All Publications


  • Evidence for a Sensitive Period in the Effects of Early Life Stress on Hippocampal Volume. Developmental science Humphreys, K. L., King, L. S., Sacchet, M. D., Camacho, C., Colich, N. L., Ordaz, S. J., Ho, T. C., Gotlib, I. H. 2018: e12775

    Abstract

    Exposure to stress has been causally linked to changes in hippocampal volume (HV). Given that the hippocampus undergoes rapid changes in the first years of life, stressful experiences during this period may be particularly important in understanding individual differences in the development of the hippocampus. One hundred seventy-eight early adolescents (ages 9-13 years; 43% male) were interviewed regarding exposure to and age of onset of experiences of stress; the severity of each stressful event was rated by an objective panel. All participants underwent structural magnetic resonance imaging, from which HVs were automatically segmented. Without considering the age of onset for stressful experiences, there was a small but statistically significant negative association of stress severity with bilateral HV. When considering the age of onset, there was a moderate and significant negative association between stress severity during early childhood (through age 5 years) and HV; there was no association between stress severity during later childhood and HV (age 6 years and older). We provide evidence of a sensitive period through age 5 years for the effects of life stress on HV in adolescence. It will be important in future research to elucidate how reduced HV stemming from early life stress may contribute to stress-related health outcomes. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1111/desc.12775

    View details for PubMedID 30471167

  • Maternal depressive symptoms, self-focus, and caregiving behavior. Journal of affective disorders Humphreys, K. L., King, L. S., Choi, P., Gotlib, I. H. 2018; 238: 465–71

    Abstract

    BACKGROUND: Parent-child interactions set the stage for child mental health and development. Given that maternal depressive symptoms are associated with poorer observed caregiving behaviors, examining potential cognitive mediators is important for identifying mechanisms underlying the intergenerational transmission of risk and possible targets for intervention.METHODS: We assessed depressive symptoms and levels of self-focus and psychological distancing from infant-centered verbal narratives obtained from 54 mothers, and examined caregiving behaviors in a structured interaction with their six-month-old infants.RESULTS: Higher depressive symptoms were associated with pronoun use in narratives (i.e., greater "I" and reduced "we" use), reflecting increased self-focus and psychological distancing. Further, increased self-focus was associated with lower levels of caregiver warmth, and mediated the association between depressive symptoms and caregiving warmth.LIMITATIONS: This observational study does not allow for causal interpretations.CONCLUSION: These findings suggest that the cognitive styles associated with depression interfere with the caregiving relationship, affecting behavior in parent-child interactions that may increase the risk for the intergenerational transmission of depression.

    View details for DOI 10.1016/j.jad.2018.05.072

    View details for PubMedID 29929156

  • Self-reported neglect, amygdala volume, and symptoms of anxiety 1 in adolescent boys CHILD ABUSE & NEGLECT Roth, M. C., Humphreys, K. L., King, L. S., Gotlib, I. H. 2018; 80: 80–89

    Abstract

    Experiences of psychosocial neglect affect the developing brain and may place individuals at increased risk for anxiety. The majority of research in this area has focused on children who have experienced severe psychosocial deprivation; it is not clear whether typical variation in neglect experienced in community samples would have the same neurobiological consequences as those documented in extreme samples. The present study examined the associations among self-reported childhood neglect, amygdala volume, and anxiety symptoms in a community sample of 138 adolescents ages 9-15 years (43% male). Linear mixed modeling yielded a three-way interaction of neglect, sex, and brain hemisphere, reflecting a significant positive association between neglect and right amygdala volume in boys. Additional analyses indicated that right amygdala volume significantly mediated the association between neglect and anxiety symptoms in boys. These findings are consistent with previous reports of larger amygdala volumes in previously institutionalized children, and with documented associations between caregiving deprivation and anxiety symptoms. The results suggest that the effects of childhood neglect on limbic structures are sex-specific and lateralized, and provide support for a neural mechanism relating childhood neglect to later difficulties in emotional functioning.

    View details for DOI 10.1016/j.chiabu.2018.03.016

    View details for Web of Science ID 000433398000008

    View details for PubMedID 29574295

    View details for PubMedCentralID PMC5953811

  • Stressful Life Events, ADHD Symptoms, and Brain Structure in Early Adolescence. Journal of abnormal child psychology Humphreys, K. L., Watts, E. L., Dennis, E. L., King, L. S., Thompson, P. M., Gotlib, I. H. 2018

    Abstract

    Despite a growing understanding that early adversity in childhood broadly affects risk for psychopathology, the contribution of stressful life events to the development of symptoms of attention-deficit/hyperactivity disorder (ADHD) is not clear. In the present study, we examined the association between number of stressful life events experienced and ADHD symptoms, assessed using the Attention Problems subscale of the Child Behavior Checklist, in a sample of 214 children (43% male) ages 9.11-13.98years (M=11.38, SD=1.05). In addition, we examined whether the timing of the events (i.e., onset through age 5years or after age 6years) was associated with ADHD symptoms. Finally, we examined variation in brain structure to determine whether stressful life events were associated with volume in brain regions that were found to vary as a function of symptoms of ADHD. We found a small to moderate association between number of stressful life events and ADHD symptoms. Although the strength of the associations between number of events and ADHD symptoms did not differ as a function of the age of occurrence of stressful experiences, different brain regions were implicated in the association between stressors and ADHD symptoms in the two age periods during which stressful life events occurred. These findings support the hypothesis that early adversity is associated with ADHD symptoms, and provide insight into possible brain-based mediators of this association.

    View details for DOI 10.1007/s10802-018-0443-5

    View details for PubMedID 29785533

  • A person-centered approach to the assessment of early life stress: Associations with the volume of stress-sensitive brain regions in early adolescence. Development and psychopathology King, L. S., Humphreys, K. L., Camacho, M. C., Gotlib, I. H. 2018: 1–13

    Abstract

    Researchers are becoming increasingly interested in linking specific forms of early life stress (ELS) to specific neurobiological markers, including alterations in the morphology of stress-sensitive brain regions. We used a person-centered, multi-informant approach to investigate the associations of specific constellations of ELS with hippocampal and amygdala volume in a community sample of 211 9- to 13-year-old early adolescents. Further, we compared this approach to a cumulative risk model of ELS, in which ELS was quantified by the total number of stressors reported. Using latent class analysis, we identified three classes of ELS (labeled typical/low, family instability, and direct victimization) that were distinguished by experiences of family instability and victimization. Adolescents in the direct victimization class had significantly smaller hippocampal volume than did adolescents in the typical/low class; ELS classes were not significantly associated with amygdala volume. The cumulative risk model of ELS had a poorer fit than did the person-centered model; moreover, cumulative ELS was not significantly associated with hippocampal or amygdala volume. Our results underscore the utility of taking a person-centered approach to identify alterations in stress-sensitive brain regions based on constellations of ELS, and suggest victimization is specifically associated with hippocampal hypotrophy observed in early adolescence.

    View details for DOI 10.1017/S0954579418000184

    View details for PubMedID 29716668

  • Differing Windows of Sensitivity to Stress in Amygdala-Ventromedial Prefrontal Cortex Structural and Functional Connectivity: Implications for the Neurobiology of Depression in Youth Ho, T., Humphreys, K., King, L., Colich, N., Schwartz, J., Leong, J., Ohashi, K., Teicher, M., Gotlib, I. ELSEVIER SCIENCE INC. 2018: S81
  • The association between early life stress and prefrontal cortex activation during implicit emotion regulation is moderated by sex in early adolescence DEVELOPMENT AND PSYCHOPATHOLOGY Colich, N. L., Williams, E. S., Ho, T. C., King, L. S., Humphreys, K. L., Price, A. N., Ordaz, S. J., Gotlib, I. H. 2017; 29 (5): 1851–64

    Abstract

    Early life stress (ELS) is a significant risk factor for the emergence of internalizing problems in adolescence. Beginning in adolescence, females are twice as likely as males to experience internalizing disorders. The present study was designed to examine sex differences in the association between ELS and internalizing problems in early pubertal adolescents, and whether and how corticolimbic function and connectivity may underlie these associations. Fifty-nine early pubertal males and 78 early pubertal females, ages 9-13 years (all Tanner Stage 3 or below) underwent functional magnetic resonance imaging as they performed an emotion label task that robustly interrogates corticolimbic function. Participants were also interviewed about their experience of ELS. Females exhibited a positive association between ELS and internalizing problems, whereas males exhibited no such association. Whole-brain and amygdala region of interest analyses indicated that whereas females exhibited a positive association between ELS and the ventrolateral prefrontal cortex during implicit emotion regulation, males showed no such association. Activation in these regions was positively associated with internalizing problems in females but not males; however, activation in these regions did not mediate the association between ELS and internalizing problems. Finally, both boys and girls exhibited an association between ELS and increased negative connectivity between the right ventrolateral prefrontal cortex and bilateral amygdala. Using a carefully characterized sample of early pubertal adolescents, the current study highlights important sex differences in the development of corticolimbic circuitry during a critical period of brain development. These sex differences may play a significant role in subsequent risk for internalizing problems.

    View details for DOI 10.1017/S0954579417001444

    View details for Web of Science ID 000425952800024

    View details for PubMedID 29162186

    View details for PubMedCentralID PMC5726300

  • Effects of Sensitivity to Life Stress on Uncinate Fasciculus Segments in Early Adolescence. Social cognitive and affective neuroscience Ho, T. C., King, L. S., Leong, J. K., Colich, N. L., Humphreys, K. L., Ordaz, S. J., Gotlib, I. H. 2017

    Abstract

    Previous research suggests that exposure to early life stress (ELS) affects the structural integrity of the uncinate fasciculus (UF), a frontolimbic white matter tract that undergoes protracted development throughout adolescence. Adolescence is an important transitional period characterized by the emergence of internalizing psychopathology such as anxiety, particularly in individuals with high levels of stress sensitivity. We examined the relations among sensitivity to ELS, structural integrity of the UF, and anxiety symptoms in 104 early adolescents. We conducted structured interviews to assess exposure to ELS and obtained subjective and objective ratings of stress severity, from which we derived an index of ELS sensitivity. We also acquired diffusion MRI and conducted deterministic tractography to visualize UF trajectories and to compute measures of structural integrity from three distinct segments of the UF: frontal, insular, temporal. We found that higher sensitivity to ELS predicted both reduced fractional anisotropy in right frontal UF and higher levels of anxiety symptoms. These findings suggest that fibers in frontal UF, which are still developing throughout adolescence, are most vulnerable to the effects of heightened sensitivity to ELS, and that reduced structural integrity of frontal UF may underlie the relation between early stress and subsequent internalizing psychopathology.

    View details for DOI 10.1093/scan/nsx065

    View details for PubMedID 28460088

  • The impact of the severity of early life stress on diurnal cortisol: The role of puberty. Psychoneuroendocrinology King, L. S., Colich, N. L., LeMoult, J., Humphreys, K. L., Ordaz, S. J., Price, A. N., Gotlib, I. H. 2017; 77: 68-74

    Abstract

    Researchers have documented dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in children and adolescents who experienced early life stress (ELS). The precise nature of this dysregulation, however, has been difficult to discern. In fact, both elevated and blunted patterns of diurnal cortisol regulation have been reported in children and adolescents exposed to greater ELS, including both reduced and heightened cortisol levels and change in cortisol across the day. These divergent findings may be due to developmental changes in the relation between ELS and HPA-axis functioning. The present study was designed to examine the role of puberty in the impact of the severity of ELS on the regulation of diurnal cortisol. Boys and girls (N=145) ages 9-13 years recruited from lower-risk communities completed an interview about their ELS experiences and at-home collection of diurnal cortisol. ELS experiences were objectively coded for severity, and children's level of pubertal development was measured using Tanner Staging. Multi-level piecewise mixed-effects models tested the effects of ELS severity and pubertal stage on cortisol levels at waking, the cortisol awakening response (CAR), and the daytime cortisol slope. While we found no significant interactive effects of pubertal stage and ELS severity on cortisol levels at waking or the daytime cortisol slope, findings indicated that pubertal stage interacted with ELS severity to predict the cortisol awakening response (CAR). Specifically, in earlier puberty, higher ELS was associated with a blunted CAR compared to lower ELS; in contrast, in later puberty, higher ELS was associated with a heightened CAR compared to lower ELS. Differences in the relation between ELS severity and the CAR were uniquely determined by puberty, and not by age. By considering and examining the role of puberty, the current study provides a developmental explanation for previous divergent findings of both blunted and heightened patterns of diurnal cortisol following ELS. These results indicate that careful attention should be given to children's pubertal status before drawing conclusions concerning the nature of diurnal cortisol dysregulation.

    View details for DOI 10.1016/j.psyneuen.2016.11.024

    View details for PubMedID 28024271

    View details for PubMedCentralID PMC5336485

  • Perceptions of Trauma and Loss among Children and Adolescents Exposed to Disasters a Mixed-Methods Study CURRENT PSYCHOLOGY King, L. S., Osofsky, J. D., Osofsky, H. J., Weems, C. F., Hansel, T. C., Fassnacht, G. M. 2015; 34 (3): 524-536