Faculty Bibliography

The objective of the study was to explore correlates of suicidal ideation among African Americans in a community-based cohort in Baltimore, Md. Participants had initiated use of heroin, crack, or cocaine by means other than injection in the prior 10 years. An interview-administered questionnaire collected information regarding drug use history, depressive symptoms, drug dependence, and suicidal thoughts and attempts within the past six months. Multiple logistic regression was used to identify factors independently associated with suicidal ideation. Of 148 persons, median age was 27 years, and 60.8% were female. Suicidal ideation was reported by 21.6% of participants. Those reporting suicidal ideation were significantly more likely to be dependent on two or more drugs (adjusted odds ratio=2.93, 95% confidence interval = 1.25, 6.88). Our findings underscore the need to integrate treatment for psychiatric comorbidity and drug dependence and target these services toward young, African-American drug users.

Surveillance data suggests that use of ecstasy in the U.S. is predominantly among white adolescent and young adults. To investigate ecstasy use among substance users in New York City we added questions to ongoing efforts to recruit heroin and cocaine users. Of 715 participants recruited, 58.3% were injection drug users (IDUs). The median age was 32 (range 17-64), 76.4% were male, 49.0% were currently homeless, 62.4% were Hispanic, 27.3% were black, and 34.5% were born outside the United States. Overall, 23.4% used ecstasy in their lifetime and 11.9% had used in the last-6 months. In multivariate logistic regression, correlates of lifetime ecstasy use included younger age, being born in the U.S., and current homelessness. We observed a significant interaction between injection drug use and race where, compared to black non-IDUs, Hispanic non-IDUs, and white IDUs were significantly more likely to have a history of lifetime ecstasy use while black IDUs were significantly less likely. These findings are limited to persons who use other drugs, but suggest that further investigation of ecstasy use in minority populations is warranted.

Recently, attention has turned to the possibility that endocrine adiposity hormones, such as leptin, may regulate appetitively motivated behavior by modulating brain dopamine function. By extension, it has been hypothesized that the increased behavioral sensitivity of food-restricted, underweight rats to psychostimulant challenge may be triggered by the accompanying hypoleptinemia. The purpose of the present study was to determine whether two weeks of continuous intracerebroventricular (ICV) infusion of leptin alters the motor-activating effect of D-amphetamine (0.75 mg/kg, IP) in food-restricted rats. Lateral ventricular infusion of leptin, using a regimen that decreases food intake and body weight in ad libitum fed rats (12 microg/day), had no effect on the locomotor response to D-amphetamine in food-restricted rats that were maintained at 80% of prerestriction body weight. This result may indicate that hypoleptinemia is not involved in the induction/maintenance of neuroadaptations that mediate enhanced behavioral sensitivity to psychostimulant challenge. Interestingly, ad libitum fed rats treated with leptin displayed an increased locomotor response to D-amphetamine that was most prominent 3-5 days after termination of the infusion. Body weights and D-amphetamine sensitivity of these subjects returned to control values by 8-10 days postinfusion. The enhanced behavioral sensitivity to D-amphetamine in leptin-treated ad libitum fed rats may be a by-product of adipose depletion and, if so, would further support involvement of a peripheral signal other than hypoleptinemia in the modulation of central sensitivity to psychostimulant challenge

BACKGROUND: Chronic food restriction augments the rewarding effect of centrally administered psychostimulant drugs and this effect may involve a previously documented upregulation of D-1 dopamine receptor-mediated MAP kinase signaling in nucleus accumbens (NAc) and caudate-putamen (CPu). Psychostimulants are known to induce striatal glutamate release, and group I metabotropic glutamate receptors (mGluR) have been implicated in the cellular and behavioral responses to amphetamine. The purpose of the present study was to evaluate whether chronic food restriction increases striatal MAP kinase signaling in response to the group I mGluR agonist, DHPG. RESULTS: Western immunoblotting was used to demonstrate that intracerebroventricular (i.c.v.) injection of DHPG (500 nmol) produces greater activation of ERK1/2 and CREB in CPu and NAc of food-restricted as compared to ad libitum fed rats. Fos-immunostaining induced by DHPG was also stronger in CPu and NAc core of food-restricted relative to ad libitum fed rats. However, i.c.v. injection of saline-vehicle produced greater activation of ERK1/2 and CREB in CPu and NAc of food-restricted relative to ad libitum fed rats, and this difference was not seen when subjects received no i.c.v. injection prior to sacrifice. In addition, although DHPG activated Akt, there was no difference in Akt activation between feeding groups. To probe whether the augmented ERK1/2 and CREB activation in vehicle-injected food-restricted rats are mediated by one or more GluR types, effects of an NMDA antagonist (MK-801, 100 nmol), AMPA antagonist (DNQX, 10 nmol), and group I mGluR antagonist (AIDA, 100 nmol) were compared to saline-vehicle. Antagonist injections did not diminish activation of ERK1/2 or CREB. CONCLUSIONS: These results indicate that a group I mGluR agonist induces phosphorylation of Akt, ERK1/2 and CREB in both CPu and NAc. However, group I mGluR-mediated signaling may not be upregulated in food-restricted rats. Rather, a physiological response to 'i.c.v. injection stress' is augmented by food restriction and appears to summate with effects of the group I mGluR agonist in activating ERK1/2 and CREB. While the augmented cellular response of food-restricted rats to i.c.v. injection treatment represents additional evidence of enhanced CNS responsiveness in these subjects, the functional significance and underlying mechanism(s) of this effect remain to be elucidated

INTRODUCTION: The negative and cognitive symptoms of schizophrenia are poorly responsive to neuroleptic treatment. Glutamatergic dysfunction may mediate some of these symptoms. Low dose D-cycloserine (DCS) is a partial agonist at the glycine site of the NMDA-associated receptor complex, noncompetitively enhancing NMDA neurotransmission. Prior studies suggest a beneficial effect of DCS on negative symptoms and cognition. This treatment trial was initiated to confirm and extend these findings. METHODS: Twenty-two male schizophrenic subjects displaying prominent negative symptoms who were stabilized on typical neuroleptics completed the study. A randomized double-blind parallel group design was used to compare the effects of 50 mg p.o. QD of DCS to placebo over 4 weeks. The two subject groups did not differ significantly in age, age of onset of illness or time on current neuroleptic treatment. Symptoms were rated by means of the SANS, BPRS and Abrams and Taylor rating scale. Cognition was assessed with the Sternberg Memory Test and the Continuous Performance Test. RESULTS: Both medication groups improved over the 4 weeks of treatment. However, there were no significant differences between the DCS and placebo group on any symptom rating. DCS effects on cognition did not differ from placebo. DISCUSSION: This study did not detect improvement in negative symptoms or cognitive performance with DCS treatment that has been found in some prior studies. This negative finding may be attributed to small sample size, relatively short duration of treatment and the overall modest effect of DCS. Future studies of DCS should be adequately powered to detect a small to medium effect size and should provide for a longer treatment phase than was used in this study in order to avoid a type II error

Hepatitis B (HBV) vaccination rates remain low among drug users. We examined correlates of vaccine acceptance and completion in two ongoing prospective studies of young injecting and non-injecting drug users in New York City. Street recruited drug users were enrolled at one of two neighbourhood locations (Harlem and the Bronx) between 2000 and 2004 and completed risk behaviour questionnaires and HBV testing. Free HBV vaccination was offered. Among 1117 participants, 26.1% (275) had a previous HBV infection, 57.9% (610) were susceptible to HBV, and 16.0% (169) had serological evidence of previous vaccination. Of the 610 participants susceptible to HBV, 466 (76.4%) returned for their results and were offered vaccination; 53.9% (251) received at least one dose of the vaccine (acceptors). Correlates of vaccine acceptance included older age, public assistance as main income source, and being recruited in the Bronx. Daily crack users were significantly less likely to initiate the vaccine series. Among 240 vaccine acceptors, 98 (40.8%) completed all three doses. Daily injectors, Hispanics, and those recruited in Harlem were less likely to complete the vaccination series. HBV vaccination acceptance among drug users seems likely in programmes that are convenient and offer remuneration; however, extended efforts are needed to improve series completion.

OBJECTIVE: Dependence on alcohol, nicotine, or illicit drugs during pregnancy continues to be a problem of major medical, social, and fetal consequences. The purpose of this systematic review was to summarize current experience that pertains to pharmacotherapy for pregnant women with specific chemical addictions. STUDY DESIGN: Studies were identified through Medline and HealthSTAR (1979-2003) that linked specific pharmacotherapy with pregnancy. This article reviews the English language literature for clinical studies that link the 2 conditions. In addition, reference lists of all articles that were obtained were evaluated for other potential citations. RESULTS: Pregnant women are excluded systematically from almost all drug trials. Most knowledge about the fetal effects from maternal substance and medication use comes from animal data and from case reports and small clinical series. With the exception of methadone and nicotine replacement, clinical experience with antiaddictive medications in pregnant women is either very limited (alcohol, stimulants) or nonexistent (cannabis, hallucinogens). CONCLUSION: Antiaddiction medications are important in the treatment of pregnant women with opioid and nicotine dependence and are of growing importance in the treatment of alcohol and stimulant dependence. Future directions will be toward increasing knowledge about current drug therapy and in developing new antiaddiction medications.

BACKGROUND: Substance abuse is an escalating problem among poor urban Latina women; little is known about their access to drug treatment and to needed social and health services. OBJECTIVE: Our objectives were to (1) examine the need and use of substance abuse treatment, health services, government entitlement programs, and social service programs among cocaine and heroin using Puerto Rican women and (2) identify whether service use predicts their prospective entry into drug treatment. RESEARCH DESIGN: This was a 3-wave longitudinal study of community substance abusing women evaluated on substance abuse and dependence using diagnostic measures, and hair and urine toxicological screens. Information was collected on self-reported need and receipt of substance abuse treatment, social services, general health services, and government entitlement programs. SUBJECTS: A community sample of cocaine-, crack-, and/or heroin-using women from copping areas in low-income urban centers of Puerto Rico were interviewed in 1997-1998 with 2 follow-up periods. RESULTS: Drug treatment, health, and social service utilization were low relative to need for services throughout all data waves. Social service utilization predicted prospective entry into drug treatment but not contacts with general health services or government entitlement programs. CONCLUSION: Drug-abusing women in low-income urban areas in Puerto Rico have substantial unmet substance abuse treatment, health, and social service needs. Mandated treatment by social service agencies may explain their clients' higher likelihood of entering drug treatment. Building linkages between service sectors to augment entry into drug treatment is essential for meeting the complex needs of this underserved population

The purpose of this study was to determine the prevalence and correlates of attempted suicide among young injection drug users (IDUs) from six study sites in five US cities. Two thousand two hundred and nineteen participants 15-30 years of age underwent interviewer-administered questionnaires relating to self-reported drug use, sociodemographics, suicidal ideation and attempts, and exposure to violence. The 6-month prevalence of suicidal ideation and attempts was 35.8% (n = 795) and 7% (n = 156), respectively. Compared to those not reporting a recent (past 6 months) suicide attempt, those attempting suicide were more likely to have a lifetime history of mental health facility admission or sexual abuse. Participants receiving drug treatment at the time of the baseline interview (53.2% versus 37.1%, odds ratio [OR] = 1.93, 95% confidence interval [CI]: 1.39, 2.67) were also more likely to report a recent attempt; as were those reporting a history of experiencing violence. These associations persisted after adjusting for age, sex, race/ethnicity, study site, and other significant covariates by multiple logistic regression. These data suggest that increased access to drug treatment, community mental health, and violence prevention programs may decrease suicidal behavior among young injection drug users.