Update on Obsessive Compulsive Disorder: from categorical proposals to symptom dimensions

El Trastorno Obsesivo Compulsivo (TOC) tiene una larga tradición en la psicopatología. Sin embargo, su heterogeneidad sintomática ha suscitado numerosas controversias. Nos proponemos llevar a cabo una revisión crítica sobre las aportaciones que diversos autores han formulado al respecto partiendo de las propuestas unitarias y categoriales del TOC hasta las propuestas heterogéneas y dimensionales que se barajan en la actualidad. Así, se revisaran cuestiones relacionadas con la psicopatología del TOC, deteniéndonos en las propuestas unitarias sobre la conceptualización del trastorno, analizando someramente el concepto del espectro obsesivo-compulsivo, como paso previo a una revisión más exhaustiva de las formulaciones dimensionales. Los resultados de la investigación desde modelos dimensionales aportan una visión, aunque incompleta, más adecuada a la heterogeneidad de las manifestaciones sintomáticas del trastorno y permiten un mejor conocimiento del mismo, tanto desde el punto de vista diagnóstico como terapéuticoObsessive Compulsive Disorder (OCD) has a long tradition in psychopathology. However, symptomatic heterogeneity has led to numerous disputes. We made a critical review of the contributions that various authors have formulated from the basis of the unitary and categorical proposals about OCD, to dimensional ones being considered today. Thus, we review issues related to the psychopathology of OCD, stopping in the unitary proposals on the conceptualization of the disorder, briefly examining the concept of obsessive compulsive spectrum, as a prelude to a more thorough review of dimensional formulations. The research results from dimensional models provide a vision, albeit incomplete, better suited to the heterogeneity of the symptomatic manifestations of the disorder and lead to better conceptualization of it, both from the standpoint of diagnosis and treatmen

Personality disorders in obsessive-compulsive disorder: A comparative study versus other anxiety disorders

Objective. The purpose of this paper is to provide evidence for the relationship between personality disorders (PDs), obsessive compulsive disorder (OCD), and other anxiety disorders different from OCD (non-OCD) symptomatology. Method. The sample consisted of a group of 122 individuals divided into three groups (41 OCD; 40 non-OCD, and 41 controls) matched by sex, age, and educational level. All the individuals answered the IPDE questionnaire and were evaluated by means of the SCID-I and SCID-II interviews. Results. Patients with OCD and non-OCD present a higher presence of PD. There was an increase in cluster C diagnoses in both groups, with no statistically significant differences between them. Conclusions. Presenting anxiety disorder seems to cause a specific vulnerability for PD. Most of the PDs that were presented belonged to cluster C. Obsessive Compulsive Personality Disorder (OCPD) is the most common among OCD. However, it does not occur more frequently among OCD patients than among other anxious patients, which does not confirm the continuum between obsessive personality and OCD. Implications for categorical and dimensional diagnoses are discussed

Effect of Cytochrome P450 and ABCB1 Polymorphisms on Imatinib Pharmacokinetics After Single-Dose Administration to Healthy Subjects

Background: Validated genomic biomarkers for oncological drugs are expanding to improve targeted therapies. Pharmacogenetics research focusing on the mechanisms underlying imatinib suboptimal response might help to explain the different treatment outcomes and drug safety profiles. Objective: To investigate whether polymorphisms in genes encoding cytochrome P450 (CYP) enzymes and ABCB1 transporter affect imatinib pharmacokinetic parameters.Methods: A prospective, multicenter, pharmacogenetic pilot study was performed in the context of two separate oral imatinib bioequivalence clinical trials, which included 26 healthy volunteers. DNA was extracted in order to analyze polymorphisms in genes CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and ABCB1. Imatinib plasma concentrations were measured by HPLC-MS/MS. Pharmacokinetic parameters were calculated by non-compartmental methods using WinNonlin software. Results: Volunteers (n = 26; aged 24 ± 3 years; 69% male) presented regular pharmacokinetic imatinib data (concentration at 24 h, 436 ± 140 ng/mL and at 72 h, 40 ± 26 ng/mL; AUC0-72 32,868 ± 10,713 ng/mL⋅h; and Cmax 2074 ± 604 ng/mL). CYP2B6 516GT carriers showed a significant reduction of imatinib concentration at 24 h (23%, 391 ng/dL vs 511 ng/dL in 516GG carriers, p = 0.005) and elimination half-life (11%, 12.6 h vs 14.1 h in 516GG carriers, p = 0.041). Carriers for CYP3A4 (*22/*22, *1/*20 and *1/*22 variants) showed a reduced frequency of adverse events compared to *1/*1 carriers (0 vs 64%, p = 0.033). The other polymorphisms analyzed did not influence pharmacokinetics or drug toxicity. Conclusion: CYP2B6 G516T and CYP3A4 *20,*22 polymorphisms could influence imatinib plasma concentrations and safety profile, after single-dose administration to healthy subjects. This finding needs to be confirmed before it is implemented in clinical practice in oncological patients under treatment with imatinib

Population pharmacokinetic modelling of imatinib in healthy subjects receiving a single dose of 400 mg

Purpose: Imatinib is indicated for treatment of CML, GIST, etc. The population pharmacokinetics (popPK) of imatinib in patients under long-term treatment are reported in literature. Data obtained from bioequivalence trials for healthy subjects were used to evaluate the influence of demographic and pharmacogenetic factors on imatinib pharmacokinetics (PK) in a collective without concurrent drugs, organ dysfunction, inflammation etc. In addition, the differences in PK between the healthy subjects and a patient cohort was examined to identify possible disease effects. Methods: 26 volunteers were administered orally with single dose of 400 mg imatinib. 16–19 plasma samples per volunteer were collected from 0.5 up to 72 h post-dose. The popPK was built and post hoc estimates were compared with previously published PK parameters evaluated by non-compartmental analysis in the same cohort. The predictivity of the model for data collected from 40 patients with gastrointestinal stromal tumors at steady state was evaluated. Results: The popPK was best described by a two-compartment transit model with first-order elimination. No significant covariates were identified, probably due to the small cohort and the narrow range of demographic covariates; CYP3A5 phenotypes appeared to have some influence on the clearance of imatinib. Good agreement between non-compartment and popPK analyses was observed with the differences of the geometric means/ median of PK estimates below 10%. The model indicated lower clearance for patients compared to healthy volunteers (p value < 0.01). Conclusion: The two-compartment transit model adequately describes the absorption and distribution of imatinib in healthy volunteers. For patients, a lower clearance of imatinib compared to healthy volunteer was estimated by the model. The model can be applied for dose individualization based on trough concentrations assuming no significant differences in absorption between patients and healthy volunteersThis work was part of the master these of Yi-Han Chien. There was no funding for this work. P. Zubiaur’s contract with CIBERehd is fnanced by the “Infraestructura de Medicina de Precisión asociada a la Ciencia y Tecnología (IMPaCT, IMP/00009)”, Instituto de Salud Carlos III (ISCIII

Incidence, hospitalization, mortality and risk factors of COVID-19 in long-term care residential homes for patients with chronic mental illness

Long-term care residential homes (LTCRH) for patients with chronic mental illness have suffered the enormous impact of COVID-19. This study aimed to estimate incidence, hospitalization, mortality, and risk factors of COVID-19 to prevent future epidemics. From March 2020 to January 2021 and before vaccination anti-SARS-CoV-2 begins, cumulate incidence rate (CIR), hospitalization rate (HR), mortality rate (MR), and risk factors of COVID-19 in the 11 LTCRH of two Health Departments of Castellon (Spain) were studied by epidemiological surveillance and an ecological design. Laboratory tests confirmed COVID-19 cases, and multilevel Poisson regression models were employed. All LTCRH participated and comprised 346 residents and 482 staff. Residents had a mean age of 47 years, 40% women, and suffered 75 cases of COVID-19 (CIR = 21.7%), five hospitalizations (HR = 1.4%), and two deaths (MR = 0.6%) with 2.5% fatality-case. Staff suffered 74 cases of the disease (CIR = 15.4%), one hospitalization (HR = 0.2%), and no deaths were reported. Risk factors associated with COVID-19 incidence in residents were private ownership, severe disability, residents be younger, CIR in municipalities where LTCRH was located, CIR in staff, and older age of the facilities. Conclusion: COVID-19 incidence could be prevented by improving infection control in residents and staff and modernizing facilities with increased public ownership

Asociación entre Artritis Reumatoidea y otras enfermedades autoinmunes

Objetivos: determinar la frecuencia de enfermedades autoinmunes (EAI) en pacientes con Artritis Reumatoidea (AR) y comparar la frecuencia de EAI entre pacientes con AR y sin AR ni otra EAI reumatológica. Material y Métodos: estudio multicéntrico, observacional, analítico, retrospectivo. Se incluyeron pacientes consecutivos con AR (ACR/EULAR 2010) y como grupo control pacientes con diagnóstico inicial de Osteoartritis primaria (OA).

The neurobiology of obsessive-compulsive disorder: new findings from functional magnetic resonance imaging (I)

Introduction. In recent years, neuroscience has shown a growing interest in applying its methods to furthering the knowledge of psychiatric disorders, and one of the fundamental tools used to do so are neuroimaging techniques. Yet, in general, few studies have been conducted in which functional magnetic resonance has been applied in this field and findings are sometimes contradictory. Aims. In this first part of our work we review the specialised bibliography and present a critical discussion on the scientific literature published to date on neuroimaging and neuropsychology of one of the most widely studied disorders from a neurobiological point of view, namely, obsessive-compulsive disorder (OCD). Development. The article outlines the basic aspects of neurobiological research into OCD, which has focused more especially on studying the cortico-striato-thalamic system. Results of this research suggest the existence of a deficit in the response inhibition as the possible cognitive substrate underlying the symptoms of OCD. In the second part, we will review the papers dealing with the use of this neuroimaging technique that have been indexed in the most commonly used medical databases on the topic since 1996. Conclusions. Response inhibition seems to be an important cognitive domain when it comes to explaining this disorder. Most studies suggest that the prefrontal cortex (orbitofrontal and cingulate), the basal ganglia and the thalamus are related with the pathogenesis of OCDIntroducción. En los últimos años, la neurociencia ha experimentado un creciente interés por aplicar sus métodos al conocimiento de los trastornos psiquiátricos y una de las herramientas fundamentales para ello son las técnicas de neuroimagen. No obstante, en general, los estudios de aplicación de la resonancia magnética funcional en este ámbito son escasos y, en ocasiones, contradictorios. Objetivo. En esta primera parte del trabajo se revisa la bibliografía especializada y se describe, de forma crítica, la literatura científica existente hasta la actualidad sobre neuroimagen y neuropsicología de uno de los trastornos más estudiados desde un punto de vista neurobiológico, como es el trastorno obsesivo-compulsivo (TOC). Desarrollo. Se exponen los aspectos básicos de la investigación neurobiológica en el TOC, que ha mostrado un especial interés en el estudio de sistema corticoestriadotalámico, y que sugiere un déficit en la inhibición de respuesta como posible sustrato cognitivo de los síntomas del TOC. En la segunda parte, se revisarán los artículos sobre la utilización de esta técnica de neuroimagen indexados en las bases de datos médicas más utilizadas sobre el tema desde 1996. Conclusión. La inhibición de respuesta parece ser un importante dominio cognitivo a la hora de explicar este trastorno. La mayoría de estudios sugiere que el córtex prefrontal (orbitofrontal y cíngulo), los ganglios basales y el tálamo se relacionan con la patogénesis del TO

Implicación del circuito corticoestriadotalámico en pacientes con trastorno obsesivo-compulsivo durante una tarea de control inhibitorio con contingencias de recompensa y castigo

Introducción. Estudios recientes sobre neuroimagen en el trastorno obsesivo-compulsivo (TOC) muestran alteraciones en el circuito frontoestriadotalámico, lo que daría lugar a una disfunción ejecutiva. Éste podría ser el sustrato neurocognitivo de los síntomas principales del TOC: obsesiones y compulsiones. Sujetos y métodos. Se comparó tanto la activación cerebral como el rendimiento conductual de un grupo de 13 pacientes con TOC comparado con un grupo control de 13 sujetos sanos a través de resonancia magnética funcional durante la ejecución de una tarea de control inhibitorio con contingencias de recompensa y castigo. Los efectos de la medicación también se analizaron. Resultados. Los análisis intragrupo mostraron un tiempo de reacción más largo durante la condición de go/no go en ambos grupos, aunque no hubo diferencias entre los grupos en la ejecución de la tarea. En relación con dicha tarea, se observó, en los sujetos sanos, una activación significativa de grandes áreas del cerebelo y de los lóbulos occipital, temporal y parietal. En comparación con los controles, los pacientes obsesivos mostraron una activación reducida en los giros frontal medial y superior derechos, la corteza cingulada anterior y el núcleo caudado, y una mayor activación en la circunvolución parietal inferior y el giro fusiforme. Se encontraron efectos de la medicación en la corteza frontal y estructuras basales. Conclusiones. Estos resultados están de acuerdo con el argumento de que la disfunción en el sistema corticoestriado en el TOC se asocia a una disminución de la actividad cerebral en respuesta a tareas cognitivas