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Department/Unit:Child and Adolescent Psychiatry

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Intestinal Predictors of Whole Blood Serotonin Levels in Children With or Without Autism

Zuniga-Kennedy, Miranda; Davoren, Micah; Shuffrey, Lauren C; Luna, Ruth Ann; Savidge, Tor; Prasad, Vinay; Anderson, George M; Veenstra-VanderWeele, Jeremy; Williams, Kent C
Hyperserotonemia, or elevated levels of whole blood serotonin (WB5-HT), was the first biomarker linked to autism spectrum disorder (ASD). Despite numerous studies investigating the etiology of hyperserotonemia, results have been inconsistent. Recent findings suggest a relationship between the immune system and hyperserotonemia. The current study investigated whether intestinal 5-HT levels, 5-HT gene expression, or intestinal cell types predict WB5-HT. Participants included thirty-one males aged 3-18 who were classified into one of three groups: ASD and functional GI issues, typically developing with GI issues, and typically developing without GI issues. Samples from a lower endoscopy were analyzed to examine the pathways in predicting WB-5HT. Results demonstrated an association between T-Lymphocytes and WB5-HT.
PMID: 35726077
ISSN: 1573-3432
CID: 5340632

Structural Brain Correlates of Childhood Inhibited Temperament: An ENIGMA-Anxiety Mega-analysis

Bas-Hoogendam, Janna Marie; Bernstein, Rachel; Benson, Brenda E; Buss, Kristin A; Gunther, Kelley E; Pérez-Edgar, Koraly; Salum, Giovanni A; Jackowski, Andrea P; Bressan, Rodrigo A; Zugman, André; Degnan, Kathryn A; Filippi, Courtney A; Fox, Nathan A; Henderson, Heather A; Tang, Alva; Zeytinoglu, Selin; Harrewijn, Anita; Hillegers, Manon H J; White, Tonya; van IJzendoorn, Marinus H; Schwartz, Carl E; Felicione, Julia M; DeYoung, Kathryn A; Shackman, Alexander J; Smith, Jason F; Tillman, Rachael M; van den Berg, Yvonne H M; Cillessen, Antonius H N; Roelofs, Karin; Tyborowska, Anna; Hill, Shirley Y; Battaglia, Marco; Tettamanti, Marco; Dougherty, Lea R; Jin, Jingwen; Klein, Daniel N; Leung, Hoi-Chung; Avery, Suzanne N; Blackford, Jennifer Urbano; Clauss, Jacqueline A; Hayden, Elizabeth P; Liu, Pan; Vandermeer, Matthew R J; Goldsmith, H Hill; Planalp, Elizabeth M; Nichols, Thomas E; Thompson, Paul M; Westenberg, P Michiel; van der Wee, Nic J A; Groenewold, Nynke A; Stein, Dan J; Winkler, Anderson M; Pine, Daniel S
Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years.1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar and to withdraw from unfamiliar people, objects, and unexpected events. This temperament is referred to as behavioral inhibition or inhibited temperament (IT).2 IT is a moderately heritable trait1 that can be measured in multiple species.3 In humans, levels of IT can be quantified from the first year of life through direct behavioral observations or reports by caregivers or teachers. Similar approaches as well as self-report questionnaires on current and/or retrospective levels of IT1 can be used later in life.
PMCID:9434711
PMID: 36038199
ISSN: 1527-5418
CID: 5364822

Clinical Presentation and Treatment of Early-Onset Behavior Disorders: The Role of Parent Emotion Regulation, Emotion Socialization, and Family Income

Highlander, April; Zachary, Chloe; Jenkins, Kaeley; Loiselle, Raelyn; McCall, Madison; Youngstrom, Jennifer; McKee, Laura G; Forehand, Rex; Jones, Deborah J
Parent emotion regulation and socialization have been linked to various aspects of child functioning. In the case of early-onset behavior disorders in particular, parent emotion regulation may be an important correlate of the coercive cycle implicated in early-onset behavior disorders thus, symptom presentation at baseline. Further, emotion socialization may be complicated by a pattern of parent-child interactions in which both supportive or unsupportive parenting behaviors in response to behavioral dysregulation may increase vulnerability for problem behavior in the future. Some work suggests standard Behavioral Parent Training may impact parent emotion regulation and socialization. Still little is known, however, about how such processes may vary by family income, which is critical given the overrepresentation of low-income children in statistics on early-onset behavior disorders. This study explored parent emotion regulation, socialization, and family income in a sample of socioeconomically diverse treatment-seeking families of young (3-8 years old) children. Findings suggest relations between parental emotion regulation, socialization, and child behavior although the pattern of associations differed at baseline and post-treatment and varied by family income. Clinical implications and future directions are discussed.
PMCID:9364231
PMID: 34378434
ISSN: 1552-4167
CID: 5401222

Recognizing and treating the emotional and behavioral effects of child maltreatment

Chapter by: Jablonka, Olga; Coble, Chanelle; Palusci, Vincent J.
in: Behavioral Pediatrics: Mental Health and Management. Fifth Edition by
[S.l.] : Nova Science Publishers, Inc., 2022
pp. 33-59
ISBN: 9798886970609
CID: 5369012

Advocacy for a coordinated and safe response for the mental health and psychosocial needs of children affected by the conflict in Ukraine [Letter]

Solerdelcoll, Mireia; Ougrin, Dennis; Cortese, Samuele
PMCID:9395799
PMID: 35997819
ISSN: 1435-165x
CID: 5331572

The day I told Karim Nader, "Don't do the study"

LeDoux, Joseph E
Karim Nader changed the course of memory research by reviving interest in the mostly forgotten topic of post-retrieval manipulations of memory. In this paper I summarize the events leading up to his ground-breaking study in my lab on so-called memory reconsolidation, and the effects of that study on the field.
PMID: 35981628
ISSN: 1873-2747
CID: 5300192

Longitudinal characterization of EEG power spectra during eyes open and eyes closed conditions in children

Isler, Joseph R; Pini, Nicolò; Lucchini, Maristella; Shuffrey, Lauren C; Morales, Santiago; Bowers, Maureen E; Leach, Stephanie C; Sania, Ayesha; Wang, Lily; Condon, Carmen; Nugent, J David; Elliott, Amy J; Friedrich, Christa; Andrew, Rebecca; Fox, Nathan A; Myers, Michael M; Fifer, William P
This study is the first to examine spectrum-wide (1 to 250 Hz) differences in electroencephalogram (EEG) power between eyes open (EO) and eyes closed (EC) resting state conditions in 486 children. The results extend the findings of previous studies by characterizing EEG power differences from 30 to 250 Hz between EO and EC across childhood. Developmental changes in EEG power showed spatial and frequency band differences as a function of age and EO/EC condition. A 64-electrode system was used to record EEG at 4, 5, 7, 9, and 11 years of age. Specific findings were: (1) the alpha peak shifts from 8 Hz at 4 years to 9 Hz at 11 years, (2) EC results in increased EEG power (compared to EO) at lower frequencies but decreased EEG power at higher frequencies for all ages, (3) the EEG power difference between EO and EC changes from positive to negative within a narrow frequency band which shifts toward higher frequencies with age, from 9 to 12 Hz at 4 years to 32 Hz at 11 years, (4) at all ages EC is characterized by an increase in lower frequency EEG power most prominently over posterior regions, (5) at all ages, during EC, decreases in EEG power above 30 Hz are mostly over anterior regions of the scalp. This report demonstrates that the simple challenge of opening and closing the eyes offers the potential to provide quantitative biomarkers of phenotypic variation in brain maturation by employing a brief, minimally invasive protocol throughout childhood.
PMID: 35968705
ISSN: 1540-5958
CID: 5340642

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

Basolateral amygdala hyperexcitability is associated with precocious developmental emergence of fear-learning in Fragile X Syndrome

Svalina, Matthew N; Rio, Christian Cea-Del; Kushner, J Keenan; Levy, Abigail; Baca, Serapio M; Guthman, E Mae; Opendak, Maya; Sullivan, Regina; Restrepo, Diego; Huntsman, Molly M
Fragile X Syndrome (FXS) is a neurodevelopmental disorder and the most common monogenic cause of intellectual disability, autism spectrum disorders (ASDs) and anxiety disorders. Loss of fragile x mental retardation protein (FMRP) results in disruptions of synaptic development during a critical period (CP) of circuit formation in the basolateral amygdala (BLA). However, it is unknown how these alterations impact microcircuit development and function. Using a combination of electrophysiologic and behavioral approaches in both male (Fmr1-/y) and female (Fmr1-/-) mice, we demonstrate that principal neurons (PNs) in the Fmr1KO BLA exhibit hyperexcitability during a sensitive period in amygdala development. This hyperexcitability contributes to increased excitatory gain in fear-learning circuits. Further, synaptic plasticity is enhanced in the BLA of Fmr1KO mice. Behavioral correlation demonstrates that fear-learning emerges precociously in the Fmr1KO mouse. Early life THIP intervention ameliorates fear-learning in Fmr1KO mice. These results suggest that CP plasticity in the amygdala of the Fmr1KO mouse may be shifted to earlier developmental timepoints.SIGNIFICANCE STATEMENTIn these studies we identify early developmental alterations in principal neurons in the FXS BLA. We show that as early as P14, excitability and feed-forward excitation, and synaptic plasticity is enhanced in Fmr1KO lateral amygdala. This correlates with precocious emergence of fear-learning in the Fmr1KO mouse. Early life THIP intervention restores CP plasticity in WT mice and ameliorates fear-learning in the Fmr1KO mouse.
PMID: 35970562
ISSN: 1529-2401
CID: 5299822

Gender Identity 5 Years After Social Transition

Olson, Kristina R; Durwood, Lily; Horton, Rachel; Gallagher, Natalie M; Devor, Aaron
BACKGROUND AND OBJECTIVES:Concerns about early childhood social transitions among transgender youth include that these youth may later change their gender identification (ie, retransition), a process that could be distressing. The current study aimed to provide the first estimate of retransitioning and to report the current gender identities of youth an average of 5 years after their initial social transitions. METHODS:The current study examined the rate of retransition and current gender identities of 317 initially transgender youth (208 transgender girls, 109 transgender boys; M = 8.1 years at start of study) participating in a longitudinal study, the Trans Youth Project. Data were reported by youth and their parents through in-person or online visits or via e-mail or phone correspondence. RESULTS:We found that an average of 5 years after their initial social transition, 7.3% of youth had retransitioned at least once. At the end of this period, most youth identified as binary transgender youth (94%), including 1.3% who retransitioned to another identity before returning to their binary transgender identity. A total of 2.5% of youth identified as cisgender and 3.5% as nonbinary. Later cisgender identities were more common among youth whose initial social transition occurred before age 6 years; their retransitions often occurred before age 10 years. CONCLUSIONS:These results suggest that retransitions are infrequent. More commonly, transgender youth who socially transitioned at early ages continued to identify that way. Nonetheless, understanding retransitions is crucial for clinicians and families to help make retransitions as smooth as possible for youth.
PMID: 35505568
ISSN: 1098-4275
CID: 5401142