Sanchez-Mora R.M.,University College of Cundinamarca |
Sanchez-Mora R.M.,National University of Colombia |
Arboleda H.,National University of Colombia |
Arboleda G.,National University of Colombia
Journal of Molecular Neuroscience | Year: 2012
The etiology of Parkinson's disease (PD) remains unknown. Mutations in several genes, including PINK1, have provided an understanding of the molecular mechanisms of this pathology.We analyzed the role of PINK1 overexpression (wild-type PINK1 or PINK1 with G309D or L347P mutations) on neurotoxicity associated with C2-ceramide exposure in CAD cells. CAD cells were transiently transfected with either PINK1 (wild type or mutated) or with empty vector and then treated with 25-μM C2-ceramide for 6 h. Cell viability and mitochondrial membrane potential were analyzed by flow cytometry, expression of Bax and Bcl-2 was determined by real-time PCR, and AKT phosphorylation was analyzed by western blot. CAD cells overexpressing wild-type PINK1 and treated with C2-ceramide showed lower percentages of depolarized mitochondria, lower expressions of Bax and higher expressions of Bcl-2 than non-transfected cells. In addition, wild-type PINK1 rescued C2-ceramide-induced inhibition of AKT phosphorylation. Overexpression of PINK1 G309D mutation caused an increase of depolarized mitochondria, a decrease of Bax and an increase in Bcl-2 expression levels. PINK1 L4347P mutation was associated with a higher drop in mitochondrial membrane potential and increased expression of Bax, with minimal variation in the expression of Bcl-2. PINK1 mutations did not result in variations of AKT phosphorylation. We suggest that by preventing mitochondrial dysfunction and reinforcing anti-apoptotic and neuronal survival pathways such as Bcl-2 and PI3K/AKT, PINK1 confers a neuroprotective effect against the neurotoxin C2-ceramide. These effects were abrogated by PINK1 mutations. © Springer Science+Business Media, LLC 2011.
Bustos A.V.G.,University College of Cundinamarca |
Jimenez M.G.,University College of Cundinamarca |
Mora R.M.S.,University College of Cundinamarca
Biochemistry and Biophysics Reports | Year: 2017
The C. elegans NB327 mutant strain is characterized for the knockdown of the dic-1 gene. The dic-1 gene is homologous to the dice-1 gene in humans, encoding the protein DICE-1 as a tumor suppressor. Absence or under-regulation of the dice-1 gene can be reflected in lung and prostate cancer [17,18]. This study evaluated the effect of EEAML on the C. elegans NB327 mutant strain. Phenotypic aspects such as morphology, body length, locomotion, and reproductive behaviour were analyzed. It is important to emphasize that the strain presents a phenotype characteristic with respect to egg laying and hatching. Reported studies showed that Annona muricata extract and its active components evidence anti-cancer and anti-tumor effects, through experimentation in vivo and in vitro models. However, neurotoxicity has been reported as a side effect. The results showed that the mutant strain NB327 was exposed to EEAML (5 mg/ml) concentration, it showed a significant decrease in average locomotion, resulting in 13 undulations in 30 s. This contrasts with the control strain's 17.5 undulations in 30 s. Similarly, the number of progenies was reduced from 188 progenies (control strain) to 114 and 92 progenies at the dose of (1 mg/ml and 5 mg/m) EEAML. The results of this study suggest that EEAML has a possible neurotoxic effect in concentrations equal to or greater than 5 mg/ml. Also, it does not have positive effects on the mutant strain of Caenorhabditis elegans NB327 phenotype. © 2017 The Authors
Mclaughlin K.A.,University of Washington |
Koenen K.C.,Columbia University |
Friedman M.J.,National Center for PTSD |
Ruscio A.M.,University of Pennsylvania |
And 18 more authors.
Biological Psychiatry | Year: 2015
BACKGROUND: Although only a few people exposed to a traumatic event (TE) develop posttraumatic stress disorder (PTSD), symptoms that do not meet full PTSD criteria are common and often clinically significant. Individuals with these symptoms sometimes have been characterized as having subthreshold PTSD, but no consensus exists on the optimal definition of this term. Data from a large cross-national epidemiologic survey are used in this study to provide a principled basis for such a definition. METHODS: The World Health Organization World Mental Health Surveys administered fully structured psychiatric diagnostic interviews to community samples in 13 countries containing assessments of PTSD associated with randomly selected TEs. Focusing on the 23,936 respondents reporting lifetime TE exposure, associations of approximated DSM-5 PTSD symptom profiles with six outcomes (distress-impairment, suicidality, comorbid feardistress disorders, PTSD symptom duration) were examined to investigate implications of different subthreshold definitions. RESULTS: Although consistently highest outcomes for distress-impairment, suicidality, comorbidity, and PTSD symptom duration were observed among the 3.0% of respondents with DSM-5 PTSD rather than other symptom profiles, the additional 3.6% of respondents meeting two or three of DSM-5 criteria B-E also had significantly elevated scores for most outcomes. The proportion of cases with threshold versus subthreshold PTSD varied depending on TE type, with threshold PTSD more common following interpersonal violence and subthreshold PTSD more common following events happening to loved ones. CONCLUSIONS: Subthreshold DSM-5 PTSD is most usefully defined as meeting two or three of DSM-5 criteria B-E. Use of a consistent definition is critical to advance understanding of the prevalence, predictors, and clinical significance of subthreshold PTSD.
Scott K.M.,University of Otago |
Von Korff M.,Group Health Research Institute |
Angermeyer M.C.,Center for Public Mental Health |
Benjet C.,National Institute of Psychiatry |
And 8 more authors.
Archives of General Psychiatry | Year: 2011
Context: The physical health consequences of childhood psychosocial adversities may be as substantial as the mental health consequences, but whether this is the case remains unclear because much prior research has involved unrepresentative samples and a selective focus on particular adversities or physical outcomes. The association between early-onset mental disorders and subsequent poor physical health in adulthood has not been investigated. Objective: To investigate whether childhood adversities and early-onset mental disorders are independently associated with increased risk of a range of adult-onset chronic physical conditions in culturally diverse samples spanning the full adult age range. Design: Cross-sectional community surveys of adults in 10 countries. Setting: General population. Participants: Adults (ie, aged ≥18 years; N=18 303), with diagnostic assessment and determination of age at onset of DSM-IV mental disorders, assessment of childhood familial adversities, and age of diagnosis or onset of chronic physical conditions. Main Outcome Measures: Risk (ie, hazard ratios) of adult-onset (ie, at age >20 years) heart disease, asthma, diabetes mellitus, arthritis, chronic spinal pain, and chronic headache as a function of specific childhood adversities and early-onset (ie, at age >21 years) DSM-IV depressive and anxiety disorders, with mutual adjustment. Results: A history of 3 or more childhood adversities was independently associated with onset of all 6 physical conditions (hazard ratios, 1.44 to 2.19). Controlling for current mental disorder made little difference to these associations. Early-onset mental disorders were independently associated with onset of 5 physical conditions (hazard ratios, 1.43 to 1.66). Conclusions: These results are consistent with the hypothesis that childhood adversities and early-onset mental disorders have independent, broad-spectrum effects that increase the risk of diverse chronic physical conditions in later life. They require confirmation in a prospectively designed study. The long course of these associations has theoretical and research implications. ©2011 American Medical Association. All rights reserved.
Merikangas K.R.,National Health Research Institute |
Jin R.,Harvard University |
He J.-P.,National Health Research Institute |
Kessler R.C.,Harvard University |
And 11 more authors.
Archives of General Psychiatry | Year: 2011
Context: There is limited information on the prevalence and correlates of bipolar spectrum disorder in international population-based studies using common methods. Objectives: To describe the prevalence, impact, patterns of comorbidity, and patterns of service utilization for bipolar spectrum disorder (BPS) in the World Health Organization World Mental Health Survey Initiative. Design, Setting, and Participants: Crosssectional, face-to-face, household surveys of 61 392 community adults in 11 countries in the Americas, Europe, and Asia assessed with the World Mental Health version of the World Health Organization Composite International Diagnostic Interview, version 3.0, a fully structured, lay-administered psychiatric diagnostic interview. Main Outcome Measures: Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) disorders, severity, and treatment. Results: The aggregate lifetime prevalences were 0.6% for bipolar type I disorder (BP-I), 0.4% for BP-II, 1.4% for subthreshold BP, and 2.4% for BPS. Twelve-month prevalences were 0.4% for BP-I, 0.3% for BP-II, 0.8% for subthreshold BP, and 1.5% for BPS. Severity of both manic and depressive symptoms as well as suicidal behavior increased monotonically from subthreshold BP to BP-I. By contrast, role impairment was similar across BP subtypes. Symptom severity was greater for depressive episodes than manic episodes, with approximately 74.0% of respondents with depression and 50.9% of respondents with mania reporting severe role impairment. Three-quarters of those with BPS met criteria for at least 1 other disorder, with anxiety disorders (particularly panic attacks) being the most common comorbid condition. Less than half of those with lifetime BPS received mental health treatment, particularly in low-income countries, where only 25.2% reported contact with the mental health system. Conclusions: Despite cross-site variation in the prevalence rates of BPS, the severity, impact, and patterns of comorbidity were remarkably similar internationally. The uniform increases in clinical correlates, suicidal behavior, and comorbidity across each diagnostic category provide evidence for the validity of the concept of BPS. Treatment needs for BPS are often unmet, particularly in low-income countries. ©2011 American Medical Association. All rights reserved.
Ramirez F.,University College of Cundinamarca |
Fischer G.,National University of Colombia |
Pinzon J.C.A.,National University of Education of Colombia |
Ulrichs C.,Humboldt University of Berlin
Scientia Horticulturae | Year: 2013
The cape gooseberry (Physalis peruviana L.) is a shrub found native in the Andes that bears tomato-like fruit, which are sold commercially and exported from Colombia. We describe the BBCH-based phenological scale for this crop that was developed by observing three cape gooseberry ecotype accessions during a two-year study. The proposed BBCH phenological scale uses seven principal growth stages out of the nine principal stages identified for solanaceous fruits. The principal growth stages are (0) germination, (1) leaf development, (2) formation of side shoots, (5) inflorescence emergence, (6) flowering, (7) development of fruit and (8) ripening of fruit and seed. Early growth stages (0-1) in cape gooseberry are similar to the developmental stages of other solanaceous plants. The first bifurcation (stage 2) marks the beginning of floral development (stage 5). Thereafter, simultaneous developmental stages occur throughout the plant's phenology. It is common to observe early flowers, fully open flowers, immature and mature fruits on the same plant. The BBCH phenological scale developed for cape gooseberry is a useful tool for management and research practices and for subsequent investigations on any of the developmental stages the plant passes through. © 2013 Elsevier B.V.
PubMed | National School of Management, University of Lima, Harvard University, Universitair Psychiatrisch Centrum Katholieke University Leuven and 20 more.
Type: | Journal: Psychological medicine | Year: 2017
Although there is robust evidence linking childhood adversities (CAs) and an increased risk for psychotic experiences (PEs), little is known about whether these associations vary across the life-course and whether mental disorders that emerge prior to PEs explain these associations.We assessed CAs, PEs and DSM-IV mental disorders in 23 998 adults in the WHO World Mental Health Surveys. Discrete-time survival analysis was used to investigate the associations between CAs and PEs, and the influence of mental disorders on these associations using multivariate logistic models.Exposure to CAs was common, and those who experienced any CAs had increased odds of later PEs [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.9-2.6]. CAs reflecting maladaptive family functioning (MFF), including abuse, neglect, and parent maladjustment, exhibited the strongest associations with PE onset in all life-course stages. Sexual abuse exhibited a strong association with PE onset during childhood (OR 8.5, 95% CI 3.6-20.2), whereas Other CA types were associated with PE onset in adolescence. Associations of other CAs with PEs disappeared in adolescence after adjustment for prior-onset mental disorders. The population attributable risk proportion (PARP) for PEs associated with all CAs was 31% (24% for MFF).Exposure to CAs is associated with PE onset throughout the life-course, although sexual abuse is most strongly associated with childhood-onset PEs. The presence of mental disorders prior to the onset of PEs does not fully explain these associations. The large PARPs suggest that preventing CAs could lead to a meaningful reduction in PEs in the population.
PubMed | University of Otago, National Institute Of Psychiatry Ramon Of La Fuente, University of Lima, University of Barcelona and 16 more.
Type: | Journal: JAMA psychiatry | Year: 2017
Previous research has documented significant variation in the prevalence of posttraumatic stress disorder (PTSD) depending on the type of traumatic experience (TE) and history of TE exposure, but the relatively small sample sizes in these studies resulted in a number of unresolved basic questions.To examine disaggregated associations of type of TE history with PTSD in a large cross-national community epidemiologic data set.The World Health Organization World Mental Health surveys assessed 29 TE types (lifetime exposure, age at first exposure) with DSM-IV PTSD that was associated with 1 randomly selected TE exposure (the random TE) for each respondent. Surveys were administered in 20 countries (n=34676 respondents) from 2001 to 2012. Data were analyzed from October 1, 2015, to September 1, 2016.Prevalence of PTSD assessed with the Composite International Diagnostic Interview.Among the 34676 respondents (55.4% [SE, 0.6%] men and 44.6% [SE, 0.6%] women; mean [SE] age, 43.7 [0.2] years), lifetime TE exposure was reported by a weighted 70.3% of respondents (mean [SE] number of exposures, 4.5 [0.04] among respondents with any TE). Weighted (by TE frequency) prevalence of PTSD associated with random TEs was 4.0%. Odds ratios (ORs) of PTSD were elevated for TEs involving sexual violence (2.7; 95% CI, 2.0-3.8) and witnessing atrocities (4.2; 95% CI, 1.0-17.8). Prior exposure to some, but not all, same-type TEs was associated with increased vulnerability (eg, physical assault; OR, 3.2; 95% CI, 1.3-7.9) or resilience (eg, participation in sectarian violence; OR, 0.3; 95% CI, 0.1-0.9) to PTSD after the random TE. The finding of earlier studies that more general history of TE exposure was associated with increased vulnerability to PTSD across the full range of random TE types was replicated, but this generalized vulnerability was limited to prior TEs involving violence, including participation in organized violence (OR, 1.3; 95% CI, 1.0-1.6), experience of physical violence (OR, 1.4; 95% CI, 1.2-1.7), rape (OR, 2.5; 95% CI, 1.7-3.8), and other sexual assault (OR, 1.6; 95% CI, 1.1-2.3).The World Mental Health survey findings advance understanding of the extent to which PTSD risk varies with the type of TE and history of TE exposure. Previous findings about the elevated PTSD risk associated with TEs involving assaultive violence was refined by showing agreement only for repeated occurrences. Some types of prior TE exposures are associated with increased resilience rather than increased vulnerability, connecting the literature on TE history with the literature on resilience after adversity. These results are valuable in providing an empirical rationale for more focused investigations of these specifications in future studies.