Behavioral Endpoints Research Articles

Behavioral and biochemical responses in freshwater fish Carassius auratus exposed to sertraline

Sertraline is one of the most commonly prescribed selective serotonin reuptake inhibitors and is frequently detected in the aquatic environment. However, knowledge regarding relationships among molecular or biochemical endpoints involved in modes of action (MOAs) of sertraline and ecologically important behavioral responses of fish is insufficient. The present study aimed to investigate the bioconcentration and possible adverse outcomes pathways (AOPs) in crucian carp (Carassius auratus) exposed to various concentrations of sertraline (4.36, 21.3 and 116μgL−1) for 7d. Bioconcentration factor values were in the range of 19.5–626 in liver, 6.94–285 in brain, 4.01–146 in gill and 0.625–43.1 in muscle during the entire period of exposure. Liver superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities and brain acetylcholinesterase (AChE) activity were selected as biochemical endpoints associated with MOAs. Swimming activity, shoaling, feeding rate and food consumption were determined to assess behavioral responses. Fish plasma levels of sertraline exceeding human therapeutic doses were also predicted from external exposure concentrations. Significant enhancements in CAT, GPx, AChE and swimming activities and decreases in shoaling tendency, feeding rate and food consumption were observed when fish plasma levels exceeded human therapeutic thresholds. Shoaling, feeding rate and food consumption were correlated with the activities of SOD, CAT and GST. A significant positive correlation between swimming activity and AChE activity was also observed. As such, our study provides important AOPs linking biochemical responses with ultimate ecologically relevant behavioral endpoints.

Pre-hatching fluoxetine-induced neurochemical, neurodevelopmental, and immunological changes in newly hatched cuttlefish.

Embryonic and early postembryonic development of the cuttlefish Sepia officinalis (a cephalopod mollusk) occurs in coastal waters, an environment subject to considerable pressure from xenobiotic pollutants such as pharmaceutical residues. Given the role of serotonin in brain development and its interaction with neurodevelopmental functions, this study focused on fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI, antidepressant). The goal was to determine the effects of subchronic waterborne FLX exposure (1 and 10 μg L(-1)) during the last 15 days of embryonic development on neurochemical, neurodevelopmental, behavioral, and immunological endpoints at hatching. Our results showed for the first time that organic contaminants, such as FLX, could pass through the eggshell during embryonic development, leading to a substantial accumulation of this molecule in hatchlings. We also found that FLX embryonic exposure (1 and 10 μg L(-1)) (1) modulated dopaminergic but not serotonergic neurotransmission, (2) decreased cell proliferation in key brain structures for cognitive and visual processing, (3) did not induce a conspicuous change in camouflage quality, and (4) decreased lysozyme activity. In the long term, these alterations observed during a critical period of development may impair complex behaviors of the juvenile cuttlefish and thus lead to a decrease in their survival. Finally, we suggest a different mode of action by FLX between vertebrate and non-vertebrate species and raise questions regarding the vulnerability of early life stages of cuttlefish to the pharmaceutical contamination found in coastal waters.

Amphetamine sensitization in mice is sufficient to produce both manic- and depressive-related behaviors as well as changes in the functional connectivity of corticolimbic structures

It has been suggested that amphetamine abuse and withdrawal mimics the diverse nature of bipolar disorder symptomatology in humans. Here, we determined if a single paradigm of amphetamine sensitization would be sufficient to produce both manic- and depressive-related behaviors in mice. CD-1 mice were subcutaneously dosed for 5 days with 1.8 mg/kg d-amphetamine or vehicle. On days 6–31 of withdrawal, amphetamine-sensitized (AS) mice were compared to vehicle-treated (VT) mice on a range of behavioral and biochemical endpoints. AS mice demonstrated reliable mania- and depression-related behaviors from day 7 to day 28 of withdrawal. Relative to VT mice, AS mice exhibited long-lasting mania-like hyperactivity following either an acute 30-min restraint stress or a low-dose 1 mg/kg d-amphetamine challenge, which was attenuated by the mood-stabilizers lithium and quetiapine. In absence of any challenge, AS mice showed anhedonia-like decreases in sucrose preference and depression-like impairments in the off-line consolidation of motor memory, as reflected by the lack of spontaneous improvement across days of training on the rotarod. AS mice also demonstrated a functional impairment in nest building, an ethologically-relevant activity of daily living. Western blot analyses revealed a significant increase in methylation of histone 3 at lysine 9 (H3K9), but not lysine 4 (H3K4), in hippocampus of AS mice relative to VT mice. In situ hybridization for the immediate-early gene activity-regulated cytoskeleton-associated protein (Arc) further revealed heightened activation of corticolimbic structures, decreased functional connectivity between frontal cortex and striatum, and increased functional connectivity between the amygdala and hippocampus of AS mice. The effects of amphetamine sensitization were blunted in C57BL/6J mice relative to CD-1 mice. These results show that a single amphetamine sensitization protocol is sufficient to produce behavioral, functional, and biochemical phenotypes in mice that are relevant to bipolar disorder.

Syntaxin1A-mediated Resistance and Hypersensitivity to Isoflurane in Drosophila melanogaster.

Recent evidence suggests that general anesthetics activate endogenous sleep pathways, yet this mechanism cannot explain the entirety of general anesthesia. General anesthetics could disrupt synaptic release processes, as previous work in Caenorhabditis elegans and in vitro cell preparations suggested a role for the soluble NSF attachment protein receptor protein, syntaxin1A, in mediating resistance to several general anesthetics. The authors questioned whether the syntaxin1A-mediated effects found in these reductionist systems reflected a common anesthetic mechanism distinct from sleep-related processes. Using the fruit fly model, Drosophila melanogaster, the authors investigated the relevance of syntaxin1A manipulations to general anesthesia. The authors used different behavioral and electrophysiological endpoints to test the effect of syntaxin1A mutations on sensitivity to isoflurane. The authors found two syntaxin1A mutations that confer opposite general anesthesia phenotypes: syxH3-C, a 14-amino acid deletion mutant, is resistant to isoflurane (n = 40 flies), and syxKARRAA, a strain with two amino acid substitutions, is hypersensitive to the drug (n = 40 flies). Crucially, these opposing effects are maintained across different behavioral endpoints and life stages. The authors determined the isoflurane sensitivity of syxH3-C at the larval neuromuscular junction to assess effects on synaptic release. The authors find that although isoflurane slightly attenuates synaptic release in wild-type animals (n = 8), syxH3-C preserves synaptic release in the presence of isoflurane (n = 8). The study results are evidence that volatile general anesthetics target synaptic release mechanisms; in addition to first activating sleep pathways, a major consequence of these drugs may be to decrease the efficacy of neurotransmission.

Effect of neurotoxic compounds on ephyrae of Aurelia aurita jellyfish

The aim of this study was to analyze the toxicity of two neurotoxic compounds on the ephyra stage of the Scyphozoan jellyfish Aurelia aurita, an innovative and sensitive model organism recently proposed in ecotoxicological bioassays. Indeed, jelly- fish play an important role in the marine ecosystem, being a key component of the gelatinous zooplankton and of the marine food web, but are not represented in routine ecotoxicology. In this study, ephyrae were exposed to several concentrations (0, 0.1, 0.5, 1, 5, 10, 50 mg l -1 ) of eserine (ES) and chlorpyrifos (CPF), a carbamate and an organophosphorous compound, respectively, in order to analyze their toxic effect on this model organism. Acute (% of immobility) and behavioral (% alteration of frequency of pulsations) end-points were investigated after 24 and 48 h of exposure. Exposure to both compounds caused a dose- dependent effect, and for each end-point, it was possible to quantify these effects by means of EC50. Results highlighted how these compounds reported a high toxicity for marine organisms and exerted their toxic effect on this innovative biological model (in particular, CPF resulted to be more toxic than ES), which proved to be more sensitive than other marine invertebrates commonly used for ecotoxicological bioassays.

Establishing a Clinically Relevant Large Animal Model Platform for TBI Therapy Development: Using Cyclosporin A as a Case Study.

We have developed the first immature large animal translational treatment trial of a pharmacologic intervention for traumatic brain injury (TBI) in children. The preclinical trial design includes multiple doses of the intervention in two different injury types (focal and diffuse) to bracket the range seen in clinical injury and uses two post-TBI delays to drug administration. Cyclosporin A (CsA) was used as a case study in our first implementation of the platform because of its success in multiple preclinical adult rodent TBI models and its current use in children for other indications. Tier 1 of the therapy development platform assessed the short-term treatment efficacy after 24 h of agent administration. Positive responses to treatment were compared with injured controls using an objective effect threshold established prior to the study. Effective CsA doses were identified to study in Tier 2. In the Tier 2 paradigm, agent is administered in a porcine intensive care unit utilizing neurological monitoring and clinically relevant management strategies, and intervention efficacy is defined as improvement in longer term behavioral endpoints above untreated injured animals. In summary, this innovative large animal preclinical study design can be applied to future evaluations of other agents that promote recovery or repair after TBI.

Protective effects of resveratrol on social stress‐induced neuroinflammation and depressive‐like behavior

Social stress precipitates psychiatric disorders, however only a subset of the population is susceptible. This may result from differences in coping strategy and sequent inflammation. Using a resident-intruder paradigm in rats, we previously identified two distinct phenotypic responses to stress. Active coping (AC) rats spent more time resisting in upright postures in the presence of a dominant resident rat than did passive coping (PC) rats. PC rats developed behavioral, inflammatory and neuroendocrine endpoints comparable to depression, while AC rats did not. The present study determined if resveratrol (RSV, 10mg/kg/day), a natural anti-inflammatory, could protect against stress-induced neuroinflammation and produce antidepressant-like effects in socially defeated rats (stress vs control 30min/day for 5 days). In PC rats, proinflammatory proteins (IL-1β, IL-6, GM-CSF) were elevated 5 days after the final social defeat within the locus coeruleus, a noradrenergic brain region implicated in depression. Alternitavely, in AC rats, certain proinflammatory cytokines were decreased (INF-ϒ and MCP-1). Flow cytometry revealed increased splenic inflammatory proteins in PC as compared to AC and controls. Elevated inflammation in the PC phenotype was also related to anhedonia in the sucrose preference test. Notably, RSV blocked the inflammation produced by social defeat and inhibited the development of depressive-like behavior. These data confirm that the depressive-like phenotype evident in PC rats may be driven by stress-induced inflammation as evidenced by anti-depressant-like effects of RSV. 5P20GM103641

Steroids in the Avian Brain: Heterogeneity across Space and Time.

Sex steroids influence a diversity of neural and behavioral endpoints in birds, including some that have little to do with reproduction per se. Recent advances in neurochemistry and molecular biology further indicate that the avian brain is comprised of a network of unique sex steroid microenvironments. Factors involved in steroid synthesis and metabolism are present in the avian brain with expression levels that vary from region to region and with activities that are, in some cases, subject to regulation over relatively slow or rapid time intervals. Advances in our ability to a) isolate steroids from brain tissue and b) precisely measure their concentrations reveal how steroid levels vary spatially and temporally. A full appreciation of sex steroid effects on the avian brain require not only measures of hormones in blood but also an understanding of the numerous and varied mechanisms whereby the brain creates such a heterogeneous steroidal environment.

Beneficial and Adverse Consequences of Increased Brain Plasticity: the Interplay Among Serotonin, Susceptibility to the Environment and Depression

Antidepressants represent the standard treatment for major depression. However, their efficacy is variable and incomplete. A growing number of studies suggest that the environment plays a major role in determining the efficacy of these drugs, specifically of selective serotonin reuptake inhibitors (SSRI). We recently hypothesized that the increase in serotonin levels induced by SSRI may not affect mood per se , but enhance neural plasticity and, consequently, renders the individual more susceptible to the environment. Thus, SSRI administration in a favorable environment would lead to a reduction of symptoms, while in a stressful environment might lead to a worse prognosis. To test this hypothesis, we treated C57BL/6 adult male mice with chronic fluoxetine while exposing them to either (i) an enriched environment, after exposure to a chronic stress period aimed at inducing a depression-like phenotype, or (ii) a stressful environment. A wide number of molecular, cellular and behavioral endpoints considered endophenotypes of depression were investigated. These include long-term potentiation, BDNF levels, hypothalamic-pituitary-axis activity, neurogenesis, anhedonia and optimistic attitude (cognitive bias). Mice treated with fluoxetine in an enriched condition improved their depression-like phenotype compared to controls, displaying an overall reduction of all endophenotypes of depression investigated. By contrast, when chronic fluoxetine administration occurred in a stressful condition, mice showed a more distinct worsening of the depression-like profile. Our findings suggest that the effect of SSRI on depression-like phenotypes in mice is not determined by the drug per se but is induced by the drug and driven by the environment. These findings may be helpful to explain variable effects of SSRI found in clinical practice and to device strategies aimed at enhancing their efficacy by means of controlling environmental conditions.

Sexual health risk reduction interventions for people with severe mental illness: a systematic review.

BackgroundDespite variability in sexual activity among people with severe mental illness, high-risk sexual behavior (e.g. unprotected intercourse, multiple partners, sex trade and illicit drug use) is common. Sexual health risk reduction interventions (such as educational and behavioral interventions, motivational exercises, counselling and service delivery), developed and implemented for people with severe mental illness, may improve participants’ knowledge, attitudes, beliefs behaviors or practices (including assertiveness skills) and could lead to a reduction in risky sexual behavior. This systematic review evaluates the effectiveness of sexual health risk reduction interventions for people with severe mental illness.MethodsThirteen electronic databases (including MEDLINE, EMBASE and PsycINFO) were searched to August 2014, and supplemented by hand-searching relevant articles and contacting experts. All controlled trials (randomized or non-randomized) comparing the effectiveness of sexual health risk reduction interventions with usual care for individuals living in the community with severe mental illness were included. Outcomes included a range of biological, behavioral and proxy endpoints. Narrative synthesis was used to combine the evidence.ResultsThirteen controlled trials (all from the USA) were included. Although there was no clear and consistent evidence that interventions reduce the total number of sex partners or improved behavioral intentions in sexual risk behavior, positive effects were generally observed in condom use, condom protected intercourse and on measures of HIV knowledge, attitudes to condom use and sexual behaviors and practices. However, the robustness of these findings is low due to the large between study variability, small sample sizes and low-to-moderate quality of included studies.ConclusionsThere is insufficient evidence at present to fully support or reject the identified sexual health risk reduction interventions for people with severe mental illness. Given the serious consequences of high-risk sexual behaviors, there is an urgent need for well-designed UK based trials, as well as training and support for staff implementing sexual health risk reduction interventions.Trial registrationPROSPERO CRD42013003674.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-015-1448-4) contains supplementary material, which is available to authorized users.

Stroke warning campaigns: delivering better patient outcomes? A systematic review.

BackgroundPatient delay in presenting to hospital with stroke symptoms remains one of the major barriers to thrombolysis treatment, leading to its suboptimal use internationally. Educational interventions such as mass media campaigns and community initiatives aim to reduce patient delays by promoting the signs and symptoms of a stroke, but no consistent evidence exists to show that such interventions result in appropriate behavioral responses to stroke symptoms.MethodsA systematic literature search and narrative synthesis were conducted to examine whether public educational interventions were successful in the reduction of patient delay to hospital presentation with stroke symptoms. Three databases, MEDLINE, CINAHL, and PsycINFO, were searched to identify quantitative studies with measurable behavioral end points, including time to hospital presentation, thrombolysis rates, ambulance use, and emergency department (ED) presentations with stroke.ResultsFifteen studies met the inclusion criteria: one randomized controlled trial, two time series analyses, three controlled before and after studies, five uncontrolled before and after studies, two retrospective observational studies, and two prospective observational studies. Studies were heterogeneous in quality; thus, meta-analysis was not feasible. Thirteen studies examined prehospital delay, with ten studies reporting a significant reduction in delay times, with a varied magnitude of effect. Eight studies examined thrombolysis rates, with only three studies reporting a statistically significant increase in thrombolysis administration. Five studies examined ambulance usage, and four reported a statistically significant increase in ambulance transports following the intervention. Three studies examining ED presentations reported significantly increased ED presentations following intervention. Public educational interventions varied widely on type, duration, and content, with description of intervention development largely absent from studies, limiting the potential replication of successful interventions.ConclusionsPositive intervention effects were reported in the majority of studies; however, methodological weaknesses evident in a number of studies limited the generalizability of the observed effects. Reporting of specific intervention design was suboptimal and impeded the identification of key intervention components for reducing patient delay. The parallel delivery of public and professional interventions further limited the identification of successful intervention components. A lack of studies of sound methodological quality using, at a minimum, a controlled before and after design was identified in this review, and thus studies incorporating a rigorous study design are required to strengthen the evidence for public interventions to reduce patient delay in stroke. The potential clinical benefits of public interventions are far-reaching, and the challenge remains in translating knowledge improvements and correct behavioral intentions to appropriate behavior when stroke occurs.

The use of growth and behavioral endpoints to assess the effects of pesticide mixtures upon aquatic organisms.

Aquatic communities are often subject to complex contaminant mixtures, usually at sublethal concentrations, that can cause long-term detrimental effects. Chemicals within mixtures can effectively interact, resulting in synergism, antagonism or additivity. We investigated the tertiary mixture effects of two pyrethroids, lambda-cyhalothrin and permethrin, and the organophosphate chlorpyrifos, evaluating sublethal endpoints; immobility and growth, on Chironomus dilutus in 10-day exposures. We utilized a toxic units (TU) approach, based on median lethal concentrations (LC50) for each compound. The concepts of independent action and concentration addition were used to compare predicted mixture toxicity to observed mixture toxicity. Increased immobility resulted from mixture concentrations ≥1 TU (7.45ng/L lambda-cyhalothrin×24.90ng/L permethrin×129.70ng/L chlorpyrifos), and single pesticides concentrations ≥0.25 TU (5.50ng/L lambda-cyhalothrin, 24.23ng/L permethrin, 90.92ng/L chlorpyrifos, respectively). Growth was inhibited by pesticide mixtures ≥0.125 TU (1.04ng/L lambda-cyhalothrin×3.15ng/L permethrin×15.47ng/L chlorpyrifos), and singly by lambda-cyhalothrin ≥0.25 TU (5.50ng/L), and permethrin ≥0.167 TU (18.21ng/L). The no observed effect concentrations (NOEC) for immobility and growth, for both mixture and single-pyrethroid exposure, were up to 8.0 and 12.0 times respectively lower than the corresponding NOEC for survival. The median effective concentrations (EC50) for growth (mixture and single-pyrethroid exposure) were up to 7.0 times lower than the respective LC50. This study reinforces that the integration of sublethal endpoints in monitoring efforts is powerful in discerning toxic effects that would otherwise be missed by solely utilizing traditional toxicity assessments.

Long-term behavioral impairment following acute embryonic ethanol exposure in zebrafish

BackgroundDevelopmental exposure to ethanol has long been known to cause persisting neurobehavioral impairment. However, the neural and behavioral mechanisms underlying these deficits and the importance of exposure timing are not well-characterized. Given the importance of timing and sequence in neurodevelopment it would be expected that alcohol intoxication at different developmental periods would result in distinct neurobehavioral consequences. MethodsZebrafish embryos were exposed to ethanol (0%, 1%, 3%) at either 8–10 or 24–27h post-fertilization (hpf) then reared to adolescence and evaluated on several behavioral endpoints. Habituation to a repeated environmental stimulus and overall sensorimotor function were assessed using a tap startle test; measurements of anxiety and exploration behavior were made following introduction to a novel tank; and spatial discrimination learning was assessed using aversive control in a three-chambered apparatus. Overt signs of dysmorphogenesis were also scored (i.e. craniofacial malformations, including eye diameter and midbrain-hindbrain boundary morphology). ResultsEthanol treated fish were more active both at baseline and following a tap stimulus compared to the control fish and were hyperactive when placed in a novel tank. These effects were more prominent following exposure at 24–27hpf than with the earlier exposure window, for both dose groups. Increases in physical malformation were only present in the 3% ethanol group; all malformed fish were excluded from behavioral testing. DiscussionThese results suggest specific domains of behavior are affected following ethanol exposure, with some but not all of the tests revealing significant impairment. The behavioral phenotypes following distinct exposure windows described here can be used to help link cellular and molecular mechanisms of developmental ethanol exposure to functional neurobehavioral effects.

Behavioral and electrophysiological analysis of general anesthesia in 3 background strains of Drosophila melanogaster

General anesthetics achieve behavioral unresponsiveness via a mechanism that is incompletely understood. The study of genetic model systems such as the fruit fly Drosophila melanogaster is crucial to advancing our understanding of how anesthetic drugs render animals unresponsive. Previous studies have shown that wild-type control strains differ significantly in their sensitivity to general anesthetics, which potentially introduces confounding factors for comparing genetic mutations placed on these wild-type backgrounds. Here, we examined a variety of behavioral and electrophysiological endpoints in Drosophila, in both adult and larval animals. We characterized these endpoints in 3 commonly used fly strains: wild-type Canton Special (CS), and 2 commonly used white-eyed strains, isoCJ1 and w1118. We found that CS and isoCJ1 show remarkably similar sensitivity to isoflurane across a variety of behavioral and electrophysiological endpoints. In contrast, w1118 is resistant to isoflurane compared to the other 2 strains at both the adult and larval stages. This resistance is however not reflected at the level of neurotransmitter release at the larval neuromuscular junction (NMJ). This suggests that the w1118 strain harbors another mutation that produces isoflurane resistance, by acting on an arousal pathway that is most likely preserved between larval and adult brains. This mutation probably also affects sleep, as marked differences between isoCJ1 and w1118 have also recently been found for behavioral responsiveness and sleep intensity measures.

Candidate Gene Knockdown in Celiac Disease.

RNA interference (RNAi) is a powerful genetic tool that has created new opportunities in cell biology by allowing the specific modulation of gene expression under controlled conditions. Knockdown of genes associated with disease can provide valuable information pertaining to their function and potentially their role in the disease etiology. In the context of celiac disease, it allows us to examine closely the cellular changes that occur when the expression levels of genes of interest are reduced. Utilizing informative assays that demonstrate changes in cell behavior or other measurable endpoints such as cytokine production or migratory phenotypes can further our understanding of the pathogenic mechanisms in this prevalent autoimmune disorder. This chapter outlines protocols for examining the effects of RNAi on candidate genes and subsequent changes to migratory phenotype, transmigration, and adhesion.

Accessing Data Resources in the Mouse Phenome Database for Genetic Analysis of Murine Life Span and Health Span

Understanding the source of genetic variation in aging and using this variation to define the molecular mechanisms of healthy aging require deep and broad quantification of a host of physiological, morphological, and behavioral endpoints. The murine model is a powerful system in which to understand the relations across age-related phenotypes and to identify research models with variation in life span and health span. The Jackson Laboratory Nathan Shock Center of Excellence in the Basic Biology of Aging has performed broad characterization of aging in genetically diverse laboratory mice and has placed these data, along with data from several other major aging initiatives, into the interactive Mouse Phenome Database. The data may be accessed and analyzed by researchers interested in finding mouse models for specific aging processes, age-related health and disease states, and for genetic analysis of aging variation and trait covariation. We expect that by placing these data in the hands of the aging community that there will be (a) accelerated genetic analyses of aging processes, (b) discovery of genetic loci regulating life span, (c) identification of compelling correlations between life span and susceptibility for age-related disorders, and (d) discovery of concordant genomic loci influencing life span and aging phenotypes between mouse and humans.

Nonhuman primate models in translational regenerative medicine.

Humans and nonhuman primates (NHPs) are similar in size, behavior, physiology, biochemistry, structure and function of organs, and complexity of the immune system. Research on NHPs generates complementary data that bridge translational research from small animal models to humans. NHP models of human disease offer unique opportunities to develop stem cell-based therapeutic interventions that directly address relevant and challenging translational aspects of cell transplantation therapy. These include the use of autologous induced pluripotent stem cell-derived cellular products, issues related to the immune response in autologous and allogeneic setting, pros and cons of delivery techniques in a clinical setting, as well as the safety and efficacy of candidate cell lines. The NHP model allows the assessment of complex physiological, biochemical, behavioral, and imaging end points, with direct relevance to human conditions. At the same time, the value of using primates in scientific research must be carefully evaluated and timed due to expense and the necessity for specialized equipment and highly trained personnel. Often it is more efficient and useful to perform initial proof-of-concept studies for new therapeutics in rodents and/or other species before the pivotal studies in NHPs that may eventually lead to first-in-human trials. In this report, we present how the Southwest National Primate Research Center, one of seven NIH-funded National Primate Research Centers, may help the global community in translating promising technologies to the clinical arena.

Dealing With Missing Behavioral Endpoints in Health Promotion Research by Modeling Cognitive Parameters in Cost-Effectiveness Analyses of Behavioral Interventions: A Validation Study.

Cost-effectiveness analyses (CEAs) of behavioral interventions typically use physical outcome criteria. However, any progress in cognitive antecedents of behavior change may be seen as a beneficial outcome of an intervention. The aim of this study is to explore the feasibility and validity of incorporating cognitive parameters of behavior change in CEAs. The CEA from a randomized controlled trial on smoking cessation was reanalyzed. First, relevant cognitive antecedents of behavior change in this dataset were identified. Then, transition probabilities between combined states of smoking and cognitions at 6 weeks and corresponding 6 months smoking status were obtained from the dataset. These rates were extrapolated to the period from 6 to 12 months in a decision analytic model. Simulated results were compared with the 12 months' observed cost-effectiveness results. Self-efficacy was the strongest time-varying predictor of smoking cessation. Twelve months' observed CEA results for the multiple tailoring intervention versus usual care showed € 3188 had to be paid for each additional quitter versus € 10,600 in the simulated model. The simulated CEA showed largely similar but somewhat more conservative results. Using self-efficacy to enhance the estimation of the true behavioral outcome seems a feasible and valid way to estimate future cost-effectiveness.

Behavioral response of juvenile rainbow trout exposed to an herbicide mixture

Fish are capable of sensing water-borne chemicals at sub-lethal concentrations. Inadequate behavioral responses to physiological and environmental stimuli owing to adverse effects of aquatic toxicants can have serious implications for survival.In this study we exposed juvenile rainbow trout (Oncorhynchus mykiss) during 5 days to a low-concentration mixture of three co-occurring herbicides: atrazine, linuron and metolachlor, at maximum concentrations of 4.5, 4.9 and 13.4μgL−1, respectively. Our hypothesis was that fish behavior – swimming activity and interactions between individuals – would be modified due to exposure to the mixture. We studied these behaviors by observing fish twice-daily throughout the exposure period at 30-s intervals for 5min, registering the vertical distribution of fish in the water column and the number of agoniztic acts between all individuals.Fish exposed to the mixture of herbicides were hypoactive and spent more time in the lower parts of the aquaria in comparison to non-exposed controls, reflecting inhibited swimming activity. Average swimming height of exposed fish decreased significantly with the number of agoniztic acts, whilst in control groups there was no significant relationship between the two behaviors. Overall, behavior of fish exposed for a short time to the herbicide mixture was altered in comparison to control-fish behavior. The behavioral endpoints chosen here were easily observed, simple to quantify, and of ecological relevance.

Association of weekly suicide rates with temperature anomalies in two different climate types.

Annual suicide deaths outnumber the total deaths from homicide and war combined. Suicide is a complex behavioral endpoint, and a simple cause-and-effect model seems highly unlikely, but relationships with weather could yield important insight into the biopsychosocial mechanisms involved in suicide deaths. This study has been designed to test for a relationship between air temperature and suicide frequency that is consistent enough to offer some predictive abilities. Weekly suicide death totals and anomalies from Toronto, Ontario, Canada (1986–2009) and Jackson, Mississippi, USA (1980–2006) are analyzed for relationships by using temperature anomaly data and a distributed lag nonlinear model. For both analysis methods, anomalously cool weeks show low probabilities of experiencing high-end suicide totals while warmer weeks are more likely to experience high-end suicide totals. This result is consistent for Toronto and Jackson. Weekly suicide totals demonstrate a sufficient association with temperature anomalies to allow some prediction of weeks with or without increased suicide frequency. While this finding alone is unlikely to have immediate clinical implications, these results are an important step toward clarifying the biopsychosocial mechanisms of suicidal behavior through a more nuanced understanding of the relationship between temperature and suicide.