Lower structural integrity of the uncinate fasciculus is associated with a history of child maltreatment and future psychological vulnerability to stress

Abstract

The experience of child maltreatment is a significant risk factor for the development of later internalizing disorders such as depression and anxiety. This risk is particularly heightened after exposure to additional, more contemporaneous stress. While behavioral evidence exists for such “stress sensitization,” little is known about the mechanisms mediating such relationships, particularly within the brain. Here we report that the experience of child maltreatment independent of recent life stress, gender, and age is associated with reduced structural integrity of the uncinate fasciculus, a major white matter pathway between the amygdala and ventromedial prefrontal cortex, in young adults. We further demonstrate that individuals with lower uncinate fasciculus integrity at baseline who subsequently experience stressful life events report higher levels of internalizing symptomatology at follow-up. Our findings suggest a novel neurobiological mechanism linking child maltreatment with later internalizing symptoms, specifically altered structural connectivity within the brain’s threat-detection and emotion regulation circuitry.

Altered brain network integrity after childhood maltreatment: A structural connectomic DTI-study

“…No previous studies have tried to quantify the entire WM connectome by applying graph theoretical approaches, constraining an empirical basis from which to inform directional hypotheses. In contrast, building on previous work discussed above [Hanson et al, ; van Harmelen et al, ; Teicher et al, ], we hypothesized that (a) due to the timing of adversity during critical cortical maturation periods (birth to 3 years), children with a history of maltreatment would show global reductions in brain network connectivity, consistent with a systemic and global influence of adversity on WM development, (b) based on previous findings showing structural and functional alterations as well as increased stress‐related vulnerability in the PFC and temporal lobe, we expected group differences in lobar and regional parameters of WM integrity in these a‐priori regions and, (c) global structural network alterations would be associated with indices of HPA‐functioning (basal morning cortisol) as well as measures related to the maltreatment experience and internalizing psychopathology as shown previously by Hanson et al [].…”

“…Childhood maltreatment is a major risk factor for children's social, emotional and neural development, rendering these children at high risk for a range of adverse outcomes at all stages of development [MacMillan and Fleming, ]. Indeed, childhood maltreatment has been associated with poorer educational and economic attainment [Zielinski, ], physical and psychological well‐being [Hanson et al, ; Nusslock and Miller, ], as well as impaired social cognition [Flynn et al, ; Puetz et al, ; Puetz et al, ]. There is increasing consensus among researchers that severe stress in the form of childhood maltreatment triggers a cascade of neurobiological changes in the developing brain via the hypothalamic‐pituitary‐adrenal (HPA) axis [Lupien et al, ].…”

“…Excess exposure to glucocorticoids can ultimately alter neural structure and subsequent function in the prenatal and postnatal phase [Lupien et al, ; Murmu et al, ]. Considering the ability of the prefrontal and limbic structures to influence the organism's ability to cope with, and recover from stress [Carlyle et al, ; Sanchez, ; Sapolsky et al, ], it is not surprising that neuroimaging studies have documented long‐lasting structural changes in these brain areas associated with stress‐related disorders, such as depression and anxiety [Etkin and Wager ], especially in individuals who have been maltreated in childhood [Hanson et al, ; van Harmelen et al, ; Teicher et al, ; Dannlowski et al, ; Kaufman and Charney, ; Kelly et al, ; DeBrito et al, ; Teicher and Samson, ].…”

A novel ecological account of prefrontal cortex functional development.

“…For instance, a number of studies have found that adversity experienced early in childhood results in delayed cortical development, relative to those who do not experience adversity, as measured by delayed gray matter maturation and decreased cortical thickness within PFC (Hair, Hanson, Wolfe, & Pollak, 2015; Mackey et al, 2015; McLaughlin et al, 2014; Noble et al, 2015), as well as significant reductions in white matter tracts between PFC and other cortical and subcortical regions (Eluvathingal, 2006; Hanson et al, 2013; Hanson, Knodt, Brigidi, & Hariri, 2015; Sheridan, Fox, Zeanah, McLaughlin, & Nelson, 2012). These structural changes are paralleled by worse performance on classic measures of executive functions (see Brito & Noble, 2014; Hackman & Farah, 2009; S. B.…”

The complex neurobiology of resilient functioning after child maltreatment

“…Since, the structure of the white matter connection between the amygdala and the ventromedial PFC (the uncinate fasciculus) was predictive of adult internalizing symptoms (Hanson, Knodt, Brigidi, & Hariri, 2015) . Therefore, future studies on the neurobiology of resilience after CM may benefit from studying key brain structures and their growth trajectories, as well as the structural connectivity between these regions.…”