and After Their First Antipsychotic Treatment: Relation to Cognitive Functions and Psychopathology.
abstract: We have previously reported associations between frontal D2/3 receptor binding potential positive symptoms and cognitive deficits in antipsychotic-naïve schizophrenia patients. Here, we examined the effect of dopamine D2/3 receptor blockade on cognition. Additionally, we explored the relation between frontal D2/3 receptor availability and treatment effect on positive symptoms.
  
  
  
  Twenty-five antipsychotic-naïve first-episode schizophrenia patients were examined with the Positive and Negative Syndrome Scale, tested with the cognitive test battery Cambridge Neuropsychological Test Automated Battery, scanned with single-photon emission computerized tomography using the dopamine D2/3 receptor ligand [(123)I]epidepride, and scanned with MRI. After 3 months of treatment with either risperidone (n=13) or zuclopenthixol (n=9), 22 patients were reexamined.
  
  
  
  Blockade of extrastriatal dopamine D2/3 receptors was correlated with decreased attentional focus (r = -0.615, P=.003) and planning time (r = -0.436, P=.048). Moreover, baseline frontal dopamine D2/3 binding potential and positive symptom reduction correlated positively (D2/3 receptor binding potential left frontal cortex rho = 0.56, P=.003; D2/3 receptor binding potential right frontal cortex rho = 0.48, P=.016).
  
  
  
  Our data support the hypothesis of a negative influence of D2/3 receptor blockade on specific cognitive functions in schizophrenia. This is highly clinically relevant given the well-established association between severity of cognitive disturbances and a poor functional outcome in schizophrenia. Additionally, the findings support associations between frontal D2/3 receptor binding potential at baseline and the effect of antipsychotic treatment on positive symptoms.
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, Glostrup, Denmark (Drs Nørbak-Emig, Ebdrup, Fagerlund, Rasmussen, and Glenthøj); University of Copenhagen, Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen, Denmark (Drs Nørbak-Emig and Glenthøj); Neurobiology Research Unit and Epilepsy Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Svarer and Pinborg); Department of Education, Centre for Research in Compulsory Schooling, Aarhus University, Denmark (Dr Allerup); Functional Imaging Unit, Department of Diagnostics, Copenhagen University Hospital, Glostrup Hospital, Denmark (Dr Rostrup); Department of Clinical Physiology and Nuclear Medicine, Copenhagen University, Bispebjerg Hospital, Denmark (Dr Friberg).
authors.forename: Henrik
authors.initials: H
authors.lastname: Nørbak-Emig
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, Glostrup, Denmark (Drs Nørbak-Emig, Ebdrup, Fagerlund, Rasmussen, and Glenthøj); University of Copenhagen, Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen, Denmark (Drs Nørbak-Emig and Glenthøj); Neurobiology Research Unit and Epilepsy Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Svarer and Pinborg); Department of Education, Centre for Research in Compulsory Schooling, Aarhus University, Denmark (Dr Allerup); Functional Imaging Unit, Department of Diagnostics, Copenhagen University Hospital, Glostrup Hospital, Denmark (Dr Rostrup); Department of Clinical Physiology and Nuclear Medicine, Copenhagen University, Bispebjerg Hospital, Denmark (Dr Friberg).
authors.forename: Bjørn H
authors.initials: BH
authors.lastname: Ebdrup
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, Glostrup, Denmark (Drs Nørbak-Emig, Ebdrup, Fagerlund, Rasmussen, and Glenthøj); University of Copenhagen, Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen, Denmark (Drs Nørbak-Emig and Glenthøj); Neurobiology Research Unit and Epilepsy Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Svarer and Pinborg); Department of Education, Centre for Research in Compulsory Schooling, Aarhus University, Denmark (Dr Allerup); Functional Imaging Unit, Department of Diagnostics, Copenhagen University Hospital, Glostrup Hospital, Denmark (Dr Rostrup); Department of Clinical Physiology and Nuclear Medicine, Copenhagen University, Bispebjerg Hospital, Denmark (Dr Friberg).
authors.forename: Birgitte
authors.initials: B
authors.lastname: Fagerlund
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, Glostrup, Denmark (Drs Nørbak-Emig, Ebdrup, Fagerlund, Rasmussen, and Glenthøj); University of Copenhagen, Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen, Denmark (Drs Nørbak-Emig and Glenthøj); Neurobiology Research Unit and Epilepsy Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Svarer and Pinborg); Department of Education, Centre for Research in Compulsory Schooling, Aarhus University, Denmark (Dr Allerup); Functional Imaging Unit, Department of Diagnostics, Copenhagen University Hospital, Glostrup Hospital, Denmark (Dr Rostrup); Department of Clinical Physiology and Nuclear Medicine, Copenhagen University, Bispebjerg Hospital, Denmark (Dr Friberg).
authors.forename: Claus
authors.initials: C
authors.lastname: Svarer
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, Glostrup, Denmark (Drs Nørbak-Emig, Ebdrup, Fagerlund, Rasmussen, and Glenthøj); University of Copenhagen, Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen, Denmark (Drs Nørbak-Emig and Glenthøj); Neurobiology Research Unit and Epilepsy Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Svarer and Pinborg); Department of Education, Centre for Research in Compulsory Schooling, Aarhus University, Denmark (Dr Allerup); Functional Imaging Unit, Department of Diagnostics, Copenhagen University Hospital, Glostrup Hospital, Denmark (Dr Rostrup); Department of Clinical Physiology and Nuclear Medicine, Copenhagen University, Bispebjerg Hospital, Denmark (Dr Friberg).
authors.forename: Hans
authors.initials: H
authors.lastname: Rasmussen
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, Glostrup, Denmark (Drs Nørbak-Emig, Ebdrup, Fagerlund, Rasmussen, and Glenthøj); University of Copenhagen, Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen, Denmark (Drs Nørbak-Emig and Glenthøj); Neurobiology Research Unit and Epilepsy Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Svarer and Pinborg); Department of Education, Centre for Research in Compulsory Schooling, Aarhus University, Denmark (Dr Allerup); Functional Imaging Unit, Department of Diagnostics, Copenhagen University Hospital, Glostrup Hospital, Denmark (Dr Rostrup); Department of Clinical Physiology and Nuclear Medicine, Copenhagen University, Bispebjerg Hospital, Denmark (Dr Friberg).
authors.forename: Lars
authors.initials: L
authors.lastname: Friberg
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, Glostrup, Denmark (Drs Nørbak-Emig, Ebdrup, Fagerlund, Rasmussen, and Glenthøj); University of Copenhagen, Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen, Denmark (Drs Nørbak-Emig and Glenthøj); Neurobiology Research Unit and Epilepsy Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Svarer and Pinborg); Department of Education, Centre for Research in Compulsory Schooling, Aarhus University, Denmark (Dr Allerup); Functional Imaging Unit, Department of Diagnostics, Copenhagen University Hospital, Glostrup Hospital, Denmark (Dr Rostrup); Department of Clinical Physiology and Nuclear Medicine, Copenhagen University, Bispebjerg Hospital, Denmark (Dr Friberg).
authors.forename: Peter N
authors.initials: PN
authors.lastname: Allerup
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, Glostrup, Denmark (Drs Nørbak-Emig, Ebdrup, Fagerlund, Rasmussen, and Glenthøj); University of Copenhagen, Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen, Denmark (Drs Nørbak-Emig and Glenthøj); Neurobiology Research Unit and Epilepsy Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Svarer and Pinborg); Department of Education, Centre for Research in Compulsory Schooling, Aarhus University, Denmark (Dr Allerup); Functional Imaging Unit, Department of Diagnostics, Copenhagen University Hospital, Glostrup Hospital, Denmark (Dr Rostrup); Department of Clinical Physiology and Nuclear Medicine, Copenhagen University, Bispebjerg Hospital, Denmark (Dr Friberg).
authors.forename: Egill
authors.initials: E
authors.lastname: Rostrup
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, Glostrup, Denmark (Drs Nørbak-Emig, Ebdrup, Fagerlund, Rasmussen, and Glenthøj); University of Copenhagen, Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen, Denmark (Drs Nørbak-Emig and Glenthøj); Neurobiology Research Unit and Epilepsy Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Svarer and Pinborg); Department of Education, Centre for Research in Compulsory Schooling, Aarhus University, Denmark (Dr Allerup); Functional Imaging Unit, Department of Diagnostics, Copenhagen University Hospital, Glostrup Hospital, Denmark (Dr Rostrup); Department of Clinical Physiology and Nuclear Medicine, Copenhagen University, Bispebjerg Hospital, Denmark (Dr Friberg).
authors.forename: Lars H
authors.initials: LH
authors.lastname: Pinborg
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research & Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Copenhagen University Hospital, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, Glostrup, Denmark (Drs Nørbak-Emig, Ebdrup, Fagerlund, Rasmussen, and Glenthøj); University of Copenhagen, Faculty of Health and Medical Sciences, Department of Clinical Medicine, Copenhagen, Denmark (Drs Nørbak-Emig and Glenthøj); Neurobiology Research Unit and Epilepsy Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (Drs Svarer and Pinborg); Department of Education, Centre for Research in Compulsory Schooling, Aarhus University, Denmark (Dr Allerup); Functional Imaging Unit, Department of Diagnostics, Copenhagen University Hospital, Glostrup Hospital, Denmark (Dr Rostrup); Department of Clinical Physiology and Nuclear Medicine, Copenhagen University, Bispebjerg Hospital, Denmark (Dr Friberg). birte.glenthoj@cnsr.dk.
authors.forename: Birte Y
authors.initials: BY
authors.lastname: Glenthøj
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D001288:Attention / Q000187:drug effects; D003006:Clopenthixol / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D003718:Denmark; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D057054:Molecular Imaging; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000187:drug effects* / Q000378:metabolism; D018967:Risperidone / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use*; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D012565:Schizophrenic Psychology; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; C581293:DRD2 protein, human; C493593:DRD3 protein, human; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D003006:Clopenthixol; D018967:Risperidone
keywords: SPECT; Schizophrenia; antipsychotic-naïve; cognition; epidepride; frontal dopamine D2/3 receptor; psychopathology
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