The Intergenerational Exposome Program (IGNITE)
There is a new exciting collaboration between PENN OBGYN and the CHOP/Lifespan Brain Institute (LiBl)! This new collaboration seeks to understand the influence of environmental exposures, starting with prenatal exposures, have on developmental trajectories. The IGNITE workgroup, led by Raquel Gur, MD, PhD and colleagues, is currently conducting a longitudinal study of approximately 900 diverse women recruited during pregnancy at the start of the COVID-19 pandemic. Virtual assessments will take place with a subgroup of these women and their 12 month old children. The study's analysis will focus on the relationship between COVID related exposures, distress, mental health, environmental risk factors, racial disparities, and the influence these factors have on children's developmental trajectories. The aim is to identify modifiable risk and resilience factors that impact maternal and child mental health, laying the groundwork for culturally-informed interventions. Congratulations to all the DCAPBS and LiBl investigators who are doing this exciting work!
Fine-tuning Disrupted Brain Circuitry With Focal Gene Therapy
Collaborative research between DCAPBS developmental neurobiologist and psychiatrist Stewart Anderson and pediatric neurology brain circuitry of epilepsy researcher Doug Coulter: Fine-tuning Disrupted Brain Circuitry With Focal Gene Therapy. Drs. Anderson and Coulter have been studying an experimental model of the 22q11.2 deletion syndrome, a relatively common genetic mutation associated with intellectual disability, attentional and learning challenges, and a highly increased risk of schizophrenia. The animals experience similar cognitive disruptions, including weakness in both social and spatial memory. Recordings from brain slices discovered that these disruptions were associated with elevated but "noisier" activity in a part of the forebrain called the hippocampus. The team then used an adeno-associated virus, an approach currently approved for gene therapy in humans for example in blindness, to focally introduce an artifical receptor that is expressed in those same brain cells that were hyperactive. Exposure of the animals to a "designer drug" that only activates the artificial receptor results in an reduced excitatory activity by those previously hyperactive cells. This reduction could be fine-tuned by varying the amount of the designer drug provided. Remarkably, the team was able to find a dose range that successfully normalized the spatial memory problems in adult 22q11.2 deletion in animals. Correcting symptom-related behavioral abnormalities by focal, and tunable, gene therapy targeting specific brain circuits has tremendous promise for future studies aimed at both prevention and treatment of medication-resistant pediatric neuopsychiatric disorders.This work has recently been published in the journal of Biological Psychiatry and was recently chosen for a Cornerstone article.