TJovanovic1, K Prendergast2, AC Korgan2, SA George1, TL Bale2

Trauma exposure during development significantly increases risk for psychopathology, including posttraumatic stress disorder (PTSD), which is twice as common in women as men. One of the hallmark symptoms of PTSD is threat reactivity, which can be measured in the laboratory using fear conditioning methods. In our prior work we have found that fear-potentiated startle to threat signals was heightened in women who experienced sexual trauma during adolescence. This same sensitive period of development was associated with increased blood levels of keratinocytes and keratin-associated proteins. Our current work is examining the long-term impact of adolescent exposure to interpersonal violence in men and women using fear-potentiated startle and proteomic analyses related to the 17q21 gene cluster. Preliminary results of this ongoing study replicate prior findings showing increased fear responses, altered fear extinction, and changes associated with keratinocytes. In addition, we have observed significant sex differences in the above measures. These data suggest robust long-term effects of interpersonal trauma on skin cells in women, which may be associated with Merkel cell signaling, and could lead to novel interventions for PTSD. Such interventions could be optimized and personalized based on an individual’s proteomic and psychophysiological biomarkers.

1Department of Psychiatry, Wayne State University, Detroit, MI

2Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO

TL Bale1, AC Korgan1, IJ Sibley1, T Jovanovic2

Childhood trauma experience increases risk for neuropsychiatric and neurodevelopmental disorders, including posttraumatic stress disorder (PTSD), autism spectrum disorders (ASDs), and attention deficit/hyperactivity disorder (ADHD). We recently utilized a Gene x Environment x Development (GxExD) interactions approach in a study where we found that women exposed to interpersonal violence trauma (the E) uniquely during adolescence (the D), but not childhood or adulthood, had novel protein biomarkers (the G) associated with a sensory cell system in the skin, Merkel cells (MC). Merkel cell mechanosensory signaling is important in gentle and social touch, inflammation-induced pain, and the skin’s neuroendocrine stress response. Interestingly, many of the genes identified in our study belong to a 17q21 gene cluster, suggesting an epigenetically regulated site altered by adolescent trauma. We developed a preclinical mouse model using chemogenetics in which studies can examine biological mechanisms connecting developmental timing of stress with sensory alterations in MC responses. To validate this model using a KRT14^Cre x DREADD-Gq transgenic cross to activate MCs, we identified expected somatosensory brain regions activated by MC stimulation following CNO treatment. Further, we identified the behavioral changes and valence of acute and chronic MC stimulation in male and female mice. Finally, we determined a significant effect of MC activation prior to conditioned fear extinction that did not impact fear conditioning. Extinction effects were also context dependent but did not show an effect of sex. Combined, these experiments provide validation of a preclinical mouse model in which further studies can now examine a potential functional link between mechanosensory Merkel cells and the pathology and sensory symptomatology in PTSD.

1Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO

2Department of Psychiatry, Wayne State University, Detroit, MI

Diego Luiz Rovaris, Ph.D.

In this talk, I will present findings from a collaborative effort within the Latin American Genomics Consortium (LAGC) that aims to deepen our understanding of the genetic architecture of Attention-Deficit/Hyperactivity Disorder (ADHD) in ancestrally and environmentally diverse populations. I will explore how Latin America's contrasting environments — shaped by regional socioeconomic, cultural, and healthcare disparities — influence genetic signals and add complexity to psychiatric genomic interpretation. I will also share recent findings on the high prevalence of childhood trauma among adults with ADHD, and discuss how early life stress is linked to increased comorbidity and greater symptom severity. Beyond advocating for equitable representation, I will highlight how including underrepresented populations can uncover novel insights into gene–environment interactions and the biological mechanisms underlying mental illness.

Department of Physiology and Biophysics,
Institute of Biomedical Sciences, University of São Paulo, Brazil

Rodrigo Grassi-Oliveira, MD, PhD

Cocaine use disorder (CUD) is a severe psychiatric condition shaped by cumulative exposure to environmental adversities across the lifespan. In this talk, I will present human data highlighting how both prenatal cocaine exposure and lifetime exposure to potentially traumatic events (PTEs) influence the epigenetic landscape in individuals with CUD. In newborns with prenatal cocaine exposure (PCE), we observed significant alterations in DNA methylation profiles at birth, including reduced gestational epigenetic age and lower BDNF levels, alongside elevated epigenetic scores for psychiatric and metabolic phenotypes. These findings indicate that the biological imprint of prenatal adversity is detectable at birth. In adulthood, analysis from a large Brazilian cohort (N = 1,250) revealed that 84.9% of individuals with CUD had a history of PTEs, compared to 33.3% in non-psychiatric controls. Traumatic exposures included life-threatening events, physical violence, sexual assault, and severe childhood adversities. Our epigenome-wide association study identified distinct DNA methylation profiles associated with both CUD and PTE exposure, particularly at loci such as AHRR, SOCS3, and FKBP5, which are involved in immune regulation and stress response. Importantly, we detected independent effects of trauma, as well as group × trauma interactions, at multiple CpG sites, underscoring the complex biological interplay between addiction and early adversity. These human data emphasize that trauma across the lifespan—beginning in utero—modifies key epigenetic pathways, contributing to vulnerability for cocaine use disorder. Such insights advance our understanding of trauma-informed addiction science and may inform future prevention and treatment strategies.

Aarhus University, Denmark