Publications by Year: In Press

In Press
Wang, X., Xie, H., Chen, T., Cotton, A. S., Salminen, L. E., Logue, M. W., Clarke-Rubright, E. K., et al. (In Press). Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis. Molecular Psychiatry. Publisher's VersionAbstract
Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = −0.111 to −0.068, FDR corrected P values \textless 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.
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Colich, N. L., Sheridan, M. A., Humphreys, K. L., Wade, M., Tibu, F., Nelson, C. A., Zeanah, C. H., et al. (In Press). Heightened sensitivity to the caregiving environment during adolescence: implications for recovery following early-life adversity. Journal of Child Psychology and Psychiatry. Publisher's VersionAbstract

Background: Adolescence has been proposed to be a period of heightened sensitivity to environmental influence. If true, adolescence may present a window of opportunity for recovery for children exposed to early-life adversity. Recent evidence supports adolescent recalibration of stress response systems following early-life adversity. However, it is unknown whether similar recovery occurs in other domains of functioning in adolescence. Methods: We use data from the Bucharest Early Intervention Project – a randomized controlled trial of foster care for children raised in psychosocially depriving institutions – to examine the associations of the caregiving environment with reward processing, executive functioning, and internalizing and externalizing psychopathology at ages 8, 12, and 16 years, and evaluate whether these associations change across development. Results: Higher quality caregiving in adolescence was associated with greater reward responsivity and lower levels of internalizing and externalizing symptoms, after covarying for the early-life caregiving environment. The associations of caregiving with executive function and internalizing and externalizing symptoms varied by age and were strongest at age 16 relative to ages 8 and 12 years. This heightened sensitivity to caregiving in adolescence was observed in both children with and without exposure to early psychosocial neglect. Conclusions: Adolescence may be a period of heightened sensitivity to the caregiving environment, at least for some domains of functioning. For children who experience early psychosocial deprivation, this developmental period may be a window of opportunity for recovery of some functions. Albeit correlational, these findings suggest that it may be possible to reverse or remediate some of the lasting effects of early-life adversity with interventions that target caregiving during adolescence. Keywords: Institutionalization; reward; executive function; psychopathology; adolescence.

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Grisanzio, K. A., Sasse, S. F., Nook, E. C., Lambert, H. K., McLaughlin, K. A., & Somerville, L. H. (In Press). Voluntary pursuit of negatively valenced stimuli from childhood to early adulthood. Developmental Science. Publisher's VersionAbstract
Although common sense suggests that we are motivated to pursue positive and avoid negative experiences, previous research shows that people regularly seek out negative experiences. In the current study, we characterized this tendency from childhood to young adulthood. Due to the known increases in risky behavior and sensation seeking in adolescence, we hypothesized that adolescents would show an increased engagement with negatively valenced stimuli compared to children and adults. Participants aged 4–25 (N = 192) completed a behavioral task assessing motivation to engage with negative, positive, and neutral images. On each trial, participants viewed two small images and selected one to view at a larger size for up to 10s. Trials were organized into three valence conditions: negative versus positive images (matched on arousal), negative versus neutral images, and positive versus neutral images. Although participants chose positive images more than neutral or negative images, participants selected negative images frequently, even when given a positive (28% of trials) or neutral (42% of trials) alternative. Contrary to expectations, the tendency to choose negative images was highest in early childhood and decreased linearly with increasing age, and the tendency to choose positive images increased linearly with age. These results provide insight into how motivation to engage with emotional stimuli varies across age. It is possible that the novelty and rarity of negative experiences drives children to pursue these stimuli. Alternatively, children may find negative images less aversive, which would caution against assuming that these stimuli elicit the same motivational states in individuals of all ages.
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Miller, A. B., Machlin, L., McLaughlin, K. A., & Sheridan, M. A. (In Press). Deprivation and psychopathology in the Fragile Families Study: A 15-year longitudinal investigation. Journal of Child Psychology and Psychiatry. Publisher's VersionAbstract
Background Early adversity consistently predicts youth psychopathology. However, the pathways linking unique dimensions of early adversity, such as deprivation, to psychopathology are understudied. Here, we evaluate a theoretical model linking early deprivation exposure with psychopathology prospectively through language ability. Methods Participants included 2,301 youth (47.5% female) enrolled in the Fragile Families and Child Wellbeing Study. We include data from assessment points at ages 1, 3, 5, 9, and 15. Latent factors for deprivation and threat were modeled from multiple indicators at ages 1 and 3. Youth language ability was assessed at Age 5. Indicators of psychopathology were assessed at ages 5, 9, and 15. A structural equation model tested longitudinal paths to internalizing and externalizing psychopathology from experiences of deprivation and threat. Results Deprivation from birth to Age 3 was associated with an indirect effect on internalizing and externalizing symptoms in early childhood (Age 5), later childhood (Age 9), and adolescence (Age 15) via language ability in early childhood (Age 5). Early threat exposure was associated with increased internalizing and externalizing psychopathology across all ages. There was no significant indirect effect from threat to psychopathology via language ability. Conclusions The effects of deprivation on psychopathology during early childhood, late childhood, and adolescence are explained, in part, through early childhood language ability. Results provide insight into language ability as a possible opportunity for intervention.
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Jenness, J. L., Peverill, M., Miller, A. B., Heleniak, C., Robertson, M. M., Sambrook, K. A., Sheridan, M. A., et al. (In Press). Alterations in neural circuits underlying emotion regulation following child maltreatment: a mechanism underlying trauma-related psychopathology. Psychological Medicine , 1–10.Abstract
BACKGROUND: Disruptions in neural circuits underlying emotion regulation (ER) may be a mechanism linking child maltreatment with psychopathology. We examined the associations of maltreatment with neural responses during passive viewing of negative emotional stimuli and attempts to modulate emotional responses. We investigated whether the influence of maltreatment on neural activation during ER differed across development and whether alterations in brain function mediated the association between maltreatment and a latent general psychopathology ('p') factor. METHODS: Youth aged 8-16 years with (n = 79) and without (n = 72) exposure to maltreatment completed an ER task assessing neural responses during passive viewing of negative and neutral images and effortful attempts to regulate emotional responses to negative stimuli. P-factor scores were defined by a bi-factor model encompassing internalizing and externalizing psychopathology. RESULTS: Maltreated youth had greater activation in left amygdala and salience processing regions and reduced activation in multiple regions involved in cognitive control (bilateral superior frontal gyrus, middle frontal gyrus, and dorsal anterior cingulate cortex) when viewing negative v. neutral images than youth without maltreatment exposure. Reduced neural recruitment in cognitive control regions mediated the association of maltreatment with p-factor in whole-brain analysis. Maltreated youth exhibited increasing recruitment with age in ventrolateral prefrontal cortex during reappraisal while control participants exhibited decreasing recruitment with age. Findings were similar after adjusting for co-occurring neglect. CONCLUSIONS: Child maltreatment influences the development of regions associated with salience processing and cognitive control during ER in ways that contribute to psychopathology.
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Dennis, E. L., Disner, S. G., Fani, N., Salminen, L. E., Logue, M., Clarke, E. K., Haswell, C. C., et al. (In Press). Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium. Molecular Psychiatry , 1–16. Publisher's VersionAbstract
A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18–83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen’s d = −0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.
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