Cortical folding in patients with bipolar disorder or unipolar depression

Cortical folding in patients with bipolar disorder or unipolar depression

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J Psychiatry Neurosci 2009;34(2):127-35

Jani Penttilä, MD, PhD; Marie-Laure Paillère-Martinot, MD, PhD; Jean-Luc Martinot, MD, PhD; Damien Ringuenet, MD; Michèle Wessa, PhD; Josselin Houenou, MD; Thierry Gallarda, MD; Frank Bellivier, MD, PhD; André Galinowski, MD, MSc; Pascale Bruguière, PhD; François Pinabel, MD; Marion Leboyer, MD, PhD; Jean-Pierre Olié, MD, PhD; Edouard Duchesnay, PhD; Eric Artiges, MD, PhD; Jean-François Mangin, PhD; Arnaud Cachia, PhD

Penttilä, Paillère-Martinot, Martinot, Ringuenet, Wessa, Houenou, Duchesnay, Artiges, Mangin, Cachia — INSERM, U797 Research Unit “Neuroimaging & Psychiatry,” the CEA, “Neuroimaging & Psychiatry” U797 Unit, Hospital Department Frédéric Joliot & Neurospin, Paris Sud University, Orsay, and Rene Descartes University, Paris; Paillère-Martinot — Assistance Publique–Hôpitaux de Paris (AP-HP), Department of Adolescent Medicine, Maison de Solenn, Cochin Hospital, Paris; Ringuenet — AP-HP; Department of Psychiatry and Addictology, Paul Brousse Hospital, Villejuif, France; Wessa — Department of Cognitive and Clinical Neuroscience, University of Heidelberg, Central Institute of Mental Health, Mannheim, Germany; Houenou, Bellivier, Leboyer — AP-HP; Department of Psychiatry, Chenevier-Mondor Hospital, Créteil; Gallarda — SHU, Department of Psychiatry, Sainte Anne Hospital, Paris; Bellivier, Leboyer — INSERM, U 995, IMRB, Department of Genetics, Psychiatry Genetics, Creteil, F-94000, University Paris 12, Faculty of Medicine, IFR10, Creteil; Galinowski, Olié — INSERM, Pathophysiologie des Maladies Psychiatriques, U894-7, Université Paris Descartes, Faculté de Médecine Paris Descartes, SHU, Hôpital Sainte-Anne, Paris; Bruguière — INSERM, U731, Paris, F 75013, University Pierre & Marie Curie-Paris 6, UMR S 731, Paris, F 75013, AP-HP, Pitié-Salpêtrière Hospital, Department of Physical Medicine and Rehabilitation; Pinabel — AP-HP, Department of Adult Psychiatry, Kremlin-Bicêtre Hospital, France; Duchesnay, Mangin — LNAO, NeuroSpin I2BM, Saclay, France

Abstract

Background: Analysis of cortical folding may provide insight into neurodevelopment deviations, which, in turn, can predispose to depression that responds particularly poorly to medications. We hypothesized that patients with treatment-resistant depression would exhibit measurable alterations in cortical folding.

Methods: We computed hemispheric global sulcal indices (g-SIs) in T1-weighted magnetic resonance images obtained from 76 patients and 70 healthy controls. We separately searched for anatomic deviations in patients with bipolar disorder (16 patients with treatment-resistant depression, 25 with euthymia) and unipolar depression (35 patients with treatment-resistant depression).

Results: Compared with healthy controls, both groups of patients with treatment-resistant depression exhibited reduced g-SIs: in the right hemisphere among patients with bipolar disorder and in both hemispheres among those with unipolar depression. Patients with euthymic bipolar disorder did not differ significantly from depressed patients or healthy controls. Among patients with bipolar disorder who were taking lithium, we found positive correlations between current lithium dose and g-SIs in both hemispheres.

Limitations: We cannot estimate the extent to which the observed g-SI reductions are linked to treatment resistance and to what extent they are state-dependent. Furthermore, we cannot disentangle the impact of medications from that of the affective disorder. Finally, there is interindividual variation and overlap of g-SIs among patients and healthy controls that need to be considered when interpreting our results.

Conclusion: Reduced global cortical folding surface appears to be characteristic of patients with treatment-resistant depression, either unipolar or bipolar. In patients with bipolar disorder, treatment with lithium may modify cortical folding surface.

Résumé

Contexte : L’examen des plissements du cortex pourrait fournir un argument en faveur de déviations de son développement qui, en retour, prédisposeraient certains individus à la dépression réfractaire à la pharmacothérapie. Nous avons formulé l’hypothèse que les patients ayant une dépression réfractaire au traitement présenteraient des anomalies mesurables des plissements corticaux.

Méthodes : Nous avons calculé des indices hémisphériques globaux de sulcation (g-SI) à partir des images par résonance magnétique pondérées en T1 obtenues chez 76 patients et de 70 témoins sains. Nous avons recherché des déviations anatomiques de manière séparée chez des patients atteints de trouble bipolaire (16 patients ayant une dépression réfractaire au traitement et 25 en état euthymique) et chez des patients ayant une dépression unipolaire (35 patients atteints de dépression réfractaire au traitement).

Résultats : Comparativement aux témoins sains, les 2 groupes de patients atteints de dépression réfractaire au traitement présentaient une diminution des g-SI : dans l’hémisphère droit chez les patients atteints de trouble bipolaire et bilatéralement chez les patients atteints de dépression unipolaire. Les patients ayant un trouble bipolaire euthymique ne différaient pas significativement des patients déprimés ou des témoins sains. Parmi les patients ayant un trouble bipolaire qui prenaient du lithium, nous avons observé des corrélations positives entre la dose actuelle de lithium et les indices de sulcation dans les 2 hémisphères. Limites : Nous ne pouvons déterminer dans quelle mesure les réductions des indices observées sont liées à la résistance au traitement ou à l’état des patients. En outre, nous ne pouvons distinguer l’impact des médicaments de celui des troubles affectifs. Enfin, l’existance d’une variation inter-individuelle et d’un chevauchement des valeurs des g-SI entre patients et témoins doit être prise en compte dans l’interprétation des résultats.

Conclusion : La réduction globale de la surface des plissements corticaux semble caractéristique des patients ayant une dépression réfractaire au traitement qu’elle soit unipolaire ou bipolaire. Chez les patients atteints de trouble bipolaire, le traitement au lithium pourrait modifier la surface des sillons corticaux.


Competing interests: None declared for Drs. Paillère-Martinot, Martinot, Ringuenet, Wessa, Houenou, Bellivier, Galinowski, Bruguière, Leboyer, Olié, Duchesnay, Artiges, Mangin and Cachia. Dr. Penttilä has received speaker fees from Servier Finland. Drs. Gallarda and Pinabel have received travel assistance from Lilly.

Submitted Mar. 20, 2008; Revised May 22, Sep. 2, 2008; Accepted Sep. 3, 2008

Contributors: Drs. Penttilä, Paillère-Martinot, Martinot and Cachia designed the study. Drs. Paillère-Martinot, Martinot, Ringuenet, Wessa, Houenou, Gallarda, Bellivier, Galinowski, Bruguière, Pinabel, Leboyer, Olié, Artiges acquired the data. Drs. Penttilä, Paillère-Martinot, Cachia, Duchesnay and Mangin analyzed the data. Drs. Penttilä, Paillère-Martinot and Cachia wrote the article. Drs. Penttilä, Paillère-Martinot, Martinot, Ringuenet, Wessa, Houenou, Gallarda, Bellivier, Galinowski, Bruguière, Pinabel, Leboyer, Olié, Duchesnay, Artiges, Mangin and Cachia reviewed the article. All authors gave final approval for publication.

Acknowledgements: This study was supported in part by a grant from the “Programme Hospitalier de Recherche Clinique, Délégation à la Recherche Clinique de l’Assistance Publique-Hôpitaux de Paris” (given to M.L.P.M.) and the Health Ministry of France (PHRC/AOM-98099, given to M.L.P.M.), by an INSERM–PROGRESS grant (given to M.L.P.M.) and by a grant from the French National Agency for Research (PSYMARKER/APV05137LSA). M.L.P.M. was also supported by an APHP–INSERM interface grant. J.P. received personal grants from the Finnish Cultural Foundation and the Sigrid Jusélius Foundation, Finland. A.C. received post-doc grants from INSERM. D.R. was supported by the “Fondation pour la Recherche Médicale” and by the Atomic Energy Commission of France. M.W. was supported by a grant from the Deutsche Forschungsgemeinschaft, Germany (We3638/1-1) and J.H. by a grant from the French National Academy of Medicine. We would like to thank D. Rivière and Y. Cointepas for their fruitful support with the BrainVISA and Anatomist software.

Correspondence to: Dr. M.-L. Paillère-Martinot, Maison de Solenn, Hôpital Cochin, 97 boul. de Port-Royal, 75014 Paris, France; fax 33 1 6986 7810; ml.paillere@cch.aphp.fr