Kathryn J. Gill

Drug and alcohol use among patients with schizophrenia and related psychoses: Levels and consequences.

Patients with schizophrenia and related psychoses frequently use, abuse and become dependent on psychoactive substances. Local surveys indicate differences in both types and patterns of substances used. A cross-sectional survey was conducted to document abuse in 207 successive outpatients presenting to a psychiatric continuing care facility in a large Canadian city. Nicotine, alcohol and cannabis were the most frequently abused substances in the cohort. Excluding nicotine, 44.9% met criteria for lifetime and 14.0% for current abuse/dependence. Cocaine, heroin, hallucinogen, amphetamine, and inhalant use were rarely reported. Patients with current substance abuse/dependence and a psychotic disorder (dual diagnosis, DD) had significantly higher Positive and Negative Symptom Scale (PANSS) positive scores than lifetime-DD or those with a single diagnosis (SD). Significantly more current-DD (69.0%) patients were depressed (HAM-D score > or =12) compared to SD (45.6%). Furthermore, current-DD (27.6%) patients were more likely than SD (4.5%) to be medication non-compliant. Patients with current-DD were more likely to smoke cigarettes (88.9%) compared to those with SD (49.6%) and they had significantly longer histories of cigarette smoking (19.1 for DD vs. 11.5 years for SD). The smoking behavior of the DD population is discussed in terms of enhanced risk for alcohol abuse, as well as effects on antipsychotic blood levels and metabolism.

The Impact of Depression on the Outcome of Addictions Treatment

The objectives of this study were to examine the prevalence and presentation of depression among patients with substance use disorders, and to explore the relationship between depression and the outcome of addictions treatment. Seventy-five patients were consecutively recruited upon entering addictions treatment, and were assessed by clinical and semi-structured interviews, Hamilton Rating Scale for Depression, Global Assessment Scale, and Beck Depression Inventory. At intake, 22.4% of patients had primary depressive disorders, 8.4% had substance-induced depressions, and 5.6% had mixed features of primary and substance-induced depressions. Female and alcoholic patients were more likely to suffer from both primary and substance-induced depressions. At 3 months, 93.3% of patients were reinterviewed. Depressed patients had longer duration of abstinence and greater decreases in symptomatology. Patients with substance-induced depression achieved almost complete discontinuation of primary substance use. Depression had a significant impact on addictions treatment outcome, but many important predictors of outcome have not yet been identified.

Early recovery from alcohol dependence: Factors that promote or impede abstinence

The objectives of this prospective follow-up study were to identify factors that promote or impede the early recovery process and to examine whether drinking status at 4 weeks predicts later abstinence. Patients with alcohol use disorders were assessed by clinical and semistructured interviews upon entering addiction treatment (N = 175) and were followed up biweekly to monitor their alcohol use. During the first 4 weeks of treatment, 57% (n = 100) of patients slipped or relapsed on alcohol, whereas 43% (n = 75) were fully abstinent. Patients who slipped or relapsed were more likely to report nondependent use of a secondary substance, meet criteria for a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis II Cluster B personality disorder, have a higher level of impulsivity, and have more severe social problems at intake. The final logistic regression model accounted for 37% of the variance in drinking status. Patients who slipped or relapsed early in treatment were likely to continue to struggle to maintain abstinence at 12 weeks.

A 12-month prospective follow-up study of patients with schizophrenia-spectrum disorders and substance abuse : Changes in psychiatric symptoms and substance use

While it is widely known that patients with schizophrenia-spectrum psychoses and co-occurring substance use disorders are more difficult to manage, there is limited data on the course of their psychiatric symptoms when they remain in treatment over time. This prospective 12-month study evaluated changes in psychiatric symptoms and substance use to ascertain if the co-existence of substance use disorders influences ratings of psychiatric symptoms at follow-up. 147 outpatients in a continuing care program were assessed at intake and followed prospectively for 12 months. Psychiatric symptoms were measured at baseline and 12-month follow-up using the Positive and Negative Syndrome Scale (PANSS) and Hamilton Depression Rating Scale (HAM-D). Subjective psychological distress was rated with the Brief Symptom Inventory (BSI) and quality of life by the Satisfaction with Life Domains Scale (SDLS). Drug and alcohol use was measured with the Addiction Severity Index (ASI). 50.3% of patients were diagnosed with dual disorders (DD) (current and lifetime). The most common primary substances of abuse were alcohol (35.6%) and cannabis (35.1%). DD subjects had higher baseline PANSS positive scores but experienced a greater reduction at 12 months compared to single diagnosis (SD) patients. Severity of substance abuse as measured by ASI composite scores did not decrease significantly between baseline and 12 months. DD patients with schizophrenia and related psychoses treated for their psychiatric illness showed a reduction in PANSS scores over 12 months, even when their substance use remained largely unchanged. However, co-morbidity cases continued to show higher depression and anxiety ratings. Ongoing substance abuse appears to be related to levels of depression as 62.5% of DD-current versus 34.7% of SD patients had HAM-D scores in the depressed range at 12-month follow-up. Implications for treatment are discussed.

The regulation of alcohol consumption in rats: The role of alcohol-metabolizing enzymes—Catalase and aldehyde dehydrogenase

Aldehyde dehydrogenase (ALDH) and catalase enzymatic activities in brain were assayed and compared to measures of alcohol consumption in two groups of animals screened and maintained on free-choice alcohol access under different conditions. In the first group of Long-Evans rats screened and maintained in home cages, mean alcohol intake was 3.49 g/kg/day with a range of 1.69-5.33 g/kg/day. When alcohol intake (g/kg), total ALDH, low K(m) ALDH, and catalase activities were entered in a multiple regression, a significant correlation of r = 0.51 (p < 0.05) was obtained. In the second group of rats consisting of Long-Evans, P, and NP rats screened using a drinkometer procedure, a multiple correlation between ALDH and catalase enzyme activities and alcohol intake of r = 0.42 (p < 0.05) was obtained. There was a strong relationship between the frequency of alcohol drinking bouts and the activities of catalase and ALDH (r = 0.68, p < 0.0001). The P rats had significantly higher catalase activities than either the NP or Long-Evans rats. The results of the present study confirmed earlier reports on the role of alcohol-metabolizing enzymes in the regulation of alcohol intake. The results also highlighted the fact that the activity of these alcohol-metabolizing enzymes may play a mediating role in patterns of alcohol intake displayed by animals selected for high and low alcohol drinking and also unselected animals.

Quantitative trait loci for novelty/stress-induced locomotor activation in recombinant inbred (RI) and recombinant congenic (RC) strains of mice

The objective of the present study was to map and compare quantitative trait loci (QTLs) for an anxiety-related trait (novelty/stress-induced activation) in the AXB/BXA recombinant inbred (RI) and AcB/BcA recombinant congenic (RC) strains of mice derived from the A/J and C57BL/6J inbred progenitor strains. Activational responses to a novel open field (OF) were measured under identical stressful conditions (no prior handling or exposure to testing procedures) in both the RI and RC strains. Naive male and female mice were weighed, injected with IP saline and locomotor activity was monitored in a computerized OF apparatus for 15 min. Measures obtained from this experimental design included: (1) total activity scores, (2) time course of response (5 min time blocks over the 15 min session). Data for the RI strains were subjected to a QTL analysis using composite interval mapping. Significant loci were identified on chr 5 (D5Mit356, 41 cM), chr 8 (D8Mit305, 37 cM) and chr 14 (D14Mit36, 6 3cM). Single locus association analysis of the AcB/BcA RC strains identified 15 putative regions, 7 of which overlapped regions independently mapped in the RI strains on chr 1 (58.5-63.1cM), chr 4 (21.9-28.6 cM), chr 5 (19-45 & 74-86 cM), chr 6 (0.5-20.4cM), chr 9 (15-38 cM), chr 13 (47cM) and chr 19 (47cM). The loci identified on chr 5 near D5Mit356 (41cM) in both the AXB/BXA RIS and AcB/BcA RCS maps to a region containing the genes for several GABA(A) receptor subunits. Additionally, the present study provides further confirmation of a frequently identified QTL on chromosome 1. The results are discussed in the context of previous QTL studies of anxiety-related traits that have used genetic crosses that include the A or B6 progenitors.

Personality disorders among alcoholic outpatients: prevalence and course in treatment.

Objective: To determine the prevalence of concurrent personality disorders (PDs) among alcoholic men and women seeking outpatient treatment, and to examine their effect on the course of alcohol treatment. Method: Patients with alcohol use disorders (n = 165) were assessed by clinical and semi-structured interviews, as well as self-report scales, to measure levels of psychological distress, impulsivity, social functioning, and addiction severity at treatment intake. PD diagnoses were assessed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Personality Disorder (SCID-II). Course in treatment was monitored prospectively for 12 weeks. Results: Using the results of the SCID-II (n = 138), the sample was divided into 3 groups—that is, no PD 41% (n = 57), Cluster B PD 32% (n = 44), and other PD 27% (n = 37). The 3 groups did not differ in their alcohol use severity at intake. However, the Cluster B PD group achieved alcohol milestones at a younger age. Subjects with a PD had more severe psychological and social problems at intake. The Cluster B PD group showed significantly higher levels of impulsivity at intake, greater likelihood of early treatment dropout, and quicker times to first slip and to relapse. Conclusions: This study supports the high prevalence of concurrent PDs, particularly Cluster B PDs, among treatment-seeking alcoholics. The relation between observed high levels of impulsivity and worse course in early alcohol treatment among people with a Cluster B PD merits further investigation.

Substance Abuse in an Urban Aboriginal Population

Abstract This work is the result of a research program developed from a research partnership between the Native Mental Health Research Team of McGill University and the Native Friendship Centre of Montreal, a Native-run urban community-based service organization. The aims of the study were to examine substance abuse as well as physical and mental health among an urban Aboriginal population. The nature and severity of drug or alcohol problems in this population were explored. Data was collected through structured interviews with urban Aboriginal people in the greater Montreal area (n = 202). Results indicate that the majority of the sample were single, unemployed, and had lived in the urban area for a long time (mean of 9.96 V .76 years). Approximately two thirds of the sample were current alcohol drinkers and cigarette smokers and one third of the sample reported having a current drug or alcohol problem. Results indicate that individuals who abused substances were more likely to live with someone who had a drug or alcohol problem. Substance abusers also had a greater history of legal problems with more convictions, time spent in jail, and were more likely to be on probation or parole. A large proportion of the sample reported having significant medical problems that required treatment, and substance abusers were less likely to have identification needed to access medical services. Results indicated high levels of psychological distress in the general sample (depression, anxiety, suicidal ideation, attempted suicide). These phenomena were augmented by substance abuse problems. In particular, substance abusers had a history of more suicide attempts, and were more likely to have been the victims of abuse.

Sensitivity of AXB/BXA recombinant inbred lines of mice to the locomotor activating effects of cocaine: a quantitative trait loci analysis.

The present study was conducted in order to characterize putative quantitative trait loci (QTL) for cocaine-induced activation in the AXB/BXA recombinant inbred (RI) lines of mice. Locomotor activity was measured in the AXB/BXA and progenitor A/J and C57BL/6J strains using a computerized open-field apparatus following saline or cocaine (0, 5, 10, 20 mg/kg) administration (i.p.). Analyses were conducted on phenotypes including both novelty (responses under initial saline conditions) and cocaine-induced locomotor activity. Significant differences were observed across RI lines on all measures. Gender differences in sensitivity to the activating effects of cocaine were not observed. The wide and continuous distributions of phenotypic responses in the AXB/BXA RI lines suggested polygenic regulation. Initial basal locomotor activity was significantly correlated with cocaine-induced activation (raw scores) (r = 0.60, P = 0.0021) but not with cocaine difference scores (r = 0.370, P = 0.082). Simple regression and interval mapping were used to initially identify significant gene markers associated with novelty and cocaine-induced activation. Subsequently, composite interval mapping was used to increase the accuracy in mapping individual loci. QTL analysis of cocaine-induced activation (difference scores--20 mg/kg dose) identified significant loci on chromosomes 12 (23 cM), and 15 (46.8 cM). The significant QTLs were identified on chromosomes 12 and 15 map to regions in proximity to genes for the somatostatin 1 (Smstr1 -23 cM) and 3 (Smstr3 -46.3 cM) receptors, respectively. Further research employing AcB/BcA recombinant congenic lines of mice will be employed to confirm the QTL on chromosomes 12 and 15 identified in the present study.

Utilizing buprenorphine–naloxone to treat illicit and prescription-opioid dependence

Objectives To review current evidence on buprenorphine–naloxone (bup/nx) for the treatment of opioid-use disorders, with a focus on strategies for clinical management and office-based patient care. Quality of evidence Medline and the Cochrane Database of Systematic Reviews were searched. Consensus reports, guidelines published, and other authoritative sources were also included in this review. Apart from expert guidelines, data included in this review constitute level 1 evidence. Findings Bup/nx is a partial μ-opioid agonist combined with the opioid antagonist naloxone in a 4:1 ratio. It has a lower abuse potential, carries less stigma, and allows for more flexibility than methadone. Bup/nx is indicated for both inpatient and ambulatory medically assisted withdrawal (acute detoxification) and long-term substitution treatment (maintenance) of patients who have a mild-to-moderate physical dependence. A stepwise long-term substitution treatment with regular monitoring and follow-up assessment is usually preferred, as it has better outcomes in reducing illicit opioid use, minimizing concomitant risks such as human immunodeficiency virus and hepatitis C transmission, retaining patients in treatment and improving global functioning. Conclusion Bup/nx is safe and effective for opioid detoxification and substitution treatment. Its unique pharmaceutical properties make it particularly suitable for office-based maintenance treatment of opioid-use disorder.