精神分裂症的中枢单胺递质代谢研究

目的：比较精神分裂症治疗前后中枢5－羟色胺（5－HT）,高香草酸（HVA）,4－羟基苯乙二醇（MHPG）,5－羟吲哚醋酸（5－HIAA）相互作用的差异。方法：应用高效液相色谱（HPLC）对40例首发后经8周治疗的精神分裂症患者脑脊液5－HT,HVA,MHPG,5－HIAA进行检测,并以比值作为相互作用的指标。结果：精神分裂症组HVA／MHPG,5－HTAA／5－HT比值较对照组明显降低。治疗后HVA／MHPG比值两组间差异消失,而HVA／5－HIAA组间差异仍有显著性。结论：以阳性症状为主的精神分裂症存在5－HIAA／5－HT的降低及多巴胺和去甲肾上腺素相互作用的异常。     

脑脊液5-羟色胺和多巴胺及其代谢产物在病毒性脑炎和精神分裂症鉴别诊断中的价值

目的探讨脑脊液5-羟色胺（5-HT）、多巴胺（DA）及其代谢产物水平在病毒性脑炎和精神分裂症鉴别诊断中的价值。方法对病毒性脑炎和脑膜脑炎患者（简称病脑组）67例、精神分裂症患者37例和病例对照患者21例采用高效液相色谱法（HPLC）检测其脑脊液中5-HT、DA、5-羟吲哚乙酸（5-HIAA）和高香草酸（HVA）水平,并进行比较。结果（1）病脑组5-HT、5-HIAA、5-HIAA／HVA和5-HT／DA均明显低于病例对照组（P〈0．05～0．01）,而HVA则明显高于病例对照组（P〈0．01）;病脑组脑脊液中5-HIAA、5-HIAA／5．HT和5-H｜AA／HVA日月显低于精神分裂症组（均P〈0．01）,而HVA／DA则高于精神分裂症组（P〈0．05）;精神分裂症组脑脊液中5-HIAA／5-HT高于病例对照组（P〈0．05）,5-HT／DA低于病例对照组（P〈0．05）。（2）病脑组有精神症状者脑脊液中5-HIAA浓度低于无精神症状者（P〈0．05）,5-HT、5．HIAA、5-HIAA／5．HT和5-HIAA／HVA均低于精神分裂症组（P〈0．05～0．01）,而HVA／DA高于精神分裂症组（P〈0．05）。结论病毒性脑炎患者脑脊液中可能存在5-HT和DA系统失衡;脑脊液中5-HT、DA及其代谢产物的水平可能有助于病毒性脑炎和精神分裂症的鉴别诊断。     

抑郁症患者血浆白细胞介素与单胺代谢产物的研究

目的：探讨抑郁症患抗抑郁症治疗前后的细胞免疫及单胺类神经递质代谢产物的改变。方法：采用酶联免疫吸附法和高效液相电化学检测法，对40例抑郁症患在治疗前和抗抑郁药治疗4周后的血浆细胞因子白介素2（IL－2）和白介素6（IL－6），以及单胺代谢产物5－羟吲哚乙酸（5－HIAA）、3-甲基－4－羟－苯乙二醇（MHPG）和高香草酸（HVA）的浓度进行测定，并以20名健康人作为对照组。结果：（1）抑郁症组治疗前血浆IL－2、IL－6浓度明显高于正常对照组（P＜0．01），经过4周抗抑郁剂治疗后，随着病情显好转IL－2、IL－6较治疗前显降低（P＜0．01）；（2）抑郁症组治疗前血浆T－HIAA、MHPG、HVA浓度显低于正常对照组（P＜0．05），治疗后5－HIAA、MHPG明显高于治疗前（P＜0．05）；（3）治疗前后血浆5－HIAA的差值与治疗前后IL－2、IL－6的差值均呈显的负相关（P＜0．05）。结论：（1）抑郁症患可能伴有免疫激活和炎症反应。（2）抑郁症患存在中枢5－HT和NE功能低下。（3）IL－2、IL－6可影响中枢的5－HT活动。     

无先兆偏头痛患者血单胺类递质变化的研究

目的 了解5－羟色胺（5－TH）、5－羟吲哚乙酸（5－HIAA）、多巴胺（DA）、去甲肾上腺素（NE）在无先兆偏头痛发病中的作用。方法 用荧光分光光度法检测35例无先兆偏头痛患者（发作期16例、间歇期19例）和23例正常人血浆及血小板5－HT、5－HIAA、DA、NE含量。结果 无先兆偏头痛患者发作期组血浆5－HT含量低于对照组（P＜0.05),而5－HIAA含量高于对照组（P＜0.01）;间歇期组5－HT含量高于发作期组,而5－HIAA含量低于发作期组（P＜0.01）;发作期组血浆DA、NE含量均低于对照组（P＜0.01）间歇期组血浆DA与发作期组相比亦有显著性差异（P＜0.01）。无先兆偏头痛患者发作期组血小板5－HT含量高于对照组和间歇期组,而5－HIAA含量低于对照组和间歇期组（P＜0.01）;而发作期组血小板NE含量高于对照组和间歇期组（P＜0.01）;DA含量则低于对照组和间歇期组（P＜0.01）。结论 单胺类递质对偏头痛的发生可能有重要意义。     

精神分裂症中枢—5羟色胺代谢的再探讨

了解性别因素对精神分裂症中枢５—羟色胺（５—ＨＴ）代谢的影响。方法应用高效液相色谱（ＨＰＬＣ）对３０例男性精神分裂症、３７例女性精神分裂症、２１例男性对照组、９例女性对照组脑脊液中５—ＨＴ及其代谢产物５—羟吲哚乙酸（５—ＨＩＡＡ）进行测试。结果男、女病例组及男、女对照组四组间５—ＨＴ、５—ＨＩＡＡ水平显著不同（Ｆ＝４．２６５，Ｐ＝０．０１７；Ｆ＝５．８９６，Ｐ＝０．００４）；同时还揭示男性精神分裂症５—ＨＩＡＡ显著低于男性正常对照组（ｑ＝４．０７７２，Ｐ＜０．０１）和女性精神分裂症５—ＨＩＡＡ显著低于女性正常对照组（ｑ＝４．６２１，Ｐ＜０．０１），但未见有病例组５—ＨＴ和５—ＨＩＡＡ的性别差异，亦未见有正常对照组的性别差异。结论不论男性还是女性精神分裂症其５—ＨＩＡＡ均低于相应对照组，表明精神分裂症有５—ＨＴ代谢低下。     

家族性与散发性精神分裂症中枢5—羟色胺多巴胺相互作用比较

应用高压液相色谱(HPLC)对20例家族性和47例散发性精神分裂症进行了脑脊液中5-羟色胺(5-HT)、多巴胺(DA)及代谢产物5-羟吲哚乙酸(5-HIAA)、高香草酸(HVA)进行测试，并以它们的比值作为两者相互作用指标，结果发现家族性精神分裂症患者5-HIAA／HVA比值显著高于散发性精神分裂症（t=2．086，P=0．041)，而两组5-HT／DA未见著显性差异，本文就这种相互作用指标与阳性家族史的关系进行了对论。     

精神分裂症中枢与外周5—羟色胺类物质的关系

目的 了解精神分裂症治疗前后中枢与外周5－HT及其前体和代谢产物变化的相互关系。方法 应用高效液相色谱（HPLC）对21例首次发病后经8周治疗的精神分裂症患者脑脊液的血清5－HT、5－HIAA、TRP进行检测,并作治疗前后的相关性分析。结果 除治疗后的脑脊液和血清TRP二者呈负相关外,其余两容积内的各值均无相关性。结论 血清5－羟色胺类物质的含量不能反映中枢这类物质的浓度,经典抗精神病药主要作用于中枢。     

帕金森病患者立体定向手术前后脑脊液单胺类递质含量的改变

目的　研究帕金森病 (PD)患者脑立体定向手术前后脑脊液 (CSF)中单胺类递质含量的变化。方法测定 2 6例原发性PD患者 (PD组 )脑立体定向术前、后CSF中多巴胺 (DA)、5 羟色胺 (5 HT)、去甲肾上腺素 (NE)及其代谢产物高香草酸 (HVA)、5 羟吲哚乙酸 (5 HIAA)、3 甲氧基 4羟基苯乙二醇 (MHPG)的含量 ,另外测定 2 5例外科疾病腰麻手术患者 (对照组 )CSF中HVA、5 HIAA、MHPG含量。结果　PD组CSF中HVA、5 HIAA、MHPG含量明显低于对照组 (P <0 0 0 1、P <0 0 5、P <0 0 0 1) ;手术后组的CSF中DA、HVA ,、5 HT、5 HIAA、NE、MHPG含量明显高于手术前组 (其中DA、HVA、5 HT、5 HIAA和NE均P <0 0 0 1;MHPGP <0 0 5 )。结论　PD患者CSF单胺类神经递质代谢产物含量明显降低 ,脑立体定向术可提高PD患者脑部单胺类神经递质及其代谢产物的含量 ,其发生机制可能与DA能神经元的保护作用有关     

立体定向手术对难治性精神分裂症患者脑脊液多巴胺的影响

目的　探讨立体定向手术对难治性精神分裂症患者中枢多巴胺 (DA)代谢的影响。方法　高效液相色谱 电化学检测法 (HPLC ECD)测定 33例立体向手术治疗前后的精神分裂症患者及 30例对照者脑脊液 (CSF)中DA及高香草酸 (HVA)水平。结果　精神分裂症患者手术前CSF中DA、HVA水平显著高于对照组 (P <0 0 5 ) ;手术后DA、HAV水平显著下降 (P <0 0 5 )。结论　立体定向手术能纠正难治性精神分裂症患者中枢DA代谢的紊乱。     

精神分裂症与5—HT2A受体基因相关联

目的：探讨中国汉族人群精神分裂症与5－HT2A受体基因T102C多态性之间的关系。方法：选择精神分裂症患者286例,按病期分一般组和慢性组;以291例正常人对照,也按现年龄相应地分为一般对照组和慢性对照组,分生物学技术采用PCR扩增及MSPI内切酶酶切技术,检测各组研究对象的5－HT2A受体基因的基因型和等位基因的频率分布,结果：一般组精神分裂症患者5－HT2A受体基因A2／A2型频率及A2等位基因频率均显著高于对照组（ZA2／A2＝2．97,P＜0．05;ZA2＝2．19,P＜0．05）。经关联分析,其OR值分别为2．35（P＜0．05）和1．45（P＜0．05）。结论：提示中国汉族人群中5－HT2A受体基因多态性可能与精神分裂症呈正关联,而与慢性精神分裂症无关联。     

Monoamine metabolites in cerebrospinal fluid and behavioral ratings in patients with early and late onset of Alzheimer dementia

Patients with Alzheimer disease (AD, onset less than 65 years of age, n = 13) and senile dementia of the Alzheimer type (SDAT, onset greater than or equal to 65 years of age, n = 28) were investigated for cerebrospinal fluid (CSF) content of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) and compared with a group of controls (n = 26). A geriatric rating scale, the Gottfries-Br?ne-Steen scale, was used to assess impairment of motor performance, intellectual and emotional functioning, and symptoms common in dementia disorders. The HVA levels in CSF were significantly lower in the AD group than in the SDAT group and controls. MHPG was slightly but significantly increased in the SDAT group when compared with the controls. The HVA and 5-HIAA concentrations were correlated negatively with impairment of motor performance in the SDAT group; 5-HIAA correlated positively with impaired performance in the AD group; and 5-HIAA/HVA ratios were correlated positively with the performance variables. HVA correlated significantly and negatively with "impaired wakefulness" and "inability to increase tempo" in the SDAT group. 5-HIAA and the ratio 5-HIAA/HVA correlated significantly and positively with some items measuring intellectual and emotional impairment. In the AD group, "anxiety" and "fear-panic" correlated positively with 5-HIAA and "restlessness" with MHPG. The data indicate qualitative differences in the CSF monoamine pattern between AD and SDAT.     

CSF monoamine patterns in pathological gamblers and healthy controls

Previous reports on compounds in the cerebrospinal fluid (CSF) of pathological gamblers have focused on disturbed NA, DA and 5-HT function in the central nervous system. We have analysed precursors, transmitters and transmitter metabolites in 3 x 6 ml of CSF obtained from one female and 11 male pathological gamblers and 11 healthy male controls lumbar punctured at the L4-5 level after 8 h of fasting without preceding strict bedrest. Pathological gamblers displayed lower CSF levels of tryptophan and 5-HT while the opposite was the case for 5-HIAA, tyrosine, DA, HVA, DOPAC and HMPG. In contrast to previous studies, the NA level did not differ between pathological gamblers and healthy controls. A disrupted CSF gradient was noted for tryptophan, 5-HT, DA, HVA, DOPAC, NA and HMPG, but only in pathological gamblers. A disrupted gradient was found for 5-HIAA in both pathological gamblers and healthy controls. The results are in line with the presence of altered indoleamine and catecholamine function in pathological gamblers as well as an altered CSF transport from the brain to the lumbar compartment in such gamblers.     

抑郁症患者自杀与脑脊液单胺代谢产物的关系

目的：探讨抑郁症患者自杀与脑脊液单胺代谢产物之间的关系。方法：应用高效液相色谱法，测定24例抑郁症患者(自杀组10例，无自杀组14例)及25例对照组5-羟色胺(5-HT)代谢产物5-羟吲哚乙酸(5-HIAA)，去甲肾上腺素(NE)代谢产物3-甲基-4-羟苯乙二醇(MHPG)及多巴胺(DA)代谢产物高香草酸(HVA)的浓度。结果：抑郁症自杀组5-HIAA浓度显著低于对照组，男性自杀组5-HIAA浓度、HVA浓度和HVA／MHPG比值均显著低于男性对照组，女性则无显著差异：结论：抑郁症患者自杀可能与5-HT和DA功能低下以及DA和NE之间的关系改变有关。     

Serotonin and monoamine metabolites in cerebrospinal fluid in children: interrelationships and the influence of age, sex and precursor]

Cerebrospinal fluid and blood were taken from 15 non-neurologic children. Tryptophan(Trp), 5-HTP, 5-HT, 5-HIAA, HVA, MHPG in CSF, and 5-HT, free and total Trp(F-Trp and T-Trp) in serum were determined by HPLC method. Results showed that Trp, 5-HTP, 5-HT, 5-HIAA in CSF were positively correlated significantly. Good correlations were also found between F-Trp in serum and Trp in CSF (C-Trp), 5-HIAA and HVA, 5-HTP and MHPG. C-Trp, 5-HTP, 5-HT, 5-HIAA and HVA declined significantly with increasing age. MHPG was higher in male than in female children.     

Low platelet-poor plasma concentrations of serotonin in patients with combat-related posttraumatic stress disorder.

BACKGROUND: Combat-related posttraumatic stress disorder (CR-PTSD) is associated with a dysregulation of various neurotransmitter systems. METHODS: We assessed levels of platelet-poor plasma (PPP) norepinephrine (NE), and serotonin (5-HT), and 24-hour urinary excretion of NE, dopamine (DA), and homovanillic acid (HVA) in 17 male outpatients with untreated chronic CR-PTSD (age, 33.1 +/- 7.4 years) and 10 normal control subjects (age, 35.8 +/- 2.7 years). RESULTS: Compared with the control subjects, the PTSD patients showed significantly lower PPP 5-HT levels, elevated PPP NE levels, and significantly higher mean 24-hour urinary excretion of all three catecholamines (NE, DA, and HVA). The 24-hour urinary HVA values of the CR-PTSD patients correlated significantly and positively with the total Impact of Event Scale scores and the avoidance symptoms cluster scores, and the PPP 5-HT levels correlated negatively with the Hamilton Anxiety Rating Scale scores. The PPP NE/5-HT ratio was significantly higher in the study group than in the control subjects. CONCLUSIONS: We believe this combined enhanced noradrenergic activity and diminished 5-HT activity may be relevant to the neurobiology of CR-PTSD.     

The levels of monoamines and their metabolites in the brain structures of rats with an experimental anxiodepressive state induced by administration of an inhibitor of dipeptidyl peptidase 4 in the early postnatal period

In a model of an experimental anxiodepressive state induced by postnatal administration of an inhibitor of dipeptidyl peptidase 4 (DPP-4), we studied peculiarities of the turnover of dopamine (DA), noradrenaline (NA), and serotonin (5-HT) in the brain structures of rats at ages of 1, 3, and 7 months. In males, the major changes in the functional activity of the DA system, which are related to a decrease in DA turnover according to the HVA/DA ratio, were observed in the striatum. In males at an age of 7 months, we found an increase in the NA level in the hypothalamus. In females, changes in the state of the DA system included a decrease in the level of DA and its metabolites in the nucleus accumbens (1 and 3 months), the level of DOPAC in the hypothalamus (3 months), and the level of DA in the striatum (7 months). At all ages, in the hippocampus of females, we found an increase in the functional activity of 5-HT, according to the 5-HIAA/5-HT and 5-HIAA level. In the frontal cortex of females at an age of 3 months we found a decrease in the 5-HIAA/5-HT ratio and an increase in the DOPAC/DA ratio, while at the age of 7 months, we observed an increase in 5-HT. These changes in the activity of the central monoaminergic systems may reflect specific features of the functioning of the pathological system of the anxiodepressive state in the CNS that determine the character of the formation and dynamics of emotional behavioral disturbances of male and female rats.     

Dopamine may be 'hyper' with respect to noradrenaline metabolism, but 'hypo' with respect to serotonin metabolism in children with attention-deficit hyperactivity disorder

Noradrenaline: Hechtman (J Psychiat Neurosci 1994;19:193) argued for a role for frontal dopamine (DA) and noradrenaline (NA) in ADHD, where Oades (Prog Neurobiol 1987;29:365) has described lateralised functional impairments. Mechanisms (e.g. via alpha-2 sites) for stimulating low NA activity in ADHD children (J Am Acad Child Adolesc Psychiatry 1997;36:1688) in order to promote interactions with mesocortical DA have been discussed (J Psychopharmacology 1997;11:151; Psychiatr Res 1994;52:305). We described with indicators of overall transmitter metabolism (monoamines, metabolites in 24 h urine samples (Behav Brain Res 1997;88:95)) significantly lower utilisation ratios (MHPG/NA) in ADHD children with respect to healthy controls. Interestingly, a comparison of between catecholamine levels (DA/NA) showed a correlation with the conditioned blocking measure of selective attention recorded at the time of collection. This measure was negatively associated with blocking in controls. These results are consistent with reports of lower DOPEG and increased DOPAC in ADHD urine (J Child Adolesc Psychopharmacol 1996;6:63) and indicate that the relatively hyperactive DA versus NA systems may have functional consequences. Serotonin: the relevance for ADHD of an association of impulsivity with low serotonin (5-HT) metabolism (Behav Brain Sci 1986;9:319) has long been played down. Yet, some symptoms have been related to CSF measures of the metabolite 5-HIAA, and in particular the HVA/5-HIAA ratio has been reported to correlate with ratings of activity (Psychiatr Res 1994;52:305). We find that while urinary measures of 5-HIAA are somewhat higher, the ratio HVA/5-HIAA is markedly lower in ADHD children versus controls. In these ADHD children 5-HIAA levels were negatively related to d-prime measures in a continuous performance task (CPTax), and the HVA/5-HIAA was negatively associated with conditioned blocking. These results suggest a relatively low DA versus 5-HT activity may have functional consequences, albeit in a subgroup of ADHD. This is consistent with drug-induced prolactin changes reported by Verbaten et al. (Eur Child Adolesc Psychiatry 1999;8:30).     

CSF amine metabolites in depression.

The amine metabolites, namely homovanillic acid (HVA) and 5-hydroxy indoleacetic acid (5-HIAA) were measured in cerebrospinal fluid (CSF) of depressives (n = 30) and controls (n = 30). Depressed patients had significantly lower HVA levels than controls. No significant differences were noted between the two groups in 5-HIAA levels. However, the differences between the groups for the CSF HVA/5-HIAA ratio were larger than those for the CSF HVA alone (p less than 0.01 versus p less than 0.025, respectively). HVA levels correlated positively with monoamine oxidase activity and adenosine deaminase activity.     

Regional studies of serotonin and dopamine metabolism and quantification of serotonin uptake sites in human cerebral cortex

Summary An increasing number of studies have indicated that neuronal metabolism of serotonin (5-HT) and other monoamines may be altered in patients with affective disorders and in completed suicides. However, studies have yielded discordant results. The purpose of this study was to determine the regional variation of 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), (5-HT) and 5-HT uptake sites within the human cerebral cortex.Our sample consisted of 19 patients who died suddenly and accidently. Cortical concentrations of 5-HIAA, HVA and 5-HT were measured in six regions using an HPLC. 5-HT uptake sites in cortex were examined using [³H] Paroxetine.5-HT values within each brain were fairly constant in cortical regions studied except for the posterior parietal areas. By contrast, 5-HIAA values showed a trend towards a rostro-caudal increase, with peak values seen at sections corresponding to the post-central gyrus and the occipital pole. Using the ratio of 5-HIAA/5-HT as a crude index of 5-HT turnover, there was a progressive rostro-caudal increase of values which achieved statistical significance: the posterior superior parietal area and the occipital pole displayed a greater ratio than the other four cortical regions. HVA values were highest in the pre-central region and decreased both rostrally and caudally. 5-HIAA and HVA values were correlated positively in 5 of 6 cortical areas, while 5-HIAA and 5-HT were correlated in areas 4 and 5. Results obtaining using [³H]-Paroxetine suggest that 5-HT uptake sites in the human cortex are distributed rather uniformally and are not correlated with 5-HT levels.     

Modification of gonadectomy-induced increases in brain monoamine metabolism by steroid hormones in male and female rats

Concentrations of monoamines (dopamine, DA; serotonin, 5-HT) and their major metabolites (homovanillic acid — HVA; dihydroxyphenylacetic acid — DOPAC; 5-hydroxyindolacetic acid — 5-HIAA) were measured in selected brain areas of chronically gonadectomized, steroid- or oil-treated male and female rats. Concentrations of DOPAC and HVA were markedly increased in the hypothalamus (male, female), striatum (male, female) and brainstem (male) following gonadectomy, whereas the levels of DA remained unaltered in most of the brain areas examined. Most of the changes were reversed or attenuated by chronic estradiol (EB) substitution. In contrast, chronic treatment with physiological concentrations of testosterone (TP) reduced indexes of DA turnover only in the striatum of ovariectomized (OVX) and brainstem of orchidectomized (ORDX) rats. ORDX-related increases in striatal levels of DOPAC and HVA were not reversed by either EB or TP. ORDX increased the levels of 5-HIAA (hypothalamus, striatum) and decreased those of 5-HT (hypothalamus, hippocampus). These changes were reversed by chronic treatment with either TP or EB. Brain metabolism of 5-HT remained unaltered following OVX.

Gonadectomy and chronic steroid replacement therapy appear to alter brain monoamine metabolism in a brain region and sex-dependent manner. Our data demonstrate that gonadectomy-related increases in the activity of brain monoaminergic neurons in both male and female rats was attenuated more effectively with physiological concentrations of estradiol than with testosterone. Insensitivity of monoaminergic neurons in a number of brain areas (e.g., hypothalamus, striatum) to the action of testosterone was evident in both sexes.