Faculty Bibliography

Prepulse inhibition (PPI) represents an attenuation of the startle reflex following the presentation of a weak prepulse at brief intervals prior to the startle eliciting pulse. It has been shown that increases in striatal dopamine levels decrease PPI; because dopamine release is sensitive to estrogen, it is likely that PPI varies across the menstrual cycle. Cross-sectional studies looking at estrogen effects suggest that this may be true. In this study, we compare effects of menstrual phase on PPI in a between-group design (men, follicular phase women, and luteal phase women) as well as a within-subjects design (women across the two phases). The study found a between-group as well as a within-subjects effect of phase on PPI. PPI in follicular phase women did not differ significantly from PPI in men. However, PPI was reduced in luteal women compared to follicular women. These data provide evidence that ovarian hormones affect sensorimotor gating

Hepatitis C virus (HCV) burdens injection drug users (IDUs) with prevalence estimated from 60-100% compared to around 5% among noninjection drug users (non-IDUs). We present preliminary data comparing the risk for HCV among IDUs and non-IDUs to inform new avenues of HCV prevention and intervention planning. Two cohorts, new IDUs (injecting < or =3 years) and non-IDUs (smoke/sniff heroine, crack or cocaine < or =10 years), ages 15-40, were street-recruited in New York City. Participants underwent risk surveys and HCV serology at baseline and 6-month follow-up visits. Person-time analysis was used to estimate annual HCV incidence. Of 683 non-IDUs, 653 were HCV seronegative, 422 returned for at least 1 follow-up visit, and 1 became HCV seropositive. Non-IDUs contributed 246.3 person-years (PY) yielding an annual incident rate of 0.4/100 PY (95% Confidence Interval [CI]=0.0-1.2). Of 260 IDUs, 114 were HCV seronegative, 62 returned for at least 1 follow-up visit, and 13 became HCV seropositive. IDUs contributed 36.3 PY yielding an annual incidence rate of 35.9/100 PY (95%CI=19.1-61.2). Among IDUs, HCV seroconverters tended to be younger (median age 25 vs. 28, respectively), and inject more frequently (61.5% vs. 34.7%, respectively) than non-seroconverters. These interim data suggest that IDUs may have engaged in high-risk practices prior to being identified for prevention services. Preventing or at least delaying transition into injection could increase opportunity to intervene. Identifying risk factors for transition into injection could inform early prevention to reduce onset of injection and risk of HCV.

Current approaches to prevention of blood-borne infections in injection drug users include referral to drug abuse treatment, access to sterile syringes, bleach disinfection of injection equipment, and education about not sharing equipment. However, rates of some blood-borne infections (e.g., hepatitis C virus) remain elevated among injection drug users, especially early after initiation into injection drug use. With lower infection rates in noninjectors and transition into injection drug use occurring most commonly among these noninjectors, prevention of transition into injection drug use as an additional step to reduce risk for acquisition and transmission of blood-borne infections merits closer attention.

The Expanded Syringe Access Demonstration Program (ESAP), which was intended to increase access to syringes for injection drug users (IDUs), went into effect in New York State on 1 January 2001. ESAP allowed prescription-authorized health care providers to register to distribute syringes without a prescription. In spring 2002, we conducted a random postal survey of 1100 providers in New York City to evaluate involvement in ESAP and willingness to furnish IDUs with syringes. Among 363 nurse practitioners, physicians, and physician assistants responding, 16.9% knew about ESAP, and 2.0% believed they were registered; 50.5% would consider distributing syringes to patients who were IDUs. Most of those unwilling to distribute syringes were concerned about legal and moral issues. More respondents agreed that providers should prescribe syringes than distribute syringes (41.1% vs. 22.7%; P<.0001). These results suggest that many providers are willing to furnish IDUs with syringes but are unaware of the current law.

BACKGROUND: Atypical antipsychotics are increasingly used in clinical practice in the management of borderline personality disorder (BPD), and a small but growing body of literature supports their efficacy. Here, we report the results of a double-blind, placebo-controlled study of olanzapine as a treatment for BPD. METHOD: Forty BPD patients (25 female, 15 male) were randomly assigned in equal numbers to olanzapine and placebo. Diagnoses were made using the Structured Clinical Interview for DSM-IV Axis II Personality Disorders and the Mini-International Neuropsychiatric Interview. Patients with schizophrenia, bipolar disorder, or current major depression were excluded. Olanzapine dosage was flexible, and the dose range was 2.5 to 20 mg/day, with most patients receiving 5 to 10 mg/day. No concomitant psychotropic medications were allowed. Patients were assessed at baseline and at 2, 4, 8, and 12 weeks. The primary outcome was change in the total score for the 9 BPD criteria on a 1-to-7 Likert scale, the Clinical Global Impressions scale modified for borderline personality disorder (CGI-BPD), using an analysis of covariance model including baseline score as covariate. Data were collected from July 2000 to April 2002. RESULTS: Olanzapine was found to be significantly (p <.05) superior to placebo on the CGI-BPD at endpoint, with separation occurring as early as 4 weeks. Similar results were found for the single-item Clinical Global Impressions scale. Weight gain was significantly (p =.027) greater in the olanzapine group. CONCLUSIONS: This study supports the efficacy of olanzapine for symptoms of BPD in a mixed sample of women and men. Further studies with olanzapine and other atypical antipsychotics are needed.

Results of behavioral and c-fos immunohistochemical studies have suggested that chronic food restriction and maintenance of animals at 75-80% of free-feeding body weight may increase d-1 dopamine (DA) receptor function. The purpose of the present study was to determine whether D-1 DA receptor binding and/or mitogen-activated protein kinase (MAPK) signaling in caudate-putamen (CPu) and nucleus accumbens (NAc) are increased in food-restricted subjects. In the first experiment, saturation binding of the D-1 DA receptor antagonist [3H]SCH-23390 indicated no difference between food-restricted and ad libitum fed rats with regard to density or affinity of d-1 binding sites in CPu or NAc. In the second experiment, activation of extracellular signal-regulated kinases (ERK1/2) and cyclic AMP response element-binding protein (CREB) by i.c.v. injection of the D-1 DA receptor agonist SKF-82958 (20 microg) were markedly greater in food-restricted than ad libitum fed rats. Given a prior finding that SKF-82958 does not differentially stimulate adenylyl cyclase in CPu or NAc of food-restricted versus ad libitum fed subjects, the present results suggest that increased D-1 DA receptor-mediated ERK1/2 MAP kinase signaling may mediate the enhanced downstream activation of CREB, c-fos, and behavioral responses in food-restricted subjects. It is of interest that food restriction also increased the activation of c-Jun N-terminal protein kinase/stress-activated protein kinase, but this effect was no greater in rats injected with SKF-82958 than in those injected with saline vehicle. This represents additional evidence of increased striatal cell signaling in food-restricted subjects, presumably in response to the i.c.v. injection procedure, although the underlying receptor mechanisms remain to be determined. There were no differences between feeding groups in protein levels of the major phosphatases, MKP-2 and PP1. The upregulation of striatal MAP kinase signaling in food-restricted animals may adaptively serve to facilitate associative learning but, at the same time, increase vulnerability to the rewarding and addictive properties of abused drugs

A multi-site, open-label study of methylphenidate for treating patients with comorbid diagnoses of attention deficit/hyperactivity disorder and cocaine dependence was performed. Forty-one participants, who met DSM-IV criteria for adult attention deficit/hyperactivity disorder and cocaine dependence, were enrolled into this ten week outpatient study. The targeted total daily dose of methylphenidate was 60 mg (20 mg TID). Participants received individual substance abuse therapy throughout the trial. Safety measures included adverse events, vital signs, and electrocardiograms. Methylphenidate's efficacy was assessed by both objective and subjective measures. Seventy percent of the participants completed final study measures. Safety measures indicated that methylphenidate was well tolerated by the participants. Subjective efficacy measures suggested that participants evidenced improvement in both cocaine dependence and adult attention deficit/hyperactivity disorder symptoms. Quantitative benzoylecgonine indicated that only those participants categorized as being compliant showed improvement. A double-blind, placebo-controlled study of methylphenidate for this population may be warranted

OBJECTIVE: Pharmacy syringe sales without a prescription became legal in New York State on January 1, 2001 through the Expanded Syringe Access Demonstration Program (ESAP). At the same time, Pharmacy use among Black and Hispanic injection drug users was found to be significantly lower when compared to Whites. The purpose of this study was to assess the factors that could explain the relationship between race/ethnicity and pharmacy use. DESIGN: Data were combined from 2 on-going injection drug user (IDU) studies in 2 New York City neighborhoods. Social and behavioral factors independently associated with ever purchasing a nonprescription syringe in the past 6 months and examined using cross-sectional logistic regression. RESULTS: Of 337 IDUs, the majority were male (79%), Hispanic (73%) and had a mean age of 35 years. In bivariate analysis, IDUs who reported pharmacy use were less likely to be Black or Hispanic, older, and to have reported recent syringe exchange program (SEP) attendance compared to non-pharmacy users. Additionally, pharmacy users were more likely to have knowledge of ESAP, and report discrimination by police in the past year compared to non-users. After adjustment for recent SEP attendance (adjusted odds ratio [AOR]=0.27; 95% confidence interval [CI]=0.14-0.55), ESAP knowledge (AOR=13.11; 95% CI=6.54-26.31), discrimination by police (AOR=3.56; 95% CI=1.73-7.35), and discrimination due to race (AOR=0.25, 95% CI=0.11-0.58), race/ethnicity was not a significant predictor of pharmacy use. CONCLUSIONS: Race/ethnicity may not be an important determinant of ESAP when more salient social circumstances, such as past discrimination, are considered. Educational efforts should be enhanced to reach those who continue to perceive barriers to ESAP.