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Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.
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Encéfalo , Equidade de Gênero , Masculino , Adulto , Humanos , Feminino , Encéfalo/diagnóstico por imagem , Fatores SexuaisRESUMO
OBJECTIVES: Schizophrenia-related psychosis is associated with abnormalities in white matter (WM) microstructure and structural brain dysconnectivity. However, the pathological process underlying such changes is unknown. We sought to investigate the potential association between peripheral cytokine levels and WM microstructure during the acute phase of first-episode psychosis (FEP) in a cohort of drug-naïve patients. METHODS: Twenty-five non-affective FEP patients and 69 healthy controls underwent MRI scanning and blood collection at study entry. After achieving clinical remission, 21 FEP were reassessed; 38 age and biological sex-matched controls also had a second assessment. We measured fractional anisotropy (FA) of selected WM regions-of-interest (ROIs) and plasma levels of four cytokines (IL-6, IL-10, IFN-γ, and TNF-α). RESULTS: At baseline (acute psychosis), the FEP group showed reduced FA relative to controls in half the examined ROIs. Within the FEP group, IL-6 levels were negatively correlated with FA values. Longitudinally, patients showed increments of FA in several ROIs affected at baseline, and such changes were associated with reductions in IL-6 levels. CONCLUSIONS: A state-dependent process involving an interplay between a pro-inflammatory cytokine and brain WM might be associated with the clinical manifestation of FEP. This association suggests a deleterious effect of IL-6 on WM tracts during the acute phase of psychosis.
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Transtornos Psicóticos , Substância Branca , Humanos , Substância Branca/patologia , Citocinas , Estudos Longitudinais , Interleucina-6 , Imagem de Tensor de Difusão , Encéfalo/patologia , AnisotropiaRESUMO
Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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Tonsila do Cerebelo/anatomia & histologia , Corpo Estriado/anatomia & histologia , Hipocampo/anatomia & histologia , Desenvolvimento Humano/fisiologia , Neuroimagem , Tálamo/anatomia & histologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tonsila do Cerebelo/diagnóstico por imagem , Criança , Pré-Escolar , Corpo Estriado/diagnóstico por imagem , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tálamo/diagnóstico por imagem , Adulto JovemRESUMO
Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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Córtex Cerebral/anatomia & histologia , Córtex Cerebral/diagnóstico por imagem , Desenvolvimento Humano/fisiologia , Neuroimagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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Variação Biológica da População/fisiologia , Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Desenvolvimento Humano/fisiologia , Imageamento por Ressonância Magnética , Neuroimagem , Caracteres Sexuais , Espessura Cortical do Cérebro , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. METHODS: We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries. RESULTS: There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing. CONCLUSION: Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Núcleo Caudado , Criança , Humanos , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Mood disorders are the most frequent psychiatric disorders in patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS). The pathophysiological mechanisms in common between TLE and mood disorders include abnormalities in the serotonergic pathway. We aimed to evaluate the association between serotonin transporter genetic polymorphisms - 5-HTTLPR and 5-HTTVNTR - and the presence of mood disorders in patients with TLE-HS. METHODS: We evaluated 119 patients with TLE-HS, with and without psychiatric disorder; 146 patients diagnosed with major depressive disorder (MDD), and 113 healthy volunteers. Individuals were genotyped for the 5-HTTLPR and 5-HTTVNTR polymorphisms. RESULTS: No difference was observed between the TLE-HS groups, healthy controls, and MDD without epilepsy. There was a correlation between the 12-allele of the 5-HTTVNTR and the family history of patients with epilepsy with TLE-HS (pâ¯=â¯0.013). CONCLUSIONS: In this study conducted in two Brazilian centers, the serotonin transporter polymorphisms evaluated cannot be associated with depressive disorder in patients with TLE-HS. Still, they do have some influence over some clinical characteristics of epilepsy in TLE-HS. These data may not be reproduced in other populations with distinct ethnic characteristics.
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Transtorno Depressivo Maior , Epilepsia do Lobo Temporal , Brasil , Depressão , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/patologia , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Humanos , Polimorfismo Genético/genética , Esclerose/genética , Esclerose/patologia , Proteínas da Membrana Plasmática de Transporte de Serotonina/genéticaRESUMO
INTRODUCTION: Neuroimaging studies have shown callosal abnormalities among maltreated subjects, but little is known about the functional and neurobiological correlates of these supposed developmental alterations. The aim of this study was to investigate childhood maltreatment (CM), neurocognitive functioning, cortisol levels, and corpus callosum (CC) integrity among adolescents. METHODS: One hundred and seven subjects underwent magnetic resonance imaging (MRI) with voxel-based diffusion-tensor imaging (DTI) and the Crossed Finger Localization Test (CFLT). Psychopathology was investigated with the Schedule for Affective Disorders and Schizophrenia (K-SADS-PL); CM was detailed by the Childhood Trauma Questionnaire (CTQ), and salivary cortisol levels were measured by immunoassay. RESULTS: Higher levels of CM were associated with current lower CFLT scores, mainly in the CROSSED condition, involving interhemispheric communication of sensorimotor information (p < .05) and with reduced fractional anisotropy (FA) in the splenium of the CC (p < .01). Deficits in the CFLT were also associated with higher cortisol levels (p < .05). CONCLUSION: The association among CM, neuropsychological abnormalities, callosal microstructure alterations, and cortisol levels suggests an altered pattern of brain interhemispheric connectivity among maltreated adolescents. Further studies are needed to investigate the extent to which these sensorimotor deficits and abnormal cortisol levels may be possible mediators of negative neurodevelopmental trajectories and adult psychopathology.
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Imagem de Tensor de Difusão , Hidrocortisona , Adolescente , Adulto , Anisotropia , Corpo Caloso/diagnóstico por imagem , Humanos , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data. METHODS: Structural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures). RESULTS: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood. CONCLUSIONS: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Cérebro , Neuroimagem/métodos , Transtorno Obsessivo-Compulsivo , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/psicologia , Cérebro/diagnóstico por imagem , Cérebro/patologia , Cérebro/fisiopatologia , Criança , Feminino , Desenvolvimento Humano/fisiologia , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/fisiopatologia , Transtorno Obsessivo-Compulsivo/psicologia , Tamanho do Órgão , Psicopatologia , Relatório de Pesquisa , Análise de SistemasRESUMO
Studies of habenula (Hb) function and structure provided evidence of its involvement in psychiatric disorders, including schizophrenia and bipolar disorder. Previous studies using magnetic resonance imaging (manual/semiautomated segmentation) have reported conflicting results. Aiming to improve Hb segmentation reliability and the study of large datasets, we describe a fully automated protocol that was validated against manual segmentations and applied to 3 datasets (childhood/adolescence and adult bipolar disorder and schizophrenia). It achieved reliable Hb segmentation, providing robust volume estimations across a large age range and varying image acquisition parameters. Applying it to clinically relevant datasets, we found smaller Hb volumes in the adult bipolar disorder dataset and larger volumes in the adult schizophrenia dataset compared with healthy control subjects. There are indications that Hb volume in both groups shows deviating developmental trajectories early in life. This technique sets a precedent for future studies, as it allows for fast and reliable Hb segmentation and will be publicly available.
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Habenula , Transtornos Mentais , Adolescente , Adulto , Criança , Habenula/diagnóstico por imagem , Habenula/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/fisiopatologia , Reprodutibilidade dos TestesRESUMO
Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal application of ML requires large, multi-site datasets. We applied ML (support vector machines) to MRI data (regional cortical thickness, surface area, subcortical volumes) from 853 BD and 2167 control participants from 13 cohorts in the ENIGMA consortium. We attempted to differentiate BD from control participants, investigated different data handling strategies and studied the neuroimaging/clinical features most important for classification. Individual site accuracies ranged from 45.23% to 81.07%. Aggregate subject-level analyses yielded the highest accuracy (65.23%, 95% CI = 63.47-67.00, ROC-AUC = 71.49%, 95% CI = 69.39-73.59), followed by leave-one-site-out cross-validation (accuracy = 58.67%, 95% CI = 56.70-60.63). Meta-analysis of individual site accuracies did not provide above chance results. There was substantial agreement between the regions that contributed to identification of BD participants in the best performing site and in the aggregate dataset (Cohen's Kappa = 0.83, 95% CI = 0.829-0.831). Treatment with anticonvulsants and age were associated with greater odds of correct classification. Although short of the 80% clinically relevant accuracy threshold, the results are promising and provide a fair and realistic estimate of classification performance, which can be achieved in a large, ecologically valid, multi-site sample of BD participants based on regional neurostructural measures. Furthermore, the significant classification in different samples was based on plausible and similar neuroanatomical features. Future multi-site studies should move towards sharing of raw/voxelwise neuroimaging data.
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Transtorno Bipolar , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Humanos , Aprendizado de Máquina , Imageamento por Ressonância Magnética , NeuroimagemRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD); however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean fractional anisotropy (FA) from 43 regions of interest (ROI) and average whole-brain FA were entered into univariate mega- and meta-analyses to differentiate patients with BD from HC. Mega-analysis revealed significantly lower FA in patients with BD compared with HC in 29 regions, with the highest effect sizes observed within the corpus callosum (R2 = 0.041, Pcorr < 0.001) and cingulum (right: R2 = 0.041, left: R2 = 0.040, Pcorr < 0.001). Lithium medication, later onset and short disease duration were related to higher FA along multiple ROIs. Results of the meta-analysis showed similar effects. We demonstrated widespread WM abnormalities in BD and highlighted that altered WM connectivity within the corpus callosum and the cingulum are strongly associated with BD. These brain abnormalities could represent a biomarker for use in the diagnosis of BD. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.
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Transtorno Bipolar/patologia , Encéfalo/patologia , Substância Branca/patologia , Adulto , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Substância Branca/diagnóstico por imagemRESUMO
We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain.
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OBJECTIVE: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies. METHODS: Cortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707). RESULTS: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample. CONCLUSIONS: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.
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Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Adolescente , Adulto , Fatores Etários , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Estudos de Casos e Controles , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Escalas de Graduação Psiquiátrica , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: The severity of substance use disorder (SUD) is currently defined by the sum of DSM-5 criteria. However, little is known about the validity of this framework or the role of additional severity indicators in relapse prediction. This study aimed to investigate the relationship between DSM-5 criteria, neurocognitive functioning, substance use variables and cocaine relapse among inpatients with cocaine use disorder (CUD). METHODS: 128 adults aged between 18 and 45 years were evaluated; 68 (59 males, 9 females) had CUD and 60 (52 males, 8 females) were healthy controls. For the group with CUD, the use of other substances was not an exclusion criterion. Participants were tested using a battery of neurocognitive tests. Cocaine relapse was evaluated 3 months after discharge. RESULTS: Scores for attention span and working memory were worse in patients compared to controls. Earlier onset and duration of cocaine use were related to poorer inhibitory control and global executive functioning, respectively; recent use was related to worse performance in inhibitory control, attention span and working memory. More DSM-5 criteria at baseline were significantly associated with relapse. CONCLUSIONS: Recent cocaine use was the most predictive variable for neurocognitive impairments, while DSM-5 criteria predicted cocaine relapse at three months post treatment. The integration of neurocognitive measures, DSM-5 criteria and cocaine use variables in CUD diagnosis could improve severity differentiation. Longitudinal studies using additional biomarkers are needed to disentangle the different roles of severity indicators in relapse prediction and to achieve more individualized and effective treatment strategies for these patients.
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Transtornos Relacionados ao Uso de Cocaína/psicologia , Transtornos Neurocognitivos/induzido quimicamente , Índice de Gravidade de Doença , Adolescente , Adulto , Atenção/efeitos dos fármacos , Estudos de Casos e Controles , Manual Diagnóstico e Estatístico de Transtornos Mentais , Função Executiva/efeitos dos fármacos , Feminino , Humanos , Estudos Longitudinais , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Recidiva , Adulto JovemRESUMO
BACKGROUND: There is evidence of an imbalance in the neuromodulatory system mediated by serotonin (5-HT) in patients with drug-resistant temporal lobe epilepsy (TLE). This study analyzed the monoamine oxidase A promoter variable number of tandem repeats (MAOA-uVNTR) polymorphism in patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Therefore, we assessed the association between this genetic variant and seizure predisposition and severity in patients with TLE-HS. METHODS: One hundred nineteen patients with TLE-HS and 113 healthy volunteers were assessed. First, we genotyped all individuals for the MAOA-uVNTR genetic polymorphism. Second, we compared patients and controls and evaluated clinical variants of epilepsy. RESULTS: There was no difference between the TLE-HS and control groups regarding genotypic and allelic distributions of MAOA-uVNTR polymorphism (p = 1.000). Higher transcription alleles of the MAOA-uVNTR were associated with higher seizure frequency (p = 0.032) and bilateral tonic-clonic seizures (p = 0.016). CONCLUSIONS: In a selected group of patients with TLE-HS, the polymorphism MAOA-uVNTR was associated with some aspects of epilepsy severity, namely seizure frequency and bilateral tonic-clonic seizures.
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Epilepsia do Lobo Temporal/genética , Repetições Minissatélites/genética , Monoaminoxidase/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Convulsões/genética , Adulto , Eletroencefalografia , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/diagnóstico por imagem , Feminino , Genótipo , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Convulsões/etiologia , Estatísticas não Paramétricas , Adulto JovemRESUMO
BACKGROUND: Temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) is the most frequent form of drug-resistant epilepsy in adults. Mood disorders are the most frequent psychiatric comorbidities observed in these patients. Common pathophysiological mechanisms of epilepsy and psychiatric comorbidities include abnormalities in the serotonin pathway. The primary goal of this study was to determine the possible association between polymorphisms of genes encoding the serotonin receptors 5HT1A (rs6295), 5HT1B (rs6296), and 5HT2C (rs6318) and the presence of mood disorders in patients with TLE-HS. Our secondary goal was to evaluate the possible association between these variants and susceptibility to develop seizures in TLE-HS. METHODS: We assessed 119 patients with TLE-HS, with and without psychiatric comorbidities; 146 patients with major depressive disorder; and 113 healthy volunteers. Individuals were genotyped for the rs6295, rs6296, and rs6318 polymorphisms. RESULTS: No difference was observed between the group with TLE-HS, healthy controls, and the group with major depressive disorder without epilepsy regarding the polymorphisms that were evaluated. There was no correlation between rs6318, rs6295, rs6296, and epilepsy-related factors and history of psychiatric comorbidities. CONCLUSIONS: Our work suggests that the studied polymorphisms were not related to the presence of TLE, psychiatric comorbidities in TLE, and epilepsy-related factors.
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Transtorno Depressivo Maior/genética , Epilepsia Resistente a Medicamentos/genética , Epilepsia do Lobo Temporal/genética , Hipocampo , Polimorfismo Genético/genética , Receptores de Serotonina/genética , Adolescente , Adulto , Idoso , Criança , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/fisiopatologia , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Hipocampo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Serotonina/metabolismo , Esclerose/patologia , Adulto JovemRESUMO
Many previous magnetic resonance imaging (MRI) studies have documented sex differences in brain morphology, but the patterns of sexual brain differences in transgender women - male sex assigned at birth - with a diagnosis of gender dysphoria (TW) have been rarely investigated to date. We acquired T1-weighted MRI data for the following four (n = 80) groups: treatment-naïve TW (TNTW), TW treated with cross-sex hormones for at least one year (TTW), cisgender men, and cisgender women (cisgender individuals as controls). Differences in whole-brain and regional white matter volume and grey matter volume (GMV) were assessed using voxel-based morphometry. We found lower global brain volumes and regional GMVs in a large portion of the posterior-superior frontal cortex in the cisgender women group than in the TTW and cisgender men groups. Additionally, both transgender groups exhibited lower bilateral insular GMVs than the cisgender women group. Our results highlight differences in the insula in both transgender groups; such differences may be characteristic of TW. Furthermore, these alterations in the insula could be related to the neural network of body perception and reflect the distress that accompanies gender dysphoria.
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Hormônios Esteroides Gonadais/administração & dosagem , Substância Cinzenta/anatomia & histologia , Pessoas Transgênero , Substância Branca/anatomia & histologia , Adulto , Antropometria , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Adulto JovemRESUMO
INTRODUCTION: Adolescence is a crucial period for neurodevelopment, but few studies have investigated the impact of early cocaine use on cognitive performance and patterns of substance use. METHODS: We evaluated 103 cocaine dependent inpatients divided in two groups: early-onset users (EOG; n=52), late-onset users (LOG; n=51), and 63 healthy controls. Neuropsychological functioning was evaluated using Digits Forward (DF) and Backward (DB), Trail Making Test (TMT), Stroop Color Word Test (SCWT), Controlled Oral Word Association Test (COWAT), Wisconsin Card Sorting Test (WCST), Rey Osterrieth Complex Figure Test (ROCFT), Frontal Assessment Battery (FAB), and Iowa Gambling Test (IGT). Use of alcohol and other drugs was assessed with the Addiction Severity Index (ASI-6). RESULTS: Analyses of covariance controlling for age, IQ and years of education showed that EOG presented worse performance in attention span (DF, p=0.020), working memory (DB, p=0.001), sustained attention (WCST, p=0.030), declarative memory (ROCFT, p=0.031) and general executive functioning (FAB, p=0.003) when compared with the control group. LOG presented impairments on divided attention (TMT, p=0.003) and general executive functioning (FAB, p=0.001) in relation to the control group. EOG presented higher use of cannabis and alcohol than LOG (p≤0.001). CONCLUSION: Early-onset cocaine users display more pronounced neuropsychological alterations than controls, as well as a greater frequency of polydrug consumption than LOG. The prominent cognitive deficits in EOG probably reflect the deleterious interference of cocaine use with early stages of neurodevelopment. This may be related to more severe clinical characteristics of substance disorder in this subgroup, including polysubstance abuse.