Howell Brittany R, McCormack Kai M, Grand Alison P, Sawyer Nikki T, Zhang Xiaodong, Maestripieri Dario, Hu Xiaoping, Sanchez Mar M
Department of Psychiatry & Behavioral Sciences, Emory University, 101 Woodruff Circle, WMB Suite 4000, Atlanta, GA 30322, USA.
Biol Mood Anxiety Disord. 2013 Dec 2;3(1):21. doi: 10.1186/2045-5380-3-21.
Early adverse experiences, especially those involving disruption of the mother-infant relationship, are detrimental for proper socioemotional development in primates. Humans with histories of childhood maltreatment are at high risk for developing psychopathologies including depression, anxiety, substance abuse, and behavioral disorders. However, the underlying neurodevelopmental alterations are not well understood. Here we used a nonhuman primate animal model of infant maltreatment to study the long-term effects of this early life stress on brain white matter integrity during adolescence, its behavioral correlates, and the relationship with early levels of stress hormones.
Diffusion tensor imaging and tract based spatial statistics were used to investigate white matter integrity in 9 maltreated and 10 control animals during adolescence. Basal plasma cortisol levels collected at one month of age (when abuse rates were highest) were correlated with white matter integrity in regions with group differences. Total aggression was also measured and correlated with white matter integrity.
We found significant reductions in white matter structural integrity (measured as fractional anisotropy) in the corpus callosum, occipital white matter, external medullary lamina, as well as in the brainstem of adolescent rhesus monkeys that experienced maternal infant maltreatment. In most regions showing fractional anisotropy reductions, opposite effects were detected in radial diffusivity, without changes in axial diffusivity, suggesting that the alterations in tract integrity likely involve reduced myelin. Moreover, in most regions showing reduced white matter integrity, this was associated with elevated plasma cortisol levels early in life, which was significantly higher in maltreated than in control infants. Reduced fractional anisotropy in occipital white matter was also associated with increased social aggression.
These findings highlight the long-term impact of infant maltreatment on brain white matter structural integrity, particularly in tracts involved in visual processing, emotional regulation, and somatosensory and motor integration. They also suggest a relationship between elevations in stress hormones detected in maltreated animals during infancy and long-term brain white matter structural effects.
早期不良经历，尤其是那些涉及母婴关系中断的经历，对灵长类动物的正常社会情感发展有害。有童年虐待史的人患精神疾病的风险很高，包括抑郁症、焦虑症、药物滥用和行为障碍。然而，潜在的神经发育改变尚不清楚。在此，我们使用一种婴儿虐待的非人灵长类动物模型，来研究这种早期生活压力对青春期大脑白质完整性的长期影响、其行为相关性，以及与早期应激激素水平的关系。
使用扩散张量成像和基于纤维束的空间统计学方法，研究9只受虐待动物和10只对照动物在青春期的白质完整性。在1月龄（虐待发生率最高时）采集的基础血浆皮质醇水平，与存在组间差异的区域的白质完整性相关。还测量了总攻击性，并将其与白质完整性相关联。
我们发现，经历母婴虐待的青春期恒河猴，其胼胝体、枕叶白质、外髓板以及脑干中的白质结构完整性（以分数各向异性衡量）显著降低。在大多数分数各向异性降低的区域，径向扩散率出现相反变化，轴向扩散率无变化，这表明纤维束完整性的改变可能涉及髓鞘减少。此外，在大多数白质完整性降低的区域，这与生命早期血浆皮质醇水平升高有关，受虐待婴儿的血浆皮质醇水平显著高于对照婴儿。枕叶白质分数各向异性降低也与社交攻击性增加有关。
这些发现突出了婴儿虐待对大脑白质结构完整性的长期影响，特别是在涉及视觉处理、情绪调节以及体感和运动整合的纤维束中。它们还表明，在受虐待动物婴儿期检测到的应激激素升高与大脑白质结构的长期影响之间存在关联。
