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1.
Biol Psychiatry ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31570195

RESUMO

BACKGROUND: The prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression. METHODS: We fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10-6) and a candidate threshold (1.6 × 10-4). RESULTS: No HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99). CONCLUSIONS: We found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.

2.
Neuroimage Clin ; 22: 101695, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30738374

RESUMO

OBJECTIVES: So far, few studies have investigated cortical thickness (CT) and surface area (SA) measures in bipolar disorder type I (BDI) in comparison to a high genetic risk group such as first-degree relatives (FR). This study aimed to examine CT and SA differences between BDI, FR and healthy controls (HC). METHODS: 3D T1 magnetic resonance images were acquired from 27 euthymic BDI patients, 24 unaffected FR and 29 HC. CT and SA measures were obtained with FreeSurfer version 5.3.0. Generalized estimating equations were used to compare CT and SA between groups. Group comparisons were repeated with restricting the FR group to 17 siblings (FR-SB) only. RESULTS: \Mean age in years was 36.3 ±â€¯9.5 for BDI, 32.1 ±â€¯10.9 for FR, 34.7 ±â€¯9.8 for FR-SB and 33.1 ±â€¯9.0 for HC group respectively. BDI patients revealed larger SA of left pars triangularis (LPT) compared to HC (p = .001). In addition, increased SA in superior temporal cortex (STC) in FR-SB group compared to HC was identified (p = .0001). CONCLUSIONS: Our result of increased SA in LPT of BDI could be a disease marker and increased SA in STC of FR-SB could be a marker related with resilience to illness.

3.
Mol Psychiatry ; 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30626913

RESUMO

Although a genetic basis of depression has been well established in twin studies, identification of genome-wide significant loci has been difficult. We hypothesized that bivariate analyses of findings from a meta-analysis of genome-wide association studies (meta-GWASs) of the broad depression phenotype with those from meta-GWASs of self-reported and recurrent major depressive disorder (MDD), bipolar disorder and schizophrenia would enhance statistical power to identify novel genetic loci for depression. LD score regression analyses were first used to estimate the genetic correlations of broad depression with self-reported MDD, recurrent MDD, bipolar disorder and schizophrenia. Then, we performed four bivariate GWAS analyses. The genetic correlations (rg ± SE) of broad depression with self-reported MDD, recurrent MDD, bipolar disorder and schizophrenia were 0.79 ± 0.07, 0.24 ± 0.08, 0.53 ± 0.09 and 0.57 ± 0.05, respectively. From a total of 20 independent genome-wide significant loci, 13 loci replicated of which 8 were novel for depression. These were MUC21 for the broad depression phenotype with self-reported MDD and ZNF804A, MIR3143, PSORS1C2, STK19, SPATA31D1, RTN1 and TCF4 for the broad depression phenotype with schizophrenia. Post-GWAS functional analyses of these loci revealed their potential biological involvement in psychiatric disorders. Our results emphasize the genetic similarities among different psychiatric disorders and indicate that cross-disorder analyses may be the best way forward to accelerate gene finding for depression, or psychiatric disorders in general.

4.
Psychiatr Genet ; 29(2): 57-60, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30531648

RESUMO

Schizophrenia is a genetically complex disease that is related to neurodevelopmental abnormalities. Several genetic polymorphisms and genetic syndromes associated with neurodevelopmental processes have been linked to schizophrenia. In this case report, we present a case with an association between microcephalic osteodysplastic primordial dwarfism type II and schizophrenia. Microcephalic osteodysplastic primordial dwarfism type II syndrome is a rare, autosomal recessive disease that occurs as a result of the mutations in the pericentrin (PCNT) gene that are responsible for cell cycle and division. In this report, we discuss the possible association between the PCNT gene and schizophrenia.


Assuntos
Antígenos/genética , Nanismo/genética , Retardo do Crescimento Fetal/genética , Microcefalia/genética , Osteocondrodisplasias/genética , Esquizofrenia/genética , Adulto , Nanismo/complicações , Feminino , Humanos , Microcefalia/complicações , Mutação , Osteocondrodisplasias/complicações , Síndrome
5.
Nat Genet ; 50(5): 668-681, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29700475

RESUMO

Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.

6.
Am J Geriatr Psychiatry ; 26(4): 451-460, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29329723

RESUMO

OBJECTIVE: Bereavement can result in unresolved and prolonged grief, often termed prolonged grief disorder (PGD). The impact of PGD on cognitive functioning is poorly understood. The aim of the study was to compare the cognitive decline, assessed by repeated measures of different cognition domains, between persons with normal and PGD and a non-grieving reference population in a 7-year follow-up study. METHODS: The study sample comprised 3126 non-demented persons, mean age: 64 years, of the Rotterdam Study. Participants were classified into three groups: no grief (reference group, N = 2,582), normal grief (N = 418), and prolonged grief disorder (N = 126). Participants were assessed with the Complicated Grief Inventory and underwent cognitive testing (Mini-Mental State Examination [MMSE], Letter-Digit Substitution test, Stroop test, Word fluency task, Word learning test). Analyses were adjusted for baseline cognition and depressive symptoms; persons with major depressive disorders were excluded. RESULTS: Compared with the reference group, participants with PGD showed a decrease in global cognitive function, MMSE scores, and World learning test (immediate and delayed) over time. Participants with normal grief did not show a stronger cognitive decline in any of cognitive tests than the reference group. CONCLUSIONS: Participants with PGD showed a stronger cognitive decline than the reference group during 7 years of follow-up. This suggests that PGD is a risk factor for cognitive decline, but this study cannot detect the psychobiological mechanism underlying this longitudinal association.

8.
Psychoneuroendocrinology ; 85: 88-95, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28843169

RESUMO

Cortisol is an important stress hormone affected by a variety of biological and environmental factors, such as the circadian rhythm, exercise and psychological stress. Cortisol is mostly measured using blood or saliva samples. A number of genetic variants have been found to contribute to cortisol levels with these methods. While the effects of several specific single genetic variants is known, the joint genome-wide contribution to cortisol levels is unclear. Our aim was to estimate the amount of cortisol variance explained by common single nucleotide polymorphisms, i.e. the SNP heritability, using a variety of cortisol measures, cohorts and analysis approaches. We analyzed morning plasma (n=5705) and saliva levels (n=1717), as well as diurnal saliva levels (n=1541), in the Rotterdam Study using genomic restricted maximum likelihood estimation. Additionally, linkage disequilibrium score regression was fitted on the results of genome-wide association studies (GWAS) performed by the CORNET consortium on morning plasma cortisol (n=12,597) and saliva cortisol (n=7703). No significant SNP heritability was detected for any cortisol measure, sample or analysis approach. Point estimates ranged from 0% to 9%. Morning plasma cortisol in the CORNET cohorts, the sample with the most power, had a 6% [95%CI: 0-13%] SNP heritability. The results consistently suggest a low SNP heritability of these acute and short-term measures of cortisol. The low SNP heritability may reflect the substantial environmental and, in particular, situational component of these cortisol measures. Future GWAS will require very large sample sizes. Alternatively, more long-term cortisol measures such as hair cortisol samples are needed to discover further genetic pathways regulating cortisol concentrations.


Assuntos
Estudo de Associação Genômica Ampla , Hidrocortisona/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Países Baixos , Saliva/química
9.
J Sex Med ; 14(7): 918-927, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28673434

RESUMO

BACKGROUND: Despite a common misconception, older adults engage in sexual behavior. However, there is limited sexual behavior research in older adults, which is often restricted to small samples, to cohorts recruiting adults from 45 years old, and to questions regarding only sexual intercourse. AIM: To assess the cross-sectional prevalence of and characteristics associated with sexual activity and physical tenderness in community-dwelling older adults. METHODS: From the Rotterdam Study, sexual activity and physical tenderness were assessed in 2,374 dementia-free, community-dwelling men and women at least 65 years old from 2009 through 2012 in the Netherlands. Analyses were stratified by sex and partner status. OUTCOMES: Sexual activity and physical tenderness (eg, fondling or kissing) in the last 6 months. Potential associated characteristics included measurements of demographics, socioeconomic position, health behavior, and health status. RESULTS: The vast majority of partnered participants (men, n = 858; women, n = 724) had experienced physical tenderness in the previous 6 months (83.7% of men and 82.9% of women) and nearly half had engaged in sexual activity (49.5% and 40.4% respectively). Very few unpartnered women (n = 675) had engaged in sexual activity (1.3%) or physical tenderness (5.2%), whereas prevalence rates were slightly higher for unpartnered men (n = 117; 13.7% or 17.1%). Engaging in sexual behavior was generally associated with younger age, greater social support, healthier behaviors, and better physical and psychological health. CLINICAL IMPLICATIONS: Findings show that older adults engage in sexual activity. It is important not to assume that an older person is not interested in sexual pleasure or that an older person is unhappy with not having a sexual partner. Offering an opportunity for open discussion of sexuality and medical assistance without imposing is a difficult balance. We encourage health care professionals to proactively address sexuality and extend knowledge about safe sex and sexual function to older adults. STRENGTHS AND LIMITATIONS: Thus far, this is one of the largest samples of sexual behavior assessment in adults older than 60 years. Limitations of this study are common in sexual behavior research, including low sexual behavior engagement among unpartnered older adults and a small sample of unpartnered men, which restricted sex- and age-specific implications. CONCLUSION: Almost half of partnered older adults engaged in sexual activity and more than two thirds engaged in physical tenderness, but very few unpartnered older adults engaged in these behaviors. The greatest barrier to being sexually active at an older age is lack of a partner, which particularly affects women. Sexuality is an important aspect of active aging. Freak-Poli R, Kirkman M, De Castro Lima G, et al. Sexual Activity and Physical Tenderness in Older Adults: Cross-Sectional Prevalence and Associated Characteristics. J Sex Med 2017;14:918-927.


Assuntos
Envelhecimento/psicologia , Comportamento Sexual , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos Transversais , Exercício , Feminino , Nível de Saúde , Humanos , Masculino , Países Baixos , Exame Físico , Prevalência , Comportamento Sexual/psicologia , Parceiros Sexuais
10.
Nat Commun ; 8: 14977, 2017 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-28443625

RESUMO

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.


Assuntos
Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Obesidade/genética , Locos de Características Quantitativas/genética , Fumar/genética , Adiposidade/genética , Adulto , Distribuição da Gordura Corporal , Índice de Massa Corporal , Epistasia Genética , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único , Circunferência da Cintura/genética , Relação Cintura-Quadril
11.
Age Ageing ; 46(1): 101-107, 2017 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-28104602

RESUMO

Background: The relation between positive psychological well-being (PPWB) and sexual behaviour is understudied in older adult groups. Objective: To examine the relation between PPWB (positive affect and life satisfaction) and sexual behaviour (sexual activity and physical tenderness) in older adults, and whether it is independent from depressive symptoms and uniform across older age groups. Design: Cross-sectional. Setting: Community-dwelling adults aged 65 years or older, Rotterdam, The Netherlands. Methods: Sexual behaviour, the Cantril Self-Anchoring Striving Scale, the Center for Epidemiological Studies Depression (CES-D) scale and partner status were assessed in 2,373 dementia-free older adults from the Rotterdam Study. Results: For partnered participants, greater positive affect and life satisfaction was associated with more sexual activity and physical tenderness. Although CES-D was negatively associated with sexual behaviour within partnered older adults, there was no association between the negative affect sub-scale and sexual behaviour. The relations were independent of depressive symptoms, physical health and chronic disease status and were observed for both sexes at all older ages. For unpartnered participants, greater life satisfaction and was associated with more physical tenderness. There was low prevalence of sexual behaviour in unpartnered participants, limiting further stratification. Conclusion: Greater PPWB was associated with more sexual behaviour in partnered, community-dwelling older adults. We are the first to demonstrate that sexual behaviour is associated with PPWB, rather than lack of depressive symptoms; and that the association was present at all ages for partnered older adults. Limited conclusions can be drawn for unpartnered older adults as their sexual behaviour was infrequent.


Assuntos
Envelhecimento/psicologia , Depressão/psicologia , Felicidade , Estado Civil , Comportamento Sexual , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Depressão/diagnóstico , Feminino , Humanos , Masculino , Países Baixos , Satisfação Pessoal , Qualidade de Vida , Inquéritos e Questionários
12.
Biol Psychiatry ; 82(5): 322-329, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28049566

RESUMO

BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. METHODS: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. RESULTS: The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10-9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10-9). CONCLUSIONS: This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.


Assuntos
Depressão/genética , Transtorno Depressivo/genética , Loci Gênicos , Predisposição Genética para Doença , Hidrolases Anidrido Ácido/genética , Grupo com Ancestrais do Continente Europeu/genética , Estudo de Associação Genômica Ampla , Humanos , Proteínas de Neoplasias/genética , Fenótipo
13.
Psychosom Med ; 79(4): 426-433, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27879552

RESUMO

OBJECTIVE: Few studies have focused on the effect of complicated grief-unresolved and prolonged grief-on the neuroendocrine systems. The present study examined the association of complicated grief and normal grief with the diurnal cortisol patterns in a large population-based study. METHODS: This study was set in the Rotterdam Study and comprised 2084 persons aged older than 55 years (mean [SD] age, 64.9 [5.5] years). Participants were assessed with the Complicated Grief Inventory and classified into no grief (n = 1922), normal grief (n = 131), or complicated grief (n = 31) if they experienced the loss in the past 2 years. Saliva samples were collected to measure cortisol levels. Morning cortisol and summary measures (area under the curve and the slope) were studied to account for the diurnal pattern of cortisol. Persons with depressive disorders were excluded, and analyses were additionally adjusted for depressive symptoms. RESULTS: Compared to normal grievers, participants with complicated grief showed lower levels of morning cortisol (11.26 vs 15.51 nmol/L; difference, -4.24; 95% confidence interval [CI] = -7.87 to -0.62; p = .022), and lower levels of overall diurnal cortisol (6.89 vs 8.98 nmol/L; difference, -2.09; 95% CI = -3.81 to -0.37; p = .017). No difference was observed in slope between both groups. Participants with complicated grief also showed lower levels of morning cortisol than the nongrievers (11.26 vs 14.71; difference, -3.46; 95% CI = -6.78 to -0.13; p = .042). In contrast, cortisol secretion patterns did not differ between persons with normal grief and nongrieving controls. CONCLUSIONS: Participants with complicated grief showed low levels of morning cortisol and low overall diurnal cortisol levels characteristic for a chronic stress reaction.


Assuntos
Ritmo Circadiano , Pesar , Hidrocortisona/análise , Idoso , Ritmo Circadiano/fisiologia , Feminino , Humanos , Hidrocortisona/fisiologia , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores de Tempo
14.
PLoS One ; 11(10): e0164348, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27736954

RESUMO

Determinants of the hypothalamic-pituitary-adrenal (HPA) axis functioning are increasingly explored in population-based studies. However, functional tests measuring the negative feedback of the HPA axis cannot easily be implemented into large observational studies. Furthermore, high doses of dexamethasone often completely suppress the HPA axis in healthy persons. This study aimed to detect the effects of the health, lifestyle and sociodemographic factors, psychiatric problems and cognitive functions on the negative feedback of the HPA axis using a very low-dose (0.25 mg) dexamethasone suppression test (DST).We evaluated the associations of several determinants with the saliva cortisol concentrations after dexamethasone intake in a confounder-adjusted model also corrected for baseline saliva cortisol concentrations in the Rotterdam Study, a large population-based study (N = 1822). We found that female sex, low income, lack of exercise, instrumental disability and smoking were all independently associated with stronger suppression of the HPA axis. Even though there were no linear associations between psychiatric measures and cortisol suppression, we found that depressive symptoms and anxiety disorders were more common in persons with non-suppression of cortisol. Conversely, psychotropic medication use was related to enhanced suppression of cortisol after DST. In this large study, we found that female gender, low socioeconomic status and poor health were all related to suppression of the HPA axis. Non-linear associations were detected between the suppression of the HPA axis and common psychiatric disorders in community-dwelling persons.


Assuntos
Dexametasona/administração & dosagem , Hidrocortisona/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Saliva/efeitos dos fármacos , Transtornos de Ansiedade/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Dexametasona/farmacologia , Retroalimentação Fisiológica/efeitos dos fármacos , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/metabolismo , Fatores de Risco , Saliva/metabolismo
15.
Psychiatry Res Neuroimaging ; 253: 1-6, 2016 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-27254084

RESUMO

The vascular depression hypothesis postulates that cerebral small vessel disease can cause or exacerbate depression in elderly persons. Numerous studies explored the association of imaging markers of cerebral small vessel disease including white matter lesions (WMLs) and lacunar infarcts with depressive symptoms or disorders. However, cerebral microbleeds have not been tested in depression. In the current study, we aimed to explore the association of WMLs, lacunar infarcts and cerebral microbleeds with depression continuum in a large population-based sample, the Rotterdam Study. Study population consisted of 3799 participants (aged 45 or over) free of dementia. WML volumes, lacunar infarcts and cerebral microbleeds were measured with brain magnetic resonance imaging. Depressive symptoms, depressive disorders and co-morbid anxiety disorders were assessed with validated questionnaires and clinical interview. WML volumes and lacunar infarcts were associated with depressive symptoms and disorders. Cerebral microbleeds, especially in deep or infratentorial brain regions, were related to depressive disorders only. Our results indicate that WMLs and lacunar infarcts might be non-specific vascular lesions seen in depressive symptoms and disorders. Association of cerebral microbleeds with more severe forms of depression may indicate impaired brain iron homeostasis or minor episodes of cerebrovascular extraversion, which may play a role in depression etiology.


Assuntos
Encéfalo/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Depressão/diagnóstico por imagem , Transtorno Depressivo/diagnóstico por imagem , Idoso , Biomarcadores , Encéfalo/patologia , Doenças de Pequenos Vasos Cerebrais/patologia , Doenças de Pequenos Vasos Cerebrais/psicologia , Depressão/patologia , Depressão/psicologia , Transtorno Depressivo/patologia , Transtorno Depressivo/psicologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inquéritos e Questionários
16.
Schizophr Res ; 169(1-3): 199-203, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26386899

RESUMO

The aim of this study was to investigate the relationship between childhood trauma (CT) and cognitive functioning in individuals with ultra-high risk for psychosis (UHR). Fifty-three individuals at UHR for psychosis were administered a neurocognitive battery that assessed attention, processing speed, verbal learning, memory, working memory, interference inhibition, and sustained attention. The CT was assessed using the short-version Childhood Trauma Questionnaire (CTQ). We dichotomized the sample by using cut-off scores for the presence of emotional, physical and sexual trauma, and physical and emotional neglect. Those with a history of physical trauma performed worse on the Digit Span Forward test, Trail making B (time), Stroop test (difference between color and word reading times), and completed categories of the Wisconsin Card Sorting Test (WCST). Physical trauma scores were correlated with WCST-completed categories, Digit Span Forward and Stroop test scores. Physical neglect scores were negatively correlated with Digit Span Forward Test scores. Most of the significant dose­response relationships between cognitive impairment and different subtypes of CT were found only in men. There was no difference between those with and without other kinds of childhood abuse or neglect in terms of cognitive impairment. Our findings suggest that a history of physical trauma has a negative impact on cognitive function in individuals at UHR for psychosis.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Adolescente , Adulto , Feminino , Humanos , Testes de Inteligência , Masculino , Testes Neuropsicológicos , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
17.
J Psychiatr Res ; 62: 31-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25649181

RESUMO

It has been difficult to identify genes affecting drug response to Selective Serotonin Reuptake Inhibitors (SSRIs). We used multiple cross-sectional assessments of depressive symptoms in a population-based study to identify potential genetic interactions with SSRIs as a model to study genetic variants associated with SSRI response. This study, embedded in the prospective Rotterdam Study, included all successfully genotyped participants with data on depressive symptoms (CES-D scores). We used repeated measurement models to test multiplicative interaction between genetic variants and use of SSRIs on repeated CESD scores. Besides a genome-wide analysis, we also performed an analysis which was restricted to genes related to the serotonergic signaling pathway. A total of 273 out of 14,937 assessments of depressive symptoms in 6443 participants, use of an SSRI was recorded. After correction for multiple testing, no plausible loci were identified in the genome-wide analysis. However, among the top 10 independent loci with the lowest p-values, findings within two genes (FSHR and HMGB4) might be of interest. Among 26 genes related to the serotonergic signaling pathway, the rs6108160 polymorphism in the PLCB1 gene reached statistical significance after Bonferroni correction (p-value = 8.1e-5). Also, the widely replicated 102C > T polymorphism in the HTR2A gene showed a statistically significant drug-gene interaction with SSRI use. Therefore, the present study suggests that drug-gene interaction models on (repeated) cross-sectional assessments of depressive symptoms in a population-based study can identify potential loci that may influence SSRI response.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Depressão/genética , Farmacogenética , Polimorfismo de Nucleotídeo Único/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Planejamento em Saúde Comunitária , Estudos Transversais , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica
18.
Depress Anxiety ; 32(9): 684-92, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25693731

RESUMO

BACKGROUND: Disturbed circadian rhythms have been associated with depression and anxiety, but it is unclear if disturbances in the 24-hr activity rhythm and sleep are independently and specifically related to these disorders. METHODS: In 1,714 middle-aged and elderly participants of the Rotterdam Study, we collected actigraphy recordings of at least 96 hr (138 ± 14 hr, mean ± standard deviation). Activity rhythms were quantified calculating the fragmentation of the rhythm, stability of the rhythm over days, and timing of the rhythm. Total sleep time, sleep onset latency, and wake after sleep onset were also estimated with actigraphy. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression scale, persons with clinically relevant depressive symptoms were interviewed to diagnose DSM-IV-depressive disorder. Anxiety disorders were determined with the Munich version of the Composite International Diagnostic Interview. RESULTS: More fragmented rhythms were associated with clinically relevant depressive symptoms (odds ratio (OR): 1.27, 95% confidence interval (CI): 1.04;1.54) and anxiety disorders (OR: 1.39, 95% CI: 1.14;1.70) after covariate adjustment. Less stable rhythms, longer sleep onset latency, and more wake after sleep onset were related to clinically relevant depressive symptoms or anxiety disorders only if not adjusted for covariates and other activity rhythm and sleep indicators. CONCLUSIONS: Our study in middle-aged and elderly persons suggests that fragmentation of the 24-hr activity rhythm is associated with depression and anxiety. Moreover, this association also largely accounts for the effect of disturbed sleep on these psychiatric disorders.


Assuntos
Transtornos de Ansiedade/fisiopatologia , Ansiedade/fisiopatologia , Ritmo Circadiano , Depressão/fisiopatologia , Transtorno Depressivo/fisiopatologia , Transtornos do Sono-Vigília/fisiopatologia , Actigrafia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Projetos de Pesquisa , Sono
19.
Psychoneuroendocrinology ; 53: 207-16, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25635613

RESUMO

The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in sleep. Nevertheless, the association of sleep and its 24-h organization with negative feedback control of the HPA axis has received limited attention in population-based studies. We explored this association in 493 middle-aged persons of the Rotterdam Study, a large population-based study (mean age 56 years, standard deviation: 5.3 years; 57% female). The negative feedback of the HPA axis was measured as the change in morning saliva cortisol after the intake of 0.25mg dexamethasone the night before. Actigraphy allowed us to measure the stability and fragmentation of the activity rhythm and to estimate total sleep time, sleep onset latency and wake after sleep onset. A sleep diary kept during the week of actigraphy was used to assess self-reported total sleep time, sleep onset latency, number of awakenings and perceived sleep quality. In our study, enhanced negative feedback of the HPA axis was found in association with unstable activity rhythms (B=0.106, 95% confidence interval (CI): 0.002; 0.210), total sleep time (B=0.108, 95%CI: 0.001; 0.215) and poor subjective sleep quality (B=0.107, 95%CI: 0.009; 0.206) after multivariate adjustment. These results indicated that the 24-h organization, duration and experience of sleep are all associated with the negative feedback control of the HPA axis.


Assuntos
Ritmo Circadiano/efeitos dos fármacos , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Hidrocortisona/metabolismo , Atividade Motora/efeitos dos fármacos , Sono/efeitos dos fármacos , Actigrafia , Estudos de Coortes , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Saliva/química
20.
Turk Psikiyatri Derg ; 25(4): 264-81, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25487624

RESUMO

OBJECTIVE: To overview and evaluate the main findings, methodological shortcomings, and time trends of the recent psychiatric epidemiology studies in Turkey, as well as to provide areas prone for development in forthcoming research. METHOD: PubMed and Turkish Psychiatry Index were screened to identify relevant studies. Any epidemiological study from 2000 to 2012 with a general population or unique sub-population sample was included. Papers and results were classified as depression, anxiety, psychotic, dissociative, conversion, personality, alcohol and substance abuse, and trauma-related disorders, and common geriatric disorders. RESULTS: There are various epidemiological studies on various psychiatric disorders in Turkey. However, there are main shortcomings and trends in research that subsequently stagnate current psychiatric epidemiological research. First, epidemiological studies were mainly conducted for academic purposes, not for addressing epidemiological issues or issues of health policy. Second, studies mainly focused on particular fields and institutions, which led to non-systematic accumulation of epidemiological results. Third, although Turkey is a natural laboratory of social conflicts and disasters, there were few studies with a focus on probable outcomes. Fourth, high-quality epidemiological studies with disseminating results tended to decrease, even in common mental disorders such as depression. Fifth, there were very few epidemiological studies using contemporary designs such as follow-up, genetic, or biomarker data in the general-population. CONCLUSION: Although psychiatric epidemiological studies of the last decade provide a suitable ground for future challenges, current trends in this research area has tended to stagnate, despite the potential for unique contributions. Forthcoming studies and researchers may notice novel methodological developments in epidemiology, with a growing attention on rapid urbanization, natural disasters, social conflicts, and migration.


Assuntos
Epidemiologia/tendências , Transtornos Mentais/epidemiologia , Humanos , Turquia
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