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Neurobehavioral and Developmental Traiectories Associated with Level of Prenatal Cocaine Exposure. 与产前可卡因暴露水平相关的神经行为和发育特征。
Pub Date : 2014-11-01 DOI: 10.13188/2332-3469.1000015
Claudia A Chiriboga, Louise Kuhn, Gail A Wasserman

Introduction: In experimental models, prenatal cocaine exposure has been found to perturb GABA and dopamine development. Clinically, abnormalities in tone, posture and state regulation are noted in early infancy but the evolution of these findings over time is not well described. The current study assesses the longitudinal effects of prenatal cocaine exposure in dose-dependent fashion on developmental & behavioral and neurological trajectories over the first 2 years of life.

Methods: Three hundred and eighty infants, 113 cocaine-exposed, were enrolled at birth from an urban hospital from 2000 to 2004. Exposure was determined by maternal interview, segmental hair analyses (RIAH) in all, and meconium and urine in a subset. Developmental, behavioral and neurological assessments were carried out blind to drug exposure at 6, 12 and 24 months of age in the 306 children who returned in follow-up. Mixed-effects linear modeling (developmental growth curve) assessed change in outcome over time.

Results: The mental developmental growth curve showed a negative slope (2.2 points) in adjusted analyses among cocaine-exposed children over the first 2 years of life. (p=.04), while the slope of the motor development growth curve did not. Adjusting for microcephaly at 6 months diminished the strength of the association between cocaine exposure and mental developmental growth curve (effect modification). Cocaine exposure was marginally associated with behavioral outcomes in adjusted analyses. Total Behavior scores and Orientation/Engagement scores improved with age. At 1 year of age, prenatal cocaine exposure was significantly associated with lower motor development scores. High rates of hypertonia (global and diparesis) identified at the 6-month visit dropped dramatically in the first 2 years of life: cocaine-exposed children showed a more rapid rate of resolution of hypertonia than unexposed children, with hypertonia improving 2.2 times faster among those with heavy cocaine exposure.

Conclusion: We found differences in mental performance over the first 2 years of life associated with prenatal cocaine exposure that was mediated by microcephaly implying that cocaine exerts a sustained teratogenic effect on brain development. Early neurological (hypertonia) and behavioral findings associated with prenatal cocaine exposure improved over time. Hypertonia did not predict long-term development impairments. Conceivably, the transient nature of neurobehavioral manifestations reflects postnatally a tendency towards homeostasis of cocaine-related embryopathic perturbations of GABA and dopaminergic systems.

在实验模型中,已经发现产前可卡因暴露会干扰GABA和多巴胺的发育。在临床上,声调、姿势和状态调节的异常在婴儿期早期被注意到,但这些发现随时间的演变并没有很好地描述。目前的研究以剂量依赖的方式评估了产前可卡因暴露对生命最初2年的发育、行为和神经轨迹的纵向影响。方法:从2000年到2004年,在一家城市医院出生的380名婴儿中,有113名暴露于可卡因。暴露是通过母亲访谈、所有人的分段毛发分析(RIAH™)和一部分人的胎便和尿液来确定的。在6个月、12个月和24个月时,对306名返回的儿童进行了药物暴露的发育、行为和神经学盲评估。混合效应线性模型(发育生长曲线)评估结果随时间的变化。结果:经校正分析,可卡因暴露儿童的智力发育生长曲线在前2年呈负斜率(2.2点)。(p=.04),而运动发育生长曲线的斜率无显著差异。在6个月时调整小头畸形降低了可卡因暴露与智力发育生长曲线之间的关联强度(效应修正)。在调整分析中,可卡因暴露与行为结果有轻微关联。总行为得分和定向/投入得分随着年龄的增长而提高。在1岁时,产前可卡因暴露与较低的运动发育评分显著相关。在6个月的随访中发现的高渗血症(全身性和排尿)的发生率在生命的前2年急剧下降:可卡因暴露的儿童比未暴露的儿童表现出更快的高渗血症的消退速度,在重度可卡因暴露的儿童中,高渗血症的改善速度快2.2倍。结论:我们发现,出生前两年的智力表现差异与产前可卡因暴露有关,这是由小头畸形介导的,这意味着可卡因对大脑发育具有持续的致畸作用。与产前可卡因暴露相关的早期神经学(高张力)和行为学发现随着时间的推移而改善。高渗不能预测长期发育障碍。可以想象,神经行为表现的短暂性反映了与可卡因相关的胚胎性GABA和多巴胺能系统扰动在出生后趋于稳态的趋势。
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引用次数: 5
Biomarker Development for Brain-Based Disorders: Recent Progress in Psychiatry. 脑基疾病的生物标志物开发:精神病学的最新进展。
Pub Date : 2013-11-01 DOI: 10.13188/2332-3469.1000006
James O Ebot Enaw, Alicia K Smith

Biomarkers are biological measures that are indicative of a specific disorder, its severity or response to treatment. They are widely used in many areas of medicine, but biomarker development for brain-based disorders lags behind. Using examples from the field of psychiatry, this article reviews the concepts of biomarkers, challenges to their development and the recent progress along those lines. In addition to discussing historical biomarker candidates such as cortisol or catecholamine levels, we include progress from recent genetic, epigenetic, proteomic, neuroimaging and EEG studies. Successful identification of biomarkers will advance the field of psychiatry towards the goal of biological tests for diagnosis, symptom management and treatment response.

生物标志物是指示特定疾病、其严重程度或对治疗反应的生物学指标。它们被广泛应用于许多医学领域,但大脑疾病的生物标志物开发滞后。本文以精神病学领域为例,回顾了生物标志物的概念、其发展面临的挑战以及最近的进展。除了讨论历史生物标记候选物,如皮质醇或儿茶酚胺水平,我们还包括最近的遗传学、表观遗传学、蛋白质组学、神经影像学和脑电图研究的进展。生物标记物的成功鉴定将推动精神病学领域朝着诊断、症状管理和治疗反应的生物测试目标迈进。
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引用次数: 14
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Journal of neurology and psychology
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