RESUMO
Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. PRACTITIONER POINTS: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.
Assuntos
Transtorno Bipolar , Imageamento por Ressonância Magnética , Obesidade , Análise de Componente Principal , Humanos , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/patologia , Adulto , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Obesidade/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Análise por Conglomerados , Adulto Jovem , Encéfalo/diagnóstico por imagem , Encéfalo/patologiaRESUMO
Since 1980's, the established/standard treatment of acute myeloid leukemia (AML) is cytarabine infusion with anthracycline (7 + 3 regimen). We compared the 7 + 3 regimen in older secondary/high-risk AML patients from a clinical trial with a matched population from the Swedish AML Registry treated with an increased cytarabine dose in induction and consolidation as recommended in the Swedish National Guidelines since 2005. After successful propensity score matching, 104 patients per group were included. The primary outcome was overall survival (OS), and standard dosed patients had a median OS of 6.4 versus 10.7 months with increased dose intensity (hazard ratio: 0.69, p = 0.012), with 5-year OS of 8.7% and 18.1%, and remission rates of 36% and 60%, respectively (p < 0.001). Median OS after allogeneic hematopoietic cell transplantation (in 27.9% per group) was 10.4 and 20.7 months, respectively. We conclude that the more intensive cytarabine schedule seems to provide improved outcomes inthe investigated AML patient group.
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Background and aims: The ICD-11 chapter on mental, behavioral and neurodevelopmental disorders contains new controversial diagnoses including compulsive sexual behavior disorder (CSBD), intermittent explosive disorder (IED) and gaming disorder. Using a vignette-based methodology, this field study examined the ability of mental health professionals (MHPs) to apply the new ICD-11 diagnostic requirements for impulse control disorders, which include CSBD and IED, and disorders due to addictive behaviors, which include gaming disorder, compared to the previous ICD-10 guidelines. Methods: Across eleven comparisons, members of the WHO's Global Clinical Practice Network (N = 1,090) evaluated standardized case descriptions that were designed to test key differences between the diagnostic guidelines of ICD-11 and ICD-10. Results: The ICD-11 outperformed the ICD-10 in the accuracy of diagnosing impulse control disorders and behavioral addictions in most comparisons, while the ICD-10 was not superior in any. The superiority of the ICD-11 was particularly clear where new diagnoses had been added to the classification system or major revisions had been made. However, the ICD-11 outperformed the ICD-10 only in a minority of comparisons in which mental health professionals were asked to evaluate cases with non-pathological high involvement in rewarding behaviors. Discussion and Conclusions: Overall, the present study indicates that the ICD-11 diagnostic requirements represent an improvement over the ICD-10 guidelines. However, additional efforts, such as training programs for MHPs and possible refinements of diagnostic guidance, are needed to avoid over-diagnosis of people who are highly engaged in a repetitive and rewarding behavior but below the threshold for a disorder.
Assuntos
Comportamento Aditivo , Transtornos Disruptivos, de Controle do Impulso e da Conduta , Humanos , Classificação Internacional de Doenças , Saúde Mental , Pessoal de SaúdeRESUMO
Background: Pedophilic disorder (PD) entails sexual attraction to prepubertal children. A risk factor for committing child sexual abuse in PD is impaired cognitive control. However, the underlying neurocognitive mechanisms remain unclear. Methods: We performed a case-control study including 51 self-identified and help-seeking males with PD and 55 matched healthy control subjects. Functional magnetic resonance imaging and a pictorial-modified Stroop task involving computer-generated sexually implicit images were used to measure response time and brain activation. Increases in response time during the pictorial-modified Stroop task are presumably due to image-induced interference in executive functions required for task performance. Results: In PD, during the presentation of images of children compared with adults, we found increased response time (p = .005; 848 ± 92 ms vs. 826 ± 88 ms), and compared with healthy control subjects, we found increased activation in the occipital, temporal (bilateral hippocampus), parietal, frontal, cingulate, and left insular cortices; caudate (bilaterally); thalamus (mediodorsal); and cerebellum. Conclusions: Presentation of child images was associated with response interference in PD and increased engagement of brain regions involved in the processing of sexual stimuli, visual perception, self-referential thought, and executive function. We conclude that processing of child images is associated with functional and behavioral alterations in PD.
RESUMO
Cross-sectional neuroimaging studies show that bipolar disorder is associated with structural brain abnormalities, predominantly observed in prefrontal and temporal cortex, cingulate gyrus, and subcortical regions. However, longitudinal studies are needed to elucidate whether these abnormalities presage disease onset or are consequences of disease processes, and to identify potential contributing factors. Here, we narratively review and summarize longitudinal structural magnetic resonance imaging studies that relate imaging outcomes to manic episodes. First, we conclude that longitudinal brain imaging studies suggest an association of bipolar disorder with aberrant brain changes, including both deviant decreases and increases in morphometric measures. Second, we conclude that manic episodes have been related to accelerated cortical volume and thickness decreases, with the most consistent findings occurring in prefrontal brain areas. Importantly, evidence also suggests that in contrast to healthy controls, who in general show age-related cortical decline, brain metrics remain stable or increase during euthymic periods in bipolar disorder patients, potentially reflecting structural recovering mechanisms. The findings stress the importance of preventing manic episodes. We further propose a model of prefrontal cortical trajectories in relation to the occurrence of manic episodes. Finally, we discuss potential mechanisms at play, remaining limitations, and future directions.
Assuntos
Transtorno Bipolar , Humanos , Mania , Estudos Transversais , Encéfalo , Córtex Pré-Frontal , Imageamento por Ressonância MagnéticaRESUMO
Background and aims: Compulsive sexual behavior disorder (CSBD) has been included as an impulse control disorder in the International Classification of Diseases (ICD-11). However, the neurobiological mechanisms underlying CSBD remain largely unknown, and given previous indications of addiction-like mechanisms at play, the aim of the present study was to investigate if CSBD is associated with structural brain differences in regions involved in reward processing. Methods: We analyzed structural MRI data of 22 male CSBD patients (mean = 38.7 years, SD = 11.7) and 20 matched healthy controls (HC; mean = 37.6 years, SD = 8.5). Main outcome measures were regional cortical thickness and surface area. We also tested for case-control differences in subcortical structures and the effects of demographic and clinical variables, such as CSBD symptom severity, on neuroimaging outcomes. Moreover, we explored case-control differences in regions outside our hypothesis including white matter. Results: CSBD patients had significantly lower cortical surface area in right posterior cingulate cortex than HC. We found negative correlations between right posterior cingulate area and CSBD symptoms scores. There were no group differences in subcortical volume. Conclusions: Our findings suggest that CSBD is associated with structural brain differences, which contributes to a better understanding of CSBD and encourages further clarifications of the neurobiological mechanisms underlying the disorder.
Assuntos
Transtornos Parafílicos , Disfunções Sexuais Psicogênicas , Humanos , Masculino , Comportamento Sexual , Comportamento Compulsivo/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact. METHODS: We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations. RESULTS: BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI. CONCLUSIONS: We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
RESUMO
Background and aims: Compulsive sexual behavior disorder (CSBD) is characterized by persistent patterns of failure to control sexual impulses resulting in repetitive sexual behavior, pursued despite adverse consequences. Despite previous indications of addiction-like mechanisms and the recent impulse-control disorder classification in the International Classification of Diseases (ICD-11), the neurobiological processes underlying CSBD are unknown. Methods: We designed and applied a behavioral paradigm aimed at disentangling processes related to anticipation and viewing of erotic stimuli. In 22 male CSBD patients (age: M = 38.7, SD = 11.7) and 20 healthy male controls (HC, age: M = 37.6, SD = 8.5), we measured behavioral responses and neural activity during functional magnetic resonance imaging (fMRI). The main outcomes were response time differences between erotic and non-erotic trials and ventral striatum (VS) activity during anticipation of visual stimuli. We related these outcomes with each other, to CSBD diagnosis, and symptom severity. Results: We found robust case-control differences on behavioral level, where CSBD patients showed larger response time differences between erotic and non-erotic trials than HC. The task induced reliable main activations within each group. While we did not observe significant group differences in VS activity, VS activity during anticipation correlated with response time differences and self-ratings for anticipation of erotic stimuli. Discussion and Conclusions: Our results support the validity and applicability of the developed task and suggest that CSBD is associated with altered behavioral correlates of anticipation, which were associated with ventral striatum activity during anticipation of erotic stimuli. This supports the idea that addiction-like mechanisms play a role in CSBD.
Assuntos
Transtornos Parafílicos , Disfunções Sexuais Psicogênicas , Comportamento Compulsivo , Literatura Erótica , Humanos , Imageamento por Ressonância Magnética , Masculino , Comportamento Sexual/fisiologiaRESUMO
BACKGROUND: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Transtorno Bipolar , Transtorno Depressivo Maior , Nascimento Prematuro , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/patologia , Córtex Cerebral , Criança , Transtorno Depressivo Maior/patologia , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética/métodos , Gravidez , Nascimento Prematuro/patologiaRESUMO
The stock market is a bellwether of socio-economic changes that may directly affect individual well-being. Using large-scale UK-biobank data generated over 14 years, we applied specification curve analysis to rigorously identify significant associations between the local stock market index (FTSE100) and 479,791 UK residents' mood, as well as their alcohol intake and blood pressure adjusting the results for a large number of potential confounders, including age, sex, linear and non-linear effects of time, research site, other stock market indexes. Furthermore, we found similar associations between FTSE100 and volumetric measures of affective brain regions in a subsample (n = 39,755; measurements performed over 5.5 years), which were particularly strong around phase transitions characterized by maximum volatility in the market. The main findings did not depend on applied effect-size estimation criteria (linear methods or mutual information criterion) and were replicated in two independent US-based studies (Parkinson's Progression Markers Initiative; n = 424; performed over 2.5 years and MyConnectome; n = 1; 81 measurements over 1.5 years). Our results suggest that phase transitions in the society, indexed by stock market, exhibit close relationships with human mood, health and the affective brain from an individual to population level.
Assuntos
Encéfalo , Investimentos em Saúde , HumanosRESUMO
AIMS: Rates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under-researched in psychiatry. METHODS: We obtained body mass index (BMI) and magnetic resonance imaging-derived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14 sites within the ENIGMA-BD Working Group. We identified regionally specific profiles of cortical thickness using K-means clustering and studied clinical characteristics associated with individual cortical profiles. RESULTS: We detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In contrast, clustering based on similarities in the cortical surface area was unrelated to BD or BMI and only tracked age and sex. CONCLUSIONS: We provide evidence that both BD and obesity are associated with similar alterations in cortical thickness, but not surface area. The fact that obesity increased the chance of having low cortical thickness could explain differences in cortical measures among people with BD. The thinner cortex in individuals with higher BMI, which was additive and similar to the BD-associated alterations, may suggest that treating obesity could lower the extent of cortical thinning in BD.
Assuntos
Transtorno Bipolar , Transtorno Bipolar/diagnóstico , Índice de Massa Corporal , Análise por Conglomerados , Humanos , Imageamento por Ressonância Magnética , Obesidade/complicações , Obesidade/diagnóstico por imagem , Lobo Temporal/patologiaRESUMO
BACKGROUND: Bipolar disorder (BD) is associated with cortical and subcortical structural brain abnormalities. It is unclear whether such alterations progressively change over time, and how this is related to the number of mood episodes. To address this question, we analyzed a large and diverse international sample with longitudinal magnetic resonance imaging (MRI) and clinical data to examine structural brain changes over time in BD. METHODS: Longitudinal structural MRI and clinical data from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) BD Working Group, including 307 patients with BD and 925 healthy control subjects, were collected from 14 sites worldwide. Male and female participants, aged 40 ± 17 years, underwent MRI at 2 time points. Cortical thickness, surface area, and subcortical volumes were estimated using FreeSurfer. Annualized change rates for each imaging phenotype were compared between patients with BD and healthy control subjects. Within patients, we related brain change rates to the number of mood episodes between time points and tested for effects of demographic and clinical variables. RESULTS: Compared with healthy control subjects, patients with BD showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippocampal cortex (0.18 Assuntos
Transtorno Bipolar
, Adulto
, Transtorno Bipolar/patologia
, Encéfalo/diagnóstico por imagem
, Encéfalo/patologia
, Afinamento Cortical Cerebral
, Feminino
, Humanos
, Imageamento por Ressonância Magnética
, Masculino
, Mania
, Pessoa de Meia-Idade
, Estudos Multicêntricos como Assunto
, Neuroimagem
, Adulto Jovem
RESUMO
MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.
Assuntos
Transtorno Bipolar , Córtex Cerebral , Imageamento por Ressonância Magnética , Neuroimagem , Transtorno Bipolar/diagnóstico por imagem , Transtorno Bipolar/patologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Humanos , Metanálise como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Bipolar disorder is highly heritable and polygenic. The polygenic risk for bipolar disorder overlaps with that of schizophrenia, and polygenic scores are normally distributed in the population. Bipolar disorder has been associated with structural brain abnormalities, but it is unknown how these are linked to genetic risk factors for psychotic disorders. METHODS: We tested whether polygenic risk scores for bipolar disorder and schizophrenia predict structural brain alterations in 98 patients with bipolar disorder and 81 healthy controls. We derived brain cortical thickness, surface area and volume from structural MRI scans. In post-hoc analyses, we correlated polygenic risk with functional hub strength, derived from resting-state functional MRI and brain connectomics. RESULTS: Higher polygenic risk scores for both bipolar disorder and schizophrenia were associated with a thinner ventromedial prefrontal cortex (vmPFC). We found these associations in the combined group, and separately in patients and drug-naive controls. Polygenic risk for bipolar disorder was correlated with the functional hub strength of the vmPFC within the default mode network. LIMITATIONS: Polygenic risk is a cumulative measure of genomic burden. Detailed genetic mechanisms underlying brain alterations and their cognitive consequences still need to be determined. CONCLUSION: Our multimodal neuroimaging study linked genomic burden and brain endophenotype by demonstrating an association between polygenic risk scores for bipolar disorder and schizophrenia and the structure and function of the vmPFC. Our findings suggest that genetic factors might confer risk for psychotic disorders by influencing the integrity of the vmPFC, a brain region involved in self-referential processes and emotional regulation. Our study may also provide an imaging-genetics vulnerability marker that can be used to help identify individuals at risk for developing bipolar disorder.
Assuntos
Transtorno Bipolar/genética , Predisposição Genética para Doença , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Esquizofrenia/genética , Envelhecimento/genética , Transtorno Bipolar/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Herança Multifatorial , Córtex Pré-Frontal/diagnóstico por imagem , Fatores de Risco , Esquizofrenia/diagnóstico por imagemRESUMO
Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.
Assuntos
Transtorno Bipolar , Tonsila do Cerebelo , Índice de Massa Corporal , Encéfalo , Humanos , Imageamento por Ressonância Magnética/métodosRESUMO
Genetic and hormonal factors have been suggested to influence human sexual orientation. Previous studied proposed brain differences related to sexual orientation and that these follow cross-sex shifted patterns. However, the neurobiological correlates of sexual orientation and how genetic factors relate to brain structural variation remains largely unexplored. Using the largest neuroimaging-genetics dataset available on same-sex sexual behavior (SSB) (n = 18,645), we employed a data-driven multivariate classification algorithm (PLS) on magnetic resonance imaging data from two imaging modalities to extract brain covariance patterns related to sex. Through analyses of latent variables, we tested for SSB-related cross-sex shifts in such patterns. Using genotype data, polygenic scores reflecting the genetic predisposition for SSB were computed and tested for associations with neuroimaging outcomes. Patterns important for classifying between males and females were less pronounced in non-heterosexuals. Predominantly in non-heterosexual females, multivariate brain patterns as represented by latent variables were shifted toward the opposite sex. Complementary univariate analyses revealed region specific SSB-related differences in both males and females. Polygenic scores for SSB were associated with volume of lateral occipital and temporo-occipital cortices. The present large-scale study demonstrates multivariate neuroanatomical correlates of SSB, and tentatively suggests that genetic factors related to SSB may contribute to structural variation in certain brain structures. These findings support a neurobiological basis to the differences in human sexuality.
Assuntos
Encéfalo/anatomia & histologia , Homossexualidade/fisiologia , Herança Multifatorial , Comportamento Sexual/fisiologia , Idoso , Bancos de Espécimes Biológicos , Encéfalo/diagnóstico por imagem , Bases de Dados Factuais , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reino UnidoRESUMO
IMPORTANCE: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. OBJECTIVE: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. MAIN OUTCOMES AND MEASURES: Interregional profiles of group difference in cortical thickness between cases and controls. RESULTS: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders. CONCLUSIONS AND RELEVANCE: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Transtorno do Espectro Autista/patologia , Transtorno Bipolar/patologia , Córtex Cerebral/patologia , Transtorno Depressivo Maior/patologia , Desenvolvimento Fetal/fisiologia , Expressão Gênica/fisiologia , Desenvolvimento Humano/fisiologia , Transtorno Obsessivo-Compulsivo/patologia , Esquizofrenia/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Espectro Autista/diagnóstico por imagem , Transtorno Bipolar/diagnóstico por imagem , Estudos de Casos e Controles , Córtex Cerebral/citologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/crescimento & desenvolvimento , Criança , Pré-Escolar , Estudos de Coortes , Biologia Computacional , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Análise de Componente Principal , Esquizofrenia/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVE: Pedophilic disorder (PD) is characterized bypersistent, intense sexual attraction to prepubertal children that the individual has acted on, or causes marked distress or interpersonal difficulty. Although prior research suggests that PD has neurodevelopmental underpinnings, the evidence remains sparse. To aid the understanding of etiology and treatment development, we quantified neurobiological and clinical correlates of PD. METHOD: We compared 55 self-referred, help-seeking, non-forensic male patients with DSM-5 PD with 57 age-matched, healthy male controls (HC) on clinical, neuropsychological, and structural brain imaging measures (cortical thickness and surface area, subcortical and white matter volumes). Structural brain measures were related to markers for aberrant neurodevelopment including IQ, and the 2nd to 4th digit ratio (2D:4D). RESULTS: PD was associated with psychiatric disorder comorbidity and ADHD and autism spectrum disorder symptoms. PD patients had lower total IQ than HC. PD individuals exhibited cortical surface area abnormalities in regions belonging to the brain's default mode network and showed abnormal volume of white matter underlying those regions. PD subjects had smaller hippocampi and nuclei accumbens than HC. Findings were not related to history of child-related sexual offending. IQ correlated negatively with global expression of PD-related brain features and 2D:4D correlated with surface area in PD. CONCLUSIONS: In the largest single-center study to date, we delineate psychiatric comorbidity, neurobiological and cognitive correlates of PD. Our morphometric findings, their associations with markers of aberrant neurodevelopment, and psychiatric comorbidities suggest that neurodevelopmental mechanisms are involved in PD. The findings may need consideration in future development of clinical management of PD patients.
Assuntos
Transtorno do Espectro Autista , Substância Branca , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Substância Branca/diagnóstico por imagemRESUMO
Both non-emotional symptoms, such as inattention, and symptoms of emotional instability (EI) are partially co-varying and normally distributed in the general population. Attention Deficit Hyperactivity Disorder (ADHD), which is associated with both inattention and emotional instability, has been related to lower reward anticipation activation in the ventral striatum. However, it is not known whether non-emotional dysregulation, such as inattention, or EI-or both-are associated with this effect. We hypothesized that altered reward processing relates specifically to EI. To test this, 29 healthy participants were recruited to this functional MRI study (n = 15 females). Reward processing was studied using a modified version of the Monetary Incentive Delay (MID) task. Brown Attention-Deficit Disorder Scales questionnaire was used to assess EI and inattention symptoms on a trait level. We observed less ventral striatal activation during reward anticipation related to the EI trait in females, also when controlling for the inattention trait, but not in the whole sample or males only. Our study suggests the existence of sex differences in the relationship between reward processing and EI/inattention traits.