ExTraPsy

Experimental & Translational Psychiatry

Leader: Dr. Alexandre Surget
Co-Leader: Pr. Wissam El Hage

Stress-, mood- and reward-processing dysfunctions are pivotal in eliciting mental disorders such as major depression (MD), anxiety-related disorders, post-traumatic stress disorders (PTSD), autism spectrum disorders (ASD), addictive disorders and attention-deficit/hyperactivity disorder (ADHD).

Our team's project is centered around three strategies:

To promote basic/clinical research that relies on multi-scale examinations of brain dysfunctions and psychiatric disorders.
To foster bidirectional translation between bench and bedside.
To favor precision psychiatry and approaches relying on biologically-based constructs. (RDoC, NIMH 2009)

Objectives

To revealing the neurobiological and neurofunctional basis of altered cognitive and affective dimensions in psychiatric disorders, focusing on disorders affecting the mood, stress and reward systems.
To identify signatures of vulnerability/resilience, for diagnosis and for treatment response/resistance.
To develop innovative, efficient preventive and therapeutic approaches in psychiatry.

Specific research axes

Neurobiological exploration

This axis aims to uncover the neurobiological mechanisms underlying stress-, mood-, cognitive- and reward- processing dysfunctions in different psychiatric disorders.

This axis includes the study of:

Developmental neuroplasticity and how they are impacted by early-life adversity (ELA).
Time perception and encoding, its neural basis and alterations in stress-related disorders (depression, PTSD).
Adult neurogenesis in depression and PTSD.
Reward-processing systems in mouse models of ASD.
Brain excitation/inhibition homeostasis.
Psycho-socio-biological correlates of addictive disorders.

Identification of relevant signatures for patient stratification, personalized prevention and therapy

This axis aims to identify relevant markers for patient stratification, from vulnerability and diagnosis to response to preventive and therapeutic interventions.

In particular, we wish to determine if neurobiological determinants qualify as candidate biomarkers in validated animal models and in patients. We also investigate the prognostic value of neurosensory (olfactory perception), neurovascular (cerebral pulsatility via ultrasound imaging), neuroanatomical changes (MRI, radiotracers for PETscans) for response to treatment. We strive to identify functional individual profiles in addictive disorders looking at the contribution of psychiatric comorbidities (especially ADHD) and using radiopharmaceutical multitracer approaches.

Development of innovative therapeutic approaches

Within this aim, we aim to characterize the neurobiological effects and therapeutic efficacy of:

Innovative neurostimulation including repetitive transcranial magnetic stimulation (rTMS), transcranial focal ultrasound stimulation (tFUS), transcranial direct current stimulation (tDCS).
Pharmacological approaches (e.g. nitric oxide and nanobodies).
Sensory stimulations.

Epistemological consideration

We study the epistemological reasons for using preclinical and clinical protocols looking at the history of animal models in biological psychiatry and the epistemological and ethical issues they raise.

Functional Groups

Exploration of Stress and mood disorders in preclinical models

Resp. Dr. Alexandre Surget

Objectives:
The Team will use preclinical models of stress, depression and PTSD in mice at different stages of development and lifespan (from juvenile to older adults),

To investigate the neurobiological underpinnings of stress-related dysfunctions
To identify biological, neurobehavioral and cognitive signatures linked to models of stress, depression and stress-related disorders
To test innovative preventive or therapeutic strategies in these models

Several projects are currently underway:

Neurobiological underpinnings of earlylife adversity (ELA)
Alterations of time perception and encoding in stressrelated disorders as a cognitive signature and their neural bases in mouse models
Impact of innovative neurostimulation strategies in depression and PTSD
Role of adult hippocampal neurogenesis in pathophysiology, prevention and treatment of depression and PTSD

Clinical research on stress, mood and reward systems dysfunctions

Resp. Pr. Wissam El-Hage

Objectives:
Developments and characterization of therapeutic efficacy of:

Innovative neurostimulation including repetitive transcranial magnetic stimulation (rTMS), transcranial focal ultrasound stimulation (tFUS), transcranial direct current stimulation (tDCS)
Pharmacological approaches (e.g. nitric oxide)
Sensory stimulations, in patients with PTSD, MD, behavioral addictions as well as in treatment-resistant MD patients

Several projects are currently underway:

Olfactory perception and stimulation in depression
Effects of nitrous oxide (N2O) as a potential fastacting antidepressant
Novel therapeutic brain stimulation strategies to be tested in homogeneous subgroups of patients and/or targeted biomarkers
Effectiveness of therapeutic interventions in different types of behavioral addictions
Association of addictive disorders with ADHD

Exploration of Social Anhedonia in preclinical models

Resp. Dr. Julie Lemerrer, Dr. Jérôme Becker

Objectives:

To identify the neurobiological underpinnings of social anhedonia and withdrawal under physiological and pathological conditions such as ASD
To develop novel therapeutic strategies to relieve behavioral domains relevant to ASD across multiple mouse models

Several projects are currently underway:

Striatal medium spiny neuron (MSN) and reward processes dysfunctions in ASD mouse models
Alterations of brain excitation/inhibition homeostasis in ASD mouse models
Identifying, characterizing and engineering singledomain antibodies (or “nanobodies”) targeting G-protein coupled receptors (GPCRs)