Publications by authors named "Rachel Marsh"

79 Publications

White matter microstructure and its relation to clinical features of obsessive-compulsive disorder: findings from the ENIGMA OCD Working Group.

Transl Psychiatry 2021 Mar 17;11(1):173. Epub 2021 Mar 17.

Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.

Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive-compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen's d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = -0.21, z = -3.21, p = 0.001) and posterior thalamic radiation (d = -0.26, z = -4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = -2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = -1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.
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http://dx.doi.org/10.1038/s41398-021-01276-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969744PMC
March 2021

A quality control pipeline for probabilistic reconstruction of white-matter pathways.

J Neurosci Methods 2021 Apr 11;353:109099. Epub 2021 Feb 11.

The Division of Child and Adolescent Psychiatry in the Department of Psychiatry, the New York State Psychiatric Institute and the College of Physicians & Surgeons, Columbia University, New York, NY, United States.

Background: One of the most well-validated tools for DTI data analysis is TRACULA, part of the FreeSurfer software. TRACULA automatically segments 18 major white matter (WM) tracts. Occasionally, tracts may be only partially reconstructed, thus requiring intervention to avoid biasing analyses. A majority of studies have not reported any quality control procedures and those that have tend to discard partially reconstructed tracts from group analyses if they cannot be salvaged during TRACULA reinitialization.

New Method: We propose a semi-automated method to improve the detection and recovery of incomplete WM tracts. We detail several steps to maximize the quality of preprocessed DTI data. The steps include: (1) a visual inspection of eddy current corrected diffusion weighted images and (2) an automated evaluation of color- encoded FA images; (3) assessment of the volume of each tract saved in the TRACULA output file; (4) re-processing of tracts with a volume smaller than a specified threshold; (5) minimal manual editing of the control points for tracts that remained partially reconstructed; and (6) final re-initiation of TRACULA.

Results: Our method can speed and improve quality control relative to tract-by-tract visual inspection and can recover data that otherwise would need to be excluded from analyses due to incomplete reconstruction.

Comparison With Existing Methods: To our knowledge, there are no publications proposing alternative methods for quality control and recovering of partially reconstructed tracts in the TRACULA environment.

Conclusions: Our method helps TRACULA users automatically access the quality of reconstructed WM tracts and semi-automatically recover those in-complete WM tracts.
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http://dx.doi.org/10.1016/j.jneumeth.2021.109099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006796PMC
April 2021

Frontoparietal and default mode network connectivity varies with age and intelligence.

Dev Cogn Neurosci 2021 Jan 27;48:100928. Epub 2021 Jan 27.

The Division of Child and Adolescent Psychiatry, Columbia University Irving Medical Center, United States. Electronic address:

Background: Anticorrelated resting state connectivity between task-positive and task-negative networks in adults supports flexible shifting between externally focused attention and internal thought. Findings suggest that children show positive correlations between task-positive (frontoparietal; FP) and task-negative (default mode; DMN) networks. FP-DMN connectivity also associates with intellectual functioning across the lifespan. We investigated whether FP-DMN connectivity in healthy children varied with age and intelligence quotient (IQ).

Methods: We utilized network-based statistics (NBS) to examine resting state functional connectivity between FP and DMN seeds in N = 133 7-25-year-olds (M = 15.80). Linear regression evaluated FP-DMN associations with IQ.

Results: We detected NBS subnetworks containing both within- and between-network connections that were inversely associated with age. Four FP-DMN connections showed more negative connectivity between FP (inferior frontal gyrus and precentral gyrus) and DMN regions (frontal medial cortex, precuneus, and frontal pole) among older participants. Frontal pole-precentral gyrus connectivity inversely associated with IQ.

Conclusions: FP-DMN connectivity was more anticorrelated at older ages, potentially indicating dynamic network segregation of these circuits from childhood to early adulthood. Youth with more mature (i.e., anticorrelated) FP-DMN connectivity demonstrated higher IQ. Our findings add to the growing body of literature examining neural network development and its association with IQ.
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http://dx.doi.org/10.1016/j.dcn.2021.100928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848769PMC
January 2021

Obsessive-Compulsive Symptoms Among Children in the Adolescent Brain and Cognitive Development Study: Clinical, Cognitive, and Brain Connectivity Correlates.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Apr 6;6(4):399-409. Epub 2020 Nov 6.

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, New York; Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.

Background: Childhood obsessive-compulsive symptoms (OCSs) are common and can be an early risk marker for obsessive-compulsive disorder. The Adolescent Brain and Cognitive Development (ABCD) Study provides a unique opportunity to characterize OCSs in a large normative sample of school-age children and to explore corticostriatal and task-control circuits implicated in pediatric obsessive-compulsive disorder.

Methods: The ABCD Study acquired data from 9- and 10-year-olds (N = 11,876). Linear mixed-effects models probed associations between OCSs (Child Behavior Checklist) and cognition (NIH Toolbox), brain structure (subcortical volume, cortical thickness), white matter (diffusion tensor imaging), and resting-state functional connectivity.

Results: OCS scores showed good psychometric properties and high prevalence, and they were related to familial/parental factors, including family conflict. Higher OCS scores related to better cognitive performance (β = .06, t = 6.28, p < .001, η= .01), particularly verbal, when controlling for attention-deficit/hyperactivity disorder, which related to worse performance. OCSs did not significantly relate to brain structure but did relate to lower superior corticostriatal tract fractional anisotropy (β = -.03, t = -3.07, p = .002, η= .02). Higher OCS scores were related to altered functional connectivity, including weaker connectivity within the dorsal attention network (β = -.04, t = -3.71, p < .001, η= .002) and weaker dorsal attention-default mode anticorrelation (β = .04, t = 3.94, p < .001, η = .002). Dorsal attention-default mode connectivity predicted OCS scores at 1 year (β = -.04, t = -2.23, p = .03, η = .03).

Conclusions: OCSs are common and may persist throughout childhood. Corticostriatal connectivity and attention network connectivity are likely mechanisms in the subclinical-to-clinical spectrum of OCSs. Understanding correlates and mechanisms of OCSs may elucidate their role in childhood psychiatric risk and suggest potential utility of neuroimaging, e.g., dorsal attention-default mode connectivity, for identifying children at increased risk for obsessive-compulsive disorder.
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http://dx.doi.org/10.1016/j.bpsc.2020.10.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035161PMC
April 2021

Cognitive Control in Pediatric Obsessive-Compulsive and Anxiety Disorders: Brain-Behavioral Targets for Early Intervention.

Biol Psychiatry 2021 Apr 20;89(7):697-706. Epub 2020 Nov 20.

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, New York; Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.

The DSM provides distinct criteria for obsessive-compulsive disorder (OCD) and various types of anxiety disorders, but phenomenological overlap, high rates of comorbidity, and early onset suggest common underlying mechanisms. This notion is further supported by use of the same treatments-cognitive behavioral therapy and serotonin reuptake inhibitor medication-for managing both OCD and non-OCD anxiety disorders in clinical settings. While early intervention with these gold standard treatments is recommended for pediatric OCD and anxiety disorders, young patients often remain symptomatic even after treatment. To guide the development of novel, mechanistically targeted treatments to better resolve OCD and anxiety symptoms, the identification of neural circuits underlying psychological constructs with relevance across disorders has been recommended. One construct that may be relevant for understanding pediatric OCD and anxiety disorders is cognitive control, given the difficulty that young patients experience in dismissing obsessions, compulsions, and worry despite recognition that these symptoms are excessive and unreasonable. In this review, we examine findings from a growing body of literature implicating brain-behavioral markers of cognitive control in pediatric OCD and anxiety disorders, including before and after treatment. We conclude by suggesting that interventions designed to enhance the functioning of the task control circuits underlying cognitive control may facilitate brain maturation to help affected youth overcome symptoms.
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http://dx.doi.org/10.1016/j.biopsych.2020.11.012DOI Listing
April 2021

Network-based functional connectivity predicts response to exposure therapy in unmedicated adults with obsessive-compulsive disorder.

Neuropsychopharmacology 2021 Apr 14;46(5):1035-1044. Epub 2021 Jan 14.

Department of Psychiatry, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 74, New York, NY, 10032, USA.

Obsessive-compulsive disorder (OCD) is associated with alterations in cortico-striato-thalamo-cortical brain networks, but some resting-state functional magnetic resonance imaging studies report more diffuse alterations in brain connectivity. Few studies have assessed functional connectivity within or between networks across the whole brain in unmedicated OCD patients or how patterns of connectivity predict response to exposure and ritual prevention (EX/RP) therapy, a first-line treatment for OCD. Herein, multiband resting-state functional MRI scans were collected from unmedicated, adult patients with OCD (n = 41) and healthy participants (n = 36); OCD patients were then offered twice weekly EX/RP (17 sessions). A whole-brain-network-based statistic approach was used to identify group differences in resting-state connectivity. We detected altered pre-treatment functional connectivity between task-positive regions in the temporal gyri (middle and superior) and regions of the cingulo-opercular and default networks in individuals with OCD. Signal extraction was performed using a reconstruction independent components analysis and isolated two independent subcomponents (IC1 and IC2) within this altered connectivity. In the OCD group, linear mixed-effects models tested whether IC1 or IC2 values predicted the slope of change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores across EX/RP treatment. Lower (more different from controls) IC2 score significantly predicted greater symptom reduction with EX/RP (Bonferroni-corrected p = 0.002). Collectively, these findings suggest that an altered balance between task-positive and task-negative regions centered around temporal gyri may contribute to difficulty controlling intrusive thoughts or urges to perform ritualistic behaviors.
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http://dx.doi.org/10.1038/s41386-020-00929-9DOI Listing
April 2021

Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters.

Transl Psychiatry 2020 10 8;10(1):342. Epub 2020 Oct 8.

Amsterdam UMC, University of Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Amsterdam, Netherlands.

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.
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http://dx.doi.org/10.1038/s41398-020-01013-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598942PMC
October 2020

Associations between Amygdala-Prefrontal Functional Connectivity and Age Depend on Neighborhood Socioeconomic Status.

Cereb Cortex Commun 2020 23;1(1):tgaa033. Epub 2020 Jul 23.

New York State Psychiatric Institute and Department of Psychiatry, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Although severe early life stress has been shown to accelerate the development of frontolimbic resting-state functional connectivity (RSFC), less is known about the effects of socioeconomic disadvantage, a prolonged and multifaceted stressor. In a cross-sectional study of 127 participants aged 5-25, we examined whether lower neighborhood socioeconomic status (SES; measured by Area Deprivation Index and neighborhood poverty and educational attainment) was associated with prematurely reduced amygdala-ventromedial prefrontal cortex (vmPFC) RSFC. We further tested whether neighborhood SES was more predictive than household SES and whether SES effects on connectivity were associated with anxiety symptoms. We found reduced basolateral amygdala-vmPFC RSFC at earlier ages in participants from more disadvantaged neighborhoods; this effect was unique to neighborhood SES and absent for household SES. Furthermore, this reduced connectivity in more disadvantaged youth and increased connectivity in more advantaged youth were associated with less anxiety; children who deviated from the connectivity pattern associated with their neighborhood SES had more anxiety. These results demonstrate that neighborhood socioeconomic disadvantage is associated with accelerated maturation of amygdala-vmPFC RSFC and suggest that the pathophysiology of pediatric anxiety depends on a child's neighborhood socioeconomic characteristics. Our findings also underscore the importance of examining SES effects in studies of brain development.
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http://dx.doi.org/10.1093/texcom/tgaa033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503474PMC
July 2020

Erosive pustular dermatosis of the scalp.

Dermatol Online J 2020 Aug 15;26(8). Epub 2020 Aug 15.

Division of Dermatology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH.

Erosive pustular dermatosis of the scalp (EPDS) is a rare inflammatory condition commonly associated with antecedent iatrogenic insult. EPDS may be diagnostically challenging owing to a lack of pathognomonic histologic findings and cutaneous manifestations that overlap with alternative dermatologic conditions. Therefore, EPDS may be more common than previously recognized. We present a 60-year-old woman with a four-year history of non-healing scalp erosions, progressive skin atrophy, and scarring alopecia despite intravenous antibiotics and intraoperative debridement who improved with systemic glucocorticoids. Our report emphasizes the importance of early recognition of EPDS when delayed wound healing and erosive disease occur in the setting of iatrogenic injury to the scalp. Timely treatment with systemic anti-inflammatory agents is paramount to prevent cicatricial alopecia and mitigate further scalp insult in EPDS.
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August 2020

Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders.

Authors:
Yash Patel Nadine Parker Jean Shin Derek Howard Leon French Sophia I Thomopoulos Elena Pozzi Yoshinari Abe Christoph Abé Alan Anticevic Martin Alda Andre Aleman Clara Alloza Silvia Alonso-Lana Stephanie H Ameis Evdokia Anagnostou Andrew A McIntosh Celso Arango Paul D Arnold Philip Asherson Francesca Assogna Guillaume Auzias Rosa Ayesa-Arriola Geor Bakker Nerisa Banaj Tobias Banaschewski Cibele E Bandeira Alexandr Baranov Núria Bargalló Claiton H D Bau Sarah Baumeister Bernhard T Baune Mark A Bellgrove Francesco Benedetti Alessandro Bertolino Premika S W Boedhoe Marco Boks Irene Bollettini Caterina Del Mar Bonnin Tiana Borgers Stefan Borgwardt Daniel Brandeis Brian P Brennan Jason M Bruggemann Robin Bülow Geraldo F Busatto Sara Calderoni Vince D Calhoun Rosa Calvo Erick J Canales-Rodríguez Dara M Cannon Vaughan J Carr Nicola Cascella Mara Cercignani Tiffany M Chaim-Avancini Anastasia Christakou David Coghill Annette Conzelmann Benedicto Crespo-Facorro Ana I Cubillo Kathryn R Cullen Renata B Cupertino Eileen Daly Udo Dannlowski Christopher G Davey Damiaan Denys Christine Deruelle Annabella Di Giorgio Erin W Dickie Danai Dima Katharina Dohm Stefan Ehrlich Benjamin A Ely Tracy Erwin-Grabner Thomas Ethofer Damien A Fair Andreas J Fallgatter Stephen V Faraone Mar Fatjó-Vilas Jennifer M Fedor Kate D Fitzgerald Judith M Ford Thomas Frodl Cynthia H Y Fu Janice M Fullerton Matt C Gabel David C Glahn Gloria Roberts Tinatin Gogberashvili Jose M Goikolea Ian H Gotlib Roberto Goya-Maldonado Hans J Grabe Melissa J Green Eugenio H Grevet Nynke A Groenewold Dominik Grotegerd Oliver Gruber Patricia Gruner Amalia Guerrero-Pedraza Raquel E Gur Ruben C Gur Shlomi Haar Bartholomeus C M Haarman Jan Haavik Tim Hahn Tomas Hajek Benjamin J Harrison Neil A Harrison Catharina A Hartman Heather C Whalley Dirk J Heslenfeld Derrek P Hibar Eva Hilland Yoshiyuki Hirano Tiffany C Ho Pieter J Hoekstra Liesbeth Hoekstra Sarah Hohmann L E Hong Cyril Höschl Marie F Høvik Fleur M Howells Igor Nenadic Maria Jalbrzikowski Anthony C James Joost Janssen Fern Jaspers-Fayer Jian Xu Rune Jonassen Georgii Karkashadze Joseph A King Tilo Kircher Matthias Kirschner Kathrin Koch Peter Kochunov Gregor Kohls Kerstin Konrad Bernd Krämer Axel Krug Jonna Kuntsi Jun Soo Kwon Mikael Landén Nils I Landrø Luisa Lazaro Irina S Lebedeva Elisabeth J Leehr Sara Lera-Miguel Klaus-Peter Lesch Christine Lochner Mario R Louza Beatriz Luna Astri J Lundervold Frank P MacMaster Luigi A Maglanoc Charles B Malpas Maria J Portella Rachel Marsh Fiona M Martyn David Mataix-Cols Daniel H Mathalon Hazel McCarthy Colm McDonald Genevieve McPhilemy Susanne Meinert José M Menchón Luciano Minuzzi Philip B Mitchell Carmen Moreno Pedro Morgado Filippo Muratori Clodagh M Murphy Declan Murphy Benson Mwangi Leila Nabulsi Akiko Nakagawa Takashi Nakamae Leyla Namazova Janardhanan Narayanaswamy Neda Jahanshad Danai D Nguyen Rosa Nicolau Ruth L O'Gorman Tuura Kirsten O'Hearn Jaap Oosterlaan Nils Opel Roel A Ophoff Bob Oranje Victor Ortiz García de la Foz Bronwyn J Overs Yannis Paloyelis Christos Pantelis Mara Parellada Paul Pauli Maria Picó-Pérez Felipe A Picon Fabrizio Piras Federica Piras Kerstin J Plessen Edith Pomarol-Clotet Adrian Preda Olga Puig Yann Quidé Joaquim Radua J Antoni Ramos-Quiroga Paul E Rasser Lisa Rauer Janardhan Reddy Ronny Redlich Andreas Reif Liesbeth Reneman Jonathan Repple Alessandra Retico Vanesa Richarte Anja Richter Pedro G P Rosa Katya K Rubia Ryota Hashimoto Matthew D Sacchet Raymond Salvador Javier Santonja Kelvin Sarink Salvador Sarró Theodore D Satterthwaite Akira Sawa Ulrich Schall Peter R Schofield Anouk Schrantee Jochen Seitz Mauricio H Serpa Esther Setién-Suero Philip Shaw Devon Shook Tim J Silk Kang Sim Schmitt Simon Helen Blair Simpson Aditya Singh Antonin Skoch Norbert Skokauskas Jair C Soares Noam Soreni Carles Soriano-Mas Gianfranco Spalletta Filip Spaniel Stephen M Lawrie Emily R Stern S Evelyn Stewart Yoichiro Takayanagi Henk S Temmingh David F Tolin David Tomecek Diana Tordesillas-Gutiérrez Michela Tosetti Anne Uhlmann Therese van Amelsvoort Nic J A van der Wee Steven J A van der Werff Neeltje E M van Haren Guido A van Wingen Alasdair Vance Javier Vázquez-Bourgon Daniela Vecchio Ganesan Venkatasubramanian Eduard Vieta Oscar Vilarroya Yolanda Vives-Gilabert Aristotle N Voineskos Henry Völzke Georg G von Polier Esther Walton Thomas W Weickert Cynthia Shannon Weickert Andrea S Weideman Katharina Wittfeld Daniel H Wolf Mon-Ju Wu T T Yang Kun Yang Yuliya Yoncheva Je-Yeon Yun Yuqi Cheng Marcus V Zanetti Georg C Ziegler Barbara Franke Martine Hoogman Jan K Buitelaar Daan van Rooij Ole A Andreassen Christopher R K Ching Dick J Veltman Lianne Schmaal Dan J Stein Odile A van den Heuvel Jessica A Turner Theo G M van Erp Zdenka Pausova Paul M Thompson Tomáš Paus

JAMA Psychiatry 2021 Jan;78(1):47-63

Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.

Importance: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood.

Objective: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia.

Design, Setting, And Participants: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244.

Main Outcomes And Measures: Interregional profiles of group difference in cortical thickness between cases and controls.

Results: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders.

Conclusions And Relevance: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.2694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450410PMC
January 2021

Multiple Plantar Poromas in a Stem Cell Transplant Patient.

Cureus 2020 Jun 22;12(6):e8773. Epub 2020 Jun 22.

Division of Dermatology and Dermatopathology, The Ohio State University Wexner Medical Center, Columbus, USA.

Poromatosis, or the formation of multiple eccrine poromas, is associated with chronic immunosuppression, lymphoproliferative neoplasms, and stem cell transplantation, though the etiology and clinical significance remain poorly understood. Eccrine poromas are asymptomatic, may appear years after treatment, and overlap morphologically with other diagnoses, particularly human papillomavirus-associated verrucae, to which immunosuppressed patients may be predisposed and commonly occur in similar sites. We report a 47-year-old female on chronic immunosuppression who developed multiple plantar eccrine poromas three years after achieving acute myeloid leukemia (AML) remission following treatment with chemotherapy, total body irradiation, and allogenic stem cell transplantation. We propose that early recognition, timely treatment, and regular follow-up skin examinations are necessary in the setting of multiple poromas to reduce the risk of malignancy and avoid delays in diagnosis.
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http://dx.doi.org/10.7759/cureus.8773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384454PMC
June 2020

Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups.

Authors:
Premika S W Boedhoe Daan van Rooij Martine Hoogman Jos W R Twisk Lianne Schmaal Yoshinari Abe Pino Alonso Stephanie H Ameis Anatoly Anikin Alan Anticevic Celso Arango Paul D Arnold Philip Asherson Francesca Assogna Guillaume Auzias Tobias Banaschewski Alexander Baranov Marcelo C Batistuzzo Sarah Baumeister Ramona Baur-Streubel Marlene Behrmann Mark A Bellgrove Francesco Benedetti Jan C Beucke Joseph Biederman Irene Bollettini Anushree Bose Janita Bralten Ivanei E Bramati Daniel Brandeis Silvia Brem Brian P Brennan Geraldo F Busatto Sara Calderoni Anna Calvo Rosa Calvo Francisco X Castellanos Mara Cercignani Tiffany M Chaim-Avancini Kaylita C Chantiluke Yuqi Cheng Kang Ik K Cho Anastasia Christakou David Coghill Annette Conzelmann Ana I Cubillo Anders M Dale Sara Dallaspezia Eileen Daly Damiaan Denys Christine Deruelle Adriana Di Martino Ilan Dinstein Alysa E Doyle Sarah Durston Eric A Earl Christine Ecker Stefan Ehrlich Benjamin A Ely Jeffrey N Epstein Thomas Ethofer Damien A Fair Andreas J Fallgatter Stephen V Faraone Jennifer Fedor Xin Feng Jamie D Feusner Jackie Fitzgerald Kate D Fitzgerald Jean-Paul Fouche Christine M Freitag Egill A Fridgeirsson Thomas Frodl Matt C Gabel Louise Gallagher Tinatin Gogberashvili Ilaria Gori Patricia Gruner Deniz A Gürsel Shlomi Haar Jan Haavik Geoffrey B Hall Neil A Harrison Catharina A Hartman Dirk J Heslenfeld Yoshiyuki Hirano Pieter J Hoekstra Marcelo Q Hoexter Sarah Hohmann Marie F Høvik Hao Hu Chaim Huyser Neda Jahanshad Maria Jalbrzikowski Anthony James Joost Janssen Fern Jaspers-Fayer Terry L Jernigan Dmitry Kapilushniy Bernd Kardatzki Georgii Karkashadze Norbert Kathmann Christian Kaufmann Clare Kelly Sabin Khadka Joseph A King Kathrin Koch Gregor Kohls Kerstin Konrad Masaru Kuno Jonna Kuntsi Gerd Kvale Jun Soo Kwon Luisa Lázaro Sara Lera-Miguel Klaus-Peter Lesch Liesbeth Hoekstra Yanni Liu Christine Lochner Mario R Louza Beatriz Luna Astri J Lundervold Charles B Malpas Paulo Marques Rachel Marsh Ignacio Martínez-Zalacaín David Mataix-Cols Paulo Mattos Hazel McCarthy Jane McGrath Mitul A Mehta José M Menchón Maarten Mennes Mauricio Moller Martinho Pedro S Moreira Astrid Morer Pedro Morgado Filippo Muratori Clodagh M Murphy Declan G M Murphy Akiko Nakagawa Takashi Nakamae Tomohiro Nakao Leyla Namazova-Baranova Janardhanan C Narayanaswamy Rosa Nicolau Joel T Nigg Stephanie E Novotny Erika L Nurmi Eileen Oberwelland Weiss Ruth L O'Gorman Tuura Kirsten O'Hearn Joseph O'Neill Jaap Oosterlaan Bob Oranje Yannis Paloyelis Mara Parellada Paul Pauli Chris Perriello John Piacentini Fabrizio Piras Federica Piras Kerstin J Plessen Olga Puig J Antoni Ramos-Quiroga Y C Janardhan Reddy Andreas Reif Liesbeth Reneman Alessandra Retico Pedro G P Rosa Katya Rubia Oana Georgiana Rus Yuki Sakai Anouk Schrantee Lena Schwarz Lizanne J S Schweren Jochen Seitz Philip Shaw Devon Shook Tim J Silk H Blair Simpson Norbert Skokauskas Juan Carlos Soliva Vila Anastasia Solovieva Noam Soreni Carles Soriano-Mas Gianfranco Spalletta Emily R Stern Michael C Stevens S Evelyn Stewart Gustavo Sudre Philip R Szeszko Leanne Tamm Margot J Taylor David F Tolin Michela Tosetti Fernanda Tovar-Moll Aki Tsuchiyagaito Theo G M van Erp Guido A van Wingen Alasdair Vance Ganesan Venkatasubramanian Oscar Vilarroya Yolanda Vives-Gilabert Georg G von Polier Susanne Walitza Gregory L Wallace Zhen Wang Thomas Wolfers Yuliya N Yoncheva Je-Yeon Yun Marcus V Zanetti Fengfeng Zhou Georg C Ziegler Kathrin C Zierhut Marcel P Zwiers Paul M Thompson Dan J Stein Jan Buitelaar Barbara Franke Odile A van den Heuvel

Am J Psychiatry 2020 09 16;177(9):834-843. Epub 2020 Jun 16.

The full list of authors in the ENIGMA working groups, author affiliations, author disclosures, and acknowledgments are provided in online supplements.

Objective: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.

Methods: Structural T-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).

Results: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.

Conclusions: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.
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http://dx.doi.org/10.1176/appi.ajp.2020.19030331DOI Listing
September 2020

An overview of the first 5 years of the ENIGMA obsessive-compulsive disorder working group: The power of worldwide collaboration.

Hum Brain Mapp 2020 Mar 10. Epub 2020 Mar 10.

SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive-compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.
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http://dx.doi.org/10.1002/hbm.24972DOI Listing
March 2020

Correction: Altered network connectivity predicts response to cognitive-behavioral therapy in pediatric obsessive-compulsive disorder.

Neuropsychopharmacology 2020 06;45(7):1241

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, NY, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41386-020-0647-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411037PMC
June 2020

Evidence for trial-by-trial dynamic adjustment of task control in unmedicated adults with OCD.

Behav Res Ther 2020 03 25;126:103572. Epub 2020 Jan 25.

Department of Psychiatry, Columbia University Medical Center, New York, NY, USA; The New York State Psychiatric Institute, New York, NY, USA.

According to the conflict monitoring theory, executive control requires two separable processes: conflict-monitoring and conflict-resolution. Deficits in executive control have been observed in adults with obsessive-compulsive disorder (OCD). However, it is not yet clear whether these deficits can be attributed to deficits in conflict-monitoring, in conflict-resolution, or in both. We examined this question by administrating the Simon task to 67 unmedicated adults with OCD and 67 matched controls. The interference effect (incongruent minus congruent) was used to measure conflict-resolution. Trial-by-trial dynamic adaptation (i.e., the Gratton effect), which is indicated by smaller interference effect after conflict-laden trials compared to after non-conflict-laden trials, was used to measure conflict-monitoring. A similar interference effect was found in both the OCD and HC groups with no significant between group differences. Following incongruent trials, the interference effect became smaller for the control group as expected, but was completely eliminated for the OCD group. These data add to the accumulating evidence indicating that conflict-resolution is not globally deficient in unmedicated OCD patients and provide direct evidence that conflict-monitoring is heightened in OCD patients. Our results challenge the assumption of cognitive inflexibility in OCD and highlight the importance of studying unmedicated subjects when investigating executive control.
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http://dx.doi.org/10.1016/j.brat.2020.103572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097911PMC
March 2020

Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium.

Brain 2020 02;143(2):684-700

Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.

Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P < 0.0001), lower modularity (P < 0.0001), and lower small-worldness (P = 0.017). Detection of community membership emphasized lower network segregation in OCD compared to healthy controls. At the regional level, there were lower (rank-transformed) centrality values in OCD for volume of caudate nucleus and thalamus, and surface area of paracentral cortex, indicative of altered distribution of brain hubs. Centrality of cingulate and orbito-frontal as well as other brain areas was associated with OCD illness duration, suggesting greater involvement of these brain areas with illness chronicity. In summary, the findings of this study, the largest brain structural covariance study of OCD to date, point to a less segregated organization of structural covariance networks in OCD, and reorganization of brain hubs. The segregation findings suggest a possible signature of altered brain morphometry in OCD, while the hub findings point to OCD-related alterations in trajectories of brain development and maturation, particularly in cingulate and orbitofrontal regions.
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http://dx.doi.org/10.1093/brain/awaa001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009583PMC
February 2020

Spatial Network Connectivity and Spatial Reasoning Ability in Children with Nonverbal Learning Disability.

Sci Rep 2020 01 17;10(1):561. Epub 2020 Jan 17.

The Division of Child and Adolescent Psychiatry in the Department of Psychiatry, the New York State Psychiatric Institute and the College of Physicians & Surgeons, Columbia University, 1051 Riverside Drive, New York, NY, 10032, USA.

Nonverbal Learning Disability (NVLD) is characterized by deficits in visual-spatial, but not verbal, reasoning. Nevertheless, the functioning of the neural circuits supporting spatial processing have yet to be assessed in children with NVLD. We compared the resting state functional connectivity of a spatial brain network among children with NVLD, children with reading disorder (RD), and typically developing (TD) children. Seventy-five participants (7-15 years old) were included in the study (20 TD, 24 NVLD, and 31 RD). Group differences in global efficiency and functional connectivity among 12 regions comprising a previously defined spatial network were evaluated. Associations with behavior were explored. Global efficiency of the spatial network associated positively with spatial ability and inversely with socioemotional problems. Within the spatial network, associations between left posterior cingulate (PCC) and right retrosplenial cortical activity were reduced in children with NVLD relative to those without spatial deficits (RD and TD). Connectivity between left PCC and right posterior cerebellum (Crus I and II) was reduced in both groups of children with learning disabilities (NVLD and RD) relative to TD children. Functional connectivity of the spatial network was atypically associated with cognitive and socioemotional performance in children with NVLD. Identifying a neurobiological substrate for NVLD provides evidence that it is a discrete clinical entity and suggests targets for treatment.
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http://dx.doi.org/10.1038/s41598-019-56003-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969178PMC
January 2020

Altered network connectivity predicts response to cognitive-behavioral therapy in pediatric obsessive-compulsive disorder.

Neuropsychopharmacology 2020 06 17;45(7):1232-1240. Epub 2020 Jan 17.

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, NY, USA.

Obsessive-compulsive disorder (OCD) is commonly associated with alterations in cortico-striato-thalamo-cortical brain networks. Yet, recent investigations of large-scale brain networks suggest that more diffuse alterations in brain connectivity may underlie its pathophysiology. Few studies have assessed functional connectivity within or between networks across the whole brain in pediatric OCD or how patterns of connectivity associate with treatment response. Resting-state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment-naive children and adolescents with OCD (12.8 ± 2.9 years) and 23 matched healthy control (HC) participants (11.0 ± 3.3 years) before participants with OCD completed a course of cognitive-behavioral therapy (CBT). Participants were re-scanned after 12-16 weeks. Whole-brain connectomic analyses were conducted to assess baseline group differences and group-by-time interactions, corrected for multiple comparisons. Relationships between functional connectivity and OCD symptoms pre- and post-CBT were examined using longitudinal cross-lagged panel modeling. Reduced connectivity in OCD relative to HC participants was detected between default mode and task-positive network regions. Greater (less altered) connectivity between left angular gyrus and left frontal pole predicted better response to CBT in the OCD group. Altered connectivity between task-positive and task-negative networks in pediatric OCD may contribute to the impaired control over intrusive thoughts early in the illness. This is the first study to show that altered connectivity between large-scale network regions may predict response to CBT in pediatric OCD, highlighting the clinical relevance of these networks as potential circuit-based targets for the development of novel treatments.
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http://dx.doi.org/10.1038/s41386-020-0613-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235012PMC
June 2020

Structural neural markers of response to cognitive behavioral therapy in pediatric obsessive-compulsive disorder.

J Child Psychol Psychiatry 2020 12 31;61(12):1299-1308. Epub 2019 Dec 31.

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, NY, USA.

Background: Cognitive behavioral therapy (CBT) is an effective, first-line treatment for pediatric obsessive-compulsive disorder (OCD). While neural predictors of treatment outcomes have been identified in adults with OCD, robust predictors are lacking for pediatric patients. Herein, we sought to identify brain structural markers of CBT response in youth with OCD.

Methods: Twenty-eight children/adolescents with OCD and 27 matched healthy participants (7- to 18-year-olds, M = 11.71 years, SD = 3.29) completed high-resolution structural and diffusion MRI (all unmedicated at time of scanning). Patients with OCD then completed 12-16 sessions of CBT. Subcortical volume and cortical thickness were estimated using FreeSurfer. Structural connectivity (streamline counts) was estimated using MRtrix.

Results: Thinner cortex in nine frontoparietal regions significantly predicted improvement in Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) scores (all ts > 3.4, FDR-corrected ps < .05). These included middle and superior frontal, angular, lingual, precentral, superior temporal, and supramarginal gyri (SMG). Vertex-wise analyses confirmed a significant left SMG cluster, showing large effect size (Cohen's d = 1.42) with 72.22% specificity and 90.00% sensitivity in predicting CBT response. Ten structural connections between cingulo-opercular regions exhibited fewer streamline counts in OCD (all ts > 3.12, Cohen's ds > 0.92) compared with healthy participants. These connections predicted post-treatment CY-BOCS scores, beyond pretreatment severity and demographics, though not above and beyond cortical thickness.

Conclusions: The current study identified group differences in structural connectivity (reduced among cingulo-opercular regions) and cortical thickness predictors of CBT response (thinner frontoparietal cortices) in unmedicated children/adolescents with OCD. These data suggest, for the first time, that cortical and white matter features of task control circuits may be useful in identifying which pediatric patients respond best to individual CBT.
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http://dx.doi.org/10.1111/jcpp.13191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326644PMC
December 2020

Association between micronutrient deficiency dermatoses and clinical outcomes in hospitalized patients.

J Am Acad Dermatol 2020 05 31;82(5):1226-1228. Epub 2019 Oct 31.

Department of Internal Medicine, Division of Dermatology, The Ohio State University Wexner Medical Center, Columbus.

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http://dx.doi.org/10.1016/j.jaad.2019.10.057DOI Listing
May 2020

Brain Volume Abnormalities in Youth at High Risk for Depression: Adolescent Brain and Cognitive Development Study.

J Am Acad Child Adolesc Psychiatry 2020 10 18;59(10):1178-1188. Epub 2019 Oct 18.

Columbia University, New York; New York State Psychiatric Institute, New York; Division of Clinical Developmental Neuroscience, Sackler Institute, New York. Electronic address:

Objective: Children of parents with depression are two to three times more likely to develop major depressive disorder than children without parental history; however, subcortical brain volume abnormalities characterizing major depressive disorder risk remain unclear. The Adolescent Brain and Cognitive Development (ABCD) Study provides an opportunity to identify subcortical differences associated with parental depressive history.

Method: Structural magnetic resonance data were acquired from 9- and 10-year-old children (N = 11,876; release 1.1, n = 4,521; release 2.0.1, n = 7,355). Approximately one-third of the children had a parental depressive history, providing sufficient power to test differences in subcortical brain volume between low- and high-risk youths. Children from release 1.1 were examined as a discovery sample, and we sought to replicate effects in release 2.0.1. Secondary analyses tested group differences in the prevalence of depressive disorders and clarified whether subcortical brain differences were present in youths with a lifetime depressive disorder history.

Results: Parental depressive history was related to smaller right putamen volume in the discovery (release 1.1; d = -0.10) and replication (release 2.0.1; d = -0.10) samples. However, in release 1.1, this effect was driven by maternal depressive history (d = -0.14), whereas in release 2.0.1, paternal depressive history showed a stronger relationship with putamen volume (d = -0.09). Furthermore, high-risk children exhibited a near twofold greater occurrence of depressive disorders relative to low-risk youths (maternal history odds ratio =1.99; paternal history odds ratio = 1.45), but youths with a lifetime depressive history did not exhibit significant subcortical abnormalities.

Conclusion: A parental depressive history was associated with smaller putamen volume, which may affect reward learning processes that confer increased risk for major depressive disorder.
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http://dx.doi.org/10.1016/j.jaac.2019.09.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165045PMC
October 2020

Task-based fMRI predicts response and remission to exposure therapy in obsessive-compulsive disorder.

Proc Natl Acad Sci U S A 2019 10 23;116(41):20346-20353. Epub 2019 Sep 23.

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, NY 10032.

Exposure and ritual prevention (EX/RP) is an effective first-line treatment for obsessive-compulsive disorder (OCD), but only some patients achieve minimal symptoms following EX/RP. Herein, we investigate whether task-based neural activity can predict who responds best to EX/RP. Unmedicated adult patients with OCD ( = 36) and healthy participants ( = 33) completed the Simon Spatial Incompatibility Task during high-resolution, multiband functional MRI (fMRI); patients were then offered twice-weekly EX/RP (17 sessions). Linear mixed-effects models were used to identify brain regions where conflict-related activity moderated the slope of change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores across treatment. Conflict-related activity in the left pallidum and 35 cortical parcels/regions significantly predicted symptom improvement with EX/RP for patients with OCD (false discovery rate-corrected < 0.05). Significant parcels/regions included cingulo-opercular and default mode network regions, specifically the anterior insula and anterior and posterior cingulate. Summarizing across these parcels/regions, greater conflict-related activity predicted greater EX/RP response and which patients achieved remission (Y-BOCS score ≤ 12; Cohen's 1.68) with >80% sensitivity and specificity. The association between brain activity and treatment response was partially mediated by patient EX/RP adherence (b = -2.99; 43.61% of total effect; = 0.02). Brain activity and adherence together were highly predictive of remission. Together, these findings suggest that cingulo-opercular and default mode regions typically implicated in task control and introspective processes, respectively, may be targets for novel treatments that augment the ability of persons with OCD to resolve cognitive conflict and thereby facilitate adherence to EX/RP, increasing the likelihood of remission.
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http://dx.doi.org/10.1073/pnas.1909199116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789627PMC
October 2019

Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium.

Biol Psychiatry 2020 06 30;87(12):1022-1034. Epub 2019 Apr 30.

Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands. Electronic address:

Background: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD.

Methods: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status.

Results: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets.

Conclusions: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.
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http://dx.doi.org/10.1016/j.biopsych.2019.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094802PMC
June 2020

Neural correlates of cognitive control deficits in children with reading disorder.

Brain Imaging Behav 2020 Oct;14(5):1531-1542

The Division of Child and Adolescent Psychiatry in the Department of Psychiatry, the New York State Psychiatric Institute and the College of Physicians & Surgeons, Columbia University, Unit 74. 10032, 1051 Riverside Drive, New York, NY, USA.

Reading disorder (RD) is characterized by deficient phonological processing, but children with RD also have cognitive control deficits, the neural correlates of which are not fully understood. We used fMRI to assess neural activity during the resolution of cognitive conflict on the Simon Spatial Incompatibility task and patterns of resting-state functional connectivity (RSFC) from task control (TC) regions in 7-12-year-old children with RD compared to their typically developing (TD) peers. Relative to TD children (n = 17), those with RD (n = 16) over-engaged a right superior/medial frontal cluster during the resolution of conflict (p = .05). Relative to TD children (n = 18), those with RD (n = 17) also showed reduced RSFC (voxel-wise p < .001; cluster-size p < .05, FDR corrected) from cingulo-opercular seeds to left hemisphere fronto-parietal and temporo-parietal reading-related regions, perhaps reflecting reduced organization of TC circuits and reduced integration with reading-related regions. Children with RD additionally showed reduced RSFC between fronto-parietal and default mode network regions. Follow-up analyses in a subset of children with both useable task and resting state data (RD = 13; TD = 17) revealed that greater conflict-related activation of the right frontal Simon task ROI associated with better word-reading, perhaps suggesting a compensatory role for this over-engagement. Connectivity from fronto-parietal seeds significantly associated with Simon task performance and word-reading accuracy in RD children. These findings suggest that altered functioning and connectivity of control circuits may contribute to cognitive control deficits in children with RD. Future studies should assess the utility of adding cognitive control training to reading remediation programs.
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http://dx.doi.org/10.1007/s11682-019-00083-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6765445PMC
October 2020

Subcortical Shape Abnormalities in Bulimia Nervosa.

Biol Psychiatry Cogn Neurosci Neuroimaging 2019 12 4;4(12):1070-1079. Epub 2019 Jan 4.

Division of Child and Adolescent Psychiatry, Columbia University Medical Center and the New York State Psychiatric Institute, New York, New York.

Background: Bulimia nervosa (BN) is associated with functional abnormalities in frontostriatal and frontolimbic circuits. Although structural alterations in the frontal portions of these circuits have been observed, this is the first study of subcortical surface morphometry and the largest study of subcortical volume in BN.

Methods: Anatomical magnetic resonance scans were acquired from 62 female participants with full and subthreshold BN (mean age ± SD, 18.7 ± 4.0 years) and 65 group-matched healthy control participants (mean age ± SD, 19.3 ± 5.7 years). General linear models were used to compare groups and assess the significance of group-by-age interactions on the shape and total volume of 15 subcortical structures (p < .05, familywise error corrected). Associations with illness severity and duration were assessed in the BN group.

Results: Subcortical volumes did not differ across groups, but vertexwise analyses revealed inward shape deformations on the anterior surface of the pallidum in BN relative to control participants that were associated with binge-eating frequency and illness duration. Inward deformations on the ventrolateral thalamus and dorsal amygdala were more pronounced with advancing age in the BN group, and inward deformations on the caudate, putamen, and amygdala were associated with self-induced vomiting frequency.

Conclusions: Our findings point to localized deformations on the surface of subcortical structures in areas that comprise both reward and cognitive control circuits. These deformations were more pronounced among older BN participants and among those with the most severe symptoms. Such precise localization of alterations in subcortical morphometry may ultimately aid in efforts to identify markers of risk and BN persistence.
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http://dx.doi.org/10.1016/j.bpsc.2018.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609503PMC
December 2019

Deficient Functioning of Frontostriatal Circuits During the Resolution of Cognitive Conflict in Cannabis-Using Youth.

J Am Acad Child Adolesc Psychiatry 2019 07 31;58(7):702-711. Epub 2018 Oct 31.

New York State Psychiatric Institute and the Department of Psychiatry, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY.

Objective: Disturbances in self-regulatory control are involved in the initiation and maintenance of addiction, including cannabis use disorder. In adults, long-term cannabis use is associated with disturbances in frontostriatal circuits during tasks that require the engagement of self-regulatory control, including the resolution of cognitive conflict. Understudied are the behavioral and neural correlates of these processes earlier in the course of cannabis use disentangled from effects of long-term use. The present study investigated the functioning of frontostriatal circuits during the resolution of cognitive conflict in cannabis-using youth.

Method: Functional magnetic resonance imaging data were acquired from 28 cannabis-using youth and 32 age-matched healthy participants during the performance of a Simon task. General linear modeling was used to compare patterns of brain activation during correct responses to conflict stimuli across groups. Psychophysiologic interaction analyses were used to examine conflict-related frontostriatal connectivity across groups. Associations of frontostriatal activation and connectivity with cannabis use measures were explored.

Results: Decreased conflict-related activity was detected in cannabis-using versus healthy control youth in frontostriatal regions, including the ventromedial prefrontal cortex, striatum, pallidum, and thalamus. Frontostriatal connectivity did not differ across groups, but negative connectivity between the ventromedial prefrontal cortex and striatum was detected in the 2 groups.

Conclusion: These findings are consistent with previous reports of cannabis-associated disturbances in frontostriatal circuits in adults and point to the specific influence of cannabis on neurodevelopmental changes in youth. Future studies should examine whether frontostriatal functioning is a reliable marker of cannabis use disorder severity and a potential target for circuit-based interventions.
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http://dx.doi.org/10.1016/j.jaac.2018.09.436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506393PMC
July 2019

Increased Functional Connectivity Between Ventral Attention and Default Mode Networks in Adolescents With Bulimia Nervosa.

J Am Acad Child Adolesc Psychiatry 2019 02 29;58(2):232-241. Epub 2018 Oct 29.

Division of Child and Adolescent Psychiatry, New York State Psychiatric Institute, New York, NY, and the Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.

Objective: Bulimia nervosa (BN) is characterized by excessive attention to self and specifically to body shape and weight, but the ventral attention (VAN) and default mode (DMN) networks that support attentional and self-referential processes are understudied in BN. This study assessed whether altered functional connectivity within and between these networks contributes to such excessive concerns in adolescents with BN early the course of the disorder.

Method: Resting-state functional magnetic resonance images were acquired from 33 adolescents with BN and 37 healthy control adolescents (12-21 years) group matched by age and body mass index. Region-of-interest analyses were performed to examine group differences in functional connectivity within and between the VAN and DMN. In addition associations of VAN-DMN connectivity with BN symptoms, body shape/weight concerns, and sustained attention were explored using the Continuous Performance Test (CPT).

Results: Compared with control adolescents, those with BN showed significantly increased positive connectivity between the right ventral supramarginal gyrus and all DMN regions and between the right ventrolateral prefrontal cortex and the left lateral parietal cortex. Within-network connectivity did not differ between groups. VAN-DMN connectivity was associated with BN severity and body shape/weight concerns in the BN group. No significant group-by-CPT interactions on VAN-DMN connectivity were detected.

Conclusion: Increased positive VAN-DMN connectivity in adolescents with BN could reflect abnormal engagement of VAN-mediated attentional processes at rest, perhaps related to their excessive attention to self-referential thoughts about body shape/weight. Future studies should further investigate these circuits as targets for the development of early interventions aimed at decreasing excessive body shape/weight concerns.
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http://dx.doi.org/10.1016/j.jaac.2018.09.433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462410PMC
February 2019

An Empirical Comparison of Meta- and Mega-Analysis With Data From the ENIGMA Obsessive-Compulsive Disorder Working Group.

Front Neuroinform 2018 8;12:102. Epub 2019 Jan 8.

Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

Brain imaging communities focusing on different diseases have increasingly started to collaborate and to pool data to perform well-powered meta- and mega-analyses. Some methodologists claim that a one-stage individual-participant data (IPD) mega-analysis can be superior to a two-stage aggregated data meta-analysis, since more detailed computations can be performed in a mega-analysis. Before definitive conclusions regarding the performance of either method can be drawn, it is necessary to critically evaluate the methodology of, and results obtained by, meta- and mega-analyses. Here, we compare the inverse variance weighted random-effect meta-analysis model with a multiple linear regression mega-analysis model, as well as with a linear mixed-effects random-intercept mega-analysis model, using data from 38 cohorts including 3,665 participants of the ENIGMA-OCD consortium. We assessed the effect sizes and standard errors, and the fit of the models, to evaluate the performance of the different methods. The mega-analytical models showed lower standard errors and narrower confidence intervals than the meta-analysis. Similar standard errors and confidence intervals were found for the linear regression and linear mixed-effects random-intercept models. Moreover, the linear mixed-effects random-intercept models showed better fit indices compared to linear regression mega-analytical models. Our findings indicate that results obtained by meta- and mega-analysis differ, in favor of the latter. In multi-center studies with a moderate amount of variation between cohorts, a linear mixed-effects random-intercept mega-analytical framework appears to be the better approach to investigate structural neuroimaging data.
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http://dx.doi.org/10.3389/fninf.2018.00102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331928PMC
January 2019

Salience network connectivity and social processing in children with nonverbal learning disability or autism spectrum disorder.

Neuropsychology 2019 Jan 8;33(1):135-143. Epub 2018 Nov 8.

Division of Child and Adolescent Psychiatry, Department of Psychiatry, Columbia University Irving Medical Center.

Objective: Nonverbal learning disability (NVLD) is a putative neurodevelopmental disorder characterized by spatial processing deficits as well as social deficits similar to those characteristic of autism spectrum disorder (ASD). Nonetheless, NVLD may be a distinct disorder that is differentially associated with the functioning and connectivity of the salience (SN) and default mode (DMN) networks that support social processing. Thus, we sought to assess and compare connectivity across these networks in children with NVLD, ASD, and typically developing children.

Method: Resting-state fMRI data were examined in 17 children with NVLD, 17 children with ASD selected from the Autism Brain Imaging Data Exchange (ABIDE), and 40 TD children (20 from ABIDE). Average DMN and SN functional connectivity and pairwise region-to-region connectivity were compared across groups. Associations with social impairment and IQ were assessed.

Results: Children with NVLD showed reduced connectivity between SN regions (anterior insula to anterior cingulate and to rostral prefrontal cortex [rPFC]), whereas children with ASD showed greater connectivity between SN regions (supramarginal gyrus to rPFC) relative to the other groups. Both clinical groups showed higher levels of parent-reported social problems, which related to altered SN connectivity in the NVLD group. No differences were detected in overall average connectivity within or between networks.

Conclusions: The social deficits common across children with NVLD and ASD may derive from distinct alterations in connectivity within the SN. Such findings represent the first step toward identifying a neurobiological signature of NVLD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322976PMC
January 2019