scholarly journals Cumulative prenatal exposure to adversity reveals associations with a broad range of neurodevelopmental outcomes that are moderated by a novel, biologically informed polygenetic score based on the serotonin transporter solute carrier family C6, member 4 (SLC6A4) gene expression

2017 ◽  
Vol 29 (5) ◽  
pp. 1601-1617 ◽  
Author(s):  
Patrícia P. Silveira ◽  
Irina Pokhvisneva ◽  
Carine Parent ◽  
Shirong Cai ◽  
Anu Sathyan Sathyapalan Rema ◽  
...  
Keyword(s):  
Serotonin Transporter ◽  
Early Life ◽  
Child Behavior Checklist ◽  
Birth Cohorts ◽  
Neurodevelopmental Outcomes ◽  
Genetic Score ◽  
Cumulative Impact ◽  
Early Life Adversity ◽  
Developmental Problems ◽  
Wide Range

AbstractWhile many studies focus on the association between early life adversity and the later risk for psychopathology, few simultaneously explore diverse forms of environmental adversity. Moreover, those studies that examined the cumulative impact of early life adversity focus uniquely on postnatal influences. The objective of this study was to focus on the fetal period of development to construct and validate a cumulative prenatal adversity score in relation to a wide range of neurodevelopmental outcomes. We also examined the interaction of this adversity score with a biologically informed genetic score based on the serotonin transporter gene. Prenatal adversities were computed in two community birth cohorts using information on health during pregnancy, birth weight, gestational age, income, domestic violence/sexual abuse, marital strain, as well as maternal smoking, anxiety, and depression. A genetic score based on genes coexpressed with the serotonin transporter in the amygdala, hippocampus, and prefrontal cortex during prenatal life was constructed with an emphasis on functionally relevant single nucleotide polymorphisms, that is, expression quantitative trait loci. Prenatal adversities predicted a wide range of developmental and behavioral alterations in children as young as 2 years of age in both cohorts. There were interactions between the genetic score and adversities for several domains of the Child Behavior Checklist (CBCL), with pervasive developmental problems remaining significant adjustment for multiple comparisons. Scores combining different prenatal adverse exposures predict childhood behavior and interact with the genetic background to influence the risk for psychopathology.

Protector and Casualty

2019 ◽  
pp. 495-522
Author(s):  
Meg Dennison ◽  
Katie McLaughlin
Keyword(s):  
Early Life ◽  
Positive Emotion ◽  
Positive Emotions ◽  
Protective Factor ◽  
Mental Health Problems ◽  
Positive Emotionality ◽  
Early Life Adversity ◽  
Adverse Experiences ◽  
Wide Range ◽  
Positive Valence

Early-life adversity is associated with elevated risk for a wide range of mental disorders across the lifespan, including those that involve disruptions in positive emotionality. Although extensive research has evaluated heightened negative emotionality and threat processing as developmental mechanisms linking early-life adversity with mental health problems, emerging evidence suggests that positive emotions play an integral, but complex, role in the association of early-life adversity with psychopathology. This chapter identifies two pathways through which positive emotion influences risk for psychopathology following early-life adversity. First, experiences of early-life adversity may alter the development of the “positive valence system”, which in turn increases risk for psychopathology. Second, the association between adversity and psychopathology may vary as a function of individual differences in positive emotionality. We consider how the development of positive emotionality—measured at psychological, behavioral and neurobiological levels—may be altered by early-life adversity, creating a diathesis for psychopathology. We additionally review evidence for the role of positive emotion, measured at multiple levels, as a protective factor that buffers against the adverse impacts of adversity. In integrating these two roles, it is proposed that characteristics of environmental adversity, including developmental timing, duration, and type of adversity, may differentially impact the development of positive emotionality, leading to a better understanding of risks associated with specific adverse experiences. Methodological issues regarding the measurement of adverse environments as well as implications for early intervention and treatment are discussed.

scholarly journals SUN-722 Liver Leptin Receptor Gene Network Moderates the Effects of Early Life Adversity on Anxiety and Depression Problems in Children and Adolescents

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Randriely Merscher Sobreira de Lima ◽  
Barbara Barth ◽  
Danusa Mar Arcego ◽  
Euclides José de Mendonça Filho ◽  
Sachin Patel ◽  
...  
Keyword(s):  
Early Life ◽  
Gene Network ◽  
Child Behavior Checklist ◽  
Cholesterol Metabolism ◽  
Emotional Behavior ◽  
Anterior Cingulate ◽  
Polygenic Risk Score ◽  
Emotional Symptoms ◽  
Early Life Adversity ◽  
Lepr Gene

Abstract Leptin is a hormone involved in the regulation of food intake, with receptors largely expressed centrally and peripherally, in structures like the hypothalamus and the liver. Beyond its well-known actions as an energy-balance regulator, leptin is linked to psychiatric disorders. Considering that the association between genetic and early environmental factors contributes to psychopathology, disruptions of leptin signaling could be a key mechanism in this interaction. To investigate this possibility, we created an expression-based polygenic risk score (ePRS) reflecting variations in the function of the LepR gene network in the liver and hypothalamus, and investigated its interaction with postnatal adversity on Child Behavior Checklist in 4 years old children (main cohort: MAVAN, N=137) and 17 years old teenagers (Replication Cohort: ALSPAC, N=2630). There is an interaction effect between adversity exposure and liver-based LepR-ePRS, increasing depressive and anxiety problems on the MAVAN cohort (β=78.16, p=0.02, β=83.77, p=0.01). In ALSPAC, the results were replicated, showing an interaction between adversity exposure and liver-based LepR-ePRS, increasing the depression score and somatic symptoms (β=24.65, p=0.005; β=33.51, p=0.009). No significant interactions were found using the hypothalamus-based LepR-ePRS (p>0.05), suggesting specificity for the liver LepR gene network to predict these behavioral outcomes. A parallel-independent component analysis showed relationships between the SNPs from the liver ePRS-LepR and gray matter density in cortical areas involved in emotion regulation (middle frontal gyrus, inferior parietal lobule and anterior cingulate). Finally, the relationship between gene and MRI components in this analysis is moderated by the history of early life adversity exposure. Enrichment analysis of the liver LepR co-expression network shows that these genes are related to biological processes including regulation of glucose transport, cholesterol metabolism and cellular glucose homeostasis, which indicates possible underlying mechanisms linking peripheral metabolism-related gene expression and the development of emotional symptoms. Our data supports the hypothesis that exposure to early adversity affects emotional behavior, and the liver LepR gene network is an important moderator of these effects. Further studies on development of emotional symptoms should consider metabolic markers to understand these complex phenotypes.

Unexpected effects of early-life adversity and social enrichment on the anxiety profile of mice varying in serotonin transporter genotype

2013 ◽  
Vol 247 ◽  
pp. 248-258 ◽  
Author(s):  
Vanessa Kloke ◽  
Rebecca S. Heiming ◽  
Stefanie Bölting ◽  
Sylvia Kaiser ◽  
Lars Lewejohann ◽  
...  
Keyword(s):  
Serotonin Transporter ◽  
Early Life ◽  
Early Life Adversity ◽  
Serotonin Transporter Genotype

scholarly journals Serotonin-related pathways and developmental plasticity: relevance for psychiatric disorders

2014 ◽  
Vol 16 (1) ◽  
pp. 29-41 ◽  
Keyword(s):  
Psychiatric Disorders ◽  
Neural Plasticity ◽  
Life Stress ◽  
Early Life ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Developmental Plasticity ◽  
Neural Circuit ◽  
Early Life Stress ◽  
Early Life Adversity ◽  
Wide Range

Risk for adult psychiatric disorders is partially determined by early-life alterations occurring during neural circuit formation and maturation. In this perspective, recent data show that the serotonin system regulates key cellular processes involved in the construction of cortical circuits. Translational data for rodents indicate that early-life serotonin dysregulation leads to a wide range of behavioral alterations, ranging from stress-related phenotypes to social deficits. Studies in humans have revealed that serotonin-related genetic variants interact with early-life stress to regulate stress-induced cortisol responsiveness and activate the neural circuits involved in mood and anxiety disorders. Emerging data demonstrate that early-life adversity induces epigenetic modifications in serotonin-related genes. Finally, recent findings reveal that selective serotonin reuptake inhibitors can reinstate juvenile-like forms of neural plasticity, thus allowing the erasure of long-lasting fear memories. These approaches are providing new insights on the biological mechanisms and clinical application of antidepressants.

scholarly journals Cohort profile for the STratifying Resilience and Depression Longitudinally (STRADL) study: A depression-focused investigation of Generation Scotland, using detailed clinical, cognitive, and neuroimaging assessments

2021 ◽  
Vol 4 ◽  
pp. 185
Author(s):  
Tina Habota ◽  
Anca-Larisa Sandu ◽  
Gordon D. Waiter ◽  
Christopher J. McNeil ◽  
J. Douglas Steele ◽  
...  
Keyword(s):  
Psychological Health ◽  
Early Life ◽  
Brain Magnetic Resonance Imaging ◽  
Family Health ◽  
Population Based ◽  
Health Study ◽  
Psychological Resilience ◽  
Birth Cohorts ◽  
Early Life Adversity ◽  
Generation Scotland

STratifying Resilience and Depression Longitudinally (STRADL) is a population-based study built on the Generation Scotland: Scottish Family Health Study (GS:SFHS) resource. The aim of STRADL is to subtype major depressive disorder (MDD) on the basis of its aetiology, using detailed clinical, cognitive, and brain imaging assessments. The GS:SFHS provides an important opportunity to study complex gene-environment interactions, incorporating linkage to existing datasets and inclusion of early-life variables for two longitudinal birth cohorts. Specifically, data collection in STRADL included: socio-economic and lifestyle variables; physical measures; questionnaire data that assesses resilience, early-life adversity, personality, psychological health, and lifetime history of mood disorder; laboratory samples; cognitive tests; and brain magnetic resonance imaging. Some of the questionnaire and cognitive data were first assessed at the GS:SFHS baseline assessment between 2006-2011, thus providing longitudinal measures relevant to the study of depression, psychological resilience, and cognition. In addition, routinely collected historic NHS data and early-life variables are linked to STRADL data, further providing opportunities for longitudinal analysis. Recruitment has been completed and we consented and tested 1,188 participants.

scholarly journals Is Early Life Adversity a Trigger towards Inflammageing?

2021 ◽  
Author(s):  
Myriam Merz ◽  
Jonathan D. Turner
Keyword(s):  
Early Life ◽  
Viral Infections ◽  
Disease Risk ◽  
Later Life ◽  
Early Life Adversity ◽  
Chronic Viral Infections ◽  
Age Related ◽  
Wide Range ◽  
Distinct Features ◽  
Near Future

There are many ‘faces’ of early life adversity (ELA), such as childhood trauma, institutionalization, abuse or exposure to environmental toxins. These have been implicated in the onset and severity of a wide range of chronic non-communicable diseases later in life. The later-life disease risk has a well-established immunological component. This raises the question as to whether accelerated immune-ageing mechanistically links early-life adversity to the lifelong health trajectory resulting in either ‘poor’ or ‘healthy’ ageing. Here we examine observational and mechanistic studies of ELA and inflammageing, highlighting common and distinct features in these two life stages. Many biological processes appear in common including reduction in telomere length, increased immuno-senescence, metabolic distortions and chronic (viral) infections. We propose that ELA shapes the developing immune, endocrine and nervous system in a non-reversible way, creating a distinct phenotype with accelerated immuno-senescence and systemic inflammation. We believe that ELA acts as an accelerator for inflammageing and age-related diseases. Furthermore, we now have the tools and cohorts to be able to dissect the interaction between early life adversity and later life phenotype. This should, in the near future, allow us to identify the ecological and mechanistic processes that are involved in ‘healthy’ or accelerated immune-ageing.

scholarly journals CUMULATIVE DISADVANTAGE OF EARLY-LIFE ADVERSITY AND HEALTH IN MIDLIFE AND LATER ADULTHOOD

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S350-S351
Author(s):  
Jooyoung Kong ◽  
Agus Surachman ◽  
Deborah Carr
Keyword(s):  
Psychological Health ◽  
Early Life ◽  
Structural Equation ◽  
Large Scale ◽  
Latent Class ◽  
Well Being ◽  
Equation Modeling ◽  
Early Life Adversity ◽  
Wide Range ◽  
Physical And Psychological Health

Abstract Cumulative dis/advantage (CDA) framework is one of the most influential theoretical frameworks in understanding how early adversity creates health disparities across adulthood. The CDA model posits that adverse experiences early in life may lead to subsequent adversities over time and accumulates across the life course. Various studies have shown that middle-aged and later adulthood are periods when accumulated disadvantages proliferate, resulting in heightened risks for an individual’s health and well-being. This symposium includes four presentations that build on such existing knowledge, and its primary aim was to further examine the complexity of how various types of adverse childhood experiences may influence physical and psychological health in middle and later adulthood. This symposium addresses a wide range of early adversities, including low socioeconomic status, parental maltreatment, and household dysfunctions. The four presentations also focus on examining various aspects of physical and psychological health outcomes in later adulthood, including measures of body mass index, physical functional ability, somatic symptoms, and clinical risk for rapid declines in kidney function. Furthermore, these presentations will demonstrate the utilization of innovative and robust methodological approaches, including latent class analysis, multilevel structural equation modeling, and latent growth modeling on examining the association between early life adversity on the long-term trajectory of change in health status using large-scale longitudinal data. Lastly, this symposium consists of an outstanding group of multidisciplinary presenters with diverse backgrounds who aim to enhance the understanding of the processes and mechanisms of CDA and how they affect individuals’ life courses.

scholarly journals Cohort profile for the STratifying Resilience and Depression Longitudinally (STRADL) study: A depression-focused investigation of Generation Scotland, using detailed clinical, cognitive, and neuroimaging assessments

2019 ◽  
Vol 4 ◽  
pp. 185 ◽  
Author(s):  
Tina Habota ◽  
Anca-Larisa Sandu ◽  
Gordon D. Waiter ◽  
Christopher J. McNeil ◽  
J. Douglas Steele ◽  
...  
Keyword(s):  
Psychological Health ◽  
Early Life ◽  
Brain Magnetic Resonance Imaging ◽  
Family Health ◽  
Population Based ◽  
Health Study ◽  
Birth Cohorts ◽  
Early Life Adversity ◽  
Generation Scotland ◽  
History Of

STratifying Resilience and Depression Longitudinally (STRADL) is a population-based study built on the Generation Scotland: Scottish Family Health Study (GS:SFHS) resource. The aim of STRADL is to subtype major depressive disorder (MDD) on the basis of its aetiology, using detailed clinical, cognitive, and brain imaging assessments. The GS:SFHS provides an important opportunity to study complex gene-environment interactions, incorporating linkage to existing datasets and inclusion of early-life variables for two longitudinal birth cohorts. Specifically, data collection in STRADL included: socio-economic and lifestyle variables; physical measures; questionnaire data that assesses resilience, early-life adversity, personality, psychological health, and lifetime history of mood disorder; laboratory samples; cognitive tests; and brain magnetic resonance imaging. Some of the questionnaire and cognitive data were first assessed at the GS:SFHS baseline assessment between 2006-2011, thus providing longitudinal measures of depression and resilience. Similarly, routine NHS data and early-life variables are linked to STRADL data, further providing opportunities for longitudinal analysis. Recruitment has been completed and we consented and tested 1,188 participants.

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