Prof. Yadid's Lab
The Neuropsychopharmacology Lab
Prof. Gal Yadid of the Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center and the Mina and Everard Goodman Faculty of Life Sciences is best known for his research on the neuropsychopharmacological mechanisms behind psychiatric disorders.
Yadid’s research group focuses on developing pharmacological and non-pharmacological treatment modalities for psychiatric disease, specifically drug addiction, depression, and Post Traumatic Stress Disorder (PTSD).
Using a bi-directional approach, Yadid and his team use behavioral models in combination with neurochemical and molecular methods to investigate the altered brain pathways behind these psychiatric disorders.
In their work on drug addiction, Yadid’s group utilizes three behavioral models to test new intervention approaches for drug seeking behavior: Conditioned Place Preference (CPP), Self-Administration, and Incubation of Craving. They are currently focused on three primary treatment modalities for this disorder.
The first is based on the administration of β-endorphin, which was found to decrease the heightened stress response associated with the compulsive behavior of the substance abuser.
The second is based on administration of the neurosteroid food supplement, DHEA, a compound they have shown to attenuate the recovering addict’s extinction response characterized by craving, drug-seeking behavior, and relapse. Yadid’s team has completed one clinical trial with DHEA and plans to conduct additional studies in a larger group of subjects in rehabilitation centers.
The third, non-pharmacological treatment modality they are exploring for drug addiction is Deep Brain Stimulation (DBS), which has traditionally been used in neurological disorders such as Parkinson’s disease. DBS involves implanting electrodes in a precise area of the brain, then using high-frequency continuous electrical current to stimulate activity in a neural circuit. They have demonstrated that in cocaine addicts, short duration DBS in the lateral habenula region of the brain results in a significant decrease in drug self-administration and relapse.
Current treatment regimens for clinical depression aimed solely at improving serotonergic or noradrenergic tone have limited efficacy. This is partly due to the fact that this disorder is characterized by a combination of symptoms, including anhedonia and loss of motivation, which are known to involve dopaminergic neurotransmission.
Yadid and his team are exploring the use of dopaminergic agents to augment the efficacy of known serotonin-based drugs. They are also investigating the use of DBS to stimulate dopaminergic neuronal activity in the ventral tegmental area (VTA) of the brain. The group has demonstrated preliminary results in achieving rapid onset, long-term improvement using acute stimulation, as opposed to continuous stimulation used in conventional DBS methods. Their technique utilizes a programmed pattern based on computational neuroscience that is designed to mimic brain activity in healthy individuals.
Post Traumatic Stress Disorder
Yadid’s team has established a new animal model designed to mimic the three primary manifestations of PTSD: re-experiencing the traumatic event, avoidance and numbing, and increased anxiety and emotional arousal.
In their innovative model, an animal is periodically exposed to a reminiscent stimulus, after which the intensity of these cluster behaviors is measured. In addition, they have identified a novel gene candidate, WFS1, associated with a significantly higher incidence of PTSD, and are exploring its predictive value for determining individuals at risk.