scholarly journals Sex and Estrous Cycle Effects on Anxiety- and Depression-related Phenotypes in Two-hit Developmental Stress Model

2019 ◽  
Author(s):  
Ivana Jaric ◽  
Devin Rocks ◽  
Heining Cham ◽  
Alice Herchek ◽  
Marija Kundakovic
Keyword(s):  
Anxiety Disorders ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Anxiety And Depression ◽  
Synergistic Activity ◽  
Stress Model ◽  
Depression And Anxiety ◽  
Developmental Stress ◽  
Behavioral Phenotypes

Stress during sensitive developmental periods can adversely affect physical and psychological development and contribute to later-life mental disorders. In particular, adverse experiences during childhood dramatically increase the risk for the development of depression and anxiety disorders. Although women of reproductive age are twice as likely to develop anxiety and depression than men of the corresponding age, little is known about sex-specific factors that promote or protect against the development of psychopathology. To examine potential developmental mechanisms driving sex disparity in risk for anxiety and depression, we established a two-hit developmental stress model including maternal separation in early life followed by social isolation in adolescence. Our study shows complex interactions between early-life and adolescent stress, between stress and sex, and between stress and female estrogen status in shaping behavioral phenotypes of adult animals. In general, increased locomotor activity and body weight reduction were the only two phenotypes where two stressors showed synergistic activity. In terms of anxiety- and depression-related phenotypes, single exposure to early-life stress had the most significant impact and was female-specific. We show that early-life stress disrupts the protective role of estrogen in females, and promotes female vulnerability to anxiety- and depression-related phenotypes associated with the low-estrogenic state. We found plausible transcriptional and epigenetic alterations in psychiatric risk genes, Nr3c1 and Cacna1c, that likely contributed to the stress-induced behavioral effects. In addition, two general transcriptional regulators, Egr1 and Dnmt1, were found to be dysregulated in maternally-separated females and in animals exposed to both stressors, respectively, providing insights into possible transcriptional mechanisms that underlie behavioral phenotypes. Our findings provide a novel insight into developmental risk factors and biological mechanisms driving sex differences in depression and anxiety disorders, facilitating the search for more effective, sex-specific treatments for these disorders.

scholarly journals The Impact of COVID-19 on Adolescent Mental Health: Preliminary Findings From a Longitudinal Sample of Healthy and At-Risk Adolescents

2021 ◽  
Vol 9 ◽  
Author(s):  
Zsofia P. Cohen ◽  
Kelly T. Cosgrove ◽  
Danielle C. DeVille ◽  
Elisabeth Akeman ◽  
Manpreet K. Singh ◽  
...  
Keyword(s):  
Psychological Functioning ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Self Report ◽  
Depression And Anxiety ◽  
Mixed Effect ◽  
Symptoms Of Depression ◽  
The Impact ◽  
At Risk Adolescents

Background: The COVID-19 pandemic has brought on far-reaching consequences for adolescents. Adolescents with early life stress (ELS) may be at particular risk. We sought to examine how COVID-19 impacted psychological functioning in a sample of healthy and ELS-exposed adolescents during the pandemic.Methods: A total of 24 adolescents (15 healthy, nine ELS) completed self-report measures prior to and during the COVID-19 pandemic. The effect of COVID-19 on symptoms of depression and anxiety were explored using linear mixed-effect analyses.Results: With the onset of the pandemic, healthy but not ELS-exposed adolescents evidenced increased symptoms of depression and anxiety (ps < 0.05). Coping by talking with friends and prioritizing sleep had a protective effect against anxiety for healthy adolescents (t = −3.76, p = 0.002).Conclusions: On average, this study demonstrated large increases in depression and anxiety in adolescents who were healthy prior to the COVID-19 pandemic, while ELS-exposed adolescents evidenced high but stable symptoms over time.

scholarly journals Developmental stress and social phenotypes: integrating neuroendocrine, behavioural and evolutionary perspectives

2017 ◽  
Vol 372 (1727) ◽  
pp. 20160242 ◽  
Author(s):  
Karen A. Spencer
Keyword(s):  
Hpa Axis ◽  
Social Behaviour ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Developmental Stress ◽  
Positive Effects ◽  
Neuroendocrine Axis ◽  
Complex Relationships ◽  
Social Behaviours

The social world is filled with different types of interactions, and social experience interacts with stress on several different levels. Activation of the neuroendocrine axis that regulates the response to stress can have consequences for innumerable behavioural responses, including social decision-making and aspects of sociality, such as gregariousness and aggression. This is especially true for stress experienced during early life, when physiological systems are developing and highly sensitive to perturbation. Stress at this time can have persistent effects on social behaviours into adulthood. One important question remaining is to what extent these effects are adaptive. This paper initially reviews the current literature investigating the complex relationships between the hypothalamic-pituitary-adrenal (HPA) axis and other neuroendocrine systems and several aspects of social behaviour in vertebrates. In addition, the review explores the evidence surrounding the potential for ‘social programming’ via differential development and activation of the HPA axis, providing an insight into the potential for positive effects on fitness following early life stress. Finally, the paper provides a framework from which novel investigations could work to fully understand the adaptive significance of early life effects on social behaviours. This article is part of the themed issue ‘Physiological determinants of social behaviour in animals'.

scholarly journals 3004 Effects of Early Life Stress on Adult Behavioral and Neural Outcomes in Rats

2019 ◽  
Vol 3 (s1) ◽  
pp. 9-10
Author(s):  
Alexandra Moussa-Tooks ◽  
Ken Mackie ◽  
John Green ◽  
Lisa Bartolomeo ◽  
Alex Gimeno ◽  
...  
Keyword(s):  
Anxiety Disorders ◽  
Life Stress ◽  
Early Life ◽  
Cannabinoid Receptors ◽  
Social Preference ◽  
Elevated Plus Maze ◽  
Early Life Stress ◽  
Female Rats ◽  
Plus Maze

OBJECTIVES/SPECIFIC AIMS: Early life stress is known to greatly impact neurodevelopment during critical periods, conferring risk for various psychopathologies, including the onset and exacerbation of schizophrenia and anxiety disorders. The endocannabinoid system is highly integrated into the stress response and may be one means by which early life stress produces such deleterious effects. Using a naturalistic, ecologically valid animal model, this study explored interactions between the stress response and endocannabinoid systems within the cerebellum, a region dense with the CB1 endocannabinoid receptors and shown to be susceptible to stress. METHODS/STUDY POPULATION: This study explored behavioral and neural impacts of early life stress in Long-Evans rats reared with or without limited access to bedding material during postnatal day (PND) 2-9. Corticosterone (CORT) levels were measured at PND8 and 70. During PND50-70, rats were assessed on Novel Object Recognition to test memory, Rotarod to evaluate cerebellar integrity, Elevated Plus Maze to assay anxiety, Social Preference, and Eyeblink Conditioning, a cerebellar-dependent and endocannabinoid-mediated task. Lipid analysis was performed on PND70 tissue samples of cerebellar interpositus (IP) nucleus via high-performance liquid chromatography and tandem mass spectrometry. RESULTS/ANTICIPATED RESULTS: Both male and female rats experiencing early life stress exhibited significantly impaired recognition memory (N = 16-20/group). Female rats having undergone stress exhibited decreased social preference compared to normally reared females (N = 11/group). Stressed males showed facilitated eyblink conditioning compared to normally reared males (N = 7-9/group). There were no group differences in rotarod or elevated plus maze performance or CORT levels at PND8 or 70 across rearing groups. At PND70, male rats experiencing early life stress exhibited a significant decrease in 2-arachidonoyl glycerol (2-AG) and arachidonic acid levels in the IP nucleus compared to normally reared males (N = 8-9/group). Compared to normally reared females, those experiencing early life stress exhibited a significant increase in prostaglandin E2 levels in the IP nucleus (N = 6-7/group). DISCUSSION/SIGNIFICANCE OF IMPACT: Early life stress, induced by limited bedding, resulted in sex-specific behavioral and lipid impairments. Results suggest that stress causes long-term alterations in endocannabinoid dynamics in males in the cerebellar IP nucleus and sex-related lipids in female cerebellum. These changes may contribute to observed long-term behavioral aberrations. Moreover, findings suggest these behavioral changes may be the result of negative-feedback dysfunction (as evidenced by decreased endocannabinoids in males) or increased neural inflammation or proliferation (as evidenced by increased prostaglandins in females). Future analysis will quantify mRNA and protein for cannabinoid receptors to better characterize aberrations to this system. Moreover, other neural regions dense with cannabinoid receptors (i.e., PFC, hippocampus) will be investigated. This work provides a basis for understanding stress impacts on the development of cognitive deficits observed in psychotic and anxiety disorders. Specifically, facilitation of eyblink conditioning complements research in humans with anxiety disorders. Broadly, understanding stress-related endocannabinoid dysregulation may provide insights into risks for, and the development of, psychopathology and uncover novel therapeutic targets with high translational power.

scholarly journals The role of emotion regulation as a mediator between early life stress and posttraumatic stress disorder, depression and anxiety in Syrian refugees

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zaynab Demir ◽  
Kerem Böge ◽  
Yan Fan ◽  
Corinna Hartling ◽  
Mazen R. Harb ◽  
...  
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Emotion Regulation ◽  
Life Stress ◽  
Early Life ◽  
Stress Disorder ◽  
Early Life Stress ◽  
Syrian Refugees ◽  
Depression And Anxiety ◽  
Cognitive Emotion Regulation ◽  
The Relationship

Abstract Early life stress is an important factor in later psychopathology, including symptoms of posttraumatic stress disorder (PTSD), depression, and anxiety. The purpose of the present study was to investigate the effect of early life stress on psychiatric symptoms within a sample of Syrian refugees. In this model, the use of cognitive emotion regulation strategies was assessed as a potential mediator of the relationship between early life stress and current symptoms of PTSD, depression, and anxiety. Bootstrap analyses were generated to test the indirect effect of emotion regulation (Cognitive Emotion Regulation Questionnaire) on the relationship between early life stress (Childhood Trauma Questionnaire), PTSD (Harvard Trauma Questionnaire), depressive (PHQ-9) and anxiety (GAD-7) symptoms in eighty-nine Syrian refugees resided in Germany (n = 49) and Jordan (n = 40). The indirect effect of maladaptive strategies was significant between early life stress and psychopathology, whereas the mediation effect of adaptive strategies was not significant. The findings provide an evidence that emotional dysregulation is an underlying factor affecting psychological symptoms in refugees with adverse childhood experiences. These results suggest targeting cognitive emotion regulation in prospective prevention and treatment strategies.

Long-Term Decreases in the Expression of Calcineurin and GABAA Receptors Induced by Early Maternal Separation Are Associated with Increased Anxiety-Like Behavior in Adult Male Rats

2020 ◽  
pp. 1-10
Author(s):  
Maryam Mahmoodkhani ◽  
Maedeh Ghasemi ◽  
Leila Derafshpour ◽  
Mohammad Amini ◽  
Nasrin Mehranfard
Keyword(s):  
Anxiety Disorders ◽  
Glutamate Receptors ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Central Area ◽  
Early Life Stress ◽  
Brain Regions ◽  
Male Rats ◽  
Lower Percentage

<b><i>Introduction:</i></b> Early life stress is a well-described risk factor of anxiety disorders in adulthood. Dysfunction in GABA/glutamate receptors and their functional regulator, calcineurin, is linked to anxiety disorders. Here, we investigated the effect of early life stress, such as repeated maternal separation (MS; 3 h per day from postnatal day [P] 2 to 11), on changes in the expression of calcineurin as well as the ionotropic glutamatergic and GABAergic receptors including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and GABA<sub>A</sub> receptors in the hippocampus and prefrontal cortex (PFC) of adolescent (P35) and adult (P62) male Wistar rats and their correlations with anxiety-like behavior in adulthood. <b><i>Methods:</i></b> The protein levels were assessed by Western blot analysis. Anxiety-like behavior was measured in the elevated plus maze (EPM) and open field (OF) tests. <b><i>Results:</i></b> MS induced a regional transient decrease of glutamate receptors expression at P35, with decreased NMDA and AMPA receptor levels, respectively, in the hippocampus and PFC, suggesting a possible decrease in excitatory synaptic strength. In contrast to glutamate receptors, MS had long-lasting influence on GABA<sub>A</sub> receptor and calcineurin levels, with reduced expression of GABA<sub>A</sub> receptor and calcineurin in both brain regions at P35 that continued into adulthood. These results were accompanied by increased anxiety behavior in adulthood, shown by lower percentage of number of total entries and time spent in the open arms of the EPM, and by lower time spent and number of entries in the OF central area. <b><i>Conclusions:</i></b> Together, our study suggests that GABA<sub>A</sub> receptors via calcineurin-dependent signaling pathways may play an important role in the expression of stress-induced anxiety-like behavior.

‘Negativity bias’ in risk for depression and anxiety: Brain–body fear circuitry correlates, 5-HTT-LPR and early life stress

NeuroImage ◽  
2009 ◽  
Vol 47 (3) ◽  
pp. 804-814 ◽  
Author(s):  
Leanne M. Williams ◽  
Justine M. Gatt ◽  
Peter R. Schofield ◽  
Gloria Olivieri ◽  
Anthony Peduto ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Negativity Bias ◽  
Depression And Anxiety ◽  
Risk For Depression

scholarly journals Long-term aberrations to cerebellar endocannabinoids induced by early-life stress

2019 ◽  
Author(s):  
Alexandra B. Moussa-Tooks ◽  
Eric Larson ◽  
Alex F. Gimeno ◽  
Emma Leishman ◽  
Lisa A. Bartolomeo ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Cannabinoid Receptors ◽  
Early Life Stress ◽  
Future Research ◽  
Developmental Stress ◽  
Specific Effects ◽  
Effects Of Stress ◽  
Arachidonoyl Glycerol

AbstractStudies of early-life stress traditionally focus on glucocorticoid signaling as a modulator of neurodevelopmental risk, but emerging evidence points to the role of the endocannabinoid system in long-term stress-induced neural remodeling. Existing studies on stress-induced endocannabinoid dysregulation have focused on changes to cerebrum that are temporally proximal to stressors, but little is known about temporally distal effects, especially in cerebellum, which is vulnerable to early developmental stress and is dense with cannabinoid receptors. Further, sex-specific effects of stress on cerebellar endocannabinoid tone are understudied. Following a naturalistic rodent model of early-life stress, limited bedding at postnatal days 2-9, adult (postnatal day 70) cerebellar and hippocampal endocannabinoids and related lipids and mRNA were assessed, and behavioral performance was evaluated. Regional and sex-specific effects were present at baseline and following early-life stress. Limited bedding impaired peripherally-measured basal corticosterone in adult males only. In the CNS, early-life stress (1) decreased 2-arachidonoyl glycerol and arachidonic acid in the cerebellar deep nuclei in males only; (2) decreased 2-arachidonoyl glycerol in females only in cerebellar Crus I; and (3) increased dorsal hippocampus prostaglandins in males only. Transcriptomics for cerebellar interpositus nucleus revealed substantial sex effects, with minimal effects of stress. Stress did impair novel object recognition in both sexes and social preference in females. Taken together, the cerebellar endocannabinoids system exhibits robust sex-specific differences, malleable through early-life stress and perhaps also contributing to sexual differentiation of the brain. The current study may foster future research into stress as a risk factor for cerebellar-related dysfunctions.

Lactobacillus paracasei PS23 reduced early-life stress abnormalities in maternal separation mouse model

2019 ◽  
Vol 10 (4) ◽  
pp. 425-436 ◽  
Author(s):  
J.F. Liao ◽  
C.C. Hsu ◽  
G.T. Chou ◽  
J.S. Hsu ◽  
M.T. Liong ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Negative Control ◽  
Lactobacillus Paracasei ◽  
Anxiety And Depression ◽  
Gut Health ◽  
Brain Health ◽  
Psychological Traits

Maternal separation (MS) has been developed as a model for inducing stress and depression in studies using rodents. The concept of the gut-brain axis suggests that gut health is essential for brain health. Here, we present the effects of administration of a probiotic, Lactobacillus paracasei PS23 (PS23), to MS mice against psychological traits including anxiety and depression. The administration of live and heat-killed PS23 cells showed positive behavioural effects on MS animals, where exploratory tendencies and mobility were increased in behavioural tests, indicating reduced anxiety and depression compared to the negative control mice (P<0.05). Mice administered with both live and heat-killed PS23 cells also showed lower serum corticosterone levels accompanied by higher serum anti-inflammatory interleukin 10 (IL-10) levels, compared to MS separated mice (P<0.05), indicating a stress-elicited response affiliated with increased immunomodulatory properties. Assessment of neurotransmitters in the brain hippocampal region revealed that PS23 affected the concentrations of dopaminergic metabolites differently than the control, suggesting that PS23 may have improved MS-induced stress levels via neurotransmitter pathways, such as dopamine or other mechanisms not addressed in the current study. Our study illustrates the potential of a probiotic in reversing abnormalities induced by early life stress and could be an alternative for brain health along the gut-brain axis.

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