Cognitive control deficit in patients with first-episode schizophrenia is associated with complex deviations of early brain development

Cognitive control deficit in patients with first-episode schizophrenia is associated with complex deviations of early brain development

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J Psychiatry Neurosci 2017;42(2):87-94

Olivier Gay, MD, PhD; Marion Plaze, MD, PhD; Catherine Oppenheim, MD, PhD; Raphael Gaillard, MD, PhD; Jean-Pierre Olié, MD, PhD; Marie-Odile Krebs, MD, PhD*; Arnaud Cachia, PhD*

Abstract

Background: Several clinical and radiological markers of early neurodevelopmental deviations have been independently associated with cognitive impairment in patients with schizophrenia. The aim of our study was to test the cumulative and/or interactive effects of these early neurodevelopmental factors on cognitive control (CC) deficit, a core feature of schizophrenia.

Methods: We recruited patients with first-episode schizophrenia-spectrum disorders, who underwent structural MRI. We evaluated CC efficiency using the Trail Making Test (TMT). Several markers of early brain development were measured: neurological soft signs (NSS), handedness, sulcal pattern of the anterior cingulate cortex (ACC) and ventricle enlargement.

Results: We included 41 patients with schizophrenia in our analysis, which revealed a main effect of ACC morphology (p = 0.041) as well as interactions between NSS and ACC morphology (p = 0.005), between NSS and handedness (p = 0.044) and between ACC morphology and cerebrospinal fluid (CSF) volume (p = 0.005) on CC measured using the TMT-B score – the TMT-A score.

Limitations: No 3- or 4-way interactions were detected between the 4 neurodevelopmental factors. The sample size was clearly adapted to detect main effects and 2-way interactions, but may have limited the statistical power to investigate higher-order interactions. The effects of treatment and illness duration were limited as the study design involved only patients with first-episode psychosis.

Conclusion: To our knowledge, our study provides the first evidence of cumulative and interactive effects of different neurodevelopmental markers on CC efficiency in patients with schizophrenia. Such findings, in line with the neurodevelopmental model of schizophrenia, support the notion that CC impairments in patients with schizophrenia may be the final common pathway of several early neurodevelopmental mechanisms.


Submitted Aug. 4, 2015; Revised Feb. 10, 2016; Revised May 2, 2016; Accepted May 16, 2016; Early-released Sept. 27, 2016

*These authors contributed equally to this work.

Acknowledgements:The authors thank the CERC and SHU teams for their help during patient enrolment and data management. This work was supported by INSERM, ANR/ERANET-NEURON (AUSZ_EUCan), Académie de Médecine (O. Gay), Fondation Deniker, Fondation NRJ and Fondation Houiez (A. Cachia).

Affiliations: From the INSERM UMR 894, Centre de Psychiatrie & Neurosciences, CNRS GDR 3557, Institut de Psychiatrie, Paris, France (Gay, Plaze, Oppenheim, Gaillard, Olié, Krebs, Cachia); the Université Paris Descartes, Sorbonne Paris Cité, Paris, France (Gay, Plaze, Oppenheim, Gaillard, Olié, Krebs, Cachia); the Service Hospitalo-Universitaire, Centre Hospitalier Sainte-Anne, Paris, France (Gay, Plaze, Gaillard, Olié, Krebs); the Service d’Imagerie Morphologique et Fonctionnelle, Centre Hospitalier Sainte-Anne, Paris, France (Oppenheim); the CNRS UMR 8240, Laboratoire de Psychologie du Développement et de l’Éducation de l’Enfant, Paris, France (Cachia); and the Institut Universitaire de France, Paris, France (Cachia).

Competing interests: None declared.

Contributors: O. Gay, M. Plaze, M.-O. Krebs and A. Cachia designed the study. O. Gay, M. Plaze, C. Oppenheim, R. Gaillard, J.-P. Olié and M.-O. Krebs acquired the data, which O. Gay, M. Plaze, M.-O. Krebs and A. Cachia analyzed. O. Gay, M. Plaze, M.-O. Krebs and A. Cachia wrote the article, which all authors reviewed and approved for publication.

DOI: 10.1503/jpn.150267

Correspondence to: Prof. A. Cachia, Centre de Psychiatrie et Neurosciences, UMR 894, INSERM – Université, Paris Descartes, Hôpital Sainte-Anne, Paris, France; arnaud.cachia@parisdescartes.fr