Facilitation of Serotonin Signaling by SSRIs is Attenuated by Social Isolation

Hypofunction of the serotonergic system is often associated with major depression and obsessive compulsive disorder (OCD). Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to treat these disorders, and require 3–6 weeks of chronic treatment before improvements in the symptoms are observed. SSRIs inhibit serotonin''s transporter, and in doing so, increase extracellular serotonin concentrations. Thus, efficacy of SSRIs likely depends upon the brain''s adaptive response to sustained increases in serotonin levels. Individual responsiveness to SSRI treatment may depend on a variety of factors that influence these changes, including ongoing stress. Social isolation is a passive, naturalistic form of chronic mild stress that can model depression in rodents. In this study, we examined how 20-day treatment with the SSRI citalopram (CIT) alters marble-burying (MB), open field behavior, and serotonin signaling in single- vs pair-housed animals. We used in vivo voltammetry to measure electrically evoked serotonin, comparing release rate, net overflow, and clearance. Pair-housed mice were significantly more responsive to CIT treatment, exhibiting reduced MB and facilitation of serotonin release that positively correlated with the frequency of electrical stimulation. These effects of CIT treatment were attenuated in single-housed mice. Notably, although CIT treatment enhanced serotonin release in pair-housed mice, it did not significantly alter uptake rate. In summary, we report that chronic SSRI treatment facilitates serotonin release in a frequency-dependent manner, and this effect is blocked by social isolation. These findings suggest that the efficacy of SSRIs in treating depression and OCD may depend on ongoing stressors during treatment.     

Antidepressant use and risk of central nervous system metastasis

Selective serotonin reuptake inhibitors (SSRIs), a class of antidepressants, were found to increase central nervous system (CNS) metastasis in mice. Our study investigated in humans whether antidepressants, and specifically SSRIs, increased the relative odds of CNS metastasis. We identified 189 cases of CNS metastasis amongst breast cancer, melanoma, and non-Hodgkin lymphoma subjects who were diagnosed with CNS metastasis or infiltration between January 1, 2005 and September 30, 2013 and 756 controls (patients without CNS metastasis or infiltration). Using logistic regression, we estimated the relative odds of CNS metastasis associated with antidepressant use adjusting for relevant covariates. The prevalence of antidepressants was 28.6?% in cases and 27.5?% in controls, whereas SSRIs were used in 16.9?% of cases and 17.3?% of controls. Among all patients, antidepressants were not associated with CNS metastasis or infiltration. No consistent patterns of association were observed in the analyses of other cancer subsets or exposure measures, with the possible exception of an increased risk of CNS metastasis associated with ‘any SSRI use’ among breast cancer patients (OR?=?1.73, 95?% CI?=?0.75, 4.04). We did not observe clear patterns of association, which may be due in part to the small sample size in many of our analyses.     

Evaluating Barriers to Bystander CPR among Laypersons before and after Compression-only CPR Training

Objective: Bystander CPR is an essential part of out-of-hospital cardiac arrest (OHCA) survival. EMS and public safety jurisdictions have embraced initiatives to teach compression-only CPR to laypersons in order to increase rates of bystander CPR. We examined barriers to bystander CPR amongst laypersons participating in community compression-only CPR training and the ability of the training to alleviate these barriers. The barriers analyzed include fear of litigation, risk of disease transmission, fear of hurting someone as a result of doing CPR when unnecessary, and fear of hurting someone as a result of doing CPR incorrectly. Methods: Laypersons attending community compression-only CPR training were administered surveys before and after community CPR training. Data were analyzed via standard statistical analyses. Results: A total of 238 surveys were collected and analyzed between September 2015 and January 2016. The most common reported motivation for attending CPR training was “to be prepared/just in case” followed by “infant or child at home.” Respondents reported that they were significantly more likely to perform CPR on a family member than a stranger in both pre-and post-training responses. Nevertheless, reported self-confidence in and likelihood of doing CPR on both family and strangers increased from pre-training to post-training. There was a statistically significant decrease in reported likelihood of all four barriers to prevent respondents from performing bystander CPR when pre-training responses were compared to post-training responses. Previous CPR training and history of having witnessed a sudden cardiac arrest (SCA) were both associated with decreased barriers to CPR, but previous training had no effect on reported likelihood of or confidence in performing CPR. Conclusion: The training initiative studied significantly reduced the reported likelihood of all barriers studied to prevent respondents from performing bystander CPR and also increased the reported confidence in doing CPR and likelihood of doing CPR on both strangers and family. However, it did not alleviate the pre-training discrepancy between likelihood of performing CPR on strangers versus family. Previous CPR training or certification had no impact on likelihood of or confidence in performing CPR.     

Current Use of Statins for Primary Prevention of Cardiovascular Disease: Patient-Reported Outcomes and Adherence

Recent updates in atherosclerotic cardiovascular disease (ASCVD) risk assessment and management guidelines have expanded the global number of statin-indicated persons, prompting clinicians to rethink conversations about initiating new statin therapy. The benefits of statins in primary prevention of ASCVD are less convincing than in secondary prevention, although higher ASCVD risk is associated with greater statin benefit. Therefore, clinicians must engage patients in a shared decision about starting new statin therapy, which should involve discussion about the risks and benefits of therapy, patient perceptions, and health status. Research has identified nonadherence to statin therapy as a factor associated with reduced clinical benefits of statin therapy. Clinicians should be aware of patient-specific factors associated with nonadherence and implement strategies to improve adherence as indicated. Data on the impact of adherence improvement strategies and the accuracy of how we currently measure adherence are lacking. Additionally, research focusing on patient preferences and reported outcomes would greatly inform practice and improve clinician–patient relationships.     

Does the home environment and the sex of the child modify the adverse effects of prenatal exposure to chlorpyrifos on child working memory?

Prenatal exposure to chlorpyrifos (CPF), an organophosphorus insecticide, has long been associated with delayed neurocognitive development and most recently with decrements in working memory at age 7. In the current paper, we expanded the previous work on CPF to investigate how additional biological and social environmental factors might create or explain differential neurodevelopmental susceptibility, focusing on main and moderating effects of the quality of the home environment (HOME) and child sex. We evaluate how the quality of the home environment (specifically, parental nurturance and environmental stimulation) and child sex interact with the adverse effects of prenatal CPF exposure on working memory at child age 7years. We did not observe a remediating effect of a high quality home environment (either parental nurturance or environmental stimulation) on the adverse effects of prenatal CPF exposure on working memory. However, we detected a borderline significant interaction between prenatal exposure to CPF and child sex (B (95% CI) for interaction term=-1.714 (-3.753 to 0.326)) suggesting males experience a greater decrement in working memory than females following prenatal CPF exposure. In addition, we detected a borderline interaction between parental nurturance and child sex (B (95% CI) for interaction term=1.490 (-0.518 to 3.499)) suggesting that, in terms of working memory, males benefit more from a nurturing environment than females. To our knowledge, this is the first investigation into factors that may inform an intervention strategy to reduce or reverse the cognitive deficits resulting from prenatal CPF exposure.