【作者】 赵一鸣；

【导师】 柯美云；

【作者基本信息】 北京协和医学院 ， 临床医学， 2009， 博士

【摘要】 一功能性呕吐患者的症状特点及心理社会因素背景与目的根据罗马Ⅲ,功能性呕吐(Functional vomiting, FV)定义为原因不明、非周期性的慢性呕吐,每周至少发作一次以上。目前FV相关的流行病学、病因及发病机制、临床特征性表现和治疗均不明确。本研究目的：通过FV问卷调查,全面了解功能性呕吐患者的人口学特点、症状谱、诱发和影响其症状的因素以及患者心理社会因素和目前的精神心理状态,为进一步探讨发病机制和有效治疗提供临床依据。对象和方法对北京协和医院消化内科门诊2008年11月～2009年5月连续入组的慢性呕吐患者进行问卷调查。排除标准：可能引起呕吐的器质性疾病、进食障碍、反刍综合征或DSM-Ⅳ(《精神疾病诊断与统计手册》第四版)所列的主要精神疾病。调查内容包括一般人口学特征、症状谱、病程、发病诱因、既往诊疗情况、心理社会情况、精神心理状态和人格等内容。结果慢性呕吐的患者共计37例,其中符合FV诊断标准的19例,符合周期性呕吐综合征诊断标准的5例。19例FV患者中,男性4名(21.1%),女性15名(78.9%)；年龄25.8±8.4岁；BMI18.7±3.3kg/m2。其余患者均为病程或呕吐发作频率不满足罗马Ⅲ中FV诊断标准。19例患者呕吐症状发生的频率符合FV诊断标准,78.9%的患者每日发作；94.7%的患者餐后发作,大部分为餐后短时间内(10-30min),呕吐过程持续数分钟,呕吐物为所进食物；所有患者呕吐发作均不需要自行诱导,63.2%的患者呕吐可以控制；52.6%的患者呕吐症状严重,对日常生活造成显著影响。主要伴随症状为进食减少、餐后饱胀不适和食欲不振；所有患者均有不同程度的重叠症状,FD最为常见(84.2%)。最常见的并发症是体重减轻。57.9%的患者呕吐发生与情绪有关；57.9%的患者经历过重大精神刺激／负性事件,10.5%的患者有过受虐史；83.3%的患者存在焦虑和／或抑郁状态；47.1%的患者具有神经质人格特征；神经质人格与焦虑抑郁状态相关。结论FV以青年女性为主；呕吐发作主要表现：多在餐后短时间内(10-30mmin),不需自行诱导,通常持续数分钟,呕吐物为所进食物。FV发病主要与情绪改变、环境应激有关,多合并精神心理状态及人格特征异常,提示心理社会因素在FV发病机制可能具有重要作用。二功能性呕吐病理生理机制的探讨背景与目的FV的病因和发病机制尚不明确,这类患者可能存在中枢性、周围性或混合性异常。本研究目的：观察FV患者胃电图、胃排空、营养餐负荷实验及胃内压测定的结果,明确FV患者是否存在内脏高敏和胃动力紊乱表现,并探讨其相关因素。对象和方法19例FV患者(男女比例4：15,年龄25.8±8.4岁),13例功能性消化不良(FD)患者(餐后不适综合征)(男女比例7：6,年龄46.7±15.8岁),14例嗳气症(BD)患者(男女比例3：10,年龄46.6±11.5岁)纳入本研究,均为消化内科门诊连续入组患者。同时纳入10例健康志愿者(男女比例2：8,年龄30.2±7.7岁)作为对照。受试者填写调查问卷(包括一般人口学特征和临床症状)和心理人格量表。对以上患者进行体表胃电图(EGG)、5小时胃排空(钡条法,5h-GE)和液体营养餐负荷试验(灌入法,LNLT)及胃内压力测定检查。同时对健康志愿者进行LNLT及胃内压测定检查作为对照。结果FV, FD、BD三组患者年龄、性别、BMI存在显著差异,FV患者更为年轻；FV、BD组均以女性为主,FD则男女比例相当；FV、FD组BMI低于BD组。三组患者均存在明显焦虑、抑郁状态,组间无明显差异。三组症状谱比较,发现胃十二指肠症状最为常见；而除呕吐之外,食欲不振和体重减轻在FV患者中更为显著。FV患者胃电图结果显示餐前、餐后主频(DF)及餐后正常节律百分比(N%)均低于正常,50%的患者存在餐后／餐前功率比(PR)异常。86.7%的FV患者存在胃排空延迟。FV患者最大饱感时液体灌入量和胃内压均低于正常,提示存在胃容受性障碍和感觉高敏。三组患者胃肌电活动与胃排空无统计学差异；FV存在明显胃部容受性障碍和感觉高敏,FD容受性高于正常,BD与HS相比无统计学差异。FV患者呕吐严重程度与餐后N%相关,恶心症状与PR相关。FV患者餐后DF、DP及饮入量与心理状态及人格特征相关。结论FV患者存在餐后胃肌电活动紊乱、排空延迟、容受性障碍和感觉高敏,提示胃动力紊乱与感觉高敏在FV病理生理机制中的重要地位。胃部容受性和敏感性是三组间最大的不同点。胃动力紊乱与心理社会因素相关,提示FV可能是是外周和中枢异常共同作用的结果。三功能性呕吐的精神心理因素与中枢机制背景与目的FV的病因和发病机制尚不明确,这类患者可能存在中枢性、周围性或混合性异常。边缘系统作为情感认知、内脏感觉与内脏运动中枢,可能在FV发病的中枢机制中扮演重要的角色。本研究目的：运用静息态fMRI检查评价FV患者是否存在中枢异常,并探讨FV发病可能的中枢机制。对象和方法8例HS(女性,年龄28.0±5.2岁)和8例FV患者(女性,年龄27.8±6.8岁)纳入本研究。首先对两组受试者排除精神疾病,并完成问卷调查(包括一般人口学特征、心理社会情况、Zung焦虑/抑郁自评量表和艾森克人格量表等)；然后对两组受试者进行静息态脑fMRI检查。选择局部一致性(regional homogeneity, ReHo)分析方法处理fMRI数据,利用双样本t检验做组间对比(P<0.05,cluster≥54),同时将胃功能检查结果与ReHo做Pearson相关分析。结果与HS相比,FV患者存在显著的焦虑抑郁状态和神经质人格特征。FV患者双侧前扣带皮质中部(MCC,BA24、32区)、左侧杏仁核、及右侧岛叶、右侧丘脑等边缘系统相关结构局部一致性(ReHo)显著增高。在边缘系统以外,左侧尾状核、双侧额叶躯体运动区和感觉区(BA6区、5区)也ReHo值增高表现。双侧枕叶(BA18、19区)、眶额皮质(BA11区)和右侧颞中回(BA39区)ReHo值低于HS。FV患者胃电餐后主频与双侧MCC、左侧额中回ReHo值负相关,与双侧楔叶、右侧颞中回ReHo值正相关。结论研究显示FV患者在静息态下边缘系统多个脑区活动异常,外周胃功能紊乱可能与特定的大脑异常活动相关。提示FV的发病可能涉及情感认知、内脏感觉、内脏运动三方面的共同作用。更多还原

【Abstract】 I Clinical Patterns and Psychosocial Aspects in Patients with Functional VomitingBackgroundAccording to the Rome Ⅲ criteria, functional vomiting (FV) is defined as recurrent, unexplained vomiting at least once per week that is not cyclical and lacks an organic basis. The clinical picture of FV remains incompletely studied, which needs to be further investigated. This study aims to explore clinical patterns, predisposing factors and psychosocial aspects in FV patients.Methods37consecutive patients who experienced chronic vomiting for at least1month were profiled by symptom questionnaires, including psychosocial influences (Zung self-rating anxiety and depression scale, SAS/SDS) and Eysenck personality questionnaire (EPQ). Exclusion criteria included organic disease to explain the recurrent vomiting, eating disorder, rumination, or major psychiatric disease according to DSM-IV.ResultsOverall,19of37patients met the Rome Ⅲ criteria of FV (4M,15F, age25.8±8.4, BMI18.7±3.3kg/m2),5of37patients were diagnosed as cyclic vomiting syndrome (CVS). All19patients had one or more episodes of vomiting per week and78.9%of them vomited every day. Postprandial vomiting occurred in94.7%of these patients (often10-30min after meals), lasting for several minutes and without self-induced maneuver. The vomitus consisted of food initially, sometimes changing to gastric juice and bile.52.6%had severe vomiting which compromised the quality of life. The most common accompanied symptoms were decreased calorie intake, postprandial fullness and anorexia. Predisposing factors included food, pressure and stress.57.9%of episodes were related to emotional changes.57.9%of FV patients had experienced negative events and10.5%had abuse history. Prevalence of abnormal psychological status in patients with FV was high and scores of SAS, SDS and EPQ-N were significantly higher than normal level. ConclusionsFV involved young female predominantly. Postprandial vomiting soon after meal without self-induced maneuver was the most common pattern of FV. Most patients were suffering from severe symptoms which impaired the quality of life. This study also indicated the association between FV and psychosocial factor and suggested its role in the pathogenesis of FV.Ⅱ Pathophysiological Mechanism of Functional VomitingBackgroundThe pathogenesis of functional vomiting (FV) remains unclear. These patients may have central, peripheral or mixed abnormalities. The objective of the study is to evaluate if there are gastric hypersensitivity and dysmotility in FV patients and to explore the possible pathogenesis of FV.Methods10healthy subjects (HS)(2M,8F, age30.2±7.7),19FV patients (4M,15F, age25.8±8.4),13functional dyspepsia (FD) patients with postprandial distress syndrome (7M,6F, age46.7±15.8) and14patients with belching disorders (BD)(3M,11F, age46.6±11.5) were enrolled in this study consecutively. GI symptoms and psychological states were evaluated by questionnaires. Cutaneous electrogastrography (EGG), gastric empting (GE) of radiopaque markers, liquid-nutrition load test (LNLT) and intragastric pressure (IGP) were performed in patients. LNLT was also performed in HS.ResultsEGG was performed on17of19FV patients. Fasting dominant frequency (DF) was almost within the normal range. However, there was a significant decrease of%N and postprandial DF.15FV patients received radiopaque marker measurements of gastric emptying and86.7%revealed delayed gastric emptying.13FV patients underwent LNLT. Compared to HS, IGP and the volume of liquid meal perfused (PV) at the maximum satiety were significantly lower in FV patients. There was no significant difference in EGG or GE among these groups. The severity of vomiting was correlated to postprandial N%and nausea was correlated to PR. There were significant correlations between postprandial DF, DP, PV and psychological states.ConclusionsPatients with FV had significant postprandial gastric dysrhythmia, delayed gastric emptying, impaired gastric accommodation and enhanced gastric sensitivity, which suggested that gastric dysmotility and hypersensitivity could play an important role in the pathogenesis of FV. There were significant differences of Gastric accommodation and sensitivity among the three groups. Gastric dysmotility was correlated to psychological states, which demonstrated its possible relationship with central abnormality.Ⅲ Psychological Influences and Central Mechanisms in Pathogenesis of FVBackgroundThe pathogenesis of functional vomiting (FV) remains unclear. These patients may have central, peripheral or mixed abnormalities. Limbic system, the central area involved in visceral sensorimotor function and mood regulation, could play a role in the pathogenesis of FV. The Purpose of this study is to explore the features of brain activity in FV patients by resting-state fMRI and to elucidate the possible central mechanisms.Methods8healthy subjects (HS)(F, age28.0±5.2) and8FV patients (F, age27.8±6.8) participated in this study. Psychological disorders were excluded by thorough clinical assessment. Both HS and FV patients completed questionnaires including SAS, SDS and EPQ. Using the regional homogeneity (ReHo) approach, we compare the brain activity between the two groups and examine the relationship between gastric function and brain activity in FV patients.ResultsFV patients had significant anxiety/depression states and neurotic personality. Compared with healthy controls, increased ReHo was found in FV patients in many limbic areas including the bilateral mid-cingulate cortex (MCC, BA24and32), left amygdala, right insular cortex, right thalamus, and other areas as left caudate nuclei, bilateral frontal sensory and motor areas (BA5and6). Decreased ReHo was found in the bilateral occipital lobe (BA18and19), bilateral orbital prefrontal cortex (BA11) and right middle temporal gyrus (BA39). Postprandial dominant frequency of electrogastrography was negatively correlated with ReHo in the bilateral MCC, left middle frontal gyrus, and was positively correlated with ReHo in the bilateral cuneus and right middle temporal gyrus.ConclusionsOur findings indicated that abnormal brain activity was distributed in limbic areas predominantly in FV patients during resting state. Some peripheral disturbance of gastric function might be related to specific abnormal patterns of brain activity. Abnormalities of cognition-emotion, visceral sensory and motor functions could contribute to the pathogenesis of FV together.更多还原