Neural correlates of clinical improvement in response to N-acetylcysteine in adolescents with non-suicidal self-injury

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Abstract

Non-suicidal self-injury (NSSI) is a serious clinical problem that is common in adolescents. Novel, biologically-informed approaches for treating NSSI in adolescents are needed to prevent negative outcomes such as chronic NSSI and future suicide attempts. N-acetylcysteine (NAC) has been used successfully to address other conditions that involve repetitive maladaptive behaviors and may have utility in addressing NSSI. This study explored neural circuit changes following an open-label, 8-week trial of NAC in female adolescents with NSSI. We measured whole-brain resting-state functional connectivity (RSFC) of the amygdala and the nucleus accumbens before and after treatment using resting-state functional neuroimaging. Usable neuroimaging data from both pre- and post-treatment were available for 18 participants. Reduction in NSSI frequency was associated with a decrease in left amygdala RSFC with right supplementary motor area (SMA), but with an increase in right amygdala RSFC with right inferior frontal cortex. For nucleus accumbens, a reduction in NSSI frequency was associated with a decrease in connectivity between right nucleus accumbens and left superior medial frontal cortex. We also report change in similar circuits accompanying clinical improvement in depression and global psychopathology measures. These preliminary findings suggest amygdala and nucleus accumbens-based circuits as potential treatment targets, and set the stage for future research designed to confirm these neural targets using randomized, placebo-controlled designs to confirm clinical efficacy and mechanisms of effect.

Original languageEnglish (US)
Article number109778
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume99
DOIs
StatePublished - Apr 20 2020

Bibliographical note

Funding Information:
The authors would like to express our sincere gratitude to the adolescents and their families who participated in this study. This study was funded by the National Institute of Mental Health ( R21MH094558 ; Cullen) and the Academic Health Center at the University of Minnesota (Faculty Research Development Grant; Cullen & Eberly). This work was carried out in part using computing resources at the University of Minnesota Supercomputing Institute.

Funding Information:
The authors would like to express our sincere gratitude to the adolescents and their families who participated in this study. This study was funded by the National Institute of Mental Health (R21MH094558; Cullen) and the Academic Health Center at the University of Minnesota (Faculty Research Development Grant; Cullen & Eberly). This work was carried out in part using computing resources at the University of Minnesota Supercomputing Institute.

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

  • Amygdala
  • N-acetylcysteine
  • Non-suicidal self-injury
  • Resting-state functional connectivity

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