Safety assessment of propylparaben in juvenile rats.

There are conflicting literature reports that parabens, useful antimicrobial additives in pharmaceuticals, may have estrogenic activity. We conducted a comprehensive study to determine whether propylparaben (PP) administration to juvenile rats is associated with adverse effects on reproductive development and function. PP was administered orally once daily to groups of Crl:CD(SD) rats at doses of 0 (vehicle), 10, 100, or 1,000 mg/kg on Postnatal Days (PNDs) 4-90. In-life observations, clinical pathology, reproductive organ weights and histopathology, landmarks of sexual maturation, estrous cyclicity and functional reproductive competence were assessed. A conventional uterotrophic assay was conducted separately using the same doses. Systemic exposures to PP and 3 metabolites were evaluated on PND 7, 21 and 83. These studies demonstrated that PP was well tolerated when administered from PND 4-90 at all doses (AUC[0-T] on PND 83 = 69.9 ng•h/mL). Para-hydroxybenzoic acid, a non-estrogenic compound, was the predominant metabolite contributing to 95% of the total exposure at 1,000 mg/kg/day on PND 7. There was no evidence of estrogenic activity at any dose, and no effects on reproductive organs or function. The No-Observed-Adverse-Effect-Level (NOAEL) was 1,000 mg/kg/day.

Assessment of a nonsteroidal aromatase inhibitor, letrozole, in juvenile rats.

BACKGROUND: The timing and duration of letrozole administration was designed to encompass the majority of postnatal development in the rat with the intent of evaluating the potential for a broad range of effects but with emphasis on expected effects on skeletal maturation. METHODS: Sprague-Dawley rats were administered letrozole via oral gavage at doses of 0.003, 0.03, and 0.3 mg/kg/day beginning on postpartum day (PPD) 7 through 91 followed by a 6-week recovery period. Clinical signs, body weight, food consumption, developmental endpoints, bone, ophthalmology, behavioral assessments, clinical/anatomic pathology, toxicokinetics, and reproductive assessments were conducted. RESULTS: Growth (body weight gain and crown-to-rump length) and food consumption were increased in females at ≥0.03 mg/kg/day and decreased in males at ≥0.003 mg/kg/day. Delayed sexual maturation in both sexes and adverse effects on reproductive function occurred at all doses. Effects on bone growth and maturation were noted in both sexes at all doses. Evidence of recovery was noted for males at 0.003 mg/kg/day and females at 0.003 and 0.03 mg/kg/day upon withdrawal of treatment. Histopathological changes in the pituitary-adrenal-gonadal axis correlated with effects on reproductive function. CONCLUSIONS: The observed effects in juvenile rats were considered predictable and primarily related to the mechanism of action of letrozole upon estrogen synthesis.

Suicide attempts: prevention of repetition.

OBJECTIVE: To present an overview of promising strategies to prevent repetition of suicidal behaviours. METHOD: This literature review on tertiary preventive interventions of suicide attempts was produced using the computerized databases PubMed and PsycINFO from January 1966 to September 2010, using French- and English-language limits and the key words: suicid* or deliberate self-harm and treatment* or therapy or intervention* or management. RESULTS: Thirteen of the 35 included studies showed statistically significant effects of fewer repeated attempts or suicides in the experimental condition. Overall, 22 studies focused on more traditional approaches, that is, pharmacological or psychological approaches. Only 2 of the 6 pharmacological treatments proved significantly superior to a placebo- a study of lithium with depression and flupenthixol with personality disorders. Eight out of 16 psychological treatments proved superior to treatment as usual or another approach: cognitive-behavioural therapy (CBT) (n = 4), (including dialectical behaviour therapy [n = 2]); psychodynamic therapy (n = 2); mixed (CBT plus psychodynamic therapy [n = 1]); and motivational approach and change in therapist (n = 1). Among the 8 studies using visit, postal, or telephone contact or green-token emergency card provision, 2 were significant: one involving telephone follow-up and the other telephone follow-up or visits. Hospitalization was not related to fewer attempts, and 1 of the 4 outreach approaches had significant results: a program involving individualized biweekly treatment. The rationale behind these single or multiple approaches still needs to be clarified. There were methodological flaws in many studies and some had very specific limited samples. CONCLUSIONS: There is a need for more research addressing the problem in definitions of outcomes and measurement of the dependent variables, gender-specific effects, and inclusion of high-risk groups. There is a need for the development and evaluation of new approaches that support collaboration with community resources and more careful assessment and comparisons of existing treatments with different populations.

Critical issues in psychological autopsy studies.

This paper reviews research based on the psychological autopsy (PA) method applied to the study of suicide. It evidences the presence of a number of methodological problems. Shortcomings concern sampling biases in the selection of control subjects, confounding influences of extraneous variables, and reliability of the assessment instruments. The absence of homogeneity among studies in the procedure employed, as well as the lack of defined guidelines for performing this type of inquiry are emphasized. Questions needing empirical investigation in the future are pointed out. It is concluded that the validity and reliability of findings emerging from the use of this method of investigation would benefit from a standardization of its application.

Cognitive correlates of serious suicidal ideation in a community sample of adolescents.

BACKGROUND: Studies indicate that a dysfunctional attributional style, problem-solving deficits and hopelessness place youths at risk of developing suicidal thoughts and engaging in suicidal behaviour. However, in the realm of suicidality in adolescent, no study has examined the linkages between these three cognitive variables and suicidal ideation in non-clinical samples while taking into account the moderating role of gender on the relationships and controlling for depression. METHODS: In this community study of 712 adolescents 14-18 years of age, through a multivariate approach, the interaction between the cognitive variables, depression and gender was examined with depression controlled in the analyses. RESULTS: Problem-solving deficits and hopelessness proved predictive of such ideation whether or not depressive symptoms were controlled in the analyses. Negative problem orientation/avoidant style was more predictive of ideation in boys than in girls. On the other hand, hopelessness was more predictive for girls than boys. LIMITATIONS: Results were based on a convenience community sample of adolescents and a cross-sectional survey. CONCLUSIONS: Results suggest that a unique explanatory model of the suicide process in adolescence that fails to take account of gender would be ill informed. Suicide prevention strategies should be differentiated according to gender with a stronger emphasis in hopelessness in female adolescents, and problem-solving deficits in male adolescents.

The Werther effect reconsidered in light of psychological vulnerabilities: results of a pilot study.

BACKGROUND: Findings from three decades of epidemiological studies suggest that media diffusion of stories about suicide is related to increases in suicidal behaviours in the population exposed to the media reports. However, we still know little about the psychological processes and personal vulnerabilities that prompt some people to engage in suicidal behaviours after exposure to media presentations of suicides. This cross-sectional study explored the possible impact of exposure to film suicide in normal young people. METHODS: Undergraduates from a university (mean age 23 years) completed a questionnaire on exposure to suicide portrayal in fictional films, in which assessment of negative emotional and cognitive reactions resulting from exposure, as well as emotional reactivity, dissociation, thought suppression, and suicidal tendencies were made. RESULTS: Of the 101 participants, 70% reported being distressed by the portrayal of a suicide in a fictional film. Among those, 33% stated they felt distressed about the portrayal for several days to several weeks. The majority of the affected participants (71%) indicated having been mentally preoccupied for some time by the portrayal and experienced intrusive memories (68%). Emotional reactivity and dissociation tendencies were significant predictors of the negative reactions to the suicide film they viewed. Participants who reported that the idea had crossed their mind to imitate the suicidal protagonist in the film were 3.45 times more likely to be suicidal and tended to present higher dissociation and thought suppression propensities compared to those who did not report these thoughts. LIMITATIONS: The results showing possible influences of suicide portrayal in fictional film on suicide related cognitions were based on a survey methodology. CONCLUSION: Results suggest that fictional suicide portrayals in the media may have a deleterious impact on viewers, and such impacts do not appear to be limited to people having a clinical profile of mental disorders, as previously assumed by researchers in the field.

Suicide, schizophrenia, and schizoid-type psychosis: role of life events and childhood factors.

The first objective was to identify the provoking events of suicide in patients with schizophrenia or schizoid-type disorder, and to assess the humiliation component of these events. The second objective was to verify if quality of care during childhood is a vulnerability factor for suicide in patients with schizophrenia or schizoid-type psychosis. Thirty-three cases of suicide with a diagnosis of schizophrenia or schizoid-type psychosis were compared with 34 living patients with a similar diagnosis. The psychological autopsy method was used. The assessments were made with the Structured Clinical Interview for the Diagnostic and Statistical Manual for Axis I mental disorders, the Life Events and Difficulties Schedule, and the Child Experiences and Child Abuse Interview. The suicide group (SG) experienced more often a recent severe event, usually of a humiliation nature, than the control group (CG). It also experienced more severe events associated with aggressive behavior or with psychiatric impairment. Contrary to expectations, the CG had worse scores than the SG for quality of care during childhood. In conclusion, suicide in schizophrenia is related both to environmental stress and to psychiatric impairment.

Comparison of determinants of research knowledge utilization by practitioners and administrators in the field of child and family social services.

BACKGROUND: An important gap exists between research production and its utilization. Few studies have examined the factors affecting knowledge utilization in the field of child and family social services. METHODS: The objectives of the study are to describe knowledge utilization by child protection administrators and practitioners (N = 477) and to compare factors related to knowledge utilization by these two occupational groups. The study was conducted with an adapted version of the Questionnaire sur l'utilisation des connaissances (Knowledge Utilization Questionnaire). Factor analysis was used to collapse data collected on the questionnaire items. Factor score for each respondent served as independent variables in three separate multivariate regression analyses to explore variables likely to predict research-based knowledge utilization. RESULTS: A minority of respondents (18%) report using on a frequent basis research-based knowledge in their practice. Relational capital between researchers and users and perceived usefulness of research based knowledge were the two factors most strongly related to utilization. There was a specificity in the factors associated with knowledge utilization according to occupational groups in child protection organizations. Use of active knowledge transfer strategies was associated with knowledge utilization by practitioners, while knowledge dissemination efforts played a more significant role for administrators. CONCLUSION: These results encourage both the use of strategies differentiated according to users and the intensification of interactions between users and researchers to foster research knowledge utilization.