Prenatal predictors of childhood anxiety disorders: An exploratory study of the role of attachment organization

2021 ◽  
pp. 1-12
Author(s):  
Megan Galbally ◽  
Stuart J. Watson ◽  
Marinus H. van IJzendoorn ◽  
Anne Tharner ◽  
Maartje Luijk ◽  
...  
Keyword(s):  
Anxiety Disorders ◽  
Life Stress ◽  
Exploratory Study ◽  
Early Life ◽  
Early Life Stress ◽  
Childhood Anxiety ◽  
Preschool Age ◽  
Hair Cortisol ◽  
Cortisol Reactivity ◽  
Childhood Anxiety Disorders

Abstract Childhood anxiety disorders (CAD) are a common childhood mental disorder and understanding early developmental pathways is key to prevention and early intervention. What is not understood is whether early life stress predictors of CAD might be both mediated by infant cortisol reactivity and moderated by infant attachment status. To address this question, this exploratory study draws on 190 women recruited in early pregnancy and followed together with their children until 4 years of age. Early life stress is operationalized as maternal depression measured using the Structured Clinical Interview for the DSM, Childhood Trauma Questionnaire, Parenting Stress Index, and antenatal maternal hair cortisol concentrations. Infant cortisol reactivity was measured at 12 months together with the Strange Situation Procedure and CAD assessed at 4 years of age using the Preschool Age Psychiatric Assessment. There was no direct association between attachment classification and CAD. Furthermore, infant cortisol reactivity neither mediated nor attachment moderated the association of early life stress predictors and CAD. However, only for infants with organized attachment classifications, higher maternal antenatal depression, and hair cortisol were associated with a higher risk of CAD.

The perinatal origins of childhood anxiety disorders and the role of early-life maternal predictors

2020 ◽  
pp. 1-9
Author(s):  
Megan Galbally ◽  
Stuart J. Watson ◽  
Elisabeth F. C. van Rossum ◽  
Wai Chen ◽  
Edo Ronald de Kloet ◽  
...  
Keyword(s):  
Anxiety Disorders ◽  
Parenting Stress ◽  
Childhood Trauma ◽  
Gestational Age ◽  
Early Life ◽  
Childhood Anxiety ◽  
Antenatal Depression ◽  
Hair Cortisol ◽  
Maternal Factors ◽  
Childhood Anxiety Disorders

Abstract Background The development of childhood anxiety disorders (CADs) is likely to depend on pathways that can be programmed by early-life risk factors. We test the hypothesis that early-life maternal factors can predict this programming effect on CAD. Methods Data were obtained from 198 women and children from the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS), a cohort study with data collected across pregnancy, postpartum and until 4 years of age. Maternal antenatal depression was measured using the Structured Clinical Interview for DSM-IV (SCID-IV), together with antenatal hair cortisol concentrations, maternal childhood trauma and parenting stress at 6 months postpartum. CAD was assessed with the Preschool Age Psychiatric Assessment and the Child Behaviour Checklist. Results Antenatal depression, a history of maternal childhood trauma and lower gestational age at birth were each associated with anxiety disorders at 4 years of age in their children. A multivariate binary logistic model with these early predictors explained approximately 9% of variance in CAD outcome at 4 years of age; however, only maternal trauma and gestational age were significant predictors in the model. The effect of early parenting stress on CAD was found to vary by the concentration of maternal antenatal hair cortisol, whereby postpartum parenting stress was associated with CAD only when there were higher maternal antenatal cortisol levels. Conclusions This study suggests the importance of maternal factors pre-conception, pregnancy and in the postnatal period, which predict CADs and this is consistent with a developmental programming hypothesis for CAD.

scholarly journals Highlights of this issue

2013 ◽  
Vol 203 (6) ◽  
pp. A22-A22
Author(s):  
Kimberlie Dean
Keyword(s):  
Eating Disorders ◽  
Randomised Controlled Trial ◽  
Anxiety Disorders ◽  
Early Life ◽  
Controlled Trial ◽  
Childhood Anxiety ◽  
Childhood Anxiety Disorders ◽  
Low Intensity ◽  
Randomised Controlled ◽  
Diagnostic Outcomes

Interventions throughout early life - antenatally, in childhood and in adolescenceTwo papers in the Journal this month describe trials of interventions targeting young people – one focused on treating anxiety disorders in childhood and another on preventing eating disorders in adolescence. While CBT for childhood anxiety disorders is known to be effective, its availability is limited. Thirlwall et al (pp. 436–444) conducted a randomised controlled trial of low-intensity guided parent-delivered CBT in a sample of children with anxiety disorders referred by primary or secondary care to a specialist clinic. Compared with waiting-list controls, the children receiving the full intervention demonstrated superior diagnostic outcomes, whereas those receiving a brief version of the intervention showed no improvements. In a linked editorial, Cartwright-Hatton (pp. 401–402) highlights the prevalence of childhood anxiety disorders, the implications of failing to treat them and the evidence supporting their treatability. She also points to the implications of findings from Thirlwall et al indicating that therapists need not be highly trained or experienced to achieve significant results.

Emotional non-acceptance links early life stress and blunted cortisol reactivity to social threat

2015 ◽  
Vol 51 ◽  
pp. 176-187 ◽  
Author(s):  
Mihai Cărnuţă ◽  
Liviu G. Crişan ◽  
Romana Vulturar ◽  
Adrian Opre ◽  
Andrei C. Miu
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Social Threat ◽  
Cortisol Reactivity

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 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.

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.

scholarly journals Early Life Stress and Child Temperament Style as Predictors of Childhood Anxiety and Depressive Symptoms: Findings from the Longitudinal Study of Australian Children

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Andrew J. Lewis ◽  
Craig A. Olsson
Keyword(s):  
Depressive Symptoms ◽  
Longitudinal Study ◽  
Life Stress ◽  
Early Life ◽  
Parental Education ◽  
Early Life Stress ◽  
Childhood Anxiety ◽  
Infant Temperament ◽  
Future Research ◽  
Stress Exposure

Objective. The purpose of this study was to determine whether the relationship between stressful infant environments and later childhood anxiety and depressive symptoms varies as a function of individual differences in temperament style.Methods. Data was drawn from the Longitudinal Study of Australian Children (LSAC). This study examined 3425 infants assessed at three time points, at 1-year, at 2/3 years and at 4/5 years. Temperament was measured using a 12-item version of Toddler Temperament Scale (TTS) and was scored for reactive, avoidant, and impulsive dimensions. Logistic regression was used to model direct relationships and additive interactions between early life stress, temperament, and emotional symptoms at 4 years of age. Analyses were adjusted for socioeconomic status, parental education, and marital status.Results. Stressful family environments experienced in the infant's first year of life (high versus low) and high reactive, avoidant, and impulsive temperament styles directly and independently predicted anxiety and depressive problems in children at 4 years of age. There was no evidence of interaction between temperament and family stress exposure.Conclusions. Both infant temperament and stress exposures are independent and notable predictors of later anxiety and depressive problems in childhood. The risk relationship between stress exposure in infancy and childhood emotion problems did not vary as a function of infant temperament. Implications for preventive intervention and future research directions are discussed.

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