Tsachi Ein-Dor

DNA methylation-expression associations have no fixed sign. Prior work showed that eQTM direction can be predicted; we asked instead what makes that direction portable across datasets, genomic loci, and tissues. Across 12 cis-eQTM datasets, positive associations increased systematically with distance from the transcription start site, whereas transcription-factor motif features contributed essentially no directional information. The sets of detected eQTMs differed substantially across datasets and tissues, yet shared CpG-gene pairs retained their sign far more often, reaching 95.4% agreement in matched blood and nasal epithelium. Progressively stricter genomic holdouts defined where this architecture generalizes and where it fails. Calibrated abstaining models provided directional annotations for 604,456 CpGs, and an independent mQTL-eQTL layer provided genetically anchored directional evidence for 103,285. These findings separate tissue-specific eQTM presence from the greater portability of eQTM direction and translate that distinction into a graded annotation resource.

The transmission of trauma across generations, particularly among descendants of Holocaust survivors, presents a complex interplay of psychological and epigenetic adaptations. This study explored the long-term impacts of Holocaust trauma on the third and fourth generations, focusing on the quality of social-emotional ties and psychopathology, as well as the epigenetic variation in the oxytocin system, the Hypothalamic-Pituitary-Adrenal (HPA) stress axis, and the Sympathetic Nervous System (SNA). Involving 371 participants, including 186 third- and fourth-generation descendants of Holocaust survivors (54.8% women, mean age = 29.67), we employed DNA methylation analysis of saliva samples to uncover these dynamics. Our findings revealed that descendants exhibited significantly lower general attachment avoidance, and a DNA methylation pattern associated with stronger activation of the oxytocin system, indicating enhanced social bonding and social emotion regulation. Conversely, they showed distinct DNA methylation patterns in CRH, CRHBP, FKBP5, and NR3C1 genes linked to increased HPA axis activation and more pronounced stress reactivity. Despite the presence of these two DNA methylation patterns, no elevated levels of psychopathology were observed. Our results highlight the dual nature of trauma transmission, with descendants displaying both vulnerabilities and resilience. While stronger oxytocin system activation may support social cohesion and stress reduction, stronger HPA axis reactivity could ensure sustained vigilance and preparedness. Our findings thus underscore the intricate balance between genetic, epigenetic, and environmental factors in shaping resilience and offer insights into the potential for long-term growth following inherited trauma.

The loss of a parent during childhood is a profound event with enduring impacts on psychological and emotional development. This study investigates the long-term effects of childhood parental loss on attachment patterns and openness to experience, with a focus on the epigenetic modulation of the oxytocin and dopamine systems. The sample included 371 participants (51.2% women, ages 26–43), of whom 33 experienced parental loss during childhood. In those individuals who lost a parent, findings revealed comparably lower attachment avoidance and a DNA methylation profile associated with a potential for increased oxytocin activity. Additionally, a DNA methylation profile associated with a potential for heightened dopamine activity was identified in this group, aligning with greater creativity. These findings highlight the intricate interplay of genetic and environmental factors in fostering resilience and personal growth, shedding light on the roles of oxytocin and dopamine in social bonding and the potential for long-term adaptation following early-life trauma.

Attachment theory is one of the most comprehensive frameworks in social and developmental psychology. It describes how selective, enduring emotional bonds between infants and their caregivers are formed and maintained throughout life. These attachment bonds exhibit distinct characteristics that are intimately tied to fundamental aspects of mammalian life, including pregnancy, birth, lactation, and infant brain development. However, there is a lack of a cohesive biological narrative that explains the psychological forces shaping attachment behavior and the emergence and consolidation of attachment patterns at a neurobiological level. Here, we propose a theoretical narrative focusing on organized attachment patterns that systematically link the two primary purposes of the attachment behavioral system: the provision of tangible protection or support and the corresponding subjective feeling of safety or security. We aim for this detailed delineation of neurobiological circuits to foster more comprehensive and interdisciplinary future research.

Peripartum depression (PPD) is a prevalent and debilitating disorder that adversely affects the development of mothers and infants. Recently, there has been a plea for increased mental health screening during the peripartum period; however, currently, there is no accurate screening tool to identify women at risk of PPD. In addition, some women do not respond to current treatment schemes and develop treatment-resistant depression. The current perspective aims to propose a unified understanding of the biological underpinnings of PPD (UmPPD) that considers the heterogeneity in the onset, symptoms cluster, and severity of PPD. Such a model could promote basic and applied research on PPD and suggest new treatment avenues. The central hub of the model is the kynurenine pathway (KP) and the KP-serotonin ratio. The forces and specific processes at play that cause an imbalance within the KP and between KP and serotonin are inflammation, stress, reproductive hormones (especially estradiol and progesterone), and oxytocin. UmPPD predicts that the most severe PPD would comprise prolonged inflammation, ongoing or multiple stressors, excessive estrogen, progesterone resistance, and avoidance of breastfeeding, skin-to-skin contact, and social proximity. These factors would be associated with a higher likelihood of developing PPD, early onset, and more significant symptom severity. In addition, subtypes of PPD would consist of different compositions and expressions of these components, with one central common factor. UmPPD could aid in directing future research and possibly detecting critical processes that could help discover, develop, and utilize novel treatments for PPD.

Background Maternal psychiatric morbidities include a range of psychopathologies; one condition is post-traumatic stress disorder (PTSD) that develops following a traumatic childbirth experience and may undermine maternal and infant health. Although assessment for maternal mental health problems is integrated in routine perinatal care, screening for maternal childbirth-related PTSD (CB-PTSD) remains lacking. Acute emotional distress in response to a traumatic event strongly associates with PTSD. The brief 13-item Peritraumatic Distress Inventory (PDI) is a common tool to assess acute distress in non-postpartum individuals. How well the PDI specified to childbirth can classify women likely to endorse CB-PTSD is unknown. Objectives We sought to determine the utility of the PDI to detect CB-PTSD in the early postpartum period. This involved examining the psychometric properties of the PDI specified to childbirth, pertaining to its factorial structure, and establishing an optimal cutoff point for the classification of women with high vs. low likelihood of endorsing CB-PTSD. Study Design A sample of 3,039 eligible women who had recently given birth provided information about their mental health and childbirth experience. They completed the PDI regarding their recent childbirth event, and a PTSD symptom screen to determine CB-PTSD. We employed Exploratory Graph Analysis (EGA) and bootstrapping analysis to reveal the factorial structure of the PDI and the optimal PDI cutoff value for CB-PTSD classification. Results Factor analysis of the PDI shows two strongly correlated stable factors based on a modified 12-item version of the PDI consisting of (1) negative emotions and (2) bodily arousal and threat appraisal in regard to recent childbirth. This structure largely accords with prior studies of individuals who experienced acute distress resulting from other forms of trauma. We report that a score of 15 or higher on the modified PDI produces strong sensitivity and specificity. 88% of women with a positive CB-PTSD screen in the first postpartum months and 93% with a negative screen are identified as such using the established cutoff. Conclusions Our work reveals that a brief self-report screening concerning a woman’s immediate emotional reactions to childbirth that uses our modified PDI tool can detect women likely to endorse CB-PTSD in the early postpartum period. This form of maternal mental health assessment may serve as the initial step of managing symptoms to ultimately prevent chronic symptom manifestation. Future research is needed to examine the utility of employing the PDI as an assessment performed during maternity hospitalization stay in women following complicated deliveries to further guide recommendations to implement maternal mental health screening for women at high risk for developing CB-PTSD.