RESUMEN
Telomeres are short tandem repeats of "TTAGGG" that protect the chromosome ends from deterioration or fusion of chromosomes. Their repeat length shortens with cell division acting as a biomarker of cellular aging. Traumatic stress events during adulthood or childhood have been associated with posttraumatic stress disorder (PTSD) and short leukocyte telomere length (LTL). This study investigated whether LTL was associated with PTSD in a Brazilian sample of sexually assaulted civilian women at two time points: baseline and 1-year follow-up. At baseline, we assessed 64 women with PTSD following sexual assault (cases) and 60 women with no previous history of sexual trauma or mental disorders (healthy controls - HC). At follow-up visit, 13 persistent PTSD cases, 11 HCs, and 11 PTSD remitters patients were evaluated. PTSD diagnosis and severity were assessed using Mini International Neuropsychiatric Interview (Diagnostic and Statistical Manual of Mental Disorders III/IV criteria) and Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), respectively. LTL was measured using multiplex real-time polymerase chain reaction (PCR). In the baseline analysis, we observed that LTL was associated with re-experiencing symptoms (B = -0.16; confidence interval (CI) 95% = -0.027--0.005; Bonferroni-adjusted p-value = 0.02), but no association was observed between other PTSD symptoms and LTL. In the longitudinal analysis, telomere shortening was no longer observed in patients with PTSD and PTSD remitters. In conclusion, our findings indicate that shorter baseline LTL is associated with early stage of PTSD re-experiencing symptoms in recently sexually assaulted women.
RESUMEN
We aimed to identify blood gene expression patterns associated to psychopathological trajectories retrieved from a large community, focusing on the emergence and remission of general psychiatric symptoms. Hundred and three individuals from the Brazilian High-Risk Cohort Study (BHRCS) for mental disorders were classified in four groups according to Child Behavior Checklist (CBCL) total score at the baseline (w0) and after 3 years (w1): low-high (L-H) (N = 27), high-low (H-L) (N = 12), high-high (H-H) (N = 34) and low-low (L-L) groups (N = 30). Blood gene expression profile was measured using Illumina HT-12 Beadchips, and paired analyses comparing w0 and w1 were performed for each group. Results: 98 transcripts were differentially expressed comparing w0 and w1 in the L-H, 33 in the H-L, 177 in the H-H and 273 in the L-L. Of these, 66 transcripts were differentially expressed exclusively in the L-H; and 6 only in the H-L. Cross-Lagged Panel Models analyses revealed that RPRD2 gene expression at w1 might be influenced by the CBCL score at w0. Moreover, COX5B, SEC62, and NDUFA2 were validated with another technique and were also differentially regulated in postmortem brain of subjects with mental disorders, indicating that they might be important not only to specific disorders, but also to general psychopathology and symptoms trajectories. Whereas genes related to metabolic pathways seem to be associated with the emergence of psychiatric symptoms, mitochondrial inner membrane genes might be important over the course of normal development. These results suggest that changes in gene expression can be detected in blood in different psychopathological trajectories.
Asunto(s)
Trastornos Mentales , Psicopatología , Adolescente , Brasil , Niño , Estudios de Cohortes , Expresión Génica , Humanos , Trastornos Mentales/genéticaRESUMEN
Obsessive-compulsive disorder (OCD) is one of 10 major debilitating neuropsychiatric disorders, according to the World Health Organization (WHO), affecting around 2.3% of people worldwide. Obsessive-compulsive symptoms are caused by shared or distinct genetic or environmental influences. Several imaging studies have detected white-matter alterations in OCD, and recent studies have demonstrated thatOCD is associated with variations in the OLIG2 gene. The aim of this study was to investigate whether OLIG2 gene is associated with OCD and its clinical features in a Brazilian sample. We genotyped three variants in OLIG2 gene, rs762178, rs1059004, and rs9653711 in 205 OCD patients and 202 healthy controls by Taqman® methodology. Genotypes and alleles distributions were analyzed by χ2 or Fisher exact tests. The rs762178 and rs9653711 polymorphisms were significantly associated with OCD (Pâ¯=â¯0.048 and 0.029, respectively). We also observed an association of rs1059004 and rs9653711 with the presence of Obsessive-Compulsive Inventory-Revised (OCI-R) obsessing (unacceptable thoughts) subscore (Pâ¯=â¯0.031 and 0.034, respectively). Moreover, the pair of loci consisting of rs762178 and rs9653711 A-G haplotype was associated with OCD (Pâ¯<â¯0.0001). The OLIG2 gene may be involved in OCD, particularly in patients showing nasty, unpleasant and uncontrollable thoughts. However, more studies in larger samples are needed to replicate these findings.
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Predisposición Genética a la Enfermedad/genética , Trastorno Obsesivo Compulsivo/genética , Factor de Transcripción 2 de los Oligodendrocitos/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Adulto , Anciano , Brasil , Femenino , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The etiology of obsessive-compulsive disorder (OCD) is largely unknown, but family, twin, neuroimaging, and pharmacological studies suggest that glutamatergic system plays a significant role on its underlying pathophysiology. We performed an association analysis of six Single Nucleotide Polymorphisms (SNPs) within SLC1A1 gene (rs12682807, rs2075627, rs3780412, rs301443, rs301430, rs301434) in a group of 199 patients and 200 healthy controls. Symptom profiles were evaluated using the Florida Obsessive-Compulsive Inventory (FOCI) and the Obsessive-Compulsive Inventory-Revised (OCI-R). SNPs were analyzed by Taqman® methodology (Thermo Fisher, Brazil). The genotype distributions were in Hardy-Weinberg equilibrium. The A-A-G (rs301434-rs3780412-rs301443) haplotype was twice as common in OCD as in controls (Pâ¯=â¯0.02). We also found significant differences between male patients and controls for rs301443 in a dominant model (Pâ¯=â¯0.04) and a protective effect of GG genotype of rs2072657 in women (Pâ¯=â¯0.02). Regarding clinical characteristics, the G-A (rs301434-rs3780412) haplotype was almost twice more common in patients with vs. without hoarding (Pâ¯=â¯0.04). Further analyses showed significant associations between hoarding and rs301434 (Pâ¯=â¯0.04) and rs3780412 (Pâ¯=â¯0.04) in women, both in a dominant model. A dominant effect was also observed on ordering dimension for rs301434 (Pâ¯=â¯0.01, in women) and rs301443 (Pâ¯=â¯0.04). Finally, the rs2072657 showed a recessive effect on neutralization (Pâ¯=â¯0.04) and checking (Pâ¯=â¯0.03, in men). These preliminary results demonstrated that the SLC1A1 may contribute to some extent the susceptibility to OCD and its symptoms. However, additional studies are still needed.
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Transportador 3 de Aminoácidos Excitadores/genética , Predisposición Genética a la Enfermedad/genética , Trastorno Obsesivo Compulsivo/genética , Adulto , Brasil , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Obsessive-Compulsive Disorder (OCD) is a complex and chronic disorder characterized by recurrent thoughts and/or repetitive behaviors. Given the potent anti-obsessional effects of the so-called serotonin reuptake inhibitors, genes related to serotonergic system may be well implicated in the etiopathogenesis of OCD. The gene encoding the serotonin transporter (SLC6A4), which shows a variable number of tandem repeat (VNTR) polymorphism in intron 2 (STin2), have been previously associated with OCD. Additionally, the serotonin 2A receptor gene (HTR2A) has two polymorphisms (A-1438G - rs6311, and T102C - rs6313), which have also been overrepresented among OCD patients. Therefore, the aim of this study is to evaluate the association of these three polymorphisms with OCD, through the examination of potential sources of heterogeneity in previous studies including age of onset, sex and symptom dimensions. METHODS: Polymorphisms were genotyped by Polymerase Chain Reaction (PCR) in a sample of 203 OCD patients and 205 healthy controls from Brazil. RESULTS: Although we did not observe any statistically significant association between the HTR2A gene polymorphisms and OCD or its clinical features, SLC6A4 STin2 polymorphism was significantly more common among OCD patients as compared to health controls. Further, a significant association between the STin2.12 allele and OCD, as well as a dominant effect of the STin2.12 allele in OCD was seen. Of note, late-onset (>18years) OCD was significantly more often seen in association with homozygosis for STin2.12 allele. No significant associations were observed with different OCD symptom dimensions. CONCLUSION: Our results indicate an important influence of the STin2 polymorphism in OCD, but more studies are warranted to confirm these results.
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Estudios de Asociación Genética/métodos , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/genética , Polimorfismo Genético/genética , Receptor de Serotonina 5-HT2A/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Adulto , Brasil/epidemiología , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/epidemiologíaRESUMEN
The etiology of OCD is largely unknown, but neuroimaging and pharmacological studies suggest that glutamatergic system plays a significant role on OCD development. We genotyped one polymorphism at GRIN2B (rs1019385) by real time Polymerase Chain Reaction in a sample of Brazilian Obsessive-Compulsive patients and healthy controls, and evaluated its influence on OCD. We found the T-allele and TT genotype to be significantly associated with OCD and ordering dimension. The T-allele was also significantly associated with checking. These preliminary results demonstrated that the GRIN2B gene may confer to some extent the susceptibility to OCD and its symptoms.
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Alelos , Genotipo , Trastorno Obsesivo Compulsivo/genética , Polimorfismo Genético , Receptores de N-Metil-D-Aspartato/genética , Adolescente , Adulto , Brasil , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Trastorno Obsesivo Compulsivo/diagnóstico , Proyectos Piloto , Adulto JovenRESUMEN
Pharmacological data and animal models support the hypothesis that the dopaminergic (DA) system is implicated in obsessive-compulsive disorder (OCD). Therefore, this case-control study assessed whether genetics variations in catechol-O-methyltransferase gene (COMT) could influence susceptibility to OCD and OCD features in a Brazilian sample. A sample of 199 patients with OCD and 200 healthy individuals was genotyped for -287A > G (rs2075507) and Val158Met (rs4680) single nucleotide polymorphisms (SNPs) by TaqMan(®) or restriction mapping. We observed a statistically significant predominance of the Met low-activity allele in the male patient group as compared to the male healthy control group. The -287A > G polymorphism's genotypes and alleles were significantly overrepresented among male individuals with ordering and female subjects with washing symptoms. We also found female hoarders to exhibit a significant higher frequency of the low activity Met/Met genotype of Val158Met polymorphism compared to female patients who did not express this dimension. Our data suggest an influence of COMT polymorphisms on OCD and OCD patients' features, such as gender, and ordering, washing, and hoarding symptom dimensions. Further studies to confirm the clinical importance of COMT SNPs in OCD are warranted.
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Catecol O-Metiltransferasa/genética , Trastorno Obsesivo Compulsivo/genética , Polimorfismo de Nucleótido Simple , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación Missense , Factores SexualesRESUMEN
Esta propuesta tiene como objetivo identificar las percepciones de graduados a respecto de las relaciones sociales establecidas con la comunidad académica. Fue utilizada la técnica de Grupo Focal y Análisis de Contenido para cosecha y análisis de datos. Fueron listados dos niveles de dificultad relativos a las situaciones vivenciadas por los alumnos. Resalté la integración de los alumnos, la relación solícita entre los alumnos y profesores, funcionarios y gestores como fáciles; las subcategorías de la intolerancia y de la falta de tiempo para el relacionamiento entre los alumnos, la falta de compromiso docente, la arrogancia y descaso de los funcionarios y la valorización de la pos en detrimento de la graduación como difíciles. Se sugiere el desarrollo de programas en habilidades sociales con participantes del medio académico destacándose la escasez de trabajos con segmentos técnicos administrativos.
Objetivou-se identificar as percepções de graduandos a respeito das relações sociais estabelecidas com a comunidade acadêmica. Utilizou-se a técnica de Grupo Focal e Análise de Conteúdo para coleta e análise dos dados. Foram elencados dois níveis de dificuldade relativos às situações vivenciadas pelos alunos. Destacam-se a integração de alunos, a relação solícita entre alunos e professores, funcionários e gestores como fáceis; as subcategorias da intolerância e da falta de tempo para o relacionamento entre os alunos, a falta de compromisso docente, a arrogância e descaso dos funcionários e a valorização da pós em detrimento da graduação como difíceis. Sugere-se o desenvolvimento de programas em habilidades sociais com participantes do meio acadêmico destacando-se a escassez de trabalhos com segmentos técnicos administrativos.
This article aims to identify the perceptions of undergraduates about the social relationships established in the academic community. Focus Group and Content Analysis were used for data collection and analysis. Two difficulty levels related to the situations experienced by students were listed. It is noteworthy that the subcategories of integration among the students, the good relationship between students and professors, staff and managers were considered easy situations; and subcategories of intolerance and lack of time for the relationship between the students, the lack of commitment of professors, the arrogance and indifference of the staff, and the appreciation of post-graduation over graduation were classified as difficult situations. We suggest the development of training programs in social skills with participants from the academic community, a rich environment of social interactions, highlighting in particular the shortage of work in this regard with the segment of administrative staff.