Wood Elizabeth K, Gabrielle Natalia, Hunter Jacob, Skowbo Andrea N, Schwandt Melanie L, Lindell Stephen G, Barr Christina S, Suomi Stephen J, Higley J Dee
Department of Psychology, Brigham Young University, Provo, UT, United States.
Department of Neuroscience, Brigham Young University, Provo, UT, United States.
Front Hum Neurosci. 2021 Apr 9;15:624676. doi: 10.3389/fnhum.2021.624676. eCollection 2021.
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, = 434 rhesus monkeys (233 males, 201 females) were reared in one of two conditions: as mother-reared controls (MR; = 269) or without adults with 24-h access to same-aged peers (PR; = 165). When subjects were six-months-old, they underwent a separation paradigm involving 4, sequential, four-day social separations from their mothers or peers, 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 allele exhibited lower baseline concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), when compared to PR subjects homozygous for the 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 early maternal absence. The results of this study confirm and extend earlier findings that early parental absence has deleterious consequences for the development of the monoamine systems, and that these consequences are modulated by the 5-HTT genotype.
多项研究表明，幼年时期父母缺失会对发育中的中枢神经系统产生有害影响。这在很大程度上被认为是因为依赖进化的刺激对于幼脑的适当产后发育是必要的，这种效应有时被称为“经验期望型大脑”，父母为规范的突触连接发育和适当的神经元存活提供必要的输入。受父母输入影响的中枢神经系统系统中，单胺系统最为主要。在本研究中，434只恒河猴（233只雄性，201只雌性）在两种条件之一中饲养：作为由母亲抚养的对照组（MR；n = 269）或在没有成年动物的情况下，可24小时接触同龄同伴（PR；n = 165）。当受试动物6个月大时，它们经历了一个分离范式，包括与母亲或同伴进行4次连续的为期4天的社会分离，每次分离后与母亲或同伴进行为期3天的团聚。在分离范式之前、每次4次社会分离结束时、最终分离后以及恢复期采集基线脑池脑脊液样本。检测脑脊液中单胺代谢物的浓度，并对一份血液样本进行血清素转运体（5-HTT）基因型的基因分型。重复早期具有里程碑意义的研究结果，与携带该等位基因纯合子的PR受试动物相比，携带该等位基因的PR受试动物血清素代谢物5-羟吲哚乙酸（5-HIAA）的基线浓度较低。MR受试动物未因基因型而产生差异。与MR受试动物相比，PR受试动物在基线时脑脊液5-HIAA浓度较低，但在社会分离期间脑脊液5-HIAA浓度较高。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-羟基苯乙二醇（MHPG）存在饲养效应，与MR受试动物相比，PR受试动物的HVA较高，MHPG较低。这些发现表明，早期母亲缺失后单胺反应存在长期缺陷。本研究结果证实并扩展了早期的研究结果，即早期父母缺失对单胺系统的发育具有有害后果，并且这些后果受5-HTT基因型的调节。
