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928. Cortical Abnormalities Associated with Pediatric and Adult Obsessive-Compulsive Disorder: Findings from the Enigma Obsessive-Compulsive Disorder Working Group
Biological Psychiatry
Saturday Abstracts
927. Subcortical Volume and Neural Connectivity in Youth with Psychosis Spectrum Symptoms Grace Jacobs1, Erin Dickie2, and Aristotle Voineskos1 University of Toronto, 2Centre for Addiction and Mental Health
1
Background: Altered subcortical region volumes, specifically in the thalamus and striatum, as well as cortico-thalamicstriatal-cortical (CTSC) connectivity have been observed in schizophrenia. Methods: In this study, structural magnetic resonance imaging was used in a child and youth sample (n5821) including children with psychosis spectrum (PS) symptoms (n5110) to further understanding of these biomarkers and their presentation in youth outside of high risk groups. Subfields of subcortical regions were identified using the segmentation tool MAGeTbrain. Correlations between these subfields and cortex-wide cortical thickness values were used to infer network connectivity. Results: Boys and girls were examined separately. Volumes of the globus pallidus and striatal subregions were found to be increasing in boys with PS, but not in typically developing male youth (right globus pallidus: r(TD)5-0.21, t(age by psychosis)5-2.38, p50.017). A similar increase in volumes in girls with PS was seen in thalamic subregions but not in those who were typically developing (left lateral dorsal area: r(PS)5 0.28, t(age by psychosis)5-2.95, p50.009). Preliminary analyses also indicate that putamen subregions in psychosis spectrum boys are negatively correlated with cortical thickness in the bank of superior temporal sulcus, precentral gyrus in the posterior frontal lobe and superior parietal lobe. Thalamic subregions in psychosis spectrum girls were negatively associated with cortical thickness in the insula. Conclusions: These findings indicate early alteration of neural circuitry in PS youth similar to what is observed in schizophrenia and provides the opportunity to improve on early interventions by targeting gender and critical developmental time points. Keywords: Structural MRI, Early psychosis, Connectivity, Subcortical, Sex-specific
928. Cortical Abnormalities Associated with Pediatric and Adult Obsessive-Compulsive Disorder: Findings from the Enigma Obsessive-Compulsive Disorder Working Group Premika Boedhoe1, Lianne Schmaal2, Paul Arnold3, Francesco Benedetti4, Jan Beucke5, Yuqi Cheng6, Damiaan Denys7, Kate Fitzgerald8, Patricia Gruner9, Marcelo Hoexter10, Chaim Huyser11, Anthony James12, Kathrin Koch13, Jun Soo Kwon14, Luisa Lazaro15, David Mataix-Cols16, Jose Menchon17, Takashi Nakamae18, Tomohiro Nakao19, Erika Nurmi20, Y. C. Janardhan Reddy20, H.Blair Simpson21, Noam Soreni22, Gianfranco Spalletta23, David Tolin24, Susanne Walitza25, Zhen Wang26, Paul Thompson27, Dan Stein28, and Odile van den Heuvel29
VU University Medical Center, 2Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, Australia, 3Mathison Centre for Mental Health Research & Education, Cumming School of Medicine, University of Calgary, 4Clinical Research Group Psychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milano, Italy, 5 Department of Psychology, Humboldt-Universität zu Berlin, 6Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China, 7Academical Medical Center, 8University of Michigan, 9Department of Psychiatry, Yale University School of Medicine, 10University of Sao Paulo - Medical School, 11De Bascule, Academic Center for Child and Adolescent Psychiatry, Amsterdam, the Netherlands, 12Department of Psychiatry, Oxford University, 13Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Germany, 14Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea, 15Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic Universitari, Barcelona, Spain, 16Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm, Sweden, 17Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain, 18Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan, 19Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, 20Obsessive-Compulsive Disorder (OCD) Clinic Department of Psychiatry National Institute of Mental Health & Neurosciences, Bangalore, India, 21Columbia University Medical College, Columbia University, 22Anxiety Treatment and Research Center, St. Joseph's Health Care, 23 Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy, 24Institute of Living/Hartford Hospital, 25 Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, 26 Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine, PR China, 27Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine of the University of Southern California, 28SU/UCT MRC Unit on Anxiety & Stress Disorders, Department of Psychiatry and Mental Health, University of Cape Town, South Africa, 29 Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands 1
Background: Brain imaging studies on structural abnormalities in OCD have been inconsistent, partially due to limited statistical power, clinical heterogeneity, and methodological differences. Here, we present data of the largest study to date on cortical brain measures in OCD patients and healthy controls by using meta- and mega-analyses. Methods: Structural T1-weighted MRI scans including 1905 OCD patients and 1760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer 5.3. Effect
Biological Psychiatry May 15, 2017; 81:S277–S413 www.sobp.org/journal
S375
Biological Psychiatry
Saturday Abstracts
sizes for differences between patients and controls were calculated using linear regression models controlling for age and gender (and ICV). Results were considered significant if the P-value exceeded a significance threshold determined by the false discovery rate (FDR) procedure at q50.05. Results: In adult OCD patients (versus controls) we found significantly lower surface area in the transverse temporal cortex and thinner cortices in the inferior parietal cortex. Medicated adult OCD patients (versus controls) showed thinner cortices in the frontal and temporal lobes. In pediatric OCD patients (versus controls) we also found significant thinner cortices in the parietal lobe. None of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD (versus controls) showed widespread surface area differences in the frontal and parietal lobes. Conclusions: The parietal cortex was consistently implicated both in adults and children. We found widespread cortical thickness abnormalities in medicated adult OCD patients and widespread surface area deficits in medicated pediatric OCD patients. These measures represent distinct morphological features and may be differentially affected by OCD and possibly moderated by medication status. Supported By: NIH: BD2k (Big Data), U54 EB020403-02 (PI: Thompson) & Neuroscience Campus Amsterdam (NCA), IPBgrant (PI’s: Schmaal / van den Heuvel) Keywords: Obsessive Compulsive Disorder (OCD), Neuroimaging, FreeSurfer, Cortical thickness, Cortical surface area
attention load. Performance and brain activation were compared between groups. Results: A group by delay interaction analysis showed that OCD patients had disorder-specific underactivation in middle anterior cingulate, while ADHD patients showed disorder-specific underactivation in left dorsolateral prefrontal cortex/dorsal inferior frontal gyrus relative to controls and each other. ADHD and OCD patients shared left insula/ventral IFG underactivation and increased activation in posterior default mode network (DMN) regions, but had disorder-specific overactivation within anterior DMN regions, in dorsal anterior cingulate for ADHD and in anterior ventromedial prefrontal cortex for OCD. Only ADHD patients were impaired in performance. Conclusions: Findings suggest that sustained attention in both disorders relative to controls is associated with decreased recruitment of regions of task-positive salience and attention networks, as well as increased activation in DMN regions. However, the specific regions showing abnormalities in each disorder were disorder-specific, with disorder-specific underactivation in ADHD in task-relevant lateral prefrontal cortex and in OCD in medial frontal cortex, and hyperactivation in both disorders in different frontal parts of the DMN. Supported By: Medical Research Council (MRC GO300155); National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London. Keywords: ADHD, OCD, fMRI, Sustained attention, Disorderspecificity
929. Shared and Disorder-Specific Neural Dysfunction during Sustained Attention in Adolescent Attention-Deficit/Hyperactivity Disorder and Obsessive/compulsive Disorder
930. Altered Neural Anticipation of an Aversive Interoceptive Experience in Women Remitted from Bulimia Nervosa
Luke Norman1, Christina Carlisi2, Anastasia Christakou3, Clodagh Murphy2, Cubillo Ana2, Andrew Simmons4, Vincent Giampietro4, Michael Brammer4, David MataixCols5, and Katya Rubia2 University of Michigan Health System, 2Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 3 Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, UK, 4Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 5Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden 1
Background: Patients with Attention-Deficit/Hyperactivity Disorder (ADHD) and obsessive/compulsive disorder (OCD) share deficits in attention. The aim was examine whether brain activation abnormalities underlying sustained attention in the two disorders were shared or disorder-specific. Methods: Twenty boys with ADHD, 20 boys with OCD and 20 healthy controls aged between 12-18 years completed a functional magnetic resonance imaging (fMRI) version of a sustained attention task with a progressively increasing
S376
Laura Berner1, Alan Simmons2, Christina Wierenga2, Amanda Bischoff-Grethe1, Martin Paulus3, Ursula Bailer4, Miki Ogasawara1, and Walter Kaye1 University of California, San Diego, 2University of California, San Diego/San Diego VA Healthcare System, 3 Laureate Institute for Brain Research, 4Medical University of Vienna 1
Background: Altered function of the neural circuits supporting body state processing, or interoception, may contribute to bulimia nervosa (BN). However, data suggest both hyper- and hyporesponsivity to interoceptive stimulation in BN. Studies using pleasant stimuli indicate that aberrant signaling during the anticipation or processing of interoceptive events may explain these mixed findings. We examined whether BN is associated with altered activation before, during, and after an unpleasant interoceptive experience. Methods: Women remitted from BN (RBN; n519) and control women (CW; n525) underwent fMRI during an inspiratory breathing load paradigm. T-tests compared group activation in interoceptive search regions of interest (voxel-wise p , 0.01, cluster-wise p , 0.05, corrected). Exploratory Huber robust regressions examined BOLD associations with clinical measures. Results: During breathing load anticipation, RBN relative to CW showed increased activation in bilateral mid-insula, left superior
Biological Psychiatry May 15, 2017; 81:S277–S413 www.sobp.org/journal
Saturday Abstracts
927. Subcortical Volume and Neural Connectivity in Youth with Psychosis Spectrum Symptoms Grace Jacobs1, Erin Dickie2, and Aristotle Voineskos1 University of Toronto, 2Centre for Addiction and Mental Health
1
Background: Altered subcortical region volumes, specifically in the thalamus and striatum, as well as cortico-thalamicstriatal-cortical (CTSC) connectivity have been observed in schizophrenia. Methods: In this study, structural magnetic resonance imaging was used in a child and youth sample (n5821) including children with psychosis spectrum (PS) symptoms (n5110) to further understanding of these biomarkers and their presentation in youth outside of high risk groups. Subfields of subcortical regions were identified using the segmentation tool MAGeTbrain. Correlations between these subfields and cortex-wide cortical thickness values were used to infer network connectivity. Results: Boys and girls were examined separately. Volumes of the globus pallidus and striatal subregions were found to be increasing in boys with PS, but not in typically developing male youth (right globus pallidus: r(TD)5-0.21, t(age by psychosis)5-2.38, p50.017). A similar increase in volumes in girls with PS was seen in thalamic subregions but not in those who were typically developing (left lateral dorsal area: r(PS)5 0.28, t(age by psychosis)5-2.95, p50.009). Preliminary analyses also indicate that putamen subregions in psychosis spectrum boys are negatively correlated with cortical thickness in the bank of superior temporal sulcus, precentral gyrus in the posterior frontal lobe and superior parietal lobe. Thalamic subregions in psychosis spectrum girls were negatively associated with cortical thickness in the insula. Conclusions: These findings indicate early alteration of neural circuitry in PS youth similar to what is observed in schizophrenia and provides the opportunity to improve on early interventions by targeting gender and critical developmental time points. Keywords: Structural MRI, Early psychosis, Connectivity, Subcortical, Sex-specific
928. Cortical Abnormalities Associated with Pediatric and Adult Obsessive-Compulsive Disorder: Findings from the Enigma Obsessive-Compulsive Disorder Working Group Premika Boedhoe1, Lianne Schmaal2, Paul Arnold3, Francesco Benedetti4, Jan Beucke5, Yuqi Cheng6, Damiaan Denys7, Kate Fitzgerald8, Patricia Gruner9, Marcelo Hoexter10, Chaim Huyser11, Anthony James12, Kathrin Koch13, Jun Soo Kwon14, Luisa Lazaro15, David Mataix-Cols16, Jose Menchon17, Takashi Nakamae18, Tomohiro Nakao19, Erika Nurmi20, Y. C. Janardhan Reddy20, H.Blair Simpson21, Noam Soreni22, Gianfranco Spalletta23, David Tolin24, Susanne Walitza25, Zhen Wang26, Paul Thompson27, Dan Stein28, and Odile van den Heuvel29
VU University Medical Center, 2Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, Australia, 3Mathison Centre for Mental Health Research & Education, Cumming School of Medicine, University of Calgary, 4Clinical Research Group Psychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milano, Italy, 5 Department of Psychology, Humboldt-Universität zu Berlin, 6Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China, 7Academical Medical Center, 8University of Michigan, 9Department of Psychiatry, Yale University School of Medicine, 10University of Sao Paulo - Medical School, 11De Bascule, Academic Center for Child and Adolescent Psychiatry, Amsterdam, the Netherlands, 12Department of Psychiatry, Oxford University, 13Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, Germany, 14Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea, 15Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic Universitari, Barcelona, Spain, 16Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm, Sweden, 17Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain, 18Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan, 19Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, 20Obsessive-Compulsive Disorder (OCD) Clinic Department of Psychiatry National Institute of Mental Health & Neurosciences, Bangalore, India, 21Columbia University Medical College, Columbia University, 22Anxiety Treatment and Research Center, St. Joseph's Health Care, 23 Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy, 24Institute of Living/Hartford Hospital, 25 Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, 26 Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine, PR China, 27Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine of the University of Southern California, 28SU/UCT MRC Unit on Anxiety & Stress Disorders, Department of Psychiatry and Mental Health, University of Cape Town, South Africa, 29 Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands 1
Background: Brain imaging studies on structural abnormalities in OCD have been inconsistent, partially due to limited statistical power, clinical heterogeneity, and methodological differences. Here, we present data of the largest study to date on cortical brain measures in OCD patients and healthy controls by using meta- and mega-analyses. Methods: Structural T1-weighted MRI scans including 1905 OCD patients and 1760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer 5.3. Effect
Biological Psychiatry May 15, 2017; 81:S277–S413 www.sobp.org/journal
S375
Biological Psychiatry
Saturday Abstracts
sizes for differences between patients and controls were calculated using linear regression models controlling for age and gender (and ICV). Results were considered significant if the P-value exceeded a significance threshold determined by the false discovery rate (FDR) procedure at q50.05. Results: In adult OCD patients (versus controls) we found significantly lower surface area in the transverse temporal cortex and thinner cortices in the inferior parietal cortex. Medicated adult OCD patients (versus controls) showed thinner cortices in the frontal and temporal lobes. In pediatric OCD patients (versus controls) we also found significant thinner cortices in the parietal lobe. None of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD (versus controls) showed widespread surface area differences in the frontal and parietal lobes. Conclusions: The parietal cortex was consistently implicated both in adults and children. We found widespread cortical thickness abnormalities in medicated adult OCD patients and widespread surface area deficits in medicated pediatric OCD patients. These measures represent distinct morphological features and may be differentially affected by OCD and possibly moderated by medication status. Supported By: NIH: BD2k (Big Data), U54 EB020403-02 (PI: Thompson) & Neuroscience Campus Amsterdam (NCA), IPBgrant (PI’s: Schmaal / van den Heuvel) Keywords: Obsessive Compulsive Disorder (OCD), Neuroimaging, FreeSurfer, Cortical thickness, Cortical surface area
attention load. Performance and brain activation were compared between groups. Results: A group by delay interaction analysis showed that OCD patients had disorder-specific underactivation in middle anterior cingulate, while ADHD patients showed disorder-specific underactivation in left dorsolateral prefrontal cortex/dorsal inferior frontal gyrus relative to controls and each other. ADHD and OCD patients shared left insula/ventral IFG underactivation and increased activation in posterior default mode network (DMN) regions, but had disorder-specific overactivation within anterior DMN regions, in dorsal anterior cingulate for ADHD and in anterior ventromedial prefrontal cortex for OCD. Only ADHD patients were impaired in performance. Conclusions: Findings suggest that sustained attention in both disorders relative to controls is associated with decreased recruitment of regions of task-positive salience and attention networks, as well as increased activation in DMN regions. However, the specific regions showing abnormalities in each disorder were disorder-specific, with disorder-specific underactivation in ADHD in task-relevant lateral prefrontal cortex and in OCD in medial frontal cortex, and hyperactivation in both disorders in different frontal parts of the DMN. Supported By: Medical Research Council (MRC GO300155); National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London. Keywords: ADHD, OCD, fMRI, Sustained attention, Disorderspecificity
929. Shared and Disorder-Specific Neural Dysfunction during Sustained Attention in Adolescent Attention-Deficit/Hyperactivity Disorder and Obsessive/compulsive Disorder
930. Altered Neural Anticipation of an Aversive Interoceptive Experience in Women Remitted from Bulimia Nervosa
Luke Norman1, Christina Carlisi2, Anastasia Christakou3, Clodagh Murphy2, Cubillo Ana2, Andrew Simmons4, Vincent Giampietro4, Michael Brammer4, David MataixCols5, and Katya Rubia2 University of Michigan Health System, 2Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 3 Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, UK, 4Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, 5Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden 1
Background: Patients with Attention-Deficit/Hyperactivity Disorder (ADHD) and obsessive/compulsive disorder (OCD) share deficits in attention. The aim was examine whether brain activation abnormalities underlying sustained attention in the two disorders were shared or disorder-specific. Methods: Twenty boys with ADHD, 20 boys with OCD and 20 healthy controls aged between 12-18 years completed a functional magnetic resonance imaging (fMRI) version of a sustained attention task with a progressively increasing
S376
Laura Berner1, Alan Simmons2, Christina Wierenga2, Amanda Bischoff-Grethe1, Martin Paulus3, Ursula Bailer4, Miki Ogasawara1, and Walter Kaye1 University of California, San Diego, 2University of California, San Diego/San Diego VA Healthcare System, 3 Laureate Institute for Brain Research, 4Medical University of Vienna 1
Background: Altered function of the neural circuits supporting body state processing, or interoception, may contribute to bulimia nervosa (BN). However, data suggest both hyper- and hyporesponsivity to interoceptive stimulation in BN. Studies using pleasant stimuli indicate that aberrant signaling during the anticipation or processing of interoceptive events may explain these mixed findings. We examined whether BN is associated with altered activation before, during, and after an unpleasant interoceptive experience. Methods: Women remitted from BN (RBN; n519) and control women (CW; n525) underwent fMRI during an inspiratory breathing load paradigm. T-tests compared group activation in interoceptive search regions of interest (voxel-wise p , 0.01, cluster-wise p , 0.05, corrected). Exploratory Huber robust regressions examined BOLD associations with clinical measures. Results: During breathing load anticipation, RBN relative to CW showed increased activation in bilateral mid-insula, left superior
Biological Psychiatry May 15, 2017; 81:S277–S413 www.sobp.org/journal