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Kevin P Hill

Publications and source records attributed to Kevin P Hill.

13 recordsLinked to original sources
PubMed2006

Polymorphism in the serotonin transporter gene and moderators of prolactin response to meta-chlorophenylpiperazine in African-American cocaine abusers and controls.

Serotonin (5-HT) function is altered in several psychiatric disorders, including cocaine dependence (CD), and its role in impulsive-aggressive behaviors has been widely studied. However, the relationship between psychopathological and behavioral dimensions and mechanisms of 5-HT alterations remains unclear. We investigated the relationship of a polymorphism in the 5' promoter region of the serotonin transporter gene (5-HTTLPR) with prolactin (PRL) response to meta-chlorophenylpiperazine (m-CPP) in a sample of 68 African-American individuals, 35 CD subjects and 33 controls. We also examined whether measures of impulsivity, hostility and sensation seeking influenced the relationship between the 5-HTTLPR polymorphism and PRL response to m-CPP in this sample. Individuals with the SS genotype showed significantly heightened PRL response to the challenge compared with the LL and LS genotypes. No influence of gender or substance abuse condition was observed. Hostility was associated with blunted PRL response in the total sample. Cocaine abuse was the most significant moderator of DeltaPRL (peak PRL-baseline PRL), and the interaction of genetic, behavioral and psychopathological measures helped predict most of the observed DeltaPRL (62.5%). Although these results need replication, variation in the 5-HTTLPR gene appears to influence measures of 5-HT function and interact with disease state and personality dimensions to account for 5-HT disturbances in African-American populations.

Adult↗
PubMed2006

Relationship of disinhibition and aggression to blunted prolactin response to meta-chlorophenylpiperazine in cocaine-dependent patients.

RATIONALE: Considerable evidence indicates that serotonergic (5-HT) mechanisms may mediate central effects of cocaine, and disinhibition and aggression. OBJECTIVE: We investigated whether prolactin (PRL) response to meta-chlorophenylpiperazine (m-CPP), a mixed 5-HT agonist/antagonist, differed between abstinent cocaine-dependent patients and controls and whether m-CPP challenge responses were related to measures of disinhibition and aggression. METHODS: Thirty-five cocaine-dependent African-American subjects who were abstinent for at least 2 weeks and 33 African-American controls underwent assessments of disinhibition and aggression and a challenge with 0.5 mg/kg of oral m-CPP. RESULTS: The PRL response to m-CPP was compared between cocaine patients and controls and between subgroups categorized high or low based on disinhibition and aggression measures. Hierarchical regressions were used to determine whether behavioral measures predicted deltaPRL (peak PRL-baseline PRL). The PRL response to m-CPP was significantly diminished in cocaine patients compared to controls. The blunting was more robust in cocaine patients with high disinhibition and aggression. Among cocaine patients, the high-disinhibition subgroup showed greater blunting than the low-disinhibition subgroup and there was a trend for the high-aggression subgroup to be more blunted than the low-aggression subgroup. The subgroups of controls did not differ from each other. A combination of disinhibition and aggression measures significantly predicted deltaPRL in cocaine patients. CONCLUSION: The results indicate that cocaine-dependent patients show disturbances in postsynaptic 5-HT function during early abstinence. It appears that the 5-HT disturbances are more pronounced in the subgroup of cocaine patients with high disinhibition and aggression.

Adult↗
PubMed2006

Relationship of prolactin response to meta-chlorophenylpiperazine with severity of drug use in cocaine dependence.

RATIONALE: Serotonergic (5-HT) mechanisms appear to mediate central effects of cocaine. Therefore 5-HT disturbances could be associated with drug severity. OBJECTIVES: We investigated whether prolactin (PRL) response to meta-chlorophenylpiperazine (m-CPP), a mixed 5-HT agonist/antagonist were associated with severity of cocaine use. METHODS: Thirty-six cocaine-dependent subjects and 33 controls underwent a challenge with 0.5 mg/kg of oral m-CPP. Severity of drug use was assessed using the Addiction Severity Index (ASI). RESULTS: The PRL response to m-CPP was significantly blunted in cocaine patients compared to controls (F = 21.86, p < 0.001). DeltaPRL (peak PRL-baseline PRL) was negatively correlated with ASI-drug (r = -0.45, p < 0.01), ASI-alcohol (r = -0.32, p < 0.05), and ASI-psychological (r = -0.41, p < 0.01) composite scores, and with the quantity, frequency and duration of drug use (r ranged from - 0.41 to - 0.32, p ranged from < 0.01 to 0.05). Hierarchical regressions showed that ASI-drug composite scores significantly predicted the variance in DeltaPRL after controlling for behavioral and demographic variables (F = 4.27, p < 0.05). CONCLUSIONS: The results indicate that disturbances in 5-HT function as reflected by a blunted response to m-CPP seem to be primarily associated with severity of drug use and to a lesser, although significant extent with behavioral traits in cocaine-dependent patients.

Adult↗
PubMed2006

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Drug Industry↗
PubMed2004

Comparison of pretreatment characteristics and treatment outcomes for alcohol-, cocaine-, and multisubstance-dependent patients.

We investigated whether pretreatment characteristics and measures of outcome differed for alcohol-, cocaine-, and multisubstance-dependent patients receiving outpatient substance abuse treatment. One hundred and forty substance dependent individuals (32 alcohol, 76 cocaine, and 32 multisubstance) enrolled in a 12-week outpatient treatment program were compared across measures of addiction severity, personality, and treatment-readiness at admission. In-treatment, end-of-treatment and 9-month follow-up assessments of treatment outcome were then compared across the three groups. Outcome measures included reduction in problem severity, abstinence, retention, number of sessions attended, dropout, and counselor and patient ratings of treatment benefit. At admission, the multisubstance group had a higher proportion of positive urines, reported more severe drug, alcohol and psychiatric problems, and displayed higher impulsivity and anxiety scores than one or both of the other groups. However, multisubstance patients were more treatment ready in terms of adopting a total abstinence orientation than alcohol or cocaine patients. While a significant reduction in symptoms occurred for the total sample during treatment as well as at follow-up, comparisons of outcomes did not consistently favor any particular group. The three groups had equivalent improvements in eleven of fourteen during-treatment and five of seven follow-up measures. Despite pretreatment differences, in severity and treatment-readiness, outcomes were more similar than different for alcohol-, cocaine-, and multisubstance-dependent patients. Clinicians should be cautious about forecasting treatment-outcomes for addicted patients based on their primary substances of abuse.

Alcoholism↗
PubMed2003

Seasonal variations in the binding of [3H]paroxetine to the platelet serotonin transporter sites in African-American cocaine-dependent patients and healthy volunteers.

Although seasonal fluctuations in several indices of serotonin function have been described, little is known about seasonality and serotonergic activity in substance abusers. We investigated whether there were seasonal differences in platelet serotonin transporter sites among cocaine dependent patients and controls. Platelet [(3)H]paroxetine binding, a measure of serotonin transporter sites, was assayed in 141 African-American cocaine-dependent subjects and in 60 race matched healthy volunteers who served as the control group. B(max) (density of serotonin transporter) and K(d) (affinity constant) values of [(3)H]paroxetine binding were compared during spring, summer, fall and winter. Consistent with our previous findings B(max) values were significantly lower in cocaine patients (639 +/- 234) than in controls (906 +/- 225) (t = 7.12, p < 0.001). Moreover, B(max) values showed a significant seasonal variation in controls with the highest values in summer and spring compared with fall and winter (F = 4.47, p < 0.01). However, there were no significant seasonal differences in B(max) values in cocaine patients. K(d) values did not show any seasonal changes in either group. There were no effects of age or gender on seasonal variations in B(max). The study demonstrates a seasonal effect on platelet serotonin uptake in healthy African-American volunteers. The lack of seasonal differences in transporter availability in cocaine patients indicates that the normal seasonal rhythm of serotonergic activity may be disturbed in cocaine abusers. Biological studies that employ platelet serotonin transporter sites as a marker of serotonin function should consider seasonal variations in these markers as a potential source of variance.

Adult↗
PubMed2003

Relationship between platelet serotonin uptake sites and treatment outcome among African-American cocaine dependent individuals.

We investigated whether platelet tritiated paroxetine binding, a measure of serotonin uptake sites differed between cocaine-dependent subjects and controls, and whether paroxetine binding was related to treatment-outcome for cocaine patients. One hundred twenty-five African-American cocaine-dependent individuals receiving outpatient treatment and 44 controls were studied. Tritiated paroxetine binding sites on platelets were assayed and standardized assessments of behavior were performed. The outcome measures were number of negative urine drug screens, days in treatment, dropout rates and number of treatment sessions attended. Cocaine patients had significantly lower Bmax values of paroxetine binding compared to controls. Furthermore, Bmax values showed a significant positive correlation with days in treatment and negative urines. A combination of Bmax and Addiction Severity Index (ASI) employment scores improved the prediction of days in treatment and a combination of Bmax and ASI drug scores enhanced the prediction of negative urines. The findings indicate that serotonergic mechanisms may be involved in cocaine dependence and may influence treatment-outcome among cocaine patients.

Adult↗
PubMed2002

Predicting treatment-outcome in cocaine dependence from admission urine drug screen and peripheral serotonergic measures.

We investigated whether urine drug screens (UDS) at admission and platelet paroxetine binding, a measure of serotonin transporter sites, were related to outcome measures for cocaine patients in treatment. Tritiated paroxetine binding sites on platelets were assayed and UDS were obtained for 105 African American cocaine-dependent outpatients. Outcome measures included number of negative urines, days in treatment, dropouts, and number of treatment sessions attended. A significant association was found between cocaine-positive UDS at admission and negative urines, treatment retention, dropouts, and treatment sessions; while Bmax values of paroxetine binding (density of serotonin transporter sites) were significantly associated with treatment retention and negative urines. Moreover, UDS and paroxetine binding combined to enhance prediction of retention and abstinence. Although both admission UDS and paroxetine binding seem to contribute individually in predicting outcome of cocaine patients, a combination of the two variables seems to have a stronger effect in terms of predicting treatment-outcome.

Adult↗
PubMed2002

Serum prolactin and response to treatment among cocaine-dependent individuals.

Considerable evidence indicates that dopaminergic mechanisms may modulate the central effects of cocaine. We investigated whether basal serum prolactin, a measure of central dopamine activity, differed between cocaine-dependent subjects and controls, and whether prolactin levels among cocaine patients were related to their response to treatment. Eighty-six African-American cocaine-dependent outpatients and 35 African-American controls were studied. Prolactin concentrations in fasting blood samples were assayed by radioimmunoassay. The outcome measures were: number of negative urine drug screens, retention in treatment, counselor ratings of improvement and discharge status. Chi-square tests and independent t-tests were used for data analyses. The basal prolactin(ng/ml) among cocaine patients (9.12 +/- 4.12) was significantly higher compared to controls (7.14 +/- 3.36) (t = 2.52, p < 0.02). Furthermore, the higher prolactin subjects (median prolactin = 7.71) had significantly fewer negative urine screens (p < 0.05) and received less favorable ratings of improvement by counselors (p < 0.01) compared to the lower prolactin group. However, the two groups did not differ significantly in treatment retention (p = 0.13) or discharge status (p = 0.08). The higher basal prolactin among cocaine patients relative to controls may reflect changes in DA activity among cocaine patients. Moreover, higher prolactin seems to be related negatively with certain measures of response to treatment among cocaine patients.

Adult↗
PubMed2002

No association between polymorphisms in the serotonin transporter gene and susceptibility to cocaine dependence among African-American individuals.

Genetic research of cocaine abuse has been relatively limited among the African-American population. Since the serotonin transporter (5HTT) may be involved in modulating effects of cocaine, we investigated whether allelic variants of the 5HTT gene may confer susceptibility to cocaine dependence among African-American individuals. One hundred and fifty-six cocaine-dependent subjects and 82 controls were studied. Polymerase chain reaction-based genotyping of a variable-number-tandem-repeat (VNTR) marker yielded three alleles designated 12, 10 and 9. Genotype and allele frequencies were compared using chi-square analyses. We found no differences between subjects and controls with respect to genotype distribution (cocaine: 12/12 = 50%, 10/12 = 35.3%, 10/10 = 13.5%, 9/12 = 1.3%; controls: 12/12 = 42.7%, 10/12 = 39.0%, 10/10 = 17.1%, 9/12 = 1.2%). Similarly, allele frequencies of the VNTR marker did not differ between the two groups (cocaine: 12 = 68.3%, 10 = 31.1%, 9 = 0.6%; controls: 12 = 62.8%, 10 = 36.6%, 9 = 0.6%). Our findings do not seem to support a relationship between VNTR polymorphisms and cocaine dependence among African-American patients. Further studies involving larger samples are required to confirm our results.

Adult↗
PubMedDate not supplied

Relationship between platelet serotonin uptake sites and measures of impulsivity, aggression, and craving among African-American cocaine abusers.

We investigated whether platelet-tritiated paroxetine binding, a measure of serotonin uptake sites, and behavioral measures of impulsivity, aggression, and craving differed between cocaine-dependent subjects and controls and whether paroxetine binding was related to these behavioral measures. One hundred and five African-American cocaine-dependent outpatients and 44 African-American controls were studied. Tritiated paroxetine binding sites on platelets were assayed, and standardized assessments of impulsivity, aggression, and craving were performed. The Bmax values of paroxetine binding were significantly reduced among cocaine patients compared to controls. Cocaine patients showed significantly higher scores on certain measures of sensation seeking, impulsivity, and aggression as compared to controls. Furthermore, paroxetine binding showed a significant negative correlation with most measures of sensation seeking, impulsivity, and aggression--though not craving--among cocaine patients. Our findings indicate that densities of serotonin uptake sites may be reduced among cocaine abusers and related to impulsive-aggressive behavioral dimensions.

Adult↗