Cerebrospinal Fluid Monoamine Research Articles

Season of Birth Variations in the Temperament and Character Inventory of Personality in a General Population

Background: Since several studies show season of birth variations in morbidity, suicidal behavior and CSF (cerebrospinal fluid) monoamine metabolites, we investigated season of birth variations in personality in the population. Methods: We analyzed by multiple logistic regressions the Temperament and Character Inventory (TCI) for 2,130 individuals taking part in the Betula prospective random cohort study of Umeå, Sweden. Results: The personality dimensions were correlated significantly with age and gender. We stratified the data according to age, gender and the season of TCI measurement. By the median split in each stratum, a high-value group and a low-value group were obtained for each of the personality dimensions. Those born during February to April were significantly more likely than those born during October to January to have high NS (novelty seeking) among women, particularly the subscale NS2 (impulsiveness vs. reflection), and to have high PS (persistence) among men. Temperament profiles also showed season of birth variations. Conclusions: We discuss the associations in the literature between personality and the monoamines serotonin and dopamine, and suggest that our results are compatible with a hypothesis of season of birth variation in the monoamine turnover. The personality traits are likely to be influenced by several genetic and environmental factors, one of them being the season of birth.

‘Cerebrospinal fluid neuropeptide Y in Prader‐Willi syndrome’

Developmental Medicine & Child NeurologyVolume 43, Issue 4 p. 286-287 Free Access ‘Cerebrospinal fluid neuropeptide Y in Prader-Willi syndrome’ Arne Åkefeldt MD PhD, Corresponding Author Arne Åkefeldt MD PhD Department of Psychiatry and Neurochemistry, Institute of Clinical Neuroscience, Göteborg University, Sahlgren University Hospital/Mölndal, SE-43180 Mölndal, SwedenCorresponding author Child and Adolescent Psychiatry Skaraborg Hospital Drottninggatan 3 A SE-542 34 Mariestad SwedenSearch for more papers by this authorRolf Ekman MD PhD, Rolf Ekman MD PhD Department of Psychiatry and Neurochemistry, Institute of Clinical Neuroscience, Göteborg University, Sahlgren University Hospital/Mölndal, SE-43180 Mölndal, SwedenSearch for more papers by this authorJan-Eric Månsson PhD, Jan-Eric Månsson PhD Department of Psychiatry and Neurochemistry, Institute of Clinical Neuroscience, Göteborg University, Sahlgren University Hospital/Mölndal, SE-43180 Mölndal, SwedenSearch for more papers by this author Arne Åkefeldt MD PhD, Corresponding Author Arne Åkefeldt MD PhD Department of Psychiatry and Neurochemistry, Institute of Clinical Neuroscience, Göteborg University, Sahlgren University Hospital/Mölndal, SE-43180 Mölndal, SwedenCorresponding author Child and Adolescent Psychiatry Skaraborg Hospital Drottninggatan 3 A SE-542 34 Mariestad SwedenSearch for more papers by this authorRolf Ekman MD PhD, Rolf Ekman MD PhD Department of Psychiatry and Neurochemistry, Institute of Clinical Neuroscience, Göteborg University, Sahlgren University Hospital/Mölndal, SE-43180 Mölndal, SwedenSearch for more papers by this authorJan-Eric Månsson PhD, Jan-Eric Månsson PhD Department of Psychiatry and Neurochemistry, Institute of Clinical Neuroscience, Göteborg University, Sahlgren University Hospital/Mölndal, SE-43180 Mölndal, SwedenSearch for more papers by this author First published: 02 March 2007 https://doi.org/10.1111/j.1469-8749.2001.tb00205.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1 Holm VA, Cassidy SB, Butler MG, Hanchett JM, Greenswag LR, Whitman BY, Greenberg R. (1993) Prader-Willi syndrome: consensus diagnostic criteria. Pediatrics 91: 398– 402. 2 Åkefeldt A, Ekman R, Gillberg C, Månsson J-E. (1998) Cerebrospinal fluidmonoamines in Prader-Willi syndrome. Biological Psychiatry 44: 1321– 8. 3 Åkefeldt A, Månsson J-E. (1998) Is monoamine oxidase activity elevated in Prader-Willi syndrome European Child & Adolescent Psychiatry 7: 163– 5. 4 Åkefeldt A, Törnhage C-J, Gillberg C. (1999) A woman with Prader-Willi syndrome gives birth to a healthy baby girl. Developmental Medicine & Child Neurology 41: 789– 90. 5 Leibowitz SF. (1986) Brain monoamines and peptides: role in the control of eating behavior. Federation Proceedings 45: 1396– 1403. 6 Lehnert H, Wurtman RJ. (1993) Amino acid control of neurotransmitter synthesis and release: physiological and clinical implications. Psychotherapy and Psychosomatics 60: 18– 32. 7 Dryden S, McCarthy HD, Malabu UH, Ware M, Williams G. (1993) Increased neuropeptide Y concentrations in specific hypothalamic nuclei of the rat following treatment with methysergide: evidence that NPY may mediate serotonin's effects on food intake. Peptides 14: 791– 6. 8 Reis A, Dittrich B, Greger Y, Buiting K, Lalande M, Gillessen-Kaesbach G, Anvret M, Horsthemke B. (1992) Imprinting mutations suggested by abnormal DNA methylation pattern in familial Angelman and Prader-Willi syndromes. American Journal of Human Genetics 54: 741– 7. 9 Widerlöv E, Lindström LH, Wahlestedt C, Ekman R. (1988) Neuropeptide Y and peptide YY as possible cerebrospinal fluid markers for major depression and schizophrenia, respectively. Journal of Psychiatric Research 22: 69– 79. Citing Literature Volume43, Issue4April 2001Pages 286-287 ReferencesRelatedInformation

Tryptophan depletion selectively reduces CSF 5-HT metabolites in healthy young men: results from single lumbar puncture sampling technique

Plasma tryptophan (Trp) depletion is a commonly used tool for determining the role of brain serotonin (5-HT) function in a variety of psychiatric disorders. This study measured the cerebrospinal fluid (CSF) monoamine metabolite response to Trp depletion and control testing in five healthy subjects utilizing a single lumbar puncture. Testing was done in a placebo-controlled, double-blind, randomized, cross-over design. Plasma-free and total Trp levels and behavioural ratings were obtained prior to and 5 h after ingestion of each amino-acid drink. CSF was obtained by performing a standard lumbar puncture 7 h after ingestion of the drink. Compared to control testing, Trp depletion caused a significant decrease of CSF 5-hydroxyindoleacetic acid (5-HIAA) (p = 0.03), but not of homovanillic acid or 3-methoxy-4-hydroxy-phenylglycol. Behavioural ratings were minimally affected in all subjects. This confirms that plasma Trp depletion reduces central nervous system measures of 5-HT function and suggests that the single lumbar puncture technique may be sufficient to detect the extent of CSF 5-HIAA changes during Trp depletion studies.

Changes of cerebrospinal fluid monoamine metabolites during long-term antidepressant treatment

This study describes the changes in cerebrospinal fluid (CSF) monoamine metabolites during antidepressant treatment for more than 6 months. Eight patients, who received antidepressant treatment after attempted suicide and then underwent lumbar punctures every 3 or 4 months, were included. Plasma drug concentrations and the clinical outcome were also measured. Consistent with previous reports about antidepressant treatment for between 3 and 6 weeks, both 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA) were significantly decreased after treatment for a mean of 15 weeks compared to pretreatment. However, after continued treatment for a mean of 30 weeks the MHPG concentration remained significantly lower than at pretreatment while 5-HIAA had returned to the pretreatment level. The clinical outcome was significantly correlated to the pretreatment 5-HIAA/MHPG ratio. These results suggest that the frequently reported reduction in CSF 5-HIAA after antidepressant treatment does not remain during long-term treatment.

Serotonin and aggression in children.

Research consistently indicates that in animals and adults, reduced central serotonergic (5-HT) function is associated with increased aggression. This relationship has been elucidated via cerebrospinal fluid monoamine metabolite levels, hormonal responses to pharmacologic challenge using serotonergic probes, platelet receptor binding studies, and, more recently, through molecular genetic approaches. In contrast, studies examining the relationship of 5-HT to aggression in children have been characterized by inconsistent findings. The literature examining the relationship between central 5-HT function and aggression is reviewed. Several hypotheses that might account for the discrepancies in the child literature are examined.

The effect of lumbar puncture stress on dopamine and serotonin metabolites in human cerebrospinal fluid

In order to examine concentrations of cerebrospinal fluid (CSF) neurochemicals, the technique of lumbar puncture is typically used. However, the effect of the intrinsic stress of undergoing a lumbar puncture on CSF monoamine concentrations in humans has not yet been established. We used lumbar puncture followed 3 h later by continuous CSF sampling to examine the effect of lumbar puncture on levels of the dopamine and serotonin metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), respectively. Additionally, we examined the effect of lumbar puncture on the CSF HVA to 5-HIAA ratio. Immediately post lumbar puncture, CSF concentrations of HVA and 5-HIAA were, respectively, only 51 and 54% of the mean levels detected hours later. However, the HVA to 5-HIAA ratio remained stable during lumbar puncture. While HVA and 5-HIAA levels in CSF obtained via lumbar puncture reflect highly variable responses to the stress of the procedure, the ratio of these metabolites is unaffected.

Changes in the cerebrospinal-fluid monoamines in rats with an immunoneutralization of the subcommissural organ-Reissner's fiber complex by maternal delivery of antibodies.

The subcommissural organ (SCO) is a brain gland secreting glycoproteins into the cerebrospinal fluid (CSF), where they aggregate forming the Reissner's fiber (RF). By the continuous addition of newly released glycoproteins, RF grows along the cerebral aqueduct, fourth ventricle, and central canal of the spinal cord. At the filum, RF-glycoproteins escape from the central canal and reach the local blood vessels. Despite a century of research, the function of the SCO remains elusive. The aim of the present investigation was to test the hypothesis that RF-glycoproteins, by binding and transporting monoamines out of the CSF, participate in the clearance of these compounds. A protocol was designed that led to the permanent immunoneutralization of the SCO through the maternal delivery of antibodies. This was achieved by transplacental transfer to the fetuses, and through the milk to the pups, of specific antibodies against SCO secretory proteins. The antibodies reached the CSF of the fetuses and pups and blocked the RF formation during the first months of life. Some of these animals died during the first postnatal weeks; those who survived displayed a rise in the CSF concentration of several monoamines, l-DOPA being the one with the highest rise. Adult rats transiently deprived of RF by a single injection of anti-RF antibodies into the CSF showed a transient rise in the CSF concentration of l-DOPA. All these results support the hypotheses that the SCO-RF complex participates in the clearance of monoamines from the CSF.

Cerebrospinal Fluid Monoaminergic Metabolites Differ in Wild Anubis and Hybrid (Anubis hamadryas) Baboons: Possible Relationships to Life History and Behavior

This article reports monoaminergic metabolite [homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG)], values from the cerebrospinal fluid (CSF) of 27 wild baboons (Papio hamadryas) aged 40 to 140 months. Animals were either anubis, or anubis with hamadryas admixture; males of the latter subspecies generally have a reduced tendency to disperse from their natal groups. Overall, the values and interrelationships among the CSF monoamine metabolites resembled data reported from closely related, captive-housed animals. For example, age was significantly correlated with HVA concentrations (r = −60, p < .05), but not with the other metabolites. Notably, males characterized by hamadryas admixture had significantly higher concentrations of HVA, 5-HIAA, and MHPG (p < .05, respectively), a result possibly driven by differences in serotonergic activity. These data provide initial evidence that variation in central monoaminergic activity, as indicated by CSF monoamine metabolite concentrations, may reflect differences in behavior and life history that have taxonomic and, perhaps, evolutionary significance.

Variations in CSF Monoamine Metabolites According to the Season of Birth

The cerebrospinal fluid (CSF) concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) as well as their ratios and correlations were analyzed in relation to the season of birth. The sample consisted of 241 drug-free patients participating in psychobiological programs and comprising the DSM-III-R diagnoses of mood, anxiety and adjustment disorders. Significant season-of-birth variations were found even after adjusting for sex, age, height, the diagnostic category and the month of lumbar puncture. Those born during February to April had significantly lower values of 5-HIAA. Values of HVA and of the ratios HVA/5-HIAA and HVA/MHPG were significantly higher for those born during October to January. Correlation coefficients also showed season-of-birth variations. These results may provide an important link for the season-of-birth variations reported for several neuropsychiatric disorders.

Family psychiatric history, cerebrospinal fluid monoamine metabolites, and temperament in infants

Background: Variations in cerebrospinal fluid (CSF) levels of the monoamine metabolites 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol, and homovanillic acid have been associated with behavioral abnormalities in nonhuman primates, and with psychopathology in studies of children and adults. Methods: We assayed monoamine metabolites in “leftover” spinal fluid from 167 neurologically normal newborn infants (0–3 months of age), and later (at age 18–21 months of age) obtained their family psychiatric histories and assessed their temperament using the Colorado Childhood Temperament Inventory (CCTI). Results: Family history of antisocial personality disorder predicted significantly lower scores for soothability ( p = .003) at 18–21 months. There were no statistically significant associations between newborn monoamine metabolite levels and any aspect of temperament on the CCTI. Conclusions: These findings suggest complex relationships between genetic liability for psychiatric disorders and CSF monoamine metabolite levels; those relationships do not seem to be mediated by infant temperament. It appears likely that interindividual differences in monoamine metabolite levels change over the course of development in humans.

Changes in Cerebrospinal Fluid Monoamine Metabolites, Tryptophan, and γ-Aminobutyric Acid during the 1st Year of Life in Normal Infants

Cerebrospinal fluid (CSF) levels of 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid, homovanillic acid, tryptophan, and γ-aminobutyric acid were measured using high-performance liquid chromatography in 102 infants during the 1st year of life (preterm and term neonates included). CSF levels are expressed versus corrected age (postnatal days – preterm days) which reflects the stage of maturity of the central nervous system. These results are compared to those obtained in CSF of 53 victims of sudden infant death syndrome (SIDS). All components were significantly higher in SIDS than in the age-matched control group. This increase does not seem to be an artefact related to death. Indeed, under the same conditions concerning postmortem time interval before CSF sampling and analysis, the levels are not significantly higher in infants who died from a known pathology than in living infants. Moreover, in living infants as regards a pathology such as asphyxia or hypoventilation in comparison with SIDS, similar profiles are observed in some neurotransmitters or metabolites. Other studies are necessary to explore further neurotransmission systems in SIDS.

CSF 5-HIAA correlates with neuroticism in depressed patients

Background: To examine for relationships between neurotransmitters and personality. Method: 27 depressed patients had cerebrospinal fluid (CSF) monoamine metabolites measured and completed the Eysenck Personality Questionnaire (EPQ). Result: CSF concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) correlated significantly with EPQ neuroticism scores. Conclusion: Central serotonin may play a role in neuroticism, a personality dimension predisposing to depression. Limitation: The positive correlation may partly reflect collinear relationships between both variables and anxiety/depression.

Blood folate, vitamin B12, and their relationships with cerebrospinal fluid monoamine metabolites, depression, and personality in suicide attempters

High prevalences of folate deficiency have been reported in psychiatric patients, and low folate and vitamin B12 concentrations have been associated with depression and low levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF). A total of 107 suicide attempters, 41 with information on CSF monoamine metabolite levels, were studied for the purpose of exploring the blood folate and serum B12 levels and their relationships with the three major monoamine metabolites in the CSF, plasma cortisol before and after dexamethasone administration, the Beck Hopelessness Scale (BHS), the Montgomery-Asberg Depression Rating Scale (MADRS), suicidality as measured with the Suicide Assessment Scale (SAS), and the Marke-Nyman Temperament (MNT) dimensions. Diagnoses were made on the basis of the DSM-III-R. Few patients had low folate or B12 levels. No significant differences appeared between the diagnostic groups. B12 correlated positively and significantly with cortisol (rsp=0.23, P=0.04). The monoamine metabolites did not correlate significantly with folate or B12. After adjustments for age, neither folate nor B12 correlated significantly with the BHS, MADRS, SAS, or MNT scores or post-dexamethasone cortisol levels. In suicide attempters without folate or B12 deficiency, blood folate and serum B12 showed no relationship with depression or low CSF 5-HIAA concentrations. We could not replicate the high prevalences of folate or B12 deficiency previously reported for psychiatric patients. Possible reasons for the negative findings are discussed.

Cerebrospinal fluid monoamines in Prader–Willi syndrome

Background: The behavioral phenotype of Prader–Willi syndrome (PWS) suggests hypothalamic dysfunction and altered neurotransmitter regulation. The purpose of this study was to examine whether there was any difference in the concentrations of monoamine metabolites in the cerebrospinal fluid (CSF) in PWS and non-PWS comparison cases. Methods: The concentration of monoamine metabolites in CSF was determined in 13 children and adolescents with PWS diagnosed on clinical and genetic criteria. The concentrations were compared with those from 56 comparison cases in healthy and other contrast groups. Results: The concentrations of dopamine and particularly serotonin metabolites were increased in the PWS group. The differences were most prominent for 5-hydroxyindoleacetic acid. The increased concentrations were found in all PWS cases independently of age, body mass index, and level of mental retardation. Conclusions: The findings implicate dysfunction of the serotonergic system and possibly also of the dopamine system in PWS individuals, and might help inform future psychopharmacologic studies.

Natural killer cell activity and CSF monoamine metabolites in suicide attempters

The aim of this study was to investigate markers of serotonin and immune function in suicidal patients. Cytotoxic activity of natural killer cells (NK) and CD16 lymphocytes were studied in 28 suicide attempters and 26 healthy controls, and related in patients to 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF). Patients with CSF 5-HIAA below the median had significantly lower NK cell activity than other patients. CD16 cell frequency was significantly lower in patients than in controls, and patients also tended to have lower NK cell cytotoxicity than healthy controls. There were no statistically significant correlations between 4-hydroxy-3methoxyphenyl glycol (HMPG), homovanillic acid (HVA), CSF cortisol and NK cell activity. The results support the hypothesis of compromised immune function in suicidal patients with evidence of disordered serotonin function.

Cytokines and monoamines in pathogenesis of multiple sclerosis

The article presents the results of research of cytokines (- and -interferons and tumor necrosis factor-а) and monoamines (adrenalin, noradrenalin, dopamin, serotonin) in blood and cerebrospinal fluid in 151 patients with multiple sclerosis. The correlation between immune, biochemical changes and clinical activity and course of disease were revealed. The immunocorrection with -interferon is recommended.

Attempted suicide characteristics and cerebrospinal fluid amine metabolites in depressed inpatients

Serotonin abnormalities have been reported in the brain of suicide victims. Evidence of a serotonin deficiency in suicide attempters is less consistent. We hypothesized that a serotonin deficiency may be present in suicide attempters whose attempt behavior more closely approximates completed suicide. Sixty-seven (67) drug-free depressed inpatients (46 suicide attempters, 21 nonattempters) underwent research clinical assessments and a lumbar puncture. Cerebrospinal fluid (CSF) monoamine metabolites were assayed. Degree of medical damage and intent of the most recent suicide attempt were rated. CSF amine metabolites did not differentiate suicide attempters as a group from nonattempters. However, reduced serotonergic activity, as indicated by lower levels of CSF-5-hydroxyindoleacetic acid (5-HIAA) was associated with a history of planned suicide attempts and with suicide attempts that resulted in greater medical damage. Other monoamine metabolites did not correlate with seriousness of suicidal behavior, except for low CSF homovanillic acid and higher medical damage. No correlation was found with violent method. Planned and more medically damaging suicide attempts appear to be associated specifically with low serotonergic activity and, therefore, resemble completed suicide both behaviorally and biochemically. It remains to be determined whether low levels of CSF 5-HIAA can predict greater medical damage in future suicide attempts.

A Nonhuman Primate Model of Type II Alcoholism? Part 2. Diminished Social Competence and Excessive Aggression Correlates with Low Cerebrospinal Fluid 5‐Hydroxyindoleacetic Acid Concentrations

The purpose of this study was to develop an animal model for behavioral features of type II, early-onset alcohol abuse. To perform this research, cerebrospinal fluid (CSF) monoamine metabolite concentrations and home-cage social behaviors of 29 rhesus macaque subjects were examined in a 4-year longitudinal study. Half of the monkeys were reared for their first 6 months with their mothers, and the other half were reared without adults, instead with access only to monkeys of similar age. When the subjects were 6 months old, and again when they were 50 months old, they underwent a series of four, 4-day social separations. We obtained cisternal CSF before and during the first and last separation of each series to quantify 5-hydroxyindoleacetic acid (5-HIAA), 3-methoxy-4-hydroxyphenylgycol (MHPG), and homovanillic acid concentrations. After the 6-month separations, subjects were placed into social groups, and social dominance rankings were assessed. Before and after the 50-month separations, social dominance rankings were evaluated again, and home-cage aggression and social behavior data were collected. Over the 3 1/2 years between CSF samplings, records were maintained of subjects' removal from their social groups for excessive aggression or treatment for wounding. Our results showed that among infants, reduced CSF 5-HIAA was correlated with low social dominance. As young adults, subjects from both rearing groups with low CSF 5-HIAA and MHPG concentrations exhibited reduced rates of social interaction and low social dominance rankings. In addition, peer-reared subjects with low CSF 5-HIAA concentrations exhibited inept social behaviors, and were frequently removed from their social groups for excessive aggression and deviant social behaviors. From these results, we conclude that the peer-rearing paradigm aggravates the untoward social consequences associated with low CSF 5-HIAA concentrations over and beyond reducing CSF 5-HIAA concentrations, suggesting that early experiences may contribute to CNS serotonin changes that increase the disposition to type II-related behaviors.

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.

Early-Onset Alcoholics Have Lower Cerebrospinal Fluid 5-Hydroxyindoleacetic Acid Levels Than Late-Onset Alcoholics

We investigated the interrelationships of age at onset of excessive alcohol consumption, family history of alcoholism, psychiatric comorbidity, and cerebrospinal fluid monoamine metabolite concentrations in abstinent, treatment-seeking alcoholics. We studied 131 recently abstinent alcoholics. Supervised abstinence was maintained on a research ward at the National Institutes of Health Clinical Center for a minimum of 3 weeks. All alcoholics received a low-monoamine diet for a minimum of 3 days before lumbar puncture. Lumbar punctures were performed in the morning after an overnight fast. Monamine metabolites and tryptophan in cerebrospinal fluid were quantified with liquid chromatography by means of electrochemical detection. Psychiatric diagnoses were established from blind-rated Schedule for Affective Disorders and Schizophrenia-Lifetime version interviews administered by a research social worker. Severity and age at onset of excessive alcohol consumption were documented with a structured lifetime drinking history questionnaire and with selected alcoholism screening questionnaires (CAGE and Michigan Alcoholism Screening Test). Family history of alcoholism was obtained from the probands. A majority of the treatment-seeking, primarily white male alcoholics had a lifetime history of psychiatric disorders other than alcoholism. None fulfilled criteria for antisocial personality disorder. Early-onset alcoholics (onset of excessive consumption before 25 years of age) had a more severe course of alcoholism and lower mean cerebrospinal fluid 5-hydroxyindoleacetic acid concentration than late-onset alcoholics. Patients who reported both parents to be alcoholics had particularly low mean cerebrospinal fluid 5-hydroxyindoleacetic acid, homovanillic acid, and tryptophan concentrations. Among treatment-seeking alcoholics, early age at onset is generally associated with a more severe course of alcoholism and lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentration.