CSF cholecystokinin, gamma-aminobutyric acid and neuropeptide Y in pathological gamblers and healthy controls.

The sulphated cholecystokinin (CCK) octapeptide (CCK-8S), the CCK tetrapeptide (CCK-4), neuropeptide Y (NPY) and gamma-aminobutyric acid (GABA) were determined in cerebrospinal fluid (CSF) obtained from 11 pathological male gamblers and 11 healthy male controls. Compared with healthy controls, pathological male gamblers displayed higher concentrations of CCK-8S, CCK-4 and GABA (but not NPY). A gradient with decreasing concentrations from the first to the third 6-ml CSF fraction was found for CCK-8S, CCK-4 and NPY, but only in pathological gamblers. Disrupted gradients were found for GABA and for NPY in healthy controls. Given that CCK is a modulator of dopamine in the reward process, the increase in CCK-8S and CCK-4 is not unexpected. The high level of GABA in pathological gamblers is in conformity with a compensatory inhibitory action on noradrenergic neurons. The CSF gradient of CCK-8S and CCK-4 in pathological male gamblers (but not healthy controls) might indicate a difference in diurnal variation. The results obtained are in line with an altered CCK and GABA function in pathological gambling.

CSF testosterone: relationship to aggression, impulsivity, and venturesomeness in adult males with personality disorder.

OBJECTIVE: Studies of various species suggest that testosterone, assayed in various compartments, is correlated with aggression and possibly related behaviors. The objective of this study was to assess the relationship between cerebrospinal fluid testosterone (CSF TEST) and measures of aggression, impulsivity, and venturesomeness in male personality disordered subjects and test the hypothesis that CSF TEST would correlate directly with each measure in this group. METHODS: Lumbar CSF for morning basal levels of testosterone were obtained from 31 male subjects with personality disorder. Aggression was assessed dimensionally through the use of the life history of aggression (LHA) assessment, and categorically by the research diagnosis of intermittent explosive disorder. Impulsiveness and venturesomeness were assessed using the Eysenck personality questionnaire - II (EPQ-II). RESULTS: CSF TEST did not correlate with measures of aggression or impulsivity but did correlate directly with venturesomeness (r = .42, p = .021). Adjusting for age and height modestly reduced the magnitude and statistical significance of this correlation. CONCLUSIONS: In contrast to some published studies, CSF TEST was not found to have a significant relationship with aggression. The presence of a modest correlation between CSF TEST and venturesomeness, but not impulsivity, in male personality-disordered subjects suggests a possible relationship between CSF TEST and a type of sensation-seeking that involves consideration of the consequences of action taken.

CSF monoamine patterns in pathological gamblers and healthy controls.

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

Suicidality, impulsivity and aggression--is there a link to 5HIAA concentration in the cerebrospinal fluid?

In biological suicide research, low cerebrospinal fluid-5-hydroxyindolacetic acid (CSF-5HIAA) concentrations have been associated with suicidality, aggression and impulsivity. However, it frequently appears that the interpretation of existing study results is flawed. The analysis of various published findings suggests that contaminating factors like impulsivity or depressive symptoms in suicide attempters are often not taken into consideration at the time of suicide. The seemingly 'robust' association of low CSF-5HIAA concentration with 'suicidality' and 'aggression' is in fact rather weak. Reported associations of subgroups of suicidal behavior (e.g. violent suicide attempts) with low CSF-5HIAA concentrations are likely to represent somewhat premature translations of findings from studies that have flaws in methodology. Furthermore, the perception of 'suicidal behavior' as autoaggressive behavior or inwardly directed aggression in the view of the authors may not be useful in biological suicide research. The construct of aggressivity is insufficiently defined, resulting in difficulties to interpret empirical data. Some evidence exists, however, that reduced CSF-5HIAA concentrations might be related to certain depressive symptoms and changes in impulsivity. More carefully designed studies are required to overcome the existing methodological shortcomings.

Suicide attempts and impulse control disorder are related to low cerebrospinal fluid 5-HIAA in mentally disordered violent offenders.

OBJECTIVE: The aim of this study was to investigate the relationship between low cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) and aggressive acts in mentally disordered violent offenders. METHOD: CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid and 4-hydroxy-3-methoxyphenyl glycol were measured in 35 drug-free men convicted of homicide and currently undergoing forensic psychiatric investigation in a high security hospital. RESULTS: The mean metabolite concentrations in the homicide offenders did not differ from those of age- and body-height matched male control subjects. One-third of the murderers had made one or several suicide attempts, and their mean concentration of spinal fluid 5-HIAA was significantly lower than that of the remaining murderers. Subjects with impulse control disorder also had lower mean CSF 5-HIAA. A consistent pattern of higher CSF 5-HIAA in subjects with more self-reported anxiety traits was observed. CONCLUSION: The association between serotonin and suicidal behaviour holds for yet another subject group. Determining CSF 5-HIAA might be worth while in the routine assessment of psychiatrically ill homicide offenders.

CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers.

BACKGROUND: There is an extensive literature describing a central serotonin deficit in alcoholic, impulsive, violent offenders and fire setters. In the present study, we investigated biochemical concomitants of impulsivity and aggressiveness, and the physiological consequences of reduced central serotonin turnover. METHODS: Forty-three impulsive and 15 nonimpulsive alcoholic offenders and 21 healthy volunteers were studied in the forensic psychiatry ward of a university psychiatric department. The subjects underwent lumbar punctures and oral glucose and aspartame challenges, and their diurnal activity rhythm was measured with physical activity monitors. Discriminant function analyses were used to investigate psychophysiological and biochemical concomitants of aggressive and impulsive behaviors. RESULTS: Alcoholic, impulsive offenders with antisocial personality disorder had low mean cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and corticotropin levels and high mean CSF testosterone concentrations. Compared with healthy volunteers, they showed increased physical activity during the daytime. Alcoholic, impulsive offenders with intermittent explosive disorder had a low mean CSF 5-HIAA concentration and blood glucose nadir after an oral glucose challenge, and desynchronized diurnal activity rhythm. Healthy volunteers had mean CSF 5-HIAA concentrations that were intermediate between those of alcoholic, impulsive and nonimpulsive offenders. Alcoholic, nonimpulsive offenders had a significantly higher mean CSF 5-HIAA concentration than all the other groups, including healthy volunteers. CONCLUSIONS: In the present sample, a low CSF 5-HIAA concentration was primarily associated with impulsivity and high CSF testosterone concentration, with aggressiveness or interpersonal violence.

Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism.

BACKGROUND: To examine whether the tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme in the biosynthesis of serotonin, may be a factor influencing serotonin turnover and behaviors controlled by serotonin. METHODS: Using a polymerase chain reaction-based method, TPH genotype was determined in DNA samples from 56 impulsive and 14 nonimpulsive, alcoholic, violent offenders and 20 healthy volunteers. RESULTS: In the behaviorally extreme impulsive group, we observed a significant association between TPH genotype and cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) concentration. No association of TPH genotype with impulsive behavior was detected. The polymorphism was also associated with a history of suicide attempts in all violent offenders, independent of impulsivity status and cerebrospinal fluid 5-HIAA concentration. CONCLUSION: In some individuals, a genetic variant of the TPH gene may influence 5-HIAA concentration in the cerebrospinal fluid and predisposition to suicidal behavior.

Monoamines, glucose metabolism, and impulse control.

We had studied cerebrospinal fluid monoamine metabolite concentrations and glucose metabolism in 58 violent offenders and impulsive fire setters in the early 1980s. We performed a follow-up study investigating recidivist crimes after release from prison and histories of suicide attempts using behavioral, diagnostic, and biochemical variables to discriminate subjects with recidivism and suicide attempts from subjects without recidivism and suicide attempts. Biochemical variables discriminated significantly between the groups.

Cerebrospinal fluid monoamine metabolite levels in male arsonists.

Cerebrospinal fluid (CSF) monoamine metabolite levels were studied in 20 arsonists, 20 habitually violent offenders, and ten healthy inpatient volunteers. The arsonists and violent offenders had been in prison an average of six months before the study. Both the raw data and data adjusted by analysis of covariance for group differences in age, height, sex, and season of the lumbar puncture showed significantly lower concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA) in the arsonists than in the other groups. The finding remained the same when arsonists with violent suicide attempts were excluded from the analysis. Although CSF concentrations of MHPG or 5-HIAA did not correlate with the severity of repeated fire-setting behavior, low blood glucose nadir in the oral glucose tolerance test (a measure of the tendency toward hypoglycemia) did. These results support the hypothesis that poor impulse control in criminal offenders is associated with low levels of certain CSF monoamine metabolites and with a hypoglycemic tendency.