Student Profile: Christen Crosta

Research Summary
As of yet, we diagnose psychiatric illnesses based on behavioral phenotypes. Moreover, we prescribe medications in a trial-and-error fashion and simply treat some symptoms, but we do not address the underlying causes of the disease. Understanding the molecular and genetic causes of psychiatric illness could allow for individualized pharmacological therapies to remedy altered molecular processes, which result in the disease phenotype. My research, focused on the molecular and genetic etiology of schizophrenia, will provide basic biological insight necessary to create more effective treatments. The glutamate hypothesis of schizophrenia suggests that positive (delusions and hallucinations), negative (flat affect, avolition, and social withdrawal), and cognitive (deficits in executive functions such as working memory, attention and decision making) symptoms of the disease are caused by reduced N-methyl-D-aspartate receptor (NMDAR) signaling. Nitric oxide synthase 1 adaptor protein (NOS1AP) negatively regulates NMDAR signaling by disrupting downstream signaling. Previous work from the Firestein Lab demonstrated that dorsolateral prefrontal cortex postmortem tissue from patients with schizophrenia express higher levels of all three NOS1AP isoforms (L, S, S’) when compared to tissue from healthy controls. In addition, the Firestein Lab identified two rare, schizophrenia-associated NOS1AP single nucleotide polymorphisms (SNPs) in a buccal cell sample from a patient with schizophrenia. This patient also had elevated levels of buccal cell NOS1AP. While working with our collaborators at the Silverstein Lab, I used Optical Coherence Tomography (OCT) to study retinal thinning in patients with schizophrenia. We found that patients with chronic schizophrenia had significantly thinner maculae in both eyes when compared to age-matched controls, while first episode patients, individuals who first experienced psychotic symptoms no more than two years ago, did not. Moreover, chronically ill patients had significantly thinner maculae than did first episode patients. Currently, I am working to build upon these two areas of research by collecting buccal cell samples from all participants in the OCT study. In this project, we aim to investigate the relationship between the following variables: SNPs in the promoter region of NOS1AP, including the two new SNPs identified by the Firestein Lab, epithelial NOS1AP mRNA and protein levels, retinal structure, clinical symptoms, and cognitive function. It is my goal that this work will help to identify important biomarkers of schizophrenia and elucidate the molecular mechanisms behind disease progression.