Nora Hamdani1, Claire Daban-Huard2, Mohamed Lajnef2, Rémi Gadel2, Philippe Le Corvoisier3, Marine Delavest4, Soufiane Carde5, Jean-Pierre Lépine6, Stéphane Jamain6, Josselin Houenou5, Bijan Galeh3, Jean-Romain Richard7, Masayuki Aoki8, Dominique Charron8, Rajagopal Krishnamoorthy9, Robert Yolken10, Faith Dickerson10, Ryad Tamouza11, Marion Leboyer2. 1. Inserm U955, Equipe 15 « Psychiatrie Génétique », Créteil F-94000, France; AP-HP, DHU Pe-PSY, Université Paris Est Créteil, Groupe Henri Mondor - Albert Chenevier, Pôle de psychiatrie et d׳Addictologie, Créteil F-94000, France; Fondation Fondamental, Fondation de coopération scientifique, Créteil F94000, France. Electronic address: nora.hamdani@ach.aphp.fr. 2. Inserm U955, Equipe 15 « Psychiatrie Génétique », Créteil F-94000, France; AP-HP, DHU Pe-PSY, Université Paris Est Créteil, Groupe Henri Mondor - Albert Chenevier, Pôle de psychiatrie et d׳Addictologie, Créteil F-94000, France; Fondation Fondamental, Fondation de coopération scientifique, Créteil F94000, France. 3. CIC 006Henri Mondor INSERM & Plateforme de Ressources Biologiques, Université Paris Est Créteil, AP-HP, France. 4. Neurospin, UNIACT Lab, Psychiatry Team, CEA Saclay, France; AP-HP, Université Paris Diderot, Service de Psychiatrie, Hôpital Lariboisiere Fernand Widal, F-75010 Paris, France. 5. Inserm U955, Equipe 15 « Psychiatrie Génétique », Créteil F-94000, France; AP-HP, DHU Pe-PSY, Université Paris Est Créteil, Groupe Henri Mondor - Albert Chenevier, Pôle de psychiatrie et d׳Addictologie, Créteil F-94000, France; Fondation Fondamental, Fondation de coopération scientifique, Créteil F94000, France; Neurospin, UNIACT Lab, Psychiatry Team, CEA Saclay, France. 6. Fondation Fondamental, Fondation de coopération scientifique, Créteil F94000, France; AP-HP, Université Paris Diderot, Service de Psychiatrie, Hôpital Lariboisiere Fernand Widal, F-75010 Paris, France. 7. Inserm U955, Equipe 15 « Psychiatrie Génétique », Créteil F-94000, France; Fondation Fondamental, Fondation de coopération scientifique, Créteil F94000, France. 8. Fondation Fondamental, Fondation de coopération scientifique, Créteil F94000, France; Jean Dausset Dept & INSERM, UMRS 940, Hôpital Saint Louis, Univ Paris Diderot, Paris F75010, France. 9. INSERM, UMRS 665, INTS, Paris, France. 10. Stanley Laboratory of Developmental Neurovirology, Johns Hopkins University Medical Center, Baltimore, USA. 11. Fondation Fondamental, Fondation de coopération scientifique, Créteil F94000, France; Stanley Research Program, Sheppard Pratt, Baltimore, MD, USA.
Abstract
BACKGROUND: Cognitive deficits are present in a large majority of Bipolar Disorder (BD) patients and known to be a marker of bad prognosis. Because, these deficits encompass several domains and no specific medical treatment seems to be effective, it is important to better understand the mechanisms underlying cognitive deterioration. As Toxoplasma gondii is known to induce the synthesis of pro-inflammatory cytokines such as IL-6, we will explore here the possible role of T. gondii in the cognitive decline observed in BD. METHODS: 42 euthymic BD patients and 36 controls were assessed for episodic verbal memory using the CVLT and for working memory and verbal ability using the WAIS III. Patients and controls were also screened for seropositivity to T. gondii and evaluated for the levels of IL-6 transcripts. RESULTS: The seropositivity for T. gondii was significantly higher in BD patients as compared to controls (p=0.005). The cognitive deterioration index (DI) was higher in BD patients (p=5.10(-6)) and correlated to high IL-6 mRNA expression only among those infected by T. gondii (rho=0.43, p=0.01). Among deteriorated patients (defined by scores above 0.10 according to Weschler׳s definition), the IL-6 mRNA expression was twice greater (p=0.01). LIMITATIONS: Our results are to be interpreted with caution because of our small sample size and the cross-sectional design. CONCLUSIONS: A long-term exposure to inflammation, measured here with IL-6 mRNA expression in T. gondii infected BD may alter cognitive functioning. IL-6 could thus be a useful predictive marker of cognitive deterioration in BD and may help to design personalized treatment.
BACKGROUND:Cognitive deficits are present in a large majority of Bipolar Disorder (BD) patients and known to be a marker of bad prognosis. Because, these deficits encompass several domains and no specific medical treatment seems to be effective, it is important to better understand the mechanisms underlying cognitive deterioration. As Toxoplasma gondii is known to induce the synthesis of pro-inflammatory cytokines such as IL-6, we will explore here the possible role of T. gondii in the cognitive decline observed in BD. METHODS: 42 euthymic BD patients and 36 controls were assessed for episodic verbal memory using the CVLT and for working memory and verbal ability using the WAIS III. Patients and controls were also screened for seropositivity to T. gondii and evaluated for the levels of IL-6 transcripts. RESULTS: The seropositivity for T. gondii was significantly higher in BD patients as compared to controls (p=0.005). The cognitive deterioration index (DI) was higher in BD patients (p=5.10(-6)) and correlated to high IL-6 mRNA expression only among those infected by T. gondii (rho=0.43, p=0.01). Among deteriorated patients (defined by scores above 0.10 according to Weschler׳s definition), the IL-6 mRNA expression was twice greater (p=0.01). LIMITATIONS: Our results are to be interpreted with caution because of our small sample size and the cross-sectional design. CONCLUSIONS: A long-term exposure to inflammation, measured here with IL-6 mRNA expression in T. gondii infected BD may alter cognitive functioning. IL-6 could thus be a useful predictive marker of cognitive deterioration in BD and may help to design personalized treatment.
Authors: Nick M Massa; Erica Duncan; Tanja Jovanovic; Kimberly Kerley; Lei Weng; Lauren Gensler; Samuel S Lee; Seth Norrholm; Abigail Powers; Lynn M Almli; Charles F Gillespie; Kerry Ressler; Bradley D Pearce Journal: Brain Behav Immun Date: 2016-11-21 Impact factor: 7.217
Authors: Gijsje J L J Snijders; Hans C van Mierlo; Marco P Boks; Marieke J H Begemann; Arjen L Sutterland; Manja Litjens; Roel A Ophoff; René S Kahn; Lot D de Witte Journal: Transl Psychiatry Date: 2019-11-20 Impact factor: 6.222