The Pan-European Collaborative Antipsychotic-Naïve Study (PECANS I)

​In the PECANS study (cohort C) the specific theme has been assessment of reward processing (fMRI) and its relation to striatal dopamine D2/3 receptor binding and psychopathology. In addition to cognition and psychophysiology, functional brain connectivity (spontaneous or resting state, brain activity (fMRI)) and structural connectivity (DTI, MTI) have also been assessed. In the coming years, participants from this cohort will be reexamined.

Between 2008 and 2013, 69 patients were included in connection with their first psychotic episode and before they had received any antipsychotic medication. 69 age- and gender-matched healthy controls were also included.

The overall goal of this study has been to contribute to the understanding of the different biological and environmental processes involved in the development of the different "schizophrenias" by linking neurochemical, morphological, information-processing, reward processing, and environmental explanations to each other in a longitudinal study of antipsychotic-naïve patients with first-episode schizophrenia. By this we hope to characterize scientifically valid composite endophenotypes that can form the basis for more effective interventions. Additionally, we have wanted to study the effects of specific interventions on these new neurobiologically based "subgroups" of schizophrenia.

The results so far have been focused on the specific modalities. Regarding the brain reward system, extensive disturbances was found in the medication naïve schizophrenia patients, and this was related to the degree of psychotic symptoms. Antipsychotic treatment normalized these disturbances, and this was related to the effect on psychotic symptoms. Further, baseline changes in other parts of the reward system predicted weight change induced by medical treatment.

Looking at the dopamine receptor, the binding of a radioactive ligand at baseline seemed to predict treatment response, as patients with a low binding showed a better treatment response than patients with a high binding. Further, the results indicated that medically induced high receptor blockade was associated wither lower level of function.

Regarding brain structure, antipsychotic-naive patients with schizophrenia displayed subtle deficits in white matter. Psychotic symptoms appeared specifically associated with specific white matter changes. Six weeks of treatment normalized white matter.  

We are currently reexamining this cohort with most of the modalities that were used at baseline. The aim is to investigate the course of illness in schizophrenia and especially the longitudinal stability of the different biological markers as well as their ability to predict the course of illness and treatment response.

 

PhD theses based on data from this cohort:

  • Mette Ødegaard Nielsen "Disturbances in the reward processes in schizophrenia: A longitudinal study in antipsychotic- naïve first-episode schizophrenic patients" (2012)
  • Signe Wegmann Düring Clausen "Effect of treatment with dopamine D2 blocker on early information processing: A longitudinal study of antipsychotic-naïve first-episode schizophrenia patients" (2014)
  • Sanne Wulff "Disturbances in the reward processes in schizophrenia and its relation to dopamine activity: A longitudinal study in antipsychotic-naive first-episode schizophrenic patients" (2015)
  • Maria Høj Jensen "The Cognitive Reserve Hypothesis of Schizophrenia" (2015)
  • Simon Anhøj "Spontaneous brain activity as an endophenotype for schizophrenia" (2016)

 

Postdoctoral projets based on data from this cohort:

  • Jayachandra Mitta Raghava "White matter micro-structure alterations before and after antipsychotic mono-therapy in antipsychotic-naive patients with schizophrenia" (expected 2017)
  • Mette Ødegaard Nielsen "Potential biomarkers predicting treatment response and outcome in schizophrenia" (expected 2018)

 

Selected articles based on data from this cohort:

  • Nielsen, M. Ø., Rostrup, E., Wulff, S., Bak, N., Lublin, H., Kapur, S. & Glenthøj, B. Alterations of the Brain Reward System in Antipsychotic Naïve Schizophrenia Patients. 2012. Biological Psychiatry. pp. 898-905.
  • Nielsen, M. O., Rostrup, E., Wulff, S., Bak, N., Broberg, B. V., Lublin, H., Kapur, S. & Glenthoj, B. Improvement of Brain Reward. Abnormalities by Antipsychotic Monotherapy in Schizophrenia. December 2012. Archives of General Psychiatry. 69, 12, s. 1195-1204.
  • Anhøj, S. J., Ford, K., Williamson, P., Glenthøj, B. Y. & Rostrup, E. Spontaneous Brain Activity as a Biomarker for Schizophrenia. 2014. Schizophrenia Research. 153, Suppl. 1, p. 198
  • Wulff, S., Pinborg, L. H., Svarer, C., Jensen, L. T., Nielsen, M. Ø., Allerup, P., Bak, N., Rasmussen, H., Frandsen, E., Rostrup, E. & Glenthøj, B. Y. Striatal D2/3 Binding Potential Values in Drug-Naïve First-Episode Schizophrenia Patients Correlate With Treatment Outcome. 2015. Schizophrenia Bulletin. 41, 5, s. 1143-52.
  • Ebdrup BH, Raghava J, Nielsen MØ, Rostrup E, Glenthøj B. Frontal fasciculi and psychotic symptoms in antipsychotic-naïve patients with schizophrenia before and after six weeks of selective dopamine D2/3 receptor blockade. 2015. Journal of Psychiatry and Neuroscience; Nov 24;41(1).
  • Nielsen, M. Ø., Rostrup, E., Wulff, S., Glenthøj, B. Y. & Ebdrup, B. H. Striatal reward activity and antipsychotic associated weight change in initially antipsychotic-naïve schizophrenia patients. 2016. JAMA Psychiatry. s. 121-8 8 s.73
  • Düring S, Glenthøj BY, Oranje B. Effects of Blocking D2/D3 Receptors on Mismatch Negativity and P3a Amplitude of Initially Antipsychotic Naïve, First Episode Schizophrenia Patients. Int J Neuropsychopharmacol. 2015 Oct 9;19(3)
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