Diurnal variation of mood and the cortisol rhythm in depression and normal states of mind

Summary A large scale chronobiological investigation was undertaken in 20 drug-free psychiatric inpatients displaying RDC major depression (endogenous subtype) in comparison to 10 healthy control subjects and 10 of the patients after clinical recovery. A series of measurements was taken 6 times a day and, in 8 of a total of 14 variables, also once a night over a period of 10 to 14 days. The following variables were assessed: mood (three different scales), performance (two tests), motor activity (three measures), salivary flow, urinary excretion of water, sodium, potassium, and free cortisol (UFC), and rectal temperature. A phase chart of the acrophases of the 8 variables with measurements taken during day and night revealed two clusters in the depressives and three in the non-depressed subjects. In the depressives, the acrophases of the mood scales clustered around the time of awakening in the morning, together with the acrophase of UFC, whereas all other acrophases clustered in the afternoon. In the non-depressed subjects, however, the mood scales reached their circadian maxima in the middle of the night around the time when sleep was interrupted to take measurements. All other acrophases corresponded roughly with those found in the depressives. The coincidence of the time course of depressed mood and cortisol excretion in the patients was interpreted as reflecting a temporal relationship between diurnal mood swings in depression and the cortisol rhythm. This interpretation was supported by the significant correlation between the acrophases of the two respective rhythms in patients showing a significant diurnal variation in mood. The mood curves of non-depressed subjects seemed unrelated to the cortisol rhythm. Probably, they mirror diurnal fluctuations of vigilance rather than fluctuations of mood. According to the literature, this rhythm is temporally related to the rhythm of melatonin secretion.     

Maternal salivary cortisol differs by fetal sex during the second half of pregnancy

Maternal salivary cortisol was measured at weekly intervals from 24 to 38 weeks gestation. The total sample consisted of 120 women enrolled in staggered intervals in such a way as to generate weekly measures of salivary cortisol during the latter half of pregnancy. Hierarchical linear modeling revealed the expected increase in unbound maternal cortisol during this period, with a slight deceleration in rate of increase at 33 weeks gestation. Women carrying male fetuses had higher levels of salivary cortisol initially as compared to women carrying female fetuses; at 30 weeks gestation there was cross-over such that higher maternal cortisol was observed in women carrying female fetuses beyond this time and through term. Results highlight the importance of considering fetal sex as a moderator of contemporaneous and predictive associations between maternal cortisol and prenatal or postnatal development.     

Associations between maternal prenatal cortisol concentrations and child outcomes: A systematic review

A frequently proposed mechanism underlying the link between maternal prenatal stress/anxiety and child outcomes is heightened concentrations of maternal cortisol. In this systematic review, empirical findings on associations between maternal prenatal cortisol concentrations and child outcomes (physical/health, cognitive/motor, psychological/behavioral, and cortisol) are summarized. The number of empirical studies that find significant associations between maternal prenatal cortisol and child outcomes is small, but the majority of the studies that do find associations show that maternal cortisol is related to altered child outcomes (e.g. more physical/health problems, lower cognitive/motor development, more psychological/behavioral problems, and higher child cortisol concentrations). Inspection of the studies reveals possible critical gestational periods for maternal cortisol to affect different child outcomes.The heterogeneity in study designs and cortisol assessment methods makes drawing strong conclusions premature. However, the fact that most studies did not find significant associations suggests that maternal cortisol may not to be the sole or even main underlying mechanism in the relation between maternal prenatal stress/anxiety and child outcomes. Limitations of the reviewed studies are discussed, and directions for future research and reporting strategies are provided.     

Ovine fetal hormonal and hypothalamic neuroendocrine responses to maternal water deprivation at late gestation

Angiotensin II (Ang II), aldosterone, and arginine-vasopressin (AVP) are three major neuropeptides or hormones that are important in the control of body fluid regulation. Dehydration during pregnancy induces alterations in maternal–fetal fluid homeostasis. It is still not clear about effects and mechanisms of maternal water deprivation on fetal neuroendocine and hormonal responses. The present study deprived water from pregnant sheep at near-term for 24 h and 48 h, and determined maternal and fetal blood osmolality and sodium levels before and immediately after water deprivation. Fetal renal excretion and plasma hormones were measured. Fetal forebrain was analyzed for cellular activation marked with Fos and Fos-B. The results showed that maternal and fetal blood osmolality and sodium were increased by water deprivation. Maternal and fetal Ang II, aldosterone, and AVP levels were elevated by 24-h and 48-h water deprivation, while fetal plasma Ang I levels were increased only under the condition of 48-h water deprivation. Intensive Fos and Fos-B expression was detected in the median preoptic nuclei and paraventricular nuclei in the fetal brain following exposure to maternal water deprivation. Double labeling demonstrated that many Fos-positive cells were AVP-containing neurons in the fetal paraventricular nucleus. Together, the results suggest that neuroendocrine and hormonal regulatory mechanisms play a role in the control of body fluid homeostasis, and relatively matured and functional at the last third of gestation, as well as the fetal hypothalamus is functional in the control of the neuropeptide in response to maternal dehydration.     

Navigating toward fetal and maternal health: the challenge of treating epilepsy in pregnancy

A rational approach to the treatment of women of childbearing potential with epilepsy has been hampered by the lack of conclusive data on the comparative teratogenic potential of different antiepileptic drugs (AEDs). Although, several cohort studies on birth defects associated with AED use during pregnancy have been published, these have generally failed to demonstrate differences in malformation rates between AEDs, probably mainly due to insufficient power. In particular, pregnancies with new generation AEDs have been too few. In recent years, pregnancy registries have been introduced to overcome this problem--EURAP (an international collaboration), the North American, and the U.K. AED and pregnancy registries are observational studies that prospectively assess pregnancy outcome after AED exposure using slightly different methods. Each has enlisted 3-5,000 pregnancies in women with epilepsy, and the North American and the U.K. have released preliminary observations. Thus the U.K. registry reported a higher malformation rate with valproate, 5.9% (4.3-8.2%; 95% CI), than with carbamazepine, 2.3% (1.4-3.7%), and lamotrigine, 2.1% (1.0-4.0%). Most of the more recent cohort studies have also identified a nonsignificant trend toward a higher teratogenicity with valproate. These signals need to be interpreted with some caution since none of the studies to date have fully assessed the impact of possible confounders, such as type of epilepsy, family history of birth defects, etc. However, with increasing number of pregnancies it should be possible in the near future for the pregnancy registries to take such confounding factors into account and thus make more reliable assessments of the causal relationship between exposure to specific AEDs and teratogenic risks. While awaiting more conclusive results, it appears reasonable to be cautious in prescribing valproate to women considering to become pregnant if other suitable treatment alternatives, and with less teratogenic potential, are available. Any attempt to change treatment should, however, be accomplished well before conception. The importance of maintained seizure control must also be kept in mind, and the woman who needs valproate to control her seizures should not be discouraged from pregnancy, provided that counseling at the best of available knowledge is given.     

Examining associations between anxiety and cortisol in high functioning male children with autism

Background

Autism spectrum disorder (ASD) is characterized by deficits in communication and social ability, as well as restricted interests and repetitive behavior. Anxiety is a persistent anticipation or apprehension about one or more situations to which a person is exposed, and affects many people, including children with ASD. Stress, by contrast, is a response to situations that are threatening, uncontrollable, or unexpected. Indices of anxiety are often measured through informants, with parents and teachers serving as the primary sources of reported anxiety in children. However, self-report measures exist, allowing current (state) and persistent (trait) anxiety to be assessed. The current study was designed to evaluate whether children with autism could identify their own levels of anxiety and the degree to which these levels were associated with symptom profile and physiological arousal.

Methods

Self-reported state and trait anxiety were collected during exposure to different stress paradigms for 40 children (21 typically developing, 19 with autistic disorder) and compared to parent reported social ability (Social Responsiveness Scale) and stress responsivity (cortisol).

Results

Significant differences were found between typically developing and children with autism for both state and trait anxiety across all conditions. Associations were identified between severity of parent-reported social impairment and both types of self-report anxiety. No relationship was found between stress (salivary cortisol) and anxiety in children with autism.

Conclusions

Children with autism are able to consistently report their persistent level of anxiety symptoms in stressful situations of benign character. Therefore, the inclusion of such measures may be useful in identifying and tracking symptoms in children with autism under appropriate circumstances.     

Stress in pregnancy and infant HPA axis function: conceptual and methodological issues relating to the use of salivary cortisol as an outcome measure

Problems regulating behaviour and emotions in infancy may be a risk factor for the development of psychopathology later in life. Compelling evidence from animal models suggests that one potential pathway to early dysregulation is fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis. According to this model, prenatal maternal stress and anxiety during sensitive periods of development can lead to enduring changes in fetal and offspring neurodevelopment and behaviour. While there is emerging evidence from human studies to suggest a link between maternal negative mood states in pregnancy and various cognitive, behavioural, and emotional disturbances in offspring, it is not yet clear whether the programming mechanism demonstrated in animal studies also applies to humans. Few studies have directly assessed HPA axis function in the infants of prenatally stressed women. Research in this area has been constrained by a number of measurement challenges unique to the assessment of cortisol in infants. This paper discusses these challenges with a view to stimulating further research in the area.     

The association of the cortisol awakening response with experimental pain ratings

Cortisol is a key stress hormone that is implicated in a variety of physiological responses. Attenuated Cortisol Awakening Response (CAR) is associated with many negative health outcomes, but little research has investigated CAR and pain. The current study examines the association of CAR with experimental acute-pain ratings in healthy men and women. Attenuated CAR was related to greater pain intensity and unpleasantness ratings. Future research should examine this association across various pain populations.     

Dopamine in the rabbit retina and striatum: Diurnal rhythm and effect of light stimulation

Summary In rabbits, dopamine levels in the retina, but not in the caudate nucleus, showed clear diurnal rhythm, with high values seen in the light phase. Thirty min exposition of dark-adapted rabbits to day-light produced no changes in dopamine levels in the retina. In rabbits treated with -methyl-p-tyrosine, the same light exposition decreased the retinal amine level by 18%, while stimulation with intensive, flickering light significantly decreased the retinal dopamine content by 36%. Experiments performed at noon and midnight, under light or dark conditions, showed the retinal dopamine levels to be very similar in groups kept either at light or dark, irrespective of the time of the day, although in animals deprived of light the amine levels were clearly lower than in those exposed to light, both at noon and midnight. Under all experimental conditions there were no significant changes in dopamine level and utilization in the caudate nucleus. The isolated and superfused retina (preloaded with [³H]-dopamine), when stimulated with flashes of white light (2 Hz, 10 min), released [³H]-radioactivity in a Ca²⁺-dependent manner. It is concluded that in rabbits, light enhances dopamine levels and utilization selectively in the retina, and the observed diurnal changes in the amine metabolism are dependent on the presence or absence of light, and not on the time of the day. The proposed physiological role(s) of the retinal dopaminergic mechanisms is discussed.     

Examining cortisol rhythmicity and responsivity to stress in children with Tourette syndrome

BACKGROUND: Tourette syndrome (TS) is characterized by motor and vocal tics, which are often exacerbated by stress. The hypothalamic-pituitary-adrenocortical (HPA) axis, a major stress response system is thus of interest for understanding TS. METHODS: Diurnal cortisol rhythms were estimated in medication-free children 7-13 years with TS (N=20) and healthy age-matched controls (N=16). Salivary samples were collected on 3 consecutive days from the home. HPA responsivity was assessed by examining cortisol in response to a mock and real MRI scan. RESULTS: The results of diurnal rhythmicity revealed a trend showing marginally lower evening cortisol for the TS group. By contrast, the TS group had higher cortisol levels in response to the stressor. There were strong, negative correlations between evening cortisol and tic severity as well as diurnal cortisol and anxiety. CONCLUSIONS: The children with TS showed increased cortisol in response to the MRI environment, supporting a model of enhanced HPA responsivity. The lower evening cortisol may be the result of chronic daily stress. Alternatively, the negative associations between cortisol and reported anxiety and tics may reflect biologically based anxiolytic properties of tic expression. Taken together, the results clearly implicate involvement of the HPA axis in the neuropathology of TS.     

Maternal generalized anxiety disorder during pregnancy and fetal brain development: A comparative study on cord blood brain-derived neurotrophic factor levels

Objectives

The study aimed to investigate whether maternal GAD during pregnancy affects fetal circulating brain-derived neurotrophic factor (BDNF), which plays important roles in neuronal development, by comparing cord blood BDNF levels in newborn infants of women with and without GAD.

Methods

Study sample included 19 women with GAD and 25 women without any psychiatric disorder. GAD and other psychiatric diagnoses were screened by means of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The blood sample for the determination of BDNF level was obtained from the umbilical cord during delivery.

Results

Cord blood BDNF levels in newborn infants of healthy women were approximately two-fold compared to newborn infants of women with GAD, and the difference was statistically significant. The duration of GAD during pregnancy was the only variable correlating with cord blood BDNF levels.

Conclusions

The study results imply that prolonged maternal GAD during pregnancy may negatively influence neurodevelopment of the fetus through lower levels of circulating BDNF.     

Effect of maternal sleep in late pregnancy on leptin and lipid levels in umbilical cord blood

ObjectivesTo study the impact of maternal sleep in late pregnancy on birth weight (BW) and leptin and lipid levels in umbilical cord blood.Study designA total of 277 healthy and singleton pregnancy women were recruited for participation in the Shanghai Sleep Birth Cohort Study (SSBC) during their 36–38 weeks of pregnancy, from May 2012 to July 2013. Maternal night sleep time (NST), sleep efficiency (SE), sleep onset latency (SOL) and the percentage of wake after sleep onset (WASO) in NST and midpoint of sleep (MSF) were measured by actigraphy for seven consecutive days. The leptin and lipid levels were determined in cord blood samples collected from the umbilical vein immediately after delivery. Birth information (birth weight, gender, delivery type, etc.) was extracted from medical records. A multivariable linear regression model was applied to examine the effect of maternal sleep in late pregnancy on newborn leptin and lipid levels in umbilical cord blood.ResultsA total of 177 women and their infants were included in the analysis. Maternal mean NST was 7.03 ± 1.10 h in late pregnancy, and 48% had a shorter sleep time (NST < 7 h). The average maternal SE was 72.54% ± 9.66%. The mean percentage WASO/NST was 21.62% ± 9.98%; the average MSF was about 3:34 (0:53); and the SOL was 46.78 ± 36.00 min. After adjustment for confounders, both maternal NST and SE were found to be significantly associated with triglyceride levels (β = −0.219, p = 0.006; β = −0.224, p = 0.006) in umbilical cord blood; and maternal NST was also observed to have positive association with newborn leptin levels (β = 0.146, p = 0.047). However, we did not find significant association between other maternal sleep parameters in late pregnancy and leptin and lipid levels and birth weight.ConclusionsShort sleep duration and poor sleep quality during late pregnancy were associated with newborn leptin and lipid levels, and efforts on improving maternal sleep during late pregnancy should be advocated for children's health.     

Age-dependent and -independent associations between depression, anxiety, DHEAS, and cortisol: from the MIPH Industrial Cohort Studies (MICS)

There is a well-established link between dysphoric mood and endocrine dysregulation, but the strength of this association may vary with age. In order to investigate this possibility we assessed anxiety and depression with overnight urinary cortisol and plasma dehydroepiandrosterone-sulphate (DHEAS) in 608 factory employees ranging between 21 and 62 years. As expected, DHEAS declined with age (r=-0.54, P<0.001) while there was a modest age-related increase in nocturnal cortisol (r=0.17, P<0.001). Depressive symptoms were associated with higher nocturnal cortisol (β=0.19, P<0.001), independent of age. While the association between anxiety and cortisol (age by anxiety interaction: β=0.11, P<0.05) became stronger with age, there was a similar decline in the DHEAS/cortisol ratio in high-anxious middle-aged adults (β=-0.10, P=0.018). The current findings suggest that dysphoric mood, and in particular anxiety, may exacerbate the effects of aging on cortisol release. Prospective studies are needed to determine the causal relations between dysphoric mood, cortisol and DHEAS across the lifespan.