Advances in human oxytocin measurement: challenges and proposed solutions.

Oxytocin, a neuropeptide known for its role in reproduction and socioemotional processes, may hold promise as a therapeutic agent in treating social impairments in patient populations. However, research has yet to uncover precisely how to manipulate this system for clinical benefit. Moreover, inconsistent use of standardized and validated oxytocin measurement methodologies-including the design and study of hormone secretion and biochemical assays-present unresolved challenges. Human studies measuring peripheral (i.e., in plasma, saliva, or urine) or central (i.e., in cerebrospinal fluid) oxytocin concentrations have involved very diverse methods, including the use of different assay techniques, further compounding this problem. In the present review, we describe the scientific value in measuring human endogenous oxytocin concentrations, common issues in biochemical analysis and study design that researchers face when doing so, and our recommendations for improving studies using valid and reliable methodologies.

Sleep Composition of Patients With Colorectal Cancer and Their Sleep-Partner Caregivers: Physical Health Correlates of Sleep Diary and Actigraphy Measurements.

BACKGROUND: Disturbed sleep is frequently identified in adult patients with cancer and their caregivers, with detrimental impact on physical health. Less known is the extent to which self-reported and actigraph-measured sleep patterns are similar between patients and their sleep-partner caregivers, and how these different modes of sleep measurements are related to physical health. METHODS: Patients diagnosed with colorectal cancer and their sleep-partner caregivers (81 dyads) completed a questionnaire for physical functioning and collected saliva samples for seven consecutive days, from which cortisol slope was quantified. Additionally, participants completed a daily sleep diary and wore actigraph for 14 consecutive days, from which sleep duration, sleep onset latency (SOL), and duration of wake after sleep onset (WASO) were calculated. RESULTS: Participants reported sleep patterns that fell within or close to the optimal range, which were similar between patients and their caregivers. Self-reported and actigraph-measured sleep duration had moderate levels of agreement (ICC = 0.604), whereas SOL and WASO had poor agreement (ICC = 0.269). Among patients, longer self-reported WASO was associated with poorer physical health and flatter cortisol slope (p ≤ 0.013). Among caregivers, longer self-reported SOL was associated with poorer physical functioning, actigraph-measured WASO was associated with steeper cortisol slope, and longer self-reported sleep markers studied than actigraph-measured were associated with poorer physical functioning (p ≤ 0.042). CONCLUSION: Findings suggest that employing multiple assessment modes for sleep and physical health is vital for comprehensive understanding of sleep health. Furthermore, when addressing patients' sleep health, it may be beneficial to include their sleep-partner caregivers who may experience similar disturbed sleep.

The associations of spirituality and Hispanic ethnicity with neuroendocrine biomarkers among patients with colorectal cancer.

OBJECTIVE: Dealing with cancer evokes not only physical and emotional distress, but may also promote resilience through spirituality. Patients with cancer are vulnerable to neuroendocrine dysregulation. This longitudinal observational study examined the degree to which spirituality was associated with neuroendocrine biomarkers and the moderating role of Hispanic ethnicity. METHODS: Participants were adults who were recently diagnosed with colorectal cancer (n = 81, 55 years old, 66% male, 63% Hispanic, 72% advanced cancer, 7 months post-diagnosis). The domains of spirituality (faith, meaning, and peace) and ethnicity (Hispanic vs. non-Hispanic) were self-reported. Cortisol and alpha amylase (sAA) were assayed from saliva samples collected at waking and bedtime on seven consecutive days. Mean levels at waking and bedtime, and diurnal slopes over seven days were calculated. Age and cancer stage were covariates. RESULTS: Overall, patients reported moderate to high levels of spirituality. General linear modeling revealed that greater faith was associated with higher levels of sAA at waking and bedtime as well as more blunted diurnal pattern of sAA only among Hispanic patients (p ≤ .045). Greater peace was associated with steeper diurnal pattern of sAA, regardless of ethnicity (B = 0.021, p = .005). Meaning and cortisol were not significantly associated with study variables. CONCLUSIONS: Findings indicate that presence of peace facing a cancer diagnosis associated with neuroendocrine regulation, whereas drawing on one's faith, particularly among Hispanic patients, associated with neuroendocrine dysregulation during the first months after the diagnosis. Further investigations of psychobiobehavioral moderators and mediators for healthy neuroendocrine functioning among patients with cancer are warranted.

Social anxiety is associated with greater peripheral oxytocin reactivity to psychosocial stress.

To date, it has been difficult to establish reliable biomarkers associated with specific forms of psychopathology. Social anxiety, for example, is associated with inconsistent biological responses to psychosocial stress on markers including cortisol and salivary alpha-amylase. Thus, it is critical that studies identify more reliable biomarkers that index patterns associated with social anxiety. Two potential candidates are the neuropeptides oxytocin and vasopressin, which have been implicated in stress responsivity across species. Studies have demonstrated a reliable increase in oxytocin, and a surrogate marker for vasopressin, following engagement in the most widely used lab-based psychosocial stress paradigm: the Trier Social Stress Test (TSST). However, no study has examined whether social anxiety moderates peripheral oxytocin or vasopressin reactivity to psychosocial stress. In 101 young adult participants, dimensionally assessed social anxiety was associated with greater plasma oxytocin, but not vasopressin, reactivity to the TSST. Results were maintained following the inclusion of depression as a covariate. Findings suggest that studying changes in peripheral oxytocin concentrations may be a method of differentiating individuals with higher levels of social anxiety.

Bioengineering the Endocrine Pancreas: Intraomental Islet Transplantation Within a Biologic Resorbable Scaffold.

Transplantation of pancreatic islets is a therapeutic option to preserve or restore ß-cell function. Our study was aimed at developing a clinically applicable protocol for extrahepatic transplantation of pancreatic islets. The potency of islets implanted onto the omentum, using an in situ-generated adherent, resorbable plasma-thrombin biologic scaffold, was evaluated in diabetic rat and nonhuman primate (NHP) models. Intraomental islet engraftment in the biologic scaffold was confirmed by achievement of improved metabolic function and preservation of islet cytoarchitecture, with reconstitution of rich intrainsular vascular networks in both species. Long-term nonfasting normoglycemia and adequate glucose clearance (tolerance tests) were achieved in both intrahepatic and intraomental sites in rats. Intraomental graft recipients displayed lower levels of serum biomarkers of islet distress (e.g., acute serum insulin) and inflammation (e.g., leptin and α2-macroglobulin). Importantly, low-purity (30:70% endocrine:exocrine) syngeneic rat islet preparations displayed function equivalent to that of pure (>95% endocrine) preparations after intraomental biologic scaffold implantation. Moreover, the biologic scaffold sustained allogeneic islet engraftment in immunosuppressed recipients. Collectively, our feasibility/efficacy data, along with the simplicity of the procedure and the safety of the biologic scaffold components, represented sufficient preclinical testing to proceed to a pilot phase I/II clinical trial.