Solid state NMR analysis of polypyrrole grown in a phosphonium ionic liquid

³¹P, ¹⁹F and ¹³C solid state NMR analysis has been used to investigate the intercalation/de-intercalation of both anions and cations in electrochemically synthesized polypyrrole films. Use of a phosphonium-based ionic liquid, tri(hexyl)(tetradecyl)phosphonium bis(trifluoromethanesulfonyl)amide, allows the separate detection of the cation and anion by analysis of the phosphorous and fluorine resonances, respectively. Initial results indicate the incorporation of both cations and anions during film growth in the ionic liquid. There is a notable change in the ³¹P chemical shift of the cation on incorporation into the film, consistent with a significant change in environment compared to the pure ionic liquid. Despite its large size, the phosphonium cation can be completely expelled from the film by oxidation.

Alcohol expectancies and drinking refusal self-efficacy mediate the association of impulsivity with alcohol misuse

Background: Recent work suggests that 2 biologically based traits convey risk for alcohol misuse: reward sensitivity ⁄ drive and (rash) impulsiveness. However, the cognitive mechanisms through which these traits convey risk are unclear. This study tested a model predicting that the risk conveyed by reward sensitivity is mediated by a learning bias for the reinforcing outcomes of alcohol consumption (i.e., positive alcohol expectancy). The model also proposed that the risk conveyed by rash impulsiveness (RI) is mediated by drinkers’ perceived ability to resist alcohol (i.e., drinking refusal self-efficacy).
Methods: Study 1 tested the model in a sample of young adults (n = 342). Study 2 tested the model in a sample of treatment-seeking substance abusers (n = 121). All participants completed a battery of personality, cognitive, and alcohol use questionnaires and models were tested using structural equation modeling.
Results: In both studies, the hypothesized model was found to provide a good fit to the data, and a better fit than alternative models. In both young adults and treatment-seeking individuals, positive alcohol expectancy fully mediated the association between reward sensitivity and hazardous alcohol use. For treatment seekers, drinking refusal self-efficacy fully mediated the association between RI and hazardous drinking. However, there was partial mediation in the young adult sample. Furthermore, neither trait was directly associated with the other cognitive mediator.
Conclusions: The hypothesized model was confirmed on a large sample of young adults and replicated on a sample of treatment-seeking substance abusers. Taken together, these findings shed further light on the mechanisms through which an impulsive temperament may convey risk for alcohol misuse.

Association of high-sensitivity C-reactive protein with de novo major depression

Background: Although there is cross-sectional evidence that changes in the immune system contribute to the pathophysiology of depression, longitudinal data capable of elucidating cause and effect relationships are lacking.

Aims: We aimed to determine whether subclinical systemic inflammation, as measured by serum high-sensitivity C-reactive protein (hsCRP) concentration, is associated with an increased risk of de novo major depressive disorder.

Method: Major depressive disorder was diagnosed using a clinical interview (SCID-I/NP). This is a retrospective cohort study; from a population-based sample of 1494 randomly selected women recruited at baseline during the period 1994-7, 822 were followed for a decade and provided measures of both exposure and outcome. Of these women, 644 (aged 20-84 years) had no prior history of depression at baseline and were eligible for analysis.

Results: During 5827 person-years of follow-up, 48 cases of de novo major depressive disorder were identified. The hazard ratio (HR) for depression increased by 44% for each standard deviation increase in log-transformed hsCRP (ln-hsCRP) (HR = 1.44, 95% CI 1.04-1.99), after adjusting for weight, smoking and use of non-steroidal anti-inflammatory drugs. Further adjustment for other lifestyle factors, medications and comorbidity failed to explain the observed increased risk for depression.

Conclusions: Serum hsCRP is an independent risk marker for de novo major depressive disorder in women. This supports an aetiological role for inflammatory activity in the pathophysiology of depression.

Association of adolescent symptoms of depression and anxiety with alcohol use disorders in young adulthood : findings from the Victorian Adolescent Health Cohort Study

Objective: To examine the association of adolescent depression and anxiety symptoms with alcohol abuse or dependence in young adulthood.

Design, setting and participants: Cohort study of the health and wellbeing of adolescents and young adults in Victoria, assessed at 8 waves (periods) of data collection, from age 14 to 24 years, between 1992 and 2003. Young people who participated in the cohort study at least once during the six adolescent assessment points (conducted 6 months apart, from age 14 to 17 years), at least once during young adulthood and who were alive at Wave 8 (n = 1758).

Main outcome measure: Alcohol abuse or dependence assessed using the alcohol and substance abuse modules of the Composite International Diagnostic Interview at age 24 years.

Results: Adolescents with moderate to high levels of depression and anxiety symptoms (measured by the revised Clinical Interview Schedule) had an increased risk of alcohol abuse or dependence in young adulthood, compared with young adults with low levels of adolescent depression and anxiety symptoms, after adjusting for potential confounding factors. Risk was higher for those with symptoms at more than two adolescent assessment points (odds ratio [OR] 1.9; 95% CI, 1.7–2.0) and for those with symptoms at one or two assessment points (OR 1.3; 95% CI, 1.2–1.4), compared with those with no above-threshold symptoms in adolescence.

Conclusions: Adolescents with depression and anxiety symptoms are at increased risk for alcohol use disorders into young adulthood. They warrant vigilance from primary care providers in relation to alcohol use well into adulthood.

Association of adolescent symptoms of depression and anxiety with daily smoking and nicotine dependence in young adulthood : findings from a 10-year longitudinal study

Aims To examine the association of adolescent depression and anxiety symptoms with daily smoking and nicotine dependence in young adulthood.

Design A prospective cohort study of adolescent and young adult health (n = 1943). Teen assessments occurred at 6-monthly intervals, with two follow-up assessments in young adulthood (wave 7, 1998; wave 8, 2001–03).

Setting Victoria, Australia.

Participants Students who participated at least once during the first six (adolescent) waves of the cohort study.

Measurements Adolescent depression and anxiety symptomswere assessed using the Revised Clinical Interview Schedule (CIS-R).Young adult tobacco usewas defined as: daily use (6 or 7 days perweek) and dependent use (>4 on the Fagerstrom Test for Nicotine Dependence).

Findings Among adolescent ‘less than daily’ smokers, those with high levels of depression and anxiety symptoms had an increased risk of reporting nicotine dependence in young adulthood [odds ratio (OR) 3.3, 95% confidence interval (CI) 1.2–9.1] compared to young adults who had low levels of adolescent depression and anxiety symptoms, after adjusting for potential confounding factors. Similarly, in the adjusted model (OR 1.9, 95% CI 1.0–3.4), among adolescent ‘daily’ smokers, those with high levels of depression and anxiety symptoms had an almost two-fold increase in the odds of reporting nicotine dependence in young adulthood compared to young adults with low levels of adolescent depression and anxiety symptoms.

Conclusions Adolescent smokerswith depression and anxiety symptoms are at increased risk for nicotine dependence into young adulthood. They warrant vigilance from primary care providers in relation to tobacco use well into adulthood.

Association of risky alcohol consumption and accreditation in the 'Good Sports' alcohol management programme

Background Involvement in community sports clubs is often associated with high levels of risky alcohol consumption; however, developing prevention-focused interventions in these settings can be complex. We examined the association of reduced risky alcohol consumption with the implementation of the Good Sports Programme (GSP)—a programme that accredits clubs in three stages, on the basis of their implementation of alcohol-related harm reduction strategies.

Methods Using a cross section of football and cricket clubs, consumption was compared between clubs accredited at level 1, 2 or 3 of the GSP and clubs not accredited (92 clubs; 1924 individuals). Drinking above Australian guidelines for short-term risk (more than four standard drinks) on the last playing day prior to the survey and drinking at the club over the last 12 months at average levels exceeding short- and long-term risk (more than two standard drinks) guidelines were also examined.

Results Multilevel modelling indicated that higher accreditation stage (0, 1, 2, 3) was associated with a 0.79 reduction in the odds of risky consumption on the playing day; a 0.85 reduction in the odds for short-term risky drinking, and a 0.86 reduction in long-term risky drinking.

Conclusions The findings suggest that higher accreditation in the GSP is associated with reduced rates of risky alcohol use at a population level.

State-related alterations of gene expression in bipolar disorder : a systematic review

Objective:  Alterations in gene expression in bipolar disorder have been found in numerous studies. It is unclear whether such alterations are related to specific mood states. As a biphasic disorder, mood state-related alterations in gene expression have the potential to point to markers of disease activity, and trait-related alterations might indicate vulnerability pathways. This review therefore evaluated the evidence for whether gene expression in bipolar disorder is state or trait related.

Methods:  A systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline for reporting systematic reviews, based on comprehensive database searches for studies on gene expression in patients with bipolar disorder in specific mood states, was conducted. We searched Medline, Embase, PsycINFO, and The Cochrane Library, supplemented by manually searching reference lists from retrieved publications.

Results:  A total of 17 studies were included, comprising 565 patients and 418 control individuals. Six studies evaluated intraindividual alterations in gene expression across mood states. Two of five studies found evidence of intraindividual alterations in gene expression between a depressed state and a euthymic state. No studies evaluated intraindividual differences in gene expression between a manic state and a euthymic state, while only one case study evaluated differences between a manic state and a depressed state, finding altered expression in seven genes. No study investigated intraindividual variations in gene expression between a euthymic state and multiple states of various polarities (depressive, manic, hypomanic). Intraindividual alterations in expression of the same genes were not investigated across studies. Only one gene (the brain-derived neurotrophic factor gene; BDNF) was investigated across multiple studies, showing no alteration between bipolar disorder patients and control individuals.

Conclusions:  There is evidence of some genes exhibiting state-related alterations in expression in bipolar disorder; however, this finding is limited by the lack of replication across studies. Further prospective studies are warranted, measuring gene expression in various affective phases, allowing for assessment of intraindividual differences.

Association of differential gene expression with imatinib mesylate and omacetaxine mepesuccinate toxicity in lymphoblastoid cell lines

Background

Imatinib mesylate is currently the drug of choice to treat chronic myeloid leukemia. However, patient resistance and cytotoxicity make secondary lines of treatment, such as omacetaxine mepesuccinate, a necessity. Given that drug cytotoxicity represents a major problem during treatment, it is essential to understand the biological pathways affected to better predict poor drug response and prioritize a treatment regime.
Methods

We conducted cell viability and gene expression assays to determine heritability and gene expression changes associated with imatinib and omacetaxine treatment of 55 non-cancerous lymphoblastoid cell lines, derived from 17 pedigrees. In total, 48,803 transcripts derived from Illumina Human WG-6 BeadChips were analyzed for each sample using SOLAR, whilst correcting for kinship structure.
Results

Cytotoxicity within cell lines was highly heritable following imatinib treatment (h2 = 0.60-0.73), but not omacetaxine treatment. Cell lines treated with an IC20 dose of imatinib or omacetaxine showed differential gene expression for 956 (1.96%) and 3,892 transcripts (7.97%), respectively; 395 of these (0.8%) were significantly influenced by both imatinib and omacetaxine treatment. k-means clustering and DAVID functional annotation showed expression changes in genes related to kinase binding and vacuole-related functions following imatinib treatment, whilst expression changes in genes related to cell division and apoptosis were evident following treatment with omacetaxine. The enrichment scores for these ontologies were very high (mostly >10).
Conclusions

Induction of gene expression changes related to different pathways following imatinib and omacetaxine treatment suggests that the cytotoxicity of such drugs may be differentially tolerated by individuals based on their genetic background.