Laboratory of molecular psychiatry and epigenetics

Current work of the laboratory focuses on some molecular processes of neuronal plasticity associated with psychiatric pathologies, such as mood disorders. In this context, we showed that a coactivator of the transcription factor CREB, called CRTC1 (CREB-Regulated Transcription Coactivator 1), is necessary for the formation and maintenance of a form of synaptic plasticity (L-LTP), which is thought to be required for learning and memory (Kovács et al., 2007. PNAS 104, 4700-4705). Based on the study of the behavior of mice lacking CRTC1 that were generated in our laboratory, the major goal of our research is to assess the role of CRTC1 in the mechanisms of neuroplasticity in relation to various psychiatric disorders, such as depression. We recently demonstrated that these mice have pathological behaviors, which are commonly associated with human depression (Breuillaud et al., 2012. Biol. Psy. 72, 528–536). Furthermore, these mice have an altered energy balance, which results in obesity appearing after the depressive-like symptoms (Breuillaud et al., 2009. Nature Med. 15, 989-990). CRTC1-deficient mice therefore represent a good animal model for studying the neurobiological basis of mood disorders as well as obesity, whose link with several psychiatric disorders has been clearly established.

In the context of translational research, we collaborate with Prof. Chin Eap, who investigates the effects of genetic polymorphisms on body mass index (BMI) and fat mass in psychiatric outpatients taking weight gain-inducing psychotropic drugs. Interestingly, his group found that patients carrying a particular CRTC1 polymorphism have a significantly lower BMI than noncarriers (Choong et al., 2013. JAMA Psychiatry 70, 1011-1019). Moreover, we try to identify epigenetic modifications (DNA methylation), specifically found in patients with schizophrenia or mood disorders (collaboration with Prof. Kim Do, Dr. Pierre Marquet, and Prof. Martin Preisig).

• Saura, C.A., and Cardinaux, J.R. (2017). Emerging Roles of CREB-Regulated Transcription Coactivators in Brain Physiology and Pathology. Trends Neurosci. 40(12), 720-733.
• Rossetti, C., Sciarra, D., Petit, J.M., Eap, C.B., Halfon, O., Magistretti, P.J., Boutrel, B., and Cardinaux, J.R. (2017). Gender-specific alteration of energy balance and circadian locomotor activity in the Crtc1 knockout mouse model of depression. Transl. Psychiatry 7(12):1269.
• Meylan, E.M., Breuillaud, L., Seredenina, T., Magistretti, P.J., Halfon, O., Luthi-Carter, R., and Cardinaux, J.R. (2016). Involvement of the agmatinergic system in the depressive-like phenotype of the Crtc1 knockout mouse model of depression. Transl. Psychiatry 6(7):e852.
• Meylan, E.M., Halfon, O., Magistretti, P.J., and Cardinaux, J.R. (2016). The HDAC inhibitor SAHA improves depressive-like behavior of CRTC1-deficient mice: Possible relevance for treatment-resistant depression. Neuropharmacology 107, 111-121.
• Breuillaud, L., Rossetti, C., Meylan, E.M., Mérinat, C., Halfon, O., Magistretti, P.J., and Cardinaux, J.R. (2012). Deletion of CREB-Regulated Transcription Coactivator 1 Induces Pathological Aggression, Depression-Related Behaviors, and Neuroplasticity Genes Dysregulation in Mice. Biol. Psychiatry 72, 528-536.
• Breuillaud, L., Halfon, O., Magistretti, P.J., Pralong, F.P., and Cardinaux, J.R. (2009). Mouse fertility is not dependent on the CREB coactivator Crtc1. Nature Medicine 15, 989-990.
• Kovács, K.A., Steullet, P., Steinmann, M., Do, K., Magistretti, P.J., Halfon, O., and Cardinaux, J.R. (2007). TORC1 is a calcium- and cAMP-sensitive coincidence detector involved in hippocampal long-term synaptic plasticity. Proc. Natl. Acad. Sci. USA 104, 4700-4705.