The Debutant Project - Cohort B

​This was the second cohort study of antipsychotic naïve first-episode patients with schizophrenia conducted at CINS/CNSR and is thus also known as cohort B. The main focus has been on serotonin2A (5-HT2A) receptors and their importance for cognitive performance, brain structure, and psychopathology. Data from this cohort are still used in several current research projects at CNSR.

Patients were included in this project between 2003 and 2008 in connection with their first psychotic episode and before they had received any antipsychotic medication. A control group of age- and gender-matched healthy controls were also included.

The participants participated in an extensive test battery including MRI, cognitive testing, psychophysiology and rating scales. Importantly, the tests were comparable to those applied in cohort A. Specific for cohort B was the investigation of the serotonin2A (5-HT2A) receptor availability assessed by PET and the ligand [18F]-Altanserin.  Additionally, a working memory paradigm (fMRI) was implemented in this cohort.

Following baseline testing, the patients were treated with individual doses of quetiapine. Quetiapine was chosen as tool compound due to its low affinity for dopamine D2 receptors and relatively high affinity for 5-HT2A receptors (no selective 5-HT2A compounds are on the market).

Key results from cohort B include the finding of significantly decreased frontal 5-HT2A receptor binding as well as evidence for an association between positive psychotic symptoms and frontal 5-HT2A receptor binding in the largest PET study of antipsychotic-naïve first-episode schizophrenia patients to date. The results challenged the exclusive role of dopamine as the final pathway leading to these symptoms in all patients (Rasmussen et al. 2010). Indeed, our results could suggest that there might be separate subgroups of patients benefitting from 5-HT2A, respectively dopamine D2 receptor blockade - and that 5-HT2A and dopamine D2 blockade might affect structural brain changes differently over time (Ebdrup et al. 2011; Rasmussen et al. 2010, 2011).

The cohort is also included in other studies at CINS/CNSR. Participants are currently being re-examined for a longitudinal investigation of cognition and brain changes and finally data from the cohort is included in CINS/CNSR's machine learning study.

 

PhD theses based on data from this project:

  • Bodil Aggernæs "Information processing in schizophrenia: A longitudinal study of first-episode, antipsychotic-naïve schizophrenia patients" (2009)
  • Hans Rasmussen "Imaging serotonin 2A receptors in schizophrenia patients before and after first antipsychotic treatment" (2009)
  • Bjørn Ebdrup " Structural Brain Changes in Antipsychotic-Naïve First-Episode Schizophrenia Patients Before and After Six Months of Antipsychotic Monotherapy" (2010)
  • Rune Andersen, "Cognition in first-episode schizophrenia: Core deficits and effects of antipsychotics" (2010)
  • Ayna Nejad, "Longitudinal study of working memory brain connectivity in antipsychotic drugnaive, first episode schizophrenia patients" (2013)
  • Lea Klærke "Investigating the association between cognition and structural brain changes in patients with schizophrenia: A long-term follow-up study" (expected 2019)

 

Postdoctoral projets based on data from this cohort:

  • Louise Baruël Johansen

 

Selected articles based on data from this project:

  • Ebdrup BH, Knop FK, Ishøy PL, Rostrup E, Fagerlund B, Lublin H, Glenthøj B. Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits. BMC Med. 2012 Aug 15;10:92.
  • Rasmussen H, Erritzoe D, Andersen R, Ebdrup BH, Aggernaes B, Oranje B, Kalbitzer J, Madsen J, Pinborg LH, Baaré 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..
  • Rasmussen H, Ebdrup BH, Erritzoe D, Aggernaes B, Oranje B, Kalbitzer J, Pinborg LH, Baaré WF, Svarer C, Lublin H, Knudsen GM, Glenthoj B. Serotonin2A receptor blockade and clinical effect in first-episode schizophrenia patients treated with quetiapine. Psychopharmacology (Berl). 2011 Feb;213(2-3):583-92.
  • Rasmussen H, Ebdrup BH, Aggernaes B, Lublin H, Oranje B, Pinborg LH, Knudsen GM, Glenthøj B. Norquetiapine and depressive symptoms in initially antipsychotic-naive first-episode schizophrenia. J Clin Psychopharmacol. 2013 Apr;33(2):266-9.
  • Rasmussen H, Ebdrup BH, Oranje B, Pinborg LH, Knudsen GM, Glenthøj B. Neocortical serotonin2A receptor binding predicts quetiapine associated weight gain in antipsychotic-naive first-episode schizophrenia patients. Int J Neuropsychopharmacol. 2014 Nov;17(11):1729-36.
  • Ebdrup BH, Glenthøj B, Rasmussen H, Aggernaes B, Langkilde AR, Paulson OB, Lublin H, Skimminge A, Baaré W. Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia. J Psychiatry Neurosci. 2010 Mar;35(2):95-104.
  • Ebdrup BH, Skimminge A, Rasmussen H, Aggernaes B, Oranje B, Lublin H, Baaré W, Glenthøj 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.
  • Hammer TB, Oranje B, Skimminge A, Aggernæs B, Ebdrup BH, Glenthøj B, Baaré W. Structural brain correlates of sensorimotor gating in antipsychotic-naive men with first-episode schizophrenia. J Psychiatry Neurosci. 2013 Jan;38(1):34-42.

 

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