Success of in vitro fertilization and its association with the levels of psychophysiological stress before and during the treatment.

Despite the advance of assisted reproduction, high rates of failure in treatment are still observed. Herein, we investigated how the psychophysiological stress profiles of patients can modulate the in vitro fertilization treatment (IVF) outcome. The women who had failure in IVF (n = 13; 65%) had higher baseline salivary cortisol awakening response and anxiety-state during treatment than patients who became pregnant (n = 7; 35%). Patients with major stress levels and religious coping style showed lower social support, which was correlated with higher anxiety. Therefore, we appointed stress modulators that negatively affect IVF and should be improved aiming to increase its success.

Welfare Improvement by Enrichment Programs in Common Marmoset Females Under Social Isolation.

Animal welfare is critical to buffer stress in captive animals and to ensure the reliability of data from studies. The most usual environmental enrichment technique (EE) for social non-human primates is the social enrichment. However, some experimental protocols require keeping individuals isolated, thus demanding other types of EE. We tested in six adult Callithrix jacchus females, single housed for experimental purpose, the stress buffering efficacy of a structural enrichment protocol (SEP) and SEP in combination with a foraging enrichment (FSEP) using  fecal cortisol and behaviors to infer stress levels. Both types of EE improved welfare in different ways, while cortisol levels decreased with both EE as compared to the baseline, autogrooming, and piloerection increased after FSEP probably due to the new foods. Therefore, these findings support alternative practices of EE when social animals are living in isolation and reinforce the positive role of structural and food enrichment for decreasing stress markers. It also encourages studies on welfare with females, since its use as an animal model has increased.

Moderators of ayahuasca's biological antidepressant action.

Introduction: The understanding of biological responses to psychedelics with antidepressant potential is imperative. Here we report how a set of acute parameters, namely emotional (depressive symptoms), cognitive (psychedelic experience), and physiological (salivary cortisol), recorded during an ayahuasca dosing session, modulated serum brain-derived neurotrophic factor (BDNF), serum cortisol (SC), serum interleukin 6 (IL-6), plasma C-reactive protein (CRP), and salivary cortisol awakening response (CAR). Methods: Results were analyzed 2 days after the psychedelic intervention (ayahuasca) versus placebo in both patients with treatment-resistant depression and healthy volunteers. These measures were assessed as part of a randomized double-blinded, placebo-controlled trial (n = 72). Results: Results revealed that larger reductions of depressive symptoms during the dosing session significantly moderated higher levels of SC in patients. Whereas lesser changes in salivary cortisol levels during the ayahuasca intervention were related to higher BDNF levels in patients with a larger clinical response in the reduction in depressive symptoms. No moderator was found for patient's CAR, IL-6, and CRP responses to ayahuasca and for all biomarker responses to ayahuasca in healthy controls and in the placebo group. Discussion: In summary, some specific emotional and physiological parameters during experimental ayahuasca session were revealed as critical moderators of the improvement of major depression biomarkers, mainly BDNF and SC two days after ayahuasca intake. These findings contribute to paving the way for future studies investigating the biological antidepressant response to psychedelic therapy.

Pathophysiology of Major Depression by Clinical Stages.

The comprehension of the pathophysiology of the major depressive disorder (MDD) is essential to the strengthening of precision psychiatry. In order to determine the relationship between the pathophysiology of the MDD and its clinical progression, analyzed by severity of the depressive symptoms and sleep quality, we conducted a study assessing different peripheral molecular biomarkers, including the levels of plasma C-reactive protein (CRP), serum mature brain-derived neurotrophic factor (mBDNF), serum cortisol (SC), and salivary cortisol awakening response (CAR), of patients with MDD (n = 58) and a control group of healthy volunteers (n = 62). Patients with the first episode of MDD (n = 30) had significantly higher levels of CAR and SC than controls (n = 32) and similar levels of mBDNF of controls. Patients with treatment-resistant depression (TRD, n = 28) presented significantly lower levels of SC and CAR, and higher levels of mBDNF and CRP than controls (n = 30). An increased severity of depressive symptoms and worse sleep quality were correlated with levels low of SC and CAR, and with high levels of mBDNF. These results point out a strong relationship between the stages clinical of MDD and changes in a range of relevant biological markers. This can assist in the development of precision psychiatry and future research on the biological tests for depression.

Changes in inflammatory biomarkers are related to the antidepressant effects of Ayahuasca.

BACKGROUND: Ayahuasca is a traditional Amazon brew and its potential antidepressant properties have recently been explored in scientific settings. We conducted a double-blind placebo-controlled trial of ayahuasca with treatment-resistant depression patients (n = 28) and healthy controls (n = 45). AIMS: We are evaluating the blood inflammatory biomarkers: C-reactive protein and interleukin 6, as a potential consequence of ayahuasca intake and their correlation with serum cortisol and brain-derived neurotrophic factor levels. Blood samples were collected at pre-treatment and 48 hours after substance ingestion to assess the concentration of inflammatory biomarkers, together with administration of the Montgomery-Åsberg Depression Rating Scale. RESULTS: At pre-treatment, patients showed higher C-reactive protein levels than healthy controls and a significant negative correlation between C-reactive protein and serum cortisol levels was revealed (rho = -0.40, n = 14). C-reactive protein in those patients was not correlated with Montgomery-Åsberg Depression Rating Scale scores. We observed a significant reduction of C-reactive protein levels across time in both patients and controls treated with ayahuasca, but not with placebo. Patients treated with ayahuasca showed a significant correlation (rho = + 0.57) between larger reductions of C-reactive protein and lower depressive symptoms at 48 hours after substance ingestion (Montgomery-Åsberg Depression Rating Scale). No significant result with respect to interleukin 6 and brain-derived neurotrophic factor was found. Furthermore, these biomarkers did not predict the antidepressant response or remission rates observed. CONCLUSIONS: These findings enhance the understanding of the biological mechanisms behind the observed antidepressant effects of ayahuasca and encourage further clinical trials in adults with depression.

Changes in Cortisol but Not in Brain-Derived Neurotrophic Factor Modulate the Association Between Sleep Disturbances and Major Depression.

Sleep disturbance is a symptom consistently found in major depression and is associated with a longer course of illness, reduced response to treatment, increased risk of relapse and recurrence. Chronic insomnia has been associated with changes in cortisol and serum brain-derived neurotrophic factor (BDNF) levels, which in turn are also changed in major depression. Here, we evaluated the relationship between sleep quality, salivary cortisol awakening response (CAR), and serum BDNF levels in patients with sleep disturbance and treatment-resistant major depression (n = 18), and in a control group of healthy subjects with good (n = 21) and poor (n = 18) sleep quality. We observed that the patients had the lowest CAR and sleep duration of all three groups and a higher latency to sleep than the healthy volunteers with a good sleep profile. Besides, low CAR was correlated with more severe depressive symptoms and worse sleep quality. There was no difference in serum BDNF levels between groups with distinct sleep quality. Taken together, our results showed a relationship between changes in CAR and in sleep quality in patients with treatment-resistant depression, which were correlated with the severity of disease, suggesting that cortisol could be a physiological link between sleep disturbance and major depression.

Effect of chronic stress during adolescence in prefrontal cortex structure and function.

Critical periods of plasticity (CPPs) are defined by developmental intervals wherein neuronal circuits are most susceptible to environmental influences. The CPP of the prefrontal cortex (PFC), which controls executive functions, extends up to early adulthood and, like other cortical areas, reflects the maturation of perineuronal nets (PNNs) surrounding the cell bodies of specialized inhibitory interneurons. The aim of the present work was to evaluate the effect of chronic stress on both structure and function of the adolescent's rat PFC. We subjected P28 rats to stressful situations for 7, 15 and 35days and evaluated the spatial distribution of histochemically-labeled PNNs in both the Medial Prefrontal Cortex (MPFC) and the Orbitofrontal Cortex (OFC) and PFC-associated behavior as well. Chronic stress affects PFC development, slowing PNN maturation in both the (MPFC) and (OFC) while negatively affecting functions associated with these areas. We speculate upon the risks of prolonged exposure to stressful environments in human adolescents and the possibility of stunted development of executive functions.

Physiological and behavioral responses to routine procedures in captive common marmosets (Callithrix jacchus).

The effect of routine captive procedures on the welfare of species used as experimental models in biomedical research is of great interest, since stress may alter the generalization and interpretation of results. This study investigated behavioral and endocrine (fecal cortisol) reactivity patterns in common marmoset (Callithrix jacchus) adult males (N = 10) and females (N = 9) subjected to three types of routine procedures in captivity: (1) moving to a same-sized cage (P1), to a smaller cage (P2), and (2) first-time pair formation (P3). Sexually dimorphic cortisol responses were detected in animals submitted to a physical environmental stressor (cage change). Females showed an increased response throughout P1, in relation to baseline (BP) cortisol, and a trend during P2. Males increased cortisol only during P2. On the other hand, males and females showed a similar endocrine response when management involved social challenge (pair formation), with both sexes increasing cortisol levels, but females exhibited a more intense and longer-lasting cortisol increase. Males and females exhibited similar behavioral responses to cage change, except for autogrooming, with males decreasing this behavior in P1. Only females demonstrated a significantly higher increase in piloerection frequency than that of males during the pair formation phase. These endocrine and behavioral changes must be taken into account when interpreting research data that involve these types of procedures. Further studies on the impacts of routine colony management are required to devise and include protocols in official husbandry guidelines.