- Email: [email protected]
969. Altered Functional Organization in Schizophrenia
Biological Psychiatry
Saturday Abstracts
Background: 22q11.2 deletion syndrome (22q11DS) is a genotype with high penetrance for schizophrenia spectrum disorders. Study of individuals with 22q11DS therefore provides an important causal window into the relationship between the genetic, neural, and behavioral correlates of schizophrenia. Resting-state fMRI Studies in schizophrenia have consistently revealed thalamic and hippocampal neural dysconnectivity. It remains unknown if similar effects can be observed in 22q11DS. Methods: A sample of youth with 22q11DS (n542) and demographically matched healthy controls (n539) were recruited and evaluated for psychotic symptoms. Neuroimaging data were acquired via single-band protocols but analyzed in line with methods provided by the Human Connectome Project (HCP). We computed functional relationships between individual-specific anatomicallydefined thalamic and hippocampal seeds and all gray matter vertices in CIFTI grayordinate space. Whole-brain type 1 error protection was achieved through nonparametric permutationbased methods. Results: 22q11DS patients displayed reciprocal disruptions in thalamic and hippocampal functional connectivity relative to controls. Thalamo-cortical coupling was increased in sensorimotor cortex, and reduced across associative networks. The opposite effect was observed for the hippocampus in regards to sensory and associative network connectivity. Conclusions: Thalamic and hippocampal dysconnectivity observed in 22q11DS suggest that high genetic risk for psychosis is linked with disruptions in large-scale corticosubcortical networks, similar to those reported in schizophrenia and in pharmacological models of psychosis. These effects highlight the translational importance of genetic deletion syndromes for informing mechanisms underlying neural disruptions observed in idiopathic schizophrenia. Keywords: 22q11 Deletion Syndrome, Schizophrenia, Thalamus, Hippocampus, Resting state functional connectivity
969. Altered Functional Organization in Schizophrenia Saba Shahab1, Erin Dickie2, Joseph D. Viviano2, George Foussias2, and Aristotle Voineskos3 1
Center for Addiction and Mental Health, University of Toronto, 2Centre for Addiction and Mental Health, 3 University of Toronto Background: Current research has shown that registration using resting-state connectivity data may provide a more accurate understanding of the functional organization of the brain. Schizophrenia is a heterogeneous disorder and patients with schizophrenia may have a different functional organization than controls. This has been explored in autism spectrum disorder but no work has been done in schizophrenia. Methods: Resting-state fMRI scans were collected on a 3T scanner for 56 patients and 56 controls, age and sex
S392
matched. A novel method was used to identify individualized locations of 80 regions-of-interest (ROI) by maximizing their correlation within 6 core intrinsic networks. To determine if patients’ node locations were different from controls, a manova using vertex coordinates was conducted. To assess variability in functional organization, an anova was conducted using euclidean distance summed across ROIs within a network. Age, sex, education, and mean framewise displacement were included as covariates in both analyses. Results: The dorsal attention node in the temporal lobe (F1,11058.07, p50.00055, q50.04) is located more posterior and anterior in patients than in controls. Patients have a more variable functional organization in the dorsal attention (F1,11054.04, p50.046) and the somatomotor (F1,11054.28, p50.041) networks. Conclusions: Patients have a shift in the temporal lobe ROI of the dorsal attention network and increased variability in the organization of two networks. Future work will involve replicating this result and using graph theoretical measures to evaluate how this finding affects network interactions. Supported By: NIH R01 Keywords: Schizophrenia, Resting state functional connectivity, fMRI resting state
970. Binge Drinking Associated with Hippocampal Structural and Functional Abnormalities in Adults with a History of Childhood Adversity Jonathan Ipser, Dan J. Stein, Hetta Gouse, Carla Freeman, and John Joska University of Cape Town Background: Although both exposure to early life adversity and alcoholism have been associated with abnormalities in hippocampal structure and function, there are no published studies assessing whether heavy episodic drinking (HED) and early life adversity in adults interact to predict differences in hippocampal volume and intrinsic functional connectivity, the purpose of the current study. Methods: Multiple regression tests were employed to compare age and gender adjusted Childhood Trauma Questionnaire (CTQ) total scores between 35 HED participants and 22 light or non-drinking (LND) adult subjects recruited from a community clinic in Cape Town. For a subset of 30 participants (HED519, LND511), hippocampal volumes were extracted from T1 scans using FreeSurfer (v. 5.3), and intrinsic functional connectivity BOLD data processed with AFNI. Results: No differences were observed between the HED and LND groups in CTQ scores or hippocampal volumes. Nevertheless, in the HED group higher CTQ total scores predicted smaller left hippocampi (Spearman rho5-0.586, p , 0.01 vs. rho50.296, p . 0.1 for LND) and increased functional connectivity between the bilateral hippocampus and clusters in the right posterior cingulate cortex and left inferior parietal cortex (FWE corrected, voxel alpha50.005, cluster extent529 3mm3 voxels).
Biological Psychiatry May 15, 2017; 81:S277–S413 www.sobp.org/journal
Saturday Abstracts
Background: 22q11.2 deletion syndrome (22q11DS) is a genotype with high penetrance for schizophrenia spectrum disorders. Study of individuals with 22q11DS therefore provides an important causal window into the relationship between the genetic, neural, and behavioral correlates of schizophrenia. Resting-state fMRI Studies in schizophrenia have consistently revealed thalamic and hippocampal neural dysconnectivity. It remains unknown if similar effects can be observed in 22q11DS. Methods: A sample of youth with 22q11DS (n542) and demographically matched healthy controls (n539) were recruited and evaluated for psychotic symptoms. Neuroimaging data were acquired via single-band protocols but analyzed in line with methods provided by the Human Connectome Project (HCP). We computed functional relationships between individual-specific anatomicallydefined thalamic and hippocampal seeds and all gray matter vertices in CIFTI grayordinate space. Whole-brain type 1 error protection was achieved through nonparametric permutationbased methods. Results: 22q11DS patients displayed reciprocal disruptions in thalamic and hippocampal functional connectivity relative to controls. Thalamo-cortical coupling was increased in sensorimotor cortex, and reduced across associative networks. The opposite effect was observed for the hippocampus in regards to sensory and associative network connectivity. Conclusions: Thalamic and hippocampal dysconnectivity observed in 22q11DS suggest that high genetic risk for psychosis is linked with disruptions in large-scale corticosubcortical networks, similar to those reported in schizophrenia and in pharmacological models of psychosis. These effects highlight the translational importance of genetic deletion syndromes for informing mechanisms underlying neural disruptions observed in idiopathic schizophrenia. Keywords: 22q11 Deletion Syndrome, Schizophrenia, Thalamus, Hippocampus, Resting state functional connectivity
969. Altered Functional Organization in Schizophrenia Saba Shahab1, Erin Dickie2, Joseph D. Viviano2, George Foussias2, and Aristotle Voineskos3 1
Center for Addiction and Mental Health, University of Toronto, 2Centre for Addiction and Mental Health, 3 University of Toronto Background: Current research has shown that registration using resting-state connectivity data may provide a more accurate understanding of the functional organization of the brain. Schizophrenia is a heterogeneous disorder and patients with schizophrenia may have a different functional organization than controls. This has been explored in autism spectrum disorder but no work has been done in schizophrenia. Methods: Resting-state fMRI scans were collected on a 3T scanner for 56 patients and 56 controls, age and sex
S392
matched. A novel method was used to identify individualized locations of 80 regions-of-interest (ROI) by maximizing their correlation within 6 core intrinsic networks. To determine if patients’ node locations were different from controls, a manova using vertex coordinates was conducted. To assess variability in functional organization, an anova was conducted using euclidean distance summed across ROIs within a network. Age, sex, education, and mean framewise displacement were included as covariates in both analyses. Results: The dorsal attention node in the temporal lobe (F1,11058.07, p50.00055, q50.04) is located more posterior and anterior in patients than in controls. Patients have a more variable functional organization in the dorsal attention (F1,11054.04, p50.046) and the somatomotor (F1,11054.28, p50.041) networks. Conclusions: Patients have a shift in the temporal lobe ROI of the dorsal attention network and increased variability in the organization of two networks. Future work will involve replicating this result and using graph theoretical measures to evaluate how this finding affects network interactions. Supported By: NIH R01 Keywords: Schizophrenia, Resting state functional connectivity, fMRI resting state
970. Binge Drinking Associated with Hippocampal Structural and Functional Abnormalities in Adults with a History of Childhood Adversity Jonathan Ipser, Dan J. Stein, Hetta Gouse, Carla Freeman, and John Joska University of Cape Town Background: Although both exposure to early life adversity and alcoholism have been associated with abnormalities in hippocampal structure and function, there are no published studies assessing whether heavy episodic drinking (HED) and early life adversity in adults interact to predict differences in hippocampal volume and intrinsic functional connectivity, the purpose of the current study. Methods: Multiple regression tests were employed to compare age and gender adjusted Childhood Trauma Questionnaire (CTQ) total scores between 35 HED participants and 22 light or non-drinking (LND) adult subjects recruited from a community clinic in Cape Town. For a subset of 30 participants (HED519, LND511), hippocampal volumes were extracted from T1 scans using FreeSurfer (v. 5.3), and intrinsic functional connectivity BOLD data processed with AFNI. Results: No differences were observed between the HED and LND groups in CTQ scores or hippocampal volumes. Nevertheless, in the HED group higher CTQ total scores predicted smaller left hippocampi (Spearman rho5-0.586, p , 0.01 vs. rho50.296, p . 0.1 for LND) and increased functional connectivity between the bilateral hippocampus and clusters in the right posterior cingulate cortex and left inferior parietal cortex (FWE corrected, voxel alpha50.005, cluster extent529 3mm3 voxels).
Biological Psychiatry May 15, 2017; 81:S277–S413 www.sobp.org/journal