Cullen Kathryn R, Schreiner Melinda Westlund, Klimes-Dougan Bonnie, Eberly Lynn E, LaRiviere Lori L, Lim Kelvin O, Camchong Jazmin, Mueller Bryon A
University of Minnesota, Medical School, Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry, United States of America.
University of Utah, Department of Psychiatry, United States of America.
Prog Neuropsychopharmacol Biol Psychiatry. 2020 Apr 20;99:109778. doi: 10.1016/j.pnpbp.2019.109778. Epub 2019 Nov 1.
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.
非自杀性自伤（NSSI）是一个严重的临床问题，在青少年中很常见。需要新颖的、基于生物学的方法来治疗青少年的NSSI，以预防诸如慢性NSSI和未来自杀企图等负面结果。N-乙酰半胱氨酸（NAC）已成功用于治疗其他涉及重复性适应不良行为的病症，可能对治疗NSSI有用。本研究探讨了在患有NSSI的女性青少年中进行的为期8周的开放标签NAC试验后神经回路的变化。我们使用静息态功能神经成像测量了治疗前后杏仁核和伏隔核的全脑静息态功能连接（RSFC）。18名参与者可获得治疗前和治疗后的可用神经成像数据。NSSI频率的降低与左侧杏仁核与右侧辅助运动区（SMA）的RSFC降低有关，但与右侧杏仁核与右侧额下回皮质的RSFC增加有关。对于伏隔核，NSSI频率的降低与右侧伏隔核与左侧额上内侧皮质之间的连接性降低有关。我们还报告了在抑郁和整体精神病理学测量的临床改善过程中类似回路的变化。这些初步发现表明，基于杏仁核和伏隔核的回路是潜在的治疗靶点，并为未来的研究奠定了基础，这些研究旨在使用随机、安慰剂对照设计来确认这些神经靶点，以证实临床疗效和作用机制。
