RESUMO
BACKGROUND: Childhood maltreatment (CM) is related to poor physical and mental health outcomes in adults. Knowledge on the impact of CM on skin diseases is limited, and no study has previously addressed the association of CM with atopic dermatitis (AD) in adult age. OBJECTIVES: To analyse the prevalence of CM in individuals with physician-diagnosed AD, and to examine the relationship between different types of CM with physician-diagnosed AD in a general population sample of German adults. METHODS: Data from 2973 participants from the cross-sectional population-based Study of Health in Pomerania (SHIP) TREND-0 were analysed (aged 20 to 83 years; 51.4% female). We administered the Childhood Trauma Questionnaire (CTQ) assessing emotional, physical and sexual abuse, and emotional and physical neglect. AD was diagnosed by dermatologists in a standardized clinical examination. We conducted logistic regression analyses adjusted for age, sex and school education to investigate the association of CM types with AD. RESULTS: Among all individuals with AD, 20.6% reported to have experienced at least one type of moderate or severe CM. Emotional and physical neglect were the most frequently reported CM types. Overall, the prevalence of CM types among individuals with AD did not differ from those among individuals without AD. We found no association of CM type with AD. CONCLUSIONS: This is the first study investigating the association of CM with AD in adults. CM was common in the present general population sample, emphasizing that CM is an important public health problem. Our findings suggest that CM is not a risk factor for AD. It might be hypothesized that AD severity is a crucial outcome, and that CM history is a factor with impact on disease severity and course rather than a risk factor for the development of AD. Longitudinal studies are required to address this question.
Assuntos
Maus-Tratos Infantis , Dermatite Atópica , Adulto , Criança , Humanos , Feminino , Masculino , Estudos Transversais , Maus-Tratos Infantis/psicologia , Estudos de Coortes , Dermatite Atópica/epidemiologia , Inquéritos e QuestionáriosRESUMO
Despite high heritability of schizophrenia, genome-wide association studies (GWAS) have not yet revealed distinct combinations of single-nucleotide polymorphisms (SNPs), relevant for mental disease-related, quantifiable behavioral phenotypes. Here we propose an individual-based model to use genome-wide significant markers for extracting first genetic signatures of such behavioral continua. 'OTTO' (old Germanic=heritage) marks an individual characterized by a prominent phenotype and a particular load of phenotype-associated risk SNPs derived from GWAS that likely contributed to the development of his personal mental illness. This load of risk SNPs is shared by a small squad of 'similars' scattered under the genetically and phenotypically extremely heterogeneous umbrella of a schizophrenia end point diagnosis and to a variable degree also by healthy subjects. In a discovery sample of >1000 deeply phenotyped schizophrenia patients and several independent replication samples, including the general population, a gradual increase in the severity of 'OTTO's phenotype' expression is observed with an increasing share of 'OTTO's risk SNPs', as exemplified here by autistic and affective phenotypes. These data suggest a model in which the genetic contribution to dimensional behavioral traits can be extracted from combinations of GWAS SNPs derived from individuals with prominent phenotypes. Even though still in the 'model phase' owing to a world-wide lack of sufficiently powered, deeply phenotyped replication samples, the OTTO approach constitutes a conceptually novel strategy to delineate biological subcategories of mental diseases starting from GWAS findings and individual subjects.
Assuntos
Estudo de Associação Genômica Ampla/métodos , Esquizofrenia/genética , Adulto , Idoso , Feminino , Heterogeneidade Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Transtornos Psicóticos/genética , Fatores de RiscoRESUMO
Few epidemiological studies presented 12-month and lifetime prevalence estimates for DSM-IV mental disorders in the adult general population by sex and age up to very old age. From 2007 to 2010, DSM-IV mental disorders were assessed with the DIA-X/M-CIDI among N = 2400 participants (aged 29-89 years) from the Study of Health in Pomerania, an epidemiological study based on a two-stage stratified cluster sample randomly drawn from the adult general population in northeastern Germany. 36.3% of the sample was affected by any 12-month and 54.8% by any lifetime mental disorder. The most frequent diagnostic groups were anxiety (12-month: 14.8%, lifetime: 23.4%), substance use (12-month: 14.5%, lifetime: 25.0%), somatoform (12-month: 12.9%, lifetime: 20.4%) and depressive (12-month: 7.3%, lifetime: 18.6%) disorders. Except for substance use (higher prevalence in men) and bipolar disorders (comparable prevalence in men and women), higher 12-month and lifetime prevalence estimates were found in women vs. men. Moreover, lower 12-month and lifetime prevalence estimates were found in older (aged 60-74 or 75-89 years) vs. younger (aged 29-44 or 45-59 years) age groups. 22.6% (men: 21.1%, women: 23.9%) of those affected by any 12-month disorder met criteria for two and 13.6% (men: 9.6%, women: 16.9%) for three or more 12-month diagnoses. Similarly, 26.4% (men: 25.7%, women: 26.9%) of those affected by any lifetime disorder met criteria for two and 22.7% (men: 19.6%, women: 25.2%) for three or more lifetime diagnoses. Our findings demonstrate the frequency of mental disorders in northeastern Germany and emphasize the need for continued prevention and intervention efforts.
Assuntos
Inquéritos Epidemiológicos/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Comorbidade , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores SexuaisRESUMO
BACKGROUND: Major depressive disorder (MDD) and bipolar disorder are associated with certain cardiovascular risk factors (CVRFs), but it is unclear whether they are associated with unfavourable changes of clinically manifest CVRFs over time. METHODS: We used baseline and 12-year follow-up (n = 1887) data from the German Health Interview and Examination Survey 1998. Multivariable linear regression models assessed associations between lifetime CIDI-diagnosed mood disorders at baseline and continuous risk factor-related outcomes (blood pressure, HbA1c, LDL-C, HDL-C, triglycerides, BMI) at follow-up. RESULTS: We did not find consistent deterioration of CVRFs in persons with compared to persons without MDD. Analyses pointed to severity of mood disorder as an important correlate of long-term changes of comorbid hypertension: while a history of mild MDD was not associated with changes in CVRFs, moderate MDD was associated with lower blood pressure [systolic: ß = - 7.5 (CI - 13.2; - 1.9); diastolic: ß = - 4.5 (CI - 7.8; - 1.3)] and a history of bipolar disorder was associated with higher systolic blood pressure at follow-up (ß = 14.6; CI 4.9-24.4). Further, severe MDD was weakly associated with a higher BMI at follow-up [ß = 1.2 (CI 0.0; 2.4)]. These outcomes were not mediated by use of psychotropic medication and remained statistically significant after adjusting for the use of antihypertensive medication. CONCLUSION: Since most investigated parameters showed no associations, participants with a lifetime history of MDD in this cohort did not carry a specific risk for a worsening of pre-existing clinically manifest CVRFs. Our findings extend evidence of MDD severity and bipolar disorder as important correlates of long-term changes of arterial hypertension and obesity.
Assuntos
Transtorno Bipolar/complicações , Doenças Cardiovasculares/epidemiologia , Transtorno Depressivo Maior/complicações , Adulto , Doenças Cardiovasculares/etiologia , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
BACKGROUND: As early as pregnancy, maternal mental stress impinges on the child's development and health. Thus, this may cause enhanced risk for premature birth, lowered fetal growth, and lower fetal birth weight as well as enhanced levels of the stress hormone cortisol and lowered levels of the bonding hormone oxytocin. Maternal stress further reduces maternal sensitivity for the child's needs which impairs the mother-child-interaction and bonding. Therefore, prevention and intervention studies on mental stress are necessary, beginning prenatally and applying rigorous research methodology, such as randomized controlled trials, to ensure high validity. METHODS: A randomized controlled trial is used to assess the impact of psychotherapy and telemedicine on maternal mental stress and the child's mental and physical health. Mentally stressed pregnant women are randomized to an intervention (IG) and a not intervened control group. The IG receives an individualized psychotherapy starting prenatal and lasting for 10 months. Afterwards, a second randomization is used to investigate whether the use of telemedicine can stabilize the therapeutic effects. Using ecological momentary assessments and video recordings, the transfer into daily life, maternal sensitivity and mother-child-bonding are assessed. Psycho-biologically, the synchronicity of cortisol and oxytocin levels between mother and child are assessed as well as the peptidome of the colostrum and breast milk, which are assumed to be essential for the adaptation to the extra-uterine environment. All assessments are compared to an additional control group of healthy women. Finally, the results of the study will lead to the development of a qualification measure for health professionals to detect mental stress, to treat it with low-level interventions and to refer those women with high stress levels to mental health professionals. DISCUSSION: The study aims to prevent the transgenerational transfer of psychiatric and somatic disorders from the mother to her child. The effects of the psychotherapy will be stabilized through telemedicine and long-term impacts on the child's and mothers' mental health are enhanced. The combination of psychotherapy, telemedicine and methodologies of ecological momentary assessment, video recording and bio banking are new in content-related and methodological manner. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00017065. Registered 02 May 2019. World Health Organization, Universal Trial Number: U1111-1230-9826. Registered 01 April 2019.
Assuntos
Mães/psicologia , Complicações na Gravidez/terapia , Cuidado Pré-Natal/métodos , Psicoterapia/métodos , Estresse Psicológico/terapia , Telemedicina/métodos , Adulto , Criança , Feminino , Humanos , Exposição Materna/efeitos adversos , Gravidez , Complicações na Gravidez/psicologia , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estresse Psicológico/psicologia , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Various fat depots including visceral (VAT), subcutaneous adipose tissue (SAT) or liver fat content (LFC) were supposed to have different influences on various entities including adipokine levels as well as insulin resistance/sensitivity. Therefore, the aim of the study was to investigate the associations of SAT, VAT and LFC with the levels of leptin and vaspin as well as insulin resistance in a general non-diabetic population. METHODS: In total, 1825 participants of the Study of Health in Pomerania were characterized according to body fat compartments and LFC determined by magnetic resonance imaging. Of those subjects, insulin resistance (HOMA-IR) and insulin sensitivity ([ISI(comp)) were determined in 981 participants and adipokines were assessed in 698 using enzyme-linked immunosorbent assay. Analyses of variance and linear regression models adjusted for age, sex, smoking, height, physical inactivity and alcohol consumption were used for analysis. RESULTS: Using the residual method to assess independently the effect of the various fat depots, a strong positive association of SAT (beta per standard deviation (s.d.) increase 0.54 (95% confidence interval (CI) 0.47-0.60)) but not VAT (beta 0.01 (95% CI -0.08 to 0.09)) and LFC (beta 0.01 (95% CI -0.06 to 0.08)) with log2-leptin levels was found independent of the HOMA-IR status. Moreover, a positive association of LFC (beta 0.17 (95% CI 0.07-0.26)) with log2-vaspin levels becomes apparent, which were mostly driven by subjects with a low HOMA-IR. With respect to HOMA-IR and ISI(comp) index, pronounced positive and inverse associations to all fat markers were revealed, respectively, with the strongest relation found for SAT and LFC. CONCLUSIONS: SAT and LFC were identified as predominant sites associated with leptin and vaspin levels, respectively. Residual analysis pointed towards a general adverse effect of disproportional triglyceride storage across physiological despots, in particular in ectopic sides such as the liver, with markers of insulin resistance.
Assuntos
Resistência à Insulina/fisiologia , Leptina/metabolismo , Serpinas/metabolismo , Gordura Subcutânea/metabolismo , Adulto , Distribuição por Idade , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Biomarcadores/metabolismo , Índice de Massa Corporal , Ensaio de Imunoadsorção Enzimática , Feminino , Alemanha/epidemiologia , Inquéritos Epidemiológicos , Humanos , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fígado/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Comportamento Sedentário , Distribuição por Sexo , Fumar/epidemiologia , Gordura Subcutânea/diagnóstico por imagem , Adulto JovemRESUMO
The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.
Assuntos
Córtex Cerebral/patologia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/patologia , Adolescente , Adulto , Encéfalo/patologia , Córtex Cerebral/diagnóstico por imagem , Feminino , Lobo Frontal/patologia , Substância Cinzenta/patologia , Giro do Cíngulo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Neuroimagem/métodos , Neuroimagem/psicologia , Córtex Pré-Frontal/patologia , Lobo Temporal/patologiaRESUMO
Anxiety disorders (ADs), namely generalized AD, panic disorder and phobias, are common, etiologically complex conditions with a partially genetic basis. Despite differing on diagnostic definitions based on clinical presentation, ADs likely represent various expressions of an underlying common diathesis of abnormal regulation of basic threat-response systems. We conducted genome-wide association analyses in nine samples of European ancestry from seven large, independent studies. To identify genetic variants contributing to genetic susceptibility shared across interview-generated DSM-based ADs, we applied two phenotypic approaches: (1) comparisons between categorical AD cases and supernormal controls, and (2) quantitative phenotypic factor scores (FS) derived from a multivariate analysis combining information across the clinical phenotypes. We used logistic and linear regression, respectively, to analyze the association between these phenotypes and genome-wide single nucleotide polymorphisms. Meta-analysis for each phenotype combined results across the nine samples for over 18 000 unrelated individuals. Each meta-analysis identified a different genome-wide significant region, with the following markers showing the strongest association: for case-control contrasts, rs1709393 located in an uncharacterized non-coding RNA locus on chromosomal band 3q12.3 (P=1.65 × 10(-8)); for FS, rs1067327 within CAMKMT encoding the calmodulin-lysine N-methyltransferase on chromosomal band 2p21 (P=2.86 × 10(-9)). Independent replication and further exploration of these findings are needed to more fully understand the role of these variants in risk and expression of ADs.
Assuntos
Transtornos de Ansiedade/genética , Estudos de Casos e Controles , Estudos de Associação Genética/métodos , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , População Branca/genéticaRESUMO
The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.
Assuntos
Encéfalo/patologia , Transtorno Depressivo Maior/patologia , Adulto , Estudos de Casos e Controles , Feminino , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodosRESUMO
BACKGROUND AND AIMS: We investigated the associations of fasting (FG) and 2-h postload (2HG) plasma glucose from oral glucose tolerance test (OGTT) with gray (GMV) and white (WMV) matter volume. METHODS AND RESULTS: We analyzed data from 1330 subjects without known diabetes mellitus, aged 21 to 81, from the second cohort (SHIP-Trend-0) of the population-based Study of Health in Pomerania (SHIP). Following the OGTT, individuals were classified in five groups (according to the American Diabetes Association criteria): normal glucose tolerance (NGT), isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFGâ¯+â¯IGT) and unknown type 2 diabetes mellitus (UDM). GMV and WMV were determined by magnetic resonance imaging. FG, 2HG and OGTT groups were associated with GMV and WMV by linear regression models adjusted for confounders. FG and 2HG were inversely associated with GMV. The adjusted mean GMV, when compared with the NGT group (584â¯ml [95% CI: 581 to 587]), was significantly lower in the groups i-IFG (578â¯ml [95% CI: 573 to 582]; pâ¯=â¯0.035) and UDM (562â¯ml [95% CI: 551 to 573]; pâ¯<â¯0.001), but not different in the i-IGT (586â¯ml [95% CI: 576 to 596]; pâ¯=â¯0.688) and IFGâ¯+â¯IGT (579â¯ml [95% CI: 571 to 586]; pâ¯=â¯0.209) groups. There were no associations of FG, 2HG and OGTT parameters with WMV. CONCLUSION: Our findings suggest that elevated FG levels, even within the prediabetic range, might already have some harmful effects on GMV.
Assuntos
Encefalopatias/epidemiologia , Substância Cinzenta , Estado Pré-Diabético/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Glicemia/metabolismo , Encefalopatias/diagnóstico por imagem , Estudos Transversais , Jejum/sangue , Feminino , Alemanha/epidemiologia , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Substância Cinzenta/diagnóstico por imagem , Humanos , Leucoencefalopatias/diagnóstico por imagem , Leucoencefalopatias/epidemiologia , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico , Prevalência , Medição de Risco , Fatores de Risco , Substância Branca/diagnóstico por imagem , Adulto JovemRESUMO
In two large genome-wide association studies, an intergenic single-nucleotide polymorphism (SNP; rs7294919) involved in TESC gene regulation has been associated with hippocampus volume. Further characterization of neurobiological effects of the TESC gene is warranted using multimodal brain-wide structural and functional imaging. Voxel-based morphometry (VBM8) was used in two large, well-characterized samples of healthy individuals of West-European ancestry (Münster sample, N=503; SHIP-TREND, N=721) to analyze associations between rs7294919 and local gray matter volume. In subsamples, white matter fiber structure was investigated using diffusion tensor imaging (DTI) and limbic responsiveness was measured by means of functional magnetic resonance imaging (fMRI) during facial emotion processing (N=220 and N=264, respectively). Furthermore, gene x environment (G × E) interaction and gene x gene interaction with SNPs from genes previously found to be associated with hippocampal size (FKBP5, Reelin, IL-6, TNF-α, BDNF and 5-HTTLPR/rs25531) were explored. We demonstrated highly significant effects of rs7294919 on hippocampal gray matter volumes in both samples. In whole-brain analyses, no other brain areas except the hippocampal formation and adjacent temporal structures were associated with rs7294919. There were no genotype effects on DTI and fMRI results, including functional connectivity measures. No G × E interaction with childhood maltreatment was found in both samples. However, an interaction between rs7294919 and rs2299403 in the Reelin gene was found that withstood correction for multiple comparisons. We conclude that rs7294919 exerts highly robust and regionally specific effects on hippocampal gray matter structures, but not on other neuropsychiatrically relevant imaging markers. The biological interaction between TESC and RELN pointing to a neurodevelopmental origin of the observed findings warrants further mechanistic investigations.
Assuntos
Proteínas de Ligação ao Cálcio/genética , Substância Cinzenta , Hipocampo/anatomia & histologia , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Moléculas de Adesão Celular Neuronais/genética , Moléculas de Adesão Celular Neuronais/metabolismo , Epistasia Genética , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Regulação da Expressão Gênica/genética , Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Genótipo , Substância Cinzenta/irrigação sanguínea , Substância Cinzenta/metabolismo , Hipocampo/irrigação sanguínea , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Oxigênio/sangue , Proteína Reelina , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Adulto JovemRESUMO
Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.
Assuntos
Dissonias/genética , Sono/genética , Adulto , Negro ou Afro-Americano/genética , Idoso , Feminino , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Autorrelato , População Branca/genéticaRESUMO
BACKGROUND: A dysfunctional network of prefrontal and (para-)limbic brain region has been suggested to underlie emotional dysregulation in borderline personality disorder (BPD). Abnormal activity in this network may be due to structural alterations in white-matter tracts connecting prefrontal and (para-)limbic brain regions. To test this hypothesis, we investigated the structural integrity of major white-matter tracts connecting these regions in BPD. METHOD: Using diffusion tensor imaging, we investigated fractional anisotropy (FA), axonal anisotropy (AD) and radial diffusivity (RD) in the uncinate fasciculus, the major white-matter tract connecting (para-)limbic and prefrontal brain regions, in 26 healthy controls (HC) and 26 BPD participants. To clarify the specificity of possible white-matter alterations among HC and BPD participants, FA, AD and RD were also investigated in the cingulum. RESULTS: We found distinct structural alterations in the uncinate fasciculus but not in the cingulum of BPD participants. Compared to HC participants, BPD participants showed lower FA and higher RD in the uncinate fasciculus. By contrast, AD did not differ in the uncinate fasciculus of HC and BPD participants. CONCLUSIONS: Our finding of abnormal FA and RD in the uncinate fasciculus indicates distinct white-matter alterations in BPD, presumably due to stress-induced myelin degeneration in the aftermath of stressful life events. Although these alterations may account for abnormal activity in brain regions implicated in emotion dysregulation, such as the amygdala, anterior cingulate cortex and prefrontal cortex, it remains to be determined whether these alterations are specific for BPD.
Assuntos
Tonsila do Cerebelo/patologia , Transtorno da Personalidade Borderline/patologia , Giro do Cíngulo/patologia , Córtex Pré-Frontal/patologia , Substância Branca/patologia , Adulto , Imagem de Tensor de Difusão , Feminino , Humanos , Vias Neurais/patologia , Adulto JovemRESUMO
Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 × 10(-6) and P=3.44 × 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P<0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P=0.001) was observed within the top-ranked SNPs (P<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.
Assuntos
Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Proteínas do Tecido Nervoso/genética , Transtorno Obsessivo-Compulsivo/genética , Estudos de Casos e Controles , Lobo Frontal/metabolismo , Humanos , Pais , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Proteínas Associadas SAP90-PSD95 , População Branca/genéticaRESUMO
Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N=18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values=1.6 × 10(-11) and 2.7 × 10(-11)), which were also in strong linkage disequilibrium (r(2)=0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value=3.9 × 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1 × 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value=2.2 × 10(-05)) and Parkinson's disease pathways (P-value=3.6 × 10(-05)).
Assuntos
Moléculas de Adesão Celular/genética , Café/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A2/genética , Ingestão de Líquidos/genética , Estudo de Associação Genômica Ampla/métodos , Antígenos de Neoplasias/genética , Proteínas Reguladoras de Apoptose/genética , Cafeína/farmacologia , Linhagem Celular , Feminino , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Predisposição Genética para Doença/genética , Humanos , Masculino , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Proteínas Serina-Treonina Quinases/genética , População Branca/genéticaRESUMO
BACKGROUND: Although some evidence suggests that borderline personality disorder (BPD) is primarily a disorder of the emotion regulation system, findings remain inconsistent. One potential explanation for this is the moderating role of dissociation. METHOD: In this study, 33 female subjects with BPD and 26 healthy controls (HC; matched by education level and nicotine intake) were presented idiographic aversive, standard unpleasant and neutral scripts. Modulation of startle reflex and electrodermal responses (skin conductance level; SCL) were measured during imagery of emotional and neutral scripts. Additionally, self-reports of emotional experience (valence and arousal) and present-state dissociation were assessed. RESULTS: Patients with BPD showed elevated levels of dissociative experiences during testing. Present-state dissociation mediated group differences in SCL and startle response between the HC and BPD groups. CONCLUSIONS: These results suggest that careful attention must be paid to the moderating effect of dissociative symptoms on the psychophysiological responses of BPD patients. Furthermore, the findings have important implications for the assessment and treatment of BPD, including the need to carefully assess BPD patients for dissociative symptoms and to incorporate the treatment of dissociation.
Assuntos
Transtorno da Personalidade Borderline/fisiopatologia , Transtornos Dissociativos/fisiopatologia , Emoções/fisiologia , Resposta Galvânica da Pele/fisiologia , Reflexo de Sobressalto/fisiologia , Adulto , Nível de Alerta/fisiologia , Transtorno da Personalidade Borderline/complicações , Transtorno da Personalidade Borderline/psicologia , Estudos de Casos e Controles , Transtornos Dissociativos/complicações , Transtornos Dissociativos/psicologia , Feminino , Humanos , Modelos Lineares , Autorrelato , Adulto JovemRESUMO
OBJECTIVE: To explore whether the increase in knowledge about the biological correlates of mental disorders over the last decades has translated into improved public understanding of mental illness, increased readiness to seek mental health care and more tolerant attitudes towards mentally ill persons. METHOD: A systematic review of all studies on mental illness-related beliefs and attitudes in the general population published before 31 March 2011, examining the time trends of attitudes with a follow-up interval of at least 2 years and using national representative population samples. A subsample of methodologically homogeneous studies was further included in a meta-regression analysis of time trends. RESULTS: Thirty-three reports on 16 studies on national time trends met our inclusion criteria, six of which were eligible for a meta-regression analysis. Two major trends emerged: there was a coherent trend to greater mental health literacy, in particular towards a biological model of mental illness, and greater acceptance of professional help for mental health problems. In contrast, however, no changes or even changes to the worse were observed regarding the attitudes towards people with mental illness. CONCLUSION: Increasing public understanding of the biological correlates of mental illness seems not to result in better social acceptance of persons with mental illness.