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

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.

SUBMITTER: Cullen KR

PROVIDER: S-EPMC7058485 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Little is known about the bio-behavioral mechanisms underlying and differentiating suicide attempts from non-suicidal self-injury (NSSI) in adolescents. Adolescents who attempt suicide or engage in NSSI often report significant interpersonal and social difficulties. Emotional face recognition ability is a fundamental skill required for successful social interactions, and deficits in this ability may provide insight into the unique brain-behavior interactions underlying suicide attempts versus NSSI in adolescents. Therefore, we examined emotional face recognition ability among three mutually exclusive groups: (1) inpatient adolescents who attempted suicide (SA, n = 30); (2) inpatient adolescents engaged in NSSI (NSSI, n = 30); and (3) typically developing controls (TDC, n = 30) without psychiatric illness. Participants included adolescents aged 13-17 years, matched on age, gender and full-scale IQ. Emotional face recognition was evaluated using the diagnostic assessment of nonverbal accuracy (DANVA-2). Compared to TDC youth, adolescents with NSSI made more errors on child fearful and adult sad face recognition while controlling for psychopathology and medication status (ps < 0.05). No differences were found on emotional face recognition between NSSI and SA groups. Secondary analyses showed that compared to inpatients without major depression, those with major depression made fewer errors on adult sad face recognition even when controlling for group status (p < 0.05). Further, compared to inpatients without generalized anxiety, those with generalized anxiety made fewer recognition errors on adult happy faces even when controlling for group status (p < 0.05). Adolescent inpatients engaged in NSSI showed greater deficits in emotional face recognition than TDC, but not inpatient adolescents who attempted suicide. Further results suggest the importance of psychopathology in emotional face recognition. Replication of these preliminary results and examination of the role of context-dependent emotional processing are needed moving forward.

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

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