Cerebrospinal Fluid 5-HIAA Levels Research Articles

Cerebrospinal fluid levels of 5-HIAA and dopamine in people with HIV and depression.

Depression is a common illness in people with HIV (PWH) and is associated with substantial morbidity and mortality. The mechanisms that underpin depression in PWH remain incompletely elucidated, and more research is therefore needed to develop effective treatments. One hypothesis is that neurotransmitter levels may be altered. These levels could be influenced by the chronic inflammation and viral persistence that occurs in PWH. We examined a panel of cerebrospinal fluid (CSF) neurotransmitters in PWH on suppressive antiretroviral therapy (ART), many of whom had a current depression diagnosis. CSF monoamine neurotransmitters and their metabolites were measured from participants in studies at the Emory Center for AIDS Research (CFAR). Only participants on stable ART with suppressed HIV RNA from both plasma and CSF were analyzed. Neurotransmitter levels were measured with high-performance liquid chromatography (HPLC). Neurotransmitters and their metabolites included dopamine (DA), homovanillic acid (HVA, a major metabolite of dopamine), serotonin (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA, a major metabolite of serotonin), and 4-hydroxy-3-methoxyphenylglycol (MHPG, a major metabolite of norepinephrine). Multivariable logistic regression was used to evaluate factors associated with depression. There were 79 PWH with plasma and CSF HIV RNA levels < 200 copies/mL at the time of the visit, and 25 (31.6%) carried a current diagnosis of depression. Participants with depression were significantly older (median age 53years versus 47years, P = 0.014) and were significantly less likely to be African American (48.0% versus 77.8%, P = 0.008). Participants with depression had significantly lower dopamine levels (median 0.49ng/mL versus 0.62ng/mL, P = 0.03) and significantly lower 5-HIAA levels (median 12.57ng/mL versus 15.41ng/mL, P = 0.015). Dopamine and 5-HIAA were highly correlated. In the multivariable logistic regression models, lower 5-HIAA was significantly associated with the depression diagnosis when accounting for other significant demographic factors. The associations between lower 5-HIAA, lower dopamine, and depression in PWH suggest that altered neurotransmission may contribute to these comorbid conditions. However, the effects of antidepressants on neurotransmitters cannot be ruled out as a factor in the 5-HIAA results.

Central nervous system monoaminergic activity in hip osteoarthritis patients with disabling pain: associations with pain severity and central sensitization.

Monoaminergic activity modulates nociceptive transmission in the central nervous system (CNS). Although pain is the most disabling symptom of osteoarthritis (OA), limited knowledge exists regarding the CNS mechanisms that amplify pain and drive sensitization processes in humans. The main objective of this study was to evaluate associations between cerebrospinal fluid (CSF) monoamine metabolites, pain severity, and central sensitization in patients with OA undergoing total hip arthroplasty (THA). Patients with OA (n = 52) and pain-free controls (n = 30) provided CSF samples for measurement of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), noradrenaline (3-methoxy-4-hydroxyphenylglycol [HMPG]), and dopamine (homovanillic acid [HVA]) monoamine metabolites. Patients with OA completed longitudinal evaluation of pain using clinical measures and quantitative sensory testing. Patients with OA had higher HMPG levels when compared with controls (P = 0.036). Within patients with OA undergoing THA, higher 5-HIAA and HVA levels were consistently associated with higher preoperative pain severity. Higher concentrations of 5-HIAA and HVA were also associated with lower conditioned pain modulation levels, whereas higher HMPG levels were linked to more efficient conditioned pain modulation. Patients with higher levels of CSF HVA exhibited increased pressure pain sensitivity (arm pressure pain detection threshold < 250 kPa vs ≥ 250 kPa, P = 0.042). Higher preoperative levels of CSF 5-HIAA predicted poorer pain control 6 months postoperatively (brief pain inventory pain severity; adjusted β = 0.010, 95% CI 0.001-0.019). In OA patients with disabling pain, higher CSF levels of serotonin and dopamine metabolites are associated with increased pain severity and central sensitization. Increased noradrenergic activity may be associated with more efficient pain inhibitory capacity.

Cerebrospinal Fluid Levels of 5-Hydroxyindoleacetic Acid in Parkinson’s Disease and Atypical Parkinsonian Syndromes

Background: Various cerebrospinal fluid (CSF) biomarkers are studied in Parkinson’s disease (PD) and atypical parkinsonian syndromes (APS). Several studies found reduced 5-hydroxyindoleacetic acid (5-HIAA), the main serotonin metabolite, in PD. There is little evidence regarding its levels in APS. Methods: We measured 5-HIAA in the CSF of 90 PD patients, 16 MSA patients, 26 progressive supranuclear palsy (PSP) patients, 11 corticobasal syndrome (CBS) patients, and 31 controls. We also compared the values in depressed and nondepressed patients. Results: There was a statistically significant difference in CSF 5-HIAA in PD and MSA compared to the control group (median in PD 15.8 μg/L, in MSA 13.6 μg/L vs. 24.3 μg/L in controls; p = 0.0008 in PD, p = 0.006 in MSA). There was no statistically significant difference in CSF 5-HIAA in PSP and CBS compared to the control group (median in PSP 22.7 μg/L, in CBS 18.7 μg/L vs. 24.3 μg/L in controls; p = 1 in both PSP and CBS). CSF 5-HIAA levels were lower in PD patients with depression compared to PD patients without depression (median 8.34 vs. 18.48, p < 0.0001). Conclusions: CSF 5-HIAA is decreased in PD and MSA. The CSF 5-HIAA levels in PSP and CBS did not differ from those of the control group. There was a tendency toward lower CSF 5-HIAA in MSA than in PD; however, the results did not reach statistical significance. These results may be explained by more severe damage of the serotonergic system in synucleinopathies (PD and MSA) than in tauopathies (PSP and CBS).

Correlation Between Salivary, Platelet and Central Serotonin Levels in Children.

Serotonin (5-HT) is a neurotransmitter synthesized in both the central nervous system (CNS) and in enterochromaffin cells of the gut. 5-HT biosynthesis is separate between the periphery and the CNS. Any observed correlations between centrally and peripherally measured 5-HT remain to be elucidated. Previous efforts have looked for a noninvasive marker of central serotonin, including serotonin in whole blood, plasma, platelets, saliva, and urine; however, results are conflicting. Finding a noninvasive marker for central serotonin turnover that can be used for diagnosis and therapeutic monitoring in patients with primary neurotransmitter deficiencies. Inclusion criterion was all children presenting with neurological symptoms whose clinical investigations included lumbar puncture (LP) for cerebrospinal fluid (CSF) collection and neurotransmitter metabolite analysis, were recruited. For central serotonin turnover, the serotonin metabolite 5-hydroxyindoleacetic acid (5HIAA) was used. Bivariate correlation between the serotonin levels in CSF (5HIAA), platelets, and saliva was calculated. Twenty-six patients (aged 6 months to 15 years) with various neurologic presentations had LP for CSF collection and neurotransmitter metabolite analysis as part of their clinical care. An additional salivary and blood sample was obtained at the same time. Eighteen patients had suitable samples for quantitative measure of serotonin. There was no correlation between platelet serotonin and CSF 5HIAA levels (Pearson's coefficient of correlation - PCC: 0.010) or between salivary serotonin and CSF 5HIAA (PCC: 0.258). There was a strong negative correlation between salivary and platelet serotonin (PCC: -0.679). Our findings suggest that salivary serotonin measurement is not a suitable noninvasive marker for measuring central serotonin turnover.

Sampling issues of cerebrospinal fluid and plasma monoamines: Investigation of the circadian rhythm and rostrocaudal concentration gradient

Biomarkers for neurodegenerative dementias offer interesting prospects regarding diagnosis and disease monitoring. Monoamines such as dopamine, (nor)adrenaline, serotonin (5-hydroxytryptamine or 5-HT), and their respective metabolites homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA), were shown to be altered in dementia, including Alzheimer's disease (AD). Biomarker research is hampered by potential confounds including the influence of time of day and volume of cerebrospinal fluid (CSF) collected. Therefore, the possibility of a circadian rhythm in CSF and plasma, and the presence of a rostrocaudal concentration gradient (RCG) in CSF for aforementioned monoamines/metabolites, were investigated.Circadian rhythmicity was assessed using reversed-phase ultra-high performance liquid chromatography with electrochemical detection (RP-UHPLC-ECD) to measure monoamine/metabolite concentrations in 271 paired CSF and plasma samples, successively collected over a period of 30 h and derived from eight healthy subjects. Plasma samples were also analyzed for melatonin, serving as positive control analyte, using ELISA. The RCG examination entailed RP-UHPLC-ECD analyses on five consecutive CSF samples derived from 10 patients with AD and 10 non-AD/control subjects.Besides a diurnal rhythm for melatonin, we found a similar rhythmicity for plasma HVA, with acrophases occurring between 02:00 and 06:00 h, in four out of seven subjects. Three and two subjects showed a circadian rhythm for CSF HVA and 5-HIAA, respectively. No rhythmicity was observed in any other compound. We found that only CSF MHPG, HVA and 5-HIAA levels differed across CSF fractions, and that these changes in 5-HIAA levels varied in the AD versus non-AD/control group. Positive correlations between CSF volume and HVA and 5-HIAA levels, indicative of a RCG, were also observed. Such a RCG could not be detected for the other monoamines/metabolites. Our results stress the importance of standardizing sampling procedures of biological fluids with respect to time of day, volume and number of samples.

Cerebrospinal fluid biogenic amines depletion and brain atrophy in adult patients with phenylketonuria.

Biogenic amines synthesis in phenylketonuria (PKU) patients with high phenylalanine (Phe) concentration is thought to be impaired due to inhibition of tyrosine and tryptophan hydroxylases and competition with amino acids at the blood-brain barrier. Dopamine and serotonin deficits might explain brain damage and progressive neuropsychiatric impairment in adult PKU patients. Ten early treated adult PKU patients (mean age 38.2 years) and 15 age-matched controls entered the study. Plasma and cerebrospinal fluid (CSF) Phe, 5-hydroxyindoleacetic acid (5-HIAA), 5-hydroxytryptophan (5-HTP), 3,4-dihydroxy-l-phenylalanine (l-DOPA) and homovanillic acid (HVA) were analyzed. Voxel-based morphometry statistical nonparametric mapping was used to test the age-corrected correlation between gray matter atrophy and CSF biogenic amines levels. 5-HIAA and 5-HTP were significantly reduced in PKU patients compared to controls. Significant negative correlations were found between CSF 5-HIAA, HVA, and 5-HTP and Phe levels. A decrease in 5-HIAA and 5-HTP concentrations correlated with precuneus and frontal atrophy, respectively. Lower HVA levels correlated with occipital atrophy. Biogenic amines deficits correlate with specific brain atrophy patterns in adult PKU patients, in line with serotonin and dopamine projections. These findings may support a more rigorous Phe control in adult PKU to prevent neurotransmitter depletion and accelerated brain damage due to aging.

Cerebrospinal fluid monoamine metabolite concentrations in depressive disorder: A meta-analysis of historic evidence

Altered monoaminergic functions have been implicated in the pathophysiology of depressive disorder. However, previously reported cerebrospinal fluid (CSF) monoamine metabolite concentrations in major depression have been inconsistent. We performed a meta-analysis of historic evidence to determine whether CSF monoamine metabolite levels were different between patients with depression and normal controls, and could be used as depression biomarkers. Relevant studies that investigated CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in patients with depression and normal controls were identified in PubMed, Web of Science, PsycINFO, and Embase databases through September 5, 2017, using a synonymous search for depression, CSF, normal, control, and each monoamine metabolite name, and in the reference lists of the acquired articles. Obtained records were individually scrutinized for eligibility. Our search strategy identified 26 studies, including our own. We employed random effects modeling and adopted “Hedges's g” as an index of effect size. In the meta-analyses, no significant difference was observed in CSF 5-HIAA or MHPG levels between patients with depressive disorder and controls. In contrast, CSF HVA was significantly decreased in patients with depression (Hedges's g = −0.30, P = 0.0000025), and these results remained significant after patients with bipolar disorder were excluded (Hedges's g = −0.37, P = 0.000061). In the meta-regression, sex was significantly associated with the Hedges's g of CSF HVA (Q = 4.41, P = 0.036). This meta-analysis revealed that only CSF HVA, and not 5-HIAA or MHPG, levels were decreased in depressive disorder. The reduction in the CSF HVA concentration in patients with depression may guide future studies on depression and serve as a useful biomarker of depressive disorder.

Comparison of the levels of the serotonin metabolite, 5-hydroxyindole acetic acid, in cerebrospinal fluid from patients with and without premature ejaculation

IntroductionPremature ejaculation (PE) is a significant problem as it can cause a loss of sexual self-confidence and a significant deterioration in quality of life. The frequency of PE varies between 9% and 27%. In the current study, we aimed to compare the levels of the serotonin metabolite 5HIAA (5 hydroxyindole acetic acid) in the cerebrospinal fluid (CSF) of patients with and without PE according to IELT (intravaginal ejaculation latency time) in order to investigate the relationship of PE with CSF 5HIAA levels. Materials and methodsA total of 60 male patients were included in the study who were planning to undergo surgery under spinal anesthesia, 30 in the patient (PE) group (all of the included patients had an IELT of <1min) and 30 in the control group (patients had an IELT of >1min). Levels of CSF 5HIAA were measured. ResultsThere was a significant negative correlation between IELT and the 5HIAA variables in all patients (r=−0.322, p=0.012). Although the average 5HIAA levels (nmol/L) were higher in the patient group (86.80±28.33) than in the control group (76.44±35.91), this difference was not significant (p=0.22). DiscussionResults of the current study bring new and different perspectives to the explanation of PE pathophysiology. There is a need for more specific and genetic studies to determine the best treatment for this common disorder.

Influence of a HTR2B Stop Codon on Glucagon Homeostasis and Glucose Excursion in Non-Diabetic Men.

Limited data are available about the role of the serotonin 2B (5-HT2B) receptor in the function of human islets. This study aimed to test whether the 5-HT2B receptor contributes to glucose, insulin, and glucagon homeostasis in humans, utilizing a hereditary loss-of-function gene mutation in the receptor, which causes a 50% reduction in the production of the receptor protein in heterozygotes. This clinical study enrolled participants recruited by newspaper advertisements and from mental status examinations. A cohort of participants from a young Finnish founder population composed of 68 non-diabetic males with a mean age of 30 was divided into groups for comparison based on being a 5-HT2B receptor loss-of-function gene mutation (HTR2B Q20*) heterozygote carrier (n=11) or not (n=57). Serum levels of glucose, insulin, and glucagon were measured in a 5 h oral glucose tolerance test using a 75 g glucose challenge. Insulin resistance, insulin sensitivity, and beta cell activity were calculated using the homeostasis model assessment (HOMA2) and whole body insulin sensitivity index (WBISI), as well as the ratio of glucagon to insulin was noted. The areas under the curves (AUCs) were also determined. Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in cerebrospinal fluid (CSF). Covariate adjusted mean score comparisons were applied. Lower glucagon secretion and decreased glucose excursion were observed among HTR2B Q20* carriers as compared with individuals who were homozygotes for the wild-type Q20 allele (controls). No differences in insulin secretion, beta cell activity, insulin resistance, or insulin sensitivity were observed. The glucagon to insulin ratio differed between the HTR2B Q20* carriers and controls. CSF levels of 5-HIAA were similar between groups. Our findings indicate that the 5-HT2B receptor may contribute to the regulation of human glucagon and glucose homeostasis and the interplay between glucagon and insulin secretion.

What Is the Nature of Serotonergic Abnormalities in Human Aggression?

T he archival report by Rylands et al. (1) in this issue of Biological Psychiatry represents exciting new work in the biology of human aggression. Although a role for central serotonin (5-HT) in human aggression has been studied for more than 30 years, the very specific aspects of how the 5-HT system may be altered in aggressive individuals are only now being examined because of newer technologies and the willingness to look beyond basic biologic principles. Rylands et al. (1) performed ligand-binding positron emission tomography studies, targeting the 5-HT transporter (SERT) and the 5-HT-2a receptor, in 14 subjects characterized as being impulsive aggressive and 13 subjects characterized as compared being not impulsive aggressive. In brief, the investigators reported that SERT availability is significantly increased in brain stem areas and reduced, although nonsignificantly, in cortical brain areas. More importantly, although the investigators reported a direct association between SERT availability and several measures of impulsivity and aggression in their subjects, they reported that the strongest association was with measures of adversity and stressful life events in childhood. They suggest, furthermore, that this latter finding points to an exciting, potential, etiologic link to altered 5-HT function and impulsive aggression in humans. In this commentary, I will discuss several aspects of this report in terms of methodology and in terms of how it relates to the field as it has developed since the late 1970s. The idea that brain 5-HT has any relationship with aggression was first proposed in the 1970s when demonstrated that altering brain levels of 5-HT uncovered an inverse relationship with aggression in animal models. In other words, when 5-HT was experimentally reduced, aggressive responding in the model animal increased, and when 5-HT was experimentally enhanced, aggressive responding decreased. The first evidence of this in human subjects was published in 1979 when Brown et al. (2) reported an inverse correlation between lifetime levels of actual aggressive behavior and lumbar cerebrospinal fluid (CSF) levels of the major 5-HT metabolite, 5-hydroxyindolacetic acid (CSF 5HIAA) in personality-disordered subjects. This was followed by the work of Linnoila et al. (3), who reported that reduced CSF 5HIAA levels in humans were linked to aggressive behavior that was specifically impulsive in nature. At the same time, Stanley et al. reported that victims of violent suicide, compared with those who also died violently but by accident, had lower numbers of SERT (4), and higher numbers of 5-HT-2, receptors in frontal cortex (5). Together this suggested that presynaptic 5HT activity was low and that postsynaptic receptors had

Cerebrospinal fluid 5-hydroxyindolacetic acid correlates directly with negative affective intensity, but not affective lability, in human subjects

Centrally acting monoamines have long been thought to be associated with component traits of behavior and emotion and are potential biological mediators of psychopathology. In this study we tested the hypothesis that centrally acting monoamines would be associated with measures of affective instability (i.e. affective intensity and affective lability) in healthy and personality disordered human subjects. In total, 57 adult subjects including 19 psychiatrically healthy volunteers and 38 personality disordered individuals were assessed for affective instability with the affective intensity measure (AIM) and the Affective Lability Scale (ALS). Samples of cerebrospinal fluid (CSF) were collected for assay of 5-hydroxyindoleacitic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxy-phenylglycol (MHPG). CSF 5-HIAA concentration correlated directly with overall AIM score and, specifically, with the AIM Negative Intensity score, in all subjects and in personality disordered subjects. This result was not affected but the addition of aggression scores or life history of mood disorder to the model. Neither CSF HVA nor MHPG were found to uniquely correlate with either AIM or ALS measure. Higher Affective Intensity scores, Negative Intensity scores, specifically, are directly correlated with higher basal levels of CSF 5-HIAA. This relationship was independent of aggression, life history of mood disorder and general personality traits.

Effects of early life stress on drinking and serotonin system activity in rhesus macaques: 5-hydroxyindoleacetic acid in cerebrospinal fluid predicts brain tissue levels

Early childhood stress is a risk factor for the development of substance-abuse disorders. A nonhuman primate model of early life stress, social impoverishment through nursery-rearing rather than mother-rearing, has been shown to produce increased impulsive and anxiety-like behaviors, cognitive and motor deficits, and increased alcohol consumption. These behavioral changes have been linked to changes in cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5-HIAA), a serotonin (5-HT) metabolite. The effects of different rearing conditions on ethanol drinking and three measures of 5-HT function in the central nervous system were evaluated, including CSF 5-HIAA levels and tissue levels of 5-HT and 5-HIAA in brain samples. Brain samples were taken from the dorsal caudate, putamen, substantia nigra (SN) pars reticulata, SN pars compacta and hippocampus. There was a clear effect of rearing condition on the 5-HT system. Overall 5-HIAA and 5-HIAA/5-HT ratio measures of 5-HT turnover were significantly lower in nursery reared compared to mother-reared animals. In addition, there was a strong within-subject correlation between CSF and brain tissue 5-HIAA levels. Ethanol drinking was greater in nursery reared monkeys, consistent with previous results. These findings show that CSF 5-HIAA measurements can be used to predict brain 5-HT activity that may be involved in behavioral outcomes such as anxiety and alcohol consumption. Thus, CSF sampling may provide a minimally invasive test for neurochemical risk factors related to alcohol abuse.

Masruha et al. reply

SIR–We read with great interest and appreciation the comments made by Duman and Durmaz regarding our article. In their letter, they suggested that our patients’ symptoms may have been caused by a secondary effect of hypermelatoninemia, as they have previously described in a published case report. In their study, a female patient exhibited symptoms of spontaneous periodic hypothermia and hyperhidrosis. She displayed extremely high levels of melatonin in her serum and 6-hydroxymelatonin sulphate in urine samples obtained during her attacks. However, subsequent 24-hour urine studies revealed the presence of 5-hydroxyindoleacetic acid (5-HIAA) at 1.9 mg (normal), vanillylmandelic acid at 1.2 mg (normal), and homovanillic acid (HVA) at 2.2 mg (normal). These data are not in agreement with our findings, as both of our patient cases consistently demonstrated decreased levels of 5-HIAA and HVA in the cerebrospinal fluid. However, this inconsistency may be explained by a difference in the sensitivity of measurements obtained from urinary samples compared with measurements obtained from cerebrospinal fluid samples. We agree that increased levels of melatonin in blood and 6hydroxymelatonin sulphate in urine could be responsible for this disorder, and that hypermelatoninemia may explain our findings of low cerebrospinal fluid levels of 5-HIAA and HVA. We think that future studies examining melatonin levels as well as the determination of cerebrospinal fluid metabolites in the serum of patients who exhibit spontaneous hypothermia and hyperhidrosis will be very important, because only the reproduction of these findings will enable the determination of hypermelatoninemia as a cause of the disorder.

Spontaneous periodic hypothermia and hyperhidrosis: its relation with spontaneous endogenous hypermelatoninemia

SIR–Recently, Rodrigues Masruha et al. reported two children diagnosed as having spontaneous periodic hypothermia and hyperhidrosis. They showed low levels of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) levels in their patients’ cerebrospinal fluid. They concluded that this is possibly a novel neurotransmitter disorder. In their clinical letter they also referred to our patient who, in 2008, was reported as having Shapiro syndrome. However, in December 2010 we republished the case with a diagnosis of hypermelatoninemia. We reported a female having spontaneous periodic hypothermia and hyperhidrosis. She had extremely high levels of melatonin in her serum and 6-hydroxymelatonin sulfate in her urine samples during her attacks. Phototherapy and then propranolol (non-selective B1 and B2 receptor blockers) completely resolved her complaints. At a later date, we also started to treat two other patients having similar symptoms with high serum melatonin levels in our clinic. Their symptoms have been resolved under the propranalol treatment during a 2-month follow-up period (unpublished data). Rodrigues Masruha et al. also reported two females with similar problems. Their HVA and 5-HIAA levels in cerebrospinal fluid were below the normal ranges. In particular, their 5-HIAA levels were seven to eight folds below the normal level. However, our patient’s subsequent 24 hour urine studies revealed 5-HIAA at 1.9mg (normal), vanillylmandelic acid at 1.2mg (normal), and HVA at 2.2mg (normal). These data are not compatible with the Rodrigues Masruha et al. findings. However, it was not possible to examine the cerebrospinal fluid 5HIAA and HVA level in our patient. 5-HIAA is a major metabolite of serotonin, and HVA is a major metabolite of dopamine. Some experimental studies reported the attenuation of 5-HIAA and dopamine level in the brain with melatonin administration. Yoshioka et al. studied the effect of melatonin administration on the release of 5-hydroxytryptamine, 5-HIAA, DOPAC (3, 4-dihydroxyphenylacetic acid), and HVA in the suprachiasmatic nuclei of rats and reported that the release of the 5-HT metabolite and 5-HIAA was significantly reduced by this treatment. In conclusion, there are many gray areas regarding the pathophysiology of spontaneous periodic hypothermia and hyperhidrosis. However, we believe hypermelatoninemia, which may be associated with an irregular control of pinealocytes by the suprachiasmatic nucleus or related pathways, is one of the markers of this disease. We suggest the examination of the serum level of melatonin in patients with complaints of spontaneous hypothermia and hyperhydrosis.

Cholesterol and CSF 5-HIAA in attempted suicide

BackgroundLow serum cholesterol has been linked to suicide and violent behaviour. The same kind of associations has been reported regarding low levels of 5-hydroxyindolacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and suicidal behaviour. The hypothesis of the link between serum cholesterol and suicide incorporate serotonin. It proposes that low cholesterol is related to altered serotonergic neurotransmission. A correlation between CSF 5-HIAA and serum cholesterol has been shown in animal studies, but has not been found in humans. AimTo study the interrelationship between serum cholesterol and CSF 5-HIAA in suicide attempters. Since both cholesterol and CSF 5-HIAA are associated with suicide and violent suicide attempts, we also investigated the correlation with suicide, violent suicide attempt method, suicide intent, hopelessness and depression severity. MethodsSerum total cholesterol and CSF 5-HIAA were measured in 42 medication free suicide attempters. Patients were assessed with Becks's Hopelessness scale (BHS), Suicide Intent Scale (SIS) and Montgomery–Åsberg depression rating scale (MADRS) and followed-up for causes of death. ResultsSerum total cholesterol and CSF 5-HIAA showed a significant positive correlation adjusted for age, body mass index and substance abuse diagnosis. Cholesterol and CSF 5-HIAA levels did not differ between violent and non-violent suicide attempters or between suicide completers and survivors. ConclusionsThese findings indicate that the serotonergic system may be connected to serum cholesterol in patients with a recent suicide attempt.

P03-294 - Cholesterol and CSF 5-HIAA in attempted suicide

IntroductionLow serum cholesterol has been linked to suicide and violent behaviour. The same kind of associations has been reported regarding low levels of 5-hydroxyindolacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and suicidal behaviour. The hypothesis of the link between serum cholesterol and suicide incorporate serotonin. It proposes that low cholesterol is related to reduced serotonergic neurotransmission, which in turn, is linked to violent and suicidal behaviour. A correlation between CSF 5-HIAA and serum cholesterol has been shown in animal-studies, but has not been found in humans.AimsTo study the interrelationship between serum cholesterol and CSF 5-HIAA in suicide attempters. Since both cholesterol and CSF 5-HIAA are associated with suicide and violent suicide-attempts, we also investigated the correlation with suicide, violent suicide attempt method, suicide intent, hopelessness and depression severity.MethodsSerum total cholesterol and CSF 5-HIAA was measured in 42 medication free suicide attempters. Patients were assessed with Becks‘s Hopelessness scale (BHS), Suicide Intent Scale (SIS) and Montgomery-Åsberg depression rating scale (MADRS) and followed-up for causes of death.ResultsSerum total cholesterol and CSF 5-HIAA showed a significant positive correlation adjusted for age, body mass index and substance abuse diagnosis. Cholesterol and CSF 5-HIAA levels did not differ between violent and non-violent suicide attempters or between suicide completers and survivors.ConclusionsThese findings indicate that the serotonergic system may be connected to serum cholesterol in patients with a recent suicide attempt.

CSF 5-HIAA, attempted suicide and suicide risk in schizophrenia spectrum psychosis

Introduction There is evidence for a relationship between low levels of 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) and suicidal behavior in mood disorder. A relationship between CSF homovanillic acid (HVA) and suicidal behavior has not been completely established. Studies done in patients with schizophrenia spectrum psychosis suffer from small numbers, short periods of follow-up and the results are contradictory. The objective of this study was to investigate the relationship between levels of CSF 5-HIAA, CSF HVA and suicidal behavior in patients with schizophrenia spectrum psychosis. Method Three hundred eighty five patients with schizophrenia spectrum psychosis admitted to the Karolinska University Hospital between 1973 and 1987 were lumbar punctured in standardized manner. Patients were followed until 2006 for a median of 26 years. Information about prior suicide attempt was retrieved from medical records and causes of death were obtained from the Causes of Death Register at the National Board of Health and Welfare. Results At the end of the follow-up 26 patients (6.8%) had died by suicide. Male gender (OR = 3.5) and attempted suicide (OR = 12.4) were risk factor for suicide when combined. There were no significant correlations between levels of CSF 5-HIAA, CSF HVA, HVA/5-HIAA ratio and attempted, violent or non-violent suicide. Conclusion Male schizophrenia spectrum psychosis patients with prior suicide attempt are at high risk for suicide. No correlation between CSF monoamine metabolites levels and suicidal behavior was found. Suicidal behavior in schizophrenia spectrum psychosis may not, in contrast to mood disorders, be predicted by levels of CSF 5-HIAA and HVA.

Homovanillic acid and 5-hydroxyindoleacetic acid levels in cerebrospinal fluid of patients with senile dementia of Alzheimer type.

The possibility of disturbed dopamine and serotonin metabolism in senile dementia of Alzheimer type was studied. The basal concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) were studied in 28 patients with senile dementia of Alzheimer type and in 13 controls of similar age with no neurological disease. The concentrations of HVA were significantly reduced in the dementia patients compared to the concentrations of the controls. The values of HVA were also significantly reduced in the most severely demented patients compared to the less severely demented ones. There was a slight but statistically significant decrease in the 5-HIAA levels in the dementia patients compared to the levels of the controls. The 5-HIAA levels were reduced in the most severely demented patients compared to the controls but not when compared with the less severely demented patients. It is concluded that in severe forms of senile dementia of Alzheimer type, there is a decrease in the levels of HVA and 5-HIAA in CSF which may reflect a decreased turnover of dopamine and serotonin. Patients diagnosed as senile dementia of Alzheimer type, but with less severe symptoms, had levels of HVA and 5-HIAA similar to controls.

Cerebrospinal fluid monoamine metabolites and suicide

Prospective studies of the serotonergic system and suicide report that low 5-hydroxyindolacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and a history of attempted suicide predict suicide risk. Low CSF homovanillic acid (HVA) is reported to be associated with past and future lethality of suicide attempts but not with suicide. The interrelationships between monoamine metabolites, violent method, suicide intent and lethality of suicidal behaviour are complex. We hypothesized that CSF 5-HIAA and HVA levels are related to suicide intent, violence and lethality of suicidal behaviour. Fifteen male suicide attempters admitted to a psychiatric ward at the Karolinska University Hospital and eight healthy male volunteers were submitted to lumbar puncture and CSF 5-HIAA and HVA were assayed. Suicide intent with the Beck Suicide Intent Scale (SIS), lethality and violence of suicidal behaviour were assessed. All patients were followed up for causes of death. Six suicides and one fatal accident were identified with death certificates. Mean CSF 5-HIAA but not CSF HVA differed between suicides and survivors. Violent suicides had higher suicide intent and CSF 5-HIAA than non-violent suicides. In violent suicides, CSF 5-HIAA levels were negatively correlated with SIS. Greater suicide intent may be associated with greater aggressive intent and predicts a violent suicide method.

P03-109 The malignant neuroleptic syndrome: Etiopathogenesis, diagnosis and clinics

MNS is a rare, acute or chronic idiosyncratic reaction to a neuroleptic medication. the syndrome is characterised by fever, muscular rigidity, altered mental status and autonomic dysfunction. MNS is caused by neuroleptics, dopamine antagonistic medications, combination of MAO and antidepresants.The main groups of theories, explaining MNS are reviewed. There is a genetic predisposition and association between MNS and human DRD2 gene A1 and A2 alleles polymorphism. There were attempts to prove MNS and serotoninergic syndrome as different forms of malignant hypertermia. Dopaminergic activity inhibition increases quantity of calcium in the sarcoplasmic reticulum, therefore muscular contraction increases and it leads to clinical MNS signs. There are theories of neuromediators interaction (changes in HVA, adrenaline, MHPG, 5-HIAA levels in cerebrospinal fluid detected during MNS), increased sympathetic activity, malignant hyperthermia, and direct toxic effect of neuroleptic medications to sceletal muscules in vitro.The main risk factors and clinical signs of MNS are summarised. MNS develops suddenly during few hours from the start of treatment with neuroleptics, in rare cases - during first 4 weeks. Usually MNS starts during first 24-72 hours. Classic MNS signs are muscular rigidity (“lead pipe”), hypertermia, elevation of CPK.MNS diagnosis is determined based on anamnesis, clinical signs, laboratorical findings and differentiation which is based by excluding other pathological conditions.