Bridging the mood and stress hormone levels between mothers and their babies: The study design and first preliminary results.

The neurobiological mechanisms involved in the influence of post-partum maternal mood fluctuations on child development are far from being understood. Here we present the design of an ongoing study aimed to test the hypothesis that the mental state of the mother has an impact on her neonate which is manifested by similarities in the neuroendocrine function of the mother and the child. The hypothesis is being tested under both stress and non-stress conditions in mothers and babies aged 3-4 days and 7-9 months. The focus will be given to correlations with maternal postpartum mood. To confirm the correctness of methodological approaches and the feasibility of the study several preliminary analyses were performed. Salivary alpha-amylase activity as a marker of sympathetic activation and cortisol as the effective hormone of the hypothalamic-pituitary-adrenocortical axis were measured. The obtained results showed the feasibility of saliva sampling in neonates using a sampling time of 120 s. The analysis of cortisol in hair revealed increased concentrations during the third trimester of pregnancy, which is consistent with the knowledge of high cortisol concentrations during pregnancy. A positive correlation was observed between salivary cortisol values before and after the stress test in mother-infant dyads at both the post-partum period and 7-9 months thereafter. Understanding the mechanisms involved in "the bridge" between the mother and her baby will help to develop necessary interventions directed to help mothers in the early postpartum period.

Relationships between antenatal corticosteroids and catecholamine blood pressure support in neonates: considering of maternal stress-related diseases.

Healthy child development is under the influence of prenatal and perinatal exposure to stress stimuli. The aim of this study is to test the hypotheses that (1) neonates requiring catecholamine blood pressure support are more often born to mothers with stress-related cardiometabolic diseases, (2) maternal stress-related diseases are associated with more frequent requirement of maternal corticosteroid treatment and (3) antenatal steroid exposure of neonates reduces the need of postnatal catecholamine support. A retrospective cohort study was performed on a sample of 427 mature (13%), preterm (64%) and extremely preterm (23%) neonates of both sexes. Mothers at risk of preterm delivery were treated with dexamethasone. The blood pressure support in neonates was performed by intravenous treatment via umbilical or epicutaneous venous catheter with dopamine (5 ug/kg/min) or dobutamine (5 ug/kg/min) or a combination of both. The results showed a lack of association between maternal stress-related diseases and the complicated outcome of their neonates. Maternal treatment with corticosteroid dexamethasone was associated with lower frequency of catecholamine blood pressure support requirement. Catecholamine support was more needed in male infants. Thus, the occurrence of maternal cardiometabolic stress-related diseases does not appear to be related to the need of catecholamine support in the neonate. In agreement with the second hypothesis, a more frequent maternal corticosteroid treatment was associated with the presence of maternal stress-related diseases. Most importantly, the obtained results support the hypothesis on positive influence of maternal glucocorticoid administration on cardiovascular outcome of the neonate, representing an additional beneficial effect of antenatal corticosteroids. LAY SUMMARY Maternal hypertension, diabetes and obesity, which belong to cardiometabolic stress-related diseases, failed to show a negative influence on neonatal health as was determined by the need of catecholamine blood pressure support in a large sample of 427 immature and mature newborns. Since glucocorticoids are often viewed as negative agents that should be avoided, the important finding of the present study is the beneficial effect of maternal corticosteroid treatment on blood pressure stability of the neonate.

Perinatal exposure to venlafaxine leads to lower anxiety and depression-like behavior in the adult rat offspring.

Depression during pregnancy and in the post-partum period is a growing health issue. Venlafaxine, a representative of serotonin and noradrenaline reuptake inhibitors, is used to treat a wide spectrum of mood disorders. However, the limited number of prenatal and perinatal studies raises the question about the long-term consequences of venlafaxine therapy. The aim of this study was to investigate the effect of venlafaxine exposure during pregnancy and lactation on anxiety-like and depression-like behaviors, as well as adrenocortical hormone concentrations in the adult rat offspring. For this purpose, rat dams were treated orally with venlafaxine from day 15 of gestation to postnatal day 20 at doses of 7.5, 37.5, and 75 mg/kg. Administration of venlafaxine during gestation and lactation affected anxiety-like and depression-like behaviors in adult rat offspring of both sexes. The animals exposed through their mothers to venlafaxine, particularly at the lowest and middle doses, were less anxious and less depressive in several relevant behavioral tests, which can be considered a deviation from the normal state. At clinically relevant doses, venlafaxine did not alter circulating level of corticosterone and aldosterone in the adult offspring. In general, the consequences of venlafaxine were dose dependent and more apparent in females. Together, these results suggest that prenatal and early postnatal exposure to venlafaxine may interfere with functional development of the brain, though not necessarily in a negative way.

Autonomic Nervous System Response to Stressors in Newly Diagnosed Patients with Multiple Sclerosis.

Autonomic dysfunction is commonly detected in patients with multiple sclerosis (MS). However, data evaluating autonomic nervous system function in early MS are limited. Present study investigates response to two different stressors in newly diagnosed MS patients, looking for the signs of autonomic dysfunction at the beginning of the disease. We examined 19 MS patients and 19 age, sex, and body mass index matched healthy controls. MS patients were newly diagnosed, untreated, and with low expanded disability status scale (EDSS) values [median 1.0 (interquartile range 1.0-1.5)]. Two stressors were used to evaluate the response of autonomic nervous system: Stroop word-color interference mental stress test and orthostasis. Plasma levels of epinephrine and norepinephrine, blood pressure (BP), and heart rate variability (HRV) parameters were evaluated. At the end of Stroop test MS patients had lower systolic BP (121 ± 15 vs. 132 ± 17 mmHg, p = 0.044), lower heart rate (79 ± 9 vs. 88 ± 16 1/min, p = 0.041), and lower epinephrine increment (10 ± 22 vs. 30 ± 38 pg/ml; p = 0.049) compared to healthy controls. Norepinephrine response was unaffected in MS, however, with lower norepinephrine levels during the test (p = 0.036). HRV parameters were similar in both groups. No differences in BP, heart rate, catecholamines, and HRV parameters between groups during orthostatic testing were found. We found slightly diminished sympathetic response to mental stress test, but unchanged response to orthostasis, in newly diagnosed untreated MS patients. The results suggest that autonomic dysfunction in MS is connected with more developed disease.

Early cognitive impairment along with decreased stress-induced BDNF in male and female patients with newly diagnosed multiple sclerosis.

The aim of this study was to evaluate neuroendocrine activation during stress in patients with recently diagnosed multiple sclerosis before starting the immunomodulatory therapy (EDSS score≤2.0). We verified the hypothesis that certain cognitive and affective dysfunction is present already at this early stage of the disease. The sample consisted of 38 subjects, which involved patients who were recently diagnosed multiple sclerosis and age- and sex-matched healthy volunteers. Stroop test served as mental stress model enabling measurement of cognitive performance. Present results showed increased state anxiety, depression scores and poorer performance in the Stroop test in the group of patients compared to healthy subjects. The cognitive dysfunction was particularly evident in male patients with simultaneously decreased concentrations of the brain-derived neurotrophic factor (BDNF) in plasma. The patients at this stage of the disease have not yet developed the hyperactivity of the hypothalamic-pituitary-adrenocortical axis. They showed normal levels of plasma copeptin and reduced aldosterone response to mental stress test in women only. Concentrations of plasma copeptin were higher in men compared to women. Very early stages of multiple sclerosis are accompanied by disturbances in psychological well-being, mild cognitive dysfunction and decreased plasma concentrations of BDNF, particularly in male patients.

Comparison of stress-induced changes in adults and pups: is aldosterone the main adrenocortical stress hormone during the perinatal period in rats?

Positive developmental impact of low stress-induced glucocorticoid levels in early development has been recognized for a long time, while possible involvement of mineralocorticoids in the stress response during the perinatal period has been neglected. The present study aimed at verifying the hypothesis that balance between stress-induced glucocorticoid and mineralocorticoid levels is changing during postnatal development. Hormone responses to two different stressors (insulin-induced hypoglycaemia and immune challenge induced by bacterial lipopolysaccharid) measured in 10-day-old rats were compared to those in adults. In pups corticosterone responses to both stressors were significantly lower than in adults, which corresponded well with the stress hyporesponsive period. Importantly, stress-induced elevations in aldosterone concentration were significantly higher in pups compared both to corticosterone elevations and to those in adulthood with comparable adrenocorticotropin concentrations in the two age groups. Greater importance of mineralocorticoids compared to glucocorticoids in postnatal period is further supported by changes in gene expression and protein levels of gluco- (GR) and mineralocorticoid receptors (MR) and selected enzymes measured by quantitative PCR and immunohystochemistry in the hypothalamus, hippocampus, prefrontal cortex, liver and kidney. Gene expression of 11beta-hydroxysteroid dehydrogenase 2 (11ß-HSD2), an enzyme enabling preferential effects of aldosterone on mineralocorticoid receptors, was higher in 10-day-old pups compared to adult animals. On the contrary, the expression and protein levels of GR, MR and 11ß-HSD1 were decreased. Presented results clearly show higher stress-induced release of aldosterone in pups compared to adults and strongly suggest greater importance of mineralocorticoids compared to glucocorticoids in stress during the postnatal period.