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Telomeres are DNA-protein complexes that cap linear DNA strands, protecting DNA from damage. When telomeres critically shorten, cells become susceptible to senescence and apoptosis. Telomerase, a cellular ribonucleoprotein enzyme, rebuilds the length of telomeres and promotes cellular viability. Leukocyte telomeres are reportedly shortened in major depression, but telomerase activity in depression has not been previously reported. Further, there are no published reports of the effects of antidepressants on telomerase activity or on the relationship between telomerase activity and antidepressant response. Peripheral blood mononuclear cell (PBMC) telomerase activity was assessed in 20 medication-free depressed individuals and 18 controls. In total, 16 of the depressed individuals were then treated with sertraline in an open-label manner for 8 weeks, and PBMC telomerase activity was reassessed in 15 of these individuals after treatment. Pre- and post-treatment symptom severity was rated with the Hamilton Depression Rating Scale. All analyses were corrected for age and sex. Pre-treatment telomerase activity was significantly elevated in the depressed individuals compared with the controls (P=0.007) and was directly correlated with depression ratings (P<0.05) across all subjects. In the depressed group, individuals with relatively lower pre-treatment telomerase activity and with relatively greater increase in telomerase activity during treatment, showed superior antidepressant responses (P<0.05 and P<0.005, respectively). This is the first report characterizing telomerase activity in depressed individuals. PBMC telomerase activity might reflect a novel aspect of depressive pathophysiology and might represent a novel biomarker of antidepressant responsiveness. [ABSTRACT FROM AUTHOR]

NicVAX, a nicotine vaccine (3′AmNic-rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double-blinded, placebo-controlled multicenter clinical trial (N = 301 smokers) tested the results of 200- and 400-µg doses administered four or five times over a period of 6 months, as compared with placebo. 3′AmNic-rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five-injection, 400-µg dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3′AmNic-rEPA elicits Abs to nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for nicotine dependence is therefore justified. [ABSTRACT FROM AUTHOR]

Aims: Nicotine addiction is a complex, chronic condition with physiological and psychological/behavioural aspects that make smoking cessation extremely difficult. This paper reviews current recommendations for smoking cessation and the efficacy of pharmacotherapy and behavioural modification techniques, used either alone or in combination, for smoking cessation. Results: Abstinence rates for pharmacotherapies range from ∼16% to ∼30% at 1-year follow-up, with efficacy odds ratios (ORs) compared with placebo of ∼1.7 for nicotine replacement therapy (NRT), ∼1.9 for bupropion sustained release and ∼3.0 for varenicline. Behaviour modification therapies have achieved quit rates of between 8% and 43% for up to 1 year, with ORs in comparison to no treatment of between ∼1.2 and ∼2.2. No direct comparisons have been made between pharmacotherapy alone and psychological behaviour strategies alone. However, combining physiological approaches with counselling significantly increases the odds of quitting compared with either technique alone. Conclusions: Applying multimodal techniques for the treatment of nicotine addiction is the recommended approach and has demonstrated the potential to improve rates of permanent abstinence in smokers attempting cessation. While the numbers of patients receiving help and advice regarding smoking cessation is increasing, the multimodal approach appears to be currently underutilised by clinicians and therefore smoking cessation strategies are not being optimised. [ABSTRACT FROM AUTHOR]

Multiple, controlled clinical trials support the efficacy of nortriptyline as a smoking cessation agent. Although therapeutic plasma nortriptyline concentrations (PNCs) are known for the treatment of depression, little is known about PNCs in smoking cessation treatment. PNCs from three randomized, placebo-controlled smoking cessation trials (N=244) were analyzed both separately and pooled. PNCs normalized for dose and weight were associated with cigarettes per day and race, but not with sex or age. Greater smoking was associated with decreased normalized PNCs. In addition, both Asian and black populations had significantly higher normalized PNCs than the white populations. Weak and inconsistent associations between PNCs and self-reported side effects were observed. PNCs were linearly related to end of treatment and long-term biochemically verified smoking abstinence. Maximum therapeutic effects were observed over a range of plasma concentrations somewhat lower than those found effective for the treatment of depression.Clinical Pharmacology & Therapeutics (2008) 83, 3, 436–442.doi: 10.1038/sj.clpt.6100307 [ABSTRACT FROM AUTHOR]

Background: Self injurious behaviour (SIB), the deliberate, repetitive infliction of self harm, is present in a wide variety of neuropsychiatric disorders, including Tourette syndrome (TS). Although SIB occurs in up to 60% of individuals with TS, and can cause significant clinical impairment and distress, little is known about its aetiology.Objective: This study examined the relationship between SIB and other behavioural features that commonly co-occur with TS in nearly 300 subjects with TS participating in three genetic studies. SIB, obsessions, compulsions, tic severity, attention deficit hyperactivity disorder related impulsivity, risk taking behaviours, and rages were systematically assessed in all subjects.Methods: Using logistic regression, a best fit model was determined for both mild to moderate SIB and severe SIB.Results: Mild/moderate SIB in TS was correlated with the presence of obsessive and compulsive symptoms such as the presence of aggressive obsessions or violent or aggressive compulsions, and with the presence of obsessive-compulsive disorder and overall number of obsessions. Severe SIB in TS was correlated with variables related to affect or impulse dysregulation; in particular, with the presence of episodic rages and risk taking behaviours. Both mild/moderate and severe SIB were also correlated with tic severity.Conclusions: This study suggests that mild/moderate and severe SIB in TS may represent different phenomena, which has implications for clinical management of these symptoms. [ABSTRACT FROM AUTHOR]

Attitudes about bipolar disorder (manic depressive disorder) and genetic testing were investigated. Three groups of subjects were surveyed including members of a manic depressive support group, medical students, and psychiatry residents. The questionnaire was intended to elicit impressions and attitudes about bipolar disorder (BP) from mental health consumers and health care providers with varying levels of personal and professional familiarity with the disorder. Attitudes towards prenatal testing and pregnancy termination were also assessed. The intention hypothetically to terminate a pregnancy was influenced by the likelihood of developing BP a well as the projected course and severity of illness. Nearly half of the total sample would terminate pregnancy if the fetus were definitely to develop an unspecified form of bipolar disorder. Presumed severity of illness was also found to be a modifying factor in the decision, with a low percentage of subjects electing to terminate for a mild course of bipolar disorder and a majority opting for termination in the case of an extremely severe presentation. Support group members were the least likely to terminate a hypothetical pregnancy in the case of a positive prenatal test and were the most likely to desire childhood testing in the absence of preventive or treatment options. The possible implications of these findings, as well as avenues of future research, are discussed. [ABSTRACT FROM PUBLISHER]

The lowering of high serum cholesterol levels may be associated with increased non-cardiac mortality due to behavioral changes, although such endpoints are likely rare. This current study sought to determine if hormonal changes accompany pharmacologically induced decreases in serum cholesterol levels. Cholesterol, dopamine, homovanillic acid (HVA), serotonin, 5-HIAA, testosterone, cortisol and pregnenolone were measured at baseline and after 4 weeks of treatment. Subjects’ cholesterol levels significantly declined within 4 weeks. Concomitant significant increase in dopamine and HVA were noted. Although this study is limited in size, it raises the possibility that cholesterol-lowering drug treatment is associated with hormonal perturbations. [ABSTRACT FROM AUTHOR]