addiction

Biomarkers of relapse and therapeutic response in addictions and mood disorders

Main field of research: 

Neurological and psychiatric diseases

Keywords: 

addiction
Mood disorders
Neuropsychophamarcology
Genomics
Biomarkers

ENP label: 

2015

Research Center / Institute: 

UMR-S 1144 Therapeutic Optimisation in Neuropsychopharmacology

Research Unit Code: 

UMRS 1144

The "Biomarkers of relapse and therapeutic response in addictions and mood disorders" team develops research on mood disordersand addiction both at the clinical and fundamental level (ranked A, AERES 2013, creation 01/01/2014).The objective is to identifyclinical, biological, genetic or imaging-based markers of the response to psychotropic drugs (in the context of drug abuse or during thetreatment for mood disorders or pain management). These markers will allow us to better predict the response (therapeutic and sideeffects) in order to improve the therapeutic monitoring of patients.

Leader

Leader: 

Personal

Team members: 

Marie-Claire CYNTHIA
Jean-Louis LAPLANCHE
Jean-Pierre LEPINE
Emmanuel CURIS
Florence VORSPAN
Vanessa BLOCH
Frank QUESTEL
Sarah SPORTICHE
Gaël DUPUY
Institutions

Principal Institution: 

Inserm

Affiliated institutions: 

Université Paris Descartes
Université Paris Diderot

Doctoral School: 

ED 436
Laboratory

Surname: 

Variabilité de réponses aux psychotropes
Publications

Publications: 

Geoffroy PA# , Scott J, Boudebesse C, Lajnef M, Henry C, Leboyer M, Bellivier F# , Etain B. Sleep in patients with remitted bipolar disorders: a meta-analysis of actigraphy studies. Acta Psychiatr Scand. 2014 28.

Bellivier F#, Geoffroy PA#, Etain B, Scott J. Sleep- and circadian rhythm-associated pathways as therapeutic targets in bipolar disorder. Expert Opin Ther Targets. 2015 Mar 2:1-17.

Boudebesse C, Geoffroy PA# , Henry C, Germain A, Scott J, Lajnef M, Leboyer M, Bellivier F# , Etain B. Eur Psychiatry. 2014 4.

Mouly S, Bloch V, Peoc'h K, Houze P, Labat L, Ksouda K, Simoneau G, Declèves X, Bergmann JF, Scherrmann JM, Laplanche JL#, Lepine JP#, Vorspan F#. Methadone dose in heroin-dependent patients: role of clinical factors, comedications, genetic polymorphisms and enzyme activity. Br J Clin Pharmacol. in press

Geoffroy PA# , Boudebesse C, Henrion A, Jamain S, Henry C, Leboyer M, Bellivier F# , Etain B. An ASMT variant associated with bipolar disorder influences sleep and circadian rhythms: a pilot study. Genes Brain Behav. 2014 13(3):299-304.

Serotonin signaling in plasticity and disease

Main field of research: 

Neuropharmacology / cell signaling

Keywords: 

addiction
dopamine
impulsivity
serotonin

ENP label: 

2012

Research Center / Institute: 

IFM - Institut du Fer à Moulin

Research Unit Code: 

UMRS 839

Our present work started from our observation that serotonin tone can be controlled by a feed-forward mechanism via 5-HT2B receptors. Recent independent investigations and our unpublished results indicate that this same serotonergic receptor may also impact local dopamine levels. The absence of 5-HT2B receptors, DA-targeting drugs induce a reduced increase in extracellular DA in NAcc, but a normal increase in dorsal striatum, thus an imbalance that could underlie addictive behaviors. Other unpublished evidence (in collaboration with D.

Leader

Leader: 

Personal

Team members: 

ROUMIER Anne
MOUTKINE Imane
DIAZ Silvina
BANAS Sophie
KOLODZIEJCZA Marta
QUENTIN Emily
SANDULACHE Miriam
Institutions

Principal Institution: 

Inserm

Affiliated institutions: 

Université Pierre et Marie Curie

University: 

Université Pierre et Marie Curie

Doctoral School: 

ED394
Laboratory

Surname: 

Marianne Coutures

Initiatives d'Excellence: 

ANR
Publications

Publications: 

Ebrahimkhani M, Oakley F, Murphy L, Mann J, Moles A, Perugorria M, Ellis E, Burt A, Douglass A, Wright M, White S, Jaffré F, Maroteaux L, Mann D. Stimulating healthy tissue regeneration by targeting the 5-HT2B receptor in chronic liver disease. Nature Medicine. 2011 Nov 27;17(12):1668-73.

El Oussini H, Bayer H, Scekic-Zahirovic J, Vercruysse P, Sinniger J, Dirrig-Grosch S, Dieterlé S, Echaniz-Laguna A, Larmet Y, Müller K, Weishaupt JH, Thal DR, van Rheenen W, van Eijk K, Lawson R, Monassier L, Maroteaux L, Roumier A, Wong PC, van den Berg LH, Ludolph AC, Veldink JH, Witting A, Dupuis L. Serotonin 2B receptor slows disease progression and prevents degeneration of spinal cord mononuclear phagocytes in amyotrophic lateral sclerosis. Acta Neuropathol. 2016 vol. 131 (3) pp. 465-80.

Li Y, Hadden C, Singh P, Mercado CP, Murphy P, Dajani NK, Lowery CL, Roberts DJ, Maroteaux L, Kilic F. GDM-associated insulin deficiency hinders the dissociation of SERT from ERp44 and down-regulates placental 5-HT uptake. Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):E5697-705.

Launay, J.-M., Hervé, P., Callebert, J., Mallat, Z., Collet, C., Doly, S., Belmer, A., Diaz, S.L., Hatia, S., Côté, F., Humbert, M., and Maroteaux, L. (2012). Serotonin 5-HT2B receptors are required for bone-marrow contribution to pulmonary arterial hypertension. Blood 2012 Feb;119(7):1772-1780.

Diaz, SL, Doly, S, Narboux-Nême, N, Fernandez, S, Mazot, P, Banas, SM, Boutourlinsky, K, Moutkine, I, Belmer, A, Roumier, A, and Maroteaux, L, 5-HT2B receptors are required for serotonin-selective antidepressant actions Molecular Psychiatry 2012 Feb;17(2):154-63.

 

Synapses in the pathophysiology of reward

Main field of research: 

Neurophysiology / systems neuroscience

Keywords: 

Synaptic plasticity
dopamine
reward
addiction
receptor trafficking

ENP label: 

2012

Research Unit Code: 

UMRS 839

The general interest of the lab is to dissect the neuronal circuits implicated in reward learning and to understand how drugs co-opt these connections.

Goal directed actions, aimed to obtain a reward, motivate our behaviors and influence our decisions.

Institutions

Principal Institution: 

Inserm

Affiliated institutions: 

Université Pierre et Marie Curie

University: 

Université Pierre et Marie Curie

Doctoral School: 

ED158
Laboratory

Initiatives d'Excellence: 

Biopsy
Publications

Publications: 

Mameli M., Bellone C., Brown T.C., Lüscher C. Cocaine inverts rules for synaptic plasticity of glutamate transmission in the VTA. Nature Neuroscience. 2011 In press

Brown T.C., Bellone C., Mameli M., Balland B., Dahan L., Lujan R., Deisseroth K., Lüscher C. Drug-driven AMPA receptor redistribution mimicked by selective dopamine neuron stimulation. PLoSOne. 2010 5(12):e15870.

Mameli M., Halbout B., Creton C., Engblom D., Parkitna J. R., Spanagel R., Lüscher C.. Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the NAc. Nat Neurosci. 2009 12:1036-41.

Engblom D., Bilbao A., Sanchis-Segura C., Dahan L., Pereau-lenz S., Balland B., Parkitna J.R., Lujan R., Halbout B., Mameli M., Parlato R., Sprengel R., Lüscher C., Schütz G., Spanagel R.. Glutamate receptors on dopamine neurons control the persistence of cocaine-seeking. Neuron 2008 59:497-508.

Mameli M., Balland B., Lujan R., Lüscher C.. Rapid synthesis and synaptic insertion of GluR2 for mGluR-LTD in the ventral tegmental area. Science. 2007 317:530-3.

Pathophysiology of Psychiatric disorders: Development and Vulnerability

Main field of research: 

Neurophysiology / systems neuroscience

Keywords: 

Psychose
Depression
addiction
anxiété
trouble bipolaire

ENP label: 

2012

Research Center / Institute: 

Institut de Psychiatrie et Neurosciences de Paris, IPNP (ex-CPN) - Centre Hospitalier Sainte Anne

Research Unit Code: 

UMRS 894

The overall goal of our research is to decipher the mechanisms involved in major mental health problems: psychosis, depression, bipolar disorder, addiction.

Leader

Leader: 

Institutions

Principal Institution: 

Inserm

Affiliated institutions: 

Université Paris Descartes

Doctoral School: 

ED BioSPC ED 158 ED 563
Laboratory

Initiatives d'Excellence: 

Idex Sorbonne Paris Cité
Publications

Publications: 

Renard J, Vitalis T, Rame M, Krebs M-O, Lenkei Z, Le Pen G, Jay TM. Chronic cannabinoid exposure during adolescence leads to long-term structural and functional changes in the prefrontal cortex. Eur Neuropsychopharmacol, 2015, in press.

Alexandre Ch, Chaumette B. Martinez G, Christia L, Dupont JM, Kebir O, Gaillard R, Amado I, Krebs MO. Paradoxical improvement of schizoprenic symptoms by a dopaminergic agonist : an example of personalized psychiatry in a CNV carrying patient. Biological Psychiatry. 2015 in press

Chan MK, Krebs MO, Cox D, Guest PC, Yolken RH, Rahmoune H, Rothermundt M, Steiner J, Leweke FM, van Beveren NJ, Niebuhr DW, Weber NS, Cowan DN, Suarez-Pinilla P, Crespo-Facorro B, Mam-Lam-Fook C, Bourgin J, Wenstrup RJ, Kaldate RR, Cooper JD, Bahn S. Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset. Transl Psychiatry. 2015 Jul 14;5:e601.

Chaumette B, Kebir O, Mam-Lam-Fook C, Morvan Y, Bourgin J, Godsil BP, Plaze M, Gaillard R, Jay TM, Krebs MO. Salivary cortisol in early psychosis: new findings and meta-analysis. Psychoneuroendocrinology, 2015 Oct 16;63:262-270.

Chaumette B, Kebir O, Mam-Lam-Fook C, Bourgin J, Godsil BP, Gaillard R, Jay TM, Krebs MO. Stress et Transition Psychotique : revue de la littérature - Encéphale in press

Neuronal signaling and gene regulation

Main field of research: 

Neuropharmacology / cell signaling

Keywords: 

striatum
Plasticité
addiction
dégénerescence neuronale
Huntington

ENP label: 

2009

Research Center / Institute: 

Institut de Biologie Paris Seine

Research Unit Code: 

U1130 UMR 8246

The main goal of our team is to unravel the intracellular events that govern cerebral plasticity and long-term behavioral alterations. We study their roles in gene regulations, neuronal adaptations in physiological (learning and memory) or pathophysiological (exposure to addictive drugs, neurodegenerative diseases) contexts. More specifically, we study these mechanisms within the striatum, the major input structure of the basal ganglia, which plays key roles in action selection and execution of movements as well as in reward-dependent learning and cognition.

Leader

Leader: 

Co leader: 

Institutions

Principal Institution: 

Inserm

Affiliated institutions: 

CNRS
Université Pierre et Marie Curie

University: 

Université Pierre et Marie Curie

Doctoral School: 

ED158
Laboratory

Surname: 

Neuroscience Paris Seine
Publications

Publications: 

Besnard A, Bouveyron N, Kappès V, Pascoli V, Pagès C, Heck N, Vanhoutte P, Caboche J (2011) Alterations of molecular and behavioral responses to cocaine by selective inhibition of Elk-1 phosphorylation. J Neurosci 31:14296-14307.

Cahill E, Pascoli V, Trifilieff P, Savoldi D, Kappès V, Lüscher C, Caboche J, Vanhoutte P (2014) D1R/GluN1 complexes in the striatum integrate dopamine and glutamate signaling to control plasticity and cocaine-induced responses. Mol. Psychiatry. doi: 10.1038/mp.2014.73.

Pascoli V, Cahill E, Bellivier F, Caboche J, Vanhoutte P (2014) Extracellular signal-Regulated kinases 1 and 2 activation by addictive drugs: A signal toward pathological adaptation. Biol. Psychiatry.

Heck N, Dos Santos M, Amairi B, Salery M, Besnard A, Herzog E, Boudier T, Vanhoutte P, Caboche J (2014) A new automated 3D detection of synaptic contacts reveals the formation of cortico-striatal synapses upon cocaine treatment in vivo. Brain Struct Funct (in press)

Pascoli V, Besnard A, Hervé D, Heck N, Pagès C, Girault JA, Caboche J, Vanhoutte P (2011) cAMP-independent tyrosine phosphorylation of NR2B mediates cocaine-induced Extracellular signal-Regulated (ERK) activation. Biol Psychiatry 69:218-227.

Imaging and Psychiatry

Main field of research: 

Neurological and psychiatric diseases

Keywords: 

Depression
schizophrenia
autism
Brain imaging
addiction

ENP label: 

2012

Research Center / Institute: 

Imagen Orsay Service Hospitalier Frédéric Joliot

Research Unit Code: 

U1000

Over the past 4 years, we have been studying psychiatric disorders and addictions that are prevalent and have a high social cost. We use magnetic resonance imaging and positron emission tomography to capture brain images in severely impaired patients and to assess the effects of treatment on brain function. We are based in the Service Hospitalier Frédéric Joliot (SHFJ), Orsay. We also collaborate with a network of psychiatrists within the Paris area and collaborate on large data sets with North Europe research teams.

 

PATHOPHYSIOLOGY

Leader

Leader: 

Institutions

Principal Institution: 

Inserm

Affiliated institutions: 

CEA

University: 

Université Paris Saclay / Université Paris Descartes

Doctoral School: 

ED158
Laboratory

Surname: 

Laboratoire Imagerie et Psychiatrie

Initiatives d'Excellence: 

IHU Necker
Publications

Publications: 

Dubol M, Trichard C, Leroy C, Sandu AL, Rahim M, Granger B, Tzavara ET, Karila L, Martinot JL, Artiges E. Dopamine Transporter and Reward Anticipation in a Dimensional Perspective: A Multimodal Brain Imaging Study. Neuropsychopharmacology. 2017 Aug 22. doi: 10.1038/npp.2017.183. [Epub ahead of print]

Stringaris A,. Martinot JL*, Schumann G*, Paillère-Martinot ML* & the IMAGEN Consortium. The brain’s response to reward anticipation and depression in adolescence: dimensionality, specificity and longitudinal predictions in a community-based sample. American Journal of Psychiatry 2015 Dec;172(12):1215-23.

Paillère-Martinot ML, Lemaitre H, Artiges E, Miranda R, Goodman R, Penttilä J, Struve M, Fadai T, Kappel V, Poustka L, Conrod P, Banaschewski T, Barbot A, Barker GJ, Büchel C, Flor H, Gallinat J, Garavan H, Heinz A, Ittermann B, Lawrence C, Loth E, Mann K, Paus T, Pausova Z, Rietschel M, Robbins TW, Smolka MN, Schumann G, Martinot JL & IMAGEN Consortium. White-matter microstructure and gray-matter volumes in adolescents with subthreshold bipolar symptoms. Molecular Psychiatry 2014, 19(4):462-70.

Sandu AL, Artiges E, Galinowski A, Gallarda T, Bellivier F, Lemaitre H, Granger B, Ringuenet D, Tzavara ET, Martinot JL, Paillère Martinot ML. Amygdala and regional volumes in treatment-resistant versus nontreatment-resistant depression patients. Depress Anxiety. 2017 Aug 9. doi: 10.1002/da.22675. [Epub ahead of print]

Artiges E, Leroy C, Dubol M, Prat M, Pepin A, Mabondo A, de Beaurepaire R, Beaufils B, Korwin JP, Galinowski A, D'Albis MA, Santiago-Ribeiro MJ, Granger B, Tzavara ET, Martinot JL, Trichard C. Striatal and Extrastriatal Dopamine Transporter Availability in Schizophrenia and Its Clinical Correlates: A Voxel-Based and High-Resolution PET Study. Schizophr Bull. 2017 Feb 8. doi: 10.1093/schbul/sbw192