Changes in Cathepsin D and Beclin-1 mRNA and protein expression by the excitotoxin quinolinic acid in human astrocytes and neurons

Quinolinic acid (QUIN) is an excitotoxin that has been implicated in the pathogenesis of several neurodegenerative diseases including Alzheimer’s disease (AD). While QUIN has been shown to induce neuronal and astrocytic apoptosis as well as excitotoxic cell death, other mechanisms such as autophagy remain unexplored. We investigated the role of Cathepsin D (CatD) and Beclin-1 (Bc1) in QUIN-treated primary human astrocytes and neurons. We demonstrated that the expression patterns of CatD, a lysosomal aspartic protease associated with autophagy, are increased at 24 h after QUIN treatment. However, unlike CatD, the expression patterns of Bc1, a tumour suppressor protein, are significantly reduced at 24 h after QUIN treatment in both brain cell types. Furthermore, we showed that the NMDA ion channel blockers, MK801, can attenuate QUIN-induced changes CatD and Bc1 expression in both astrocytes and neurons. Taken together, these results suggest that induction of deficits in CatD and Bc1 is a significant mechanism for QUIN toxicity in glial and neuronal cells. Maintenance of autophagy may play a crucial role in neuroprotection in the setting of AD.     

Medical education in substance-related disorders: components and outcome

Aims. To analyze the process of acquisition by physicians of a body of knowledge and skills in the management of substance abuse. Design. A comprehensive search of English-speaking literature was conducted over 20 years. Articles assessing the outcome of educational strategies in undergraduate, graduate and continuing medical education were examined to determine the targeted sample, the educational strategies involved and the outcomes assessed. Findings. Nine studies in undergraduate education, 11 in graduate and 11 in continuing education met the inclusion criteria. They were generally difficult to compare in design, strategy and outcome analysis. Cognitive knowledge and behavioral skills appear to be easier to obtain compared to more complex attitudinal shifts. Conclusions. There is growing consensus in the selection of a combined didactic and interactive educational strategy but few empirical data as to the more cost-effective learning interventions. Training must be reinforced at regular intervals. While the expanding panoply of interventions available to physicians should enhance the perceptions of role legitimacy and treatment optimism, cohort studies across levels of education, specialty groups and across-substance and other addictive behaviors are required to determine cost-effective educational strategies.     

Alcoholism: beliefs and attitudes among Canadian alcoholism treatment practitioners.

OBJECTIVES: To explore differences in views concerning adjunctive medications and theoretical orientation among Canadian practitioners from different professional backgrounds who treat alcoholism. METHODS: A survey of clinicians from different disciplines was conducted by mail. The response rate was 56%: 95 drug and alcohol counsellors, 46 social workers, 81 nonpsychiatrist addiction physicians, and 74 addiction psychiatrists. The number of items in the questionnaire was reduced using principal component analysis. Group differences were explored using analysis of variance with Bonferroni correction and Scheffé's posthoc comparisons. RESULTS: Physicians and nonphysicians differed in their views on the utility of medications in treating alcohol problems, the disease concept of alcohol problems, and the classification of alcohol abuse or dependence as psychiatric conditions. No group differences emerged on views regarding cognitive-behavioural treatment, pharmacological-only interventions, combined treatment, and recovery without treatment. Psychopathology in the alcoholic was significantly more likely to be considered as secondary to the use of alcohol by nonpsychiatrist physicians. Nonphysician practitioners viewed alcoholic behaviour as self-medication. CONCLUSIONS: Groups differed on questionnaire items concerning medication use and the disease concept of alcoholism. Agreement on several areas may facilitate bridging the gap across disciplines. The implications of these results are discussed.     

Psychometric evaluation of the Children of Alcoholics Screening Test (CAST) in a psychiatric sample.

The Children of Alcoholics Screening Test (CAST) is a 30-item screening instrument developed to identify children who are either living with or have lived with alcoholic parents. In a sample of 250 psychiatric patients, the CAST exhibited substantial item-total scale correlations and a high level of internal consistency reliability. Total CAST scores discriminated self-identified children of problem drinkers from control subjects and were significantly correlated with the severity of parental psychological and social complications due to alcohol misuse. Factor analysis indicated a unidimensional scale structure. CAST cut-off scores produced a low false positive and false negative rate. The psychometric properties of the CAST suggest that it is a useful screening instrument for identifying the offspring of problem drinkers and alcoholics.     

Comorbidity of major depression with substance use disorders.

OBJECTIVES: In the Canadian adult population, we aimed to 1) estimate the 12-month prevalence of major depressive disorder (MDD) in persons with a diagnosis of harmful alcohol use, alcohol dependence, and drug dependence; 2) estimate the 12-month prevalence of harmful alcohol use, alcohol dependence, and drug dependence in persons with a 12-month and lifetime diagnosis of MDD; 3) identify socioeconomic correlates of substance use disorder-major depression comorbidity; 4) determine how comorbidity impacts the prevalence of suicidal thoughts; and 5) determine how comorbidity affects mental health care used. METHODS: We examined data from the Canadian Community Health Survey: Mental Health and Well-Being (CCHS 1.2). RESULTS: The 12-month prevalences of MDD in persons with a substance use disorder (SUD) were 6.9% for harmful alcohol use (95% confidence interval [CI], 5.2 to 8.5), 8.8% for alcohol dependence (95%CI, 6.6 to 11.0), and 16.1% for drug dependence (95%CI, 10.3 to 21.9). Conversely, the 12-month prevalences of harmful alcohol use, alcohol dependence, and drug dependence in persons with a 12-month diagnosis of MDD were 12.3% (95%CI, 9.4 to 15.2), 5.8% (95%CI, 4.3 to 7.3), and 3.2% (95%CI, 2.0 to 4.4), respectively. Regression modelling did not identify any socioeconomic predictors of SUD-MDD comorbidity. Substance dependence and MDD independently predicted higher prevalence of suicidal thoughts and mental health treatment use. CONCLUSIONS: SUDs cooccur with a high frequency in cases of MDD. Clinicians and mental health services should consider routine assessment of SUDs in depression patients.     

Help-seeking behaviours of individuals with mood disorders.

OBJECTIVES: This study had the following objectives: 1) to estimate the 12-month prevalence of conventional and unconventional mental health service use by individuals with major depressive disorder (MDD) or mania in the past year, and 2) to identify factors associated with the use of conventional mental health services by individuals with MDD or mania in the past year. METHODS: We examined data from the Canadian Community Health Survey: Mental Health and Well-Being (CCHS 1.2). Respondents with MDD (n = 1563) or manic episodes (n = 393) in the past 12 months were included in this analysis. RESULTS: An estimated 63.9% of respondents with MDD and 59.0% of those with manic episodes reported having used some type of help in the past 12 months; 52.9% of those with MDD and 49.0% of those with manic episodes used conventional mental health services. Approximately 21% of respondents with either MDD or manic episodes used natural health products specifically for emotional, mental health, and drug or alcohol use problems. Respondents who reported comorbid anxiety disorders and long-term medical conditions were more likely to have used conventional mental health services. CONCLUSIONS: Relative to previous Canadian literature, our analysis suggests that the frequency of conventional mental health service use among persons with MDD has not increased significantly in the past decade. Further, the rate of conventional mental health service use by persons with manic episodes is unexpectedly low. These findings may reflect the lack of national initiatives targeting mood disorders in Canada. They have important implications for planning future education, promotion, and research efforts.     

Genetics and alcoholism: how close are we to potential clinical applications?

Rapid advancement of genetic knowledge has provided a wealth of data demonstrating a significant contribution of genes to the development of alcoholism but has suggested little in the way of clinical applicability. Twin and adoption studies suggest that 50% to 60% of the development of alcoholism is due to heritable factors, and linkage and association studies have identified chromosomal regions and individual genes that likely contribute to the development of this condition. Most of these genes are related to neurotransmitter systems and to alcohol metabolizing enzymes. We briefly review the evidence for this before discussing intermediate phenotypes of alcoholism under genetic control, pharmacogenetic aspects of alcoholism treatment, and the possibility of future clinical applications based on these areas.     

Personal Variables and the Attitudes of Medical Students Toward Substance Abuse

Medical students at The University of Calgary were surveyed about their experiences with and attitudes toward alcohol abuse using the Children of Alcoholics Screening Test (CAST), the Codependency Assessment Inventory (CDAI), the CAGE's four questions, and the Substance Abuse Attitude Survey (SAAS). Nineteen percent of the 110 respondents showed strong evidence that they were the offspring of alcoholics (CAST ≥ 6), 22% reported strong codependency traits (CDAI ≥ 30), and 22% showed evidence of alcohol problems (CAGE ≥ 2). Among the five subscales of the SAAS, three showed a significant amount of variance determined by the personal variables investigated.