Daily functioning and symptom factors contributing to attitudes toward antipsychotic treatment and treatment adherence in outpatients with schizophrenia spectrum disorders

Background: Poor adherence and negative attitudes to treatment are common clinical problems when treating psychotic disorders. This study investigated how schizophrenia core symptoms and daily functioning affect treatment adherence and attitudes toward antipsychotic medication and to compare patients using clozapine or other antipsychotics. Method: A cross-sectional study with data from 275 patients diagnosed with schizophrenia spectrum disorder. Patients adherence, attitudes, insight and side-effects were evaluated using the Attitudes toward Neuroleptic Treatment scale. Overall symptomology was measured using the Brief Psychiatric Rating Scale (BPRS), the Health of the Nation Outcome Scale (HoNOS). The functioning was assessed using activities of daily living scale, instrumental activities of daily living scale and social functioning of daily living scale. Results: Self-reported treatment adherence was high. Of the patients, 83% reported using at least 75% of the prescribed medication. Having more symptoms was related with more negative attitude towards treatment. There was a modest association with functioning and treatment adherence and attitude toward antipsychotic treatment. Attitudes affected on adherence in non-clozapine but not in clozapine groups. Conclusion: Early detection of non-adherence is difficult. Systematic evaluation of attitudes toward the treatment could be one way to assess this problem, along with optimized medication, prompt evaluation of side effects and flexible use of psychosocial treatments.Peer reviewe

TPH1A218C polymorphism and temperament in major depression

BACKGROUND: In major depression, one of the candidate genes possibly affecting the risk and severity of symptoms has been found to be tryptophan hydroxylase (TPH1). Variation in treatment response to antidepressive agents according to TPH1 genotype has also been found in several studies. However, the relationship between temperament and TPH1 genotype in major depression is poorly understood, as only one study has been published so far. There are no earlier studies on the interaction between temperament traits, antidepressive medication response and TPH1 genotype. This interaction was studied in 97 subjects with major depression treated for six weeks with selective serotonine reuptake inhibitors. METHODS: Temperament dimensions Harm Avoidance (HA), Novelty Seeking (NS), Reward Dependence (RD) and Persistence (P) scores at baseline (1) and endpoint (2) were rated with the Temperament and Character Inventory (TCI) and compared between TPH1 A218C genotypes. Multivariate analysis of co-variance (MANCOVA) was used to analyze the interaction between the TPH1 genotype, treatment response and the different temperament dimensions at baseline and endpoint. In the analysis model, treatment response was used as a covariate and TPH1 genotype as a factor. A post hoc analysis for an interaction between remission status and TPH1 A218C genotype at endpoint HA level was also performed. RESULTS: The number of TPH1 A-alleles was associated with increasing levels in NS1 and NS2 scores and decreasing levels in HA1 and HA2 scores between TPH1 A218C genotypes. In the MANCOVA model, TPH1 genotype and treatment response had an interactive effect on both HA1 and HA2 scores, and to a lesser degree on NS2 scores. Additionally, an interaction between remission status and TPH1 A218C genotype was found to be associated with endpoint HA score, with a more marked effect of the interaction between CC genotype and remission status compared to A-allele carriers. CONCLUSIONS: Our results suggest that in acute depression TPH1 A218C polymorphism and specifically the CC genotype together with the information on remission or treatment response differentiates between different temperament profiles and their changes

Attitudes to antipsychotic drugs and their side effects: a comparison between general practitioners and the general population

BACKGROUND: Attitudes towards antipsychotic medication play an important part in the treatment for schizophrenia and related disorders. We aimed measuring general practitioners' attitudes to antipsychotic drugs and their adverse side effects and comparing these with the attitudes of the general population. METHODS: Analysis and comparison of two representative samples, one comprising 100 General Practitioners (GPs), the other 791 individuals randomly selected from the general population. The setting was the German speaking cantons of Switzerland. RESULTS: General practitioners have significantly more positive attitudes towards anti-psychotic drugs than the general public. They reject widespread prejudices about the use of anti-psychotic medication significantly more than the general population. In particular the risk of dependency was assessed as 'low' by GP's (80%), in contrast to only 18% of the general population sample. In no instance did a majority of the GPs advise not tolerating any of the 10 possible adverse effects presented in this study. This is in marked contrast to the general population sample, where a majority recommended discontinuation for movement disorder (63%), strong tremor (59%), risk of dependency (55%) and feelings of unrest (54%). CONCLUSION: As well as effective management of side-effects being a vital aspect of patient and carer education, prescribing doctors need to be aware that their mentally ill patients are likely to be confronted with extremely negative public attitudes towards antipsychotic medication and with strong pressures to stop taking their medication in the event of side-effects

Association of Adherence to a Healthy Diet with Cognitive Decline in European and American Older Adults

Aim: To examine the association between a healthy diet, assessed by the Healthy Diet Indicator (HDI), and cognitive decline in older adults. Methods: Data from 21,837 participants aged ≥ 55 years from 3 cohorts (Survey in Europe on Nutrition and the Elderly, a Concerted Action[SENECA], Rotterdam Study [RS], Nurses’ Health Study [NHS]) were analyzed. HDI scores were based on intakes of saturated fatty acids, polyunsaturated fatty acids, mono- and disaccharides, protein, cholesterol, fruits and vegetables, and fiber. The Telephone Interview for Cognitive Status in NHS and Mini-Mental State Examination in RS and SENECA were used to assess cognitive function from multiple repeated measures. Using multivariable-adjusted, mixed linear regression, mean differences in annual rates of cognitive decline by HDI quintiles were estimated. Results: Multivariable-adjusted differences in rates in the highest versus the lowest HDI quintile were 0.01 (95% CI –0.01, 0.02) in NHS, 0.00 (95% CI –0.02, 0.01) in RS, and 0.00 (95% CI –0.05, 0.05) in SENECA with a pooled estimate of 0.00 (95% CI –0.01, 0.01), I 2 = 0%. Conclusions: A higher HDI score was not related to reduced rates of cognitive decline in European and American older adults

Safety and Immunogenicity of ChAd63 and MVA ME-TRAP in West African Children and Infants.

Malaria remains a significant global health burden and a vaccine would make a substantial contribution to malaria control. Chimpanzee Adenovirus 63 Modified Vaccinia Ankara Multiple epitope thrombospondin adhesion protein (ME-TRAP) and vaccination has shown significant efficacy against malaria sporozoite challenge in malaria-naive European volunteers and against malaria infection in Kenyan adults. Infants are the target age group for malaria vaccination; however, no studies have yet assessed T-cell responses in children and infants. We enrolled 138 Gambian and Burkinabe children in four different age-groups: 2-6 years old in The Gambia; 5-17 months old in Burkina Faso; 5-12 months old, and also 10 weeks old, in The Gambia; and evaluated the safety and immunogenicity of Chimpanzee Adenovirus 63 Modified Vaccinia Ankara ME-TRAP heterologous prime-boost immunization. The vaccines were well tolerated in all age groups with no vaccine-related serious adverse events. T-cell responses to vaccination peaked 7 days after boosting with Modified Vaccinia Ankara, with T-cell responses highest in 10 week-old infants. Heterologous prime-boost immunization with Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara ME-TRAP was well tolerated in infants and children, inducing strong T-cell responses. We identify an approach that induces potent T-cell responses in infants, which may be useful for preventing other infectious diseases requiring cellular immunity

Circulating B-vitamin biomarkers and B-vitamin supplement use in relation to quality of life in patients with colorectal cancer: results from the FOCUS consortium

Background: B vitamins have been associated with the risk and progression of colorectal cancer (CRC), given their central roles in nucleotide synthesis and methylation, yet their association with quality of life in established CRC is unclear.Objectives: To investigate whether quality of life 6 months postdiagnosis is associated with: 1) circulating concentrations of B vitamins and related biomarkers 6 months postdiagnosis; 2) changes in these concentrations between diagnosis and 6 months postdiagnosis; 3) B-vitamin supplement use 6 months postdiagnosis; and 4) changes in B-vitamin supplement use between diagnosis and 6 months postdiagnosis.Methods: We included 1676 newly diagnosed stage I-III CRC patients from 3 prospective European cohorts. Circulating concentrations of 9 biomarkers related to the B vitamins folate, riboflavin, vitamin B6, and cobalamin were measured at diagnosis and 6 months postdiagnosis. Information on dietary supplement use was collected at both time points. Health-related quality of life (global quality of life, functioning scales, and fatigue) was assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 6 months postdiagnosis. Confounder-adjusted linear regression analyses were performed, adjusted for multiple testing.Results: Higher pyridoxal 5'-phosphate (PLP) was cross-sectionally associated with better physical, role, and social functioning, as well as reduced fatigue, 6 months postdiagnosis. Associations were observed for a doubling in the hydroxykynurenine ratio [3-hydroxykynurenine: (kynurenic acid + xanthurenic acid + 3-hydroxyanthranilic acid + anthranilic acid); an inverse marker of vitamin B6] and both reduced global quality of life (beta = -3.62; 95% CI: -5.88, -1.36) and worse physical functioning (beta = -5.01; 95% CI: -7.09, -2.94). Dose-response relations were observed for PLP and quality of life. No associations were observed for changes in biomarker concentrations between diagnosis and 6 months. Participants who stopped using B-vitamin supplements after diagnosis reported higher fatigue than nonusers.Conclusions: Higher vitamin B6 status was associated with better quality of life, yet limited associations were observed for the use of B-vitamin supplements. Vitamin B6 needs further study to clarify its role in relation to quality of life

Dietary Vitamin D3 Supplements Reduce Demyelination in the Cuprizone Model

Vitamin D is emerging as a probably important environmental risk factor in multiple sclerosis, affecting both susceptibility and disease progression. It is not known to what extent this effect is due to a modulation of peripheral lymphocyte function, or to intrathecal effects of vitamin D. We investigated the effect of dietary vitamin D3 content on de/remyelination in the cuprizone model, which is a well established toxic model of demyelination, with no associated lymphocyte infiltration. The mice received diets either deficient of (<50 IU/kg), or supplemented with low (500 IU/kg), high (6200 IU/kg) or very high (12500 IU/kg) amounts of vit D3. Cuprizone (0.2%) was added to the diet for six weeks, starting two weeks after onset of the experimental diets. Mouse brain tissue was histopathologically evaluated for myelin and oligodendrocyte loss, microglia/macrophage activation, and lymphocyte infiltration after six weeks of cuprizone exposure, and two weeks after discontinuation of cuprizone exposure. High and very high doses of vitamin D3 significantly reduced the extent of white matter demyelination (p = 0.004) and attenuated microglia activation (p = 0.001). No differences in the density of oligodendrocytes were observed between the diet groups. Two weeks after discontinuation of cuprizone exposure, remyelination was only detectable in the white matter of mice receiving diets deficient of or with low vitamin D3 content. In conclusion, high dietary doses of vitamin D3 reduce the extent of demyelination, and attenuate microglia activation and macrophage infiltration in a toxic model of demyelination, independent of lymphocyte infiltration

Reproductive factors related to the risk of colorectal cancer by subsite: a case-control analysis

The authors hypothesized that reproductive factors of colorectal cancer, which are probably mediated by endogenous hormones, would differ according to colonic subsite. Information on reproductive factors was obtained from 372 female colorectal cancer cases (113 proximal colon, 126 distal colon, 133 rectum) and 31 061 cancer-free controls at the Aichi Cancer Center Hospital, Japan, between 1988 and 1995. Multiple logistic analysis showed that late age at interview, family history of colorectal cancer among first-degree relatives, menstrual regularity, late age at menopause, late age at first pregnancy and late age at first full-term pregnancy were significantly associated with the risk of colorectal cancer. None of the risk factors were significantly dissociated between colon and rectal cancer. In polytomous logistic regression analysis, particularly noteworthy was the fact that the odds ratios for age at menarche (P-value for heterogeneity of odds ratios = 0.010), age at first pregnancy (P = 0.016) and age at first full-term pregnancy (P = 0.028) were significantly higher for distal than for proximal colon cancer. This study supports the hypotheses that there might be an association between reproductive factors and risk of colon cancer, and that the carcinogenesis of colon cancer, by subsite, might show aetiologic distinctions. © 1999 Cancer Research Campaig

The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response

Response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably between patients. The International SSRI Pharmacogenomics Consortium (ISPC) was formed with the primary goal of identifying genetic variation that may contribute to response to SSRI treatment of major depressive disorder. A genome-wide association study of 4-week treatment outcomes, measured using the 17-item Hamilton Rating Scale for Depression (HRSD-17), was performed using data from 865 subjects from seven sites. The primary outcomes were percent change in HRSD-17 score and response, defined as at least 50% reduction in HRSD-17. Data from two prior studies, the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study (PGRN-AMPS) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, were used for replication, and a meta-analysis of the three studies was performed (N=2394). Although many top association signals in the ISPC analysis map to interesting candidate genes, none were significant at the genome-wide level and the associations were not replicated using PGRN-AMPS and STAR*D data. Top association results in the meta-analysis of response included single-nucleotide polymorphisms (SNPs) in the HPRTP4 (hypoxanthine phosphoribosyltransferase pseudogene 4)/VSTM5 (V-set and transmembrane domain containing 5) region, which approached genome-wide significance (P=5.03E-08) and SNPs 5' upstream of the neuregulin-1 gene, NRG1 (P=1.20E-06). NRG1 is involved in many aspects of brain development, including neuronal maturation and variations in this gene have been shown to be associated with increased risk for mental disorders, particularly schizophrenia. Replication and functional studies of these findings are warranted.JM Biernacka … BT Baune et. al