Evaluating challenges for improving medically unexplained symptoms in US military veterans via provider communication

Objectives: Medically unexplained symptoms (MUS) are common, with particularly high rates observed in military veterans. Effective patient-provider-communication is thought to be a key aspect of care; however there have been few empirical studies on the association between communication and outcomes for patients with MUS. We evaluate whether discussing veterans’ MUS-illness representations and good interpersonal skills have the potential to promote MUS-treatment adherence and improvement. Methods: Veterans experiencing MUS (n = 204) reported on their primary care providers’ communication about illness representations and interpersonal skills; correlation, regression, and bootstrap-mediation analyses were conducted to test hypotheses regarding veteran-reported outcomes. Main outcomes included satisfaction with the provider, MUS-treatment adherence, intentions to adhere, and expectations for MUS improvement. Results: Veterans reported infrequent discussion of MUS illness representations but high degrees of provider interpersonal skills. Communication regarding patients’ illness representations and treatment expectations was significantly related to treatment adherence and adherence intentions; provider interpersonal skills were not. Both were related to veteran satisfaction. Conclusions and practice implications: Providers’ interpersonal skills may be important in chronic illness contexts, such as MUS, by contributing to satisfaction with the provider. The current study suggests that providers may better promote MUS-treatment adherence through discussing MUS illness representations and treatment expectations

Genetic Background and Sex: Impact on Generalizability of Research Findings in Pharmacology Studies

Animal models consisting of inbred laboratory rodent strains have been a powerful tool for decades, helping to unravel the underpinnings of biological problems and employed to evaluate potential therapeutic treatments in drug discovery. While inbred strains demonstrate relatively reliable and predictable responses, using a single inbred strain alone or as a background to a mutation is analogous to running a clinical trial in a single individual and their identical twins. Indeed, complex etiologies drive the most common human diseases, and a single inbred strain that is a surrogate of a single genome, or data generated from a single sex, is not representative of the genetically diverse patient populations. Further, pharmacological and toxicology data generated in otherwise healthy animals may not translate to disease states where physiology, metabolism, and general health are compromised. The purpose of this chapter is to provide guidance for improving generalizability of preclinical studies by providing insight into necessary considerations for introducing systematic variation within the study design, such as genetic diversity, the use of both sexes, and selection of appropriate age and disease model. The outcome of implementing these considerations should be that reproducibility and generalizability of significant results are significantly enhanced leading to improved clinical translation

Luteinizing hormone acts at the hippocampus to dampen spatial memory

Luteinizing hormone (LH) rises dramatically during and after menopause, and has been correlated with an increased incidence of Alzheimer\u27s disease and decreased memory performance in humans and animal models. To test whether LH acts directly on the dorsal hippocampus to affect memory, ovariectomized female rats were infused with either the LH-homologue human chorionic gonadotropin (hCG) or the LH receptor antagonist deglycosylated-hCG (dg-hCG). Infusion of hCG into either the lateral ventricle or the dorsal hippocampus caused significant memory impairments in ovariectomized estradiol-treated females. Consistent with this, infusion of the LH antagonist dg-hCG into the dorsal hippocampus caused an amelioration of memory deficits in ovariectomized females. Furthermore, the gonadotropin-releasing hormone antagonist Antide, failed to act in the hippocampus to affect memory. These findings demonstrate a significant role for LH action in the dorsal hippocampus in spatial memory dysfunction

Evaluating challenges for improving medically unexplained symptoms in US military veterans via provider communication

Objectives: Medically unexplained symptoms (MUS) are common, with particularly high rates observed in military veterans. Effective patient-provider-communication is thought to be a key aspect of care; however there have been few empirical studies on the association between communication and outcomes for patients with MUS. We evaluate whether discussing veterans’ MUS-illness representations and good interpersonal skills have the potential to promote MUS-treatment adherence and improvement. Methods: Veterans experiencing MUS (n = 204) reported on their primary care providers’ communication about illness representations and interpersonal skills; correlation, regression, and bootstrap-mediation analyses were conducted to test hypotheses regarding veteran-reported outcomes. Main outcomes included satisfaction with the provider, MUS-treatment adherence, intentions to adhere, and expectations for MUS improvement. Results: Veterans reported infrequent discussion of MUS illness representations but high degrees of provider interpersonal skills. Communication regarding patients’ illness representations and treatment expectations was significantly related to treatment adherence and adherence intentions; provider interpersonal skills were not. Both were related to veteran satisfaction. Conclusions and practice implications: Providers’ interpersonal skills may be important in chronic illness contexts, such as MUS, by contributing to satisfaction with the provider. The current study suggests that providers may better promote MUS-treatment adherence through discussing MUS illness representations and treatment expectations.This article is published as Phillips, L. Alison, Lisa McAndrew, Benjamin Laman-Maharg, and Katharine Bloeser. "Evaluating challenges for improving medically unexplained symptoms in US military veterans via provider communication." Patient Education and Counseling 100, no. 8 (2017): 1580-1587. DOI: 10.1016/j.pec.2017.03.011. </p

The long-term effects of stress and kappa opioid receptor activation on conditioned place aversion in male and female California mice

Psychosocial stress leads to the activation of kappa opioid receptors (KORs), which induce dysphoria and facilitate depression-like behaviors. However, less is known about the long-term effects of stress and KORs in females. We examined the long-term effects of social defeat stress on the aversive properties of KOR activation in male and female California mice (Peromyscus californicus) using a conditioned place aversion paradigm. Female California mice naïve to social defeat, formed a place aversion following treatment with 2.5mg/kg of the KOR agonist U50,488, but females exposed to defeat did not form a place aversion to this dose. This supports the finding by others that social defeat weakens the aversive properties of KOR agonists. In contrast, both control and stressed males formed an aversion to 10mg/kg of U50,488. We also examined EGR1 immunoreactivity, an indirect marker of neuronal activity, in the nucleus accumbens (NAc) and found that stress and treatment with 10mg/kg of U50,488 increased EGR1 immunoreactivity in the NAc core in females but reduced activation in males. The effects of stress and U50,488 on EGR1 were specific to the NAc, as we found no differences in the bed nucleus of the stria terminalis. In summary, our data indicate important sex differences in the long-term effects of stress and indicate the need for further study of the molecular mechanisms mediating the behavioral effects of KOR in both males and females

Acute inhibition of kappa opioid receptors before stress blocks depression-like behaviors in California mice

Kappa opioid receptors (KOR) are considered to be a promising therapeutic target for stress-induced psychiatric disorders such as anxiety and depression. Preclinical data show that KOR antagonists have greater efficacy if administered before stressful experiences as opposed to afterwards. However, almost all of these studies use long-acting antagonists, leaving it unclear whether inhibition of KOR after stress is required for efficacy. Here we show that administration of the short-acting KOR antagonist AZ-MTAB before episodes of social defeat stress block the induction of anhedonia (both males and females) and social avoidance responses (females) that persist two weeks after stress. In both males and females pre-stress AZ-MTAB treatment also blunted anticipatory autogrooming behavior immediately prior to the third episode of defeat. In contrast when AZ-MTAB was administered two weeks after defeat (immediately before behavior testing) in female California mice, it was ineffective at reversing anhedonia and social avoidance. These results suggest that short-acting KOR antagonists may have greater therapeutic potential if administered before exposure to psychosocial stressors

Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis.

Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus), a species in which both males and females defend territories. We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF) protein but not mRNA in the bed nucleus of the stria terminalis (BNST) in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc). The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB) antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naïve to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females