Team "Pharmacology and neuropsychology of Emotions, related to risk - Taking and reward"

Emotion, cognition and processing of reward are crucial for action. Their functioning can be altered by disorders of the central nervous system or modulated by any number of pharmacological means. By combining complementary experimental and clinical approaches, we can address these complex problems in several ways:

• Evaluation of these processes in healthy volunteers, and in patients with neurological or psychiatric disorders (Parkinson's Disease, schizophrenia, adult or teenage addiction, depression, anxiety) who display impairments in emotion, cognition, impulsivity or risk-taking.
• Pharmacological investigation into the possibility of inducing or restoring these behavioural impairments, using drugs with a known mechanism of action.

We use well-validated methods (mood induction, emotion recognition and emotional expression, coupled with functional neuroimaging) to investigate both normal functioning, and disorders, of the central nervous system, in an interdisciplinary and interactive collaboration between basic and clinical research. This line of investigation is crucial in understanding the physiological and behavioural mechanisms implicated in these behaviours, and may eventually lead to possible strategies for treatment.

Main research themes

• Emotion and Parkinson's Disease:

The main aim of this project is to study the neurobiological mechanisms and pharmacological modulation of emotion. Neuroimaging techniques (in particular fMRI) will allow us to examine the anatomical substrates and neurobiological correlates of emotion. We hope to distinguish different components of emotional processing, such as recognition of emotion, the sensation and expression of emotion, and the social impact of emotion. We will study the same scientific questions in different populations (both healthy volunteers and patients, with and without treatment) in order to obtain complementary data-sets.

• Emotion and Schizophrenia:

  Emotional impairment in schizophrenia will also be examined. This disorder affects 1% of the general population. From among the many pathophysiological hypotheses that have been suggested, we believe that this disorder is due to a dysfunction in limbic and frontal neural circuits, which are essential for the integration of new information and the formulation of appropriate responses (the idea that dorsolateral prefrontal cortex, or its interconnections, are disconnected from other multi-modal association areas). We hope to characterise the emotional impairment in schizophrenic patients at different levels of processing (perception, sensation and expression), and to study the functional anatomy, pharmacological modulation and social repercussion of these impairments.

• Paediatric Psychopharmacology:

  A final aspect of this project concerns paediatric psychopharmacology. While the prescription of psychotropic drugs to children and adolescents is far from uncommon (estimated to be 12-18%), it is not contingent on any rigorously validated clinical criteria (Riddle et al., 1998). Childhood specificity appears only occasionally in pharmacokinetic or pharmacodynamic data. Taking into account their increasing use (in developmental disorders, schizophrenia and other psychotic illnesses, ADHD, and anti-social behaviour), we will first examine the .atypical antipsychotics' by developing several lines of investigation in parallel: pharmacokinetic and pharmacodynamic studies, neuroimaging studies, and clinical efficacy and tolerance (in particular cognitive effects).

• Neuropsychology and Pharmacology of Reward, Risk-taking and Addiction

  The propensity for risk-taking is a behavioural tendency probably determined by genetic and educational factors, as well as being learnt through conditioning. Our hypothesis is that the predilection for taking risks can be both a static personality trait whilst also varying as a function of the environment. This hypothesis will be evaluated with previously-validated measures. Pharmacological treatment can provoke behavioural change with deleterious consequences, as much for society as for the subject (e.g. driving whilst medicated). We will examine the effects of drugs thought to impair vigilance through the integration of both objective and subjective measures and, also, based upon the results of both experimental and clinical studies (for example, sedation can be studies with both animal models and neuroimaging).

• Reward and Addiction

We will study reward and addiction in three disorders : ADHD, Parkinson's Disease and schizophrenia. Taking into account the lack of data currently available, we will use three parallel approaches: pharmacoepidemiological, clinical (prevalence, clinical characteristics, risk factors) and neurobiological (clinical evaluation and functional imaging).

Research tools used

• Pharmacological intervention as a means of analysing behaviour
• Behavioural tests
• Mood induction
• IRMf

Members

Statutaires
Stéphanie Aubert-Khalfa	Chercheur				e-mail
Jean-Michel Azorin	PU-PH				e-mail
Daniel Bailly	PU-PH				e-mail
Olivier Blin	PU-PH	04.91.38.75.63	TIMONE		e-mail
Sylvie Bonin-Guillaume	PU-PH				e-mail
Eric Fakra	PH
Régine Jeanningros	Chercheur	04 91 16 45 89	GLM		e-mail
Arthur Kaladjian	PH	04 91 16 45 83			e-mail
Joelle Micallef-Roll	Maître de conférence-PH	04 91 38 46 42			e-mail
Pascale Pomietto	Chercheur	04 91 16 45 83	GLM		e-mail
Etudiants
Nathalie Besnier	Doctorant		Timone
Fajula Claire	Doctorant
Myriam El Khoury	Doctorant
Elisabeth Frauger	Doctorant		Timone
Emmanuelle Reynaud	Doctorant
Nordmann Sandra	Doctorant

Publications

You'll find below the main publications of the team: The full list is available Publications section.

• Adida, M; Clark, L; Mazzola-Pomietto, P; Kaladjian, A; Besnier, N; Azorin, JM; Jeanningros, R; Goodwin, G (2009), « Lack of insight may predict impaired decision-making in manic patients. », Bipolar Disorders, 10, 829-837
• Azorin, JM; Aubrun, E; Bertsch, J; Reed, C; Gerard, S; Lukasiewicz, M (2009), « Mixed states vs. pure mania in the French sample of the EMBLEM study: results at baseline and 24 months--European mania in bipolar longitudinal evaluation of medication  », BMC Psychiatry, 7;9:33
• Azorin, JM; Kaladjian, A (2009), « An update on the treatment of bipolar », Expert Opinion on Pharmacotherapy, 10, 161-172
• Azorin, JM; Kaladjian, A (2009), « Dépression et rythmes circadiens  », Encéphale, 35 (S2), 68-71
• Azorin, JM; Kaladjian, A (2009), « Depression and circadian rhythm », Review. French,
• Azorin, JM; Kaladjian, A (2009), « An update on the treatment of bipolar depression », Expert Opin Pharmacother, 10(2):161-72
• Azorin, JM; Kaladjian, A; Adida, M; Hantouche, EG; Hameg, A; Lancrenon, S; Akiskal, HS (2009), « Risk factors associated with lifetime suicide attempts in bipolar I patients: findings from a French National Cohort », Comprehensive Psychiatry, 115-120
• Azorin, JM; Kaladjian, A; Adida, M; Hantouche, EG; Hameg, A; Lancrenon, S; Akiskal, HS (2009), « Psychopathological Correlates of Lifetime Anxiety Comorbidity in Bipolar I Patients: Findings from a French National Cohort », Psychopathology, 24;42(6):380-386
• Bebbington, PE; Angermeyer, M; Azorin, JM; Marwaha, S; Marteau, F; Toumi, M (2009), « Side-effects of antipsychotic medication and health-related quality of life in schizophrenia », Acta Psychiatra Scandinavia Supplement , 438, 22-8
• Besnier, N; Gavaudan, G; Navez, A; Adida, M; Jollant, F; Courtet, P; Lançon, C. (2009), « Clinical features of suicide occurring in schizophrenia (I). Risk-factors identification », Encéphale , 35,176-81
• Besnier, N; Richard, F; Zendjidjian, X; Kaladjian, A; Mazzola-Pomietto, P; Adida, M; Azorin, JM (2009), « Stroop and emotional Stroop interference in unaffected relatives of patients with schizophrenic and bipolar disorders: distinct markers of vulnerability?  », World Journal of Biological Psychiatry, 25:1-10
• Blin, O; Audebert, C; Pitel, S; Kaladjian, A; Casse-Perrot, C; Zaim, M; Micallef, J; Tisne-Versailles, J; Sokoloff, P; Chopin, P; Marien, M (2009), « Effects of dimethylaminoethanol pyroglutamate (DMAE p-Glu) against memory deficits induced by scopolamine: evidence from preclinical and clinical studies. », Psychopharmacology ,
• Fakra, E; Hyde, LW; Gorka, A; Fisher, PM; Muñoz, KE; Kimak, M; Halder, I; Ferrell, RE; Manuck, SB; Hariri, AR (2009), « Effects of HTR1A C(-1019)G on amygdala reactivity and trait anxiety », Arch Gen Psychiatry, 66(1):33-40
• Kaladjian, A; Jeanningros, R; Azorin, JM; Nazarian, B; Roth, M; Anton, J.L.; Mazzola-Pomietto, P (2009), « Remission from mania is associated with a decrease in amygdala activation during motor response inhibition », Bipolar disorders , 11(5):530-8
• Mazzola-Pomietto, P; Kaladjian, A; Azorin, JM; Anton, JL; Jeanningros, R (2009), « Bilateral decrease in ventrolateral prefrontal cortex activation during motor response inhibition in mania. », Journal of Psychiatric Research, 43,432-41
• Micallef, J; Rey, M; Eusebio, A; Audebert, C; Rouby, F; Jouve, E; Tardieu, S; Blin, O (2009), « Antiparkinsonian drug-induced sleepiness: a double-blind placebo-controlled study of L-dopa, bromocriptine and pramipexole in healthy subjects », British Journal of Clinical Pharmacology, 67(3):333-40
• Pagani M, Pizzinelli P, Traon AP, Ferreri C, Beltrami S, Bareille MP, Costes-Salon MC, Béroud S, Blin O, Lucini D, Philip P (2009), « Hemodynamic, autonomic and baroreflex changes after one night sleep deprivation in healthy volunteers », Auton Neurosciences, 28;145(1-2):76-80
• Pradel, V; Frauger, E; Thirion, X; Ronfle, E; Lapierre, V; Masut, A; Coudert, C; Blin, O; Micallef, J (2009), « Impact of a prescription monitoring program on doctor-shopping for high dosage buprenorphine », Pharmacoepidemiol Drug Safety, 18(1):36-43
• Azorin, JM (2008), « From psychotic to bipolar disorders », Encéphale, 34 (S4), 127-129
• Azorin, JM; Kaladjian, A; Adida, M; Hantouche, EG; Hameg, A; Lancrenon, S; Akiskal, HS (2008), « Factors Associated with Rapid Cycling in Bipolar I Manic Patients: Findings From a French National Study », CNS Spectrums, 13-780-7
• Azorin, JM; Kaladjian, A; Adida, M; Hantouche, EG; Hameg, A; Lancrenon, S; Akiskal, HS (2008), « Toward the delineation of mania subtypes in the French National EPIMAN-II Mille Cohort: Comparisons with prior cluster analytic investigations. », European Archives of Psychiatry and Clinical Neuroscience, sous presse
• Azorin, JM; Kaladjian, A; Besnier, N; Cermolacce, M (2008), « Who is Called Schizophrenic ? », Thérapie, 63:231-5
• Azorin, JM; Murteira, S; Hansen, K; Toumi, M (2008), « Evaluation of patients on sertindole treatment after failure of other antipsychotics: a retrospective analysis », BMC Psychiatry, 14;8-16
• Bensmaïl, S; Dufossé, M; Frolov, A; Kaladjian, A; Ben Ouezdou, F (2008), « Pinch and grip control by a neural network modeling the cerebro-cerebellar System », Intelligent Automation and Soft Computing, sous presse
• Besnier, N; Kaladjian, A; Mazzola-Pomietto, P; Adida, M; Fakra, E; Jeanningros, R; Azorin, JM (2008), « Selecting material to develop an emotional Stroop test adapted to schizophrenia and bipolar disorders », The Canadian Journal of Psychiatry, 53:177-188
• Chambon, V; Franck, N; Koechlin, E; Fakra, E; Ciuperca, G; Azorin, JM; Farrer, C (2008), « The architecture of cognitive control in schizophrenia », Brain, 131:962-70
• Crocq, MA; Camus, V; Millet, B; Gliskman, J; Azorin, JM; Krebs, MO; Limosin, F; Costentin, J; Daléry, J (2008), « Clinical potentialities and perspectives for the use of aripiprazole in other disorders than its classical indications. A critical analysis of the recent literature », Encéphale , 34, 187-93
• Fakra, E; Khalfa, S; Da Fonseca, D; Besnier, N; Delaveau, P; Azorin, J-M; Blin, O (2008), « Effect of risperidone versus haloperidol on emotional responding in schizophrenic patients », Psychopharmacology, 261-272
• Jeanningros, R; Mazzola-Pomietto, P; Kaladjian, A (2008), « Corrélats neuroanatomiques des troubles impulsifs dans les états maniaques. », Information Psychiatrique, 84:121-128
• Kaladjian, A; Jeanningros, R; Azorin, JM; Nazarian, B; Roth, M; Mazzola-Pomietto, P (2008), « Reduced brain activation in euthymic bipolar patients during response inhibition: An event-related fMRI study », Psychiatry Research: Neuroimaging, , 172, 45-51
• GARCIA C, MICALLEF J, DUBREUIL D, PHILIPPOT P, JOUVE E, BLIN O. Effects of lorazepam on emotional reactivity, performance and vigilance in subjects of high and low anxiety. J Clin Psychopharmacol. 2000;20:226-33.
• GUILLERMAIN Y, MICALLEF-ROLL J, POSSAMAI CA, BLIN O, HASBROUCQ T. N-Methyl-D-Aspartate receptors and information processing: human choice reaction time under a subanaesthetic dose of ketamine.Neurosci Lett. 2001;27;303(1):29-32.
• VAIVA G, DE LENCLAVE MB, BAILLY D. Treatment of comorbid opiate addiction and attention-deficit hyperactivity disorder (residual type) with moclobemide: a case report. Prog Neuropsychopharmacol Biol Psychiatry. 2002 Apr;26(3):609-11