Development and validation of the Psychological Adaptation Scale (PAS): Use in six studies of adaptation to a health condition or risk

We introduce The Psychological Adaptation Scale (PAS) for assessing adaptation to a chronic condition or risk and present validity data from six studies of genetic conditions

Genetic and Pharmacologic Manipulation of TLR4 Has Minimal Impact on Ethanol Consumption in Rodents

Toll-like receptor 4 (TLR4) is a critical component of innate immune signaling and has been implicated in alcohol responses in preclinical and clinical models. Members of the Integrative Neuroscience Initiative on Alcoholism (INIA-Neuroimmune) consortium tested the hypothesis that TLR4 mediates excessive ethanol drinking using the following models: (1) Tlr4 knock-out (KO) rats, (2) selective knockdown of Tlr4 mRNA in mouse nucleus accumbens (NAc), and (3) injection of the TLR4 antagonist (+)-naloxone in mice. Lipopolysaccharide (LPS) decreased food/water intake and body weight in ethanol-naive and ethanol-trained wild-type (WT), but not Tlr4 KO rats. There were no consistent genotypic differences in two-bottle choice chronic ethanol intake or operant self-administration in rats before or after dependence. In mice, (+)-naloxone did not decrease drinking-in-the-dark and only modestly inhibited dependence-driven consumption at the highest dose. Tlr4 knockdown in mouse NAc did not decrease drinking in the two-bottle choice continuous or intermittent access tests. However, the latency to ethanol-induced loss of righting reflex increased and the duration decreased in KO versus WT rats. In rat central amygdala neurons, deletion of Tlr4 altered GABAA receptor function, but not GABA release. Although there were no genotype differences in acute ethanol effects before or after chronic intermittent ethanol exposure, genotype differences were observed after LPS exposure. Using different species and sexes, different methods to inhibit TLR4 signaling, and different ethanol consumption tests, our comprehensive studies indicate that TLR4 may play a role in ethanol-induced sedation and GABAA receptor function, but does not regulate excessive drinking directly and would not be an effective therapeutic target., SIGNIFICANCE STATEMENT Toll-like receptor 4 (TLR4) is a key mediator of innate immune signaling and has been implicated in alcohol responses in animal models and human alcoholics. Members of the Integrative Neuroscience Initiative on Alcoholism (INIA-Neuroimmune) consortium participated in the first comprehensive study across multiple laboratories to test the hypothesis that TLR4 regulates excessive alcohol consumption in different species and different models of chronic, dependence-driven, and binge-like drinking. Although TLR4 was not a critical determinant of excessive drinking, it was important in the acute sedative effects of alcohol. Current research efforts are directed at determining which neuroimmune pathways mediate excessive alcohol drinking and these findings will help to prioritize relevant pathways and potential therapeutic targets

Brown Lab, Public

We are a collaborative molecular modeling and bioinformatics lab at Virginia Tech. We work with individuals all over campus and at other universities to provide computational support to their research, as well as pursuing our own work on amyloid and IDPs. With this OSF, we give you information on our most commonly used techniques and example methods for generating a shared group, multi-project OSF. For information about our current projects or to view our tutorials, head to the Wiki page. To see some of our published papers and images, along with scripts and files to help you with your own molecular modeling, check our Files. Like what we are doing? Feel free to use our templates to make your research more transparent and open. If you have any questions, please contact Dr. Anne M. Brown at [email protected]

Development and validation of the Psychological Adaptation Scale (PAS): Use in six studies of adaptation to a health condition or risk

OBJECTIVE: We introduce The Psychological Adaptation Scale (PAS) for assessing adaptation to a chronic condition or risk and present validity data from six studies of genetic conditions. METHODS: Informed by theory, we identified four domains of adaptation: effective coping, self-esteem, social integration, and spiritual/existential meaning. Items were selected from the PROMIS “positive illness impact” item bank and adapted from the Rosenberg self-esteem scale to create a 20-item scale. Each domain included five items, with four sub-scale scores. Data from studies of six populations: adults affected with or at risk for genetic conditions (N=3) and caregivers of children with genetic conditions (N=3) were analyzed using confirmatory factor analyses (CFA). RESULTS: CFA suggested that all but five posited items converge on the domains as designed. Invariance of the PAS amongst the studies further suggested it is a valid and reliable tool to facilitate comparisons of adaptation across conditions. CONCLUSION: Use of the PAS will standardize assessments of adaptation and foster understanding of the relationships among related health outcomes, such as quality of life and psychological well-being. PRACTICE IMPLICATIONS: Clinical interventions can be designed based on PAS data to enhance dimensions of psychological adaptation to a chronic health condition or risk

Correction: Variants in MED12L, encoding a subunit of the Mediator kinase module, are responsible for intellectual disability associated with transcriptional defect

International audienceIn the Acknowledgements section of the paper the authors neglected to mention that the study was supported by a grant from the National Human Genome Research Institute (NHGRI) UM1HG007301 (S.H., M.L.T.). In addition, the award of MD was associated with the authors Michelle L. Thompson and Susan Hiatt instead of PhD. The PDF and HTML versions of the Article have been modified accordingly