The Role of the Maladaptive Stress Response in Mediating the Onset of Psychosis

 

Trainee:

Elizabeth Andersen

anderson

Research Mentor:

Ayse Belger

Belger

Clinical Co-mentor:

Diana Perkins

perkins
Home Department Neurobiology
Project Description Schizophrenia results from a combination of genetic and environmental insults, which through altered signaling pathways, are thought to cause reductions in dendritic spine density, deficiencies in synaptic transmission and ultimately, compromise the construction of neural circuitry. The synaptic pathologies observed in schizophrenia are potentially aggravated by environmental factors such as stress. Stress interferes with already vulnerable circuitry in schizophrenia patients to intensify cortical atrophy and threaten neural network integrity. The goal of my dissertation project in Dr. Aysenil Belger’s lab, and my research training under the Howard Hughes Translational Medicine fellowship, is to investigate the dynamic processes that mediate illness onset. To assess the neurobiological substrates of the stress response in healthy adolescents and adolescents at high risk for developing psychiatric illness, I employ a multimodal approach involving electrophysiological scalp recordings and functional magnetic resonance imaging (fMRI), as well as peripheral psychophysiological and neuroendocrine measurements. Evaluating cortical maturation and the progression of the maladaptive stress response in high risk adolescents prior to illness onset allows us to elucidate the neural mechanisms underlying the emergence of psychosis, the influence of stress exposure on symptom exacerbation, and the expression of cognitive and affective processing deficits without medication or symptom interference. Advancing our understanding of the pathophysiology of psychosis onset in vulnerable individuals will facilitate the development of innovative treatment approaches and potentially improve intervention strategies. I am also interested in examining intranasal oxytocin administration as an intervention strategy for relieving symptom precipitation in adolescents at risk for psychosis. Intranasal oxytocin administration is a low risk and minimally invasive intervention approach that may weaken the aversive effects of stress exposure on neural circuitry development and support decreased disease vulnerability in genetically high risk individuals. Furthermore, by shadowing Dr. Diana Perkins on her psychiatric rounds, participating in clinical research conferences, and learning how to administer clinical diagnostic assessments, I have the opportunity to observe and appreciate the complex heterogeneity of symptoms manifested in psychiatric disorders, and witness the potential implications of my research in clinical populations.