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Phytochemicals isolated from essential oils are effective alternatives for inhibiting microbial pathogens. Bovine protothecal mastitis is the cause of a reduction in milk production and the secretion of thin, watery milk with white flakes. In the present study, we performed in vitro susceptibility testing of the phytochemicals carvacrol, citral, and thymol in Prototheca strains isolated from cases of protothecosis in small animals and cow feces. The susceptibility of the algae to carvacrol, citral, and thymol was assessed using the modified CLSI M27-A3 broth microdilution method. The ranges of the minimum inhibitory concentrations (MIC%) of the phytochemicals in all isolates were 0.03% to 0.125% for carvacrol, 0.03% to 0.25% for citral, and 0.06% to 0.25% for thymol. Based on these results, carvacrol, citral, and thymol appear effective against Prototheca species at the tested concentrations, and may thus be useful for environmental disinfection in barns.
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Monoterpenos Acíclicos , Cimenos , Testes de Sensibilidade Microbiana , Óleos Voláteis , Compostos Fitoquímicos , Prototheca , Timol , Óleos Voláteis/farmacologia , Timol/farmacologia , Animais , Prototheca/efeitos dos fármacos , Cimenos/farmacologia , Compostos Fitoquímicos/farmacologia , Monoterpenos Acíclicos/farmacologia , Bovinos , Monoterpenos/farmacologia , Feminino , Mastite Bovina/microbiologia , Mastite Bovina/tratamento farmacológicoRESUMO
Autism spectrum disorder (ASD) is caused by combined genetic and environmental factors. Genetic heritability in ASD is estimated as 60-90%, and genetic investigations have revealed many monogenic factors. We analyzed 405 patients with ASD using family-based exome sequencing to detect disease-causing single-nucleotide variants (SNVs), small insertions and deletions (indels), and copy number variations (CNVs) for molecular diagnoses. All candidate variants were validated by Sanger sequencing or quantitative polymerase chain reaction and were evaluated using the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines for molecular diagnosis. We identified 55 disease-causing SNVs/indels in 53 affected individuals and 13 disease-causing CNVs in 13 affected individuals, achieving a molecular diagnosis in 66 of 405 affected individuals (16.3%). Among the 55 disease-causing SNVs/indels, 51 occurred de novo, 2 were compound heterozygous (in one patient), and 2 were X-linked hemizygous variants inherited from unaffected mothers. The molecular diagnosis rate in females was significantly higher than that in males. We analyzed affected sibling cases of 24 quads and 2 quintets, but only one pair of siblings shared an identical pathogenic variant. Notably, there was a higher molecular diagnostic rate in simplex cases than in multiplex families. Our simulation indicated that the diagnostic yield is increasing by 0.63% (range 0-2.5%) per year. Based on our simple simulation, diagnostic yield is improving over time. Thus, periodical reevaluation of ES data should be strongly encouraged in undiagnosed ASD patients.
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A number of genomic mutations that are thought to be strongly involved in the development of schizophrenia (SCZ) and autism spectrum disorder (ASD) have been identified. Abnormalities involving oligodendrocytes have been reported in SCZ, and as a related gene, oligodendrocyte lineage transcription factor 2 (OLIG2) has been reported to be strongly associated with SCZ. In this study, based on the common disease-rare variant hypothesis, target sequencing of candidate genes was performed to identify rare mutations with a high effect size and the possibility that the identified mutations may increase the risks of SCZ and ASD in the Japanese population. In this study, the exon region of OLIG2 was targeted; 370 patients with SCZ and 192 with ASD were subjected to next-generation sequencing. As a result, one rare missense mutation (A33T) was detected. We used the Sanger method to validate this missense mutation with a low frequency (<1%), and then carried out a genetic association analysis involving 3299 unrelated individuals (1447 with SCZ, 380 with ASD, and 1472 healthy controls) to clarify whether A33T was associated with SCZ or ASD. A33T was not found in either case group, and in only one control. We did not find evidence that p.A33T is involved in the onset of ASD or SCZ; however, associations with this variant need to be evaluated in larger samples to confirm our results.
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Transtorno do Espectro Autista , Fator de Transcrição 2 de Oligodendrócitos , Esquizofrenia , Transtorno do Espectro Autista/genética , Humanos , Mutação , Mutação de Sentido Incorreto/genética , Fator de Transcrição 2 de Oligodendrócitos/genética , Esquizofrenia/genéticaRESUMO
Autism spectrum disorder (ASD) is a highly heritable, complex disorder in which rare variants contribute significantly to disease risk. Although many genes have been associated with ASD, there have been few genetic studies of ASD in the Japanese population. In whole exomes from a Japanese ASD sample of 309 cases and 299 controls, rare variants were associated with ASD within specific neurodevelopmental gene sets, including highly constrained genes, fragile X mental retardation protein target genes, and genes involved in synaptic function, with the strongest enrichment in trans-synaptic signaling (p = 4.4 × 10-4, Q-value = 0.06). In particular, we strengthen the evidence regarding the role of ABCA13, a synaptic function-related gene, in Japanese ASD. The overall results of this case-control exome study showed that rare variants related to synaptic function are associated with ASD susceptibility in the Japanese population.
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Transtorno do Espectro Autista , Exoma , Transtorno do Espectro Autista/genética , Estudos de Casos e Controles , Exoma/genética , Predisposição Genética para Doença , Humanos , JapãoRESUMO
BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (<100 kb) exonic deletions in BD, which contrasted with the highest burden of larger (>500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25-0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD.
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Transtorno do Espectro Autista , Transtorno Bipolar , Esquizofrenia , Transtorno do Espectro Autista/genética , Transtorno Bipolar/genética , Cromatina , Variações do Número de Cópias de DNA/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Humanos , Esquizofrenia/genéticaRESUMO
The Parental Bonding Instrument (PBI) evaluates parental attitudes derived from an individual's childhood experiences with their parents. The factor structure of the PBI differs depending on variables such as psychosocial factors including culture, race, sex, and psychological and social conditions of participants. Although previous studies of the relationships between perinatal depression and parenting experiences have used the factor structures of the PBI from the general population, it is unclear whether the same factor structures are appropriate in the highly variable perinatal period. In this study, complete responses to the PBI and the Edinburgh Postnatal Depression Scale (EPDS) were received from 932 primiparas at 25 weeks of gestation and at 1 month postpartum. An exploratory factor analysis was performed on half of the responses, and it was confirmed that the three factors were care, interference, and autonomy. Confirmatory factor analysis of the remaining half of the answers showed comprehensible fitness. Each factor showed a high degree of internal consistency, and each factor of the PBI correlated with the EPDS, indicating construct validity. The reliability and validity of the PBI in perinatal Japanese women were confirmed, and it was found that the PBI had a three-factor structure.
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Relações Pais-Filho , Poder Familiar/psicologia , Pais/psicologia , Gestantes/psicologia , Adulto , Análise Fatorial , Feminino , Humanos , Japão/epidemiologia , Enfermagem Neonatal , Apego ao Objeto , Gravidez , Escalas de Graduação Psiquiátrica , Adulto JovemRESUMO
INTRODUCTION: Temperament and character of pregnant women, especially harm avoidance (HA) and self-directedness (SD) have been identified as risk factors for postpartum depression, in addition to poor social support. However, the relationship between these personality traits and social support for depressive symptoms after delivery has not been examined. METHODS: Data were extracted from a prospective cohort survey on pregnant women conducted in Nagoya, Japan that included the Temperament and Character Inventory (TCI), the Social Support Questionnaire (J-SSQ), and the Edinburgh Postnatal Depression Scale (EPDS) at approximately week 25 and 1 month postpartum. A mediation analysis using structural equation modeling (SEM) was used to test if social support in pregnancy is a mediator between personality traits and postpartum depressive symptoms. RESULTS: Thousand five hundred and fifty-nine women were included in the analysis. Both harm avoidance and SD were significantly associated with depressive symptoms (total effect: ß [SE], 0.298 [0.041], P < 0.001 for harm avoidance; total effect: ß [SE], -0.265 [0.067], P < 0.001 for SD). Mediation analysis showed that the effect of harm avoidance on depressive symptoms was partially mediated by low social support (direct effect: ß [SE], 0.193 [0.004], P < 0.001; indirect effect: ß [SE], 0.082 [0.034], P = 0.015). Self-directedness on depressive symptoms was not found to be mediated by low social support. CONCLUSION: Results indicate that poor social support worsens depressive symptoms in women with high HA during pregnancy. Limitations include a possible selection bias due to the limited target facilities; most variables being evaluated based on self-report questionnaires, and different number of samples available for analysis between harm avoidance and SD.
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Disabled 1 (DAB1) is an intracellular adaptor protein in the Reelin signaling pathway and plays an essential role in correct neuronal migration and layer formation in the developing brain. DAB1 has been repeatedly reported to be associated with neurodevelopmental disorders including schizophrenia (SCZ) and autism spectrum disorders (ASD) in genetic, animal, and postmortem studies. Recently, increasing attention has been given to rare single-nucleotide variants (SNVs) found by deep sequencing of candidate genes. In this study, we performed exon-targeted resequencing of DAB1 in 370 SCZ and 192 ASD patients using next-generation sequencing technology to identify rare SNVs with a minor allele frequency <1%. We detected two rare missense mutations (G382C, V129I) and then performed a genetic association study in a sample comprising 1763 SCZ, 380 ASD, and 2190 healthy control subjects. Although no statistically significant association with the detected mutations was observed for either SCZ or ASD, G382C was found only in the case group, and in silico analyses and in vitro functional assays suggested that G382C alters the function of the DAB1 protein. The rare variants of DAB1 found in the present study should be studied further to elucidate their potential functional relevance to the pathophysiology of SCZ and ASD.
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Dysregulation of epigenetic processes involving histone methylation induces neurodevelopmental impairments and has been implicated in schizophrenia (SCZ) and autism spectrum disorder (ASD). Variants in the gene encoding lysine demethylase 4C (KDM4C) have been suggested to confer a risk for such disorders. However, rare genetic variants in KDM4C have not been fully evaluated, and the functional impact of the variants has not been studied using patient-derived cells. In this study, we conducted copy number variant (CNV) analysis in a Japanese sample set (2605 SCZ and 1141 ASD cases, and 2310 controls). We found evidence for significant associations between CNVs in KDM4C and SCZ (p = 0.003) and ASD (p = 0.04). We also observed a significant association between deletions in KDM4C and SCZ (corrected p = 0.04). Next, to explore the contribution of single nucleotide variants in KDM4C, we sequenced the coding exons in a second sample set (370 SCZ and 192 ASD cases) and detected 18 rare missense variants, including p.D160N within the JmjC domain of KDM4C. We, then, performed association analysis for p.D160N in a third sample set (1751 SCZ and 377 ASD cases, and 2276 controls), but did not find a statistical association with these disorders. Immunoblotting analysis using lymphoblastoid cell lines from a case with KDM4C deletion revealed reduced KDM4C protein expression and altered histone methylation patterns. In conclusion, this study strengthens the evidence for associations between KDM4C CNVs and these two disorders and for their potential functional effect on histone methylation patterns.
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Transtorno do Espectro Autista , Esquizofrenia , Transtorno do Espectro Autista/genética , Variações do Número de Cópias de DNA , Predisposição Genética para Doença , Histona Desmetilases/genética , Histonas , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Esquizofrenia/genéticaRESUMO
The proportion of women who experience a depressive state after delivery differs between primiparas and multiparas, so it is important to clarify the different factors related to depression between the two groups. In this study, we confirmed the differences in depressive states, the perinatal period, and social support between primiparas and multiparas, and clarified their characteristics. Data were extracted from a prospective cohort questionnaire survey conducted on pregnant women in Japan that included sociodemographic questions, the Edinburgh Postnatal Depression Scale, and the Japanese version of the Social Support Questionnaire. We carried out the chi-square test, Student's t-test, and analysis of covariance to compare responses between primiparas and multiparas. A total of 1138 primiparas and 380 multiparas provided valid responses. We found that primiparas had higher rates of experiencing maternity blues and postpartum depression than multiparas. We also found that primiparas had higher anxiety scores than multiparas. Primiparas with postpartum depression perceived a lower number of persons available to provide social support than primiparas without postpartum depression. These findings suggest that it is important to provide pregnant women, especially for primiparas, with information that allows them to increase the number of people who can provide them with support.
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Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/psicologia , Parto/psicologia , Adulto , Ansiedade/psicologia , Transtornos de Ansiedade/psicologia , Estudos de Coortes , Depressão/psicologia , Transtorno Depressivo/psicologia , Feminino , Humanos , Japão/epidemiologia , Paridade/fisiologia , Período Pós-Parto , Gravidez , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Apoio Social , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Rare genetic variants contribute to the etiology of both autism spectrum disorder (ASD) and schizophrenia (SCZ). Most genetic studies limit their focus to likely gene-disrupting mutations because they are relatively easier to interpret their effects on the gene product. Interpretation of missense variants is also informative to some pathophysiological mechanisms of these neurodevelopmental disorders; however, their contribution has not been elucidated because of relatively small effects. Therefore, we characterized missense variants detected in NRXN1, a well-known neurodevelopmental disease-causing gene, from individuals with ASD and SCZ. METHODS: To discover rare variants with large effect size and to evaluate their role in the shared etiopathophysiology of ASD and SCZ, we sequenced NRXN1 coding exons with a sample comprising 562 Japanese ASD and SCZ patients, followed by a genetic association analysis in 4273 unrelated individuals. Impact of each missense variant detected here on cell surface expression, interaction with NLGN1, and synaptogenic activity was analyzed using an in vitro functional assay and in silico three-dimensional (3D) structural modeling. RESULTS: Through mutation screening, we regarded three ultra-rare missense variants (T737M, D772G, and R856W), all of which affected the LNS4 domain of NRXN1α isoform, as disease-associated variants. Diagnosis of individuals with T737M, D772G, and R856W was 1ASD and 1SCZ, 1ASD, and 1SCZ, respectively. We observed the following phenotypic and functional burden caused by each variant. (i) D772G and R856W carriers had more serious social disabilities than T737M carriers. (ii) In vitro assay showed reduced cell surface expression of NRXN1α by D772G and R856W mutations. In vitro functional analysis showed decreased NRXN1α-NLGN1 interaction of T737M and D772G mutants. (iii) In silico 3D structural modeling indicated that T737M and D772G mutations could destabilize the rod-shaped structure of LNS2-LNS5 domains, and D772G and R856W could disturb N-glycan conformations for the transport signal. CONCLUSIONS: The combined data suggest that missense variants in NRXN1 could be associated with phenotypes of neurodevelopmental disorders beyond the diagnosis of ASD and/or SCZ.
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Transtorno do Espectro Autista , Proteínas de Ligação ao Cálcio/genética , Moléculas de Adesão de Célula Nervosa/genética , Esquizofrenia , Transtorno do Espectro Autista/genética , Éxons , Heterozigoto , Humanos , Mutação , Esquizofrenia/genéticaRESUMO
INTRODUCTION: A history of major depressive disorder before pregnancy is one risk factor for peripartum depression. Therefore, the purpose of the present study was to examine the validation and factor structure of the Japanese version of the Inventory to Diagnose Depression, Lifetime version (IDDL) for pregnant women. METHODS: The study participants were 556 pregnant women. Factor analysis was performed to identify the factor structure, construct validity was examined based on the results of the factor analysis, and reliability was examined using Cronbach's α coefficient. RESULTS: Based on the results of the factor analysis of the IDDL, a bifactor model composed of a single general dimension along with the following five factors was extracted: (1) depression, anxiety, and irritability (items 1, 2, 8-10, and 19-21); (2) retardation, decreased concentration, indecisiveness, and insomnia (items 4, 11, 12, and 17); (3) decrease in appetite/significant weight loss (items 13 and 14); (4) increase in appetite/significant weight gain (items 15 and 16); and (5) diminished interest, pleasure, and libido (items 5-7). Cronbach's α coefficients for these five factors were as follows: 0.910, 0.815, 0.780, 0.683, and 0.803, respectively. CONCLUSIONS: The reliability, construct validity, and factor structure of the Japanese version of the IDDL were confirmed in pregnant women.
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Depressão/diagnóstico , Idioma , Complicações na Gravidez/diagnóstico , Adulto , Estudos de Coortes , Feminino , Humanos , Japão , Gravidez , Complicações na Gravidez/psicologia , Psicometria , Adulto JovemRESUMO
INTRODUCTION: The aim of the present study was to elucidate the foreseeable risk factors for suicidal ideation among Japanese perinatal women. METHODS: This cohort study was conducted in Nagoya, Japan, from July 2012 to March 2018. The Edinburgh Postnatal Depression Scale (EPDS) questionnaire was conducted at four time points: early pregnancy, late pregnancy, 5 days postpartum, and 1 month postpartum. A total of 430 women completed the questionnaires. A logistic regression analysis was performed using the presence of suicidal ideation on the EPDS as an objective variable. The explanatory variables were age, presence of physical or mental disease, smoking and drinking habits, education, hospital types, EPDS total score in early pregnancy, bonding, and quality and amount of social support, as well as the history of major depressive disorder (MDD). RESULTS: The rate of participants who were suspected of having suicidal ideation at any of the four time points was 11.6% (n=52), with the highest (n=25, 5.8%) at late pregnancy. For suicidal ideation, education level (OR: 1.19; 95% CI: 1.00-1.41; p=0.047), EPDS total points in the pregnancy period (OR: 1.25; 95% CI: 1.16-1.34; p < 0.000), a history of MDD (OR: 2.16; 95% CI: 1.00-4.79; p=0.049), and presence of mental disease (OR: 2.39; 95% CI: 1.00-5.70; p=0.049) were found to be risk factors for suicidal ideation. Age [odds ratio (OR): 0.88; 95% confidence interval (CI): 0.80-0.95; p=.002] and quality of social support (OR: 0.77; 95% CI: 0.60-0.99; p=.041) were found to be protective factors. CONCLUSION: Based on these results, effective preventive interventions, such as increasing the quality of social support and confirming the history of depression, should be carried out in pregnant depressive women at the early stage of the perinatal period.
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Introduction: The relationship between perinatal depressive symptoms, harm avoidance (HA), and a history of major depressive disorder (MDD) was examined in a prospective cohort study. Methods: This study was conducted from May 1, 2011, to December 31, 2016. A history of MDD was evaluated using the Inventory to Diagnose Depression, Lifetime version during pregnancy. Depressive state and HA were evaluated during pregnancy and at 1 month postnatal using the Edinburgh Postnatal Depression Scale (EPDS) and Temperament and Character Inventory, respectively. The relationship between these variances was examined using structural equation modeling. Results: A total of 338 participants with complete data were included in the present study. Pregnant women with compared with those without a history of MDD were observed to have a significantly higher intensity of HA and more severe depressive symptoms in both the prenatal and postnatal periods. A history of MDD affected the severity of depressive symptoms [standardized path coefficient (SPC) = 0.25, p < 0.001] and the intensity of HA during pregnancy (SPC = 0.36, p < 0.001). The intensity of HA during pregnancy affected that at 1 month postnatal (SPC = 0.78, p < 0.001), while the severity of depressive symptoms as assessed by the EPDS during pregnancy affected that at 1 month postnatal (SPC = 0.41, p < 0.001). The SPC for perinatal HA to postnatal depressive symptoms (SPC = 0.13, p = 0.014) was significant and higher than that for perinatal depressive symptoms to postnatal HA (SPC = 0.06, p = 0.087). Conclusion: The present results suggest that early intervention in pregnant women with a history of MDD or a high intensity of HA is important to prevent postnatal depressive symptoms.
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BACKGROUND: The Great East Japan Earthquake (GEJE) and tsunami of March 11, 2011 left behind many survivors, including children. This study aimed to assess changes in traumatic symptoms with time among kindergarteners who experienced GEJE as infants and to discuss the relationship between these symptoms and the disaster experience. METHODS: The 15-item Post-Traumatic Stress Symptoms for Children (PTSSC-15) questionnaire were distributed to the parents of kindergarteners (children aged 4-5 years) at 8, 20, 30, and 42 months after GEJE. Questionnaires regarding environmental damage conditions affecting the children were distributed to teachers 8 months after the tsunami. RESULTS: The number of kindergarteners was 262, 255, 236, and 202 at 8, 20, 30, and 42 months after the disaster. The PTSSC-15 total score was not different between kindergartners with and without environmental damage conditions. After 8 and 20 months, the PTSSC-15 total score of children who usually ate breakfast was significantly higher than that of children who did not. Moreover, after 30 and 42 months, the PTSSC-15 total score of kindergarteners who usually ate breakfast was not significantly higher than that of kindergarteners who did not. CONCLUSIONS: The traumatic symptoms of kindergarteners were not related to disaster experiences.
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Terremotos/estatística & dados numéricos , Trauma Psicológico/epidemiologia , Sobreviventes/estatística & dados numéricos , Tsunamis/estatística & dados numéricos , Pré-Escolar , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Japão/epidemiologia , Masculino , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Postpartum depression (PPD) is a major depressive disorder that occurs after childbirth. Objective diagnostic and predictive methods for PPD are important for early detection and appropriate intervention. DNA methylation has been recognized as a potential biomarker for major depressive disorder. In this study, we used methylation analysis and peripheral blood to search for biomarkers that could to lead to the development a predictive method for PPD. METHODS: Study participants included 36 pregnant women (18 cases and 18 controls determined after childbirth). Genome-wide DNA methylation profiles were obtained by analysis with an Infinium Human Methylation 450BeadChip. The association of DNA methylation status at each DNA methylation site with PPD was assessed using linear regression analysis. We also conducted functional enrichment analysis of PPD using The Database for Annotation, Visualization and Integrated Discovery 6.8 to explore enriched functional-related gene groups for PPD. RESULTS: In the analysis with postpartum depressed state as an independent variable, the difference in methylation frequency between the postpartum non-depressed group and the postpartum depressed group was small, and sites with genome-wide significant differences were not confirmed. After analysis by The Database for Annotation, Visualization and Integrated Discovery 6.8, we revealed four gene ontology terms, including axon guidance, related to postpartum depression. CONCLUSIONS: These findings may help with the development of an objective predictive method for PPD.
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Metilação de DNA/genética , Depressão Pós-Parto/genética , Depressão Pós-Parto/psicologia , Estudo de Associação Genômica Ampla/métodos , Adulto , Estudos de Casos e Controles , Parto Obstétrico/psicologia , Depressão Pós-Parto/diagnóstico , Diagnóstico Precoce , Feminino , Humanos , Parto/genética , Parto/psicologia , Gravidez , Fatores de RiscoRESUMO
BACKGROUND: Many women experience depressive symptoms during pregnancy and postpartum periods. These depressive symptoms are often accompanied by other inflammatory morbidities present during pregnancy. Tryptophan (TRP) metabolism has attracted considerable attention due to its influence on the onset of depression via induction of inflammation. We examined the changes in plasma levels of TRP metabolites in pregnant women with depressive symptoms during pregnancy and/or the postpartum period. METHODS: In line with a previous analysis using the Edinburgh Postnatal Depression Scale (EPDS), participants were divided into a non-depressive (ND) group, a postpartum depressive (PD) group, a temporary gestational depressive (TG) group, and a continuous depressive (CD) group. Blood samples were collected before and 1 month after delivery. The concentrations of plasma TRP metabolites were measured using high-performance liquid chromatography (HPLC). RESULTS: There are differences in plasma levels of TRP metabolites during pregnancy and postpartum periods between the ND group and the PD group, but not the TG or CD group. In the PD group, plasma levels of kynurenine (KYN) and kynurenic acid (KA), and KYN/TRP and KA/KYN ratio during the pregnancy period were higher and 3-hydroxyanthranilic acid (3HAA) during the postpartum period was lower than those in the ND group. LIMITATIONS: Histories regarding mood disorders before pregnancy were not assessed. CONCLUSIONS: The higher plasma levels of KYN and KA, and KYN/TRP and KA/KYN ratio during pregnancy period and lower plasma level of 3HAA during the postpartum period could be useful predictive and diagnostic markers of postpartum depressive symptoms.
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Depressão/metabolismo , Ácido Cinurênico/sangue , Cinurenina/sangue , Período Pós-Parto/metabolismo , Gravidez/metabolismo , Triptofano/metabolismo , Adulto , Depressão/diagnóstico , Feminino , Humanos , Inflamação/metabolismo , Escalas de Graduação Psiquiátrica , Triptofano/sangueRESUMO
Early detection of perinatal depression is an urgent issue. Our study aimed to examine the construct validity and factor structure of the Japanese version of the Edinburgh Postnatal Depression Scale (EPDS) from a prospective cohort study from pregnancy to postpartum. A total of 1075 women completed all items of the EPDS at four time points: early pregnancy, late pregnancy, 5 days postpartum and 1 month postpartum. The participants were randomly divided into two sample sets. The first sample set (n = 304) was used for exploratory factor analysis, and the second sample set (n = 771) was used for confirmatory factor analysis. As a result, the Cronbach's alpha coefficients of the EPDS items were 0.762, 0.740, 0.765 and 0.772 at the four time points. From the confirmatory factor analysis of the EPDS in a sample set of Japanese women from pregnancy to postpartum, the following three factors were detected: depression (items 7, 9), anxiety (items 4, 5) and anhedonia (items 1, 2). In conclusion, the EPDS is a useful rating scale, and its factor structure is consistently stable during the whole peripartum period.
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Depressão Pós-Parto/diagnóstico , Adulto , Anedonia , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Depressão/diagnóstico , Depressão/epidemiologia , Depressão Pós-Parto/epidemiologia , Diagnóstico Precoce , Feminino , Humanos , Japão/epidemiologia , Período Periparto , Período Pós-Parto , Gravidez , Estudos Prospectivos , Escalas de Graduação PsiquiátricaRESUMO
Compelling evidence in Caucasian populations suggests a role for copy-number variations (CNVs) in autism spectrum disorder (ASD) and schizophrenia (SCZ). We analyzed 1,108 ASD cases, 2,458 SCZ cases, and 2,095 controls in a Japanese population and confirmed an increased burden of rare exonic CNVs in both disorders. Clinically significant (or pathogenic) CNVs, including those at 29 loci common to both disorders, were found in about 8% of ASD and SCZ cases, which was significantly higher than in controls. Phenotypic analysis revealed an association between clinically significant CNVs and intellectual disability. Gene set analysis showed significant overlap of biological pathways in both disorders including oxidative stress response, lipid metabolism/modification, and genomic integrity. Finally, based on bioinformatics analysis, we identified multiple disease-relevant genes in eight well-known ASD/SCZ-associated CNV loci (e.g., 22q11.2, 3q29). Our findings suggest an etiological overlap of ASD and SCZ and provide biological insights into these disorders.
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Transtorno do Espectro Autista/genética , Variações do Número de Cópias de DNA/genética , Esquizofrenia/genética , Adolescente , Adulto , Criança , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Estresse Oxidativo/fisiologia , Adulto JovemRESUMO
BACKGROUND: Although previous studies have reported associations between bonding failure, depression, social support among mothers, and perceived rearing, the causal relationships remain unclear. METHODS: A total of 855 women (mean age, 32.4⯱â¯4.4 years) completed the Mother-Infant Bonding Questionnaire (MIBQ), the Edinburgh Postnatal Depression Scale (EPDS), the Japanese version of the Social Support Questionnaire, and the Parental Bonding Instrument in early pregnancy before week 25 (T1) and at 1 month after delivery (T2). We created a path model to clarify the causal relationships between perinatal bonding failure, depression, social support, and perceived rearing during pregnancy and at 1 month after delivery. The model was tested using structural equation modeling. RESULTS: Our recursive model showed acceptable fit (chi-squared statistic/degree of freedomâ¯=â¯2.1, comparative fit indexâ¯=â¯0.98, root mean square error of approximationâ¯=â¯0.04). It was revealed that: (1) at T1, higher overprotection significantly predicted MIBQ scores; (2) at T1, poorer social support significantly predicted both MIBQ and EPDS scores; and (3) at T1, both MIBQ and EPDS scores significantly predicted respective scores at T2. CONCLUSIONS: These results showed that bonding failure in the postpartum period was significantly influenced by mothers' own perceived rearing and social support during pregnancy. In addition, depression in the postpartum period was strongly influenced by social support during pregnancy. These findings suggest that psychosocial interventions that focus on both mothers' recollections of their own upbringing and social support during pregnancy are effective for preventing bonding failure and depression in the postpartum period.