Clinical trial NCT00207064: Neurobiological and Neurocognitive Disturbances in First-episode Schizophrenia
Official title: 5-HT2A-receptor Binding: Implications for the Pathophysiology of Schizophrenia and Effects of Treatment With Antipsychotic Drugs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Keywords: first-episode
altanserin
5-HT2A receptors
MRI
fMRI
PPI
P300
P50 gating
endophenotypes
vulnerability indicators
quetiapine
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
name: Copenhagen University Hospital, Hvidovre
name: Glostrup University Hospital, Copenhagen
name: The Danish Medical Research Council
name: Copenhagen Hospital Corporation
name: University of Copenhagen
name: AstraZeneca
First posted: 2005-09-21
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: DIAGNOSTIC

Brief summary: We want to relate disturbances in first-episode schizophrenic patients in serotonin 5-HT2A receptors, brain structure, brain function, and information processing to each other and to psychopathology. Additionally, we want to examine the influence of 5-HT2A receptor blockade on these disturbances. We expect disturbances in the serotonergic system at baseline to correlate with specific structural and functional changes and with disruption in information processing as measured with psychophysiological and neurocognitive methods - and we expect 5-HT2A receptor blockade to reverse some of the functional and cognitive impairments. We do not expect any effect of treatment on brain structure

Detailed description: Patients and matched healthy controls are examined at baseline and again after the patients have been treated for 6 months with a combined 5-HT2A- and dopamine D2- receptor blocker. We have chosen the atypical antipsychotic compound, quetiapine, for the present study since this drug is characterized by a fast koff/low affinity for the dopamine D2 receptors. The purpose of the study is to examine pathophysiological and neuropsychological mechanisms - not treatment effects. We want to characterize neurobiological and functional endophenotypes or vulnerability indicators and to study their stability over time and their relation to treatment and contemporary psychopathology. To the extent that candidate endophenotypes can be characterized as stable and independent of treatment and contemporary psychopathology they will be analysed together with similar findings from previous (identical)cohorts of schizophrenic patients. Specific disturbances will also be related to candidate genes for schizophrenia.

Eligibility criteria: Inclusion Criteria:

* First-episode schizophrenia. The controls are matched for age, gender and parental socioeconomic status

Exclusion Criteria:

* Previous antipsychotic treatment, mental retardation, organic brain damage, and for the controls a psychiatric diagnosis or first-degree relatives with a psychiatric diagnosis

Primary outcomes:
measure: 5-HT2A receptor binding and occupancy (PET)
timeFrame: Baseline and after 6 months
measure: Structural MRI
timeFrame: Baseline and after 6 months
measure: Functional MRI
timeFrame: Baseline and after 6 months
measure: Information procession as measured with psychophysiological methods (P300, PPI, P50 gating ect.)
timeFrame: Baseline and after 6 months
measure: An extensive battery of neurocognitive measures
timeFrame: Baseline and after 6 months
Secondary outcomes:
measure: PANSS
timeFrame: Baseline and after 6 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Neurobiology Research Unit, Rigshospitalet
city: Glostrup
country: Denmark
facility: Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychiatric Center Glostrup
city: Hvidovre
country: Denmark
facility: Danish Research Center for Magnetic Resonance Imaging, Hvidovre Hospital
Study officials:
affiliation: Center for Neuropsychiatric Schizophrenia Research, University of Copenhagen, Psychaitric Center Glostrup, Ndr. Ringvej, DK-2600 Glostrup, Denmark
name: Birte Glenthoj, MD, DMSc.
role: STUDY_DIRECTOR
References:
citation: Jessen K, Mandl RCW, Fagerlund B, Bojesen KB, Raghava JM, Obaid HG, Jensen MB, Johansen LB, Nielsen MO, Pantelis C, Rostrup E, Glenthoj BY, Ebdrup BH. Patterns of Cortical Structures and Cognition in Antipsychotic-Naive Patients With First-Episode Schizophrenia: A Partial Least Squares Correlation Analysis. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019 May;4(5):444-453. doi: 10.1016/j.bpsc.2018.09.006. Epub 2018 Sep 25.
citation: Ebdrup BH, Skimminge A, Rasmussen H, Aggernaes B, Oranje B, Lublin H, Baare W, Glenthoj B. Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms. Int J Neuropsychopharmacol. 2011 Feb;14(1):69-82. doi: 10.1017/S1461145710000817. Epub 2010 Aug 12.
citation: Ebdrup BH, Glenthoj B, Rasmussen H, Aggernaes B, Langkilde AR, Paulson OB, Lublin H, Skimminge A, Baare W. Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia. J Psychiatry Neurosci. 2010 Mar;35(2):95-104. doi: 10.1503/jpn.090049.
citation: Rasmussen H, Erritzoe D, Andersen R, Ebdrup BH, Aggernaes B, Oranje B, Kalbitzer J, Madsen J, Pinborg LH, Baare W, Svarer C, Lublin H, Knudsen GM, Glenthoj B. Decreased frontal serotonin2A receptor binding in antipsychotic-naive patients with first-episode schizophrenia. Arch Gen Psychiatry. 2010 Jan;67(1):9-16. doi: 10.1001/archgenpsychiatry.2009.176.