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Esther Sabban, Ph.D., professor of biochemistry and molecular biology, at New York Medical College (NYMC), has spent decades researching the mechanisms of stress and stress-related neuropsychiatric disorders with the goal of both reducing their prevalence and providing new avenues of treatment. Most recently, Dr. Sabban’s research has focused on the use of neuropeptide Y (NPY), an endogenous peptide produced in the brain, to counter Post-Traumatic Stress Disorder (PTSD) associated behavioral and biochemical impairments, as well as sex differences in stress response, with promising results.

“PTSD is a mental health condition triggered by experiencing or witnessing a terrifying event that can lead to lifelong burden that increases mortality and adverse health outcomes. Yet, no new treatments have reached the market in two decades. Thus, screening potential interventions for PTSD is of high priority,” says Dr. Sabban.

In recent preclinical studies, which were funded by two consecutive grants by the US Army, Dr. Sabban and her lab looked at the intranasal delivery of NPY, one of the most prevalent peptides in the body, which is shown to attenuate many of the harmful effects of stress and has far-reaching effects both in the central nervous system and the periphery.

“Current pharmacological treatment for stress-related neuropsychiatric disorders includes selective serotonin reuptake inhibitors (SSRIs), which take weeks to elicit an effect and reduce symptom severity rather than leading to remission of the disorders,” said Dr. Sabban.

Through the use of a single prolonged stress (SPS) model, Dr. Sabban found that delivering NPY intranasally, which delivers it to a wide range of brain regions involved in mediating the response to stress, slightly before or immediately after the stress, prevented development of many of the behavioral and molecular impairments, including anxiety, impaired social interaction, depressive-like behavior, hyperarousal, increase in plasma glucocorticoids and gene expression of the glucocorticoid receptor in the hippocampus  and several other stress-related genes in the brain.  Intranasal NPY was also effective in not only preventing but also reversing many of these deficits.

Dr. Sabban is now in the process of translating these findings to humans and setting up a clinical trial.

Another key area that Dr. Sabban and her fellow researchers, which includes Roxanna Nahvi, a student in the MD/PhD program at NYMC, have been examining is the sex differences in stress response.

“The susceptibility to stress-elicited disorders is markedly influenced by sex,” said Ms. Nahvi, who served as lead author on two of the studies. “Women are twice as likely as men to develop many stress-triggered disorders, such as PTSD, depression, anxiety and eating disorders. However, most of the studies examining putative therapeutics for stress-triggered impairments, including SPS, were performed predominantly with males.”

With NPY emerging as a promising therapeutic target for neuropsychiatric disorders, Dr. Sabban and Ms. Nahvi subsequently determined through their research that females may require a much higher dose of intranasal NPY to prevent behavioral and biochemical impairments, which could be one of reasons for greater risk of women for many stress-triggered disorders.

“A preponderance of literature indicates that NPY concentrations in the brain are lower in females than in males under both basal and stressed conditions,” said Ms. Nahvi. “This suggests that either the depressed NPY system in females may be less important for stress regulation or may contribute to their higher prevalence of stress-related disorders. Further investigation could shed new light on the mechanisms behind the heightened susceptibility of females to stress-triggered neuropsychiatric disorders and approaches to therapeutic interventions.”