No robust evidence for an interaction between early-life adversity and protective factors on global and regional brain volumes.
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ABSTRACT:
SUBMITTER: Cortes Hidalgo AP
PROVIDER: S-EPMC9636055 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
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No robust evidence for an interaction between early-life adversity and protective factors on global and regional brain volumes.
Cortes Hidalgo Andrea P AP Tiemeier Henning H Metcalf Stephen A SA Monninger Maximilian M Meyer-Lindenberg Andreas A Aggensteiner Pascal-M PM Bakermans-Kranenburg Marian J MJ White Tonya T Banaschewski Tobias T van IJzendoorn Marinus H MH Holz Nathalie E NE
Developmental cognitive neuroscience 20221025
Childhood adversity is associated with brain morphology and poor psychological outcomes, and evidence of protective factors counteracting childhood adversity effects on neurobiology is scarce. We examined the interplay of childhood adversity with protective factors in relation to brain morphology in two independent longitudinal cohorts, the Generation R Study (N = 3008) and the Mannheim Study of Children at Risk (MARS) (N = 179). Cumulative exposure to 12 adverse events was assessed across child ...[more]
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Project description:ImportanceExposure to early-life adversity alters the structural development of key brain regions underlying neurodevelopmental impairments. The association between prenatal exposure to adversity and brain structure at birth remains poorly understood.ObjectiveTo examine whether prenatal exposure to maternal social disadvantage and psychosocial stress is associated with neonatal global and regional brain volumes and cortical folding.Design, setting, and participantsThis prospective, longitudinal cohort study included 399 mother-infant dyads of sociodemographically diverse mothers recruited in the first or early second trimester of pregnancy and their infants, who underwent brain magnetic resonance imaging in the first weeks of life. Mothers were recruited from local obstetric clinics in St Louis, Missouri from September 1, 2017, to February 28, 2020.ExposuresMaternal social disadvantage and psychosocial stress in pregnancy.Main outcomes and measuresConfirmatory factor analyses were used to create latent constructs of maternal social disadvantage (income-to-needs ratio, Area Deprivation Index, Healthy Eating Index, educational level, and insurance status) and psychosocial stress (Perceived Stress Scale, Edinburgh Postnatal Depression Scale, Everyday Discrimination Scale, and Stress and Adversity Inventory). Neonatal cortical and subcortical gray matter, white matter, cerebellum, hippocampus, and amygdala volumes were generated using semiautomated, age-specific, segmentation pipelines.ResultsA total of 280 mothers (mean [SD] age, 29.1 [5.3] years; 170 [60.7%] Black or African American, 100 [35.7%] White, and 10 [3.6%] other race or ethnicity) and their healthy, term-born infants (149 [53.2%] male; mean [SD] infant gestational age, 38.6 [1.0] weeks) were included in the analysis. After covariate adjustment and multiple comparisons correction, greater social disadvantage was associated with reduced cortical gray matter (unstandardized β = -2.0; 95% CI, -3.5 to -0.5; P = .01), subcortical gray matter (unstandardized β = -0.4; 95% CI, -0.7 to -0.2; P = .003), and white matter (unstandardized β = -5.5; 95% CI, -7.8 to -3.3; P < .001) volumes and cortical folding (unstandardized β = -0.03; 95% CI, -0.04 to -0.01; P < .001). Psychosocial stress showed no association with brain metrics. Although social disadvantage accounted for an additional 2.3% of the variance of the left hippocampus (unstandardized β = -0.03; 95% CI, -0.05 to -0.01), 2.3% of the right hippocampus (unstandardized β = -0.03; 95% CI, -0.05 to -0.01), 3.1% of the left amygdala (unstandardized β = -0.02; 95% CI, -0.03 to -0.01), and 2.9% of the right amygdala (unstandardized β = -0.02; 95% CI, -0.03 to -0.01), no regional effects were found after accounting for total brain volume.Conclusions and relevanceIn this baseline assessment of an ongoing cohort study, prenatal social disadvantage was 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 associations between poverty and brain development begin in utero and are evident early in life. These findings emphasize that preventive interventions that support fetal brain development should address parental socioeconomic hardships.
| S-EPMC9006107 | biostudies-literature
Project description:OBJECTIVE: Obesity adversely affects frontal lobe brain structure and function. Here we sought to show that people who are obese versus those who are of normal weight over a 5-year period have differential global and regional brain volumes. DESIGN: Using voxel-based morphometry, contrasts were done between those who were recorded as being either obese or of normal weight over two time points in the 5 years prior to the brain scan. In a post-hoc preliminary analysis, we compared scores for obese and normal weight people who completed the trail-making task. SUBJECTS: A total of 292 subjects were examined following exclusions (for example, owing to dementia, stroke and cortical infarcts) from the Prospective Investigation of the Vasculature in Uppsala Seniors cohort with a body mass index of normal weight (<25 kg m(-2)) or obese (30 kg m(-2)). RESULTS: People who were obese had significantly smaller total brain volumes and specifically, significantly reduced total gray matter (GM) volume (GMV) (with no difference in white matter or cerebrospinal fluid). Initial exploratory whole brain uncorrected analysis revealed that people who were obese had significantly smaller GMV in the bilateral supplementary motor area, bilateral dorsolateral prefrontal cortex (DLPFC), left inferior frontal gyrus and left postcentral gyrus. Secondary more stringent corrected analyses revealed a surviving cluster of GMV difference in the left DLPFC. Finally, post-hoc contrasts of scores on the trail-making task, which is linked to DLPFC function, revealed that obese people were significantly slower than those of normal weight. CONCLUSION: These findings suggest that in comparison with normal weight, people who are obese have smaller GMV, particularly in the left DLPFC. Our results may provide evidence for a potential working memory mechanism for the cognitive suppression of appetite that may lower the risk of developing obesity in later life.
| S-EPMC3572402 | biostudies-other
Project description:AbstractThe overarching objective is to review how early exposure to adversity interacts with inflammation to alter brain maturation. Both adversity and inflammation are significant risk factors for psychopathology. Literature relevant to the effects of adversity in children and adolescents on brain development is reviewed. These studies are supported by research in animals exposed to species-relevant stressors during development. While it is known that exposure to adversity at any age increases inflammation, the effects of inflammation are exacerbated at developmental stages when the immature brain is uniquely sensitive to experiences. Microglia play a vital role in this process, as they scavenge cellular debris and prune synapses to optimize performance. In essence, microglia modify the synapse to match environmental demands, which is necessary for someone with a history of adversity. Overall, by piecing together clinical and preclinical research areas, what emerges is a picture of how adversity uniquely sculpts the brain. Microglia interactions with the inhibitory neurotransmitter GABA (specifically, the subtype expressing parvalbumin) are discussed within contexts of development and adversity. A review of inflammation markers in individuals with a history of abuse is combined with preclinical studies to describe their effects on maturation. Inconsistencies within the literature are discussed, with a call for standardizing methodologies relating to the age of assessing adversity effects, measures to quantify stress and inflammation, and more brain-based measures of biochemistry. Preclinical studies pave the way for interventions using anti-inflammation-based agents (COX-2 inhibitors, CB2 agonists, meditation/yoga) by identifying where, when, and how the developmental trajectory goes awry.
| S-EPMC8820591 | biostudies-literature
Project description:ObjectiveTo determine whether there is a correlation between obesity-related variants and regional brain volumes.MethodsBased on a mixed linear model (MLM), we analyzed the association between 1,498 obesity-related SNPs in the GWAS Catalog and 164 regional brain volumes from 29,420 participants (discovery cohort N = 19,997, validation cohort N = 9,423) in UK Biobank. The statistically significant brain regions in association analysis were classified into 6 major neural networks (dopamine (DA) motive system, central autonomic network (CAN), cognitive emotion regulation, visual object recognition network, auditory object recognition network, and sensorimotor system). We summarized the association between obesity-related variants (metabolically healthy obesity variants, metabolically unhealthy obesity variants, and unclassified obesity-related variants) and neural networks.ResultsFrom association analysis, we determined that 17 obesity-related SNPs were associated with 51 regional brain volumes. Several single SNPs (e.g., rs13107325-T (SLC39A8), rs1876829-C (CRHR1), and rs1538170-T (CENPW)) were associated with multiple regional brain volumes. In addition, several single brain regions (e.g., the white matter, the grey matter in the putamen, subcallosal cortex, and insular cortex) were associated with multiple obesity-related variants. The metabolically healthy obesity variants were mainly associated with the regional brain volumes in the DA motive system, sensorimotor system and cognitive emotion regulation neural networks, while metabolically unhealthy obesity variants were mainly associated with regional brain volumes in the CAN and total tissue volumes. In addition, unclassified obesity-related variants were mainly associated with auditory object recognition network and total tissue volumes. The results of MeSH (medical subject headings) enrichment analysis showed that obesity genes associated with brain structure pointed to the functional relatedness with 5-Hydroxytryptamine receptor 4 (5-HT4), growth differentiation factor 5 (GDF5), and high mobility group protein AT-hook 2 (HMGA2 protein).ConclusionIn summary, we found that obesity-related variants were associated with different brain volume measures. On the basis of the multiple SNPs, we found that metabolically healthy and unhealthy obesity-related SNPs were associated with different brain neural networks. Based on our enrichment analysis, modifications of the 5-HT4 pathway might be a promising therapeutic strategy for obesity.
| S-EPMC8648807 | biostudies-literature
Project description:ObjectiveNeuroimaging findings have been reported in regions of the brain associated with emotion in both adults and adolescents with depression, but few studies have investigated whether such brain alterations can be detected in adolescents with subthreshold depression, a condition at risk for major depressive disorder. In this study, we searched for differences in brain structure at age 14 years in adolescents with subthreshold depression and their relation to depression at age 16 years.MethodHigh-resolution structural magnetic resonance imaging was used to assess adolescents with self-reported subthreshold depression (n = 119) and healthy control adolescents (n = 461), all recruited from a community-based sample. Regional gray and white matter volumes were compared across groups using whole-brain voxel-based morphometry. The relationship between subthreshold depression at baseline and depression outcome was explored using causal mediation analyses to search for mediating effects of regional brain volumes.ResultsAdolescents with subthreshold depression had smaller gray matter volume in the ventromedial prefrontal and rostral anterior cingulate cortices and caudates, and smaller white matter volumes in the anterior limb of internal capsules, left forceps minor, and right cingulum. In girls, but not in boys, the relation between subthreshold depression at baseline and high depression score at follow-up was mediated by medial-prefrontal gray matter volume.ConclusionSubthreshold depression in early adolescence might be associated with smaller gray and white matter volumes in regions of the frontal-striatal-limbic affective circuit, and the occurrence of depression in girls with subthreshold depression might be influenced by medial-prefrontal gray matter volume. However, these findings should be interpreted with caution because of the limitations of the clinical assessment methods.
| S-EPMC7614311 | biostudies-literature
Project description:ObjectiveAs therapeutics are being developed to target the underlying neuropathology of Huntington disease, interest is increasing in methodologies for conducting clinical trials in the prodromal phase. This study was designed to examine the potential utility of structural MRI measures as outcome measures for such trials.MethodsData are presented from 211 prodromal individuals and 60 controls, scanned both at baseline and at the 2-year follow-up. Prodromal participants were divided into groups based on proximity to estimated onset of diagnosable clinical disease: far (>15 years from estimated onset), mid (9-15 years) and near (<9 years). Volumetric measurements of caudate, putamen, total striatum, globus pallidus, thalamus, total grey and white matter and cerebrospinal fluid were performed.ResultsAll prodromal groups showed a faster rate of atrophy than controls in striatum, total brain and cerebral white matter (especially in the frontal lobe). Neither prodromal participants nor controls showed any significant longitudinal change in cortex (either total cortical grey or within individual lobes). When normal age-related atrophy (ie, change observed in the control group) was taken into account, there was more statistically significant disease-related atrophy in white matter than in striatum.ConclusionMeasures of volume change in striatum and white-matter volume, particularly in the frontal lobe, may serve as excellent outcome measures for future clinical trials in prodromal Huntington disease. Clinical trials using white matter or striatal volume change as an outcome measure will be most efficient if the sample is restricted to individuals who are within 15 years of estimated onset of diagnosable disease.
| S-EPMC3105627 | biostudies-literature
Project description:BackgroundCongenital heart disease (CHD) is common and is associated with impaired early brain development and neurodevelopmental outcomes, yet the exact mechanisms underlying these associations are unclear.PurposeTo utilize MRI data from a cohort of fetuses with CHD as well as typically developing fetuses to test the hypothesis that expected cerebral substrate delivery is associated with total and regional fetal brain volumes.Study typeRetrospective case-control study.PopulationThree hundred eighty fetuses (188 male), comprising 45 healthy controls and 335 with isolated CHD, scanned between 29 and 37 weeks gestation. Fetuses with CHD were assigned into one of four groups based on expected cerebral substrate delivery.Field strength/sequenceT2-weighted single-shot fast-spin-echo sequences and a balanced steady-state free precession gradient echo sequence were obtained on a 1.5 T scanner.AssessmentImages were motion-corrected and reconstructed using an automated slice-to-volume registration reconstruction technique, before undergoing segmentation using an automated pipeline and convolutional neural network that had undergone semi-supervised training. Differences in total, regional brain (cortical gray matter, white matter, deep gray matter, cerebellum, and brainstem) and brain:body volumes were compared between groups.Statistical testsANOVA was used to test for differences in brain volumes between groups, after accounting for sex and gestational age at scan. PFDR-values <0.05 were considered statistically significant.ResultsTotal and regional brain volumes were smaller in fetuses where cerebral substrate delivery is reduced. No significant differences were observed in total or regional brain volumes between control fetuses and fetuses with CHD but normal cerebral substrate delivery (all PFDR > 0.12). Severely reduced cerebral substrate delivery is associated with lower brain:body volume ratios.Data conclusionTotal and regional brain volumes are smaller in fetuses with CHD where there is a reduction in cerebral substrate delivery, but not in those where cerebral substrate delivery is expected to be normal.Evidence level3 TECHNICAL EFFICACY: Stage 3.
| S-EPMC7616254 | biostudies-literature
Project description:ObjectivesTo determine whether menopausal hormone therapy (HT) affects regional brain volumes, including hippocampal and frontal regions.MethodsBrain MRI scans were obtained in a subset of 1,403 women aged 71-89 years who participated in the Women's Health Initiative Memory Study (WHIMS). WHIMS was an ancillary study to the Women's Health Initiative, which consisted of two randomized, placebo-controlled trials: 0.625 mg conjugated equine estrogens (CEE) with or without 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet. Scans were performed, on average, 3.0 years post-trial for the CEE + MPA trial and 1.4 years post-trial for the CEE-Alone trial; average on-trial follow-up intervals were 4.0 years for CEE + MPA and 5.6 years for CEE-Alone. Total brain, ventricular, hippocampal, and frontal lobe volumes, adjusted for age, clinic site, estimated intracranial volume, and dementia risk factors, were the main outcome variables.ResultsCompared with placebo, covariate-adjusted mean frontal lobe volume was 2.37 cm(3) lower among women assigned to HT (p = 0.004), mean hippocampal volume was slightly (0.10 cm(3)) lower (p = 0.05), and differences in total brain volume approached significance (p = 0.07). Results were similar for CEE + MPA and CEE-Alone. HT-associated reductions in hippocampal volumes were greatest in women with the lowest baseline Modified Mini-Mental State Examination scores (scores <90).ConclusionsConjugated equine estrogens with or without MPA are associated with greater brain atrophy among women aged 65 years and older; however, the adverse effects are most evident in women experiencing cognitive deficits before initiating hormone therapy.
| S-EPMC2677493 | biostudies-literature
Project description:IntroductionThe impact of blood pressure on brain volumes may be time-dependent or pattern-dependent.MethodsOf 1678 participants from the Atherosclerosis Risk in Communities Neurocognitive Study, we quantified the association between measures and patterns of blood pressure over three time points (∼24 or ∼15 years prior and concurrent with neuroimaging) with late life brain volumes.ResultsHigher diastolic blood pressure ∼24 years prior, higher systolic and pulse pressure ∼15 years prior, and consistently elevated or rising systolic blood pressure from ∼15 years prior to concurrent with neuroimaging, but not blood pressures measured concurrent with neuroimaging, were associated with smaller volumes. The pattern of hypertension ∼15 years prior and hypotension concurrent with neuroimaging was associated with smaller volumes in regions preferentially affected by Alzheimer's disease (e.g., hippocampus: -0.27 standard units, 95% CI: -0.51, -0.03).DiscussionHypertension 15 to 24 years prior is relevant to current brain volumes. Hypertension followed by hypotension appears particularly detrimental.
| S-EPMC4980244 | biostudies-literature
Project description:Impairments in cognitive performance are common in schizophrenia, and these contribute to poor awareness of symptoms and treatment (‘clinical insight’), which is an important predictor of functional outcome. Although relationships between cognitive impairment and reductions in regional brain volumes in patients are relatively well characterised, less is known about the brain structural correlates of clinical insight. To address this gap, we aimed to explore brain structural correlates of cognitive performance and clinical insight in the same sample. 108 patients with schizophrenia (SZH) and 94 age and gender-matched controls (CON) (from the Northwestern University Schizophrenia Data and Software Tool (NUSDAST) database) were included. SZH had smaller grey matter volume across most fronto-temporal regions and significantly poorer performance on all cognitive domains. Multiple regression showed that higher positive symptoms and poorer attention were significant predictors of insight in SZH; however, no significant correlations were seen between clinical insight and regional brain volumes. In contrast, symptomology did not contribute to cognitive performance, but robust positive relationships were found between regional grey matter volumes in fronto-temporal regions and cognitive performance (particularly executive function). Many of these appeared to be unique to SZH as they were not observed in CON. Findings suggest that while there exists a tight link between cognitive functioning and neuropathological processes affecting gross brain anatomy in SZH, this is not the case for clinical insight. Instead, clinical insight levels seem to be influenced by symptomology, attentional performance and other subject-specific variables.
| S-EPMC9261092 | biostudies-literature