scholarly journals Prenatal Exposure to Early Life Adversity and Neonatal Brain Volumes at Birth

2021 ◽  
Author(s):  
Regina L Triplett ◽  
Rachel E Lean ◽  
Amisha Parikh ◽  
J Philip Miller ◽  
Dimitrios Alexopoulos ◽  
...  
Keyword(s):  
White Matter ◽  
Prenatal Exposure ◽  
Gray Matter ◽  
Early Life ◽  
Psychosocial Stress ◽  
Social Disadvantage ◽  
Cortical Folding ◽  
Neonatal Brain ◽  
Early Life Adversity ◽  
Brain Volumes

Importance: Exposure to early life adversity alters the structural development of key brain regions underlying neurodevelopmental impairments. The extent that prenatal exposure to life adversity alters structure at birth remains poorly understood. Objective: To determine if prenatal exposure to maternal social advantage and psychosocial distress alters global and regional brain volumes and cortical folding in the first weeks of life. Design: A prospective, longitudinal study of sociodemographically-diverse mothers recruited in the first trimester of pregnancy and their infants who underwent brain magnetic resonance imaging scan in the first weeks of life. Setting: Mothers were recruited from local obstetric clinics from 2017-2020. Participants: Of 399 mother-infant dyads prospectively recruited into the parent study, 280 healthy, term-born infants (47% female, mean postmenstrual age at scan 42 weeks) were eligible for inclusion. Exposures: Maternal social advantage and psychosocial distress in pregnancy. Main Measures and Outcomes: Two measures of latent constructs were created using Confirmatory Factor Analyses spanning Maternal Social Advantage (Income to Needs ratio, Area Deprivation Index, Healthy Eating Index, education level, insurance status) and Psychosocial Stress (Perceived Stress Scale, Edinburgh Postnatal Depression Scale, Everyday Discrimination Scale, Stress and Adversity Inventory). Neonatal cortical and subcortical gray matter, white matter, cerebellar, hippocampus, and amygdala volumes were generated using semi-automated age-specific segmentation pipelines. Results: After covariate adjustment and multiple comparisons correction, greater social disadvantage (i.e., lower Advantage values) was associated with reduced cortical gray matter (p=.03), subcortical gray matter (p=.008), and white matter (p=.004) volumes and cortical folding (p=.001). Psychosocial Stress was not related to neonatal brain metrics. While social disadvantage was associated with smaller absolute volumes of the bilateral hippocampi and amygdalae, after correcting for total brain volume, there were no regional effects. Conclusions and Relevance: Prenatal exposure to social disadvantage is associated with global reductions in brain volumes and cortical folding at birth. No regional specificity for the hippocampus or amygdala was detected. Results highlight that the deleterious effects of poverty begin in utero and are evident in the first weeks of life. These findings emphasize that preventative interventions to support fetal brain development should address socioeconomic hardships for expectant parents.

scholarly journals Hair glucocorticoids are associated with childhood adversity, depressive symptoms and reduced global and lobar grey matter in Generation Scotland

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Claire Green ◽  
Aleks Stolicyn ◽  
Mathew A. Harris ◽  
Xueyi Shen ◽  
Liana Romaniuk ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Life Stress ◽  
Early Life ◽  
Childhood Adversity ◽  
Later Life ◽  
Early Life Adversity ◽  
Brain Volumes ◽  
Stable Measure ◽  
Regional Brain ◽  
Generation Scotland

AbstractHypothalamic–pituitary–adrenal (HPA) axis dysregulation has been commonly reported in major depressive disorder (MDD), but with considerable heterogeneity of results; potentially due to the predominant use of acute measures of an inherently variable/phasic system. Chronic longer-term measures of HPA-axis activity have yet to be systematically examined in MDD, particularly in relation to brain phenotypes, and in the context of early-life/contemporaneous stress. Here, we utilise a temporally stable measure of cumulative HPA-axis function (hair glucocorticoids) to investigate associations between cortisol, cortisone and total glucocorticoids with concurrent measures of (i) lifetime-MDD case/control status and current symptom severity, (ii) early/current-life stress and (iii) structural neuroimaging phenotypes, in N = 993 individuals from Generation Scotland (mean age = 59.1 yrs). Increased levels of hair cortisol were significantly associated with reduced global and lobar brain volumes with reductions in the frontal, temporal and cingulate regions (βrange = −0.057 to −0.104, all PFDR < 0.05). Increased levels of hair cortisone were significantly associated with MDD (lifetime-MDD status, current symptoms, and severity; βrange = 0.071 to 0.115, all PFDR = < 0.05), with early-life adversity (β = 0.083, P = 0.017), and with reduced global and regional brain volumes (global: β = −0.059, P = 0.043; nucleus accumbens: β = −0.075, PFDR = 0.044). Associations with total glucocorticoids followed a similar pattern to the cortisol findings. In this large community-based sample, elevated glucocorticoids were significantly associated with MDD, with early, but not later-life stress, and with reduced global and regional brain phenotypes. These findings provide important foundations for future mechanistic studies to formally explore causal relationships between early adversity, chronic rather than acute measures of glucocorticoids, and neurobiological associations relevant to the aetiology of MDD.

scholarly journals Early-life adversity is associated with differential gene expression in response to acute psychological stress: preliminary findings

2019 ◽  
Author(s):  
Idan Shalev ◽  
Waylon J. Hastings ◽  
Laura Etzel ◽  
Salomon Israel ◽  
Michael A. Russell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Experimental Design ◽  
Inflammatory Cytokines ◽  
Early Life ◽  
Psychosocial Stress ◽  
Group Status ◽  
Early Life Adversity ◽  
Acute Psychosocial Stress ◽  
Physiological Systems ◽  
Pro Inflammatory Cytokines

AbstractObjectiveExposure to early-life adversity (ELA) can result in long-term changes to physiological systems, which predispose individuals to negative health outcomes. This biological embedding of stress-responsive systems may operate via dysregulation of physiological resources in response to common stressors. The present study used a novel experimental design to test how young adults’ exposure to ELA influence neuroendocrine and inflammatory responses to acute stress.Materials and methodsParticipants were 12 males (mean age= 21.25), half of whom endorsed at least three significant adverse events up to age 18 years (‘ELA group’), and half who confirmed zero (‘controls’). Using a randomized within-subjects, between-groups experimental design, we induced acute psychosocial stress (Trier Social Stress Test, TSST), and included a no-stress control condition one week apart. During these sessions, we obtained repeated measurements of physiological reactivity, gene expression of NR3C1, FKBP5 and NFKB1, and plasma levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNFα) over a 4-hour window post-test.ResultsThe ELA group evinced significantly higher cortisol response and lower NR3C1 gene expression in response to the TSST compared with controls, while no differences were observed in the no-stress condition. Cortisol and group status interacted such that increase in cortisol predicted increase in both NR3C1 and NFKB1 expression among controls, but decrease in the ELA group. For pro-inflammatory cytokines, only IL-6 increased significantly in response to the TSST, with no differences between the two groups.ConclusionOverall, we provide preliminary findings for the biological embedding of stress via a dynamic and dysregulated pattern evidenced in response to acute psychosocial stress. ELA may program physiological systems in a maladaptive manner more likely to manifest during times of duress, predisposing individuals to the negative health consequences of everyday stressors. Future studies with larger sample size including both males and females are needed to replicate these findings.

scholarly journals Twin-Singleton Differences in Neonatal Brain Structure

2011 ◽  
Vol 14 (3) ◽  
pp. 268-276 ◽  
Author(s):  
Rebecca C. Knickmeyer ◽  
Chaeryon Kang ◽  
Sandra Woolson ◽  
J. Keith Smith ◽  
Robert M. Hamer ◽  
...  
Keyword(s):  
White Matter ◽  
Gray Matter ◽  
Gestational Age ◽  
Twin Studies ◽  
Postnatal Period ◽  
Intracranial Volume ◽  
Brain Volumes ◽  
Mri Scans ◽  
Mz Twins ◽  
The Relationship

Twin studies suggest that global and regional brain volumes are highly heritable. However, estimates of heritability vary across development. Given that all twin studies are open to the potential criticism of non-generalizability due to differences in intrauterine environment between twins and singletons, these age effects may reflect the influence of perinatal environmental factors, which are unique to twins and which may be especially evident early in life. To address this question, we compared brain volumes and the relationship of brain volumes to gestational age in 136 singletons (67 male, 69 female) and 154 twins (75 male, 79 female; 82 DZ, 72 MZ) who had received high resolution MRI scans of the brain in the first month of life. Intracranial volume, total white matter, and ventricle volumes did not differ between twins and singletons. However, cerebrospinal fluid and frontal white matter volume was greater in twins compared to singletons. While gray matter volumes at MRI did not differ between groups, the slope of the relationship between total and cortical gray matter and gestational age at the MRI scan was steeper in MZ twins compared to DZ twins. Post-hoc analyses suggested that gray matter development is delayed in MZ twins in utero and that they experience ‘catch-up’ growth in the first month of life. These differences should be taken into account when interpreting and designing studies in the early postnatal period.

scholarly journals Adiposity is related to cerebrovascular and brain volumetry outcomes in the RUN DMC study

Neurology ◽  
2019 ◽  
Vol 93 (9) ◽  
pp. e864-e878 ◽  
Author(s):  
Ilse A.C. Arnoldussen ◽  
Deborah R. Gustafson ◽  
Esther M.C. Leijsen ◽  
Frank-Erik de Leeuw ◽  
Amanda J. Kiliaan
Keyword(s):  
White Matter ◽  
Brain Imaging ◽  
Gray Matter ◽  
Diffusion Tensor ◽  
Hippocampal Volume ◽  
White Matter Hyperintensity ◽  
Brain Volumes ◽  
Brain Volumetry ◽  
Total Brain

ObjectiveAdiposity predictors, body mass index (BMI), waist circumference (WC), and blood leptin and total adiponectin levels were associated with components of cerebral small vessel disease (CSVD) and brain volumetry in 503 adults with CSVD who were ≥50 years of age and enrolled in the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC).MethodsRUN DMC participants were followed up for 9 years (2006–2015). BMI, WC, brain imaging, and dementia diagnoses were evaluated at baseline and follow-up. Adipokines were measured at baseline. Brain imaging outcomes included CSVD components, white matter hyperintensities, lacunes, microbleeds, gray and white matter, hippocampal, total brain, and intracranial volumes.ResultsCross-sectionally among men at baseline, higher BMI, WC, and leptin were associated with lower gray matter and total brain volumes, and higher BMI and WC were associated with lower hippocampal volume. At follow-up 9 years later, higher BMI was cross-sectionally associated with lower gray matter volume, and an obese WC (>102 cm) was protective for ≥1 lacune or ≥1 microbleed in men. In women, increasing BMI and overweight or obesity (BMI ≥25 kg/m2 or WC >88 cm) were associated with ≥1 lacune. Longitudinally, over 9 years, a baseline obese WC was associated with decreasing hippocampal volume, particularly in men, and increasing white matter hyperintensity volume in women and men.ConclusionsAnthropometric and metabolic adiposity predictors were differentially associated with CSVD components and brain volumetry outcomes by sex. Higher adiposity is associated with a vascular-neurodegenerative spectrum among adults at risk for vascular forms of cognitive impairment and dementias.

109. From Early Life Adversity to Adolescence Depression: White Matter Remodelling in a Translational Animal Model

2017 ◽  
Vol 81 (10) ◽  
pp. S46
Author(s):  
Severine Farley ◽  
Julien Grenier ◽  
Victor Gorgievski ◽  
Alexandre Barbe ◽  
Wojciech Jaworski ◽  
...  
Keyword(s):  
Animal Model ◽  
White Matter ◽  
Early Life ◽  
Early Life Adversity

scholarly journals Immune-Related Genetic Overlap Between Regional Gray Matter Reductions and Psychiatric Symptoms in Adolescents, and Gene-Set Validation in a Translational Model

2021 ◽  
Vol 15 ◽  
Author(s):  
Lukas Penninck ◽  
El Chérif Ibrahim ◽  
Eric Artiges ◽  
Victor Gorgievski ◽  
Sylvane Desrivières ◽  
...  
Keyword(s):  
Gray Matter ◽  
Childhood Maltreatment ◽  
Early Life ◽  
Maternal Separation ◽  
Psychiatric Symptoms ◽  
Predictive Ability ◽  
Psychotic Symptoms ◽  
Immune Gene ◽  
Early Life Adversity ◽  
Gene Set

Adolescence is a period of vulnerability for the maturation of gray matter (GM) and also for the onset of psychiatric disorders such as major depressive disorder (MDD), bipolar disorder and schizophrenia. Chronic neuroinflammation is considered to play a role in the etiology of these illnesses. However, the involvement of neuroinflammation in the observed link between regional GM volume reductions and psychiatric symptoms is not established yet. Here, we investigated a possible common immune-related genetic link between these two phenomena in european adolescents recruited from the community. Hippocampal and medial prefrontal cortex (mPFC) were defined a priori as regions of interest (ROIs). Their GM volumes were extracted in 1,563 14-year-olds from the IMAGEN database. We found a set of 26 SNPs that correlated with the hippocampal volumes and 29 with the mPFC volumes at age 14. We formed two ROI-Related Immune-gene scores (RRI) with the inflammation SNPs that correlated to hippocampal GM volume and to mPFC GM volume. The predictive ability of both RRIs with regards to the presence of psychiatric symptoms at age 18 was investigated by correlating the RRIs with psychometric questionnaires obtained at age 18. The RRIs (but not control scores constructed with random SNPs) correlated with the presence of depressive symptoms, positive psychotic symptoms, and externalizing symptoms in later adolescence. In addition, the effect of childhood maltreatment, one of the major environmental risk factors for depression and other mental disorders, interacted with the RRI effect. We next sought to validate this finding by investigating our set of inflammatory genes in a translational animal model of early life adversity. Mice were subjected to a protocol of maternal separation at an early post-natal age. We evaluated depressive behaviors in separated and non-separated mice at adolescence and their correlations with the concomitant expression of our genes in whole blood samples. We show that in mice, early life adversity affected the expression of our set of genes in peripheral blood, and that levels of expression correlated with symptoms of negative affect in adolescence. Overall, our translational findings in adolescent mice and humans provide a novel validated gene-set of immune-related genes for further research in the early stages of mood disorders.

scholarly journals The 5-HTTLPR genotype, early life adversity and cortisol responsivity to psychosocial stress in women

BJPsych Open ◽  
2018 ◽  
Vol 4 (4) ◽  
pp. 180-185 ◽  
Author(s):  
Jurate Aleknaviciute ◽  
Joke H. M. Tulen ◽  
Yolanda B. de Rijke ◽  
Mark van der Kroeg ◽  
Cornelis G. Kooiman ◽  
...  
Keyword(s):  
Childhood Maltreatment ◽  
Life Stress ◽  
Early Life ◽  
Psychosocial Stress ◽  
Social Stress ◽  
Stress Test ◽  
Early Life Stress ◽  
Trier Social Stress Test ◽  
Early Life Adversity ◽  
Personality Psychopathology

BackgroundThe serotonin transporter gene-linked polymorphic region (5-HTTLPR) has previously been associated with hypothalamus–pituitary–adrenal axis function. Moreover, it has been suggested that this association is moderated by an interaction with stressful life experiences.AimsTo investigate the moderation of cortisol response to psychosocial stress by 5-HTTLPR genotype, either directly or through an interaction with early life stress.MethodA total of 151 women, 85 of which had personality psychopathology, performed the Trier Social Stress Test while cortisol responsivity was assessed.ResultsThe results demonstrate a main effect of genotype on cortisol responsivity. Women carrying two copies of the long version of 5-HTTLPR exhibited stronger cortisol responses to psychosocial stress than women with at least one copy of the short allele (P = 0.03). However, the proportion of the variance of stress-induced cortisol responsivity explained by 5-HTTLPR genotype was not further strengthened by including early life adversity as a moderating factor (P = 0.52).ConclusionsOur results highlight the need to clarify gender-specific biological factors influencing the serotonergic system. Furthermore, our results suggest that childhood maltreatment, specifically during the first 15 years of life, is unlikely to exert a moderating influence of large effect on the relationship between the 5-HTTLPR genotype and cortisol responsivity to psychosocial stress.Declaration of interestNone.

scholarly journals Early-life adversity and orbitofrontal and cerebellar volumes in adults with obsessive–compulsive disorder: Voxel-based morphometry study

2016 ◽  
Vol 208 (1) ◽  
pp. 34-41 ◽  
Author(s):  
Samantha J. Brooks ◽  
Vanesh Naidoo ◽  
Annerine Roos ◽  
Jean-Paul Fouché ◽  
Christine Lochner ◽  
...  
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Childhood Trauma ◽  
Early Life ◽  
Voxel Based Morphometry ◽  
Obsessive Compulsive ◽  
Early Life Adversity ◽  
Brain Volumes ◽  
Compulsive Disorder ◽  
Physical Neglect ◽  
The Impact

BackgroundEarly-life adversity is a risk for obsessive–compulsive disorder (OCD), but the impact at the neural level is less clear.AimsTo investigate the association between brain volumes and early-life adversity in individuals with a diagnosis of OCD only.MethodThe Childhood Trauma Questionnaire (CTQ-28) was used to assess early-life adversity in 21 participants with OCD and 25 matched healthy controls. The relationship between global and regional brain volume and early-life adversity was measured using voxel-based morphometry (VBM). All data were corrected for multiple comparisons using family-wise error (FWE) at P<0.05.ResultsIn the OCD group, correlations with total CTQ scores were positively associated with a larger right orbitofrontal cortex volume. Physical neglect was higher in the OCD group than in controls and was positively associated with larger right cerebellum volume in the OCD group only.ConclusionsLarger brain volumes may reflect underlying developmental neuropathology in adults with OCD who also have experience of childhood trauma.

scholarly journals Accumbofrontal tract integrity is related to early life adversity and feedback learning

2021 ◽  
Author(s):  
Bryan V. Kennedy ◽  
Jamie L. Hanson ◽  
Nicholas J. Buser ◽  
Wouter van den Bos ◽  
Karen D. Rudolph ◽  
...  
Keyword(s):  
White Matter ◽  
Early Life ◽  
Structural Connectivity ◽  
Poor Mental Health ◽  
Reward Learning ◽  
Behavioral Alterations ◽  
White Matter Tracts ◽  
Early Life Adversity ◽  
Feedback Learning ◽  
Corticostriatal Circuit

AbstractAbuse, neglect, exposure to violence, and other forms of early life adversity (ELA) are incredibly common and significantly impact physical and mental development. While important progress has been made in understanding the impacts of ELA on behavior and the brain, the preponderance of past work has primarily centered on threat processing and vigilance while ignoring other potentially critical neurobehavioral processes, such as reward-responsiveness and learning. To advance our understanding of potential mechanisms linking ELA and poor mental health, we center in on structural connectivity of the corticostriatal circuit, specifically accumbofrontal white matter tracts. Here, in a sample of 77 youth (Mean age = 181 months), we leveraged rigorous measures of ELA, strong diffusion neuroimaging methodology, and computational modeling of reward learning. Linking these different forms of data, we hypothesized that higher ELA would be related to lower quantitative anisotropy in accumbofrontal white matter. Furthermore, we predicted that lower accumbofrontal quantitative anisotropy would be related to differences in reward learning. Our primary predictions were confirmed, but similar patterns were not seen in control white matter tracts outside of the corticostriatal circuit. Examined collectively, our work is one of the first projects to connect ELA to neural and behavioral alterations in reward-learning, a critical potential mechanism linking adversity to later developmental challenges. This could potentially provide windows of opportunity to address the effects of ELA through interventions and preventative programming.

Sign in / Sign up

Export Citation Format

Share Document