Inflammatory biomarkers and perinatal depression: A systematic review.

BACKGROUND: Approximately 10 to 20% of pregnant women worldwide experience perinatal depression (PND), a depressive episode with onset during pregnancy or after childbirth. We performed a systematic review to identify, summarize and discuss studies on inflammatory biomarkers described in relation to PND. METHOD: Inclusion criteria defined the selection of observational studies written in English, French, Spanish or Portuguese, that evaluate analytical levels of inflammatory molecules (protein levels) in biological fluids in women, with a diagnosis of depression using ICD/DSM diagnostic criteria or depressive symptoms assessed by standardized psychometric instruments, during pregnancy and/or postpartum. Case reports, experimental studies, reviews, qualitative analysis, meta-analysis, gray literature or replicated data were excluded. Three electronic databases were used for search (Pubmed, Web of Science and PsychInfo) and quality assessment of selected studies were performed using the Newcastle-Ottawa Scale. Data extraction included study design; number of subjects; obstetric information; tools and timepoints of depression and inflammatory markers assessment. RESULTS: 56 studies (sample size for cross-sectional and case-control studies ranging from 10 to 469; sample size for longitudinal studies ranging from 26 to 467), where the major aim was to analyze the association between depression and inflammatory biomarkers during pregnancy and postpartum period were included in this systematic review. Overall, the findings of our systematic review lend support to the hypothesis that several inflammatory markers may be associated with peripartum depressive symptoms. The associations were somewhat different looking at pregnancy compared to the delivery time-point and postpartum, and mainly referred to increased levels of IL-6, IL-8, CRP and TNF-α among depressed. DISCUSSION: In summary, our systematic review findings provide evidence supporting the hypothesis that several inflammatory markers may correlate with peripartum depressive symptoms. However, our work also highlighted notable differences in the timing of biological sampling for inflammatory markers and in the methodologies used to assess depression during the perinatal period. Additionally, variations were observed in how inflammatory biomarkers and depression were approached, including their classification as exposure or outcome variables, and the timing of assessments. It is essential for future research to investigate the influence of biological fluids and the timing of assessments for both inflammatory biomarkers and depression to gain a deeper understanding of their association. This comprehensive exploration is pivotal for elucidating the intricate relationship between inflammation and perinatal depression.

Helping behavior in rats (Rattus norvegicus) when an escape alternative is present.

Prosocial behavior in rats is known to occur in response to a familiar rat's distress, but the motivations underlying prosocial behavior remain elusive. In this study, we adapted the experimental setting of Ben-Ami Bartal, Decety, and Mason (2011) to explore different motivations behind helping behavior in adolescent rats. In the original setting, a free rat is placed in an arena where a cagemate is trapped inside a restrainer that can only be opened from the outside by the free rat. Here we added a dark compartment to the experimental setting that allowed the free rat to escape the arena and the distress evoked by the trapped cagemate, based on rodents' aversion to bright areas. As a control, we tested rats in the same arena but with the door to the dark area closed. Our results showed that all free rats, except one in the escape condition, learned to open the restrainer's door. However, in the escape condition, rats took significantly longer to open the restrainer to the cagemates when compared with rats that could not escape. To further explore the motivations underlying these group differences in door-opening latencies, we measured both rats' behavior. We found that struggling behavior (i.e., distress) in the trapped rat did not affect door-opening, whereas exploratory behavior (i.e., proactive/positive behavior) in both rats contributed to shorter times. Our results highlight that adolescent rats show prosocial behavior even when they can escape without helping and contribute to demonstrate the role of positive emotional states in prosocial behavior. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Associations between fetal testosterone and pro-social tendencies, anxiety and autistic symptoms in Williams syndrome: a preliminary study.

Objective: Fetal testosterone (fT) has organizational effects on the developing human nervous system and can be reliably estimated by the ratio between the length of the second and fourth digits - 2D:4D. Previous studies reported altered patterns of fT in some developmental disabilities (e.g. ASD) relative to typically developing individuals (TD). Williams syndrome (WS) is a rare genetic disorder characterized by exacerbated empathy and social approach and heightened anxiety. Recent reports also highlight the co-occurrence of significant levels of autistic symptoms. Despite constituting an interesting model to study androgenic contributions to social behavior, no studies have sought to explore fT in WS. The main aims of this preliminary study were two-fold: (a) to compare 2D:4D in WS and TD; (b) to analyze the pattern of associations between 2D:4D and hypersociability, affective and cognitive empathy, anxiety and autistic symptoms in WS. Methods: 2D:4D were measured from digital scans of the ventral surface of the right hand. Hypersociability, empathy, anxiety and autistic symptoms were obtained from parental reports. Results: There were no significant differences in 2D:4D between WS than TD. In WS lower fT (higher 2D:4D) was significantly associated with hypersociability and affective empathy, as well as marginally associated with anxiety/depression scores. In contrast, cognitive empathy was marginally and negatively associated with 2D:4D, while levels of autistic symptoms were unrelated with this measure. Conclusion: Our results suggest that fT may be implicated in the emergence of several cardinal features of WS, namely hypersociability, affective empathy and anxiety, but not in ASD symptoms.

Differential activation of the default mode network in jet lagged individuals.

Long-term exposure to transmeridian flights has been shown to impact cognitive functioning. Nevertheless, the immediate effects of jet lag in the activation of specific brain networks have not been investigated. We analyzed the impact of short-term jet lag on the activation of the default mode network (DMN). A group of individuals who were on a transmeridian flight and a control group went through a functional magnetic resonance imaging acquisition. Statistical analysis was performed to test for differences in the DMN activation between groups. Participants from the jet lag group presented decreased activation in the anterior nodes of the DMN, specifically in bilateral medial prefrontal and anterior cingulate cortex. No areas of increased activation were observed for the jet lag group. These results may be suggestive of a negative impact of jet lag on important cognitive functions such as introspection, emotional regulation and decision making in a few days after individuals arrive at their destination.

The behavioral and immunological impact of maternal separation: a matter of timing.

Maternal separation (MS), an early life stressful event, has been demonstrated to trigger neuropsychiatric disorders later in life, in particular depression. Experiments using rodents subjected to MS protocols have been very informative for the establishment of this association. However, the mechanism by which MS leads to neuropsychiatric disorders is far from being understood. This is probably associated with the multifactorial nature of depression but also with the fact that different research MS protocols have been used (that vary on temporal windows and time of exposure to MS). In the present study, MS was induced in rats in two developmental periods: for 6 h per day for 14 days between postnatal days 2-15 (MS2-15) and 7-20 (MS7-20). These two periods were defined to differ essentially on the almost complete (MS2-15) or partial (MS7-20) overlap with the stress hypo-responsive period. Behavioral, immunological, and endocrine parameters, frequently associated with depressive-like behavior, were analyzed in adulthood. Irrespectively from the temporal window, both MS exposure periods led to increased sera corticosterone levels. However, only MS2-15 animals displayed depressive and anxious-like behaviors. Moreover, MS2-15 was also the only group presenting alterations in the immune system, displaying decreased percentage of CD8(+) T cells, increased spleen T cell CD4/CD8 ratio, and thymocytes with increased resistance to dexamethasone-induced cell death. A linear regression model performed to predict depressive-like behavior showed that both corticosterone levels and T cell CD4/CD8 ratio explained 37% of the variance observed in depressive-like behavior. Overall, these findings highlight the existence of "critical periods" for early life stressful events to exert programing effects on both central and peripheral systems, which are of relevance for distinct patterns of susceptibility to emotional disorders later in life.

Diverse physical growth trajectories in institutionalized Portuguese children below age 3: relation to child, family, and institutional factors.

OBJECTIVE: To identify and analyze diverse longitudinal trajectories of physical growth of institutionalized children and their relation to child, family, and institutional factors. METHODS: 49 institutionalized children were studied for 9 months after admission. Weight, height, and head circumference were measured on 4 occasions, beginning at admission. Data were analyzed using latent class analysis, yielding diverse patterns of growth for each feature, and relations with child characteristics, early family risk factors, and institutional relational care were investigated. RESULTS: For each growth feature, 4 classes emerged: "Persistently Low," "Improving," "Deteriorating," and "Persistently High." Younger age at admission was a risk factor for impaired physical growth across all domains. Physical characteristics at birth were associated with trajectories across all domains. Lower prenatal risk and better institutional relational care were associated with Improving weight over time. CONCLUSIONS: Discussion highlights the role of children's physical features at birth, prenatal risk, and caregiver's cooperation with the child in explaining differential trajectories.

Interleukin-10: a key cytokine in depression?

An increasing body of evidence implicates proinflammatory cytokines in psychiatric disorders, namely, in depression. Of notice, recent studies showed that anti-inflammatory cytokines, such as IL-10, also modulate depressive-like behavior. In this article, we propose that the anti-inflammatory cytokine IL-10 is a putative link between two of the most widely reported phenomenon observed in depressed patients: the disruption of the hypothalamic-pituitary-adrenal axis and the imbalanced production of cytokines. If so, IL-10 might represent a novel target for antidepressant therapy.

The impact of age on emotional and cognitive behaviours triggered by experimental neuropathy in rats.

Chronic pain syndromes encompass several clinical entities that frequently affect the individuals' emotional and cognitive behaviours which, in turn, can also alter pain perception. Additionally, both pain perception and motivational-affective behaviours change with increasing age. In order to evaluate the influence of age upon the interaction between chronic pain and affective/cognitive behaviours, 3-, 10- and 22-month-old rats with 1 month neuropathy (spared nerve injury, SNI model) were compared with age-matched sham-operated controls in the open field (OF; locomotor and exploratory behaviours), elevated plus-maze (EPM; anxiety-like behaviour), forced swimming (FST; depressive-like behaviour), working memory water maze (WM; spatial short-term memory), Morris water maze (MWM; spatial reference memory) and spatial reversal (behavioural flexibility) tests. Locomotor and exploratory activities decreased steadily with age and were further reduced by SNI. Aging was associated with increased anxiety-like behaviour, which was potentiated by SNI in both 3- and 22-month-old rats. The performance in the FST was affected by SNI but only in mid-aged animals. Cognitive performances in the MWM and spatial reversal tests deteriorated with age; however, the SNI lesion was only detrimental in the reversal task to mid-aged animals. Our data demonstrate that the influence of neuropathic pain on affective and cognitive behaviours is age dependent and varies with the behavioural domain that is tested. Importantly, mid-aged animals seem to be more susceptible to depression and cognitive deterioration associated to chronic pain than young and old groups.

Glucocorticoids and neuro- and behavioural development.

Epidemiological evidence links exposure to stress hormones during fetal or early postnatal development with lifetime prevalence of cardiac, metabolic, auto-immune, neurological and psychiatric disorders. This has led to the concept of 'developmental programming through stress'. Importantly, these effects (specifically, hypertension, hyperglycaemia and neurodevelopmental and behavioural abnormalities) can be reproduced by exposure to high glucocorticoid levels, indicating a crucial role of glucocorticoids in their causation. However, there can be important differences in outcome, depending on the exact time of exposure, as well as duration and receptor selectivity of the glucocorticoid applied. The mechanisms underlying programming by stress are still unclear but it appears that these environmental perturbations exploit epigenetic modifications of DNA and/or histones to induce stable modifications of gene expression. Programming of neuro- and behavioural development by glucocorticoids and stress are important determinants of lifetime health and should be a consideration when choosing treatments in obstetric and neonatal medicine.

IL-10 modulates depressive-like behavior.

The role of pro-inflammatory cytokines in psychiatric disorders has been the focus of great research attention in recent years. Paradoxically, the same is not true for anti-inflammatory cytokines. In the present study, we assessed the behavioral profile of animals with altered expression of the anti-inflammatory cytokine IL-10. We performed a battery of tests to assess anxiety, depressive-like and cognitive behaviors in mice overexpressing IL-10 (PMT10) and IL-10(-/-) animals; in the later mice we also tested the behavioral effect of IL-10 administration. In the forced-swimming test, IL-10(-/-) females displayed increased depressive-like behavior; importantly, this phenotype was reverted by the injection of IL-10. Moreover, mice overexpressing IL-10 presented a decreased depressive-like behavior. Despite the presence of a similar trend, male animals did not reach significant differences in depressive-like behavior. Assessment in the open-field showed that the absence of IL-10 decreased the percentage of time spent in the center of the arena in both male and female mice, while male animals overexpressing IL-10 revealed an opposite behavior. For both sexes, imbalance in IL-10 levels did not affect spatial reference memory. In conclusion, variations in IL-10 expression are associated with an altered depressive-like behavior, but do not influence cognitive performance. Interestingly, IL-10 imbalance produced more profound behavioral changes in females than in male animals. This is in accordance with clinical data demonstrating an increased susceptibility of women to mood disorders, suggesting an interplay between anti-inflammatory cytokines and sexual steroids.