The current system of psychiatric diagnosis does not include characteristics that delineate patterns of symptoms, severity of illness or prognostic features. This greatly hinders progress in our understanding of mental illness and development of more specific treatments. The deficit syndrome is thought to be a more homogeneous subgroup of schizophrenia that is characterized by primary and enduring negative symptoms. It is associated with greater global impairment, lower quality of life, and poorer long-term outcome. We propose to use multimodal neuroimaging to study 20 schizophrenia patients with the deficit syndrome, 20 schizophrenia patients without the deficit syndrome, and 20 matched healthy controls. We will use (1) Diffusion Tensor Imaging to measure structural white matter integrity, (2) Magnetic Resonance Spectroscopy to measure neurometabolic white matter integrity, and (3) resting state functional MRI to measure functional connectivity to test the hypotheses that white matter integrity and related functional connectivity patterns differ between deficit and non-deficit schizophrenia. Using complementary neuroimaging techniques will allow generating a broad characterization of structural and neurometabolic white matter abnormalities and their functional consequences in the deficit syndrome. The results of proposed study might not only lead to identification of biomarkers that can assist in identification of patients at risk for developing the deficit syndrome before the clinical picture manifests, it will also provide the training necessary to prepare the candidate for an independent research career with focus on translational research in psychotic disorders.
The deficit syndrome is a subtype of schizophrenia that is associated with greater global impairment, lower quality of life, and poorer long-term prognosis. Abnormal white matter development may result in specific white matter integrity and resulting functional connectivity abnormalities in deficit schizophrenia. If successful, this study will provde neuroimaging biomarkers that could be utilized to identify patients who are at risk for developing the deficit syndrome before the clinical picture emerges.
| Kraguljac, Nina Vanessa; Carle, Matthew; Frölich, Michael A et al. (2018) Mnemonic Discrimination Deficits in First-Episode Psychosis and a Ketamine Model Suggests Dentate Gyrus Pathology Linked to N-Methyl-D-Aspartate Receptor Hypofunction. Biol Psychiatry Cogn Neurosci Neuroimaging 3:231-238 |
| Birur, Badari; Kraguljac, Nina Vanessa; Shelton, Richard C et al. (2017) Brain structure, function, and neurochemistry in schizophrenia and bipolar disorder-a systematic review of the magnetic resonance neuroimaging literature. NPJ Schizophr 3:15 |
| Kraguljac, N V; Frölich, M A; Tran, S et al. (2017) Ketamine modulates hippocampal neurochemistry and functional connectivity: a combined magnetic resonance spectroscopy and resting-state fMRI study in healthy volunteers. Mol Psychiatry 22:562-569 |
