Profiling nonhuman primate germline RNA to understand the legacy of early life stress

Morin, Elyse; Garza, Kristie M.; Aoued, Hadj; Sannigrahi, Soma; Siebert, Erin R.; Howell, Brittany R.; Walum, Hasse; Sánchez, Mar M.; Dias, Brian

doi:10.1002/jez.2501

Cited by 4 publications

(5 citation statements)

References 63 publications

(89 reference statements)

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“…McCormack et al, , 2009K. M. McCormack et al, 2022;Morin et al, 2019Morin et al, , 2020Morin et al, , 2022Wakeford et al, 2018) and profiled total RNA in circulating plasma EVs obtained from adolescent macaques that had received nurturing care (CONT) or maltreatment (MALT) from their mothers as infants. From these EVassociated RNA signatures, our results suggest that perturbations of the immune system, cellular energetics and translation ought to be considered as biomarkers of infant maltreatment and possible mediators of detrimental physiological and behavioral consequences of such maltreatment.…”

Section: Discussionmentioning

confidence: 99%

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RNA in extracellular vesicles during adolescence reveal immune, energetic and microbial imprints of early life adversity

Korobkova

Morin

Aoued³

et al. 2023

Preprint

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Exposure to early life adversity (ELA), including childhood maltreatment, is one of the most significant risk factors for the emergence of neuropsychiatric disorders in adolescence and adulthood. Despite this relationship being well established, the underlying mechanisms remain unclear. One way to achieve this understanding is to identify molecular pathways and processes that are perturbed as a consequence of childhood maltreatment. Ideally, these perturbations would be evident as changes in DNA, RNA or protein profiles in easily accessible biological samples collected in the shadow of childhood maltreatment. In this study, we isolated circulating extracellular vesicles (EVs) from plasma collected from adolescent rhesus macaques that had either experienced nurturing maternal care (CONT) or maternal maltreatment (MALT) in infancy. RNA sequencing of RNA in plasma EVs and gene enrichment analysis revealed that genes related to translation, ATP synthesis, mitochondrial function and immune response were downregulated in MALT samples, while genes involved in ion transport, metabolism and cell differentiation were upregulated. Interestingly, we found that a significant proportion of EV RNA aligned to the microbiome and that MALT altered the diversity of microbiome-associated RNA signatures found in EVs. Part of this altered diversity suggested differences in prevalence of bacterial species in CONT and MALT animals noted in the RNA signatures of the circulating EVs. Our findings provide evidence that immune function, cellular energetics and the microbiome may be important conduits via which infant maltreatment exerts effects on physiology and behavior in adolescence and adulthood. As a corollary, perturbations of RNA profiles related to immune function, cellular energetics and the microbiome may serve as biomarkers of responsiveness to ELA. Our results demonstrate that RNA profiles in EVs can serve as a powerful proxy to identify biological processes that might be perturbed by ELA and that may contribute to the etiology of neuropsychiatric disorders in the aftermath of ELA.

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Section: Discussionmentioning

confidence: 99%

“…Coverage was computed using the bedtools coverage function on each stranded .bam file. To ensure robustness, like we did in Morin et al, 2022, our analyses were performed on genes on the sense strand with >= 80% coverage.…”

Section: Bioinformatics Analysismentioning

confidence: 99%

RNA in extracellular vesicles during adolescence reveal immune, energetic and microbial imprints of early life adversity

Korobkova

Morin

Aoued³

et al. 2023

Preprint

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“…Regardless of the metaphoric details, the essence was about her vulnerability, her 'core feeling', originating from personal and transgenerational trauma. She was 'certain that there could exist genetic information telling you that you are vulnerable, which could manifest as metaphors' (see e.g., (Dias and Ressler, 2013;Morin et al, 2021;Wolynn, 2016)).…”

Section: Case Descriptionmentioning

confidence: 99%

“…With regard to transgenerational inheritance of trauma, in addition to epigenetic mechanisms leaving no cognitive trace (Morin et al, 2021), trauma could also be picked up from the behavior of parents, grandparents, relatives, or anyone. Reactions by triggered parents could overwhelm their children, causing exiled parts to emerge.…”

Section: The Role Of Trauma In the Etiology Of Psychosismentioning

confidence: 99%

“…Wolynn reviewed current research into the epigenetic inheritance of trauma, i.e., the evidence on the genetic transgenerational inheritance of trauma (Wolynn, 2016). Research on mice indicated that trauma triggers could be epigenetically inherited by the offspring (Dias and Ressler, 2013;Morin et al, 2021). Levine, the inventor of the somatic experiencing method (Kuhfuß et al, 2021;Winblad et al, 2018), provided an introductory overview of the role of memory in trauma, including the long history of the role of the phylogenetically more ancient structures of the brain in trauma (Levine, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Ayahuasca in the treatment of bipolar disorder with psychotic features–A retrospective case study

Turkia¹

2023

Preprint

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Ayahuasca is a plant-based brew of indigenous Amazonian origin. It has psychedelic, anti-inflammatory, neuroprotective, cytotoxic, and anti-parasitic effects, which are primarily due to monoamine oxidase inhibitors (MAOIs) and N,N-dimethyltryptamine (DMT). This article describes the case of a woman in her late thirties with complex trauma due to severe, years-long sexual abuse in early childhood, resulting in a decades-long chronic condition involving suicidality. She was diagnosed with bipolar disorder and borderline personality disorder, but refused to accept either of them. She presented with delusional parasitosis and deep dissociation. Despite being severely psychotic in private, she appeared high-functioning in public, hiding most of her symptoms. In her mid-thirties, she participated in an ayahuasca ceremony in a legal setting. It resolved her suicidality, eliminated her social isolation, and reduced her shame related to her early trauma. Nine more ceremonies alleviated her distress further. Her abuser also participated in an ayahuasca ceremony and confirmed her memories of childhood abuse. The first interview was conducted 1.5 years after her first ceremony, and a follow-up interview 2.5 years later. She had experienced sixteen additional ceremonies, recognized the validity of her bipolar disorder diagnosis, and believed her early trauma to be its sole cause. Her core trauma remained partially unresolved, but her dissociative symptoms continued to decrease. She had observed several other instances of psychosis and bipolar disorder in which ayahuasca had resulted in positive effects. This case study contributes to a better understanding of the use of ayahuasca in bipolar disorder and severe traumatization. It also reviews the current state-of-the-art in the treatment of bipolar disorder using low-dose ayahuasca, and a case in which bipolar disorder was resolved with LSD.

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Profiling nonhuman primate germline RNA to understand the legacy of early life stress

et al. 2021

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Exposure to stress is a risk factor for perturbed mental health, including impoverished regulation of emotional and physiological responses that accompany anxiety and mood disorders, substance abuse and behavioral disorders. Such disruptions to well‐being could be triggered by discrete environmental events or pervasive early life stress (ELS) resulting for example from adverse caregiving. Recent data mostly collected from rodents exposed to anthropogenic stressors suggest that one way via which the detrimental effects of such stress extend beyond the exposed population to future offspring is via stress‐induced alterations of RNA found in the paternal germline. In contrast, less attention has been paid to how naturally occurring stress in males might influence offspring biology and behavior. In this study, we used a translational nonhuman primate model of ELS caused by naturally occurring adverse caregiving of infant macaques to (1) profile total RNA in the adolescent male germline, and (2) identify how those RNA profiles are affected by exposure to ELS. Our findings that the top 100 transcripts identified correspond to transcripts related to germline biology and reproduction demonstrate the validity and feasibility of profiling RNA in the germline of rhesus macaques. While our small sample sizes precluded definitive assessment of stress‐induced alterations of RNA in the male germline of rhesus macaques that experienced ELS, our study sets the foundation for future investigations of how early adversity might alter the male germline, across species and in experimental protocols that involve anthropogenic vs natural stressors.

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Profiling nonhuman primate germline RNA to understand the legacy of early life stress

Cited by 4 publications

References 63 publications

RNA in extracellular vesicles during adolescence reveal immune, energetic and microbial imprints of early life adversity

RNA in extracellular vesicles during adolescence reveal immune, energetic and microbial imprints of early life adversity

Ayahuasca in the treatment of bipolar disorder with psychotic features–A retrospective case study

Profiling nonhuman primate germline RNA to understand the legacy of early life stress

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