Resting State Functional Magnetic Resonance Imaging Alterations In Psychosis Spectrum Disorders




Samudra, Niyatee

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BACKGROUND: Many psychiatric disorders, especially those on the psychosis spectrum, are as yet without good diagnostic and treatment options. Neuroimaging research, most recently research into brain functional connectivity via resting-state fMRI, may provide a window into this problem, creating possibilities for discovering disease state-specific biomarkers important for diagnosis or to follow treatment efficacy. Hippocampal hyperactivity is known to be a feature of schizophrenia. The anterior hippocampus in particular, because of its structural connectivity relationships to frontal and limbic areas, may have specific connectivity alterations in psychosis spectrum disorders. In addition, it is important to understand whether putative changes in hippocampal functional connectivity are unique to a particular conventional (Diagnostic and Statistical Manual) psychosis disorder or whether they are present in multiple psychosis spectrum disorders, as this helps establish a biological foundation for psychosis. This work examines hippocampal functional connectivity changes in psychosis spectrum disorders in light of a possible imaging signature for psychosis. It is best understood in light of the work done by the Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium, a multi-site study group to establish imaging and molecular biomarkers across the psychosis dimension. OBJECTIVES: 1) To understand abnormal hippocampal connectivity and its targets in the rest of the brain in psychosis spectrum disorders. 2) To assess whether hippocampal connectivity changes are specific to one DSM diagnostic group or common across the psychosis spectrum. 3) To correlate hippocampal connectivity alterations with specific cognitive and clinical outcomes.
METHODS: We tested resting state connectivity in 88 participants with psychosis disorders (21 schizophrenia; 40 schizoaffective disorder; 27 psychotic bipolar I disorder) and 65 healthy controls. Image processing and seed-based, voxel-wise connectivity analyses were carried out in the Analysis of Functional Neuroimaging (AFNI) software package to understand differential connectivity in psychosis spectrum vs. healthy controls using whole, anterior, and posterior hippocampal seeds. Connectivity measures for psychosis participants, as assessed by z-scores, were correlated with multiple clinical and cognitive measures. RESULTS: We found no significant differences in hippocampal functional connectivity across the three DSM diagnoses tested, thus justifying combining the groups for an analysis versus healthy controls. For the whole psychosis group, there were strong reductions in anterior hippocampal connectivity to anterior neocortical regions, including medial frontal and anterior cingulate cortices, as well as to superior temporal gyrus, precuneus, thalamus and cerebellum. Posterior hippocampal seeds also demonstrated decreased connectivity in psychosis subjects, with fewer regions of altered connectivity and a predominantly posterior/cerebellar distribution. Whole hippocampal outcomes were consistent with anterior/posterior hippocampal connectivity changes. These changes did not correspond to measures of cognition, medication effect, or clinical symptoms. CONCLUSION: This research underlines the possibility of a neuroimaging signature for psychosis spectrum disorders consisting of decreased predominantly anterior hippocampal connectivity with frontal and temporal regions, among others. The changes observed do not seem to correspond to medication effect or demographic variables in our analysis, thereby suggesting a primary disease effect. Further research is necessary to establish a hippocampal network in psychosis which may serve as a biomarker, with implications for more definitive diagnosis and treatment response prediction.

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