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High early life stress and aberrant amygdala activity: risk factors for elevated neuropsychiatric symptoms in HIV+ adults

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Abstract

Relative to HIV-negative adults, HIV+ adults report elevated levels of early life stress (ELS). In non-HIV samples, high ELS has been linked to abnormalities in brain structure and function, as well as increased risk of neuropsychiatric symptoms. Yet, little is known about the neural effects of high ELS, and their relation to elevated neuropsychiatric symptoms, in HIV+ adults. Recent studies have revealed combined effects of HIV and high ELS on amygdala morphometry. Aberrant amygdala activity is prominently implicated in studies of neuropsychiatric symptomology in non-HIV samples. Hence, this preliminary study examined: 1) the combined effects of HIV and high ELS on amygdala activity, and 2) the relation between amygdala activity and neuropsychiatric symptoms in HIV+ adults. We included 28 HIV+ adults and 25 demographically-matched HIV-negative control (HC) adults. ELS exposure was quantified using a retrospective ELS questionnaire, which defined four groups: HIV+ Low-ELS (N = 15); HIV+ High-ELS (N = 13); HC Low-ELS (N = 16); and HC High-ELS (N = 9). Participants completed a battery of neuropsychiatric measures. BOLD fMRI assessed amygdala reactivity during explicit observation of fearful/angry faces. High-ELS participants demonstrated reduced levels of amygdala reactivity relative to Low-ELS participants. HIV+ High-ELS participants reported higher levels of neuropsychiatric symptoms than all other groups. In the HIV+ group, lower amygdala responses were associated with higher neuropsychiatric symptoms, particularly depression, anxiety, and alexithymia. Collectively, these results suggest that high ELS exposure is a significant risk factor for neuropsychiatric symptoms in HIV+ adults. Furthermore, our results implicate ELS-related abnormalities in amygdala activity in the etiology of neuropsychiatric symptoms in HIV+ adults.

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Acknowledgments

We thank all of the individuals who participated in this study. In addition, we gratefully acknowledge Karen T. Tashima, MD, Timothy P. Flanigan, MD, and the teams at The Miriam Hospital Immunology Center and the Manhattan HIV Brain Bank, who provided valuable aid in our recruitment efforts. Finally, we also thank Rachal Hegde for her assistance in preparing this manuscript.

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Authors and Affiliations

  1. Department of Neurology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1052, New York, NY, 10029, USA

    Uraina S. Clark & Susan Morgello

  2. Department of Psychology, University of Georgia, Athens, GA, USA

    Lawrence H. Sweet

  3. Department of Psychiatry and Human Behavior, The Warren Alpert Medical School of Brown University, Providence, RI, USA

    Lawrence H. Sweet, Noah S. Philip & Ronald A. Cohen

  4. Providence VA Medical Center, Providence, RI, USA

    Noah S. Philip

  5. Departments of Aging and Geriatric Research, Neurology, and Psychiatry, University of Florida College of Medicine, Gainesville, FL, USA

    Ronald A. Cohen

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  1. Uraina S. Clark
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Correspondence to Uraina S. Clark.

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Funding

This work was supported by grants from the National Institutes of Health (Grants K23 MH096628 [USC], R25 MH080663 [USC], R01 MH074368 [RAC], R25 MH083635 [USC], and P30 AI042853 [RAC]), the Brown University MRI Research Facility [USC], and the US Department of Veterans Affairs (Grant IK2 CX00724 [NSP]). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the NIH or Department of Veterans Affairs.

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The authors declare that they have no conflicts of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Clark, U.S., Sweet, L.H., Morgello, S. et al. High early life stress and aberrant amygdala activity: risk factors for elevated neuropsychiatric symptoms in HIV+ adults. Brain Imaging and Behavior 11, 649–665 (2017). https://doi.org/10.1007/s11682-016-9542-5

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