Cumulative Risk on Oxytocin-Pathway Genes Impairs Default Mode Network Connectivity in Trauma-Exposed Youth

Abstract

Background: Although the default mode network (DMN) is a core network essential for brain functioning, little is known about its developmental trajectory, particularly on factors associated with its coherence into a functional network. In light of adult studies indicating DMN's susceptibility to stress-related conditions, we examined links between variability on oxytocin-pathway genes and DMN connectivity in youth exposed to chronic war-related trauma Methods: Following a cohort of war-exposed children from early childhood, we imaged the brains of 74 preadolescents (age 11-13 years; 39 war-exposed) during rest using magnetoencephalography (MEG). A cumulative risk index on oxytocin-pathway genes was constructed by combining single nucleotide polymorphisms on five genes previously linked with social deficits and psychopathology; OXTR rs1042778, OXTR rs2254298, OXTRrs53576, CD38 rs3796863, and AVPR1A RS3. Avoidant response to trauma reminders in early childhood and anxiety disorders in late childhood were assessed as predictors of disruptions to DMN theta connectivity.Results: Higher vulnerability on oxytocin-pathway genes predicted greater disruptions to DMN theta connectivity. Avoidant symptoms in early childhood and generalized anxiety disorder in later childhood were related to impaired DMN connectivity. In combination, stress exposure, oxytocin-pathway genes, and stress-related symptoms explained 24.6% of the variance in DMN connectivity, highlighting the significant effect of stress on the maturing brain.Conclusions: Findings are the first to link the oxytocin system and maturation of the DMN, a core system sustaining autobiographical memories, alteration of intrinsic and extrinsic attention, mentalization, and sense of self. Results suggest that oxytocin may buffer the effects of chronic early stress on the DMN, particularly theta rhythms that typify the developing brain.

Investigating default mode network connectivity disruption in children of mothers with depression

“…Such a parallel in the depressive profile is consistent with extant research indicating that exposure to maternal depression in early childhood increases rates of child anxiety disorders while exposure to maternal depression by late childhood/adolescence leads to depression. 79100,101 Both maternal caregiving and child socio-emotional outcomes have been linked with DMN activity, 18,84 and our findings are consistent with this research. Mother-child reciprocity and children's empathic capacities predicted normative versus aberrant DMN connectivity in preadolescence above and beyond exposure to maternal depression.…”

“…18 In both studies, the decreased connectivity implicated connectivity with RAG. 18,84 The RAG plays a key role in social cognition and emotion regulation, which are impaired in children of mothers with depression. [85][86][87] The reduced connectivity of the RAG with the PCC and dMPFC found in both studies supports the hypothesis that early maternal depression that abates before the child reaches puberty may be registered in the brain as early trauma.…”

“…Several limitations should be acknowledged. First, although longer MEG recordings of the resting state are preferable, previous experiments with children 18,84 have indicated that children are unable to stay still in isolated shielded environments for longer periods. Second, we did not conduct assessments of mothers and children between 6 and 10 years, which could have allowed for a more fine-grained clinical grouping.…”

An Investgation About the Relationship Between Vasopressin and Oxytocin in Persistent Type Functional Neurological Symptom Disorder

“…A recent study found that cumulative stress associated with PTSD and anxiety caused impairment in the neural pathways, associated with endurance in adulthood through the oxytocin and AVP pathway. 43 The limitations of our study include the limited number of cases, the absence of male patients and the lack of evaluation in the acute period. Our results are difficult to generalize due to the fact that our sample was consisted of female patients.…”

“…Cumulative stress has different effects than acute stress. A recent study found that cumulative stress associated with PTSD and anxiety caused impairment in the neural pathways, associated with endurance in adulthood through the oxytocin and AVP pathway [ 43 ].…”