Luciana Monica, Hanson Karen L, Whitley Chester B
Department of Psychology, University of Minnesota, 75 East River Road, Minneapolis, MN 55455, USA.
Psychopharmacology (Berl). 2004 Aug;175(1):18-25. doi: 10.1007/s00213-004-1775-0. Epub 2004 Mar 13.
Classic phenylketonuria (PKU) is due to an inborn error of metabolism resulting in an inability to metabolize the amino acid phenylalanine. To avoid mental retardation, affected individuals observe a phenylalanine-restricted diet. When dietary control is poor, deficits in prefrontally mediated cognitive functions have been observed. It has been suggested that these deficits are due to disruptions in the mesocortical dopamine system that projects to the prefrontal cortex.
In this study, dopamine system reactivity was examined in individuals with PKU, relative to age-matched controls, using the non-specific DA antagonist haloperidol, in a repeated measures placebo-controlled design. Outcome variables included neuroendocrine, physiological, and cognitive measures.
Regardless of drug condition, PKU participants differed from control participants in their blood phenylalanine and tyrosine levels, and in their times to complete measures of attention and working memory. Also, relative to placebo, haloperidol influenced several variables irrespective of group status, including serum prolactin secretion, times to complete attention and working memory tasks, and accuracy of working memory performance. An interaction between group and drug condition was observed for the digit span task, where PKU participants exhibited greater relative impairments on haloperidol. When composite indices of impairment were derived, PKU participants demonstrated selective disruption in executive function on haloperidol relative to control subjects.
Findings are consistent with the presence of frontostriatal dysfunction in PKU but are less consistent with the notion that PFC dopamine function is specifically affected.
经典型苯丙酮尿症（PKU）是一种先天性代谢缺陷，导致无法代谢氨基酸苯丙氨酸。为避免智力发育迟缓，患者需遵循低苯丙氨酸饮食。当饮食控制不佳时，已观察到前额叶介导的认知功能存在缺陷。有人认为这些缺陷是由于投射到前额叶皮质的中脑皮质多巴胺系统受到干扰所致。
在本研究中，采用重复测量的安慰剂对照设计，使用非特异性多巴胺拮抗剂氟哌啶醇，对苯丙酮尿症患者与年龄匹配的对照组进行多巴胺系统反应性检查。结果变量包括神经内分泌、生理和认知指标。
无论药物状况如何，苯丙酮尿症患者在血苯丙氨酸和酪氨酸水平以及完成注意力和工作记忆测量的时间方面与对照组存在差异。此外，相对于安慰剂，氟哌啶醇影响了几个变量，与组别状态无关，包括血清催乳素分泌、完成注意力和工作记忆任务的时间以及工作记忆表现的准确性。在数字广度任务中观察到组别与药物状况之间的相互作用，即苯丙酮尿症患者在氟哌啶醇作用下表现出更大的相对损伤。当得出综合损伤指数时，苯丙酮尿症患者在氟哌啶醇作用下相对于对照组表现出执行功能的选择性破坏。
研究结果与苯丙酮尿症存在额纹状体功能障碍一致，但与前额叶皮质多巴胺功能受到特异性影响的观点不太一致。
