Low 5-HIAA Levels Research Articles

Updated Parkinson's disease motor subtypes classification and correlation to cerebrospinal homovanillic acid and 5-hydroxyindoleacetic acid levels

IntroductionMotor classifications of Parkinson's Disease (PD) have been widely used. This paper aims to update a subtype classification using the MDS-UPDRS-III and determine if cerebrospinal neurotransmitter profiles (HVA and 5-HIAA) differ between these subtypes in a cohort from the Parkinson's Progression Marker Initiative (PPMI). MethodsUPDRS and MDS-UPDRS scores were collected for 20 PD patients. Akinetic-rigid (AR), Tremor-dominant (TD), and Mixed (MX) subtypes were calculated using a formula derived from UPDRS, and a new ratio was developed for subtyping patients with the MDS-UPDRS. This new formula was subsequently applied to 95 PD patients from the PPMI dataset, and subtyping was correlated to neurotransmitter levels.Data were analyzed using receiver operating characteristic models and ANOVA. ResultsCompared to previous UPDRS classifications, the new MDS-UPDRS TD/AR ratios produced significant areas under the curve (AUC) for each subtype. The optimal sensitivity and specificity cutoff scores were ≥0.82 for TD, ≤0.71 for AR, and >0.71 and <0.82 for Mixed. Analysis of variance showed that the AR group had significantly lower HVA and 5-HIAA levels than the TD and HC groups. A logistic model using neurotransmitter levels and MDS-UPDRS-III could predict the subtype classification. ConclusionsThis MDS-UPDRS motor classification system provides a method to transition from the original UPDRS to the new MDS-UPDRS. It is a reliable and quantifiable subtyping tool for monitoring disease progression. The TD subtype is associated with lower motor scores and higher HVA levels, while the AR subtype is associated with higher motor scores and lower 5-HIAA levels.

Genetic association of nucleus accumbens 5-hydroxyindoleacetic acid level and alcohol preference drinking in a quasi-congenic male mice: Potential modulation by Grm7 gene polymorphism

ObjectiveTo test the hypothesis that predisposition to high alcohol drinking behavior is genetically associated with hypoactive serotonergic function in the Nucleus Accumbens (NAc). MethodAlcohol avoiding C5A3 and alcohol preferring I5B25A mice of the Quasi-congenic Recombinant QTL Introgression (RQI) mouse strains were subjected to in vivo microdialysis in the NAc. Neurotransmitter and metabolite contents were analyzed by HPLC and samples were collected in three phases: Baseline, Control, and Alcohol. Samples were collected with 20 min intervals. ResultsBetween-strain differences restricted to small chromosome segments significantly affected both alcohol preference drinking and NAc 5-HIAA levels [F1,13 = 5.569 p=.035 (General Linear Model Repeated Measures ANOVA and Tests of Between-Subjects Effects)]. Whole genome biallelic DNA marker genotyping allowed the identification of 16 differential microsatellite markers associated with low 5-HIAA levels and excessive alcohol drinking. Chromosome 6 markers were linked to Grm7 (51.19 centimorgan), a reported candidate gene for modulation of addiction. The results are consistent with earlier reports of association of low 5-HIAA and high alcohol consumption in rats and primates, including Homo sapiens. ConclusionLow NAc 5-HIAA and high alcohol consumption are genetically associated in a quasi-congenic mouse model carrying variants of the Grm7 gene. We propose that constitutional polymorphism in Grm7 may modulate CRF neuron activity via altered mGluR7 expression thus targeting CRF pathways to substance use circuits. This raises the possibility of modulation of DRN 5-HT neurons leading to hypo- or hyper-serotonergic condition in NAc and higher or lower alcohol preference drinking.

An exploration of the associations of pregnancy and perinatal features with cytokines and tryptophan/kynurenine metabolism in children with attention-deficit hyperactivity disorder (ADHD)

Intra-individual variability of the characteristics of children with attention-deficit hyperactivity (ADHD) may reflect compromised glial energy supply in the synapse. We reported recently that while serum levels of a glial marker, the cytokine S100B, were not seriously altered, levels of other cytokines and tryptophan metabolites were related to symptoms, attention and variability. Here, we explore with a regression analysis whether levels of these substances were associated with features of the index pregnancy of potential aetiological significance. Serum was taken from 35 children with DSM-IV ADHD (14 on medication) and 21 typically developing controls to measure 8 cytokines (S100B, IL-2, IL-6, IL-10, IL-13, IL-16, TNF-α and IFN-γ) and 5 metabolites (Tryptophan, Kynurenine, Kynurenate [KA], 3-hydroxy-kynurenine [3HK] and 5-hydroxyindole acetic acid [5-HIAA]). The mothers received a 124-item questionnaire on features surrounding the pregnancy. (1) For children with ADHD, a shorter pregnancy and smaller birth weight were associated statistically with increased 3HK and IFN-γ and for obstetric problems with decreased TNF-α levels. (2) Maternal smoking related to decreasing kynurenine and increasing 3HK and S100B levels in ADHD children. Paternal smoking was associated with increased tryptophan in the controls and increased IL-6 levels in ADHD children. (3) The taking of supplements often related to decreasing TNF-α, increasing IL-10 and lower 5-HIAA levels in the ADHD children. Less 5-HIAA but more tryptophan was associated with earlier and later life events, respectively. (4) Increased IL-16 and 5-HIAA levels in the ADHD group related to reports of poorer infant health. Unexpectedly, more child care (seafood and time together) in ADHD than healthy families was implicated by lower tryptophan levels and an altered balance of pro-inflammatory cytokines. Across measures control families generally showed either non-significant associations or the opposite to those of the ADHD group. In ADHD children more than controls, the balance of potentially toxic or protective kynurenine metabolites and of pro- over anti-inflammatory cytokines may reflect the perinatal experience associated with stress, but not with maternal illness.

Cerebrospinal Fluid Monoaminergic Metabolites in Wild Papio anubis and P. hamadryas Are Concordant with Taxon-specific Behavioral Ontogeny

We used a cross-sectional sample to compare ontogenetic trajectories in the concentrations of monoamine neurotransmitter metabolites in cerebrospinal fluid of wild anubis (Papio anubis, n = 49) and hamadryas (P. hamadryas, n = 54) baboons to test the prediction that they would differ, especially in males, in association with their distinct behavioral ontogenies. Values of all 3 metabolites [3-methoxy-4-hydroxyphenylglycol (MHPG), the norepinephrine metabolite; 5-hydroxyindoleacetic acid (5-HIAA), the serotonin metabolite; and homovanillic acid (HVA), the dopamine metabolite] declined consistently with dentally-calibrated maturation, and few taxon-related differences were apparent among juveniles. Adult females were too few for adequate comparison, but a discriminant function suggested that they might differ by taxon. Adult males of the 2 species differed strikingly from juveniles and from each other. Contrary to our initial hypothesis, adult male anubis had significantly lower HVA and MHPG, and higher 5-HIAA levels, than predicted from the overall, age-related trend, and MHPG continued to decline with age among adults. As young adults, male hamadryas had low 5-HIAA and a high HVA/5-HIAA ratio, while older males [normatively one-male unit (OMU) leaders] showed a reversal in the trend, with 5-HIAA rising and the HVA/5-HIAA ratio tending to fall. We speculate that the results are related to the dispersing and philopatric ontogenies of anubis and hamadryas males, respectively. Adult male anubis, whose fitness depends on building social networks with nonkin, have high relative serotonin activity, commonly associated with greater social circumspection and skill. Young adult male hamadryas, living among agnatic kin and mating opportunistically, exhibit low 5-HIAA levels, generally associated with impulsivity and social irresponsibility. This reverses as a male approaches the age at which he is normatively the leader of a one-male unit (OMU), and his fitness depends on his maintaining stable relationships with other leaders and with females.

Individual Differences in Pavlovian Autoshaping of Lever Pressing in Rats Predict Stress-Induced Corticosterone Release and Mesolimbic Levels of Monoamines

Pavlovian autoshaping CRs are directed and reflexive consummatory responses targeted at objects repeatedly paired with rewarding substances. To evaluate the hypothesis that autoshaping may provide an animal learning model of vulnerability to drug abuse, this study relates individual differences in lever-press autoshaping CR performance in rats to stress-induced corticosterone release and tissue monoamine levels in the mesolimbic dopamine tract. Long–Evans rats ( n = 14) were given 20 sessions of Pavlovian autoshaping training wherein the insertion of a retractable lever CS was followed by the response-independent presentation of food US. Large between-subjects differences in lever-press autoshaping CR performance were observed, with group high CR frequency ( n = 5) performing many more lever press CRs than group low CR frequency ( n = 9). Tail-blood samples were obtained before and after the 20th autoshaping session, then 24 h later the rats were sacrificed and dissection yielded tissue samples of nucleus accumbens (NAC), prefrontal cortex (PFC), caudate putamen (CP), and ventral tegmental area (VTA). Serum levels of postsession corticosterone were elevated in group high CR frequency. HPLC revealed that group high CR frequency had higher tissue levels of dopamine and DOPAC in NAC, lower levels of DOPAC/DA turnover in CP, and lower levels of 5-HIAA and lower 5-HIAA/5-HT turnover in VTA. The neurochemical profile of rats that perform more autoshaping CRs share some features of vulnerability to drug abuse.

Is there a suicidality syndrome independent of specific major psychiatric disorder? Results of a split half multiple regression analysis.

Biological findings such as low 5-HIAA levels in cerebrospinal fluid (CSF) in suicidal patients compared to non-suicidal patients independent of the type of psychiatric disorder indicate a broad basis for suicidality. It is therefore important to ask whether a suicidality syndrome can be delineated on a phenomenological level, and whether it is independent of specific major psychiatric disorders which are otherwise considered to be aetiologically different. This paper reports on a study of 2383 schizophrenic and 1920 depressive unselected patients with and without suicidality. They were assessed during the first 24 h after admission to a psychiatric in-patient facility using a comprehensive psychopathological assessment (AMDP system). Using multiple variance analysis and logistic regression analysis based on single symptoms, for both suicidal and non-suicidal patients it was shown that a suicidality syndrome independent of the underlying illness can be delineated. In schizophrenia as well as in major affective disorders it was found that hopelessness, ruminative thinking, social withdrawal and lack of activity are core symptoms of this suicidal syndrome. The finding of a suicidality syndrome, not associated with a specific major affective disorder, indicates the need to identify this syndrome, which should be seen as an independent dimension and diagnosed separately, and not regarded merely as a secondary symptom of major psychiatric disorders, particularly affective disorders.

Comparison of cerebrospinal fluid monoamine metabolite levels in dominant-aggressive and non-aggressive dogs

Aggression has been shown to be related to reduced serotonergic activity in humans and non-human primates, and in rodents. We now studied the relationship between cerebrospinal fluid (CSF) monoamine metabolites and canine aggression in 21 dominant-aggressive dogs ( Canis familiaris) and 19 controls. The diagnosis of dominance-related aggression was based upon a history of biting family members in contexts associated with dominance challenges. Post-mortem CSF 5-HIAA, MHPG and HVA were measured by high-performance liquid chromatography using electrochemical detection. Concentrations of CSF 5-HIAA ( P = 0.01) and HVA ( P < 0.001) were lower in the aggressive group (median values: 5-HIAA 202.0 pmol/ml; HVA 318.0 pmol/ml) than in controls (5-HIAA 298.0 pmol/ml; HVA 552.0 pmol/ml). No differences were noted in CSF MHPG levels. Differences in 5-HIAA were maintained after controlling for breed and age of dogs, but HVA differences may have been breed-dependent. Lower levels of 5-HIAA ( P = 0.02) and HVA ( P = 0.04) were found in the subgroup of aggressive dogs with a history of biting without warning (5-HIAA 196.0 pmol/ml; HVA 302.0 pmol/ml) compared to dogs that warned (5-HIAA 244.0 pmol/ml; HVA 400.0 pmol/ml). This study suggests that reduced serotonergic function is associated with aggressive behavior and impaired impulse control in dogs, a finding that is consistent with observations in primates, and suggests that serotonin modulates aggressive behavior throughout mammals.

Mean genes and the biology of aggression: a critical review of recent animal and human research.

Recent genetic work has suggested that abnormalities in serotonin biochemistry are directly causally linked to aggressive behavior, and there appears to be a consensus in the psychiatric literature that low levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid are specifically associated with impulsive violent behavior. We review the limitations of the genetic studies and conduct a meta-analysis of 39 studies linking 5-HIAA to aggression in humans. No differences in mean 5-HIAA levels were found between groups of violent impulsive psychiatric patients and groups of subjects diagnosed with other psychiatric or medical conditions not considered to involve violence once these levels had been corrected for three nonpsychiatric sources of variation (age, sex and height). However, mean 5-HIAA levels in both of these groups were lower than the mean corrected level in groups of normal healthy volunteers. The results confirm an association between low 5-HIAA levels and psychiatric disorders, but fail to support any specific relationship between low 5-HIAA levels and impulsive aggression or criminality. It is premature and misleading to speak of "mean genes" (Hen 1996) or a specific neurochemistry of aggressive behavior.

Changes in dopamine, serotonin and their metabolites in discrete brain areas of rat offspring after in utero exposure to cocaine or related drugs.

The concentrations of dopamine (DA), serotonin (5HT) and their metabolites were quantified in 5 brain areas of rats exposed to saline, cocaine (15 mg/kg b.i.d.), amitriptyline (10 mg/kg), or amfonelic acid (AFA, 1.5 mg/kg) throughout gestation. Male pups from 3 similarly treated dams were fostered to 2 surrogate dams. The process of breeding and rearing was repeated 4 times with new dams to build the groups to 4-12, since only one pup per litter was used for any one measurement. AFA was used to mimic the dopamine (DA) uptake blockade and stimulant properties of cocaine and amitriptyline was used to mimic the other pharmacological effects of cocaine. At postnatal days (PND) 30, 60, and 180, one pup per litter was removed for HPLC analysis of monoamines. A second pup received 0.3 mg/kg haloperidol, catalepsy assessed after 1 hr, and the brain used for analysis. The cataleptic response to haloperidol was unaffected by any prenatal treatment. The striatum from PND 30 cocaine rats had decreased levels of DA without a decrease in DA metabolites. At PND 60 in cocaine exposed rats, DA and DOPAC concentrations were increased, and 5HT levels were decreased in the striatum. The amitriptyline-exposed group exhibited decreased 5HT and 5-HIAA levels in the striatum. The hypothalamus of the cocaine group had lower levels of 5-HIAA, and other brain areas had a trend for lower levels of 5HT and 5-HIAA. At PND 180, DOPAC was increased in the striatum and prefrontal cortex of the cocaine group. Haloperidol-induced altered monoamine metabolism was unaffected by any prenatal treatment at any age. These data suggest that age-related changes in the DA and 5HT neurotransmission systems occur in rats exposed prenatally to cocaine. However, the ability of the dopaminergic system to respond to a challenge by a DA receptor blocker is unaltered by these in utero treatments.

Relationships between clinical effects and monoamine metabolites and amino acids in sulpiride-treated schizophrenic patients

Twenty-four acutely ill schizophrenic patients (DSM-III-R), 18-42 years old, were treated for 6 weeks with sulpiride. Sulpiride was administered in three different daily dosages (400, 800 or 1200 mg) according to a double dummy blind randomized administration schedule. The psychopathology of the patients was rated by the Comprehensive Psychopathological Rating Scale (CPRS) and the Nurse's Observation Scale for Inpatient Evaluation (NOSIE). The monoamine metabolites homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA), 4-hydroxy-3-methoxy-phenylglycol (HMPG) and the amino acids tyrosine, tryptophan, glutamate and glutamine were measured in serum before and once a week during sulpiride treatment. There were no significant correlations between the CPRS or the NOSIE morbidity scores and the biochemical measures before drug treatment. HVA levels were not correlated to rating scores during treatment, but after 6 weeks HVA had decreased significantly in the patients with a good response but not in the patients with a poor response. A negative relationship between 5-HIAA levels and depressive and negative symptoms was found. Non-responders according to the subscale for depression had low 5-HIAA levels throughout the treatment. An increase of tryptophan was correlated to improvement in the early part of treatment. High levels of glutamate or glutamine were found in non-responders before treatment. During treatment an increase of the glutamate level was correlated to improvement. Low levels of glutamine were related to improvement according to global and NOSIE (total) rating scores. Peripheral biochemical measures may be a valuable tool in the study of pathophysiological mechanisms and treatment effects in patients with schizophrenia.

Cerebrospinal Fluid and Urinary Biogenic Amines in Depressed Patients and Healthy Controls

The National Institute of Mental Health-Clinical Research Branch Collaborative Study investigated 132 drug-free, severely depressed patients and 80 healthy controls. Forty-five percent of the depressed patients excreted markedly elevated levels of urinary epinephrine (E) and metanephrine (MET), while only 5% of healthy controls did so. Using gaussian mixture distributions, we identified two subgroups of depressed patients: one excreting normal levels and the other excreting high levels of urinary E, MET, norepinephrine, and normetanephrine. Cerebrospinal fluid homovanillic acid levels were low in a subgroup of depressed patients. When analyzed by subgroup, the elevated E + MET group had markedly lower cerebrospinal fluid homovanillic acid levels than controls, whereas depressed patients with normal catecholamine levels did not. Since it has been postulated that there are two subgroups of depressed patients, those with low 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and normal 5-hydroxyindoleacetic acid (5-HIAA) levels and those with normal MHPG levels and low 5-HIAA levels, several analyses were performed to see if such a group could be identified. Our analysis failed to find evidence of a subgroup of depressives with low MHPG and normal 5-HIAA levels or normal MHPG and low 5-HIAA levels.

Neuropsychological Correlates of Urinary Amine Metabolites in Tourette's Syndrome

The relationships between neuropsychological performance and urinary amine metabolite levels (HVA, 5-HIAA, MHPG) were examined in a sample of 27 medication-free patients with Tourette's Syndrome. Correlations with specific metabolites indicated neuropsychological deficit associated with higher levels of HVA and lower levels of 5-HIAA. Variables computed to express the interaction of the various neurotransmitter systems provided strong and consistent support for such interactions in the underlying mechanism of the neurobehavioral deficits observed in these patients. The implications of these findings and directions for future research were discussed.

Reconciling the role of central serotonin neurons in human and animal behavior

AbstractAnimal research suggests that central serotonergic neurons are involved in behavioral suppression, particularly anxiety-related inhibition. The hypothesis linking decreased serotonin transmission to reduced anxiety as the mechanism in the anxiolytic activity of benzodiazepines conflicts with most clinical observations. Serotonin antagonists show no marked capacity to alleviate anxiety. On the other hand, clinical signs of reduced serotonergic transmission (low 5-HIAA levels in the cerebrospinal fluid) are frequently associated with aggressiveness, suicide attempts, and increased anxiety. The target article attempts to reconcile such human and animal findings by investigating whether anxiety reduction or increased impulsivity is more Likely to account for animal behavioral changes associated with decreased serotonergic transmission. The effects of manipulating central serotonin in experimental anxiety paradigms in animals (punishment, extinction, novelty) are reviewed and compared with the effects of antianxiety drugs. Anxiety seems neither necessary nor sufficient to induce control by serotonergic neurons on behavior. Further evidence suggests that behavioral effects of anxiolytics thought to be mediated by decreases in anxiety are not caused by the ability of these drugs to reduce serotonin transmission. Blockade of serotonin transmission, especially at the level of the substantia nigra, results in a shift of behavior toward facilitation of responding. This behavioral shift is particularly marked when there is competition between acting and restraining response tendencies and when obstacles prevent the immediate attainment of an anticipated reward. It is proposed that serotonergic neurons are involved not only in behavioral arousal but also in enabling the organism to arrange or tolerate delay before acting. Decreases in serotonin transmission seem to be associated with the increased performance of behaviors that are usually suppressed, though not necessarily because of the alleviation of anxiety, which might contribute to the suppression.

5-HIAA in cerebrospinal fluid of patients with status epilepticus.

Cerebrospinal fluid concentration of 5-hydroxyindolacetic acid (5-HIAA) was determined in 15 patients soon after recovery from status epilepticus. Similarly, patients with generalised epilepsy and persons without epilepsy, serving as controls, were also studied. The level of 5-HIAA was significantly reduced in all epileptic patients with or without status epilepticus, as compared with the nonepileptic control group. However, there was no statistical difference between patients with status epilepticus and those with generalised epilepsy. Among patients with epilepsy, low 5-HIAA levels in CSF could not be correlated with frequency or severity of seizures, or with antiepileptic drugs. A link between CSF 5-HIAA and susceptibility of humans to epilepsy may indicate a possible future therapeutic approach.

Depression, violent suicide tied to low metabolite level

Starting in the 1960s, investigators began to note several biologic characteristics associated with suicidal behavior: high excretion of 17-hydroxycorticosteroids in urine, low monoamine oxidase (MAO) activity in blood platelets, blunted thyroid stimulating hormone response to thyroid releasing hormone and, finally, low levels of dopamine metabolite, homovanillic acid (HVA), and of serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). Because low 5-HIAA levels were reported also in depressives and because patients are often both suicidal and depressed, more recent research has focused on the link between low 5-HIAA levels, depression, and suicidal behavior. At this year's Seventh World Congress of Psychiatry in Vienna, the nature of this link further unfolded. Eugene S. Paykel, MD, FRCP, FRCPsych, reported that major depression seems to precede a moderately high proportion of [actual] suicides but much lower proportion of attempted suicides. The latter behavior probably characterizes distinct group, added

Depression, violent suicide tied to low metabolite level

Starting in the 1960s, investigators began to note several biologic characteristics associated with suicidal behavior: high excretion of 17-hydroxycorticosteroids in urine, low monoamine oxidase (MAO) activity in blood platelets, blunted thyroid stimulating hormone response to thyroid releasing hormone and, finally, low levels of a dopamine metabolite, homovanillic acid (HVA), and of a serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF). Because low 5-HIAA levels were reported also in depressives and because patients are often both suicidal and depressed, more recent research has focused on the link between low 5-HIAA levels, depression, and suicidal behavior. At this year's Seventh World Congress of Psychiatry in Vienna, the nature of this link further unfolded. Eugene S. Paykel, MD, FRCP, FRCPsych, reported that major depression seems to precede "a moderately high proportion of [actual] suicides but a much lower proportion of attempted suicides." The latter behavior probably characterizes a distinct group, added

5‐hydroxytryptamine and depression: a model for the interaction of normal variance with pathology.

1 Theories linking 5-hydroxytryptamine (5-HT) with depression are briefly reviewed. The various experimental strategies adopted to investigate this relationship, examination of autopsy data, CSF metabolite data, 5-HT re-uptake patterns in human blood platelets and imipramine binding studies in human platelets, are discussed. 2 Recent studies of 5-hydroxyindole acetic acid (5-HIAA) levels in cerebrospinal fluid have revealed a linkage between low 5-HIAA levels and suicide, aggression and impulsivity. Decreases in the number of imipramine binding sites have also been found in brains of suicide victims. 3 The available data lead to the conclusion that decreased 5-hydroxytryptaminergic function may be associated with an increased risk of depression, suicide, and some types of aggression.

Aggression, suicide, and serotonin: relationships to CSF amine metabolites.

In an earlier, separate study, the authors found that human aggression and suicide (a specific aggression-related behavior) were associated with lower levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), a serotonin metabolite. That study focused on subjects with personality disorders without affective illness. In the present study they examine the life history of aggression and history of suicidal behavior in 12 subjects with borderline personality disorders without major affective disorder. Histories of aggressive behaviors and of suicide attempts were significantly associated with each other, and each was significantly associated with lower 5-HIAA levels. Altered serotonin metabolism may be a highly significant contributing factor to these behaviors in whatever diagnostic group they occur.

錐体外路系疾患髄液におけるモノアミン代謝物質

Homovanillic acid (HVA), a major metabolite of dopamine, and 5-hydroxyindoleacetic acid (5HIAA), a major metabolite of serotonin, were measured in the lumbar CSF of 7 patients with Huntington's chorea, one patient with senile chorea, 5 patients with a clinical diagnosis of dentatorubropallidoluysian atrophy (DRPLA), 2 patients with essential myoclonus, 8 patients with Parkinson's disease and 10 normal subjects as controls. HVA levels in patients with DRPLA and Parkinson's disease were significantly lower than that of the controls. HVA levels were not altered in Huntington's chorea. One patient with senile chorea showed low HVA level. 5HIAA levels in Parkinson's disease were significantly lower than that of the controls. Two patients with essential myoclonus showed low 5HIAA levels. These results suggest that dopaminergic neurons in the central nervous system (CNS) might be impaired in DRPLA and Parkinson's disease, and that serotonergic neurons in the CNS might also be impaired in Parkinson's disease.