SLC25A24 gene methylation and gray matter volume in females with and without conduct disorder: an exploratory epigenetic neuroimaging study.
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SUBMITTER: Farrow E
PROVIDER: S-EPMC8463588 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Obesity has become a major public and individual health problem due to its high worldwide prevalence and its relation with comorbid conditions. According to previous studies, obesity is related to an increased risk of cognitive impairment and dementia. This systematic review aims to further examine the present state of the art about the association between obesity and gray matter volume (GMV) as assessed by magnetic resonance imaging (MRI). A search was conducted in Pubmed, SCOPUS and Cochrane of those studies released before 1 February 2021 including MRIs to assess the GMVs in obese participants. From this search, 1420 results were obtained, and 34 publications were finally included. Obesity was mainly measured by the body mass index, although other common types of evaluations were used (e.g., waist circumference, waist-to-hip ratio and plasma leptin levels). The selected neuroimaging analysis methods were voxel-based morphometry (VBM) and cortical thickness (CT), finding 21 and 13 publications, respectively. There were 30 cross-sectional and 2 prospective longitudinal studies, and 2 articles had both cross-sectional and longitudinal designs. Most studies showed a negative association between obesity and GMV. This would have important public health implications, as obesity prevention could avoid a potential risk of GMV reductions, cognitive impairment and dementia.
| S-EPMC8391982 | biostudies-literature
Project description:ObjectiveStructural neuroimaging studies have demonstrated lower regional gray matter volume in adolescents with severe substance and conduct problems. These research studies, including ours, have generally focused on male-only or mixed-sex samples of adolescents with conduct and/or substance problems. Here we compare gray matter volume between female adolescents with severe substance and conduct problems and female healthy controls of similar ages.HypothesesFemale adolescents with severe substance and conduct problems will show significantly less gray matter volume in frontal regions critical to inhibition (i.e. dorsolateral prefrontal cortex and ventrolateral prefrontal cortex), conflict processing (i.e., anterior cingulate), valuation of expected outcomes (i.e., medial orbitofrontal cortex) and the dopamine reward system (i.e. striatum).MethodsWe conducted whole-brain voxel-based morphometric comparison of structural MR images of 22 patients (14-18 years) with severe substance and conduct problems and 21 controls of similar age using statistical parametric mapping (SPM) and voxel-based morphometric (VBM8) toolbox. We tested group differences in regional gray matter volume with analyses of covariance, adjusting for age and IQ at p<0.05, corrected for multiple comparisons at whole-brain cluster-level threshold.ResultsFemale adolescents with severe substance and conduct problems compared to controls showed significantly less gray matter volume in right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, medial orbitofrontal cortex, anterior cingulate, bilateral somatosensory cortex, left supramarginal gyrus, and bilateral angular gyrus. Considering the entire brain, patients had 9.5% less overall gray matter volume compared to controls.ConclusionsFemale adolescents with severe substance and conduct problems in comparison to similarly aged female healthy controls showed substantially lower gray matter volume in brain regions involved in inhibition, conflict processing, valuation of outcomes, decision-making, reward, risk-taking, and rule-breaking antisocial behavior.
| S-EPMC4441424 | biostudies-literature
Project description:BACKGROUND:The serotonin transporter (5-HTT) and the 5-HTTLPR/rs25531 polymorphisms in its gene (SLC6A4) have been associated with depression, increased stress-response, and brain structural alterations such as reduced hippocampal volumes. Recently, epigenetic processes including SLC6A4 promoter methylation were shown to be affected by stress, trauma, or maltreatment and are regarded to be involved in the etiology of affective disorders. However, neurobiological correlates of SLC6A4 promoter methylation have never been studied or compared to genotype effects by means of human neuroimaging hitherto METHODS:Healthy subjects were recruited in two independent samples (N?=?94, N?=?95) to obtain structural gray matter images processed by voxel-based morphometry (VBM8), focusing on hippocampal, amygdala, and anterior cingulate gyrus gray matter structure. SLC6A4 promoter methylation within an AluJb element and 5-HTTLPR/rs25531 genotypes were analyzed in view of a possible impact on local gray matter volume RESULTS:Strong associations of AluJb methylation and hippocampal gray matter volumes emerged within each sample separately, which in the combined sample withstood most conservative alpha-corrections for the entire brain. The amygdala, insula, and caudate nucleus showed similar associations. The 5-HTTLPR/rs25531 showed no main effect on gray matter, and the effect of methylation rates on hippocampal structure was comparable among the genotype groups CONCLUSIONS:Methylation within the AluJb appears to have strong effects on hippocampal gray matter volumes, indicating that epigenetic processes can alter brain structures crucially involved in stress-related disorders. Different ways of regulating SLC6A4 expression might involve exonization or transcription factor binding as potentially underlying mechanisms, which, however, is speculative and warrants further investigation.
| S-EPMC6869452 | biostudies-literature
Project description:Widespread cortical gray matter alternations in people with schizophrenia are correlated with both psychotic symptoms and cognitive/behavioral abnormalities, including the impairments of exploratory eye movement (EEM). Particularly, the loss of gray matter density is specifically related to deficits of the responsive search score (RSS) of EEM in schizophrenia. It is unknown, however, whether the schizophrenia-related RSS deficits are associated with certain psychotic symptoms, such as hallucinations.In 33 participants with schizophrenia, the measurement of EEM, assessment of the hallucination severity using Positive and Negative Syndrome Scale (PANSS) and a voxel-based morphometric analysis of cortical gray matter volume (GMV) were conducted to investigate the relationships between the RSS of EEM, symptom severity, and GMV. In 29 matched healthy controls, the measurement of EEM and a voxel-based morphometric analysis of cortical GMV were also conducted to investigate the relationship between the RSS of EEM and GMV.In participants with schizophrenia, the hallucination severity was significantly negatively correlated with both the RSS and the GMV of a large number of brain regions in the frontal, temporal, parietal, orbitofrontal, calcarine, cingulate, and insular cortices, and rolandic operculum, hippocampus, parahippocampal gyrus, and thalamus. Also in participants with schizophrenia, the RSS was significantly positively correlated with the GMV in the left supplementary motor area (SMA), left superior frontal cortex (SFG), bilateral precentral gyri, bilateral postcentral gyri, and bilateral middle frontal cortices. More importantly, the GMV of the SMA, SFG, and precentral gyrus in the left hemisphere was not only significantly negatively correlated with the hallucination severity but also significantly positively correlated with the RSS. No significant correlation could be revealed between the RSS and the GMV of any brain regions in healthy controls.There was a significantly negative association between the hallucination severity and the RSS of EEM, suggesting that the RSS may be a potential biomarker for predicting the hallucination severity of schizophrenia. Also, the GMV of the left SMA, SFG, and precentral gyrus may be the common substrates underlying both hallucination induction and the RSS in people with schizophrenia.
| S-EPMC6045825 | biostudies-other
Project description:Structure and function are closely related in the healthy human brain. In patients with chronic heroin exposure, brain imaging studies have identified long-lasting changes in gray matter (GM) volume. More recently, we showed that acute application of heroin in dependent patients results in hypoperfusion of fronto-temporal areas compared with the placebo condition. However, the relationship between structural and cerebral blood flow (CBF) changes in heroin addiction has not yet been investigated. Moreover, it is not known whether there is any interaction between the chronic structural changes and the short and long-term effects on perfusion caused by heroin. Using a double-blind, within-subject design, heroin or placebo (saline) was administered to 14 heroin-dependent patients from a stable heroin-assisted treatment program, in order to observe acute short-term effects. Arterial spin labeling (ASL) was used to calculate perfusion quantification maps in both treatment conditions, while Voxel-Based Morphometry (VBM) was conducted to calculate regional GM density. VBM and ASL data were used to calculate homologous correlation fields by Biological Parametric Mapping (BPM) and a whole-brain Pearson r correlation. We correlated each perfusion condition (heroin and placebo) separately with a VBM sample that was identical for the two treatment conditions. It was assumed that heroin-associated perfusion is manifested in short-term effects, while placebo-associated perfusion is more related to long-term effects. In order to restrict our analyses to fronto-temporal regions, we used an explicit mask for our analyses. Correlation analyses revealed a significant positive correlation in frontal areas between GM and both perfusion conditions (heroin and placebo). Heroin-associated perfusion was also negatively correlated with GM in the inferior temporal gyrus on both hemispheres. These findings indicate that, in heroin-dependent patients, low GM volume is positively associated with low perfusion within frontal regions.
| S-EPMC3801154 | biostudies-literature
Project description:BackgroundDespite decades of research, there is continued uncertainty regarding whether autism is associated with a specific profile of gray matter (GM) structure. This inconsistency may stem from the widespread use of voxel-based morphometry (VBM) methods that combine indices of GM density and GM volume. If GM density or volume, but not both, prove different in autism, the traditional VBM approach of combining the two indices may obscure the difference. The present study measures GM density and volume separately to examine whether autism is associated with alterations in GM volume, density, or both.MethodsDifferences in MRI-based GM density and volume were examined in 6-25 year-olds with a diagnosis of autism spectrum disorder (n = 213, 80.8% male, IQ 47-154) and a typically developing (TD) sample (n = 190, 71.6% male, IQ 67-155). High-resolution T1-weighted anatomical images were collected on a single MRI scanner. Regional density and volume were estimated via whole-brain parcellation comprised of 1625 parcels. Parcel-wise analyses were conducted using generalized additive models while controlling the false discovery rate (FDR, q < 0.05). Volume differences in the 68-region Desikan-Killiany atlas derived from Freesurfer were also examined, to establish the generalizability of findings across methods.ResultsNo density differences were observed between the autistic and TD groups, either in individual parcels or whole brain mean density. Increased volume was observed in autism compared to the TD group when controlling for Age, Sex, and IQ, both at the level of the whole brain (total volume) and in 45 parcels (2.8% of total parcels). Parcels with greater volume included inferior, middle, and superior temporal gyrus, inferior and superior frontal gyrus, precuneus, and fusiform gyrus. Converging evidence from a standard Freesurfer pipeline also identified greater volume in a number of overlapping regions.LimitationsThe method for determining "density" is not a direct measure of neuronal density, and this study cannot reveal underlying cellular differences. While this study represents possibly the largest single-site sample of its kind, it is underpowered to detect very small differences.ConclusionsThese results provide compelling evidence that autism is associated with regional GM volumetric differences, which are more prominent than density differences. This underscores the importance of examining volume and density separately, and suggests that direct measures of volume (e.g. region-of-interest or tensor-based morphometry approaches) may be more sensitive to autism-relevant differences in neuroanatomy than concentration/density-based approaches.
| S-EPMC8633367 | biostudies-literature
Project description:A positive association between brain size and intelligence is firmly established, but whether region-specific anatomical differences contribute to general intelligence remains an open question. Results from voxel-based morphometry (VBM) - one of the most widely used morphometric methods - have remained inconclusive so far. Here, we applied cross-validated machine learning-based predictive modeling to test whether out-of-sample prediction of individual intelligence scores is possible on the basis of voxel-wise gray matter volume. Features were derived from structural magnetic resonance imaging data (N = 308) using (a) a purely data-driven method (principal component analysis) and (b) a domain knowledge-based approach (atlas parcellation). When using relative gray matter (corrected for total brain size), only the atlas-based approach provided significant prediction, while absolute gray matter (uncorrected) allowed for above-chance prediction with both approaches. Importantly, in all significant predictions, the absolute error was relatively high, i.e., greater than ten IQ points, and in the atlas-based models, the predicted IQ scores varied closely around the sample mean. This renders the practical value even of statistically significant prediction results questionable. Analyses based on the gray matter of functional brain networks yielded significant predictions for the fronto-parietal network and the cerebellum. However, the mean absolute errors were not reduced in contrast to the global models, suggesting that general intelligence may be related more to global than region-specific differences in gray matter volume. More generally, our study highlights the importance of predictive statistical analysis approaches for clarifying the neurobiological bases of intelligence and provides important suggestions for future research using predictive modeling.
| S-EPMC7473979 | biostudies-literature
Project description:ObjectiveChefs exert expert motor and cognitive performances on a daily basis. Neuroimaging has clearly shown that that long-term skill learning (i.e., athletes, musicians, chess player or sommeliers) induces plastic changes in the brain thus enabling tasks to be performed faster and more accurately. How a chef's expertise is embodied in a specific neural network has never been investigated.MethodsEleven Italian head chefs with long-term brigade management expertise and 11 demographically-/ psychologically- matched non-experts underwent morphological evaluations.ResultsVoxel-based analysis performed with SUIT, as well as, automated volumetric measurement assessed with Freesurfer, revealed increased gray matter volume in the cerebellum in chefs compared to non-experts. The most significant changes were detected in the anterior vermis and the posterior cerebellar lobule. The magnitude of the brigade staff and the higher performance in the Tower of London test correlated with these specific gray matter increases, respectively.ConclusionsWe found that chefs are characterized by an anatomical variability involving the cerebellum. This confirms the role of this region in the development of similar expert brains characterized by learning dexterous skills, such as pianists, rock climbers and basketball players. However, the nature of the cellular events underlying the detected morphological differences remains an open question.
| S-EPMC5300254 | biostudies-literature
Project description:Diet and nutrition play a key role in the promotion and maintenance of good health, as they are important modifiable risk factors for chronic diseases. A growing number of studies indicate that optimal food intake and optimal physical activity are essential for the gray matter volume (GMV). However, the precise definition of "optimal" is extremely difficult and a topic of several studies. In the current research, we used the magnetic resonance imaging (MRI)-based normalized GMV (nGMV), for monitoring brain conditions based on GMV. By analyzing the relationship between the nGMV of 171 healthy Japanese participants and the results of a brief self-administered diet history questionnaire (BDHQ), we found that while nGMV was high in the participants with high intake of milk and yogurt, it was low in the participants of "alcohol and animal foods dietary pattern" (high intake of alcohol and animal foods). On the other hand, another food pattern "vegetable-animal balanced dietary pattern" (balanced intake of vegetables and animal foods) has no significant association with nGMV, indicating that although a diet consisting of a good balance of vegetables and animal foods may not lead to brain atrophy, it might not positively contribute to a higher nGMV. nGMV, as an objective measure of the association between food intake and the brain, might provide useful information for "optimal" food intake for GMV.
| S-EPMC6828934 | biostudies-literature
Project description:Bilateral vestibular failure (BVF) is a severe chronic disorder of the labyrinth or the eighth cranial nerve characterized by unsteadiness of gait and disabling oscillopsia during head movements. According to animal data, vestibular input to the hippocampus is proposed to contribute to spatial memory and spatial navigation. Except for one seminal study showing the association of impaired spatial navigation and hippocampal atrophy, patient data in BVF are lacking. Therefore, we performed a voxel-wise comparison of the hippocampal gray matter volume (GMV) in a clinically representative sample of 27 patients with incomplete BVF and 29 age- and gender-matched healthy controls to test the hypothesis of hippocampal atrophy in BVF. Although the two groups did not generally differ in their hippocampal GMV, a reduction of GMV in the bilateral hippocampal CA3 region was significantly correlated with increased vestibulopathy-related clinical impairment. We propose that GMV reduction in the hippocampus of BVF patients is related to the severity of vestibular-induced disability which is in line with combined hippocampal atrophy and disorders of spatial navigation in complete vestibular deafferentation due to bilateral nerve section. Clinically, however, the most frequent etiologies of BVF cause incomplete lesions. Accordingly, hippocampus atrophy and deficits in spatial navigation occur possibly less frequently than previously suspected. Hum Brain Mapp 37:1998-2006, 2016. © 2016 Wiley Periodicals, Inc.
| S-EPMC6867258 | biostudies-literature