Early life stress, cortisol, frontolimbic connectivity, and depressive symptoms during puberty

AbstractEarly life stress (ELS) is a risk factor for the development of depression in adolescence; the mediating neurobiological mechanisms, however, are unknown. In this study, we examined in early pubertal youth the associations among ELS, cortisol stress responsivity, and white matter microstructure of the uncinate fasciculus and the fornix, two key frontolimbic tracts; we also tested whether and how these variables predicted depressive symptoms in later puberty. A total of 208 participants (117 females; M age = 11.37 years; M Tanner stage = 2.03) provided data across two or more assessment modalities: ELS; salivary cortisol levels during a psychosocial stress task; diffusion magnetic resonance imaging; and depressive symptoms. In early puberty there were significant associations between higher ELS and decreased cortisol production, and between decreased cortisol production and increased fractional anisotropy in the uncinate fasciculus. Further, increased fractional anisotropy in the uncinate fasciculus predicted higher depressive symptoms in later puberty, above and beyond earlier symptoms. In post hoc analyses, we found that sex moderated several additional associations. We discuss these findings within a broader conceptual model linking ELS, emotion dysregulation, and depression across the transition through puberty, and contend that brain circuits implicated in the control of hypothalamic–pituitary–adrenal axis function should be a focus of continued research.

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Associations of waking cortisol with DHEA and testosterone across the pubertal transition: Effects of threat-related early life stress

10.1101/691279 ◽

2019 ◽

Cited By ~ 1

Author(s):

Lucy S. King ◽

Madelaine G. Graber ◽

Natalie L. Colich ◽

Ian H. Gotlib

Keyword(s):

Sex Hormones ◽

Hpa Axis ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Subsequent Development ◽

Tanner Stage ◽

Early Puberty ◽

Pubertal Stage ◽

Mental And Physical Health

AbstractAtypical regulation of the hypothalamic-pituitary-adrenal (HPA) axis is a putative mechanism underlying the association between exposure to early life stress (ELS) and the subsequent development of mental and physical health difficulties. Recent research indicates that puberty is a period of HPA-axis plasticity during which the effects of exposure to ELS on cortisol regulation may change. In particular, increases in the sex hormones that drive pubertal maturation, including dehydroepiandrosterone (DHEA) and testosterone, may be implicated in pubertal recalibration of cortisol regulation. In the current study, we examined the associations among levels of objectively-rated threat-related ELS and salivary waking cortisol, DHEA, and testosterone in a sample of 178 adolescents (55% female) who were in early puberty at baseline (Tanner stages 1-3; mean Tanner stage[SD]=1.93[0.64]; mean age[SD]=11.42[1.04]) and were followed up approximately two years later (mean Tanner stage[SD]=3.46[0.86]; mean age[SD]=13.38[1.06]). Using multi-level modeling, we disaggregated the effects of between-individual levels and within-individual increases in pubertal stage and sex hormones on change in cortisol. Controlling for between-individual differences in average pubertal stage, the association between levels of cortisol and DHEA was more strongly positive among adolescents who evidenced greater within-individual increases in pubertal stage across time. Both higher average levels and greater within-individual increases in DHEA and testosterone were associated with increases in cortisol across time, indicating positive coupling of developmental changes in these hormones; however, coupling was attenuated in adolescents who were exposed to more severe threat-related ELS prior to puberty. These findings advance our understanding of the development of the HPA-axis and its association with childhood environmental risk during puberty.

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Three-way interaction effects of early life stress, positive parenting and FKBP5 in the development of depressive symptoms in a general population

Journal of Neural Transmission ◽

10.1007/s00702-021-02405-0 ◽

2021 ◽

Author(s):

Rebecka Keijser ◽

Susanne Olofsdotter ◽

Kent W. Nilsson ◽

Cecilia Åslund

Keyword(s):

Young Adults ◽

Depressive Symptoms ◽

Life Stress ◽

Early Life ◽

Differential Susceptibility ◽

Early Life Stress ◽

Interaction Effects ◽

Positive Parenting ◽

Depressive Symptomology ◽

Patterns Of Interaction

AbstractFKBP5 gene–environment interaction (cG × E) studies have shown diverse results, some indicating significant interaction effects between the gene and environmental stressors on depression, while others lack such results. Moreover, FKBP5 has a potential role in the diathesis stress and differential susceptibility theorem. The aim of the present study was to evaluate whether a cG × E interaction effect of FKBP5 single-nucleotide polymorphisms (SNPs) or haplotype and early life stress (ELS) on depressive symptoms among young adults was moderated by a positive parenting style (PASCQpos), through the frameworks of the diathesis stress and differential susceptibility theorem. Data were obtained from the Survey of Adolescent Life in Västmanland Cohort Study, including 1006 participants and their guardians. Data were collected during 2012, when the participants were 13 and 15 years old (Wave I: DNA), 2015, when participants were 16 and 18 years old (Wave II: PASCQpos, depressive symptomology and ELS) and 2018, when participants were 19 and 21 years old (Wave III: depressive symptomology). Significant three-way interactions were found for the FKBP5 SNPs rs1360780, rs4713916, rs7748266 and rs9394309, moderated by ELS and PASCQpos, on depressive symptoms among young adults. Diathesis stress patterns of interaction were observed for the FKBP5 SNPs rs1360780, rs4713916 and rs9394309, and differential susceptibility patterns of interaction were observed for the FKBP5 SNP rs7748266. Findings emphasize the possible role of FKBP5 in the development of depressive symptoms among young adults and contribute to the understanding of possible differential susceptibility effects of FKBP5.

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Early Life Stress Predicts Depressive Symptoms in Adolescents During the COVID-19 Pandemic: The Mediating Role of Perceived Stress

SSRN Electronic Journal ◽

10.2139/ssrn.3606441 ◽

2020 ◽

Author(s):

Ian H. Gotlib ◽

Lauren R. Borchers ◽

Rajpreet Chahal ◽

Anthony J. Gifuni ◽

Tiffany Ho

Keyword(s):

Depressive Symptoms ◽

Perceived Stress ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Mediating Role

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Early Life Stress Predicts Depressive Symptoms in Adolescents During the COVID-19 Pandemic: The Mediating Role of Perceived Stress

10.31234/osf.io/4dkaf ◽

2020 ◽

Author(s):

Ian Gotlib ◽

Lauren Borchers ◽

Rajpreet Chahal ◽

Anthony Gifuni ◽

Giana Isabella Teresi ◽

...

Keyword(s):

Depressive Symptoms ◽

San Francisco ◽

Perceived Stress ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Mediating Role ◽

Symptoms Of Depression ◽

Bay Area ◽

Background Exposure

Background: Exposure to early life stress (ELS) is alarmingly prevalent, and has been linked to the high rates of depression documented in adolescence. Researchers have theorized that ELS may increase adolescents’ vulnerability or reactivity to the effects of subsequent stressors, placing them at higher risk for developing symptoms of depression. Methods: We tested this formulation in a longitudinal study by assessing levels of stress and depression during the COVID-19 pandemic in a sample of adolescents from the San Francisco Bay Area (N=100; 43 male; ages 13-20 years) who had been characterized 4-7 years earlier (M=5.27, SD=0.75 years) with respect to exposure to ELS and symptoms of depression. Results: As expected, severity of ELS predicted levels of depressive symptoms during the pandemic (r(98)=0.25, p=.012), which were higher in females than in males (t(98)=-3.36, p=.001). Importantly, the association between ELS and depression was mediated by adolescents’ reported levels of stress, even after controlling for demographic and other COVID-19-related variables. Conclusions: These findings underscore the importance of monitoring the mental health of vulnerable children and adolescents during this pandemic and targeting perceived stress and isolation in high-risk youth.

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Associations Between Self-Reported and Objectively Recorded Early Life Stress, FKBP5 Polymorphisms, and Depressive Symptoms in Midlife

Biological Psychiatry ◽

10.1016/j.biopsych.2015.10.022 ◽

2016 ◽

Vol 80 (11) ◽

pp. 869-877 ◽

Cited By ~ 23

Author(s):

Jari Lahti ◽

Heidi Ala-Mikkula ◽

Eero Kajantie ◽

Kadri Haljas ◽

Johan G. Eriksson ◽

...

Keyword(s):

Depressive Symptoms ◽

Life Stress ◽

Early Life ◽

Early Life Stress

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The effect of a mindfulness-based stress intervention on neurobiological and symptom measures in adolescents with early life stress: a randomized feasibility study

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03295-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zsofia P. Cohen ◽

Kelly T. Cosgrove ◽

Elisabeth Akeman ◽

Sara Coffey ◽

Kent Teague ◽

...

Keyword(s):

Mental Health ◽

Depressive Symptoms ◽

Stress Reduction ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Medium Effect ◽

Control Group ◽

Treatment As Usual ◽

Symptom Level

Abstract Background Early life stress (ELS) has been linked to poor mental and physical health outcomes in adolescence and adulthood. Mindfulness reduces symptoms of depression and anxiety and improves cognitive and social outcomes in both youth and adults. However, little is known whether mindfulness can mitigate against the adverse neurobiological and psychological effects of ELS. This study aimed to examine the feasibility of conducting a group mindfulness intervention in adolescents with ELS and provide preliminary indication of potential effects on stress-related biomarkers and mental health symptoms. Methods Forty adolescents were randomized to receive either eight sessions of Mindfulness-Based Stress Reduction for Teens in group format (MBSR-T; n = 21) or Treatment as Usual Control group (CTRL; n = 17). Outcomes were assessed at baseline and follow-up and included measures associated with neurobiological functioning (immune and endocrine biomarkers) and self-reported mental health (depressive) symptoms. Linear mixed effects models were used to assess the effects of group and time on these outcome measures. Results Sixteen of the 21 adolescents completed the intervention, attending an average of 6.5 sessions. The model examining cortisol responses to stress induction revealed medium effects trending toward significance (Cohen’s d = .56) for anticipatory cortisol levels in the MBSR-T relative to CTRL groups. No significant effects were found in models examining C-reactive protein or interleukin 6 inflammatory markers. The model examining depressive symptoms revealed a medium effect for symptom reduction (Cohen’s d = .69) in the MBSR-T relative to CTRL groups. Conclusions This study demonstrated feasibility of conducting a group-based MBSR-T intervention for adolescents with ELS. There was some evidence for efficacy on a symptom level with potential subtle changes on a biological level. Future larger studies are needed to determine the efficacy of group-based mindfulness interventions in this population. Trial registration Identifier #NCT03633903, registered 16/08/2018.

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Erratum to “Early life stress and HPA axis function independently predict adult depressive symptoms in metropolitan Cebu, Philippines”

American Journal of Physical Anthropology ◽

10.1002/ajpa.24265 ◽

2021 ◽

Vol 175 (1) ◽

pp. 308-308

Keyword(s):

Depressive Symptoms ◽

Hpa Axis ◽

Life Stress ◽

Early Life ◽

Early Life Stress

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A Polygenic Score for Body Mass Index is Associated with Depressive Symptoms via Early Life Stress: Evidence for gene-environment correlation

10.1101/536938 ◽

2019 ◽

Cited By ~ 1

Author(s):

Reut Avinun ◽

Ahmad R. Hariri

Keyword(s):

Mental Health ◽

Body Mass Index ◽

Depressive Symptoms ◽

Body Mass ◽

Indirect Effect ◽

Genetic Risk ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Gene Environment

ABSTRACTBackgroundIncreasing childhood overweight and obesity rates are associated with not only adverse physical, but also mental health outcomes, including depression. These negative outcomes may be caused and/or exacerbated by the bullying and shaming overweight individuals experience. As body mass index (BMI) can be highly heritable, we hypothesized that a genetic risk toward higher BMI, will predict higher early life stress (ELS), which in turn will predict higher depressive symptoms in adulthood. Such a process will reflect an evocative gene-environment correlation (rGE) wherein an individual’s genetically influenced phenotype evokes a reaction from the environment that subsequently shapes the individual’s health.MethodsWe modeled genetic risk using a polygenic score of BMI derived from a recent large GWAS meta-analysis. Self-reports were used for the assessment of ELS and depressive symptoms in adulthood. The discovery sample consisted of 524 non-Hispanic Caucasian university students from the Duke Neurogenetics Study (DNS; 278 women, mean age 19.78±1.23 years) and the independent replication sample consisted of 5 930 white British individuals from the UK biobank (UKB; 3 128 women, mean age 62.66±7.38 years).ResultsA significant mediation effect was found in the DNS (indirect effect=.207, bootstrapped SE=.10, 95% CI: .014 to .421), and then replicated in the UKB (indirect effect=.04, bootstrapped SE=.01, 95% CI: .018 to .066). Higher BMI polygenic scores were associated with higher depressive symptoms through the experience of higher ELS.ConclusionsOur findings suggest that evocative rGE may contribute to weight-related mental health problems and stress the need for interventions that aim to reduce weight bias, specifically during childhood.

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