Project Details

Description

Schizophrenia spectrum disorders and suicidal behavior are major public health problems affectingVeterans. Each year, the VA provides care to approximately 100,000 schizophrenia patients, accounting fornearly 12% of the VA’s total healthcare costs. At the same time, recent studies indicate that Veterans exhibithigher suicide risk compared with the general U.S. population. The PI’s ongoing clinical cognitive neuroscienceresearch at the VA uses neuroimaging and psychophysiological approaches and primarily focuses on thesetwo areas: elucidating the neurobiology of schizophrenia and suicidal behavior. Identification of promising newtargets for intervention in schizophrenia and suicide prevention are critically important goals of the VA. The PI’strack record of federal funding and peer-reviewed publications in these two areas has helped advance the field. The PI’s new VA CSR&D Merit Award aims to identify the neural correlates and psychophysiology of normalemotional reactivity and regulation in healthy control Veterans and pathological severity of emotiondysregulation in Veterans with major depressive disorder (MDD) at low (non-suicidal psychiatric controls) andhigh-risk (suicidal ideators and suicide attempters) for suicide. Participants receive baseline functional MRIscans and a psychophysiological paradigm that provides a reliable, non-verbal, low-cost measure of emotionprocessing (i.e. affective startle modulation). The psychophysiology session is repeated at a 6-month follow-up;clinical symptom assessments are done at baseline, 6-, and 12-month follow-up. Understanding brain circuitryanomalies underlying dysregulated emotional expression and psychological mediators that give rise to andpredict suicidal behavior and distinguish between ideators and attempters has clear public health importance.This newly-funded VA Merit study promises to help uncover the mechanisms by which biological andpsychological factors give rise to suicidal behavior and may aid in prospectively identifying Veterans at greatestrisk for suicide. The goal of the PI’s current schizophrenia-spectrum research (funded by her previous VA CSR&D MeritAward) is to begin to translate pre-clinical scientific research in schizophrenia into the clinical arena. In order toidentify promising new targets for intervention in schizophrenia, a better understanding of its pathologicalcircuitry and underlying genetic susceptibilities is required. Her work uses diffusion tensor imaging (DTI) andstructural MRI to characterize white matter abnormalities in frontal-temporal regions. DTI fiber tractographyallows quantification of the integrity of white matter connectivity in the brain. Various susceptibility genes areimplicated in white matter abnormalities and schizophrenia (e.g., NRG1 and ERBB4). Together with hermultidisciplinary VA-Icahn School of Medicine at Mount Sinai (ISMMS) colleagues who bring expertise ingenetics, the PI’s work investigates a model of white matter disorganization in schizophrenia. Data arecurrently being analyzed and published from her recent VA Merit study of 60 individuals with schizotypalpersonality disorder (SPD) and 60 healthy controls who received MRI and were genotyped. This workevaluates white matter organization and examines the relationship between white matter connectivity(fractional anisotropy and tractography DTI measures), white matter volume (structural MRI), allelic variation intwo underlying susceptibility genes (NRG1 and ERBB4), and cognitive impairment/deficit symptoms across thespectrum. SPD participants are studied as our choice of phenotype as they represent a form of schizophreniawithout the confounding artifacts of chronic antipsychotic treatment, long-term psychosis, and hospitalization. Impact: This Research Career Scientist Award will allow the PI to augment her highly collaborative VAresearch and mentoring of promising VA MIRECC fellows and clinician-scientists. The PI’s current VA Merit isthe first study at the JJPVAMC to conduct research 3T MRI scans. The PI’s goal is to further expand her MRIresearch program in schizophrenia and suicidal behavior at the JJPVAMC.

StatusActive
Effective start/end date1/04/1831/03/23

Funding

  • U.S. Department of Veterans Affairs: $174,057.00

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