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Randomized Controlled Trial of the Effects of High-Dose Ondansetron on Clinical Symptoms and Brain Connectivity in Obsessive-Compulsive and Tic Disorders

Stern, Emily R; Collins, Katherine A; Bragdon, Laura B; Eng, Goi Khia; Recchia, Nicolette; Coffey, Barbara J; Leibu, Evan; Murrough, James W; Tobe, Russell H; Iosifescu, Dan V; Burdick, Katherine E; Goodman, Wayne K
OBJECTIVE/UNASSIGNED:receptor antagonist ondansetron. The present study employed an experimental medicine approach to test the effects of 4 weeks of high-dose ondansetron compared to placebo on SP severity and brain connectivity in a cohort of individuals with OCD and/or Tourette's disorder. METHODS/UNASSIGNED:Of 51 participants who completed the study, 27 were assigned to receive 24 mg/day of ondansetron and 24 to receive placebo. Analyses examined changes in SP severity and, for participants with OCD, overall OCD severity from baseline to final visit. Functional MRI data were collected at both visits for analysis of intrinsic functional connectivity metrics characterizing global correlation (reflecting area "hubness") and local correlation (reflecting near-neighbor coherence). RESULTS/UNASSIGNED:There were no significant differences between ondansetron and placebo in the reduction of SP or overall OCD severity in the full sample. In a subsample of participants with OCD taking concomitant serotonin reuptake inhibitors (SRIs), ondansetron was associated with a significant decrease in overall OCD severity and global connectivity of the medial sensorimotor cortex compared with placebo. Longitudinal reductions in SP severity were related to decreases in right sensorimotor hubness in both groups, and to brainstem local coherence only in participants taking ondansetron. CONCLUSIONS/UNASSIGNED:There was no effect of high-dose ondansetron on SP. However, when used as an augmentation to SRIs, ondansetron reduced overall OCD severity, which may be related to changes in the "hubness" of the sensorimotor cortex. Ondansetron's ability to modulate brainstem connectivity may underlie its variable effectiveness in reducing SP.
PMID: 39876680
ISSN: 1535-7228
CID: 5780852

Using capacity assessments and tailored technical assistance to advance trauma informed care integration at the organizational level

Senter, Lindsay; Baumgartner, Sabrina R; Crinklaw, Allyson; Rebella, Emily; Hurley, Beth; McCauley, Kelly; Bryant, Lindsay; Loeb, Brita; Cervantes, Paige; Bogdewic, Stephanie; Horwitz, Sarah; Cicatelli, Barbara
BACKGROUND:The prevalence of trauma among individuals with HIV has prompted efforts to integrate trauma-informed care (TIC) into HIV care and treatment to improve health outcomes. A TIC Implementation Model, developed by a US capacity-building organization focuses on organizational changes, aligning cultural and physical environments, emphasizing values like safety and trustworthiness, engaging leadership, and training staff in skills-based TIC services. Despite growing research, gaps remain in understanding the relationship between organizational capacity, provider knowledge, and the dosage of technical assistance (TA) required to sustain TIC integration. Researchers investigated how the project team adapted the type and amount of TA based on initial Cultural Assessment scores (measuring core TIC values) and its impact on Implementation Status scores. METHODS:This study focuses on eight of 20 HIV care agencies in New Jersey that had largely met their TIC implementation goals by Spring 2022. As part of the TIC Implementation Model to measure agency capacity and implementation progress over time, agency staff and clients completed a Cultural Assessment (n = 72) and Physical Assessment (n = 43); staff completed a Pre/Post Training Survey (n = 296); and implementation teams at 8 agencies completed an Implementation Status Assessment Tool. Additionally, TA Logs capturing the details of TA meetings with the eight agencies were recorded by project staff. Data from these tools were analyzed in aggregate by agency using descriptive and correlational analyses. RESULTS:Results demonstrated responsive TA correlated with agencies' baseline capacity. Agencies with lower capacity received significantly more frequent and extended TA encounters, which were associated with higher implementation scores and improvements in cultural environments for staff and clients (e.g., new protocols for staff response plans). CONCLUSIONS:These findings underscore the importance of tailored TA in fostering diverse organizational cultures conducive to TIC implementation. For HIV care agencies, successful TIC implementation can impact health behaviors and outcomes for clients impacted by trauma. The TIC Implementation Model significantly advanced organizations' ability to transform their culture and systems, increasing their capacity to implement and sustain TIC integration. These results align with existing research that emphasizes when time is invested to shift organizational culture and develop leadership, new practices can effectively be implemented and scaled-up.
PMCID:11773949
PMID: 39875879
ISSN: 1472-6963
CID: 5780832

Emotion processing difficulties in ADHD: a Bayesian meta-analysis study

Soler-Gutiérrez, Ana-María; Sánchez-Carmona, Alberto J; Albert, Jacobo; Hinojosa, José Antonio; Cortese, Samuele; Bellato, Alessio; Mayas, Julia
We investigated whether there is an emotional processing deficit in ADHD and whether this only applies to specific emotional categories. In this PRISMA-compliant systematic review based on a pre-registered protocol ( https://osf.io/egp7d ), we searched MEDLINE, PsycINFO, ERIC, Scopus and Web of Science databases until 3rd December 2023, to identify empirical studies comparing emotional processing in individuals meeting DSM (version III to 5-TR) or ICD (version 9 or 10) criteria for Attention Deficit/Hyperactivity Disorder (ADHD) and in a non-psychiatric control group. Study quality was assessed with the Appraisal tool for Cross-Sectional Studies (AXIS). Eighty studies were included and meta-analysed (encompassing 6191 participants and 465 observations). Bayesian meta-analyses were conducted to compare individuals with ADHD and non-psychiatric controls on overall emotional processing measures (meta-analysis 1) and across emotional categories (meta-analysis 2). The type of stimulus employed, outcome measurement reported, age, sex, and medication status were analysed as moderators. We found poorer performance in both overall emotion processing (g =  - 0.65) and across emotional categories (anger g =  - 0.37; disgust g =  - 0.24; fear g =  - 0.37; sadness g =  - 0.34; surprise g =  - 0.26; happiness/positive g =  - 0.31; negative g =  - 0.20; neutral g =  - 0.25) for individuals with ADHD compared to non-psychiatric controls. Scales items and accuracy outcome being the most effective moderators in detecting such differences. No effects of age, sex, or medication status were found. Overall, these results show that impaired emotional processing is a relevant feature of ADHD and suggest that it should be systematically assessed in clinical practice.
PMID: 39853403
ISSN: 1435-165x
CID: 5802622

Latest clinical frontiers related to autism diagnostic strategies

Cortese, Samuele; Bellato, Alessio; Gabellone, Alessandra; Marzulli, Lucia; Matera, Emilia; Parlatini, Valeria; Petruzzelli, Maria Giuseppina; Persico, Antonio M; Delorme, Richard; Fusar-Poli, Paolo; Gosling, Corentin J; Solmi, Marco; Margari, Lucia
The diagnosis of autism is currently based on the developmental history, direct observation of behavior, and reported symptoms, supplemented by rating scales/interviews/structured observational evaluations-which is influenced by the clinician's knowledge and experience-with no established diagnostic biomarkers. A growing body of research has been conducted over the past decades to improve diagnostic accuracy. Here, we provide an overview of the current diagnostic assessment process as well as of recent and ongoing developments to support diagnosis in terms of genetic evaluation, telemedicine, digital technologies, use of machine learning/artificial intelligence, and research on candidate diagnostic biomarkers. Genetic testing can meaningfully contribute to the assessment process, but caution is required when interpreting negative results, and more work is needed to strengthen the transferability of genetic information into clinical practice. Digital diagnostic and machine-learning-based analyses are emerging as promising approaches, but larger and more robust studies are needed. To date, there are no available diagnostic biomarkers. Moving forward, international collaborations may help develop multimodal datasets to identify biomarkers, ensure reproducibility, and support clinical translation.
PMID: 39879991
ISSN: 2666-3791
CID: 5780972

Genomics yields biological and phenotypic insights into bipolar disorder

O'Connell, Kevin S; Koromina, Maria; van der Veen, Tracey; Boltz, Toni; David, Friederike S; Yang, Jessica Mei Kay; Lin, Keng-Han; Wang, Xin; Coleman, Jonathan R I; Mitchell, Brittany L; McGrouther, Caroline C; Rangan, Aaditya V; Lind, Penelope A; Koch, Elise; Harder, Arvid; Parker, Nadine; Bendl, Jaroslav; Adorjan, Kristina; Agerbo, Esben; Albani, Diego; Alemany, Silvia; Alliey-Rodriguez, Ney; Als, Thomas D; Andlauer, Till F M; Antoniou, Anastasia; Ask, Helga; Bass, Nicholas; Bauer, Michael; Beins, Eva C; Bigdeli, Tim B; Pedersen, Carsten Bøcker; Boks, Marco P; Børte, Sigrid; Bosch, Rosa; Brum, Murielle; Brumpton, Ben M; Brunkhorst-Kanaan, Nathalie; Budde, Monika; Bybjerg-Grauholm, Jonas; Byerley, William; Cabana-Domínguez, Judit; Cairns, Murray J; Carpiniello, Bernardo; Casas, Miquel; Cervantes, Pablo; Chatzinakos, Chris; Chen, Hsi-Chung; Clarence, Tereza; Clarke, Toni-Kim; Claus, Isabelle; Coombes, Brandon; Corfield, Elizabeth C; Cruceanu, Cristiana; Cuellar-Barboza, Alfredo; Czerski, Piotr M; Dafnas, Konstantinos; Dale, Anders M; Dalkner, Nina; Degenhardt, Franziska; DePaulo, J Raymond; Djurovic, Srdjan; Drange, Ole Kristian; Escott-Price, Valentina; Fanous, Ayman H; Fellendorf, Frederike T; Ferrier, I Nicol; Forty, Liz; Frank, Josef; Frei, Oleksandr; Freimer, Nelson B; Fullard, John F; Garnham, Julie; Gizer, Ian R; Gordon, Scott D; Gordon-Smith, Katherine; Greenwood, Tiffany A; Grove, Jakob; Guzman-Parra, José; Ha, Tae Hyon; Hahn, Tim; Haraldsson, Magnus; Hautzinger, Martin; Havdahl, Alexandra; Heilbronner, Urs; Hellgren, Dennis; Herms, Stefan; Hickie, Ian B; Hoffmann, Per; Holmans, Peter A; Huang, Ming-Chyi; Ikeda, Masashi; Jamain, Stéphane; Johnson, Jessica S; Jonsson, Lina; Kalman, Janos L; Kamatani, Yoichiro; Kennedy, James L; Kim, Euitae; Kim, Jaeyoung; Kittel-Schneider, Sarah; Knowles, James A; Kogevinas, Manolis; Kranz, Thorsten M; Krebs, Kristi; Kushner, Steven A; Lavebratt, Catharina; Lawrence, Jacob; Leber, Markus; Lee, Heon-Jeong; Liao, Calwing; Lucae, Susanne; Lundberg, Martin; MacIntyre, Donald J; Maier, Wolfgang; Maihofer, Adam X; Malaspina, Dolores; Manchia, Mirko; Maratou, Eirini; Martinsson, Lina; Mattheisen, Manuel; McGregor, Nathaniel W; McInnis, Melvin G; McKay, James D; Medeiros, Helena; Meyer-Lindenberg, Andreas; Millischer, Vincent; Morris, Derek W; Moutsatsou, Paraskevi; Mühleisen, Thomas W; O'Donovan, Claire; Olsen, Catherine M; Panagiotaropoulou, Georgia; Papiol, Sergi; Pardiñas, Antonio F; Park, Hye Youn; Perry, Amy; Pfennig, Andrea; Pisanu, Claudia; Potash, James B; Quested, Digby; Rapaport, Mark H; Regeer, Eline J; Rice, John P; Rivera, Margarita; Schulte, Eva C; Senner, Fanny; Shadrin, Alexey; Shilling, Paul D; Sigurdsson, Engilbert; Sindermann, Lisa; Sirignano, Lea; Siskind, Dan; Slaney, Claire; Sloofman, Laura G; Smeland, Olav B; Smith, Daniel J; Sobell, Janet L; Soler Artigas, Maria; Stein, Dan J; Stein, Frederike; Su, Mei-Hsin; Sung, Heejong; Świątkowska, Beata; Terao, Chikashi; Tesfaye, Markos; Tesli, Martin; Thorgeirsson, Thorgeir E; Thorp, Jackson G; Toma, Claudio; Tondo, Leonardo; Tooney, Paul A; Tsai, Shih-Jen; Tsermpini, Evangelia Eirini; Vawter, Marquis P; Vedder, Helmut; Vreeker, Annabel; Walters, James T R; Winsvold, Bendik S; Witt, Stephanie H; Won, Hong-Hee; Ye, Robert; Young, Allan H; Zandi, Peter P; Zillich, Lea; ,; Adolfsson, Rolf; Alda, Martin; Alfredsson, Lars; Backlund, Lena; Baune, Bernhard T; Bellivier, Frank; Bengesser, Susanne; Berrettini, Wade H; Biernacka, Joanna M; Boehnke, Michael; Børglum, Anders D; Breen, Gerome; Carr, Vaughan J; Catts, Stanley; Cichon, Sven; Corvin, Aiden; Craddock, Nicholas; Dannlowski, Udo; Dikeos, Dimitris; Etain, Bruno; Ferentinos, Panagiotis; Frye, Mark; Fullerton, Janice M; Gawlik, Micha; Gershon, Elliot S; Goes, Fernando S; Green, Melissa J; Grigoroiu-Serbanescu, Maria; Hauser, Joanna; Henskens, Frans A; Hjerling-Leffler, Jens; Hougaard, David M; Hveem, Kristian; Iwata, Nakao; Jones, Ian; Jones, Lisa A; Kahn, René S; Kelsoe, John R; Kircher, Tilo; Kirov, George; Kuo, Po-Hsiu; Landén, Mikael; Leboyer, Marion; Li, Qingqin S; Lissowska, Jolanta; Lochner, Christine; Loughland, Carmel; Luykx, Jurjen J; Martin, Nicholas G; Mathews, Carol A; Mayoral, Fermin; McElroy, Susan L; McIntosh, Andrew M; McMahon, Francis J; Medland, Sarah E; Melle, Ingrid; Milani, Lili; Mitchell, Philip B; Morken, Gunnar; Mors, Ole; Mortensen, Preben Bo; Müller-Myhsok, Bertram; Myers, Richard M; Myung, Woojae; Neale, Benjamin M; Nievergelt, Caroline M; Nordentoft, Merete; Nöthen, Markus M; Nurnberger, John I; O'Donovan, Michael C; Oedegaard, Ketil J; Olsson, Tomas; Owen, Michael J; Paciga, Sara A; Pantelis, Christos; Pato, Carlos N; Pato, Michele T; Patrinos, George P; Pawlak, Joanna M; Ramos-Quiroga, Josep Antoni; Reif, Andreas; Reininghaus, Eva Z; Ribasés, Marta; Rietschel, Marcella; Ripke, Stephan; Rouleau, Guy A; Roussos, Panos; Saito, Takeo; Schall, Ulrich; Schalling, Martin; Schofield, Peter R; Schulze, Thomas G; Scott, Laura J; Scott, Rodney J; Serretti, Alessandro; Smoller, Jordan W; Squassina, Alessio; Stahl, Eli A; Stefansson, Hreinn; Stefansson, Kari; Stordal, Eystein; Streit, Fabian; Sullivan, Patrick F; Turecki, Gustavo; Vaaler, Arne E; Vieta, Eduard; Vincent, John B; Waldman, Irwin D; Weickert, Cynthia S; Weickert, Thomas W; Werge, Thomas; Whiteman, David C; Zwart, John-Anker; Edenberg, Howard J; McQuillin, Andrew; Forstner, Andreas J; Mullins, Niamh; Di Florio, Arianna; Ophoff, Roel A; Andreassen, Ole A; ,
Bipolar disorder is a leading contributor to the global burden of disease1. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown2. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings3, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder4, highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder.
PMID: 39843750
ISSN: 1476-4687
CID: 5778012

Building Community Through Data: The value of a Researcher Driven Open Science Ecosystem

Adams, Meredith C B; Bann, Carla M; Bayman, Emine Ozgur; Chao, Maria; Hergenroeder, Georgene W; Knott, Charles; Lindquist, Martin A; Luo, Z David; Martin, Rosemarie; Martone, Maryann E; McCarthy, John; McCumber, Micah; Meropol, Sharon B; Ridenour, Ty A; Saavedra, Lissette M; Sarker, Abeed; Anstrom, Kevin J; Thompson, Wesley K
PMID: 39836639
ISSN: 1526-4637
CID: 5802192

Insulin sensitivity and insulin secretion in adults with Friedreich's Ataxia: the role of skeletal muscle

Tamaroff, Jaclyn; Nguyen, Sara; Wilson, Neil E; Stefanovski, Darko; Xiao, Rui; Scattergood, Theresa; Capiola, Christopher; Schur, Gayatri Maria; Dunn, Julia; Dedio, Anna; Wade, Kristin; Shah, Hardik; Sharma, Rohit; Mootha, Vamsi K; Kelly, Andrea; Lin, Kimberly Y; Lynch, David R; Reddy, Ravinder; Rickels, Michael R; McCormack, Shana E
INTRODUCTION/BACKGROUND:Friedreich's Ataxia (FRDA) is a multi-system disorder caused by frataxin deficiency. FRDA-related diabetes mellitus (DM) is common. Frataxin supports skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity, a mediator of insulin sensitivity. Our objective was to test the association between skeletal muscle health and insulin sensitivity and secretion in adults with FRDA without DM. METHODS:Case-control study (NCT02920671). Glucose and insulin metabolism (stable-isotope oral glucose tolerance tests), body composition (dual-energy x-ray absorptiometry), physical activity (self-report), and skeletal muscle OXPHOS capacity (creatine chemical exchange saturation transfer MRI) were assessed. RESULTS:Participants included 11 individuals with FRDA (4 female), median age 27y (IQR 23, 39), BMI 26.9kg/m2 (24.1, 29.4), and 24 controls (11 female), 29y (26, 39), 24.4kg/m2 (21.8, 27.0). Fasting glucose was higher in FRDA (91 vs. 83mg/dL (5.0 vs. 4.6mmol/L), p<0.05). Individuals with FRDA had lower insulin sensitivity (WBISI 2.8 vs. 5.3, p<0.01), higher post-prandial insulin secretion (insulin secretory rate iAUC 30-180 minutes, 24,652 vs. 17,858, p<0.05), and more suppressed post-prandial endogenous glucose production (-0.9% vs. 26.9% of fasting EGP, p<0.05). In regression analyses, lower OXPHOS and inactivity explained some of the difference in insulin sensitivity. More visceral fat contributed to lower insulin sensitivity independent of FRDA. Insulin secretion accounting for sensitivity (disposition index) was not different. CONCLUSIONS:Lower mitochondrial OXPHOS capacity, inactivity, and visceral adiposity contribute to lower insulin sensitivity in FRDA. Higher insulin secretion appears compensatory, and when inadequate, could herald DM. Further studies are needed to determine if muscle- or adipose-focused interventions could delay FRDA-related DM.
PMID: 39109797
ISSN: 1945-7197
CID: 5730712

Reciprocal relationships between adolescent mental health difficulties and alcohol consumption

Kiri, Janet; Hall, James; Cortese, Samuele; Brandt, Valerie
The directionality of the relationship between adolescent alcohol consumption and mental health difficulties remains poorly understood. This study investigates the longitudinal relationship between alcohol use frequency, internalizing and externalizing symptoms from the ages of 11 to 17. We conducted a random-intercept cross-lagged panel model across three timepoints (ages: 11yrs, 14yrs, 17yrs; 50.4% female) in the Millennium Cohort Study (N = 10,647). Survey weights were used to account for attrition. At each timepoint, past month alcohol use frequency was self-reported, parents and cohort members reported internalizing/externalizing symptoms using the Strengths and Difficulties Questionnaire. We controlled for alcohol expectancies, sex, and four cumulative risk indices (perinatal risk, early childhood adverse parenting, longitudinal parent-level risk occurrence, and persistent household socioeconomic deprivation). More frequent past month alcohol use at age 11 predicted increased internalizing symptoms at age 14 (β = 0.06; p =.01). More frequent past month alcohol use at age 14 predicted increased externalizing symptoms at age 17 (β = 0.11; p <.001). Increased internalizing symptoms consistently predicted reduced alcohol use at the next timepoint throughout the study period (11 years: β= -0.04; p =.03; 14 years: β= -0.09; p <.001). Increased externalizing symptoms at age 11 predicted increased alcohol consumption at age 14 (β = 0.06; p =.004). Frequent adolescent alcohol consumption represents a significant risk for subsequent mental health difficulties. Externalizing symptoms and alcohol use frequency appear to exacerbate one another. Internalizing symptoms may reduce the risk of frequent alcohol consumption. Incorporating routine alcohol screening into adolescent mental health treatment settings could reduce the risk of comorbid externalizing and alcohol use disorders.
PMID: 39825937
ISSN: 1435-165x
CID: 5777862

Sleep health among sexual and gender minority people in the United States: A scoping review

Leonard, Sarah I; Castiblanco, Maya R; Chang, Audrey; Belloir, Joseph; Caceres, Billy A; Bruzzese, Jean-Marie; Jackman, Kasey B
Sleep has been found to be essential to physical and mental health. Sexual and gender minority (SGM; e.g., lesbian, gay, bisexual, transgender, nonbinary) individuals experience significant health disparities, and emerging research indicates that this includes disparities in sleep health. However, the current literature on sleep health in this population has not previously been rigorously reviewed. This scoping review provides a comprehensive overview and synthesis of the current literature on SGM sleep health in the United States. Following established scoping review methodology, we systematically searched PubMed, CINAHL, PsycINFO, LGBTQ + Source, and Scopus; 76 studies met inclusion criteria. Included studies indicated significant sleep disparities exist for SGM people, particularly sexual minority women and gender minority people. Social determinants of health, including bullying and discrimination, were associated with worse sleep health. Included studies were heterogeneous and had methodological weaknesses, leaving opportunities for future research. Overall, findings point to the need for more rigorous research to advance understanding of sleep health across SGM subgroups and inform interventions to improve sleep health among SGM people, given the known negative impact of poor sleep on overall health.
PMID: 39874816
ISSN: 1878-5506
CID: 5780752

Zuranolone Safety and Tolerability in Adults with Postpartum Depression: Analyses from SKYLARK, a 50 mg Placebo-Controlled Study

Meltzer-Brody, Samantha; Shirikjian, Lara; Cooke, Jennifer; LaGuerre, Kevin; Moseley, Margaret K; Li, Sigui; Kile, Deidre; Forrestal, Fiona; Ona, Victor; Levin, Seth; Kotecha, Mona; Lasser, Robert; Joseph, Judith F
ORIGINAL:0017674
ISSN: 1092-8529
CID: 5853932