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270. White Matter Microstructure and Cognition in Early Schizophrenia
Biological Psychiatry
Thursday Abstracts
Keywords: structural neuroimaging, Schizophrenia, Diffusion Tensor Imaging (DTI), Auditory Hallucination
Beth-Israel Deaconess Hospital, 2Beth Israel Deaconess Medical Center, 3McLean Hospital/Harvard Medical School
270. White Matter Microstructure and Cognition in Early Schizophrenia
Background: In patients with chronic psychotic disorders, the severity of ‘negative symptoms’ of schizophrenia (e.g. apathy, social withdrawal, and amotivation) is the strongest predictor of functional outcomes such as employment and educational attainment. Existing antipsychotic medications are not effective in ameliorating these symptoms. Despite the significant impact of these symptoms, and the lack of pharmacologic interventions, our understanding of their pathophysiology is limited. We sought to better understand how these symptoms are related to neural circuit dysfunction. Methods: We sought to understand how negative symptoms of schizophrenia are reflected in spontaneous brain network dynamics. We clinically characterized and collected ‘resting state’ functional Magnetic Resonance Imaging scans from a cohort of 71 subjects with schizophrenia or schizoaffective disorder. We applied a data-driven approach to these data using Multivariate Distance Matrix Regression (MDMR) to identify brain regions whose connectivity varies with the severity of negative symptoms as measured by the PANSS. Results: This analysis revealed that dysconnectivity between the frontal (BA10) and parietal cortices strongly correlated (P,.0001) with negative symptom severity. This correlation remained highly significant despite correction for movement and medication effects. This dysconnectivity was not related to the severity of positive symptoms of schizophrenia or mood symptoms. Conclusions: Here we demonstrate that dysconnectivity in large scale fronto-parietal networks is associated with the severity negative symptoms of schizophrenia. This finding does not appear to be related to other symptoms of psychosis or mood disorders. The localization of the anatomical deficit is consistent with substantial literature implicating frontal pole lesions with amotivation and apathy. Supported By: NIMH 5 K23 MH100623; Taplin Family Foundation Keywords: Negative Symptoms, Schizophrenia, Schizoaffective disorder, resting state functional MRI
Sinead Kelly1, Olivia Lutz2, Daniel Berman2, Li Yao2, Synthia Guimond2, Luke Mike2, Heidi Thermenos2, Marek Kubicki3, Shaun Eack4, and Matcheri Keshavan5 1
Beth Israel Deaconess Med. Ctr. & Harvard Medical School, 2Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, 3Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, 4University of Pittsburgh School of Social Work, 5Harvard Medical School
Background: White matter (WM) alterations have been characterised in schizophrenia. In this study we aim to delineate WM alterations and their association with cognition in the early stages of the disorder. This sample is part of an on-going, longitudinal treatment project, examining neurological changes during cognitive remediation therapy. We are reporting baseline results for biological markers to later assess during treatment. Methods: We analyzed DTI data from 18 controls and 40 schizophrenia patients (diagnosis , 8 years). Mean age525.02 years (SD54.41) and 39 males.: Fractional anisotropy (FA) maps were analysed using ENIGMA-DTI protocols. FA for six WM regions of interest were extracted. A MANCOVA model was used to test for case/control FA differences, covarying for age and sex. Partial correlations between FA, MATRICS Battery and The Awareness of Social Inference Test (TASIT) were conducted. Results: No significant case/control differences were observed for FA. For patients, positive correlations between FA and verbal learning were observed in the anterior limb of internal capsule (ALIC (R50.45; p50.01)) and splenium of corpus callosum (R50.38, p50.034). A positive correlation was observed between FA of the ALIC and TASIT (R50.38, p50.019). Results did not survive Bonferroni correction. Conclusions: We observed no significant case/controls differences in FA. As data collection is ongoing, future analyses may be better powered to detect WM differences. The strongest association for FA and cognition was observed in the ALIC that connects the thalamus and frontal cortex. Future analyses of this data may help to identify regions of WM that are susceptible to change during cognitive therapy. Supported By: NIMH RO1 MH 92440 Keywords: Schizophrenia, Cognitive Remediation, Diffusion Tensor Imaging (DTI), Neurocognition, Social Cognition
271. Negative Symptoms of Schizophrenia and FrontoParietal Circuit Dysfunction Roscoe Brady1, Neeraj Tandon2, Matcheri Keshavan2, and Dost Ongur3
1
272. Ventricles, Corpus Callosum and MIR137 in Large N Study of Schizophrenia Elisabetta del Re1, Gabriëlla Blokland2, Tracey Petryshen3, Ofer Pasternak4, Yogesh Rathi4, Martha Shenton4, and Robert McCarley5 1 Harvard Medical School-VA Boston HealthCare System, 2 Center for Human Genetic Research, Massachusetts General Hospital, 3Massachusetts General Hospital, 4Brigham & Women's Hospital, Harvard Medical School, 5Harvard Medical School Background: There is an unexplored convergence of data on lateral ventricles and corpus callosum abnormalities with impaired functioning and cognition in schizophrenia (SZ) that points to a unique opportunity to identify SZ subgroups in relation to genetics, particularly the schizophrenia GWAS risk gene miR137. We present here a recently funded NIH study (September 26, 2016), that is focused on exploring this convergence.
Biological Psychiatry May 15, 2017; 81:S1–S139 www.sobp.org/journal
S111
Thursday Abstracts
Keywords: structural neuroimaging, Schizophrenia, Diffusion Tensor Imaging (DTI), Auditory Hallucination
Beth-Israel Deaconess Hospital, 2Beth Israel Deaconess Medical Center, 3McLean Hospital/Harvard Medical School
270. White Matter Microstructure and Cognition in Early Schizophrenia
Background: In patients with chronic psychotic disorders, the severity of ‘negative symptoms’ of schizophrenia (e.g. apathy, social withdrawal, and amotivation) is the strongest predictor of functional outcomes such as employment and educational attainment. Existing antipsychotic medications are not effective in ameliorating these symptoms. Despite the significant impact of these symptoms, and the lack of pharmacologic interventions, our understanding of their pathophysiology is limited. We sought to better understand how these symptoms are related to neural circuit dysfunction. Methods: We sought to understand how negative symptoms of schizophrenia are reflected in spontaneous brain network dynamics. We clinically characterized and collected ‘resting state’ functional Magnetic Resonance Imaging scans from a cohort of 71 subjects with schizophrenia or schizoaffective disorder. We applied a data-driven approach to these data using Multivariate Distance Matrix Regression (MDMR) to identify brain regions whose connectivity varies with the severity of negative symptoms as measured by the PANSS. Results: This analysis revealed that dysconnectivity between the frontal (BA10) and parietal cortices strongly correlated (P,.0001) with negative symptom severity. This correlation remained highly significant despite correction for movement and medication effects. This dysconnectivity was not related to the severity of positive symptoms of schizophrenia or mood symptoms. Conclusions: Here we demonstrate that dysconnectivity in large scale fronto-parietal networks is associated with the severity negative symptoms of schizophrenia. This finding does not appear to be related to other symptoms of psychosis or mood disorders. The localization of the anatomical deficit is consistent with substantial literature implicating frontal pole lesions with amotivation and apathy. Supported By: NIMH 5 K23 MH100623; Taplin Family Foundation Keywords: Negative Symptoms, Schizophrenia, Schizoaffective disorder, resting state functional MRI
Sinead Kelly1, Olivia Lutz2, Daniel Berman2, Li Yao2, Synthia Guimond2, Luke Mike2, Heidi Thermenos2, Marek Kubicki3, Shaun Eack4, and Matcheri Keshavan5 1
Beth Israel Deaconess Med. Ctr. & Harvard Medical School, 2Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, 3Psychiatry Neuroimaging Laboratory, Brigham and Women’s Hospital, Harvard Medical School, 4University of Pittsburgh School of Social Work, 5Harvard Medical School
Background: White matter (WM) alterations have been characterised in schizophrenia. In this study we aim to delineate WM alterations and their association with cognition in the early stages of the disorder. This sample is part of an on-going, longitudinal treatment project, examining neurological changes during cognitive remediation therapy. We are reporting baseline results for biological markers to later assess during treatment. Methods: We analyzed DTI data from 18 controls and 40 schizophrenia patients (diagnosis , 8 years). Mean age525.02 years (SD54.41) and 39 males.: Fractional anisotropy (FA) maps were analysed using ENIGMA-DTI protocols. FA for six WM regions of interest were extracted. A MANCOVA model was used to test for case/control FA differences, covarying for age and sex. Partial correlations between FA, MATRICS Battery and The Awareness of Social Inference Test (TASIT) were conducted. Results: No significant case/control differences were observed for FA. For patients, positive correlations between FA and verbal learning were observed in the anterior limb of internal capsule (ALIC (R50.45; p50.01)) and splenium of corpus callosum (R50.38, p50.034). A positive correlation was observed between FA of the ALIC and TASIT (R50.38, p50.019). Results did not survive Bonferroni correction. Conclusions: We observed no significant case/controls differences in FA. As data collection is ongoing, future analyses may be better powered to detect WM differences. The strongest association for FA and cognition was observed in the ALIC that connects the thalamus and frontal cortex. Future analyses of this data may help to identify regions of WM that are susceptible to change during cognitive therapy. Supported By: NIMH RO1 MH 92440 Keywords: Schizophrenia, Cognitive Remediation, Diffusion Tensor Imaging (DTI), Neurocognition, Social Cognition
271. Negative Symptoms of Schizophrenia and FrontoParietal Circuit Dysfunction Roscoe Brady1, Neeraj Tandon2, Matcheri Keshavan2, and Dost Ongur3
1
272. Ventricles, Corpus Callosum and MIR137 in Large N Study of Schizophrenia Elisabetta del Re1, Gabriëlla Blokland2, Tracey Petryshen3, Ofer Pasternak4, Yogesh Rathi4, Martha Shenton4, and Robert McCarley5 1 Harvard Medical School-VA Boston HealthCare System, 2 Center for Human Genetic Research, Massachusetts General Hospital, 3Massachusetts General Hospital, 4Brigham & Women's Hospital, Harvard Medical School, 5Harvard Medical School Background: There is an unexplored convergence of data on lateral ventricles and corpus callosum abnormalities with impaired functioning and cognition in schizophrenia (SZ) that points to a unique opportunity to identify SZ subgroups in relation to genetics, particularly the schizophrenia GWAS risk gene miR137. We present here a recently funded NIH study (September 26, 2016), that is focused on exploring this convergence.
Biological Psychiatry May 15, 2017; 81:S1–S139 www.sobp.org/journal
S111