Video-Coded Maternal Behaviours and Stress Reactivity in Preschoolers of Mothers with Depression

Parents play an important role in supporting their children’s social-emotional development and well-being. Social buffering theory suggests that positive parent-child relationships are associated to children’s ability to cope with acute stress. One method utilized to measure parent-child relationships is through observed video-coded interactions, but in the context of acute stress, there is an identified gap in standardized video coding systems. We created a video coding scheme to capture maternal behaviours associated with children’s stress reactivity and recovery in a sample of mothers with clinical depression and their preschool aged children (N = 40). Mother-child dyads participated in a baseline assessment of a larger clinical trial study via online videoconferencing platform. Children partook in an acute stressor task alongside salivary cortisol and heart rate measurements. Video recordings of maternal behaviours were collected both during and after the acute stressor task. Transcriptions of maternal behaviours were recorded to inform the microanalytic coding scheme development. These transcriptions were consolidated into codes based on established systems and clinical theory. Partial construct validity of the video coding scheme was found when comparing the observed maternal behaviours with a standardized questionnaire of parenting behaviour. Results indicate that observed global maternal involvement during the online stressor task produced a blunting effect on children’s stress reactivity. However, no associations between mothers’ parenting behaviours after the stressor and children’s stress physiology were found. Results may inform parenting interventions aimed at supporting children’s well-being.

Isoflurane stress induces glucocorticoid production in mouse lymphoid organs

Glucocorticoids (GCs) are secreted by the adrenal glands and locally produced by lymphoid organs. Adrenal GC secretion at baseline and in response to stressors is greatly reduced during the stress hyporesponsive period (SHRP) in neonatal mice (postnatal day (PND) 2-12). It is unknown whether lymphoid GC production increases in response to stressors during the SHRP. Here, we administered an acute stressor (isoflurane anesthesia) to mice before, during, and after the SHRP and measured systemic and local GCs via mass spectrometry. We administered isoflurane, vehicle control (oxygen), or neither (baseline) at PND 1, 5, 9, or 13 and measured progesterone and 6 GCs in blood, bone marrow, thymus, and spleen. At PND1, blood and lymphoid GC levels were high and did not respond to stress. At PND5, blood GC levels were very low and increased slightly after stress, while lymphoid GC levels were also low but, increased greatly after stress. At PND9, blood and lymphoid GC levels were similar at baseline and increased similarly after stress. At PND13, blood GC levels were higher than lymphoid GC levels at baseline, and blood GC levels showed a greater response to stress. These data demonstrate the remarkable plasticity of GC physiology during the postnatal period, show that local steroid levels do not reflect systemic steroid levels, provide insight into the SHRP, and identify a potential mechanism by which early-life stressors can alter immunity in adulthood.

Reduced adaptation of glutamatergic stress response is associated with pessimistic expectations in depression

Stress is a significant risk factor for the development of major depressive disorder (MDD), yet the underlying mechanisms remain unclear. Preclinically, adaptive and maladaptive stress-induced changes in glutamatergic function have been observed in the medial prefrontal cortex (mPFC). Here, we examine stress-induced changes in human mPFC glutamate using magnetic resonance spectroscopy (MRS) in two healthy control samples and a third sample of unmedicated participants with MDD who completed the Maastricht acute stress task, and one sample of healthy control participants who completed a no-stress control manipulation. In healthy controls, we find that the magnitude of mPFC glutamate response to the acute stressor decreases as individual levels of perceived stress increase. This adaptative glutamate response is absent in individuals with MDD and is associated with pessimistic expectations during a 1-month follow-up period. Together, this work shows evidence for glutamatergic adaptation to stress that is significantly disrupted in MDD.

Role of CORT Duration and Estradiol Dependence for Stress-level of CORT to Inhibit Pulsatile LH Secretion in Female Mice

Two common responses to stress include elevated circulating glucocorticoids and impaired luteinizing hormone (LH) secretion. We have shown that a chronic stress-level of corticosterone (CORT) can slow LH pulses in female mice and that this reduction required estradiol. In addition, the decrease in LH secretion was associated with a suppression in neuronal activation of arcuate kisspeptin (Kiss1) neurons, regarded as the LH pulse generator. Although the increment of the chronic CORT rise was physiological, the duration of the rise exceeded that of a normal CORT response to an acute stressor. Therefore, the goal of the current study was to investigate whether an acute, exogenous CORT rise is sufficient to inhibit LH pulses and arcuate Kiss1 expression, and whether estradiol is necessary for this inhibition. For this study, adult C57bl6 female mice were ovariectomized and implanted with either an implant filled with oil (OVX) or 100 ng estradiol (OVX+E), which approximates a diestrus level of estradiol. Blood samples to measure pulsatile LH were collected every 6 minutes for 90 minutes prior to and following the initiation of CORT or saline treatment. Animals were randomly assigned to receive one of 4 treatments: a single injection of CORT (0.6 mg/kg, i.p) or saline, or three successive injections separated by 30 minutes of CORT (3xCORT) or saline (3xSaline). This dose of CORT elicited a CORT elevation similar to the endogenous CORT rise induced by restraint stress. One injection of CORT elicited an elevation for 30 minutes; the three-injection paradigm elevated CORT for 90 minutes, the entirety of the post injection LH sampling period. Regardless of estradiol status, LH did not differ between the pre and post injection period in mice administered a single injection of CORT or saline. In contrast, in OVX+E mice, 3xCORT significantly slowed the frequency of LH pulses (pulses/90 min: 2.7±0.2 vs 1.4±0.3; pre vs post, p<0.05) compared to mice given 3xSaline (pulses/90 min: 2.9±0.4 vs 2.8±0.4; pre vs post, p>0.05). Interestingly, in OVX mice, there was no impairment of LH secretion in response to either 3xCORT (pulses/90 min: 4.9±0.4 vs 4.7±0.5; pre vs post, p>0.05) or 3xSaline. Knowing that glucocorticoid receptors are present in arcuate Kiss1 cells, we investigated the effect of CORT on Kiss1 expression. Brains were collected 3 hrs following the initiation of the 3xSaline or 3xCORT treatment, and the arcuate nucleus was micropunched for measurement of Kiss1. In OVX+E mice, Kiss1 expression in the arcuate nucleus was suppressed 47% by 3xCORT compared to 3xSaline treated mice (p<0.05). Collectively these data show that an acute CORT rise is sufficient to impair pulsatile LH secretion and Kiss1 expression, but the rise has to be sustained for more than 30 minutes and requires the presence of estradiol. Whether CORT is acting directly or indirectly on arcuate Kiss1 neurons to impair LH secretion remains to be determined.

An intact Krüppel-like factor 9 gene is required for acute liver Period 1 mRNA response to restraint stress

The clock protein period 1 (PER1) is a central component of the core transcription-translation feedback loop governing cell-autonomous circadian rhythms in animals. Transcription of Per1 is directly regulated by the glucocorticoid (GC) receptor (GR), and Per1 mRNA is induced by stressors or injection of GC. Circulating GCs may synchronize peripheral clocks with the central pacemaker located in the suprachiasmatic nucleus of the brain. Krüppel-like factor 9 (KLF9) is a zinc finger transcription factor that, like Per1, is directly regulated by liganded GR, and it associates in chromatin at clock- and clock-output genes, including at Per1. We hypothesized that KLF9 modulates stressor-dependent Per1 transcription. We exposed wild type (WT) and Klf9 null mice (Klf9 -/-) of both sexes to 1 hr restraint stress, which caused similar 2-2.5 fold increases in plasma corticosterone (B) in each genotype and sex. While WT mice of both sexes showed a 2-fold increase in liver Per1 mRNA level after restraint stress, this response was absent in Klf9 -/- mice. However, injection of B in WT and Klf9 -/- mice induced similar increases in Per1 mRNA. Our findings support that an intact Klf9 gene is required for liver Per1 mRNA responses to an acute stressor, but a possible role for GCs in this response requires further investigation.