A variety of studies show that parental absence early in life leads to deleterious effects on the developing CNS. This is thought to be largely because evolutionary-dependent stimuli are necessary for the appropriate postnatal development of the young brain, an effect sometimes termed the “experience-expectant brain”, with parents providing the necessary input for normative synaptic connections to develop and appropriate neuronal survival to occur. Principal among CNS systems affected by parental input are the monoamine systems. In the present study, N=434 rhesus monkeys (233 males, 201 females) were reared in one of two conditions: as mother-reared controls (MR; n=269) or without adults with 24-hour access to same-aged peers (PR; n=165). When subjects were six-months-old, they underwent a separation paradigm involving 4, sequential, four-day social separations from their mothers (MR) or peers (PR), with each separation followed by three-day reunions with their mothers or their peers. Prior to the separation paradigm, baseline cisternal CSF samples were obtained, as well as at the end of each the four social separations, and after final separation, during a recovery period. CSF was assayed for concentrations of monoamine metabolites and a blood sample was genotyped for the serotonin transporter (5-HTT) genotype. Replicating earlier landmark findings, PR subjects with the s allele exhibited lower baseline concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), when compared to PR subjects homozygous for the L allele. MR subjects were undifferentiated by genotype. PR subjects exhibited lower CSF 5-HIAA concentrations during baseline, but higher CSF 5-HIAA during social separations, when compared to MR subjects. There were rearing effects for the dopamine metabolite homovanillic acid (HVA) and for the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), with PR subjects showing higher HVA and lower MHPG when compared to MR subjects. These findings indicate that there are long-term deficits in the response of monoamines following maternal absence. The results of this study confirm and extend earlier findings that early life parental absence has deleterious consequences for the development of the monoamine systems, and that these consequences are modulated by the 5-HTT genotype.

中文翻译：

---

早期饲养条件影响基线和社会分离应激期间的单胺代谢水平：非人类灵长类动物模型（猕猴）


各种研究表明，生命早期父母缺席会对正在发育的中枢神经系统产生有害影响。这被认为主要是因为进化依赖性刺激对于年轻大脑的适当出生后发育是必要的，这种效应有时被称为“体验预期大脑”，父母为规范突触连接提供必要的输入，以发育和适当的神经元生存发生。受父母输入影响的中枢神经系统中主要是单胺系统。在本研究中，N = 434 只恒河猴（233 只雄性，201 只雌性）在以下两种条件之一下饲养：作为母亲饲养的对照（MR；n = 269）或没有成年猴，可以 24 小时与同龄同伴接触（PR；n=165）。当受试者六个月大时，他们经历了一种分离范式，包括 4 次连续的、与母亲 (MR) 或同龄人 (PR) 为期四天的社交分离，每次分离后都会与母亲或同伴进行为期三天的团聚。同行。在分离范例之前，以及在四次社会分离结束时以及最终分离后的恢复期间，获取基线脑池脑脊液样本。检测脑脊液中单胺代谢物的浓度，并对血样进行血清素转运蛋白 (5-HTT) 基因型的基因分型。与 L 等位基因纯合子的 PR 受试者相比，带有 s 等位基因的 PR 受试者表现出较低的血清素代谢物 5-羟基吲哚乙酸 (5-HIAA) 基线浓度，这重复了早期的里程碑式发现。 MR 受试者未因基因型而分化。与 MR 受试者相比，PR 受试者在基线期间表现出较低的 CSF 5-HIAA 浓度，但在社会分离期间表现出较高的 CSF 5-HIAA 浓度。 多巴胺代谢物高香草酸 (HVA) 和去甲肾上腺素代谢物 3-甲氧基-4-羟基苯基乙二醇 (MHPG) 存在饲养效应，与 MR 受试者相比，PR 受试者表现出较高的 HVA 和较低的 MHPG。这些发现表明，母亲缺席后，单胺反应存在长期缺陷。这项研究的结果证实并扩展了早期的发现，即生命早期父母缺席对单胺系统的发育产生有害后果，并且这些后果是由 5-HTT 基因型调节的。