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Chronic Mild Sleep Restriction Does Not Lead to Marked Neuronal Alterations Compared to Maintained Adequate Sleep in Adults

Li, Xue-Ying; Yoncheva, Yuliya; Yan, Chao-Gan; Castellanos, Francisco Xavier; St-Onge, Marie-Pierre
BACKGROUND:Sleep restriction (SR) has been shown to upregulate neuronal reward networks in response to food stimuli but prior studies were short-term and employed severe SR paradigms. OBJECTIVE:Our goal was to determine whether mild SR, achieved by delaying bedtimes by 1.5h, influences neuronal networks responsive to food stimuli compared to maintained adequate sleep (AS) >7h/night. METHODS:A randomized controlled crossover study with two 6-wk phases, AS (≥7h sleep/night) and SR (-1.5h/night relative to screening), was conducted. Adults with adequate sleep duration, measured using wrist-actigraphy over a 2-wk screening period, and self-reported good sleep quality were enrolled. Resting-state and food-stimulated functional neuroimaging (fMRI) was performed at endpoint of each phase. Resting-state fMRI data analyses included a priori region-of-interest seed-based functional connectivity, whole-brain voxel-wise analyses, and network analyses. Food-task fMRI analyses compared brain activity patterns in response to food cues between conditions. Paired-sample t-tests tested differences between conditions. RESULTS:Twenty-six participants (16 males; age 29.6±5.3y, body mass index 26.9±4.0kg/m2) contributed complete data. Total sleep time was 7h30±28min/night during AS vs. 6h12±26min/night during SR. We employed different statistical approaches to replicate prior studies in the field and to apply more robust approaches that are currently advocated in the field. Using uncorrected P<0.01, cluster ≥10 voxels thresholds, we replicate prior findings of increased activation in response to foods in reward networks after SR vs. AS (right insula, right inferior frontal gyrus, and right supramarginal gyrus). These findings did not survive more rigorous analytical approaches (Gaussian Random Field theory correction at two-tailed voxel P<0.001, cluster P<0.05). CONCLUSIONS:Results suggest that mild SR leads to increased reward responsivity to foods but with low confidence given failure to meet significance from rigorous statistical analyses. Further research is necessary to inform the mechanisms underlying the role of sleep on food intake regulation. CLINICAL TRIAL REGISTRATION/BACKGROUND:NCT02960776;
PMID: 38104943
ISSN: 1541-6100
CID: 5612572

Aberrant resting-state functional connectivity of the globus pallidus interna in first-episode schizophrenia

Qi, Wei; Wen, Zhenfu; Chen, Jingyun; Capichioni, Gillian; Ando, Fumika; Chen, Zhe Sage; Wang, Jijun; Yoncheva, Yuliya; Castellanos, Francisco X; Milad, Mohammed; Goff, Donald C
BACKGROUND:The striatal-pallidal pathway plays an important role in cognitive control and modulation of behaviors. Globus pallidus interna (GPi), as a primary output structure, is crucial in modulating excitation and inhibition. Studies of GPi in psychiatric illnesses are lacking given the technical challenges of examining this small and functionally diverse subcortical structure. METHODS:71 medication-naïve first episode schizophrenia (FES) participants and 73 healthy controls (HC) were recruited at the Shanghai Mental Health Center. Clinical symptoms and imaging data were collected at baseline and, in a subset of patients, 8 weeks after initiating treatment. Resting-state functional connectivity of sub-regions of the GP were assessed using a novel mask that combines two atlases to create 8 ROIs in the GP. RESULTS: = 0.486, p < 0.001). CONCLUSIONS:Our results implicate striatal-pallidal-thalamic pathways in antipsychotic efficacy. If replicated, these findings may reflect failure of neurodevelopmental processes in adolescence and early adulthood that decrease functional connectivity as an index of failure of the limbic/associative GPi to appropriately inhibit irrelevant signals in psychosis.
PMID: 37716202
ISSN: 1573-2509
CID: 5593342

1.93 Testing Continued Effectiveness Through Multiple Modifications of an Empirically Supported Treatment for Organization, Time Management, and Planning Deficits in ADHD and Related Disorders [Meeting Abstract]

Gallagher, R; Haroon, M; Yoncheva, Y; Conlon, G; Abikoff, H; Castellanos, F X
Objectives: Organizational skills training (OST) for youth with ADHD is an efficacious treatment that addresses impairments at home and in school. Modifications of OST were conducted to treat children with or without ADHD, to reduce treatment barriers, and to respond to changes in school demands during the COVID-19 pandemic.
Method(s): After an initial RCT documenting OST efficacy, 3 further studies involved: 1) an open replication of the original RCT confirming improvements in organization, time management, and planning (OTMP) in children diagnosed with ADHD (N = 15) using twice-weekly in-person visits; 2) a subsequent open trial investigating children with deficient organizational skills with or without ADHD and altering delivery to involve a combination of in-person and virtual meetings (N = 29); and 3) a third study with subjects with low OTMP skills who do not necessarily have ADHD, receive treatment with combined in-person and virtual delivery or, in response to COVID-19 restrictions, fully virtual delivery (N = 27, thus far), and, in response to remote school delivery, have altered OST content to fit varied school instruction demands (eg, use of electronic documents instead of papers) while adhering to the principles of OST. Change was measured on the Children's Organizational Skills Scales (COSS).
Result(s): 1) Improvements in OTMP skills (parent ratings d = 3.73; teacher ratings d = 1.12) in the first open study were comparable to the initial RCT findings. 2) In study 2, parents also reported substantial improvements (d = 3.04), and teachers reported large changes (d = 0.88) in pre-post comparisons. 3) In the ongoing RCT, subjects who received treatment immediately were reported to have large changes by parents (d = 2.17) and moderate changes by teachers (d = 0.47) when compared to waitlist controls.
Conclusion(s): Initial analyses indicate that OST leads to OTMP improvements in children struggling with disorganization with and without ADHD diagnosis. Improvements are found when treatment is delivered fully in-person, delivered in hybrid in-person and virtual meetings, or delivered fully virtually. OST could help children with or without ADHD improve behavioral and emotional adjustment at home and in school, when treatment delivery is modified to increase treatment availability, and when school demands are varied. ADHD, CBT, EBP
ISSN: 1527-5418
CID: 5511342

Virtual Ontogeny of Cortical Growth Preceding Mental Illness

Patel, Yash; Shin, Jean; Abé, Christoph; Agartz, Ingrid; Alloza, Clara; Alnæs, Dag; Ambrogi, Sonia; Antonucci, Linda A; Arango, Celso; Arolt, Volker; Auzias, Guillaume; Ayesa-Arriola, Rosa; Banaj, Nerisa; Banaschewski, Tobias; Bandeira, Cibele; BaÅŸgöze, Zeynep; Cupertino, Renata Basso; Bau, Claiton H D; Bauer, Jochen; Baumeister, Sarah; Bernardoni, Fabio; Bertolino, Alessandro; Bonnin, Caterina Del Mar; Brandeis, Daniel; Brem, Silvia; Bruggemann, Jason; Bülow, Robin; Bustillo, Juan R; Calderoni, Sara; Calvo, Rosa; Canales-Rodríguez, Erick J; Cannon, Dara M; Carmona, Susanna; Carr, Vaughan J; Catts, Stanley V; Chenji, Sneha; Chew, Qian Hui; Coghill, David; Connolly, Colm G; Conzelmann, Annette; Craven, Alexander R; Crespo-Facorro, Benedicto; Cullen, Kathryn; Dahl, Andreas; Dannlowski, Udo; Davey, Christopher G; Deruelle, Christine; Díaz-Caneja, Covadonga M; Dohm, Katharina; Ehrlich, Stefan; Epstein, Jeffery; Erwin-Grabner, Tracy; Eyler, Lisa T; Fedor, Jennifer; Fitzgerald, Jacqueline; Foran, William; Ford, Judith M; Fortea, Lydia; Fuentes-Claramonte, Paola; Fullerton, Janice; Furlong, Lisa; Gallagher, Louise; Gao, Bingchen; Gao, Si; Goikolea, Jose M; Gotlib, Ian; Goya-Maldonado, Roberto; Grabe, Hans J; Green, Melissa; Grevet, Eugenio H; Groenewold, Nynke A; Grotegerd, Dominik; Gruber, Oliver; Haavik, Jan; Hahn, Tim; Harrison, Ben J; Heindel, Walter; Henskens, Frans; Heslenfeld, Dirk J; Hilland, Eva; Hoekstra, Pieter J; Hohmann, Sarah; Holz, Nathalie; Howells, Fleur M; Ipser, Jonathan C; Jahanshad, Neda; Jakobi, Babette; Jansen, Andreas; Janssen, Joost; Jonassen, Rune; Kaiser, Anna; Kaleda, Vasiliy; Karantonis, James; King, Joseph A; Kircher, Tilo; Kochunov, Peter; Koopowitz, Sheri-Michelle; Landén, Mikael; Landrø, Nils Inge; Lawrie, Stephen; Lebedeva, Irina; Luna, Beatriz; Lundervold, Astri J; MacMaster, Frank P; Maglanoc, Luigi A; Mathalon, Daniel H; McDonald, Colm; McIntosh, Andrew; Meinert, Susanne; Michie, Patricia T; Mitchell, Philip; Moreno-Alcázar, Ana; Mowry, Bryan; Muratori, Filippo; Nabulsi, Leila; Nenadić, Igor; O'Gorman Tuura, Ruth; Oosterlaan, Jaap; Overs, Bronwyn; Pantelis, Christos; Parellada, Mara; Pariente, Jose C; Pauli, Paul; Pergola, Giulio; Piarulli, Francesco Maria; Picon, Felipe; Piras, Fabrizio; Pomarol-Clotet, Edith; Pretus, Clara; Quidé, Yann; Radua, Joaquim; Ramos-Quiroga, J Antoni; Rasser, Paul E; Reif, Andreas; Retico, Alessandra; Roberts, Gloria; Rossell, Susan; Rovaris, Diego Luiz; Rubia, Katya; Sacchet, Matthew; Salavert, Josep; Salvador, Raymond; Sarró, Salvador; Sawa, Akira; Schall, Ulrich; Scott, Rodney; Selvaggi, Pierluigi; Silk, Tim; Sim, Kang; Skoch, Antonin; Spalletta, Gianfranco; Spaniel, Filip; Stein, Dan J; Steinsträter, Olaf; Stolicyn, Aleks; Takayanagi, Yoichiro; Tamm, Leanne; Tavares, Maria; Teumer, Alexander; Thiel, Katharina; Thomopoulos, Sophia I; Tomecek, David; Tomyshev, Alexander S; Tordesillas-Gutiérrez, Diana; Tosetti, Michela; Uhlmann, Anne; Van Rheenen, Tamsyn; Vazquez-Bourgón, Javier; Vernooij, Meike W; Vieta, Eduard; Vilarroya, Oscar; Weickert, Cynthia; Weickert, Thomas; Westlye, Lars T; Whalley, Heather; Willinger, David; Winter, Alexandra; Wittfeld, Katharina; Yang, Tony T; Yoncheva, Yuliya; Zijlmans, Jendé L; Hoogman, Martine; Franke, Barbara; van Rooij, Daan; Buitelaar, Jan; Ching, Christopher R K; Andreassen, Ole A; Pozzi, Elena; Veltman, Dick; Schmaal, Lianne; van Erp, Theo G M; Turner, Jessica; Castellanos, F Xavier; Pausova, Zdenka; Thompson, Paul; Paus, Tomas
BACKGROUND:Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS:Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS:Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS:Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
PMID: 35489875
ISSN: 1873-2402
CID: 5217792

Greater male than female variability in regional brain structure across the lifespan

Wierenga, Lara M; Doucet, Gaelle E; Dima, Danai; Agartz, Ingrid; Aghajani, Moji; Akudjedu, Theophilus N; Albajes-Eizagirre, Anton; Alnaes, Dag; Alpert, Kathryn I; Andreassen, Ole A; Anticevic, Alan; Asherson, Philip; Banaschewski, Tobias; Bargallo, Nuria; Baumeister, Sarah; Baur-Streubel, Ramona; Bertolino, Alessandro; Bonvino, Aurora; Boomsma, Dorret I; Borgwardt, Stefan; Bourque, Josiane; den Braber, Anouk; Brandeis, Daniel; Breier, Alan; Brodaty, Henry; Brouwer, Rachel M; Buitelaar, Jan K; Busatto, Geraldo F; Calhoun, Vince D; Canales-Rodríguez, Erick J; Cannon, Dara M; Caseras, Xavier; Castellanos, Francisco X; Chaim-Avancini, Tiffany M; Ching, Christopher Rk; Clark, Vincent P; Conrod, Patricia J; Conzelmann, Annette; Crivello, Fabrice; Davey, Christopher G; Dickie, Erin W; Ehrlich, Stefan; Van't Ent, Dennis; Fisher, Simon E; Fouche, Jean-Paul; Franke, Barbara; Fuentes-Claramonte, Paola; de Geus, Eco Jc; Di Giorgio, Annabella; Glahn, David C; Gotlib, Ian H; Grabe, Hans J; Gruber, Oliver; Gruner, Patricia; Gur, Raquel E; Gur, Ruben C; Gurholt, Tiril P; de Haan, Lieuwe; Haatveit, Beathe; Harrison, Ben J; Hartman, Catharina A; Hatton, Sean N; Heslenfeld, Dirk J; van den Heuvel, Odile A; Hickie, Ian B; Hoekstra, Pieter J; Hohmann, Sarah; Holmes, Avram J; Hoogman, Martine; Hosten, Norbert; Howells, Fleur M; Hulshoff Pol, Hilleke E; Huyser, Chaim; Jahanshad, Neda; James, Anthony C; Jiang, Jiyang; Jönsson, Erik G; Joska, John A; Kalnin, Andrew J; Klein, Marieke; Koenders, Laura; KolskÃ¥r, Knut K; Krämer, Bernd; Kuntsi, Jonna; Lagopoulos, Jim; Lazaro, Luisa; Lebedeva, Irina S; Lee, Phil H; Lochner, Christine; Machielsen, Marise Wj; Maingault, Sophie; Martin, Nicholas G; Martínez-Zalacaín, Ignacio; Mataix-Cols, David; Mazoyer, Bernard; McDonald, Brenna C; McDonald, Colm; McIntosh, Andrew M; McMahon, Katie L; McPhilemy, Genevieve; van der Meer, Dennis; Menchón, José M; Naaijen, Jilly; Nyberg, Lars; Oosterlaan, Jaap; Paloyelis, Yannis; Pauli, Paul; Pergola, Giulio; Pomarol-Clotet, Edith; Portella, Maria J; Radua, Joaquim; Reif, Andreas; Richard, Geneviève; Roffman, Joshua L; Rosa, Pedro Gp; Sacchet, Matthew D; Sachdev, Perminder S; Salvador, Raymond; Sarró, Salvador; Satterthwaite, Theodore D; Saykin, Andrew J; Serpa, Mauricio H; Sim, Kang; Simmons, Andrew; Smoller, Jordan W; Sommer, Iris E; Soriano-Mas, Carles; Stein, Dan J; Strike, Lachlan T; Szeszko, Philip R; Temmingh, Henk S; Thomopoulos, Sophia I; Tomyshev, Alexander S; Trollor, Julian N; Uhlmann, Anne; Veer, Ilya M; Veltman, Dick J; Voineskos, Aristotle; Völzke, Henry; Walter, Henrik; Wang, Lei; Wang, Yang; Weber, Bernd; Wen, Wei; West, John D; Westlye, Lars T; Whalley, Heather C; Williams, Steven Cr; Wittfeld, Katharina; Wolf, Daniel H; Wright, Margaret J; Yoncheva, Yuliya N; Zanetti, Marcus V; Ziegler, Georg C; de Zubicaray, Greig I; Thompson, Paul M; Crone, Eveline A; Frangou, Sophia; Tamnes, Christian K
For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
PMID: 33044802
ISSN: 1097-0193
CID: 4632482

Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets

Postema, Merel C; Hoogman, Martine; Ambrosino, Sara; Asherson, Philip; Banaschewski, Tobias; Bandeira, Cibele E; Baranov, Alexandr; Bau, Claiton H D; Baumeister, Sarah; Baur-Streubel, Ramona; Bellgrove, Mark A; Biederman, Joseph; Bralten, Janita; Brandeis, Daniel; Brem, Silvia; Buitelaar, Jan K; Busatto, Geraldo F; Castellanos, Francisco X; Cercignani, Mara; Chaim-Avancini, Tiffany M; Chantiluke, Kaylita C; Christakou, Anastasia; Coghill, David; Conzelmann, Annette; Cubillo, Ana I; Cupertino, Renata B; de Zeeuw, Patrick; Doyle, Alysa E; Durston, Sarah; Earl, Eric A; Epstein, Jeffery N; Ethofer, Thomas; Fair, Damien A; Fallgatter, Andreas J; Faraone, Stephen V; Frodl, Thomas; Gabel, Matt C; Gogberashvili, Tinatin; Grevet, Eugenio H; Haavik, Jan; Harrison, Neil A; Hartman, Catharina A; Heslenfeld, Dirk J; Hoekstra, Pieter J; Hohmann, Sarah; Høvik, Marie F; Jernigan, Terry L; Kardatzki, Bernd; Karkashadze, Georgii; Kelly, Clare; Kohls, Gregor; Konrad, Kerstin; Kuntsi, Jonna; Lazaro, Luisa; Lera-Miguel, Sara; Lesch, Klaus-Peter; Louza, Mario R; Lundervold, Astri J; Malpas, Charles B; Mattos, Paulo; McCarthy, Hazel; Namazova-Baranova, Leyla; Nicolau, Rosa; Nigg, Joel T; Novotny, Stephanie E; Oberwelland Weiss, Eileen; O'Gorman Tuura, Ruth L; Oosterlaan, Jaap; Oranje, Bob; Paloyelis, Yannis; Pauli, Paul; Picon, Felipe A; Plessen, Kerstin J; Ramos-Quiroga, J Antoni; Reif, Andreas; Reneman, Liesbeth; Rosa, Pedro G P; Rubia, Katya; Schrantee, Anouk; Schweren, Lizanne J S; Seitz, Jochen; Shaw, Philip; Silk, Tim J; Skokauskas, Norbert; Soliva Vila, Juan C; Stevens, Michael C; Sudre, Gustavo; Tamm, Leanne; Tovar-Moll, Fernanda; van Erp, Theo G M; Vance, Alasdair; Vilarroya, Oscar; Vives-Gilabert, Yolanda; von Polier, Georg G; Walitza, Susanne; Yoncheva, Yuliya N; Zanetti, Marcus V; Ziegler, Georg C; Glahn, David C; Jahanshad, Neda; Medland, Sarah E; Thompson, Paul M; Fisher, Simon E; Franke, Barbara; Francks, Clyde
OBJECTIVE:Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. METHODS:We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. RESULTS:There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing. CONCLUSION/CONCLUSIONS:Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.
PMID: 33748971
ISSN: 1469-7610
CID: 4822272

Monitoring New Symptoms After COVID-19 Infection Among Primary Care Patients in New York City

Terlizzi, Kelly; Kutscher, Eric; Yoncheva, Yuliya
INTRODUCTION:COVID-19 affects multiple organ systems causing substantial long-term morbidity. The implications of the Post-Acute Sequelae of SARS-CoV-2 infection, particularly for primary care, remain unknown. This cross-sectional study examines new symptoms reported at primary care encounters during three post-acute follow-up intervals after initial SARS-CoV-2 infection. METHODS:Electronic health record data from the NYU Langone COVID Deidentified Dataset were queried for adults with a positive SARS-CoV-2 PCR test, and then restricted to those with a new ICD-10-CM code documented at a post-acute COVID-related primary care follow-up >14 days after testing positive. New diagnoses and the corresponding Clinical Classifications Software Refined categories were assessed at the following intervals: 0.5-3 months ("subacute"), 3-6 months ("prolonged"), and 6-9 months ("persistent"). RESULTS:Out of 3,154 patients, a new ICD-10-CM code was documented among 499 patients (∼16%). Respiratory complaints, including cough, shortness of breath, dyspnea, and hypoxemia, were most common. Malaise and fatigue were reported consistently among 10-13% of patients at all three time-intervals. Musculoskeletal pain, circulatory symptoms, and sleep-wake disorders were also observed at primary care follow-up. CONCLUSION:This cross-sectional study provides support of a post-acute COVID syndrome, demonstrating that patients continue to experience symptoms after the acute infection period. Extensive follow-up data allowed for examining new symptoms up to 9 months after initial SARS-CoV-2 infection. Understanding of the course of multi-organ post-acute sequelae is restricted by cross-sectional study design limitations. Standardized, sequelae-related ICD-10-CM codes to specify the type and duration of post-acute COVID-related symptoms would enable better monitoring of the growing number of SARS-CoV-2 infection survivors.
PMID: 34535527
ISSN: 1558-7118
CID: 5026722

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

Patel, Yash; Parker, Nadine; Shin, Jean; Howard, Derek; French, Leon; Thomopoulos, Sophia I; Pozzi, Elena; Abe, Yoshinari; Abé, Christoph; Anticevic, Alan; Alda, Martin; Aleman, Andre; Alloza, Clara; Alonso-Lana, Silvia; Ameis, Stephanie H; Anagnostou, Evdokia; McIntosh, Andrew A; Arango, Celso; Arnold, Paul D; Asherson, Philip; Assogna, Francesca; Auzias, Guillaume; Ayesa-Arriola, Rosa; Bakker, Geor; Banaj, Nerisa; Banaschewski, Tobias; Bandeira, Cibele E; Baranov, Alexandr; Bargalló, Núria; Bau, Claiton H D; Baumeister, Sarah; Baune, Bernhard T; Bellgrove, Mark A; Benedetti, Francesco; Bertolino, Alessandro; Boedhoe, Premika S W; Boks, Marco; Bollettini, Irene; Del Mar Bonnin, Caterina; Borgers, Tiana; Borgwardt, Stefan; Brandeis, Daniel; Brennan, Brian P; Bruggemann, Jason M; Bülow, Robin; Busatto, Geraldo F; Calderoni, Sara; Calhoun, Vince D; Calvo, Rosa; Canales-Rodríguez, Erick J; Cannon, Dara M; Carr, Vaughan J; Cascella, Nicola; Cercignani, Mara; Chaim-Avancini, Tiffany M; Christakou, Anastasia; Coghill, David; Conzelmann, Annette; Crespo-Facorro, Benedicto; Cubillo, Ana I; Cullen, Kathryn R; Cupertino, Renata B; Daly, Eileen; Dannlowski, Udo; Davey, Christopher G; Denys, Damiaan; Deruelle, Christine; Di Giorgio, Annabella; Dickie, Erin W; Dima, Danai; Dohm, Katharina; Ehrlich, Stefan; Ely, Benjamin A; Erwin-Grabner, Tracy; Ethofer, Thomas; Fair, Damien A; Fallgatter, Andreas J; Faraone, Stephen V; Fatjó-Vilas, Mar; Fedor, Jennifer M; Fitzgerald, Kate D; Ford, Judith M; Frodl, Thomas; Fu, Cynthia H Y; Fullerton, Janice M; Gabel, Matt C; Glahn, David C; Roberts, Gloria; Gogberashvili, Tinatin; Goikolea, Jose M; Gotlib, Ian H; Goya-Maldonado, Roberto; Grabe, Hans J; Green, Melissa J; Grevet, Eugenio H; Groenewold, Nynke A; Grotegerd, Dominik; Gruber, Oliver; Gruner, Patricia; Guerrero-Pedraza, Amalia; Gur, Raquel E; Gur, Ruben C; Haar, Shlomi; Haarman, Bartholomeus C M; Haavik, Jan; Hahn, Tim; Hajek, Tomas; Harrison, Benjamin J; Harrison, Neil A; Hartman, Catharina A; Whalley, Heather C; Heslenfeld, Dirk J; Hibar, Derrek P; Hilland, Eva; Hirano, Yoshiyuki; Ho, Tiffany C; Hoekstra, Pieter J; Hoekstra, Liesbeth; Hohmann, Sarah; Hong, L E; Höschl, Cyril; Høvik, Marie F; Howells, Fleur M; Nenadic, Igor; Jalbrzikowski, Maria; James, Anthony C; Janssen, Joost; Jaspers-Fayer, Fern; Xu, Jian; Jonassen, Rune; Karkashadze, Georgii; King, Joseph A; Kircher, Tilo; Kirschner, Matthias; Koch, Kathrin; Kochunov, Peter; Kohls, Gregor; Konrad, Kerstin; Krämer, Bernd; Krug, Axel; Kuntsi, Jonna; Kwon, Jun Soo; Landén, Mikael; Landrø, Nils I; Lazaro, Luisa; Lebedeva, Irina S; Leehr, Elisabeth J; Lera-Miguel, Sara; Lesch, Klaus-Peter; Lochner, Christine; Louza, Mario R; Luna, Beatriz; Lundervold, Astri J; MacMaster, Frank P; Maglanoc, Luigi A; Malpas, Charles B; Portella, Maria J; Marsh, Rachel; Martyn, Fiona M; Mataix-Cols, David; Mathalon, Daniel H; McCarthy, Hazel; McDonald, Colm; McPhilemey, Genevieve; Meinert, Susanne; Menchón, José M; Minuzzi, Luciano; Mitchell, Philip B; Moreno, Carmen; Morgado, Pedro; Muratori, Filippo; Murphy, Clodagh M; Murphy, Declan; Mwangi, Benson; Nabulsi, Leila; Nakagawa, Akiko; Nakamae, Takashi; Namazova, Leyla; Narayanaswamy, Janardhanan; Jahanshad, Neda; Nguyen, Danai D; Nicolau, Rosa; O'Gorman Tuura, Ruth L; O'Hearn, Kirsten; Oosterlaan, Jaap; Opel, Nils; Ophoff, Roel A; Oranje, Bob; García de la Foz, Victor Ortiz; Overs, Bronwyn J; Paloyelis, Yannis; Pantelis, Christos; Parellada, Mara; Pauli, Paul; Picó-Pérez, Maria; Picon, Felipe A; Piras, Fabrizio; Piras, Federica; Plessen, Kerstin J; Pomarol-Clotet, Edith; Preda, Adrian; Puig, Olga; Quidé, Yann; Radua, Joaquim; Ramos-Quiroga, J Antoni; Rasser, Paul E; Rauer, Lisa; Reddy, Janardhan; Redlich, Ronny; Reif, Andreas; Reneman, Liesbeth; Repple, Jonathan; Retico, Alessandra; Richarte, Vanesa; Richter, Anja; Rosa, Pedro G P; Rubia, Katya K; Hashimoto, Ryota; Sacchet, Matthew D; Salvador, Raymond; Santonja, Javier; Sarink, Kelvin; Sarró, Salvador; Satterthwaite, Theodore D; Sawa, Akira; Schall, Ulrich; Schofield, Peter R; Schrantee, Anouk; Seitz, Jochen; Serpa, Mauricio H; Setién-Suero, Esther; Shaw, Philip; Shook, Devon; Silk, Tim J; Sim, Kang; Simon, Schmitt; Simpson, Helen Blair; Singh, Aditya; Skoch, Antonin; Skokauskas, Norbert; Soares, Jair C; Soreni, Noam; Soriano-Mas, Carles; Spalletta, Gianfranco; Spaniel, Filip; Lawrie, Stephen M; Stern, Emily R; Stewart, S Evelyn; Takayanagi, Yoichiro; Temmingh, Henk S; Tolin, David F; Tomecek, David; Tordesillas-Gutiérrez, Diana; Tosetti, Michela; Uhlmann, Anne; van Amelsvoort, Therese; van der Wee, Nic J A; van der Werff, Steven J A; van Haren, Neeltje E M; van Wingen, Guido A; Vance, Alasdair; Vázquez-Bourgon, Javier; Vecchio, Daniela; Venkatasubramanian, Ganesan; Vieta, Eduard; Vilarroya, Oscar; Vives-Gilabert, Yolanda; Voineskos, Aristotle N; Völzke, Henry; von Polier, Georg G; Walton, Esther; Weickert, Thomas W; Weickert, Cynthia Shannon; Weideman, Andrea S; Wittfeld, Katharina; Wolf, Daniel H; Wu, Mon-Ju; Yang, T T; Yang, Kun; Yoncheva, Yuliya; Yun, Je-Yeon; Cheng, Yuqi; Zanetti, Marcus V; Ziegler, Georg C; Franke, Barbara; Hoogman, Martine; Buitelaar, Jan K; van Rooij, Daan; Andreassen, Ole A; Ching, Christopher R K; Veltman, Dick J; Schmaal, Lianne; Stein, Dan J; van den Heuvel, Odile A; Turner, Jessica A; van Erp, Theo G M; Pausova, Zdenka; Thompson, Paul M; Paus, Tomáš
Importance/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED: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/UNASSIGNED:Interregional profiles of group difference in cortical thickness between cases and controls. Results/UNASSIGNED: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/UNASSIGNED: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.
PMID: 32857118
ISSN: 2168-6238
CID: 4650132

Post-COVID primary care needs [Meeting Abstract]

Kutscher, E; Terlizzi, K; Yoncheva, Y
BACKGROUND: Covid-19 disease, resulting from the virus SARS-CoV-2, has caused significant morbidity and mortality across the globe. In the acute setting, Covid-19 is characterized by its inflammatory impact, notably leading to acute respiratory distress syndrome, increased risk of blood clots, cardiomyopathy, and acute kidney injury. Long-term complications known as longhaul Covid, chronic Covid, or post-Covid syndrome include fatigue, depression, persistent respiratory complaints, and decreased quality of life. However, little research exists to elucidate the primary care needs of those who have recovered from Covid-19. This longitudinal observational study describes healthcare usage patterns and new medical diagnoses after acute Covid-19 infection.
METHOD(S): We queried the NYU Langone COVID Deidentified Dataset for adults 18+ years old with a positive SARS-CoV-2 PCR test. Patients had at least one visit in the NYU Langone Health system >2 weeks before and >2 weeks after infection (n = 2940). We further narrowed this cohort to patients with a primary care encounter where a Covid-19 related concern was documented at follow-up (n = 454; 57% female; 22%=18-42 years, 51%=43-67 years, 27%=68+ years old). The median length of follow-up was 6 weeks (IQR=3.6-10.1 weeks, max=38 weeks). ICD-10 codes and the Clinical Classification Software Refined (CCSR) categories were used to identify diagnoses newly developed after Covid-19 infection or symptoms that persisted beyond the initial 14-day infection period.
RESULT(S): Of 2,940 patients with pre and post-infection visits, only 454 (15%) sought primary care for a Covid-19 related concern. Respiratory signs and symptoms were the most common complaint. Prevalent diagnoses included cough (8%), hypoxia or respiratory failure (8%), and shortness of breath (7%). Malaise and fatigue (7%), musculoskeletal pain (6%), and generalized weakness and deconditioning (5%) were also common. Nutritional deficiencies were documented among 28 patients (6%), most often for vitamin D deficiency (5%). Palpitations (5%) and nonspecific chest pain (such as chest tightness or discomfort, 3%) as well as deep vein thrombosis and pulmonary emboli (4%) were also reported.
CONCLUSION(S): Most patients with a Covid-19 diagnosis did not seek follow-up, consistent with reports that Covid-19 predominantly causes acute illness. For patients who developed new or persistent symptoms, the most common complaints were respiratory concerns, malaise and fatigue, and musculoskeletal pain. The persistence of these symptoms in our cohort suggests that patients may indeed present a constellation of symptoms after acute Covid-19 infection. Updated longitudinal queries and further research may continue to highlight the importance of tailoring longer term primary care for those who have recovered from acute Covid infection. LEARNING OBJECTIVE #1: Identify common symptoms of patients returning to primary care more than 2 weeks after Covid-19 infection LEARNING OBJECTIVE #2: Determine need for primary care follow-up after Covid-19 recovery
ISSN: 1525-1497
CID: 4986662

Evaluation of long-term renal function post-COVID [Meeting Abstract]

Kutscher, E; Terlizzi, K; Yoncheva, Y
BACKGROUND: The spread of SARS-CoV-2 has caused mortality and long-lasting morbidity worldwide. Acutely, COVID-19 may elevate risk of blood clots, cardiomyopathy, and acute kidney injury. For many critically ill patients, dialysis has been essential in managing infection. Long-term, the impact of COVID-19 on renal function remains unknown. This longitudinal observational study examines basic renal function indexed by serum creatinine and estimated Glomerular Filtration Rate (eGFR) measured ~10-26 weeks after COVID-19 onset.
METHOD(S): We queried the NYU Langone COVID Deidentified Dataset for adults with a positive SARS-CoV-2 PCR test and excluded End-Stage Renal Disease (ESRD) patients (3%). The cohort had a creatinine test from a Basic or Comprehensive Metabolic Panel >2 weeks before and >2 weeks after infection (n=501; 54% female; 18%=18-42 years, 39%=43-67 years, 43%=68+ year old). Within- patient pre- vs. post-COVID creatinine change change was normalized by the patient's latest pre- COVID creatinine test. To gauge the putative clinical relevance of creatinine change in understanding risk for deterioration to ESRD, renal function stratified by eGFR (ml/min/1.73m2 ), available only for n=221 (44% of cohort), is illustrated in the figure below.
RESULT(S): Post-COVID creatinine levels were greater (1.327 mg/dL +/- 0.06, mean +/- SEM) than pre- COVID levels (1.248 mg/dL +/- 0.07) representing a post-COVID increase change =0.093 (Cohen's d effect size=0.15, t500=3.3, p<0.001). This creatinine change was captured at a pre-/post-interval=192.5 +/- 3.1 days (mean +/- SEM), corresponding to 129.5 +/- 3.1 days after a COVID-19 infection (min=2 weeks, IQR=10-26 weeks, max=38 weeks).
CONCLUSION(S): In an early COVID-19 epicenter, we show preliminary evidence of sustained creatinine increases in a cohort without ESRD around 3- 6 months following COVID-19 onset. Future work should isolate the role of pre-existing risk factors and link potentially new renal dysfunction more directly to COVID-19. Given the long-term follow-up data available in this study, we recommend that primary care providers track renal function in patients following COVID-19 infection to screen for emergent renal disease and adjust any renally dosed medications. LEARNING OBJECTIVE #1: Identify changes in renal function after recovery from COVID-19 infection LEARNING OBJECTIVE #2: Depict patterns of long-term renal function changes post-COVID
ISSN: 1525-1497
CID: 4986692