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Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder

Strom, Nora I; Gerring, Zachary F; Galimberti, Marco; Yu, Dongmei; Halvorsen, Matthew W; Abdellaoui, Abdel; Rodriguez-Fontenla, Cristina; Sealock, Julia M; Bigdeli, Tim; Coleman, Jonathan R; Mahjani, Behrang; Thorp, Jackson G; Bey, Katharina; Burton, Christie L; Luykx, Jurjen J; Zai, Gwyneth; Alemany, Silvia; Andre, Christine; Askland, Kathleen D; Bäckman, Julia; Banaj, Nerisa; Barlassina, Cristina; Nissen, Judith Becker; Bienvenu, O Joseph; Black, Donald; Bloch, Michael H; Børte, Sigrid; Bosch, Rosa; Breen, Michael; Brennan, Brian P; Brentani, Helena; Buxbaum, Joseph D; Bybjerg-Grauholm, Jonas; Byrne, Enda M; Cabana-Dominguez, Judit; Camarena, Beatriz; Camarena, Adrian; Cappi, Carolina; Carracedo, Angel; Casas, Miguel; Cavallini, Maria Cristina; Ciullo, Valentina; Cook, Edwin H; Crosby, Jesse; Cullen, Bernadette A; De Schipper, Elles J; Delorme, Richard; Djurovic, Srdjan; Elias, Jason A; Estivill, Xavier; Falkenstein, Martha J; Fundin, Bengt T; Garner, Lauryn; Gironda, Christina; Goes, Fernando S; Grados, Marco A; Grove, Jakob; Guo, Wei; Haavik, Jan; Hagen, Kristen; Harrington, Kelly; Havdahl, Alexandra; Höffler, Kira D; Hounie, Ana G; Hucks, Donald; Hultman, Christina; Janecka, Magdalena; Jenike, Eric; Karlsson, Elinor K; Kelley, Kara; Klawohn, Julia; Krasnow, Janice E; Krebs, Kristi; Lange, Christoph; Lanzagorta, Nuria; Levey, Daniel; Lindblad-Toh, Kerstin; Macciardi, Fabio; Maher, Brion; Mathes, Brittany; McArthur, Evonne; McGregor, Nathaniel; McLaughlin, Nicole C; Meier, Sandra; Miguel, Euripedes C; Mulhern, Maureen; Nestadt, Paul S; Nurmi, Erika L; O'Connell, Kevin S; Osiecki, Lisa; Ousdal, Olga Therese; Palviainen, Teemu; Pedersen, Nancy L; Piras, Fabrizio; Piras, Federica; Potluri, Sriramya; Rabionet, Raquel; Ramirez, Alfredo; Rauch, Scott; Reichenberg, Abraham; Riddle, Mark A; Ripke, Stephan; Rosário, Maria C; Sampaio, Aline S; Schiele, Miriam A; Skogholt, Anne Heidi; Sloofman, Laura G; Smit, Jan; Artigas, María Soler; Thomas, Laurent F; Tifft, Eric; Vallada, Homero; van Kirk, Nathanial; Veenstra-VanderWeele, Jeremy; Vulink, Nienke N; Walker, Christopher P; Wang, Ying; Wendland, Jens R; Winsvold, Bendik S; Yao, Yin; Zhou, Hang; ,; ,; Agrawal, Arpana; Alonso, Pino; Berberich, Götz; Bucholz, Kathleen K; Bulik, Cynthia M; Cath, Danielle; Denys, Damiaan; Eapen, Valsamma; Edenberg, Howard; Falkai, Peter; Fernandez, Thomas V; Fyer, Abby J; Gaziano, J M; Geller, Dan A; Grabe, Hans J; Greenberg, Benjamin D; Hanna, Gregory L; Hickie, Ian B; Hougaard, David M; Kathmann, Norbert; Kennedy, James; Lai, Dongbing; Landén, Mikael; Hellard, Stéphanie Le; Leboyer, Marion; Lochner, Christine; McCracken, James T; Medland, Sarah E; Mortensen, Preben B; Neale, Benjamin M; Nicolini, Humberto; Nordentoft, Merete; Pato, Michele; Pato, Carlos; Pauls, David L; Piacentini, John; Pittenger, Christopher; Posthuma, Danielle; Ramos-Quiroga, Josep Antoni; Rasmussen, Steven A; Richter, Margaret A; Rosenberg, David R; Ruhrmann, Stephan; Samuels, Jack F; Sandin, Sven; Sandor, Paul; Spalletta, Gianfranco; Stein, Dan J; Stewart, S Evelyn; Storch, Eric A; Stranger, Barbara E; Turiel, Maurizio; Werge, Thomas; Andreassen, Ole A; Børglum, Anders D; Walitza, Susanne; Hveem, Kristian; Hansen, Bjarne K; Rück, Christian; Martin, Nicholas G; Milani, Lili; Mors, Ole; Reichborn-Kjennerud, Ted; Ribasés, Marta; Kvale, Gerd; Mataix-Cols, David; Domschke, Katharina; Grünblatt, Edna; Wagner, Michael; Zwart, John-Anker; Breen, Gerome; Nestadt, Gerald; Kaprio, Jaakko; Arnold, Paul D; Grice, Dorothy E; Knowles, James A; Ask, Helga; Verweij, Karin J; Davis, Lea K; Smit, Dirk J; Crowley, James J; Scharf, Jeremiah M; Stein, Murray B; Gelernter, Joel; Mathews, Carol A; Derks, Eske M; Mattheisen, Manuel
Obsessive-compulsive disorder (OCD) affects ~1% of children and adults and is partly caused by genetic factors. We conducted a genome-wide association study (GWAS) meta-analysis combining 53,660 OCD cases and 2,044,417 controls and identified 30 independent genome-wide significant loci. Gene-based approaches identified 249 potential effector genes for OCD, with 25 of these classified as the most likely causal candidates, including WDR6, DALRD3 and CTNND1 and multiple genes in the major histocompatibility complex (MHC) region. We estimated that ~11,500 genetic variants explained 90% of OCD genetic heritability. OCD genetic risk was associated with excitatory neurons in the hippocampus and the cortex, along with D1 and D2 type dopamine receptor-containing medium spiny neurons. OCD genetic risk was shared with 65 of 112 additional phenotypes, including all the psychiatric disorders we examined. In particular, OCD shared genetic risk with anxiety, depression, anorexia nervosa and Tourette syndrome and was negatively associated with inflammatory bowel diseases, educational attainment and body mass index.
PMID: 40360802
ISSN: 1546-1718
CID: 5844232

Efficacy of cognitive behavioral therapies with a trauma focus for posttraumatic stress disorder: An individual participant data meta-analysis

Wright, Simonne L; Karyotaki, Eirini; Sijbrandij, Marit; Cuijpers, Pim; Bisson, Jonathan I; Papola, Davide; Witteveen, Anke B; Back, Sudie E; Bichescu-Burian, Dana; Capezzani, Liuva; Cloitre, Marylene; Devilly, Grant J; Elbert, Thomas; Mello, Marcelo Feijo; Ford, Julian D; Grasso, Damion; Gray, Richard; Haller, Moira; Hunt, Nigel; Kleber, Rolf J; König, Julia; Kullack, Claire; Laugharne, Jonathan; Liebman, Rachel; Lee, Christopher William; Lely, Jeannette; Markowitz, John C; Monson, Candice; Nijdam, Mirjam J; Norman, Sonya; Olff, Miranda; Orang, Tahereh Mina; Ostacoli, Luca; Paunovic, Nenad; Petkova, Eva; Rosner, Rita; Schauer, Maggie; Schmitz, Joy M; Schnyder, Ulrich; Smith, Brian; Vujanovic, Anka A; Zang, Yinyin; Seedat, Soraya
OBJECTIVE:This individual participant data meta-analysis aimed to investigate the effectiveness of cognitive behavioral therapy with a trauma focus (CBT-TF) for posttraumatic stress disorder (PTSD). Furthermore, we examined the effect of moderators on PTSD symptom severity. METHOD/METHODS:This study included randomized controlled trials comparing CBT-TF to an inactive or active comparison group for adults with PTSD. The primary and secondary outcomes were PTSD symptom severity and remission, respectively. Moderators included sociodemographic and clinical variables. RESULTS:Twelve studies compared CBT-TF with inactive (n = 625) and 11 with active comparison conditions (n = 706). The one-stage individual participant data meta-analysis found that CBT-TF was more effective than inactive comparison conditions (β = -0.78; OR = 2.34) and not significantly different from active comparison conditions (β = 0.02; OR = 0.53) in reducing PTSD symptom severity and achieving PTSD remission, respectively. When comparing CBT-TF with inactive treatments, moderator analysis found that divorced participants had greater PTSD symptoms postintervention following CBT-TF than participants who were single, cohabitating, or married receiving CBT-TF, both in the completer (β = 0.93) and full-sample (β = 0.59) analyses. For the active treatment comparison, moderator analysis found that participants taking psychotropic medication had lower PTSD symptoms following CBT-TF than those not taking psychotropic medication in the completer analysis (β = -0.39). CONCLUSION/CONCLUSIONS:Based on our moderator analyses, further research is needed to understand the effect of psychotropic medication on the CBT-TF intervention process. Moreover, divorced participants with PTSD receiving CBT-TF might benefit from enhanced support. (PsycInfo Database Record (c) 2025 APA, all rights reserved).
PMID: 40388148
ISSN: 1939-2117
CID: 5852862

High-resolution volumetric dynamic magnetic resonance imaging of the wrist using an 8-channel flexible receive coil

Zi, Ruoxun; Abbas, Batool; Wang, Bili; Walczyk, Jerzy; Brown, Ryan; Petchprapa, Catherine; Fishbaugh, James; Gerig, Guido; Block, Kai Tobias; Lattanzi, Riccardo
OBJECTIVE:Real-time imaging is useful for the evaluation of wrist instability. However, currently available real-time magnetic resonance imaging (MRI) methods are limited due to their 2D nature or provide insufficient temporal resolution and image quality for quantitative kinematic analysis. This work introduces a novel approach for volumetric dynamic MRI of the wrist joint during active motion and demonstrates the feasibility of tracking carpal bone motion. MATERIALS AND METHODS/METHODS:A flexible 8-element 3 T wrist receive coil and 3D-printed support platform for guiding motion were designed for dynamic wrist imaging. 2D real-time images were acquired using a fat-saturated FLASH sequence with radial sampling and reconstructed with the GRASP algorithm. Corresponding volumetric dynamic wrist images were obtained by assembling 2D real-time images into 3D snapshots using autodetected MRI-visible markers for slice alignment. The proposed method was demonstrated for radial-ulnar deviation on five healthy volunteers. RESULTS:The flexible wrist coil provided high SNR while allowing a wide range of wrist movements. 2D real-time wrist images were acquired with a temporal resolution of 48 ms/frame with negligible streaking artifacts. Carpal bones and metacarpal bones were properly aligned in the assembled dynamic volumes for all five subjects. The excellent bone-to-tissue contrast enabled accurate segmentation of the individual carpal bones on the assembled dynamic volumes. CONCLUSION/CONCLUSIONS:This work introduces a novel wrist coil and demonstrates that real-time volumetric dynamic examination of the moving wrist is feasible. The achieved image quality and high temporal resolution could enable automatic segmentation of carpal bones and quantitative kinematic assessment for evaluating wrist instability.
PMID: 39560769
ISSN: 1432-2161
CID: 5758362

Global psychiatrists' opinions about hikikomori from biopsychosocial perspectives: International case vignette survey

Tan, Marcus P J; Hayakawa, Kohei; Nakagami, Yukako; Pereira-Sanchez, Victor; Park, Seon Cheol; Park, Yong Chon; Moon, Seok Woo; Choi, Tae Young; Xiang, Yu-Tao; Sim, Kang; Horinouchi, Toru; Avasthi, Ajit; Grover, Sandeep; Kallivayalil, Roy Abraham; Rai, Yugesh; Shalbafan, Mohammadreza; Chongsuksiri, Pavita; Udomratn, Pichet; Kathriarachchi, Samudra T; Javed, Afzal; Chong, Mian-Yoon; Chay-Hoon, Tan; Inada, Toshiya; Murai, Toshiya; Nakao, Tomohiro; Kanba, Shigenobu; Lin, Shih-Ku; Sartorius, Norman; Shinfuku, Naotaka; Kato, Takahiro A
AIM/UNASSIGNED:(prolonged social isolation), and how they formulate and treat such cases. METHODS/UNASSIGNED:case vignette was sent to psychiatrists of 34 countries around the world. Participants rated for the vignette: frequency of similar cases in one's practicing country; and aspects of formulation, diagnosis, suicide risk, and treatment plan. RESULTS/UNASSIGNED:In total, 344 complete responses from 34 countries were returned. Eight countries/areas had 10 or more respondents: Japan (61), South Korea (54), Nepal (48), Iran (40), Thailand (32), India (23), Hong Kong (12), and UK (10); the remainder were placed in the "others" group (64). Respondents from all countries except Thailand felt that similar cases were seen. Diverse patterns of response were obtained regarding formulation and treatment. Japan, South Korea, and "others" favored psychosocial aspects in the formulation, while Iran, Nepal, and India favored biological factors. Most respondents felt the case could be treated by an outpatient visit, while others preferred hospitalization. Psychotherapy was rated highly as an intervention; Iran, South Korea, and "others" also rated pharmacotherapy highly. CONCLUSION/UNASSIGNED:patients.
PMCID:12099068
PMID: 40416471
ISSN: 2769-2558
CID: 5855052

Editorial: Physical Exercise as a Treatment for Anxiety and Depression in Children and Adolescents? The Devil is in the Details [Editorial]

Cortese, Samuele; Solmi, Marco; Gosling, Corentin J
PMID: 40449582
ISSN: 1527-5418
CID: 5854642

Maternal reflective functioning in pregnancy and parenting during the preschool period

Drury, Georgina; Elezi, Jessica; Kondor, Lyndsey; Beeghly, Marjorie; Trentacosta, Christopher J; Thomason, Moriah E; Stacks, Ann M
Parental reflective functioning (PRF) refers to a parent's ability to understand their own and their child's mental states and connect them to behaviors. This longitudinal study evaluated (1) associations among prenatal PRF, using the Pregnancy Interview, demographics, prenatal maternal depressive symptoms, and maternal-fetal attachment and (2) whether prenatal PRF predicted parenting quality assessed during unstructured and challenging mother-child interaction tasks beyond infancy, after controlling for cumulative risk. Data were collected in an urban community sample of women in the midwestern US. Prenatal PRF was positively associated with maternal educational attainment and negatively associated with cumulative demographic risk, but not with depressive symptoms or maternal-fetal attachment. Controlling for cumulative risk, hierarchical regressions showed that prenatal PRF was the sole significant predictor of positive parenting at 36 months, observed during a challenging teaching task but not during free play. Prenatal PRF did not predict negative parenting. These patterns persisted when analyses were repeated within a subsample of Black mothers, with PRF again being the sole significant predictor of positive parenting. Further attention to cultural variations in PRF and parenting in future research is warranted.
PMID: 40440056
ISSN: 1097-0355
CID: 5854772

Inpatient Child and Adolescent Psychiatry Youth with Autism and/or Intellectual Disabilities: Clinical Characteristics and Considerations

Morris, Arielle M; Lynch, Sean; Kasdin, Rachel G; Hill, Isabela; Shah, Salonee; Shanker, Parul; Becker, Timothy D; Staudenmaier, Paige; Leong, Alicia W; Martin, Dalton; Rice, Timothy
Children and adolescents with autism spectrum disorder and/or an intellectual disability (ASD/ID) are psychiatrically hospitalized at disproportionately higher rates than youth without ASD/ID. Despite this, few studies have compared the clinical courses of youth with and without ASD/ID in inpatient (IP) child and adolescent psychiatry (CAP) settings. This study used a cross-sectional design of all youth (M = 14.0 years, SD = 2.6 years) admitted to an urban IP unit between 2018 and 2021 to examine differences between ASD/ID and non-ASD/ID youth across dimensions of sociodemographic and psychiatric history and clinical course. 1101 Patients were included in the study and 170 (15.4%) had a history of ASD/ID. ASD/ID youth were more likely to be younger, be male, have histories of violence, and on average have more prior hospitalizations and existing psychotropic prescriptions than their non-ASD/ID counterparts. ASD/ID youth were less likely than their non-ASD/ID peers to be admitted for suicidality and more likely to be admitted for aggression; they had longer average lengths of stay, received more IP emergency medications for agitation, and experienced greater polypharmacy at discharge. The IP psychiatric clinical course of ASD/ID youth differs from that of non-ASD/ID youth, suggesting that ASD/ID youth often present to IP settings with externalizing symptoms. Findings highlight the importance of clinical strategies tailored to the unique needs of ASD/ID youth to improve their care in general IP CAP settings.
PMID: 40437185
ISSN: 1573-3432
CID: 5854652

Characterizing Long COVID Symptoms During Early Childhood

Gross, Rachel S; Thaweethai, Tanayott; Salisbury, Amy L; Kleinman, Lawrence C; Mohandas, Sindhu; Rhee, Kyung E; Snowden, Jessica N; Tantisira, Kelan G; Warburton, David; Wood, John C; Kinser, Patricia A; Milner, Joshua D; Rosenzweig, Erika B; Irby, Katherine; Flaherman, Valerie J; Karlson, Elizabeth W; Chibnik, Lori B; Pant, Deepti B; Krishnamoorthy, Aparna; Gallagher, Richard; Lamendola-Essel, Michelle F; Hasson, Denise C; Katz, Stuart D; Yin, Shonna; Dreyer, Benard P; Blancero, Frank; Carmilani, Megan; Coombs, K; Fitzgerald, Megan L; Letts, Rebecca J; Peddie, Aimee K; Aschner, Judy L; Atz, Andrew M; Banerjee, Dithi; Bogie, Amanda; Bukulmez, Hulya; Clouser, Katharine; Cottrell, Lesley A; Cowan, Kelly; D'Sa, Viren A; Dozor, Allen; Elliott, Amy J; Faustino, E Vincent S; Fiks, Alexander G; Gaur, Sunanda; Gennaro, Maria L; Gordon, Stewart; Hasan, Uzma N; Hester, Christina M; Hogan, Alexander; Hsia, Daniel S; Kaelber, David C; Kosut, Jessica S; Krishnan, Sankaran; McCulloh, Russell J; Michelow, Ian C; Nolan, Sheila M; Oliveira, Carlos R; Olson, Lynn M; Pace, Wilson D; Palumbo, Paul; Raissy, Hengameh; Reyes, Andy; Ross, Judith L; Salazar, Juan C; Selvarangan, Rangaraj; Stein, Cheryl R; Stevenson, Michelle D; Teufel, Ronald J; Werzberger, Alan; Westfall, John M; Zani, Kathleen; Zempsky, William T; Zimmerman, Emily; Bind, Marie-Abele C; Chan, James; Guan, Zoe; Morse, Richard E; Reeder, Harrison T; Metz, Torri D; Newburger, Jane W; Truong, Dongngan T; Foulkes, Andrea S; Stockwell, Melissa S; ,; ,
IMPORTANCE:Recent studies have identified characteristic symptom patterns of long COVID (LC) in adults and children older than 5 years. However, LC remains poorly characterized in early childhood. This knowledge gap limits efforts to identify, care for, and prevent LC in this vulnerable population. OBJECTIVES:To identify symptoms that had the greatest difference in frequency comparing children with a history of SARS-CoV-2 infection to those without, to identify differences in the types of symptoms by age group (infants/toddlers [0-2 years] vs preschool-aged children [3-5 years]), and to derive an index that can be used in research studies to identify young children with LC. DESIGN, SETTING, AND PARTICIPANTS:This was a multisite longitudinal cohort study with enrollment from over 30 US health care and community settings, including infants, toddlers, and preschool-aged children with and without SARS-CoV-2 infection history. Study data were analyzed from May to December 2024. EXPOSURE:SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES:LC and 41 symptoms among infants/toddlers and 75 symptoms among preschool-aged children. RESULTS:The study included 472 infants/toddlers (mean [SD] age, 12 [9] months; 278 infected with SARS-CoV-2; 194 uninfected; 234 male [50%]; 73 Black or African American [16%]; 198 Hispanic, Latino, or Spanish [43%]; 242 White [52%]) and 539 preschool-aged children (mean [SD] age, 48 [10] months; 399 infected with SARS-CoV-2; 140 uninfected; 277 female [51%]; 70 Black or African American [13%]; 210 Hispanic, Latino, or Spanish [39%]; 287 White [54%]). The median (IQR) time between first infections and completion of symptom surveys was 318 (198-494) days for infants/toddlers and 520 (330-844) days for preschool-aged children. A research index was derived for each age group based on symptoms most associated with infection history. The index is calculated by summing scores assigned to each prolonged symptom that was present, where higher scores indicate greater magnitude of association with history of SARS-CoV-2 infection: poor appetite (5 points), trouble sleeping (3.5 points), wet cough (3.5 points), dry cough (3 points), and stuffy nose (0.5 points) for infants/toddlers, and daytime tiredness/sleepiness/low energy (6.5 points) and dry cough (3 points) for preschool-aged children. Among infants/toddlers with infection, 40 of 278 (14%) were classified as having probable LC by having an index of at least 4 points. Among preschool-aged children, 61 of 399 (15%) were classified as having probable LC by having an index of at least 3 points. Participants with higher indices often had poorer overall health, lower quality of life, and perceived delays in developmental milestones. CONCLUSIONS AND RELEVANCE:This cohort study identified symptom patterns and derived research indices that were distinct between the 2 age groups and differed from those previously identified in older ages, demonstrating the need to characterize LC separately across age ranges.
PMID: 40554463
ISSN: 2168-6211
CID: 5911972

Unveiling Disparities: The Case for Group-Specific Analyses in Child Psychiatry [Editorial]

Janecka, Magdalena; Medina, Candice; Zaks, Nina; Ben Messaoud, Khaoula; Khachadourian, Vahe; Croen, Lisa A
PMID: 40414283
ISSN: 1527-5418
CID: 5855022

Breaking the Cycle: Predicting Agitation Crises in Child and Adolescent Inpatient Psychiatry

Burns, Ricky; Lynch, Sean T; Staudenmaier, Paige; Becker, Timothy D; Shanker, Parul; Martin, Dalton; Leong, Alicia; Rice, Timothy
This study examined biopsychosocial factors associated with the use of intramuscular (IM) agitation emergency medication in child and adolescent psychiatric inpatients. A retrospective review of 1,101 patients hospitalized between June 2018-November 2021 at an urban teaching hospital identified predictors of IM medication use through linear regression analysis. Among these patients, 196 received IM medication during their stay. Female sex was associated with a lower likelihood of receiving IM treatment, while factors such as prior involvement with child protective services, a history of violence, previous psychiatric hospitalizations, and use of multiple home psychiatric medications increased the likelihood. Agitation episodes pose risks to both patients and staff, underscoring the importance of early identification and intervention. Understanding these risk factors may guide proactive strategies to reduce the frequency and severity of agitation and limit reliance on emergency pharmacological interventions. Further research is needed to refine predictive models and explore non-pharmacological management approaches.
PMID: 40377832
ISSN: 1573-3327
CID: 5844742