CREUTZBERG, KERSTIN

GRASSI'OLIVEIRA, RODRIGO

ORSO, RODRIGO

RIVA, MARCO A.

Thiago Wendt Viola

TRACTENBERG, SAULO

Veronica Begni

Repositório Institucional da PUCRS

Poster AbstractsBiologicalPsychiatryP136. Trauma Exposure, Endocannabinoid Signaling,and Variation in Frontolimbic White Matter Pathways inChildrenHilary Marusak1, Austin Morales1, Breanna Borg1,Julia Evanski1, and Clara Zundel11Wayne State UniversityBackground: The endocannabinoid system plays a key rolein modulating brain development throughout the lifespan,including myelination. Recent studies link a common variant(C385A) in the fatty acid amide hydrolase (FAAH) gene tohigher endocannabinoid levels, lower anxiety, and alteredfrontolimbic development. Frontolimbic pathways demonstratea protracted maturational course across childhood andadolescence, are associated with anxiety, and are sensitive toenvironmental stressors (e.g., trauma exposure). Here, weexamined the impact of trauma exposure and the FAAH C385Avariant on anxiety and frontolimbic white matter integrity inchildren.Methods: We leveraged data from the Adolescent BrainCognitive Development (ABCD) study (n¼10,774; M±SDage¼9.92±0.62 years; 47.9% female). Saliva samples wereused for genotyping and parents reported on their child’sanxiety symptoms (Child Behavior Checklist) and traumaexposure (Kiddie Schedule for Affective Disorders andSchizophrenia). Fractional anisotropy (FA) was estimated fromDTI data for frontolimbic pathways.Results: Forty-five percent of youth were FAAH A-allelecarriers (55% non-carriers) and 36% were exposed to trauma(64% unexposed). Relative to controls, trauma-exposed youthdemonstrated higher anxiety symptoms and higher FA of theright and left uncinate (p<0.05). There was no main effect ofFAAH C385A or trauma-by-FAAH interaction on anxietysymptoms. Compared to non-carriers, A-allele carriersdemonstrated higher FA in the left and right fornix and para-hippocampal cingulum (p<0.05). There were also trauma-by-FAAH interactions for FA in the left and right fornix, and leftparahippocampal cingulum (p<0.05).Conclusions: Results highlight the role of trauma exposureand endocannabinoid signaling in modulating frontolimbicdevelopment and anxiety risk in children.Supported By: NIMHKeywords: Endocannabinoids, Childhood Trauma, DiffusionTensor Imaging, Gray Matter, White Matter, Resting StateP137. Differential Effects of Early Life Stress DuringSensitive Periods of Development on Anxiety-LikeBehavior and Gene Expression Response in Adult MiceSaulo Tractenberg1, Thiago Wendt Viola1, Rodrigo Orso1,Kerstin Creutzberg2, Veronica Begni2, Marco Riva2, andRodrigo Grassi-Oliveira31Pontifical Catholic University of Rio Grande do Sul(PUCRS), 2University of Milan, 3Aarhus UniversityBackground: Preclinical ELS models (e.g., maternal sepa-ration) have been extensively used to investigateS142 Biological Psychiatry May 1, 2022; 91:S88eS381 www.sobp.orgbiomolecular changes underlying the behavioral outcomes inresponse to stress exposure during early postnatal period.However, it still unclear how the reprograming effects ofthese early stress experiences could interact with the expo-sure to a second stressor during later periods of develop-ment, such as adolescence. To address that, this studyinvestigated how maternal separation would interact withchronic adolescence stress exposure on anxiety-likeresponse, gene and protein expression of GR and FKBP5 inthe hippocampus.Methods: Balb/c mice were submitted to prolongedmaternal separation (MS); unpredictable chronic stress(UCS); second hit stress model (MS+UCS) or animal facilityrearing (AFR) conditions. Two independent cohorts were runto evaluate baseline biomarker parameters and behavioralphenotype using three classical anxiety-like behavior tasks.Corticosterone levels (CORT), gene expression of glucocor-ticoid receptor (GR) and FKBP5, as well as GR protein levelswere measured.Results: As expected we found a robust effect of UCS con-dition revealing an increase on anxiety-like parameters, CORTresponse and GR and FKBP5 gene expression. Interestingly,MS+UCS animals showed an inhibited behavioral and bio-logical response in GR and FKBP5 mRNA expression and inGR protein levels. GR protein were found increased in cytosol,while reduced in the nucleus.Conclusions: Our findings suggested that animals exposedto MS exhibited a blunted reactivity response when challengedwith a second stressor in adolescence. Blunted stressresponse could reflect a differential second hit effect failing toadequate the biological and behavioral response to the envi-ronmental challenge.Supported By: This work was supported by the Brazilianfunding agencies: Conselho Nacional de Pesquisa e Desen-volvimento (CNPq) [grant numbers: 442776/2018-7, 307130/2018-5] and Coordenação de Aperfeiçoamento de Pessoal deNível Superior e Brasil (CAPES).Keywords: Early Life Stress, Animal Model, Maternal Sepa-ration, Unpredictable Chronic Mild Stress, Anxiety-Like Be-haviorP138. Prefrontal Connections to the Extended Amyg-dala and Their Role in Early-Life Inhibited Temperamentin Adolescent Rhesus MonkeysLillian Campos1, Carly Drzewiecki1, Do Tromp2,John P. Capitanio1, and Andrew S. Fox11University of California, Davis, 2University of Wisconsin-MadisonBackground: The extended amygdala has been implicated inthe expression of fear and anxiety, and is thought to mediateearly-life risk for psychopathology. How these regions interactwith newly expanded areas of the primate frontal cortex re-mains largely unknown. Using a well-validated primate model,we leverage a multimodal neuroimaging to explore the contri-butions of prefrontal-connections in early-life inhibitedtemperament, a risk factor for the future development ofstress-related psychopathologies/journal

Differential Effects of Early Life Stress During Sensitive Periods of Development on Anxiety-Like Behavior and Gene Expression Response in Adult Mice

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Differential Effects of Early Life Stress During Sensitive Periods of Development on Anxiety-Like Behavior and Gene Expression Response in Adult Mice

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