Effect of apomorphine infusion on plasma homovanillic acid in normal subjects

Previous experiments suggest that pharmacological perturbations of the brain dopaminergic system may be reflected by concentrations of plasma homovanillic acid. This study examined the ability of apomorphine infusion to reduce plasma homovanillic acid concentrations in normal subjects. The data suggests that apomorphine does not reduce plasma homovanillic acid concentration.     

The effects of diet and physical activity on plasma homovanillic acid in normal human subjects

This study examines the effect of diet and moderate physical activity on plasma levels of the dopamine metabolite homovanillic acid (HVA) in healthy young males. At weekly intervals, subjects were fed four isocaloric meals: polycose (pure carbohydrate), sustecal, low monoamine, and high monoamine. Moderate physical activity consisted of 30 minutes of exercise on a bicycle ergometer. The effect of diet on plasma HVA (pHVA) was highly significant. Compared to the polycose meal, the high monoamine meal significantly increased pHVA. Moderate physical activity also significantly increased pHVA. Future clinical studies using pHVA in man as an index of brain dopamine function should control for the effects of both diet and physical activity.     

Effects of fenfluramine on plasma homovanillic acid in healthy subjects

Summary The specificity of fenfluramine as a pharmacological probe of the serotonin system has been questioned, since animal studies with high dose 1-fenfluramine show increases in striatal levels of the dopamine metabolite homo-vanillic acid. To test the specificity of fenfluramine in humans with clinical doses, we compared plasma homovanillic acid (pHVA) concentration in healthy volunteers after administration of fenfluramine (60 mg) and placebo. There were no significant effects on pHVA, which supports previous findings that at doses used in pharmacological challenge paradigms, the effect of fenfluramine on the dopamine system is insufficient to alter measures of its change.     

Acute administration of alprazolam has no effect on plasma homovanillic acid concentration in normal subjects.

Alprazolam has been suggested as an adjuvant to neuroleptic drugs in the treatment of schizophrenic patients. In an attempt to investigate whether alprazolam has an effect on dopaminergic neurotransmission, plasma homovanillic acid concentrations were measured for 24 h following a challenge with 3 mg of alprazolam or placebo in eight healthy subjects. Alprazolam had no effect on plasma homovanillic acid which may suggest that this agent is devoid of activity at the dopaminergic system in normal subjects.     

Effect of m-chlorophenylpiperazine on plasma homovanillic acid concentrations in healthy subjects.

In view of the abundant anatomical and functional interactions between serotonin and dopamine systems, this study examined the effect of the serotonin agonist, m-chlorophenylpiperazine (mCPP) on plasma concentrations of the dopamine metabolite, homovanillic acid. Plasma prolactin levels, body temperature, and mCPP blood level were also measured. mCPP (0.35 mg/kg) and placebo were administered orally to 10 healthy men in a randomized double-blind design. Variables were measured for 210 min after administration of capsules. mCPP raised prolactin and temperature as compared to placebo, but did not affect plasma homovanillic acid concentrations. Results suggest that mCPP does not alter dopamine function.     

Neurochemical studies on tardive dyskinesia. I. Urinary homovanillic acid and plasma prolactin

Forty-two schizophrenic patients under chronic neuroleptic treatment (11-24 years) were studied, 20 without and 22 with tardive dyskinetic symptomatology. Blood and urine samples were collected on 3 consecutive days. Plasma prolactin (PRL) and urinary homovanillic acid (HVA) values were higher in both tardive dyskinetic and nontardive dyskinetic groups, compared to normals. The increased PRL and HVA values were not related to tardive dyskinesia but to the actual neuroleptic dose. The subgroup of patients with actual dose under 900 chlorpromazine equivalents had normal PRL values and increased HVA at low significance level compared to normals, while the subgroup with doses over 900 equivalents had highly significant (p less than 0.001) increased PRL and HVA values. Thus, the actual neuroleptic dose determines plasma PRL and urinary HVA excretion in patients chronically treated with neuroleptics.     

A comparison of plasma homovanillic acid concentrations in schizophrenic patients and normal controls

Plasma homovanillic acid concentrations, a potential index of central dopamine turnover, were examined in normal control subjects and chronic schizophrenic patients over a 12-hour period, including the period of sleep. Plasma homovanillic acid concentrations were lower in schizophrenic patients compared with normal controls at all times; however, within the group of schizophrenics, the more symptomatic patients had higher plasma homovanillic acid concentrations than the less severely ill patients. These data are consistent with a more complex role of dopamine in schizophrenia than was previously conceptualized.     

Tardive dyskinesia and plasma homovanillic acid

Using 61 patients with tardive dyskinesia (TD) and 25 normal controls, we explored the possibility that plasma HVA may reflect alterations in central dopamine activity or clinical aspects of TD. There were no significant differences between the two groups in plasma HVA level. Analyses of variance with age and sex as independent variables revealed that the major variance in plasma HVA was accounted for by age in both TD patients (p less than 0.001) and normals (p less than 0.049). Examining the TD patients alone, using multiple regression analysis, revealed that age, neuroleptic dose, and severity of TD accounted for 40% of the variance in plasma HVA in males, with age alone accounting for 28%. By comparison, females showed no association to neuroleptic dose or severity, and age only accounted for 8.9%. When severity of TD was the criterion variable, neuroleptic dose, plasma HVA, and age accounted for 20% of the variance in severity in female TD patients and showed no relationship in males. Possible implications of these differing findings in male and female TD patients are discussed.     

Effect of yohimbine on plasma homovanillic acid in panic disorder patients and normal controls

The effects of oral yohimbine (20 mg) or placebo or both drugs on plasma homovanillic acid (HVA) were evaluated in patients with panic disorder and normal controls. Panic disorder patients had similar HVA values at baseline compared with normal controls, and yohimbine failed to produce appreciable changes in HVA in both groups. These findings are discussed within the context of catecholaminergic theories of panic disorder.     

Free and conjugated plasma homovanillic acid in schizophrenic patients

It has recently been suggested that the plasma level of homovanillic acid (HVA) may provide an index of central dopaminergic activity in humans. Clinical studies have shown that in schizophrenic patients, plasma HVA levels increase with the severity of psychopathology. However, these studies only considered the plasma free HVA fraction whereas investigations on conjugated HVA in humans are sparse and results remain controversial. The aim of this study was to measure both plasma free and conjugated HVA in healthy volunteers and drug-free schizophrenic patients. The mean values and the ranges of plasma free HVA in volunteers and patients were similar to those described in the literature. A substantial and significant increase in plasma free HVA was observed in schizophrenic patients compared with normal subjects. In contrast, plasma conjugated HVA was significatively decreased in schizophrenics. The plasma total HVA was nevertheless higher in schizophrenics compared with controls. No significant correlations were observed between plasma HVA levels and the clinical features of schizophrenic patients rated by various psychiatric scales. These findings suggest that there is an imbalance between plasma free and conjugated HVA in schizophrenic patients, who present an increase in total HVA when compared with controls. Paranoid schizophrenic patients, who present mainly positive symptoms, show the most marked plasma free/conjugated HVA imbalance.     

Effects of carbamazepine on prolactin secretion in normal subjects and in epileptic subjects

The effects of carbamazepine (CBZ) on spontaneous secretion of prolactin (PRL) and after stimulation with thyrotropin releasing hormone (TRH) were evaluated. Volunteer subjects after acute CBZ administration, and epileptic subjects with complex partial seizures chronically treated with CBZ, were examined. In an epileptic group, CBZ did not change TRH stimulatory effect on PRL secretion. No appreciable changes of PRL spontaneous secretion were observed, and only a small increase of sleep-entrained values with preservation of the normal secretory circadian rhythm was noted, both in normal subjects and in epileptic subjects. This result could be explained by a serotoninergic activity of PRL changes produced by CBZ in these various conditions agrees with the absence of published reports of CBZ side effects associated with hyperprolactinemia.     

Measurement of plasma homovanillic acid concentrations in schizophrenic patients

1. Several lines of evidence suggest that abnormalities of central dopaminergic transmission may be involved in the expression of some schizophrenic symptoms. However, elucidation of the role of dopamine (DA) in schizophrenia has eluded investigative efforts partially because no accurate and easily repeatable measure of brain DA activity exists. 2. The development of a technique to measure homovanillic acid in plasma has offered the possibility of performing serial measurements of this major DA metabolite. 3. Assuming that plasma homovanillic acid (PHVA) concentrations is an index of brain DA activity, measurement of PHVA can play a role in elucidating the DA abnormality in schizophrenia. 4. Results to date suggest that plasma homovanillic acid concentrations are lower in chronic schizophrenic patients compared to normal controls, and that PHVA values correlate with schizophrenic symptom severity. 5. In addition, PHVA levels were shown to initially rise and subsequently decline during chronic neuroleptic administration in treatment responsive but not in treatment refractory schizophrenic patients.     

Absent prolactin response to l-tryptophan in normal and acromegalic subjects

l-tryptophan (5 g orally), the precursor of serotonin, was administered to 10 patients with acromegaly and eight control subjects. In normal subjects, there was no significant change in serum prolactin after l-tryptophan. In subjects with acromegaly, there was no significant net change in serum prolactin after l-tryptophan relative either to the baseline value before l-tryptophan or to values obtained on a control day without l-tryptophan. Activation of serotoninergic pathways by oral administration of the serotonin precursor l-tryptophan has no effect on serum prolactin in normal or acromegalic subjects.     

Elevated plasma homovanillic acid in depressed females with melancholia and psychosis

Plasma free homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured before drug treatment in 29 patients diagnosed as having major depression with melancholia and in 18 control subjects. Plasma HVA was significantly elevated in the total group of female melancholic patients when compared with female controls or male melancholics. Most female patients with psychotic melancholia had elevated HVA levels. These differences were not found in male patients. No significant differences were found for plasma MHPG.     

利培酮对精神分裂症患者血浆高香草酸的影响

目的　探讨利培酮对精神分裂症患者中枢多巴胺代谢产物血浆高香草酸 (pHVA)的影响。方法　 30例精神分裂症住院患者 (患者组 )纳入研究 ,利培酮治疗平均剂量为 (3 2± 1 1)mg/d ,共观察 6周。以阳性和阴性症状量表 (PANSS)评定疗效 ,以高效液相库仑阵列电化学检测法测定患者治疗前后的 pHVA含量。 30例健康志愿者作为对照组 ,检测pHVA水平。 结果　 (1)患者组治疗前 pHVA含量 [(7 9± 4 0 ) μg /L]与对照组含量 [(8 8± 4 1) μg /L]的差异无显著性 (P >0 0 5 ) ,而患者组治疗后 pHVA含量 [(5 3± 2 7) μg/L]明显低于治疗前 (P <0 0 1) ;(2 )治疗前患者组 pHVA与PANSS阳性症状评分 [(2 0 7± 4 1)分 ]存在正相关 (r =0 39,P <0 0 0 1) ,与基线PANSS阴性症状评分 [(19 7± 5 1)分 ]存在负相关 (r =- 0 35 ,P <0 0 1) ;(3)基础pHVA含量及其治疗前后差值[(2 6± 1 3) μg/L]与PANSS阳性症状评分减分值 [(10 8± 4 1)分 ]均分别呈正相关 (r =0 4 8,P <0 0 1;r=0 6 0 ,P <0 0 0 1)。结论　患者组治疗前pHVA可部分反映精神分裂症症状 (尤其是阳性症状 )的严重程度 ,基础 pHVA含量及治疗前后pHVA水平的变化与利培酮治疗阳性症状的疗效相关。     

Control of exogenous factors affecting plasma homovanillic acid concentration

Measurements of plasma homovanillic acid (pHVA) concentrations appear to be a valid research strategy in psychiatric disorders in which a central dopamine (DA) abnormality has been implicated. This study provides guidance about the control of some of the exogenous factors affecting pHVA concentrations. Fasting for 14 hours eliminates the dietary effects on pHVA in healthy human subjects. Changing position, walking for 30 minutes, or smoking two cigarettes has no effect on pHVA concentrations.     

Correlation between plasma homovanillic acid levels and the response to atypical antipsychotics in male patients with schizophrenia

OBJECTIVE: The authors investigated the effects of atypical antipsychotic drugs-olanzapine, perospirone, and quetiapine-on plasma homovanillic acid (pHVA) in male patients with chronic schizophrenia. METHODS: In this prospective, open-label study, the subjects were 30 inpatients who were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for schizophrenia. The authors switched patients from typical antipsychotic drugs to olanzapine, perospirone, or quetiapine. Each patient gave informed consent for the research. pHVA was assessed before and after switching medications. RESULTS: After the switch, the authors found a significant improvement in psychotic symptoms, nonsignificant improvement in extrapyramidal symptoms, and a nonsignificant reduction in pHVA. In addition, the baseline pHVA correlated positively with the score changes from baseline in the Brief Psychiatric Rating Scale (BPRS) total, positive, and negative symptoms in the group with a whole sample and in the olanzapine-treated group, and with the score changes in the BPRS total and positive symptoms in the quetiapine-treated group. CONCLUSION: Our findings indicated that the preswitching pHVA levels could be used to predict changes in the psychotic symptoms of male patients with chronic schizophrenia when switching to atypical antipsychotic drugs.