White matter microstructure mediates the pairwise relationship between childhood maltreatment, microRNA-9, and the severity of major depressive disorder.
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ABSTRACT:
SUBMITTER: Liu X
PROVIDER: S-EPMC11374261 | biostudies-literature | 2024 Sep
REPOSITORIES: biostudies-literature
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White matter microstructure mediates the pairwise relationship between childhood maltreatment, microRNA-9, and the severity of major depressive disorder.
Liu Xinyi X He Cancan C Bai Ying Y Fan Dandan D Zang Feifei F Zhang Hongxing H Zhang Haisan H Yao Honghong H Zhang Zhijun Z Xie Chunming C
Chinese medical journal 20240808 17
Similar Datasets
Project description:Childhood maltreatment has been known to produce long-lasting impairments in behavioral, cognitive and social functioning, but their underlying mechanisms are not well-understood. A better understanding of their underlying mechanisms will aid in developing effective preventive interventions. Nineteen adolescent volunteers with no personal history of a psychiatric illness, but who were exposed to maltreatment during childhood, and 13 adolescent volunteers with no personal or family history of a psychiatric disorder (controls) underwent diffusion tensor imaging (DTI) studies. The participants were then followed longitudinally at 6-month intervals for up to 5 years to determine the onset of mood and substance use disorders. The associations among fractional anisotropy (FA) values obtained from the DTI scans at baseline and psychopathology at follow-up were examined. At baseline, adolescents exposed to childhood maltreatment had significantly lower FA values in the left and right superior longitudinal fasciculi, right cingulum bundle projecting to the hippocampus, left inferior fronto-occipital fasciculus, and splenium of the corpus callosum compared with controls. Adolescents who developed major depressive disorder at follow-up had significantly lower FA values in the superior longitudinal fasciculi and the right cingulum-hippocampal projection compared with their counterparts who did not develop the illness. Adolescents who developed substance use disorder during follow-up had significantly lower FA values in the right cingulum-hippocampal projection than their counterparts without the disorder. These preliminary results suggest that white matter disruptions observed in adolescents exposed to childhood maltreatment may be associated with increased vulnerability to psychopathology, specifically depressive and substance use disorders.
| S-EPMC3473335 | biostudies-other
Project description:Whether plasticity of white matter (WM) microstructure relates to therapeutic response in major depressive disorder (MDD) remains uncertain. We examined diffusion tensor imaging (DTI) correlates of WM structural connectivity in patients receiving electroconvulsive therapy (ECT), a rapidly acting treatment for severe MDD. Tract-Based Spatial Statistics (TBSS) applied to DTI data (61 directions, 2.5 mm(3) voxel size) targeted voxel-level changes in fractional anisotropy (FA), and radial (RD), axial (AD) and mean diffusivity (MD) in major WM pathways in MDD patients (n=20, mean age: 41.15 years, 10.32 s.d.) scanned before ECT, after their second ECT and at transition to maintenance therapy. Comparisons made at baseline with demographically similar controls (n=28, mean age: 39.42 years, 12.20 s.d.) established effects of diagnosis. Controls were imaged twice to estimate scanning-related variance. Patients showed significant increases of FA in dorsal fronto-limbic circuits encompassing the anterior cingulum, forceps minor and left superior longitudinal fasciculus between baseline and transition to maintenance therapy (P<0.05, corrected). Decreases in RD and MD were observed in overlapping regions and the anterior thalamic radiation (P<0.05, corrected). Changes in DTI metrics associated with therapeutic response in tracts showing significant ECT effects differed between patients and controls. All measures remained stable across time in controls. Altered WM microstructure in pathways connecting frontal and limbic areas occur in MDD, are modulated by ECT and relate to therapeutic response. Increased FA together with decreased MD and RD, which trend towards normative values with treatment, suggest increased fiber integrity in dorsal fronto-limbic pathways involved in mood regulation.
| S-EPMC4012285 | biostudies-literature
Project description:Background: Childhood maltreatment (CM) is a common psychological stressor associated with multiple mental disorders. While CM is associated with vulnerability to depression and anxiety, little is known about the specific mechanism underlying this relationship.Objective: This study aimed to investigate the white matter (WM) of healthy adults with CM and their relationships with depression and anxiety to provide biological evidence for the development of mental disorders in subjects with childhood trauma.Methods: The CM group included 40 healthy adults with CM. The non-CM group included 40 healthy adults without CM. Diffusion tensor imaging (DTI) data were collected, and tract-based spatial statistics (TBSS) were applied to the whole brain to assess WM differences between the two groups; post-hoc fibre tractography was used to characterise the developmental differences; and mediation analysis was used to assess the relationships among the Child Trauma Questionnaire (CTQ) results, DTI indices, and depression and anxiety scores.Results: Relative to the non-CM group, the CM group revealed significantly lower fractional anisotropy (FA) in the right posterior corona radiata (PCR-R), right anterior corona radiata (ACR-R), left super corona radiata (SCR-L), anterior thalamic radiation (ATR), and right posterior limb of the internal capsule (PLIC-R). Additionally, shorter fibre bundles passed through the PCR-R, ACR-R, and ATR in the CM group compared with the non-CM group. Besides, the length of the ACR-R mediated the relationship between CM and trait anxiety.Conclusions: The alteration of white matter microstructure associated with childhood trauma in healthy adults may reflect biomarkers of childhood trauma. Besides, an alteration of WM microstructure in healthy adults with CM mediates the association between CM and trait anxiety, which may represent the vulnerability to developing mental disorders after childhood trauma experiences.
| S-EPMC9970228 | biostudies-literature
Project description:The prefrontal cortex, amygdala, hippocampus, and hypothalamus are important components of the neural network that mediates the healthy learning, expression, and regulation of emotion. These brain regions are connected by white matter pathways that include the cingulum bundle, uncinate fasciculus, and fornix/stria terminalis. Individuals with trauma and stress-related disorders show dysfunction of the cognitive-affective processes supported by the brain regions these white matter tracts connect. Therefore, variability in the microstructure of these white matter pathways may play an important role in the cognitive-affective dysfunction related to post-traumatic stress disorder. Thus, the current study used diffusion weighted imaging to assess the white matter microstructure of the cingulum bundle, uncinate fasciculus, and fornix/stria terminalis acutely (< 1 month) following trauma. Further, we assessed both acute (i.e., < 1 month) and subacute (i.e., 3 months post-trauma) post-traumatic stress symptom severity. White matter microstructure (assessed < 1 month post-trauma) of the uncinate fasciculus and fornix/stria terminalis varied with acute post-traumatic stress severity (assessed < 1 month post-trauma). Further, white matter microstructure (assessed < 1 month post-trauma) of the cingulum bundle and fornix/stria terminalis varied with subacute post-traumatic stress severity (assessed 3 months post-trauma). The current results suggest white matter architecture of the prefrontal cortex - amygdala network plays an important role in the development of trauma and stress-related disorders.
| S-EPMC6551328 | biostudies-literature
Project description:Childhood maltreatment (CM) is a major risk factor for developing the major depressive disorder (MDD), however, the neurobiological mechanism linking CM and MDD remains unclear. We recruited 34 healthy controls (HCs) and 44 MDD patients to complete the childhood maltreatment experience assessment with Childhood Trauma Questionnaire (CTQ) and resting-state fMRI scan. Multivariate linear regression analysis was employed to identify the main effects of CM and depressive symptoms total and subfactors scores on bilateral anterior and posterior insula functional connectivity (IFC) networks, respectively. Mediation analysis was performed to investigate whether IFC strength mediates the association between CM and depressive symptoms. MDD patients showed significantly decreased connectivity in the dorsal medial prefrontal cortex and increased connectivity in the medial frontal gyrus in the bipartite IFC networks, compared to HCs. The main effects of CM and depressive symptoms showed a large discrepancy on the anterior and posterior IFC networks, which primarily located in the frontal-limbic system. Further, conjunction analysis identified the overlapping regions linking CM and depressive symptoms were mainly implicated in self-regulation and cognitive processing circuits. More important, these IFC strengths could mediate the association between different types of CM, especially for childhood abuse and childhood neglect, and depressive symptoms in those overlapping regions. We demonstrated that early exposure to CM may increase the vulnerability to depression by influencing brain's self-regulating and cognitive processing circuitry. These findings provide new insight into the understanding of pathological mechanism underlying CM-induced depressive symptoms.
| S-EPMC8891292 | biostudies-literature
Project description:BackgroundChildhood maltreatment may contribute to brain alterations in posttraumatic stress disorder (PTSD). We previously found that PTSD was associated with white matter compromise, or lower fractional anisotropy (FA), in the left inferior longitudinal fasciculus (ILF). In this study, including non-PTSD controls, we examined whether ILF FA was associated with maltreatment exposures, including those that meet DSM-IV criterion A (physical abuse, sexual abuse) and those that typically do not (emotional abuse, emotional neglect, physical neglect). We hypothesized that lower FA would be associated with PTSD diagnosis and with both categories of maltreatment.MethodsNinety-three participants (51 female), ages 20-50, were enrolled, including 32 with lifetime DSM-IV PTSD, 27 trauma-exposed non-PTSD controls, and 34 healthy controls. Participants completed structured interviews, the Childhood Trauma Questionnaire (CTQ), and diffusion-weighted imaging (36 directions). Probabilistic tractography (using FreeSurfer's TRACULA) was used to assess diffusion metrics in the ILF.ResultsContrary to our hypothesis, there was no significant effect of diagnostic group on FA. In contrast, higher CTQ scores were significantly associated with lower FA in the ILF bilaterally. This association of maltreatment with lower FA remained statistically significant after controlling for diagnostic group, and it was significant for both criterion-A-type and noncriterion-A-type maltreatment categories.ConclusionsThis work contributes to a growing body of literature indicating that different forms of childhood maltreatment are associated with altered white matter microstructure in the ILF, an association pathway involved in integrating visual information from occipital regions with emotion processing functions of the anterior temporal lobe.
| S-EPMC6955831 | biostudies-literature
Project description:Sex differences in white matter microstructure have been robustly demonstrated in the adult brain using both conventional and advanced diffusion-weighted magnetic resonance imaging approaches. However, sex differences in white matter microstructure prior to adulthood remain poorly understood; previous developmental work focused on conventional microstructure metrics and yielded mixed results. Here, we rigorously characterized sex differences in white matter microstructure among over 6000 children from the Adolescent Brain Cognitive Development study who were between 9 and 10 years old. Microstructure was quantified using both the conventional model-diffusion tensor imaging (DTI)-and an advanced model, restriction spectrum imaging (RSI). DTI metrics included fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). RSI metrics included normalized isotropic, directional, and total intracellular diffusion (N0, ND, NT). We found significant and replicable sex differences in DTI or RSI microstructure metrics in every white matter region examined across the brain. Sex differences in FA were regionally specific. Across white matter regions, boys exhibited greater MD, AD, and RD than girls, on average. Girls displayed increased N0, ND, and NT compared to boys, on average, suggesting greater cell and neurite density in girls. Together, these robust and replicable findings provide an important foundation for understanding sex differences in health and disease.
| S-EPMC9842921 | biostudies-literature
Project description:We investigated whether HIV disease severity was associated with alterations in structural brain connectivity, and whether those alterations in turn were associated with cognitive deficits in youth with perinatally acquired HIV (PHIV).PHIV youth (n = 40) from the Pediatric HIV/AIDS Cohort Study (PHACS) (mean age: 16?±?2 years) were included to evaluate how current and past disease severity measures (recent/nadir CD4%; peak viral load) relate to white matter microstructure within PHIV youth. PHIV youth were compared with 314 controls from the Pediatric Imaging, Neurocognition and Genetics (PING) study.Diffusion tensor imaging and tractography were utilized to assess white matter microstructure. Mediation analyses were conducted to examine whether microstructure alterations contributed to relationships between higher disease severity and specific cognitive domains in PHIV youth.Whole brain fractional anisotropy was reduced, but radial and mean diffusivity were increased in PHIV compared with control youth. Within PHIV youth, more severe past HIV disease was associated with reduced fractional anisotropy of the right inferior fronto-occipital (IFO) and left uncinate tracts; elevated mean diffusivity of the F minor; and increased streamlines comprising the left inferior longitudinal fasciculus (ILF). Associations of higher peak viral load with lower working memory performance were partly mediated by reductions in right IFO fractional anisotropy levels.Our findings suggest that PHIV youth have a higher risk of alterations in white matter microstructure than typically developing youth, and certain alterations are related to past disease severity. Further, white matter alterations potentially mediate associations between HIV disease and working memory.
| S-EPMC4487416 | biostudies-literature
Project description:BACKGROUND:Air pollution has been related to brain structural alterations, but a relationship with white matter microstructure is unclear. OBJECTIVES:We assessed whether pregnancy and childhood exposures to air pollution are related to white matter microstructure in preadolescents. METHODS:We used data of 2,954 children from the Generation R Study, a population-based birth cohort from Rotterdam, Netherlands (2002-2006). Concentrations of 17 air pollutants including nitrogen oxides (NOX), particulate matter (PM), and components of PM were estimated at participants' homes during pregnancy and childhood using land-use regression models. Diffusion tensor images were obtained at child's 9-12 years of age, and fractional anisotropy (FA) and mean diffusivity (MD) were computed. We performed linear regressions adjusting for socioeconomic and lifestyle characteristics. Single-pollutant analyses were followed by multipollutant analyses using the Deletion/Substitution/Addition (DSA) algorithm. RESULTS:In the single-pollutant analyses, higher concentrations of several air pollutants during pregnancy or childhood were associated with significantly lower FA or higher MD (p<0.05). In multipollutant models of pregnancy exposures selected by DSA, higher concentration of fine particles was associated with significantly lower FA [-0.71 (95% CI: -1.26, -0.16) per 5 μg/m3 fine particles] and higher concentration of elemental silicon with significantly higher MD [0.06 (95% CI: 0.01, 0.11) per 100 ng/m3 silicon]. Multipollutant models of childhood exposures selected by DSA indicated significant associations of NOX with FA [-0.14 (95% CI: -0.23, -0.04) per 20-μg/m3 NOX increase], and of elemental zinc and the oxidative potential of PM with MD [0.03 (95% CI: 0.01, 0.04) per 10-ng/m3 zinc increase and 0.07 (95% CI: 0.00, 0.44) per 1-nmol DTT/min/m3 oxidative potential increase]. Mutually adjusted models of significant exposures during pregnancy and childhood indicated significant associations of silicon during pregnancy, and zinc during childhood, with MD. DISCUSSION:Exposure in pregnancy and childhood to air pollutants from tailpipe and non-tailpipe emissions were associated with lower FA and higher MD in white matter of preadolescents. https://doi.org/10.1289/EHP4709.
| S-EPMC7064320 | biostudies-literature
Project description:Changes in cerebral cortical anatomy have been tied to the clinical course of attention deficit hyperactivity disorder (ADHD). We now ask if alterations in white matter tract microstructure are likewise linked with the adult outcome of childhood ADHD. Seventy-five young adults, 32 with ADHD persisting from childhood and 43 with symptom remission were contrasted against 74 never-affected comparison subjects. Using diffusion tensor imaging, we defined fractional anisotropy, a metric related to white matter microstructure, along with measures of diffusion perpendicular (radial) and parallel (axial) to the axon. Analyses were adjusted for head motion, age and sex, and controlled for multiple comparisons and medication history. Tract-based analyses showed that greater adult inattention, but not hyperactivity-impulsivity, was associated with significantly lower fractional anisotropy in the left uncinate (standardized β=-0.37, t=3.28, p=0.002) and inferior fronto-occipital fasciculi (standardized β=-0.37, t=3.29, p=0.002). The ADHD group with symptoms persisting into adulthood had significantly lower fractional anisotropy than the never-affected controls in these tracts, differences associated with medium to large effect sizes. By contrast, the ADHD group that remitted by adulthood did not differ significantly from controls. The anomalies were found in tracts that connect components of neural systems pertinent to ADHD, such as attention control (inferior fronto-occipital fasciculus) and emotion regulation and the processing of reward (the uncinate fasciculus). Change in radial rather than axial diffusivity was the primary driver of this effect, suggesting pathophysiological processes including altered myelination as future targets for pharmacological and behavioral interventions.
| S-EPMC4289964 | biostudies-literature