La prise de décision est un processus adaptatif essentiel dont l’efficacité dépend de processus exécutifs, motivationnels, émotionnels et donc de l’intégrité de différents circuits cérébraux. Au sein d’une population saine, il existe des variabilités individuelles décisionnelles influencées par des facteurs génétiques, épigénétiques et environnementaux. De plus, de nombreuses pathologies mentales, neurobiologiques et neurodégénératives provoquent des altérations des processus décisionnels. Ainsi, déterminer des traits comportementaux et des substrats neurobiochimiques impliqués dans ce dysfonctionnement représente un intérêt majeur.Nous avons développé, chez la souris, un test de prise de décision, basé sur le test classiquement utilisé chez l’homme (l’Iowa Gambling Task), qui reproduit une situation incertaine, complexe et conflictuelle de choix : le Mouse Gambling Task (MGT). Grâce à une approche différentielle du comportement, nous avons observé des différences spontanées de capacités décisionnelles : certaines souris ont un comportement rigide et évitent toute pénalité (souris safe), d’autres ont un comportement exploratoire quitte à prendre des risques (souris risky), et une majorité des souris a un comportement intermédiaire (souris average). Nous avons ensuite révélé que les souris safe ont un comportement plus anxieux, une activation préfrontale plus faible que les autres groupes à l’issu du MGT, et un taux de sérotonine à l’état basal plus faible au niveau du cortex préfrontal. Les souris risky ont un comportement plus risqué dans plusieurs tests comportementaux et sont moins sensibles à la récompense. De plus, elles présentent un faible taux de sérotonine au niveau du cortex orbitofrontal ainsi qu’un taux de dopamine, noradrénaline et sérotonine plus important au niveau hippocampique.Afin de tester l’effet d’une modification de l’environnement sur les profils décisionnels caractérisés précédemment, nous avons réalisé le MGT sur un groupe de souris soumises soit à une dette aiguë de sommeil (DAS) soit à une dette chronique de sommeil (DCS). Nous avons alors montré qu’une DCS n’a pas d’effet sur les profils décisionnels mais qu’une DAS accentue ces profils décisionnels: les animaux safe deviennent d’autant plus rigides et évitent encore d’avantage les pénalités alors que les animaux risky choisissent systématiquement les options plus risquées, en adoptant un comportement rigide. Ces observations comportementales peuvent s’expliquer par un métabolisme sérotoninergique diminué au niveau du cortex orbitofrontal et augmenté au niveau hippocampique, ainsi que par un taux élevé de dopamine au niveau du striatum dorsal, structure cérébrale clé des processus d’automatisation.Par conséquent, le MGT permet de révéler, chez des souris consanguines saines, les caractéristiques comportementales et neurobiologiques individuelles de stratégies décisionnelles inadaptées pouvant être amplifiées par un stress environnemental. Ce modèle permettra, notamment, de déterminer les facteurs de vulnérabilité au développement de certaines psychopathologies (l’addiction et la dépression, par exemple) dont le manque de sommeil pourrait être un déclencheur ou un amplificateur. / Affective abilities that rely on the integrity of several neural circuits. In healthy subjects, inter-individual variability during decision-making exists due to genetic, epigenetic and environmental factors. Moreover, many psychiatric and neurobiological disorders are characterized by poor decision-making processes. Therefore, determining behavioral traits and neurobiological substrates involved in these processes is of major interest to unravel markers that could predict the emergence of neuropathologies.Based on the Iowa Gambling Task in humans, we developed a decision-making task in mice that assesses their ability to choose between several conflicting options under uncertainty. Thanks to a differential approach of mice’s behavior, we show that decision-making skills differed between mice: some mice exhibit a rigid behavior and avoid penalty (safe mice); others maintained exploratory behavior even if they took risks (risky mice); a majority of mice exhibit an intermediate behavior (average mice). We found that a combination of behavioral characteristics related to different psychopathologies in humans were specifically associated with extreme behavior in mice: safe mice exhibited a more anxious behavior, a lower prefrontal activation after the MGT than others subgroups of performance together with a lower basal rate of serotonin in the prefrontal cortex. Risky mice displayed a riskier behavior in various behavioral tasks, were less sensitive to reward, and had a lower basal rate of serotonin in the orbitofrontal cortex as well as a higher basal rate of serotonin, dopamine and noradrenaline in the hippocampus.To investigate the consequences of environmental changes on decision-making individual profiles, we performed the MGT on groups of mice either under Acute Sleep Dept (ASD) or under chronic sleep debt (CSD). We show that CSD didn't play any apparent effect but that ASD emphasized decision-making profiles: safe mice became drastically more rigid and avoided penalty; and risky mice chose systematically riskier options and developed rigid and unefficient decisions. These behavioral data could be explained by a decreased serotonin metabolism in the orbitofrontal cortex, an increase in the hippocampus and a high level of dopamine in the caudate putamen, the key brain area of habits.Therefore, in healthy inbred mice the MGT reveals individual inadapted decision-making strategies which are characterized by behavioral and neurobiological substrates exacerbated by an environmental stress. This paradigm also allows the determination of mice vulnerability to develop psychopathologies (e.g. depression, addiction) for which sleep debt could a trigger or a magnifier.

Após um trauma, características de resiliência protegem o indivíduo de desenvolver o transtorno de estresse pós-traumático (TEPT) ou outro transtorno mental. O TEPT é um transtorno mental e comportamental, caracterizado por alta morbidade e grandes prejuízos sociais. Resiliência é o processo de negociação, de manejo e de adaptação frente a uma situação de estresse significativo ou trauma. Acredita-se que fatores ambientais e neurobiológicos estejam envolvidos na capacidade de resiliência e no desenvolvimento de TEPT. Método: estudo transversal de casos e controles pareados por sexo e idade. Foram estudados 33 pacientes com TEPT e 33 controles saudáveis que sofreram trauma. Os instrumentos usados foram a Escala de Resiliência, o Questionário de Estilo Defensivo (DSQ), o Questionário de Trauma na Infância (CTQ) e o instrumento Parental Bonding (PBI). As variáveis biológicas estudadas foram cortisol sérico, Interleucina-6 (IL-6) e Interleucina-10 (IL-10) séricas. Resultado: Houve diferença significativa entre os grupos no fator I da escala de resiliência (p=0,019); nos mecanismos de defesas maduras, maiores em resilientes (p<0,001); no abuso emocional (p=0,001) e físico (p=0,003) durante a infância maior em pacientes com TEPT; e em níveis de IL-10 menores em TEPT (p=0,029). Os níveis de IL-6 e cortisol sérico não mostraram diferença significativa. Conclui-se que a resiliência e o trauma na infância parecem ter influência no desfecho de TEPT e que níveis reduzidos de IL-10 em pacientes com TEPT demonstram a alteração do sistema imune nesta patologia. / After a traumatic event, characteristics of resilience protect individuals from developing posttraumatic stress disorder (PTSD) or other mental conditions. PTSD is a mental and behavioral disorder characterized by high morbidity and significant social impairment. Resilience is the process of negotiating, handling and adapting to a highly stressful situation or trauma. Environmental and neurobiological factors are believed to be involved in the capacity for resilience and the development of PTSD. Method: Cross-sectional study of cases and controls matched for age and sex, consisting of 33 patients with PTSD and 33 healthy controls who experienced trauma. Instruments used were the Resilience Scale, Defense Style Questionnaire (DSQ), Childhood Trauma Questionnaire (CTQ) and the Parental Bonding Instrument (PBI). The biological variables studied were serum cortisol, Interleukin-6 (IL-6) and Interleukin-10 (IL-10) levels. Result: There was a significant intergroup difference in factor I of the resilience scale (p=0.019), with higher results in resilient subjects for mature defense mechanisms (p<0.001) and among patients with PTSD for emotional (p=0.001) and physical abuse (p=0.003) during childhood, as well as lower IL-10 levels for PTSD (p=0.029). No significant difference was recorded in serum cortisol and IL-6 levels. It was concluded that resilience and childhood trauma influence the outcome of PTSD and that lower IL-10 levels in patients with PTSD indicate immune system alterations in this pathology.

Após um trauma, características de resiliência protegem o indivíduo de desenvolver o transtorno de estresse pós-traumático (TEPT) ou outro transtorno mental. O TEPT é um transtorno mental e comportamental, caracterizado por alta morbidade e grandes prejuízos sociais. Resiliência é o processo de negociação, de manejo e de adaptação frente a uma situação de estresse significativo ou trauma. Acredita-se que fatores ambientais e neurobiológicos estejam envolvidos na capacidade de resiliência e no desenvolvimento de TEPT. Método: estudo transversal de casos e controles pareados por sexo e idade. Foram estudados 33 pacientes com TEPT e 33 controles saudáveis que sofreram trauma. Os instrumentos usados foram a Escala de Resiliência, o Questionário de Estilo Defensivo (DSQ), o Questionário de Trauma na Infância (CTQ) e o instrumento Parental Bonding (PBI). As variáveis biológicas estudadas foram cortisol sérico, Interleucina-6 (IL-6) e Interleucina-10 (IL-10) séricas. Resultado: Houve diferença significativa entre os grupos no fator I da escala de resiliência (p=0,019); nos mecanismos de defesas maduras, maiores em resilientes (p<0,001); no abuso emocional (p=0,001) e físico (p=0,003) durante a infância maior em pacientes com TEPT; e em níveis de IL-10 menores em TEPT (p=0,029). Os níveis de IL-6 e cortisol sérico não mostraram diferença significativa. Conclui-se que a resiliência e o trauma na infância parecem ter influência no desfecho de TEPT e que níveis reduzidos de IL-10 em pacientes com TEPT demonstram a alteração do sistema imune nesta patologia. / After a traumatic event, characteristics of resilience protect individuals from developing posttraumatic stress disorder (PTSD) or other mental conditions. PTSD is a mental and behavioral disorder characterized by high morbidity and significant social impairment. Resilience is the process of negotiating, handling and adapting to a highly stressful situation or trauma. Environmental and neurobiological factors are believed to be involved in the capacity for resilience and the development of PTSD. Method: Cross-sectional study of cases and controls matched for age and sex, consisting of 33 patients with PTSD and 33 healthy controls who experienced trauma. Instruments used were the Resilience Scale, Defense Style Questionnaire (DSQ), Childhood Trauma Questionnaire (CTQ) and the Parental Bonding Instrument (PBI). The biological variables studied were serum cortisol, Interleukin-6 (IL-6) and Interleukin-10 (IL-10) levels. Result: There was a significant intergroup difference in factor I of the resilience scale (p=0.019), with higher results in resilient subjects for mature defense mechanisms (p<0.001) and among patients with PTSD for emotional (p=0.001) and physical abuse (p=0.003) during childhood, as well as lower IL-10 levels for PTSD (p=0.029). No significant difference was recorded in serum cortisol and IL-6 levels. It was concluded that resilience and childhood trauma influence the outcome of PTSD and that lower IL-10 levels in patients with PTSD indicate immune system alterations in this pathology.

Após um trauma, características de resiliência protegem o indivíduo de desenvolver o transtorno de estresse pós-traumático (TEPT) ou outro transtorno mental. O TEPT é um transtorno mental e comportamental, caracterizado por alta morbidade e grandes prejuízos sociais. Resiliência é o processo de negociação, de manejo e de adaptação frente a uma situação de estresse significativo ou trauma. Acredita-se que fatores ambientais e neurobiológicos estejam envolvidos na capacidade de resiliência e no desenvolvimento de TEPT. Método: estudo transversal de casos e controles pareados por sexo e idade. Foram estudados 33 pacientes com TEPT e 33 controles saudáveis que sofreram trauma. Os instrumentos usados foram a Escala de Resiliência, o Questionário de Estilo Defensivo (DSQ), o Questionário de Trauma na Infância (CTQ) e o instrumento Parental Bonding (PBI). As variáveis biológicas estudadas foram cortisol sérico, Interleucina-6 (IL-6) e Interleucina-10 (IL-10) séricas. Resultado: Houve diferença significativa entre os grupos no fator I da escala de resiliência (p=0,019); nos mecanismos de defesas maduras, maiores em resilientes (p<0,001); no abuso emocional (p=0,001) e físico (p=0,003) durante a infância maior em pacientes com TEPT; e em níveis de IL-10 menores em TEPT (p=0,029). Os níveis de IL-6 e cortisol sérico não mostraram diferença significativa. Conclui-se que a resiliência e o trauma na infância parecem ter influência no desfecho de TEPT e que níveis reduzidos de IL-10 em pacientes com TEPT demonstram a alteração do sistema imune nesta patologia. / After a traumatic event, characteristics of resilience protect individuals from developing posttraumatic stress disorder (PTSD) or other mental conditions. PTSD is a mental and behavioral disorder characterized by high morbidity and significant social impairment. Resilience is the process of negotiating, handling and adapting to a highly stressful situation or trauma. Environmental and neurobiological factors are believed to be involved in the capacity for resilience and the development of PTSD. Method: Cross-sectional study of cases and controls matched for age and sex, consisting of 33 patients with PTSD and 33 healthy controls who experienced trauma. Instruments used were the Resilience Scale, Defense Style Questionnaire (DSQ), Childhood Trauma Questionnaire (CTQ) and the Parental Bonding Instrument (PBI). The biological variables studied were serum cortisol, Interleukin-6 (IL-6) and Interleukin-10 (IL-10) levels. Result: There was a significant intergroup difference in factor I of the resilience scale (p=0.019), with higher results in resilient subjects for mature defense mechanisms (p<0.001) and among patients with PTSD for emotional (p=0.001) and physical abuse (p=0.003) during childhood, as well as lower IL-10 levels for PTSD (p=0.029). No significant difference was recorded in serum cortisol and IL-6 levels. It was concluded that resilience and childhood trauma influence the outcome of PTSD and that lower IL-10 levels in patients with PTSD indicate immune system alterations in this pathology.