Publications by authors named "Pino Alonso"

88 Publications

Sleep disturbances in obsessive-compulsive disorder: influence of depression symptoms and trait anxiety.

BMC Psychiatry 2021 Jan 14;21(1):42. Epub 2021 Jan 14.

Department of Psychiatry, Bellvitge University Hospital. Bellvitge Biomedical Research Institute (IDIBELL), Neurosciences Group - Psychiatry and Mental Health, Feixa Llarga s/n. 08907, L'Hospitalet de Llobregat, Barcelona, Spain.

Background: Sleep disturbances have been reported in obsessive-compulsive disorder (OCD) patients, with heterogeneous results. The aim of our study was to assess sleep function in OCD and to investigate the relationship between sleep and the severity of obsessive-compulsive (OC) symptoms, depressive symptoms and trait anxiety.

Methods: Sleep quality was measured in 61 OCD patients and 100 healthy controls (HCs) using the Pittsburgh Sleep Quality Index (PSQI). Multiple linear regression was conducted to explore the association between sleep and psychopathological measures; a mediation analysis was also performed.

Results: OCD patients showed poor sleep quality and more sleep disturbances compared to HCs. The severity of depression, trait anxiety and OC symptomatology were correlated with poor sleep quality. Multiple linear regression analyses controlling for potential confounders revealed that the severity of depression and trait anxiety were independently related to poor sleep quality in OCD. A mediation analysis showed that both the severity of trait anxiety and depression mediate the relationship between the severity of OC symptoms and poor sleep quality among patients with OCD.

Conclusions: Our findings support the existence of sleep disturbances in OCD. Trait anxiety and depression play a key role in sleep quality among OCD patients.
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http://dx.doi.org/10.1186/s12888-021-03038-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809865PMC
January 2021

Sex differences in the association between obsessive-compulsive symptom dimensions and diurnal cortisol patterns.

J Psychiatr Res 2021 Jan 14;133:191-196. Epub 2020 Dec 14.

Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Neurosciences Group-Psychiatry and Mental Health, Barcelona, Spain; Department of Clinical Sciences, Universitat de Barcelona, Spain. Electronic address:

Previous studies in non-clinical populations suggest that obsessive-compulsive symptoms are associated with hypothalamic-pituitary-adrenal (HPA) axis measures and that there are sex differences in these associations. We aimed to replicate these findings in a sample of 57 patients with obsessive-compulsive disorder (OCD) and 98 healthy subjects. Current and lifetime OCD symptom dimensions were assessed with the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS). Depressive symptoms and state and trait anxiety were also assessed. The following HPA axis measures were analysed in saliva: the diurnal cortisol slope (calculated using two formulas: [1] awakening to 11 p.m. [AWE diurnal slope] and [2] considering fixed time points [FTP diurnal slope] from 10 a.m. to 11 p.m.) and the dexamethasone suppression test ratio (DSTR) after 0.25 mg of dexamethasone. Multiple linear regression analyses were conducted to explore the contribution of OCD symptom dimensions to each HPA axis measure while adjusting for age, sex, BMI, smoking, trait anxiety and depressive symptoms. A sex-specific association between current ordering/symmetry symptoms and AWE diurnal cortisol slope (positive association [flattened slope] in men, inverse association [stepper slope] in women) was found. Two similar sex by OCD dimensions interactions were found for lifetime aggressive and ordering/symmetry symptoms and both (FTP, AWE) diurnal cortisol slopes. Current and lifetime hoarding symptoms were associated to a more flattened FTP diurnal cortisol slope in women. The DSTR was not associated with OCD symptoms. The lifetime interference in functionality was associated with a more flattened AWE diurnal cortisol slope. In conclusion, our study suggests that there are sex differences in the association between OCD subtypes and specific HPA axis measures.
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http://dx.doi.org/10.1016/j.jpsychires.2020.12.017DOI Listing
January 2021

Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters.

Transl Psychiatry 2020 10 8;10(1):342. Epub 2020 Oct 8.

Amsterdam UMC, University of Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Amsterdam, Netherlands.

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.
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http://dx.doi.org/10.1038/s41398-020-01013-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598942PMC
October 2020

Corrigendum to `Exploring Genetic Variants in Obsessive Compulsive Disorder Severity: A GWAS Approach.' Journal of Affective Disorders 267 (2020) 23-32.

J Affect Disord 2020 Sep 18;274:1222. Epub 2020 Jun 18.

OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain; Department of Clinical Sciences, Bellvitge Campus, University of Barcelona, Barcelona, Spain; CIBERSAM (Centro de Investigación en Red de Salud Mental), Instituto de Salud Carlos III, Spain.

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http://dx.doi.org/10.1016/j.jad.2020.05.157DOI Listing
September 2020

Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups.

Authors:
Premika S W Boedhoe Daan van Rooij Martine Hoogman Jos W R Twisk Lianne Schmaal Yoshinari Abe Pino Alonso Stephanie H Ameis Anatoly Anikin Alan Anticevic Celso Arango Paul D Arnold Philip Asherson Francesca Assogna Guillaume Auzias Tobias Banaschewski Alexander Baranov Marcelo C Batistuzzo Sarah Baumeister Ramona Baur-Streubel Marlene Behrmann Mark A Bellgrove Francesco Benedetti Jan C Beucke Joseph Biederman Irene Bollettini Anushree Bose Janita Bralten Ivanei E Bramati Daniel Brandeis Silvia Brem Brian P Brennan Geraldo F Busatto Sara Calderoni Anna Calvo Rosa Calvo Francisco X Castellanos Mara Cercignani Tiffany M Chaim-Avancini Kaylita C Chantiluke Yuqi Cheng Kang Ik K Cho Anastasia Christakou David Coghill Annette Conzelmann Ana I Cubillo Anders M Dale Sara Dallaspezia Eileen Daly Damiaan Denys Christine Deruelle Adriana Di Martino Ilan Dinstein Alysa E Doyle Sarah Durston Eric A Earl Christine Ecker Stefan Ehrlich Benjamin A Ely Jeffrey N Epstein Thomas Ethofer Damien A Fair Andreas J Fallgatter Stephen V Faraone Jennifer Fedor Xin Feng Jamie D Feusner Jackie Fitzgerald Kate D Fitzgerald Jean-Paul Fouche Christine M Freitag Egill A Fridgeirsson Thomas Frodl Matt C Gabel Louise Gallagher Tinatin Gogberashvili Ilaria Gori Patricia Gruner Deniz A Gürsel Shlomi Haar Jan Haavik Geoffrey B Hall Neil A Harrison Catharina A Hartman Dirk J Heslenfeld Yoshiyuki Hirano Pieter J Hoekstra Marcelo Q Hoexter Sarah Hohmann Marie F Høvik Hao Hu Chaim Huyser Neda Jahanshad Maria Jalbrzikowski Anthony James Joost Janssen Fern Jaspers-Fayer Terry L Jernigan Dmitry Kapilushniy Bernd Kardatzki Georgii Karkashadze Norbert Kathmann Christian Kaufmann Clare Kelly Sabin Khadka Joseph A King Kathrin Koch Gregor Kohls Kerstin Konrad Masaru Kuno Jonna Kuntsi Gerd Kvale Jun Soo Kwon Luisa Lázaro Sara Lera-Miguel Klaus-Peter Lesch Liesbeth Hoekstra Yanni Liu Christine Lochner Mario R Louza Beatriz Luna Astri J Lundervold Charles B Malpas Paulo Marques Rachel Marsh Ignacio Martínez-Zalacaín David Mataix-Cols Paulo Mattos Hazel McCarthy Jane McGrath Mitul A Mehta José M Menchón Maarten Mennes Mauricio Moller Martinho Pedro S Moreira Astrid Morer Pedro Morgado Filippo Muratori Clodagh M Murphy Declan G M Murphy Akiko Nakagawa Takashi Nakamae Tomohiro Nakao Leyla Namazova-Baranova Janardhanan C Narayanaswamy Rosa Nicolau Joel T Nigg Stephanie E Novotny Erika L Nurmi Eileen Oberwelland Weiss Ruth L O'Gorman Tuura Kirsten O'Hearn Joseph O'Neill Jaap Oosterlaan Bob Oranje Yannis Paloyelis Mara Parellada Paul Pauli Chris Perriello John Piacentini Fabrizio Piras Federica Piras Kerstin J Plessen Olga Puig J Antoni Ramos-Quiroga Y C Janardhan Reddy Andreas Reif Liesbeth Reneman Alessandra Retico Pedro G P Rosa Katya Rubia Oana Georgiana Rus Yuki Sakai Anouk Schrantee Lena Schwarz Lizanne J S Schweren Jochen Seitz Philip Shaw Devon Shook Tim J Silk H Blair Simpson Norbert Skokauskas Juan Carlos Soliva Vila Anastasia Solovieva Noam Soreni Carles Soriano-Mas Gianfranco Spalletta Emily R Stern Michael C Stevens S Evelyn Stewart Gustavo Sudre Philip R Szeszko Leanne Tamm Margot J Taylor David F Tolin Michela Tosetti Fernanda Tovar-Moll Aki Tsuchiyagaito Theo G M van Erp Guido A van Wingen Alasdair Vance Ganesan Venkatasubramanian Oscar Vilarroya Yolanda Vives-Gilabert Georg G von Polier Susanne Walitza Gregory L Wallace Zhen Wang Thomas Wolfers Yuliya N Yoncheva Je-Yeon Yun Marcus V Zanetti Fengfeng Zhou Georg C Ziegler Kathrin C Zierhut Marcel P Zwiers Paul M Thompson Dan J Stein Jan Buitelaar Barbara Franke Odile A van den Heuvel

Am J Psychiatry 2020 09 16;177(9):834-843. Epub 2020 Jun 16.

The full list of authors in the ENIGMA working groups, author affiliations, author disclosures, and acknowledgments are provided in online supplements.

Objective: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.

Methods: Structural T-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).

Results: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.

Conclusions: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.
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http://dx.doi.org/10.1176/appi.ajp.2020.19030331DOI Listing
September 2020

Looking into the genetic bases of OCD dimensions: a pilot genome-wide association study.

Transl Psychiatry 2020 05 18;10(1):151. Epub 2020 May 18.

OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain.

The multidimensional nature of obsessive-compulsive disorder (OCD) has been consistently reported. Clinical and biological characteristics have been associated with OCD dimensions in different ways. Studies suggest the existence of specific genetic bases for the different OCD dimensions. In this study, we analyze the genomic markers, genes, gene ontology and biological pathways associated with the presence of aggressive/checking, symmetry/order, contamination/cleaning, hoarding, and sexual/religious symptoms, as assessed via the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS) in 399 probands. Logistic regression analyses were performed at the single-nucleotide polymorphism (SNP) level. Gene-based and enrichment analyses were carried out for common (SNPs) and rare variants. No SNP was associated with any dimension at a genome-wide level (p < 5 × 10). Gene-based analyses showed one gene to be associated with hoarding (SETD3, p = 1.89 × 10); a gene highly expressed in the brain and which plays a role in apoptotic processes and transcriptomic changes, and another gene associated with aggressive symptoms (CPE; p = 4.42 × 10), which is involved in neurotrophic functions and the synthesis of peptide hormones and neurotransmitters. Different pathways or biological processes were represented by genes associated with aggressive (zinc ion response and lipid metabolism), order (lipid metabolism), sexual/religious (G protein-mediated processes) and hoarding (metabolic processes and anion transport) symptoms after FDR correction; while no pathway was associated with contamination. Specific genomic bases were found for each dimension assessed, especially in the enrichment analyses. Further research with larger samples and different techniques, such as next-generation sequencing, are needed to better understand the differential genetics of OCD dimensions.
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http://dx.doi.org/10.1038/s41398-020-0804-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235014PMC
May 2020

Exploring genetic variants in obsessive compulsive disorder severity: A GWAS approach.

J Affect Disord 2020 04 29;267:23-32. Epub 2020 Jan 29.

OCD Clinical and Research Unit, Psychiatry Department, Hospital Universitari de Bellvitge, Barcelona, Spain; Department of Clinical Sciences, Bellvitge Campus, University of Barcelona, Barcelona, Spain; CIBERSAM (Centro de Investigación en Red de Salud Mental), Instituto de Salud Carlos III, Spain.

Background: The severity of Obsessive-Compulsive Disorder (OCD) varies significantly among probands. No study has specifically investigated the genetic base of OCD severity. A previous study from our group found an OCD polygenic risk score to predict pre- and post-treatment severity. This study explores the genomic bases of OCD severity.

Methods: We administered the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) to 401 patients at their first visit to our clinic to measure their OCD severity. Genotyping data was collected by using the Infinium PsychArray-24 BeadChip kit (Illumina). We analyzed genetic association with OCD severity in a linear regression analysis at single-nucleotide polymorphism (SNP)- and gene-levels, this last also considering rare variants. Enrichment analyses were performed from gene-based analyses' results.

Results: No SNP reached significant association (p < 10) with the YBOCS. Six markers showed suggestive association (p < 10). The top SNP was an intergenic variant in chromosome 2: rs7578149 (p < 1.89 × 10), located in a region suggestively associated with MDD. Linkage disequilibrium was found for two clusters of SNPs located between SLC16A14 and SP110 in chromosome 2, all of them forming one peak of association. Enrichment analyses revealed OCD genes to be associated with porin activity (FDR = 0.01) and transmembrane structure (FDR = 0.04).

Limitations: The size of the sample and the transversal nature of the severity measure are limitations of this study.

Conclusion: This study contributes to better characterize OCD at an individual level, helping to know more about the prognosis of the disorder and develop more individualized treatments.
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http://dx.doi.org/10.1016/j.jad.2020.01.161DOI Listing
April 2020

Sex-specific association between the cortisol awakening response and obsessive-compulsive symptoms in healthy individuals.

Biol Sex Differ 2019 12 2;10(1):55. Epub 2019 Dec 2.

Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Carlos III Health Institute, Madrid, Spain.

Background: Previous studies have shown associations between obsessive-compulsive disorder (OCD) and hypothalamic-pituitary-adrenal axis activity (HPA). We aimed to investigate the association between obsessive-compulsive (OC) symptoms and HPA axis functionality in a non-clinical sample and to explore whether there are sex differences in this relationship.

Methods: One hundred eighty-three healthy individuals without any psychiatric diagnosis (80 men, 103 women; mean age 41.3 ± 17.9 years) were recruited from the general population. The Obsessive-Compulsive Inventory Revised (OCI-R) was used to assess OC symptoms. State-trait anxiety, perceived stress, and stressful life events were also assessed. Saliva cortisol levels were determined at 6 time points (awakening, 30 and 60 min post-awakening, 10:00 a.m., 23:00 p.m. and 10:00 a.m. the following day of 0.25 mg dexamethasone intake [that occurred at 23:00 p.m.]). Three HPA axis measures were calculated: cortisol awakening response (CAR), cortisol diurnal slope, and cortisol suppression ratio after dexamethasone (DSTR). Multiple linear regression analyses were used to explore the association between OC symptoms and HPA axis measures while adjusting for covariates. Our main analyses were focused on OCI-R total score, but we also explored associations with specific OC symptom dimensions.

Results: No significant differences were observed between males and females in OC symptoms, anxiety measures, stress, or cortisol measures. In the multiple linear regression analyses between overall OC symptoms and HPA axis measures, a female sex by OC symptoms significant interaction (standardized beta = - 0.322; p = 0.023) for the CAR (but not cortisol diurnal slope nor DSTR) was found. Regarding specific symptom dimensions, two other sex interactions were found: a blunted CAR was associated with obsessing symptoms in women, whereas a more flattened diurnal cortisol slope was associated with ordering symptoms in men.

Conclusions: There are sex differences in the association between OC symptoms and HPA axis measures in healthy individuals.
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http://dx.doi.org/10.1186/s13293-019-0273-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889548PMC
December 2019

A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder.

Mol Psychiatry 2019 Oct 29. Epub 2019 Oct 29.

KU Leuven and/or UZ Leuven and/or UPC KU Leuven, Leuven, Belgium.

Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.
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http://dx.doi.org/10.1038/s41380-019-0562-6DOI Listing
October 2019

Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium.

Biol Psychiatry 2020 06 30;87(12):1022-1034. Epub 2019 Apr 30.

Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands. Electronic address:

Background: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD.

Methods: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status.

Results: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets.

Conclusions: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.
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http://dx.doi.org/10.1016/j.biopsych.2019.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094802PMC
June 2020

Differential patterns of brain activation between hoarding disorder and obsessive-compulsive disorder during executive performance.

Psychol Med 2020 03 25;50(4):666-673. Epub 2019 Mar 25.

Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute - IDIBELL, Barcelona, Spain.

Background: Preliminary evidence suggests that hoarding disorder (HD) and obsessive-compulsive disorder (OCD) may show distinct patterns of brain activation during executive performance, although results have been inconclusive regarding the specific neural correlates of their differential executive dysfunction. In the current study, we aim to evaluate differences in brain activation between patients with HD, OCD and healthy controls (HCs) during response inhibition, response switching and error processing.

Methods: We assessed 17 patients with HD, 18 patients with OCD and 19 HCs. Executive processing was assessed inside a magnetic resonance scanner by means of two variants of a cognitive control protocol (i.e. stop- and switch-signal tasks), which allowed for the assessment of the aforementioned executive domains.

Results: OCD patients performed similar to the HCs, differing only in the number of successful go trials in the switch-signal task. However, they showed an anomalous hyperactivation of the right rostral anterior cingulate cortex during error processing in the switch-signal task. Conversely, HD patients performed worse than OCD and HC participants in both tasks, showing an impulsive-like pattern of response (i.e. shorter reaction time and more commission errors). They also exhibited hyperactivation of the right lateral orbitofrontal cortex during successful response switching and abnormal deactivation of frontal regions during error processing in both tasks.

Conclusions: Our results support that patients with HD and OCD present dissimilar cognitive profiles, supported by distinct neural mechanisms. Specifically, while alterations in HD resemble an impulsive pattern of response, patients with OCD present increased error processing during response conflict protocols.
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http://dx.doi.org/10.1017/S0033291719000515DOI Listing
March 2020

An examination of orbitofrontal sulcogyral morphology in obsessive-compulsive disorder.

Psychiatry Res Neuroimaging 2019 04 22;286:18-23. Epub 2019 Feb 22.

Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne & Melbourne Health, Melbourne, Australia. Electronic address:

Obsessive-compulsive disorder (OCD) has been consistently associated with structural and functional alteration of the orbitofrontal cortex (OFC) and its subcortical connections. In exploring these alterations, a neurodevelopmental basis to OCD has been suggested. While some studies have examined outcomes of early cortical maturation processes, such as global cortical thickness and gyrification, no work has specifically examined the OFC. Within the OFC, three types of sulcogyral patterns have been identified as a result of variance in cortical folding. The distribution of these patterns has been found to differ in patients of various neuropsychiatric disorders relative to the general population, however no study has yet investigated this distribution in individuals with OCD. Eighty OCD patients and 78 healthy controls were evaluated using magnetic resonance imaging, with identification of the sulcogyral pattern based on the method of Chiavaras and Petrides (2000). While gross changes in OFC sulcogyral patterning did not distinguish OCD patients from healthy controls, expression of both the Type II and Type III patterns was significantly associated with increased OCD illness severity. This finding indicates that early neurodevelopmental factors may influence illness severity.
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http://dx.doi.org/10.1016/j.pscychresns.2019.02.004DOI Listing
April 2019

Pharmacological treatment of obsessive compulsive disorder in adults: A clinical practice guideline based on the ADAPTE methodology.

Rev Psiquiatr Salud Ment 2019 Apr - Jun;12(2):77-91. Epub 2019 Mar 5.

Servicio de Psiquiatría, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Madrid, España.

Despite the existence of effective evidence-based treatments for the management of obsessive-compulsive disorder (OCD), the therapeutic approach to this disease remains suboptimal. The availability of a therapeutic pharmacological guideline for OCD could help to improve the management of the disease in our setting and to reduce the burden of disease for the patient. With the sponsorship of the Spanish Society of Psychiatry, a group of experts has developed a guideline for the pharmacological treatment of OCD based on the recommendations of existing guidelines and following the methodology of the ADAPTE Collaboration. This article summarises the process of preparing this guideline and the recommendations adopted by consensus by a guideline panel grouped into five areas of interest: acute treatment, duration of treatment, predictors of response and special symptoms, partial response to lack of response to treatment, and special populations.
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http://dx.doi.org/10.1016/j.rpsm.2019.01.003DOI Listing
January 2020

Mapping Alterations of the Functional Structure of the Cerebral Cortex in Obsessive-Compulsive Disorder.

Cereb Cortex 2019 12;29(11):4753-4762

Centro Investigación Biomédica en Red de Salud Mental, CIBERSAM, Barcelona, Spain.

We mapped alterations of the functional structure of the cerebral cortex using a novel imaging approach in a sample of 160 obsessive-compulsive disorder (OCD) patients. Whole-brain functional connectivity maps were generated using multidistance measures of intracortical neural activity coupling defined within isodistant local areas. OCD patients demonstrated neural activity desynchronization within the orbitofrontal cortex and in primary somatosensory, auditory, visual, gustatory, and olfactory areas. Symptom severity was significantly associated with the degree of functional structure alteration in OCD-relevant brain regions. By means of a novel imaging perspective, we once again identified brain alterations in the orbitofrontal cortex, involving areas purportedly implicated in the pathophysiology of OCD. However, our results also indicated that weaker intracortical activity coupling is also present in each primary sensory area. On the basis of previous neurophysiological studies, such cortical activity desynchronization may best be interpreted as reflecting deficient inhibitory neuron activity and altered sensory filtering.
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http://dx.doi.org/10.1093/cercor/bhz008DOI Listing
December 2019

Do polygenic risk and stressful life events predict pharmacological treatment response in obsessive compulsive disorder? A gene-environment interaction approach.

Transl Psychiatry 2019 02 4;9(1):70. Epub 2019 Feb 4.

Institut d' Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat (Barcelona), Spain.

The rate of response to pharmacological treatment in Obsessive-compulsive disorder (OCD) oscillates between 40 and 70%. Genetic and environmental factors have been associated with treatment response in OCD. This study analyzes the predictive ability of a polygenic risk score (PRS) built from OCD-risk variants, for treatment response in OCD, and the modulation role of stressful life events (SLEs) at the onset of the disorder. PRSs were calculated for a sample of 103 patients. Yale-Brown Obsessive Compulsive Scale (YBOCS) scores were obtained before and after a 12-week treatment. Regression analyses were performed to analyze the influence of the PRS and SLEs at onset on treatment response. PRS did not predict treatment response. The best predictive model for post-treatment YBOCS (post YBOCS) included basal YBOCS and age. PRS appeared as a predictor for basal and post YBOCS. SLEs at onset were not a predictor for treatment response when included in the regression model. No evidence for PRS predictive ability for treatment response was found. The best predictor for treatment response was age, agreeing with previous literature specific for SRI treatment. Suggestions are made on the possible role of neuroplasticity as a mediator on this association. PRS significantly predicted OCD severity independent on pharmacological treatment. SLE at onset modulation role was not evidenced. Further research is needed to elucidate the genetic and environmental bases of treatment response in OCD.
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http://dx.doi.org/10.1038/s41398-019-0410-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362161PMC
February 2019

An Empirical Comparison of Meta- and Mega-Analysis With Data From the ENIGMA Obsessive-Compulsive Disorder Working Group.

Front Neuroinform 2018 8;12:102. Epub 2019 Jan 8.

Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

Brain imaging communities focusing on different diseases have increasingly started to collaborate and to pool data to perform well-powered meta- and mega-analyses. Some methodologists claim that a one-stage individual-participant data (IPD) mega-analysis can be superior to a two-stage aggregated data meta-analysis, since more detailed computations can be performed in a mega-analysis. Before definitive conclusions regarding the performance of either method can be drawn, it is necessary to critically evaluate the methodology of, and results obtained by, meta- and mega-analyses. Here, we compare the inverse variance weighted random-effect meta-analysis model with a multiple linear regression mega-analysis model, as well as with a linear mixed-effects random-intercept mega-analysis model, using data from 38 cohorts including 3,665 participants of the ENIGMA-OCD consortium. We assessed the effect sizes and standard errors, and the fit of the models, to evaluate the performance of the different methods. The mega-analytical models showed lower standard errors and narrower confidence intervals than the meta-analysis. Similar standard errors and confidence intervals were found for the linear regression and linear mixed-effects random-intercept models. Moreover, the linear mixed-effects random-intercept models showed better fit indices compared to linear regression mega-analytical models. Our findings indicate that results obtained by meta- and mega-analysis differ, in favor of the latter. In multi-center studies with a moderate amount of variation between cohorts, a linear mixed-effects random-intercept mega-analytical framework appears to be the better approach to investigate structural neuroimaging data.
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http://dx.doi.org/10.3389/fninf.2018.00102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331928PMC
January 2019

Intrinsic functional and structural connectivity of emotion regulation networks in obsessive-compulsive disorder.

Depress Anxiety 2019 02 25;36(2):110-120. Epub 2018 Sep 25.

Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain.

Despite emotion regulation being altered in patients with obsessive-compulsive disorder (OCD), no studies have investigated its relation to multimodal amygdala connectivity. We compared corticolimbic functional and structural connectivity between OCD patients and healthy controls (HCs), and correlated this with the dispositional use of emotion regulation strategies and with OCD severity. OCD patients (n = 73) and HCs (n = 42) were assessed for suppression and reappraisal strategies using the Emotion Regulation Questionnaire (ERQ) and for OCD severity using the Yale-Brown Obsessive-Compulsive Scale. Resting-state functional magnetic resonance imaging (rs-fMRI) connectivity maps were generated using subject-specific left amygdala (LA) and right amygdala (RA) masks. We identified between-group differences in amygdala whole-brain connectivity, and evaluated the moderating effect of ERQ strategies. Significant regions and amygdala seeds were used as targets in probabilistic tractography analysis. Patients scored higher in suppression and lower in reappraisal. We observed higher rs-fMRI RA-right postcentral gyrus (PCG) connectivity in HC, and in patients this was correlated with symptom severity. Reappraisal scores were associated with higher negative LA-left insula connectivity in HC, and suppression scores were negatively associated with LA-precuneus and angular gyri connectivity in OCD. Structurally, patients showed higher mean diffusivity in tracts connecting the amygdala with the other targets. RA-PCG connectivity is diminished in patients, while disrupted emotion regulation is related to altered amygdala connectivity with the insula and posterior brain regions. Our results are the first showing, from a multimodal perspective, the association between amygdala connectivity and specific emotional processing domains, emphasizing the importance of amygdala connectivity in OCD pathophysiology.
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http://dx.doi.org/10.1002/da.22845DOI Listing
February 2019

FKBP5 polymorphisms and hypothalamic-pituitary-adrenal axis negative feedback in major depression and obsessive-compulsive disorder.

J Psychiatr Res 2018 09 9;104:227-234. Epub 2018 Aug 9.

Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Neurosciences Group - Psychiatry and Mental Health, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Carlos III Health Institute, Spain; Department of Clinical Sciences, School of Medicine, Universitat de Barcelona, Barcelona, Spain. Electronic address:

Major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) have both been linked to abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. Polymorphisms in the genes involved in HPA axis activity, such as FKBP5, and their interactions with childhood trauma have been associated with stress-related mental disorders. Our goal was to study the role of FKBP5 genetic variants in HPA axis negative feedback regulation as a possible risk factor for different mental disorders such as MDD and OCD, while controlling for childhood trauma, anxiety and depressive symptoms. The sample included 266 participants divided into three groups: 1) MDD (n = 89 [n = 73 melancholic; n = 3 atypical]), 2) OCD (n = 51; 39% with comorbid MDD [n = 13 melancholic; n = 7 atypical]) and 3) healthy controls (n = 126). Childhood trauma, trait anxiety and depressive symptoms were assessed. HPA negative feedback was analyzed using the dexamethasone suppression test ratio (DSTR) after administration of 0.25 mg of dexamethasone. Twelve SNPs in the FKBP5 gene were selected for genotyping. Multiple linear regressions, after adjusting for the covariates considered, showed a reduced DSTR in individuals with the rs9470079-A variant that was significant after correction for multiple testing. Childhood trauma did not moderate the association between the rs9470079 and DSTR. Our results support the evidence that FKBP5 genetic variation could lead to abnormal HPA axis negative feedback independent of diagnosis. Therefore, this association can be identified as a transdiagnostic feature, offering an interesting opportunity to identify patients with higher stress vulnerability. Further studies focusing on the influence of FKBP5 on measurable biological endophenotypes are needed.
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http://dx.doi.org/10.1016/j.jpsychires.2018.08.003DOI Listing
September 2018

Hypothalamic-pituitary-adrenal axis activity in the comorbidity between obsessive-compulsive disorder and major depression.

Psychoneuroendocrinology 2018 07 14;93:20-28. Epub 2018 Apr 14.

Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Carlos III Health Institute, Spain; Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Neurosciences Group - Psychiatry and Mental Health. Barcelona, Spain; Department of Clinical Sciences, School of Medicine, Universitat de Barcelona, Barcelona, Spain.

Major depressive disorder (MDD) is the most common psychiatric comorbidity in patients with obsessive-compulsive disorder (OCD). Hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been described in both disorders and might play a role in the association between them. We aimed to study the role of HPA axis activity in the comorbidity between OCD and MDD, while controlling for psychopathological dimensions such as anxiety and depressive symptoms. We studied 324 participants belonging to four diagnostic groups: 1) MDD (n = 101), 2) OCD with comorbid MDD (n = 33), 3) OCD without MDD (n = 52), and 4) healthy subjects (n = 138). State anxiety, trait anxiety and depressive symptoms were assessed. Three HPA axis measures were analyzed in saliva: cortisol awakening response (CAR), diurnal cortisol slope (calculated using two formulas: [1] awakening to 11 p.m. [AWE diurnal slope]; [2] considering fixed time points [FTP diurnal slope] from 10 a.m. to 11 p.m.), and dexamethasone suppression test ratio after 0.25 mg of dexamethasone (DSTR). Multiple linear regression analyses were conducted to explore the contribution of clinical diagnosis and symptom dimensions to each HPA axis measure. A more flattened FTP diurnal cortisol slope was observed for OCD patients with comorbid MDD. Regarding the CAR and DSTR, a significant interaction was found between trait anxiety and OCD, as OCD patients with greater trait anxiety showed an increased CAR and reduced cortisol suppression after dexamethasone administration. Our results suggest that trait anxiety plays an important role in the relationship between HPA axis measures and OCD/MDD comorbidity.
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http://dx.doi.org/10.1016/j.psyneuen.2018.04.008DOI Listing
July 2018

A transcultural study of hoarding disorder: Insights from the United Kingdom, Spain, Japan, and Brazil.

Transcult Psychiatry 2018 04 6;55(2):261-285. Epub 2018 Mar 6.

27106 Karolinska Institutet.

Though problematic hoarding is believed to be a universal human behavior, investigations of clinically-defined hoarding disorder (HD) have been confined almost exclusively to Western countries. The current investigation sought to describe and directly compare the features of individuals meeting diagnostic criteria for HD across four distinct cultural settings. Participants were 82 individuals meeting DSM-5 diagnostic criteria for HD, recruited and assessed by trained clinicians at one of four project sites: London, Barcelona, Fukuoka, and Rio de Janeiro. A series of semi-structured interviews and self-report scales were administered, including assessments of socio-demographic characteristics, psychiatric comorbidity, and severity of hoarding and related features. Results indicate that the severity and core features of HD, as well as the cognitions and behaviors commonly associated with this condition, are largely stable across cultures. However, some differences in patient demographics-in particular age, marital status, and clinical expression-as well as comorbid psychiatric features also emerged. These findings confirm that HD, as defined in DSM-5, exists and presents with similar phenomenology across the studied cultures. Future, more fine-grained, research will be needed to study the features of the disorder in additional cultures (e.g., non-industrialized nations) and to evaluate the impact of these cultural aspects on the design of interventions for the disorder.
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http://dx.doi.org/10.1177/1363461518759203DOI Listing
April 2018

Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group.

Am J Psychiatry 2018 05 15;175(5):453-462. Epub 2017 Dec 15.

From the Department of Psychiatry and the Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam; Amsterdam Neuroscience, Amsterdam; Orygen, National Centre of Excellence in Youth Mental Health, Melbourne; the Centre for Youth Mental Health, University of Melbourne, Melbourne; the Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; the Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain; Centro de Investigación Biomèdica en Red de Salud Mental (CIBERSAM), Barcelona; the Department of Clinical Sciences, University of Barcelona, Barcelona; the Margaret and Wallace McCain Centre for Child, Youth, and Family Mental Health, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto; the Centre for Brain and Mental Health, Hospital for Sick Children, Toronto; the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn.; the Mathison Centre for Mental Health Research and Education, Hotchkiss Brain Institute and Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Canada; the Department of Psychiatry, Institute of Psychiatry, University of São Paulo School of Medicine, São Paulo, Brazil; Psychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milan, Italy; the Department of Psychology, Humboldt-Universität zu Berlin, Berlin; the Obsessive-Compulsive Disorder (OCD) Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India; the Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich; the Magnetic Resonance Image Core Facility, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona; the Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic Universitari, Barcelona; the Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China; the Institute of Human Behavioral Medicine, SNU-MRC, Seoul, Republic of Korea; the Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome; the Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam; the Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam; the Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles; the Department of Psychiatry, University of Michigan, Ann Arbor; the Department of Psychiatry, University of Cape Town, Cape Town, South Africa; Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, Republic of Korea; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey; Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; the Bascule, Academic Center for Child and Adolescent Psychiatry, Amsterdam; the Department of Child and Adolescent Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam; the Department of Psychiatry, Oxford University, Oxford, U.K.; the Department of Neuroradiology and the TUM-Neuroimaging Center (TUM-NIC), Klinikum rechts der Isar, Technische Universität München, Munich; the Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; the Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea; Institut d'Investigacions Biomèdiques, August Pi i Sunyer (IDIBAPS), Barcelona; the Department of Medicine, University of Barcelona, Barcelona; the SU/UCT MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, Stellenbosch, South Africa; the Department of Psychiatry, Columbia University Medical College, and New York State Psychiatric Institute, New York; the Department of Clinical Neuroscience, Center for Psychiatry Research, Karolinska Institutet, Stockholm; the Mood Disorders Clinic and the Anxiety Treatment and Research Center, St. Joseph's HealthCare, Hamilton, Ontario; the Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Centro Fermi-Enrico Fermi Historical Museum of Physics and Study and Research Center, Rome; ATR Brain Information Communication Research Laboratory Group, Kyoto, Japan; the Center for Mathematics, Computing, and Cognition, Universidade Federal do ABC, Santo Andre, Brazil; the Center for OCD and Related Disorders, New York State Psychiatric Institute, New York; the Department of Psychobiology and Methodology of Health Sciences, Universitat Autònoma de Barcelona; the Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston; the Clinical Neuroscience and Development Laboratory, Olin Neuropsychiatry Research Center, Hartford, Conn.; the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; the James J. Peters VA Medical Center, Bronx, N.Y.; the Institute of Living, Hartford Hospital, Hartford, Conn.; the Shanghai Key Laboratory of Psychotic Disorders, Shanghai, China; and the Department of Psychiatry, Seoul National University Hospital, Seoul, Republic of Korea.

Objective: Brain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken.

Method: T-weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume.

Results: In adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortex and a thinner inferior parietal cortex. Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from -0.10 to -0.33.

Conclusions: The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.
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http://dx.doi.org/10.1176/appi.ajp.2017.17050485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106947PMC
May 2018

Dispositional use of emotion regulation strategies and resting-state cortico-limbic functional connectivity.

Brain Imaging Behav 2018 Aug;12(4):1022-1031

Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain.

Neuroimaging functional connectivity (FC) analyses have shown that the negative coupling between the amygdala and cortical regions is linked to better emotion regulation in experimental settings. Nevertheless, no studies have examined the association between resting-state cortico-amygdalar FC and the dispositional use of emotion regulation strategies. We aim at assessing the relationship between the resting-state FC patterns of two different amygdala territories, with different functions in the emotion response process, and trait-like measures of cognitive reappraisal and expressive suppression. Forty-eight healthy controls completed the Emotion Regulation Questionnaire (ERQ) and underwent a resting-state functional magnetic resonance imaging acquisition. FC maps of basolateral and centromedial amygdala (BLA/CMA) with different cortical areas were estimated with a seed-based approach, and were then correlated with reappraisal and suppression scores from the ERQ. FC between left BLA and left insula and right BLA and the supplementary motor area (SMA) correlated inversely with reappraisal scores. Conversely, FC between left BLA and the dorsal anterior cingulate cortex correlated directly with suppression scores. Finally, FC between left CMA and the SMA was inversely correlated with suppression. Top-down regulation from the SMA seems to account for the dispositional use of both reappraisal and suppression depending on the specific amygdala nucleus being modulated. In addition, modulation of amygdala activity from cingulate and insular cortices seem to also account for the habitual use of the different emotion regulation strategies.
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http://dx.doi.org/10.1007/s11682-017-9762-3DOI Listing
August 2018

Social context modulates cognitive markers in Obsessive-Compulsive Disorder.

Soc Neurosci 2018 10 3;13(5):579-593. Epub 2017 Aug 3.

a Center for Brain and Cognition, Department of Technology , Universitat Pompeu Fabra , Barcelona , Spain.

Error monitoring, cognitive control and motor inhibition control are proposed as cognitive alterations disrupted in obsessive-compulsive disorder (OCD). OCD has also been associated with an increased sensitivity to social evaluations. The effect of a social simulation over electrophysiological indices of cognitive alterations in OCD was examined. A case-control cross-sectional study measuring event-related potentials (ERP) for error monitoring (Error-Related Negativity), cognitive control (N2) and motor control (LRP) was conducted. We analyzed twenty OCD patients and twenty control participants. ERP were recorded during a social game consisting of a visual discrimination task, which was performed in the presence of a simulated superior or an inferior player. Significant social effects (different ERP amplitudes in Superior vs. Inferior player conditions) were found for OCD patients, but not for controls, in all ERP components. Performing the task against a simulated inferior player reduced abnormal ERP responses in OCD to levels observed in controls. The hierarchy-induced ERP effects were accompanied effects over reaction times in OCD patients. Social context modulates signatures of abnormal cognitive functioning in OCD, therefore experiencing a social superiority position impacts over cognitive processes in OCD such as error monitoring mechanisms. These results open the door for the research of new therapeutic choices.
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http://dx.doi.org/10.1080/17470919.2017.1358211DOI Listing
October 2018

Quantifying dimensional severity of obsessive-compulsive disorder for neurobiological research.

Prog Neuropsychopharmacol Biol Psychiatry 2017 10 1;79(Pt B):206-212. Epub 2017 Jul 1.

Sunnybrook Health Sciences Centre, Centre for Addiction and Mental Health, 2075 Bayview Avenue, Suite FG42, Toronto, ON M4N 3M5, Canada. Electronic address:

Current research to explore genetic susceptibility factors in obsessive-compulsive disorder (OCD) has resulted in the tentative identification of a small number of genes. However, findings have not been readily replicated. It is now broadly accepted that a major limitation to this work is the heterogeneous nature of this disorder, and that an approach incorporating OCD symptom dimensions in a quantitative manner may be more successful in identifying both common as well as dimension-specific vulnerability genetic factors. As most existing genetic datasets did not collect specific dimensional severity ratings, a specific method to reliably extract dimensional ratings from the most widely used severity rating scale, the Yale-Brown Obsessive Compulsive Scale (YBOCS), for OCD is needed. This project aims to develop and validate a novel algorithm to extrapolate specific dimensional symptom severity ratings in OCD from the existing YBOCS for use in genetics and other neurobiological research. To accomplish this goal, we used a large data set comprising adult subjects from three independent sites: the Brazilian OCD Consortium, the Sunnybrook Health Sciences Centre in Toronto, Canada and the Hospital of Bellvitge, in Barcelona, Spain. A multinomial logistic regression was proposed to model and predict the quantitative phenotype [i.e., the severity of each of the five homogeneous symptom dimensions of the Dimensional YBOCS (DYBOCS)] in subjects who have only YBOCS (categorical) data. YBOCS and DYBOCS data obtained from 1183 subjects were used to build the model, which was tested with the leave-one-out cross-validation method. The model's goodness of fit, accepting a deviation of up to three points in the predicted DYBOCS score, varied from 78% (symmetry/order) to 84% (cleaning/contamination and hoarding dimensions). These results suggest that this algorithm may be a valuable tool for extracting dimensional phenotypic data for neurobiological studies in OCD.
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http://dx.doi.org/10.1016/j.pnpbp.2017.06.037DOI Listing
October 2017

Basolateral amygdala-ventromedial prefrontal cortex connectivity predicts cognitive behavioural therapy outcome in adults with obsessive-compulsive disorder.

J Psychiatry Neurosci 2017 Nov;42(6):378-385

From the Institut de Neuropsiquiatria i Addiccions, Hospital del Mar, Barcelona and IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain (Fullana); CIBERSAM, Instituto de Salud Carlos III, Spain (Fullana, Alonso, Cardoner, Real, López-Solà, Segalàs, Subirà, Menchón, Soriano-Mas); the Department of Psychiatry, Autonomous University of Barcelona, Spain (Fullana, Cardoner); the Department of Psychiatry, Columbia University Medical Center, New York, NY, USA, and Division of Clinical Therapeutics, New York State Psychiatric Institute, New York, NY, USA (Fullana, Zhu, Simpson); the Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Hospitalet de Llobregat, Barcelona, Spain (Alonso, Real, Segalàs, Subirà, Menchón, Soriano-Mas); the Department of Clinical Sciences, School of Medicine, University of Barcelona, Barcelona, Spain (Alonso, Menchón); the Depression and Anxiety Unit, Mental Health Department, Parc Taulí Sabadell University Hospital, Barcelona, Spain (Cardoner, López-Solà); the New York State Psychiatric Institute, New York, NY, USA, and Columbia Psychiatry, Columbia University, New York, NY, USA (Galfalvy); the Division of Child and Adolescent Psychiatry, Department of Psychiatry, New York State Psychiatric Institute and College of Physicians and Surgeons, Columbia University, New York, NY, USA (Marsh); and the Department of Psychobiology and Methodology of Health Sciences, Universitat Autònoma de Barcelona, Spain (Soriano-Mas).

Background: Cognitive behavioural therapy (CBT), including exposure and ritual prevention, is a first-line treatment for obsessive-compulsive disorder (OCD), but few reliable predictors of CBT outcome have been identified. Based on research in animal models, we hypothesized that individual differences in basolateral amygdala-ventromedial prefrontal cortex (BLA-vmPFC) communication would predict CBT outcome in patients with OCD.

Methods: We investigated whether BLA-vmPFC resting-state functional connectivity (rs-fc) predicts CBT outcome in patients with OCD. We assessed BLA-vmPFC rs-fc in patients with OCD on a stable dose of a selective serotonin reuptake inhibitor who then received CBT and in healthy control participants.

Results: We included 73 patients with OCD and 84 healthy controls in our study. Decreased BLA-vmPFC rs-fc predicted a better CBT outcome in patients with OCD and was also detected in those with OCD compared with healthy participants. Additional analyses revealed that decreased BLA-vmPFC rs-fc uniquely characterized the patients with OCD who responded to CBT.

Limitations: We used a sample of convenience, and all patients were receiving pharmacological treatment for OCD.

Conclusion: In this large sample of patients with OCD, BLA-vmPFC functional connectivity predicted CBT outcome. These results suggest that future research should investigate the potential of BLA-vmPFC pathways to inform treatment selection for CBT across patients with OCD and anxiety disorders.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5662459PMC
http://dx.doi.org/10.1503/jpn.160215DOI Listing
November 2017

Brain alterations in low-frequency fluctuations across multiple bands in obsessive compulsive disorder.

Brain Imaging Behav 2017 Dec;11(6):1690-1706

Department of Psychiatry, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Feixa Llarga s/n, 08907, L'Hospitalet de Llobregat, Barcelona, Spain.

The extent of functional abnormalities in frontal-subcortical circuits in obsessive-compulsive disorder (OCD) is still unclear. Although neuroimaging studies, in general, and resting-state functional Magnetic Resonance Imaging (rs-fMRI), in particular, have provided relevant information regarding such alterations, rs-fMRI studies have been typically limited to the analysis of between-region functional connectivity alterations at low-frequency signal fluctuations (i.e., <0.08 Hz). Conversely, the local attributes of Blood Oxygen Level Dependent (BOLD) signal across different frequency bands have been seldom studied, although they may provide valuable information. Here, we evaluated local alterations in low-frequency fluctuations across different oscillation bands in OCD. Sixty-five OCD patients and 50 healthy controls underwent an rs-fMRI assessment. Alterations in the fractional amplitude of low-frequency fluctuations (fALFF) were evaluated, voxel-wise, across four different bands (from 0.01 Hz to 0.25 Hz). OCD patients showed decreased fALFF values in medial orbitofrontal regions and increased fALFF values in the dorsal-medial prefrontal cortex (DMPFC) at frequency bands <0.08 Hz. This pattern was reversed at higher frequencies, where increased fALFF values also appeared in medial temporal lobe structures and medial thalamus. Clinical variables (i.e., symptom-specific severities) were associated with fALFF values across the different frequency bands. Our findings provide novel evidence about the nature and regional distribution of functional alterations in OCD, which should contribute to refine neurobiological models of the disorder. We suggest that the evaluation of the local attributes of BOLD signal across different frequency bands may be a sensitive approach to further characterize brain functional alterations in psychiatric disorders.
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http://dx.doi.org/10.1007/s11682-016-9601-yDOI Listing
December 2017

Cortical thickness in obsessive-compulsive disorder: multisite mega-analysis of 780 brain scans from six centres.

Br J Psychiatry 2017 01 19;210(1):67-74. Epub 2016 May 19.

Jean-Paul Fouche, MSc, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Stefan du Plessis, MD, Department of Psychiatry, University of Stellenbosch, Cape Town, South Africa; Coenie Hattingh, MSc, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa; Annerine Roos, PhD, MRC Unit on Anxiety & Stress Disorders, Department of Psychiatry, University of Stellenbosch, Cape Town, South Africa; Christine Lochner, PhD, MRC Unit on Anxiety & Stress Disorders, Department of Psychiatry, University of Stellenbosch, Cape Town, South Africa; Carles Soriano-Mas, PhD, Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain, Carlos III Health Institute, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain, and Department of Psychobiology and Methodology in Health Sciences, Universitat Autònoma de Barcelona, Spain; Joao R. Sato, PhD, Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, Santo Andre, Brazil and Laboratório Interdisciplinar de Neurociências Clínicas, Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil; Takashi Nakamae, MD, PhD, Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Seiji Nishida, MD, PhD, Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan; Jun Soo Kwon, MD, PhD, Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea and Institute of Human Behavioral Medicine, SNU-MRC, Seoul, Republic of Korea and Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea; Wi Hoon Jung, PhD, Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; David Mataix-Cols, PhD, Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Marcelo Q. Hoexter, MD, PhD, Laboratório Interdisciplinar de Neurociências Clínicas, Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil and Department & Institute of Psychiatry, University of Sao Paulo Medical School, Sao Paulo, Brazil; Pino Alonso, MD, PhD, Department of Psychiatry, Bellvitge University Hospital-IDIBELL, Barcelona, Spain and Carlos III Health Institute, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain, and Department of Clinical Sciences, Faculty of Medicine, University of Barcelona, Spain; Stella J. de Wit, MD, Department of Psychiatry, VU University Medical Centre, Amsterdam, The Netherlands; Dick J. Veltman, MD, PhD, Department of Psychiatry, VU University Medical Centre, Amsterdam, The Netherlands; Dan J. Stein, MD, PhD, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa and MRC Unit on Anxiety & Stress Disorders, Department of Psychiatry, University of Stellenbosch, Cape Town, South Africa; Odile A. van den Heuvel, MD, PhD, Department of Psychiatry, VU University Medical Centre, Amsterdam, The Netherlands, Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.

Background: There is accumulating evidence for the role of fronto-striatal and associated circuits in obsessive-compulsive disorder (OCD) but limited and conflicting data on alterations in cortical thickness.

Aims: To investigate alterations in cortical thickness and subcortical volume in OCD.

Method: In total, 412 patients with OCD and 368 healthy adults underwent magnetic resonance imaging scans. Between-group analysis of covariance of cortical thickness and subcortical volumes was performed and regression analyses undertaken.

Results: Significantly decreased cortical thickness was found in the OCD group compared with controls in the superior and inferior frontal, precentral, posterior cingulate, middle temporal, inferior parietal and precuneus gyri. There was also a group × age interaction in the parietal cortex, with increased thinning with age in the OCD group relative to controls.

Conclusions: Our findings are partially consistent with earlier work, suggesting that group differences in grey matter volume and cortical thickness could relate to the same underlying pathology of OCD. They partially support a frontostriatal model of OCD, but also suggest that limbic, temporal and parietal regions play a role in the pathophysiology of the disorder. The group × age interaction effects may be the result of altered neuroplasticity.
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http://dx.doi.org/10.1192/bjp.bp.115.164020DOI Listing
January 2017

Removing and reimplanting deep brain stimulation therapy devices in resistant OCD (when the patient does not respond): case report.

BMC Psychiatry 2016 Feb 6;16:26. Epub 2016 Feb 6.

Psychiatry Department, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), C/ Feixa Llarga s/n, 08907 Hospitalet del Llobregat, Barcelona, Spain.

Background: Deep brain stimulation (DBS) is emerging as a promising tool in the treatment of refractory obsessive-compulsive disorder (OCD) but the search for the best target still continues. This issue is especially relevant when particularly resistant profiles are observed in some patients, which have been ascribed to individual responses to DBS according to differential patterns of connectivity. As patients have been implanted, new dilemmas have emerged, such as what to do when the patient does not respond to surgery.

Case Presentation: Here we describe a 22-year-old male with extremely severe OCD who did not respond to treatment with DBS in the nucleus accumbens, but who did respond after explanting and reimplanting leads targeting the ventral capsule-ventral striatum region. Information regarding the position of the electrodes for both surgeries is provided and possible brain structures affected during stimulation are reviewed. To our knowledge this case is the first in the literature reporting the removal and reimplantation of DBS leads for therapeutical benefits in a patient affected by a mental disorder.

Conclusion: The capability for explantation and reimplantation of leads should be considered as part of the DBS therapy reversibility profile in resistant mental disorders, as it allows application in cases of non-response to the first surgery.
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http://dx.doi.org/10.1186/s12888-016-0730-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744631PMC
February 2016

Incompleteness and not just right experiences in the explanation of Obsessive-Compulsive Disorder.

Psychiatry Res 2016 Feb 7;236:1-8. Epub 2016 Jan 7.

OCD Clinical and Research Unit, Department of Psychiatry, Hospital Universitario de Bellvitge, Barcelona, Spain; CIBERSAM (Centro de Investigación en Red de Salud Mental), Carlos III Health Institute, Spain. Electronic address:

In the past decade, not just right experiences (NJRE) and incompleteness (INC) have attracted renewed interest as putative motivators of symptoms in obsessive-compulsive disorder (OCD), beyond harm avoidance (HA). This study examines, in 267 non-clinical undergraduates and 47 OCD patients, the differential contributions of HA, INC, and NJRE to the different OCD symptom dimensions and the propensity to have the disorder. The results indicate that although both the NJRE and INC range from normality to OCD, their number and intensity significantly increase as the obsessional tendencies increase, which suggests that they are vulnerability markers for OCD. Although they cannot be considered fully specific to OCD, they are more important in explaining OCD symptoms than general distress and harm-related beliefs, and they are also better indicators of OCD severity than HA. In light of the operationalization of both NJRE and INC across the items on their respective questionnaires, the two constructs seem to capture different aspects of the same complex underlying construct: whereas INC might refer to a relatively stable disposition or trait of engaging in compulsive rituals, NJRE resemble obsessions more, and the appraisals that individuals ascribe to the experience would motivate the compulsions.
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http://dx.doi.org/10.1016/j.psychres.2016.01.012DOI Listing
February 2016

Factors Associated with Long-Term Sickness Absence Due to Mental Disorders: A Cohort Study of 7.112 Patients during the Spanish Economic Crisis.

PLoS One 2016 5;11(1):e0146382. Epub 2016 Jan 5.

Psychiatry Department, Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.

Background: Mental health problems are very common and often lead to prolonged sickness absence, having serious economic repercussions for most European countries. Periods of economic crisis are important social phenomena that are assumed to increase sickness absence due to mental disorders, although research on this topic remains scarce. The aim of this study was to gather data on long-term sickness absence (and relapse) due to mental disorders in Spain during a period of considerable socio-economic crisis.

Methods: Relationships were analyzed (using chi-squared tests and multivariate modelling via binary logistic regression) between clinical, social/employment-related and demographic factors associated and long-term sickness absence (>60 consecutive days) due to mental disorders in a cohort of 7112 Spanish patients during the period 2008-2012.

Results: Older age, severe mental disorders, being self-employed, having a non-permanent contract, and working in the real estate and construction sector were associated with an increased probability of long-term sickness absence (gender had a mediating role with respect to some of these variables). Relapses were associated with short-term sick leave (return to work due to 'improvement') and with working in the transport sector and public administration.

Conclusions: Aside from medical factors, other social/employment-related and demographic factors have a significant influence on the duration of sickness absence due to mental disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146382PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701450PMC
August 2016