Individuals with ADHD focus excessively on specific stimuli without the ability to discriminate between the relevant and the non-relevant. Hyperactivity and impulsivity are also components of the condition. Executive function and, therefore, attention and behavioral inhibition are primary activities of the frontal lobes. MRIs of individuals diagnosed with ADHD demonstrate decreased activation of the frontal cortex, including lower levels of neurotransmitters. Neurotransmitters in the frontal lobe are primarily the catecholamines, dopamine and norepinephrine. ADHD medications target these neurotransmitters, increasing their availability. Serotonergic receptors, which have been linked to attention capability, may also play a role in ADHD pathophysiology.

患有ADHD的个体过分注重具体的刺激，但是他们没有能力区别哪种是相关刺激，哪种是不相关刺激。于是多动和冲动就变成了这类疾病的组成部分。在大脑中，脑前叶的主要活动为执行、抑制注意力和行为。通过MRI图像显示，患有ADHD的机体的脑前叶灰质活化功能下降，神经递质不足。脑前叶中的神经递质主要是儿茶酚胺、多巴胺以及去甲肾上腺素。治疗ADHD的药物靶向目标就是这些神经递质，他们来提高这些神经递质的效能。从药理病理学来说，与注意力密切相关的5-羟色胺受体，在治疗ADHD方面也起着重要的作用。

ADHD is thought to result from a complex interplay between genes and environment. Variants of the gene that codes for dopamine-related proteins, including transport, receptor and enzyme proteins, have been implicated in ADHD. Recognized environmental contributors to ADHD include head injuries, food preservatives and dyes, toxins, infectious exposure, food allergens, and nutrient insufficiencies. A full understanding of the genetics of ADHD may depend upon understanding multiple gene-environment interactions.

ADHD一般被认为是由基因和环境之间复杂的相互作用产生的。基因的变异，特别是多巴胺密码子的变异，常常表明机体患有ADHD。多巴胺与蛋白质和酶类蛋白质密切相关，在蛋白质中又与其运输、接收作用有关。可以造成ADHD的环境因素有头部受伤、添加防腐剂和染色剂的食物、毒素、感染、食物过敏原和营养物质缺乏等。对ADHD的遗传学分析必须要建立在理解多种基因-环境相互影响的基础上。

At 12 years of age, PJ was on an overwhelming pharmacopoeia, including cetirizine, albuterol, levalbuterol inhaler, flunisolide, cimetidine, acetaminophen and ibuprofen without good result. While methylphenidate, speciflcally designed to address low prefrontal cortex catecholamine status, did not improve his school performance in any measurable way, it did cause growth retardation and was therefore discontinued. Side effects of his medications may also have contributed to the pathogenesis of his numerous complaints. For example, cimetidine has been associated with nutritional deficiencies and gastrointestinal bacterial overgrowth from gastric acid inhibition. Glutathione depletion results from acetaminophen use, and intestinal permeability increases with use of nonsteroidal anti-inflammatory medications such as ibuprofen. Flunisolide has also been shown to inhibit growth in children.

12岁的时候，PJ总是需要吃包括西替利嗪、沙丁胺醇、左旋沙丁胺醇吸入剂、氟尼缩松、甲氰咪胍、对乙酰氨基酚、布洛芬在内的许多药物，但是并没有达到很好的效果。此外，服用利他灵也没有改善他在学校的表现，反而造成了他的发育迟缓，因此他不再服用利他灵这种专门解决额前叶灰质儿茶酚胺分泌不足的特制药物。他体内许多病状的发病机制其实都和他服用的药物副作用有关，例如，用来抑制胃酸的甲氰咪胍会导致营养不良和胃肠道真菌感染；服用乙酰氨酚则会引起谷胱甘肽缺乏症；像布洛芬这样的非甾体类抗炎药则会使肠通透性过高；氟尼缩松则会抑制儿童的生长。

Very low levels of zinc and magnesium and low-normal levels of other minerals were found. These findings were not surprising given PJ's poor diet, GI inflammation and cimetidine use. Zinc deficiency is implicated in asthma, atopic dermatitis, allergies and ADHD. Magnesium deficiency is also implicated in headaches, insomnia, muscle cramps and spasms. Copper and manganese are important cofactors in the antioxidant enzyme superoxide dismutase. Chromium as chromodulin may increase cellular glucose uptake by potentiating insulin receptor activity.

由于长期的不良饮食习惯，再加上PJ自身的胃肠道炎症以及甲氰咪胍的服用，不难发现PJ体内锌和镁元素的不足以及其他矿物质的缺乏，比如，锌的缺乏会造成哮喘、特异性皮炎、过敏和ADHD；镁的缺乏则会造成头痛、失眠、肌肉痉挛；铜和锰是超氧化物歧化酶的重要辅因子；铬元素，例如含铬调节子则会通过加强胰岛素受体的活动来增强细胞内的葡萄糖摄取。

DMPS (2,3-dimercapto-l-propanesulfonic acid) provocation challenge demonstrated an elevated urine lead level . Although whole blood assay is considered the gold standard for identifying lead toxicity, urinary lead concentration has also been shown to increase with toxicity.'6 On account of the fact that exposure to lead may result in cognitive deficits at levels commonly encountered in blood, numerous recommendations have been made to reduce it to safer threshold levels.'6 Lead toxicity and environmental toxins such as household mold have been linked to cognitive and behavioral problems, including ADHD, in children. Sources of lead include toys, paint, contaminated soil, lead plumbing, and glazed pottery.;` Essential mineral deficiencies may allow for increased uptake of toxic metals. Thus, the patient must be tested for and treated with essential minerals during chelation therapy.

DMPS（2，3-二疏基-1丙磺酸）则会激发机体的尿铅含量升高。尽管全血检查被认为是检测铅中毒最标准的办法，但是尿铅浓度的升高同样可以检测机体是否中毒。由于暴露在空气中的铅可能会进入血液，导致机体产生认知功能障碍，所以现在有许多的建议认为，应当把环境中的铅减少到其安全阈值范围内。铅的毒性和环境中的毒素，例如家用模具中的毒素，通常都会导致儿童认知和行为障碍，包括ADHD。因此，患者应接受铅中毒测试，以此在螯合疗法中使用必要的矿物质元素。

The result demonstrated that levels of the fat-soluble vitamins in PJ's serum were low (for E, A, and D) or undetectable (for beta carotene). Such a pattern can indicate fat malabsorption, but in PJ's case the cause was thought to be poor dietary habits. The low level of vitamin D probably played a role in PJ's unbalanced immune response, contributing to both his chronic infections and hypersensitivities. Hypovitaminosis D has been implicated in asthma, general development problems, and mood disorders.'' The optimal level of serum vitamin D is now thought to lie between 40 to 70 ng/mL; individuals with serious diseases should maintain levels between 55 to 70 ng/mL.

检测结果显示，PJ血清中的脂溶性维生素不足（包括维生素E、A和D）或缺乏（包括β-胡萝卜素）。这种情况一般是由脂肪吸收障碍引起的，但是对PJ来说，这更像是由他不良的饮食习惯所造成的。维生素D的不足很可能导致了PJ免疫应答的失调，因此造成慢性感染和超敏现象。此外，缺乏维生素D还会引起哮喘、生长发育以及情绪障碍等问题。现如今认为，血清中维生素D的最优水平是40-70ng/mL,一般患有严重疾病的机体水平应维持在55-70ng/mL。

It also revealed a functional need for B6. Elevations of the organic acids xanthurenate and kynurenate demonstrated a B}, insufficiency, because the enzymes required to metabolize them further are B6, dependent.'0 A number of PJ's symptoms may have been attributable to insufficient B6 including ADHD, mood disturbances, and insomnia.

同样反映出了机体对维生素B6的功能需求。从有机酸检测报告中可以看出，机体的黄尿酸和犬尿胺酸水平反映出了机体内维生素B6的缺乏，是因为需要代谢它们的正是与B6相关的酶。PJ的许多症状都是由缺乏B6引起的，包括ADHD、情绪紊乱和失眠。

Plasma free fatty acid levels (primarily that of palmitic acid) roughly approximate plasma triglyceride levels.;`' The numerous high-normal saturated fatty acids shown in Figure 3 indicated that, at age 12, PJ probably had higher than optimal triglyceride levels most likely caused by insulin-stimulated up-regulation of liver fatty acid synthesis. Given PJ's high-sugar diet, early onset of dysinsulinemia was not surprising, although mild chromium deficiency could be another underlying factor contributing to dysinsulinemia. The elevated levels of trans fatty acids (TFAs) shown in Figure 3 were further evidence of PJ's poor food choices. TFAs are strongly implicated in metabolic syndrome and cardiovascular disease.

血浆游离脂肪酸水平（主要是软脂酸水平）与血浆甘油三酯水平大致相似。通过检测结果中大量的正常高饱和脂肪酸可以看出，作为一个12岁的孩子，PJ体内的甘油三酯水平明显过高，这很有可能是胰岛素刺激肝脏脂肪酸合成作用上调引起的。虽然铬元素的轻度缺乏也可能导致PJ的胰岛素水平失调，但由于PJ之前高糖的饮食习惯，就不难发现PJ出现早发性胰岛素水平失调的原因。反式脂肪酸的升高更加显示出PJ之前不良的饮食习惯，反式脂肪酸通常和机体的代谢综合征还有心血管疾病具有相关性。

Of the polyunsaturated omega fatty acids, the pro-inflammatory eicosanoid precursor arachidonic acid(AA) was very elevated (Figure 3) and was found in much greater quantity than the anti-inflammatory omega-3 fatty acid eicosapentaenoic acid (EPA), creating a relative deficiency of EPA. AA is implicated in the pathogenesis of allergies and asthma,while EPA insufficiency and a low EPA/AA ratio are implicated in ADHD.

通过对多元不饱和Omega脂肪酸的检测，作为促进炎症的类二十烷酸的前体，机体内花生四烯酸（AA）的水平明显提高，而且明显要高于作为抑制炎症的Omega-3脂肪酸和二十碳五烯酸（EPA）的水平，这就导致了机体内EPA的缺乏。AA水平的提高会引起过敏、哮喘的症状，而EPA的不足与EPA/AA的比值较低，则会导致ADHD。

The plasma fatty acid analysis revealed that, had PJ continued with his present diet and lifestyle, he would have incurred, as an adult, an increased risk of continued inflammatory conditions including heart disease, diabetes, and cancer. Addressing these findings early not only treated his initial complaints, but significantly reduced his future risk of ill health.

血浆性脂肪酸分析显示，如果PJ继续保持他现在的饮食和生活习惯，等他长大的时候，他将会有炎症甚至心脏病、肥胖和癌症等更大的风险。及早发现这些情况，不仅可以早期治疗PJ的病症，而且可以在很大程度上为他的未来减少健康方面的风险。

ELISA testing for IgG response to 90 different foods demonstrated a strong positive reaction to dairy (+3), a reaction to peanuts (+2), and mild positive reactions (+1 or +2) to seven other foods, indicating intestinal hyperpermeability and GI inflammation (Figure 4).These sensitivities are associated with the pathogenesis of atopic dermatitis, asthma and ADHD.4z-as Additionally, PJ's IgG antigliadin antibodies were trending high at 17 units. Clinical experience warranted minimizing gluten intake.

通过免疫球蛋白G对90种不同食物的酶连锁免疫检测显示，PJ对奶制品有强烈的过敏反应（+3），对花生也是（+2），对其他几种食物也有轻微的过敏现象（+1或者+2），表明PJ的小肠通透性过高，而且患有胃肠道炎症。这些过敏反应与特异性皮炎、哮喘以及ADHD的发病机制有着密切的联系。另外，PJ的抗麦胶蛋白含量也接近了17个单位，临床经验证明在这种情况下应当减少谷蛋白的摄取。

When introduced into the diet prior to age 1, as in the case of PJ, gluten-containing grains are associated with a statistically significant increase in the incidence of celiac disease in susceptible patients. Furthermore, the use of soy formula in infants with a first-degree relative with allergies (as in the case of PJ) is associated with increased incidence of allergies, food intolerances, and eczema.`'6 Early antibiotic use is also associated with an increased incidence of atopic conditions, including asthma.

正如PJ一样，在1岁前引入饮食，其自身体内的麸质就已经与易患的腹腔疾病显示出正比关系，而且，对于患有过敏的婴幼儿来说，他们那时所服用的豆制品，将加大过敏、食物不耐受和湿疹的风险。早期服用的抗生素也会增加过敏的症状，比如哮喘。

The urinary neurotransmitter metabolites for dopamine and serotonin, homovanillate (HVA) and 5-hydroxyindoleacetate (5-HIAA), were low normal in PJ, suggesting lower total body neurotransmitter turnover. Corroborative evidence of the risk of serotonin insufficiency was found in the low-normal plasma tryptophan, the amino acid precursor to serotonin. Furthermore, two important nutrients involved in dopamine and serotonin synthesis, B} and magnesium, were both reported as insufficient in PJ. Genetic and metabolic research has linked imbalances, with regard to uptake, synthesis, and breakdown of CNS dopamine and serotonin, to ADHD, although no consistent pattern has been noted.s'.sz Serotonin imbalance has also been implicated in insomnia and IBS.

作为尿路中枢神经递质代谢产物，PJ体内的多巴胺、血清素、高香草酸（HVA）和5-吲哚乙酸（5-HIAA）含量低于正常范围，这说明PJ体内的神经递质分泌失调。血浆中的色氨酸以及血清素低于正常范围，可以更加印证机体内的血清素分泌不足。不仅如此，两种与多巴胺和血清素合成相关的重要营养物质，维生素B6和镁，在PJ的病例中也表现出不足。有关于失衡的遗传性和代谢性研究，以及有关于中枢神经系统（CNS）多巴胺和血清素的吸收、合成、分解性研究，虽然两者并没有一致的研究模式，但它们都和ADHD相关。血清素分泌失衡还可以导致失眠和肠道应激综合症（IBS）。

ADHD is thought to be an issue of insufficient prefrontal cortex catecholamine production caused by a complex interplay between gene predisposition and environment exposures. The standard therapeutic goal is therefore designed to increase prefrontal cortex catecholamine production.The case of PJ, however, suggested that ADHD may be a condition involving multiple system imbalances, with comorbidities such as dysgraphia, IBS, reflux, atopy, and environmental allergies sharing similar etiologic factors. Environmental causes of ADHD inPJ's case appeared to be gluten sensitivity, lead exposure, and poor diet, which in turn contributed to intestinal hyperpermeability, IgG food sensitivities, and significant nutrient deficiencies. Interestingly, while neurotransmitter imbalances were identified on laboratory testing, their involvement in the etiology of his condition appeared secondary to other issues. Treating multiple system dysfunctions led to remarkable resolution of PJ's ADHD, his dysgraphia, and all of his other complaints. Use of a systems approach, including an extensive history with comprehensive laboratory assessment, allowed the causal factors to be identified and treated. While ADHD is the most prevalent behavioral disorder in children and a very costly health condition,' z medication therapy comes with significant risks and often very limited success. Therefore, clinicians must become skilled in the use of other approaches, such as the comprehensive assessment, dietary modifications, and nutritional therapies exemplified by this case.

ADHD是由基因和环境相互作用下，机体额前叶灰质分泌儿茶酚胺不足导致的一种神经障碍类疾病。其标准的治疗目标是促进额前叶灰质分泌儿茶酚胺。然而，PJ的病例却说明，ADHD是由机体内多种系统失调引起的，并且可以造成多种并发症的疾病。这些并发症包括书写障碍、肠道易激综合征、反流、遗传性过敏以及环境过敏，在病理生理学上，它们的发病机制都很相似。在PJ的病例中，造成PJ患有ADHD的环境原因包括谷蛋白过敏、铅暴露，导致小肠通透性过高的不良饮食习惯，免疫球蛋白食物过敏以及必需营养物质的缺乏。有趣的是，从实验室检测结果分析得出的神经递质分泌失衡，也导致了之后他其他病情的继续发展。多种系统失调的治愈，是PJ的ADHD、书写障碍和其他症状治疗的关键步骤。利用拥有广泛历史的综合性实验检测的系统性研究方法，常见的病因得到了快速定位和治疗。作为儿童最常见的一种行为障碍，同时也是花销较大的医疗问题之一，药物治疗ADHD伴随着巨大的风险，其成功的例子寥寥无几。因此，就像本病例中所示，医生在治疗ADHD的同时，必须熟练掌握应用其他辅助治疗手段，比如对患者提出综合性评估、改善饮食和营养物质补充建议。