Coplan J D, Trost R C, Owens M J, Cooper T B, Gorman J M, Nemeroff C B, Rosenblum L A
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Arch Gen Psychiatry. 1998 May;55(5):473-7. doi: 10.1001/archpsyc.55.5.473.
In an earlier study, infant primates were nursed by mothers randomly assigned to variable foraging demand (VFD) or nonvariable foraging conditions (non-VFD). A group of grown VFD-reared subjects demonstrated elevations of cisternal cerebrospinal fluid (CSF) corticotropin-releasing factor concentrations and decreased CSF cortisol levels vs non-VFD counterparts. To further characterize neurobiological sequelae of disturbed early rearing, CSF concentrations of serotonin, dopamine, and norepinephrine metabolites (5-hydroxyindoleacetic acid, homovanillic acid, and 3-methoxy-4-hydroxyphenethyleneglycol [MHPG], respectively) and of somatostatin were determined.
Second CSF taps were obtained from the previously studied cohort of 30 subjects and from 28 age-matched ad libitum-reared control subjects. Relevant assays were performed.
All neurochemicals assayed except MHPG were elevated in the VFD-reared compared with non-VFD subjects. In the VFD group, statistically significant positive correlations between corticotropin-releasing factor and each neurochemical was found, except for MHPG. In the non-VFD subjects, no significant correlations with corticotropin-releasing factor were observed. No effect of age was evident.
Reducing the predictability of maternal foraging demand during early rearing was associated with elevations of cisternal somatostatin and of serotonin and dopamine metabolite concentrations in grown offspring. The corticotropin-releasing factor elevations reported previously were positively correlated with all the elevated CSF parameters of the current study. The findings support the notion that adverse early rearing experiences in primates have longstanding and complex effects on a range of neurochemicals relevant to emotional regulation. Replication in prospective age-controlled studies is warranted.
在一项早期研究中，幼年灵长类动物由被随机分配到可变觅食需求（VFD）或不变觅食条件（非VFD）的母亲哺育。与非VFD组的对应动物相比，一组由VFD饲养长大的受试动物显示出脑池脑脊液（CSF）促肾上腺皮质激素释放因子浓度升高，而CSF皮质醇水平降低。为了进一步描述早期抚养受干扰后的神经生物学后遗症，测定了CSF中5-羟色胺、多巴胺和去甲肾上腺素代谢产物（分别为5-羟吲哚乙酸、高香草酸和3-甲氧基-4-羟基苯乙二醇[MHPG]）以及生长抑素的浓度。
对先前研究的30名受试动物和28名年龄匹配的自由饲养对照动物进行第二次CSF抽取，并进行相关检测。
与非VFD组受试动物相比，VFD饲养长大的动物中，除MHPG外，所有检测的神经化学物质水平均升高。在VFD组中，发现促肾上腺皮质激素释放因子与每种神经化学物质之间存在统计学上显著的正相关，但与MHPG无关。在非VFD组受试动物中，未观察到与促肾上腺皮质激素释放因子有显著相关性。未发现年龄有明显影响。
在幼年时期降低母体觅食需求的可预测性与成年后代脑池生长抑素以及5-羟色胺和多巴胺代谢产物浓度升高有关。先前报道的促肾上腺皮质激素释放因子升高与本研究中所有升高的CSF参数呈正相关。这些发现支持了这样一种观点，即灵长类动物早期的不良抚养经历对一系列与情绪调节相关的神经化学物质有长期而复杂的影响。有必要在前瞻性年龄对照研究中进行重复验证。
