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Biomarkers and clinical predictors of long-term course in obsessivecompulsive disorder: A prospective cohort study
- S. López-Rodriguez, P. Alonso Ortega, C. Segalàs Cosi, E. Real Barrero, S. Bertolín Triquell, C. Soriano Mas, Á. Carracedo Alvarez, J. M. Menchón Magriña
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S231
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Introduction
The purpose of the research project is to analyze the long-term evolution of obsessive-compulsive disorder (OCD) from of a study of a cohort of patients prospectively followed over a period ranging from 5 to 20 years, treated for according to therapeutic guidelines mediating serotonin reuptake inhibitors (IRS) and drug enhancers (antipsychotics) and cognitive behavioral therapy and evaluated in a standardized manner.
ObjectivesTo assess the long-term course of Obsessive-Compulsive Disorder (OCD) in a cohort of patients treated according to current clinical guidelines; to analyse possible prognostic factors associated with the long-term course of the disorder including clinical and sociodemographic variables, as well as genetic and neuroimaging biomarkers, and their interaction, and finally to study neuroanatomical and functional cerebral connectivity changes after 15 years of treatment in a subsample of patients.
MethodsProspective, descriptive, and observational study of a cohort of OCD patients, receiving treatment at the Department of Psychiatry of Hospital de Bellvitge since 1998, according to a standardized protocol. Follow-up period ranges from 5 (n=423), to 10 (n= 247) and 15 years (123). Baseline clinical and sociodemographic assessment, long-term evolution and information on treatments provided are available for the whole sample. Data on whole exome sequencing is available for 300 of the patients included in the cohort and baseline structural neuroimaging and cerebral functional connectivity has been analysed in 168 subjects. To expand the analysis of genetic biomarkers, we propose the study of de novo variants through exome analysis of 50 trios (patient and both parents) selected among those subjects that have reached 15 years of follow-up (25 trios with patients within the “long-term remission” group and 25 trios with patients with chronic OCD). De novo variants detected in the trio analysis will be replicated in the rest of the sample. A structural and resting state MRI will be obtained in a subsample of 100 patients recruited among those who have completed a minimum follow-up period of 15 years, to assess cerebral changes associated with the long-term course of the disorder.
Resultsin the current moment the recruitment period of the study has ended and all the data is being statistically analysed in order to provide solid results in a short period of time.
ConclusionsThe identification of those factors associated with an increased risk of chronic disease is an element essential to offer personalized treatment to our patients and improve their prognosis, emphasizing the intensive use of those therapeutic strategies for which we can predict a better response and modifying to the extent of, if possible, environmental factors or factors of access to treatment that contribute to perpetuate obsessive symptoms.
Disclosure of InterestNone Declared
Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study
- Gamze Erzin, Lotta-Katrin Pries, Jim van Os, Laura Fusar-Poli, Philippe Delespaul, Gunter Kenis, Jurjen J. Luykx, Bochao D. Lin, Alexander L. Richards, Berna Akdede, Tolga Binbay, Vesile Altınyazar, Berna Yalınçetin, Güvem Gümüş-Akay, Burçin Cihan, Haldun Soygür, Halis Ulaş, Eylem Şahin Cankurtaran, Semra Ulusoy Kaymak, Marina M. Mihaljevic, Sanja Andric-Petrovic, Tijana Mirjanic, Miguel Bernardo, Gisela Mezquida, Silvia Amoretti, Julio Bobes, Pilar A. Saiz, Maria Paz García-Portilla, Julio Sanjuan, Eduardo J. Aguilar, Jose Luis Santos, Estela Jiménez-López, Manuel Arrojo, Angel Carracedo, Gonzalo López, Javier González-Peñas, Mara Parellada, Nadja P. Maric, Cem Atbaşoğlu, Alp Ucok, Köksal Alptekin, Meram Can Saka, Genetic Risk and Outcome of Psychosis (GROUP) investigators, Celso Arango, Micheal C. O’Donovan, Bart P. F. Rutten, Sinan Guloksuz
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- Journal:
- European Psychiatry / Volume 64 / Issue 1 / 2021
- Published online by Cambridge University Press:
- 19 March 2021, e25
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Background
A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls.
MethodsThis cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate.
ResultsES-SCZ was associated with the GAF dimensions in patients (symptom: B = −1.53, p-value = 0.001; disability: B = −1.44, p-value = 0.001), siblings (symptom: B = −3.07, p-value < 0.001; disability: B = −2.52, p-value < 0.001), and healthy controls (symptom: B = −1.50, p-value < 0.001; disability: B = −1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group.
ConclusionsOur findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.
Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum
- L.-K. Pries, G. A. Dal Ferro, J. van Os, P. Delespaul, G. Kenis, B. D. Lin, J. J. Luykx, A. L. Richards, B. Akdede, T. Binbay, V. Altınyazar, B. Yalınçetin, G. Gümüş-Akay, B. Cihan, H. Soygür, H. Ulaş, E. Şahin Cankurtaran, S. Ulusoy Kaymak, M. M. Mihaljevic, S. Andric Petrovic, T. Mirjanic, M. Bernardo, G. Mezquida, S. Amoretti, J. Bobes, P. A. Saiz, M. Paz García-Portilla, J. Sanjuan, E. J. Aguilar, J. L. Santos, E. Jiménez-López, M. Arrojo, A. Carracedo, G. López, J. González-Peñas, M. Parellada, N. P. Maric, C. Atbaşoğlu, A. Ucok, K. Alptekin, M. Can Saka, Genetic Risk and Outcome of Psychosis (GROUP) investigators, C. Arango, M. O'Donovan, S. Tosato, B. P. F. Rutten, S. Guloksuz
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- Journal:
- Epidemiology and Psychiatric Sciences / Volume 29 / 2020
- Published online by Cambridge University Press:
- 17 November 2020, e182
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Aims
Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene–environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum.
MethodsThe sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components).
ResultsBoth genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene–environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions.
ConclusionsThe interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.
A replication study of JTC bias, genetic liability for psychosis and delusional ideation
- Cécile Henquet, Jim van Os, Lotta K. Pries, Christian Rauschenberg, Philippe Delespaul, Gunter Kenis, Jurjen J. Luykx, Bochao D. Lin, Alexander L. Richards, Berna Akdede, Tolga Binbay, Vesile Altınyazar, Berna Yalınçetin, Güvem Gümüş-Akay, Burçin Cihan, Haldun Soygür, Halis Ulaş, Eylem S. Cankurtaran, Semra U. Kaymak, Marina M. Mihaljevic, Sanja S. Petrovic, Tijana Mirjanic, Miguel Bernardo, Gisela Mezquida, Silvia Amoretti, Julio Bobes, Pilar A. Saiz, Maria P. García-Portilla, Julio Sanjuan, Eduardo J. Aguilar, Jose L. Santos, Estela Jiménez-López, Manuel Arrojo, Angel Carracedo, Gonzalo López, Javier González-Peñas, Mara Parellada, Nadja P. Maric, Cem Atbaşoğlu, Alp Ucok, Köksal Alptekin, Meram C. Saka, Celso Arango, Michael O'Donovan, Bart P.F. Rutten, Sinan Gülöksüz
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- Journal:
- Psychological Medicine / Volume 52 / Issue 9 / July 2022
- Published online by Cambridge University Press:
- 13 October 2020, pp. 1777-1783
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Background
This study attempted to replicate whether a bias in probabilistic reasoning, or ‘jumping to conclusions’(JTC) bias is associated with being a sibling of a patient with schizophrenia spectrum disorder; and if so, whether this association is contingent on subthreshold delusional ideation.
MethodsData were derived from the EUGEI project, a 25-centre, 15-country effort to study psychosis spectrum disorder. The current analyses included 1261 patients with schizophrenia spectrum disorder, 1282 siblings of patients and 1525 healthy comparison subjects, recruited in Spain (five centres), Turkey (three centres) and Serbia (one centre). The beads task was used to assess JTC bias. Lifetime experience of delusional ideation and hallucinatory experiences was assessed using the Community Assessment of Psychic Experiences. General cognitive abilities were taken into account in the analyses.
ResultsJTC bias was positively associated not only with patient status but also with sibling status [adjusted relative risk (aRR) ratio : 4.23 CI 95% 3.46–5.17 for siblings and aRR: 5.07 CI 95% 4.13–6.23 for patients]. The association between JTC bias and sibling status was stronger in those with higher levels of delusional ideation (aRR interaction in siblings: 3.77 CI 95% 1.67–8.51, and in patients: 2.15 CI 95% 0.94–4.92). The association between JTC bias and sibling status was not stronger in those with higher levels of hallucinatory experiences.
ConclusionsThese findings replicate earlier findings that JTC bias is associated with familial liability for psychosis and that this is contingent on the degree of delusional ideation but not hallucinations.
High-throughput genotyping assay for the large-scale genetic characterization of Cryptosporidium parasites from human and bovine samples
- J. L. ABAL-FABEIRO, X. MASIDE, J. LLOVO, X. BELLO, M. TORRES, M. TREVIÑO, L. MOLDES, A. MUÑOZ, A. CARRACEDO, C. BARTOLOMÉ
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- Parasitology / Volume 141 / Issue 4 / April 2014
- Published online by Cambridge University Press:
- 15 November 2013, pp. 491-500
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The epidemiological study of human cryptosporidiosis requires the characterization of species and subtypes involved in human disease in large sample collections. Molecular genotyping is costly and time-consuming, making the implementation of low-cost, highly efficient technologies increasingly necessary. Here, we designed a protocol based on MALDI-TOF mass spectrometry for the high-throughput genotyping of a panel of 55 single nucleotide variants (SNVs) selected as markers for the identification of common gp60 subtypes of four Cryptosporidium species that infect humans. The method was applied to a panel of 608 human and 63 bovine isolates and the results were compared with control samples typed by Sanger sequencing. The method allowed the identification of species in 610 specimens (90·9%) and gp60 subtype in 605 (90·2%). It displayed excellent performance, with sensitivity and specificity values of 87·3 and 98·0%, respectively. Up to nine genotypes from four different Cryptosporidium species (C. hominis, C. parvum, C. meleagridis and C. felis) were detected in humans; the most common ones were C. hominis subtype Ib, and C. parvum IIa (61·3 and 28·3%, respectively). 96·5% of the bovine samples were typed as IIa. The method performs as well as the widely used Sanger sequencing and is more cost-effective and less time consuming.
Analysis of BRCA1 and BRCA2 in breast and breast/ovarian cancer families shows population substructure in the Iberian peninsula
- A. VEGA, M. TORRES, J. I. MARTÍNEZ, C. RUIZ-PONTE, F. BARROS, A. CARRACEDO
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- Journal:
- Annals of Human Genetics / Volume 66 / Issue 1 / January 2002
- Published online by Cambridge University Press:
- 25 April 2002, pp. 29-36
- Print publication:
- January 2002
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An estimated 5–10% of all breast and ovarian cancers are due to an inherited predisposition, representing a rather large number of patients. In Spain 1/13–1/14 women will be diagnosed with breast cancer during their lifetime. Two major breast cancer genes, BRCA1 and BRCA2, have been identified. To date, several hundred pathogenic mutations in these two genes have been published or reported to the Breast Cancer Information Core, BIC database (http://www.nhgri.nih.gov/Intramural_research_Lab transfer/Bic/index.html). In the present study, 30 Spanish breast and breast/ovarian cancer families (29 from Galicia, NW Spain, and 1 from Catalonia, NE Spain) were screened for mutations in the BRCA1 and BRCA2 genes. The analysis of these genes was carried out by SSCP for shorter exons and direct sequencing in the case of longer ones. Mutations were found in 8 of the 30 families studied (26.66%). It is important to note that all mutations were detected within the BRCA1 gene: 330 A>G, 910_913delGTTC, 2121 C>T, 3958_3962delCTCAGinsAGGC, and 5530 T>A. The BRCA1 330 A>G mutation was found in four unrelated families and accounted for 50% of all identified mutations.
Hotspot volcanism close to a passive continental margin: the Canary Islands
- J. C. CARRACEDO, S. DAY, H. GUILLOU, E. RODRÍGUEZ BADIOLA, J. A. CANAS, F. J. PÉREZ TORRADO
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- Geological Magazine / Volume 135 / Issue 5 / September 1998
- Published online by Cambridge University Press:
- 01 September 1998, pp. 591-604
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The Canarian Archipelago is a group of volcanic islands on a slow-moving oceanic plate, close to a continental margin. The origins of the archipelago are controversial: a hotspot or mantle plume, a zone of lithospheric deformation, a region of compressional block-faulting or a rupture propagating westwards from the active Atlas Mountains fold belt have been proposed by different authors. However, comparison of the Canarian Archipelago with the prototypical hotspot-related island group, the Hawaiian Archipelago, reveals that the differences between the two are not as great as had previously been supposed on the basis of older data. Quaternary igneous activity in the Canaries is concentrated at the western end of the archipelago, close to the present-day location of the inferred hotspot. This is the same relationship as seen in the Hawaiian and Cape Verde islands. The latter archipelago, associated with a well-defined but slow-moving mantle plume, shows anomalies in a plot of island age against distance which are comparable to those seen in the Canary Islands: these anomalies cannot therefore be used to argue against a hotspot origin for the Canaries. Individual islands in both archipelagoes are characterized by initial rapid growth (the ‘shield-building’ stages of activity), followed by a period of quiescence and deep erosion (erosion gap) which in turn is followed by a ‘post-erosional’ stage of activity. The absence of post-shield stage subsidence in the Canaries is in marked contrast with the major subsidence experienced by the Hawaiian Islands, but is comparable with the lack of subsidence evident in other island groups at slow-moving hotspots, such as the Cape Verdes. Comparison of the structure and structural evolution of the Canary Islands with other oceanic islands such as Hawaii and Réunion reveals many similarities. These include the development of triple (‘Mercedes Star’) rift zones and the occurrence of giant lateral collapses on the flanks of these rift zones. The apparent absence of these features in the post-erosional islands may in part be a result of their greater age and deeper erosion, which has removed much of the evidence for their early volcanic architecture. We conclude that the many similarities between the Canary Islands and island groups whose hotspot origins are undisputed show that the Canaries have been produced in the same way.
Age and geometry of an aborted rift flank collapse: the San Andres fault system, El Hierro, Canary Islands
- S. J. DAY, J. C. CARRACEDO, H. GUILLOU
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- Geological Magazine / Volume 134 / Issue 4 / July 1997
- Published online by Cambridge University Press:
- 01 July 1997, pp. 523-537
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The catastrophic slope failures and landslides that occur in the final stages of lateral collapses of volcanoes destroy much of the evidence for precursory deformation and the early stages of the collapses concerned. Aborted or incomplete collapse structures, although rare, are rich sources of information on these stages of development of catastrophic collapses. The San Andres fault system, on the volcanic island of El Hierro, is a relatively young (between about 545 and about 261–176 ka old) but inactive lateral collapse structure. It appears to represent an aborted giant landslide. It is developed along the flank of a steep-sided volcanic rift zone, and is bounded by a discrete strike-slip fault zone at the up-rift end, closest to the centre of the island. This geometry differs markedly from that of collapse structures on stratovolcanoes but bears some similarities to that of active fault systems on Hawaii. Although the fault system has undergone little erosion, cataclasites which formed close to the palaeosurface are well exposed. These cataclasites are amongst the first fault rocks to be described from volcano lateral collapse structures and include the only pseudotachylytes to have been identified in such structures to date. Their development at unusually shallow depths is attributed to large movements on the fault in a single event, the inferred aborted landslide, and a lack of pressurized pore water. The absence of pressurized fluids in the slumping block may have caused the San Andres fault system to cease moving, rather than develop into a giant volcanic landslide. The recognition that the San Andres fault system is inactive greatly reduces the estimated volcanic hazard associated with El Hierro. However, the lack of evidence for precursory deformation prior to the aborted landslide event is disturbing as it implies that giant lateral collapses can occur on steep-sided oceanic islands with little warning.