Importance Adolescence is a neurodevelopmental period during which experience-dependent plasticity in brain circuitry may confer vulnerability to depression as well as resilience to disorder. Little is known, however, about the neural mechanisms that underlie resilience during this critical period of brain development.

Objective To examine neural functional connectivity correlates of resilience in adolescent females at high and low familial risk for depression who did and did not develop the disorder.

Design, Setting, and Participants A longitudinal study was conducted at Stanford University from October 1, 2003, to January 31, 2017. Sixty-five female adolescents participated in the study: 20 at high risk in whom depression did not develop (resilient), 20 at high risk in whom depression developed (converted), and 25 at low risk with no history of psychopathology (control).

Main Outcomes and Measures We compared functional connectivity between resilient and converted, and between resilient and control, adolescent females using voxelwise 2-sided t tests to examine neural markers of resilience to depression as the main outcomes of interest. Specifically, we assessed differences in connectivity of the limbic (amygdala seed), salience (anterior insula seed), and executive control (dorsolateral prefrontal cortex seed) networks, implicated in emotion regulation. We also examined the association between functional connectivity and life events.

Results Of the 65 participants (mean [SD] age, 18.9 [2.5] years), adolescent females in the resilient group had greater connectivity between the amygdala and orbitofrontal cortex (z score = 0.23; P < .001) and between the dorsolateral prefrontal cortex and frontotemporal regions (z score = 0.24; P < .001) than did converted adolescent females. In adolescent females in the resilient group only, strength of amygdala-orbitofrontal cortex connectivity was correlated with positive life events (r₁₈ = 0.48; P = .03). Resilient adolescent females had greater connectivity within frontal (z score = 0.07; P < .001) and limbic (z score = 0.21; P < .001) networks than did control individuals. Both high-risk groups had greater salience network connectivity: the converted group had greater intranetwork connectivity than did the resilient (z score = 0.13; P < .001) and control (z score = 0.10; P < .001) groups, and the adolescent females in the resilient group had greater salience network connectivity with the superior frontal gyrus than did the converted (z score = 0.24; P < .001) adolescent females.

Conclusions and Relevance Resilient adolescent females have compensatory functional connectivity patterns in emotion regulatory networks that correlate with positive life events, suggesting that experience-dependent plasticity within these networks may confer resilience to depression. Further studies are warranted concerning connectivity-associated targets for promoting resilience in high-risk individuals.

重要性 青春期是一个神经发育时期，在此期间，大脑回路中依赖于经验的可塑性可能会导致对抑郁症的易感性以及对疾病的恢复力。然而，关于在大脑发育的这个关键时期构成复原力的神经机制知之甚少。

目的 研究患有抑郁症和未患抑郁症的具有高和低家族抑郁风险的青春期女性的神经功能连接性与复原力的相关性。

设计、设置和参与者 从 2003 年 10 月 1 日到 2017 年 1 月 31 日，在斯坦福大学进行了一项纵向研究。65 名女性青少年参与了研究：20 名处于高危状态且没有发展成抑郁症（有复原力）， 20 名患有抑郁症的高风险患者（转化），25 名低风险患者，没有精神病理学史（对照）。

主要结果和测量我们使用体素 2 边 t检验比较了恢复力和转化率之间以及恢复力和控制力之间的功能连接性，以检查抑郁恢复力的神经标志物作为感兴趣的主要结果。具体来说，我们评估了与情绪调节有关的边缘（杏仁核种子）、显着性（前岛叶种子）和执行控制（背外侧前额叶皮层种子）网络连接的差异。我们还检查了功能连接和生活事件之间的关联。

结果 在 65 名参与者（平均 [SD] 年龄，18.9 [2.5] 岁）中，弹性组中的青春期女性在杏仁核和眶额皮质之间（z得分 = 0.23；P  < .001）以及背外侧前额叶之间的连通性更强。皮质和额颞叶区域（z评分 = 0.24；P  < .001）比转化的青春期女性。仅在弹性组的青春期女性中，杏仁核-眶额皮质连接的强度与积极的生活事件相关（r ₁₈  = 0.48；P  = .03）。有弹性的青春期女性在额叶内有更大的连通性（z得分 = 0.07；P < .001) 和边缘 ( z评分 = 0.21; P  < .001) 网络比对照个体。两个高风险组都具有更大的显着网络连通性：转换组的网络内连通性高于弹性组（z得分 = 0.13；P  < .001）和控制组（z得分 = 0.10；P  < .001），而弹性组中的青春期女性与额上回的显着网络连接性高于转换后的青春期女性（z评分 = 0.24；P  < .001）。

结论和相关性 有弹性的青春期女性在情绪调节网络中具有与积极的生活事件相关的补偿性功能连接模式，这表明这些网络中依赖于经验的可塑性可能会赋予对抑郁症的适应力。需要进一步研究与连通性相关的目标，以促进高风险个体的复原力。