RESUMEN

CD4-mimetics (CD4mcs) are small molecule compounds that mimic the interaction of the CD4 receptor with HIV-1 envelope glycoproteins (Env). Env from primary viruses normally samples a "closed" conformation that occludes epitopes recognized by CD4-induced (CD4i) non-neutralizing antibodies (nnAbs). CD4mcs induce conformational changes on Env resulting in the exposure of these otherwise inaccessible epitopes. Here, we evaluated the capacity of plasma from a cohort of 50 people living with HIV to recognize HIV-1-infected cells and eliminate them by antibody-dependent cellular cytotoxicity (ADCC) in the presence of a potent indoline CD4mc. We observed a marked heterogeneity among plasma samples. By measuring the levels of different families of CD4i Abs, we found that the levels of anti-cluster A, anti-coreceptor binding site, and anti-gp41 cluster I antibodies are responsible for plasma-mediated ADCC in the presence of CD4mc. IMPORTANCE: There are several reasons that make it difficult to target the HIV reservoir. One of them is the capacity of infected cells to prevent the recognition of HIV-1 envelope glycoproteins (Env) by commonly elicited antibodies in people living with HIV. Small CD4-mimetic compounds expose otherwise occluded Env epitopes, thus enabling their recognition by non-neutralizing antibodies (nnAbs). A better understanding of the contribution of these antibodies to eliminate infected cells in the presence of CD4mc could lead to the development of therapeutic cure strategies.

RESUMEN

BACKGROUND: Chronic inflammation persists in some people living with human immunodeficiency virus (HIV) during antiretroviral therapy and is associated with premature aging. The glycoprotein 120 (gp120) subunit of HIV-1 envelope sheds and can be detected in plasma, showing immunomodulatory properties even in the absence of detectable viremia. We evaluated whether plasma soluble gp120 (sgp120) and a family of gp120-specific anti-cluster A antibodies, linked to CD4 depletion in vitro, contribute to chronic inflammation, immune dysfunction, and subclinical cardiovascular disease in participants of the Canadian HIV and Aging Cohort Study with undetectable viremia. METHODS: Cross-sectional assessment of sgp120 and anti-cluster A antibodies was performed in 386 individuals from the cohort. Their association with proinflammatory cytokines and subclinical coronary artery disease was assessed using linear regression models. RESULTS: High levels of sgp120 and anti-cluster A antibodies were inversely correlated with CD4+ T cell count and CD4/CD8 ratio. The presence of sgp120 was associated with increased levels of interleukin 6. In participants with detectable atherosclerotic plaque and detectable sgp120, anti-cluster A antibodies and their combination with sgp120 levels correlated positively with the total volume of atherosclerotic plaques. CONCLUSIONS: This study showed that sgp120 may act as a pan toxin causing immune dysfunction and sustained inflammation in a subset of people living with HIV, contributing to the development of premature comorbid conditions.

Asunto(s)

Infecciones por VIH , VIH-1 , Humanos , Viremia , Estudios de Cohortes , Estudios Transversales , Canadá , Infecciones por VIH/tratamiento farmacológico , Anticuerpos Anti-VIH , Glicoproteínas , Proteína gp120 de Envoltorio del VIH

RESUMEN

AIM: Interpersonal sensitivity and mistrust are the main characteristics of cluster A personality disorders (CAPD) which might be due to the high accessibility to negative suggestions from environments. Yet the exact associations between hypnotic suggestibility and their personality disorder functioning styles remain unclear. METHODS: We invited 36 patients with CAPD and 115 healthy volunteers to undergo the Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C) and Parker Personality Measure (PERM). RESULTS: Compared to controls; patients scored higher on PERM paranoid; schizoid; schizotypal; borderline; avoidant; and dependent styles; on the SHSS:C total and "challenge suggestions", and the passing rates of "hand lowering", "arm rigidity", "dream", and "arm immobilization". In patients, "dream" negatively predicted the schizoid; "hallucinated voice" negatively the schizotypal; "mosquito hallucination" positively the histrionic and dependent; and "arm immobilization" negatively the avoidant style. CONCLUSIONS: Our results suggested that the insusceptibility to perceptual suggestions from others and the high control over body contribute to the paranoid attitude and interpersonal avoidance in CAPD. These findings help to understand the cause of interpersonal problems in these patients and suggest the trial of hypnotherapy for them.

RESUMEN

A new dimensional-based framework was proposed, the Hierarchical Taxonomy of Psychopathology (HiTOP). This study aimed to develop a specific version of the Dimensional Clinical Personality Inventory 2 (IDCP-2), focused on the assessment of the schizoid personality disorder (SZPD) according to the HiTOP. In stage 1, we developed a new factor to cover all SZPD traits, as presented in the HiTOP. Six factors (one new and five from the IDCP-2) composed the IDCP-SZPD. In stage 2, 434 adults from the community, aged from 18 to 67 years (M=31.6, SD=9.7), completed factors from three self-report measures: the IDCP-SZPD, PID-5, and FFaVA. The IDCP-SZPD factors and total score presented high reliability. Correlations and a bootstrap two-sample t-test comparison corroborated the expectations. Although we found evidence supporting the use of the IDCP-SZPD for the measurement of SZPD traits, further research is needed to verify the replicability of the present findings in samples composed of SZPD patients. (AU)

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Um novo framework dimensional foi proposto, o Hierarchical Taxonomy of Psychopathology (HiTOP). O objetivo deste estudo foi desenvolver uma versão específica do Inventário Dimensional Clínico da Personalidade 2 (IDCP-2), com foco na avaliação do transtorno da personalidade esquizoide (TPE) de acordo com o HiTOP. No estágio 1, foi desenvolvido um novo fator, buscando cobrir todos os traços do TPE apresentados no HiTOP. Compuseram o IDCP-SZPD seis fatores (um novo e cinco do IDCP-2). No estágio 2, 434 adultos da população geral, com idade entre 18 e 67 anos (M = 31.6; DP = 9,7), completaram fatores de três medidas de autorrelato: IDCP-SZPD, PID-5 e FFaVA. Os fatores do IDCP-SZPD e o escore total apresentaram alta precisão. Correlações e comparações via bootstrap two-sample t teste corroboraram as expectativas. Embora evidências favoráveis tenham sido observadas para o uso do IDCP-SZPD, na avaliação de traços do TPE, estudos futuros devem verificar a replicabilidade dos achados em amostras de pacientes com TPE. (AU)

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Un nuevo framework dimensional fue propuesto, el Hierarchical Taxonomy of Psychopathology (HiTOP). El objetivo fue el de desarrollar una versión específica del Inventario Dimensional Clínico de Personalidad 2 (IDCP-2), centrado en la evaluación del trastorno esquizoide de la personalidad (TPE) según el HiTOP. En la etapa 1 se desarrolló un nuevo factor para cubrir todos los rasgos del TPE presentados en el HiTOP. Seis factores (uno nuevo y cinco del IDCP-2) compusieron el IDCP-SZPD. En la etapa 2, 434 adultos de la comunidad, con edades comprendidas entre 18 y 67 años (M =31,6, DS=9,7), completaron los factores de tres medidas de auto-informe: IDCP-SZPD, PID-5 y FFaVA. Los factores del IDCP-SZPD y el puntaje total mostraron una alta confiabilidad. Las correlaciones y la comparación del bootstrap two-sample t test corroboraron las expectativas. Aunque se observaron evidencias favorables para el uso de la IDCP-SZPD para la medición de rasgos de TPE, los estudios posteriores deberían verificar la replicabilidad de los presentes hallazgos en muestras compuestas por pacientes con TPE. (AU)

Asunto(s)

Humanos , Femenino , Adolescente , Persona de Mediana Edad , Anciano , Trastorno de Personalidad Esquizoide/diagnóstico , Psicometría , Análisis por Conglomerados

RESUMEN

HIV-1-infected individuals raise a polyclonal antibody response targeting multiple envelope glycoprotein (Env) epitopes. Interestingly, two classes of non-neutralizing CD4-induced (CD4i) antibodies, present in the majority of HIV-1-infected individuals have been described to mediate antibody-dependent cellular cytotoxicity (ADCC) in the presence of small CD4 mimetic compounds (CD4mc). These antibodies recognize the coreceptor binding site (CoRBS) and the constant region one and two (C1C2 or inner domain cluster A) of the gp120. In combination with CD4mc they have been shown to stabilize an antibody-vulnerable Env conformation, known as State 2A. Here we evaluated the importance of these two families of Abs in ADCC responses by immunizing guinea pigs with gp120 immunogens that have been modified to elicit or not these types of antibodies. Underlying the importance of anti-CoRBS and anti-cluster A Abs in stabilizing State 2A, ADCC responses were only observed in the presence of these two types of CD4i antibodies. Altogether, our results suggest that these two families of CD4i antibodies must be taken into account when considering future strategies relying on the use of CD4mc to eliminate HIV-1-infected cells in vivo.

RESUMEN

Iron-sulfur (Fe-S) clusters play important roles in electron transfer, metabolic and biosynthetic reactions, and the regulation of gene expression. Understanding the biogenesis of Fe-S clusters is therefore relevant to many fields. In the complex process of Fe-S protein formation, the A-type assembly protein (ATAP) family, which consists of several subfamilies, plays an essential role in Fe-S cluster formation and transfer and is highly conserved across the tree of life. However, the taxonomic distribution, motif compositions, and the evolutionary history of the ATAP subfamilies are not well understood. To address these problems, our study investigated the taxonomic distribution of 321 species from a broad cross-section of taxa. Then, we identified common and specific motifs in multiple ATAP subfamilies to explain the functional conservation and nonredundancy of the ATAPs, and a novel, essential motif was found in Eumetazoa IscA1, which has a newly found magnetic function. Finally, we used phylogenetic analytical methods to reconstruct the evolution history of this family. Our results show that two types of ErpA proteins (nonproteobacteria-type ErpA1 and proteobacteria-type ErpA2) exist in bacteria. The ATAP family, consisting of seven subfamilies, can be further classified into two types of ATAPs. Type-I ATAPs include IscA, SufA, HesB, ErpA1, and IscA1, with an ErpA1-like gene as their last common ancestor, whereas type-II ATAPs consist of ErpA2 and IscA2, duplicated from an ErpA2-like gene. During the mitochondrial endosymbiosis, IscA became IscA1 in eukaryotes and ErpA2 became IscA2 in eukaryotes, respectively.

Asunto(s)

Evolución Molecular , Duplicación de Gen , Proteínas Hierro-Azufre/biosíntesis , Secuencias de Aminoácidos/genética , Proteínas Bacterianas/genética , Filogenia

RESUMEN

In the structural biology of bacterial substrate-binding proteins (SBPs), a growing number of comparisons between substrate-bound and substrate-free forms of metal atom-binding (cluster A-I) SBPs have revealed minimal structural differences between forms. These observations contrast with SBPs that bind substrates such as amino acids or nucleic acids and may undergo >60° rigid-body rotations. Substrate transfer in these SBPs is described by a Venus flytrap model, although this model may not apply to all SBPs. In this report, structures are presented of substrate-free (apo) and reconstituted substrate-bound (holo) YfeA, a polyspecific cluster A-I SBP from Yersinia pestis. It is demonstrated that an apo cluster A-I SBP can be purified by fractionation when co-expressed with its cognate transporter, adding an alternative strategy to the mutagenesis or biochemical treatment used to generate other apo cluster A-I SBPs. The apo YfeA structure contains 111 disordered protein atoms in a mobile helix located in the flexible carboxy-terminal lobe. Metal binding triggers a 15-fold reduction in the solvent-accessible surface area of the metal-binding site and reordering of the 111 protein atoms in the mobile helix. The flexible lobe undergoes a 13.6° rigid-body rotation that is driven by a spring-hammer metal-binding mechanism. This asymmetric rigid-body rotation may be unique to metal atom-binding SBPs (i.e. clusters A-I, A-II and D-IV).

Asunto(s)

Transportadoras de Casetes de Unión a ATP/química , Proteínas Bacterianas/química , Yersinia pestis/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , Cristalografía por Rayos X , Modelos Moleculares , Conformación Proteica , Zinc/metabolismo

Asunto(s)

Remediación Cognitiva , Trastorno de la Personalidad Esquizotípica , Terapia Cognitivo-Conductual , Guanfacina , Humanos , Habilidades Sociales

RESUMEN

OBJECTIVE: Impaired cognition is a hallmark of schizophrenia spectrum disorders, including schizotypal personality disorder, and it is the best predictor of functional outcome. Cognitive remediation therapy has demonstrated efficacy for improving cognition, augmenting other rehabilitation efforts in schizophrenia, and effecting gains in real-world functioning. Pharmacological augmentation of cognitive remediation has been attempted, but the effects of augmentation on combined therapies, such as cognitive remediation and social skills training, have not been studied. METHODS: Twenty-eight participants with schizotypal personality disorder enrolled in an 8-week, randomized, double-blind, placebo-controlled trial of guanfacine plus cognitive remediation and social skills training (15 guanfacine, 13 placebo). Cognition was assessed with the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB), social cognition with the Movie for the Assessment of Social Cognition (MASC), and functional capacity with the University of California San Diego Performance-Based Skills Assessment (UPSA). RESULTS: A statistically significant pre- versus posttreatment effect was observed for MCCB speed of processing, verbal learning, and visual learning and UPSA total score. A significant time-by-medication (guanfacine, placebo) interaction was observed for MCCB reasoning and problem solving and UPSA total score; the time-by-treatment interaction approached significance for MASC hypomentalizing errors. CONCLUSIONS: Both guanfacine and cognitive remediation plus social skills training were well tolerated, with no side effects or dropouts. Participants treated with cognitive remediation, social skills training, and guanfacine demonstrated statistically significant improvements in reasoning and problem solving, as well as in functional capacity and possibly social cognition, compared with those treated with cognitive remediation, social skills training, and placebo. Cognitive remediation plus social skills training may be an appropriate intervention for individuals with schizotypal personality disorder, and guanfacine appears to be a promising pharmaceutical augmentation to this psychosocial intervention.

Asunto(s)

Agonistas de Receptores Adrenérgicos alfa 2/uso terapéutico , Remediación Cognitiva/métodos , Guanfacina/uso terapéutico , Trastorno de la Personalidad Esquizotípica/terapia , Habilidades Sociales , Adulto , Terapia Combinada , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas

RESUMEN

HIV-1 conceals epitopes of its envelope glycoproteins (Env) recognized by antibody (Ab)-dependent cellular cytotoxicity (ADCC)-mediating antibodies. These Abs, including anti-coreceptor binding site (CoRBS) and anti-cluster A antibodies, preferentially recognize Env in its "open" conformation. The binding of anti-CoRBS Abs has been shown to induce conformational changes that further open Env, allowing interaction of anti-cluster A antibodies. We explored the possibility that CoRBS Abs synergize with anti-cluster A Abs to engage Fc-gamma receptors to mediate ADCC. We found that binding of anti-CoRBS and anti-cluster A Abs to the same gp120 is required for interaction with soluble dimeric FcγRIIIa in enzyme-linked immunosorbent assays (ELISAs). We also found that Fc regions of both Abs are required to optimally engage FcγRIIIa and mediate robust ADCC. Taken together, our results indicate that these two families of Abs act together in a sequential and synergistic fashion to promote FcγRIIIa engagement and ADCC.IMPORTANCE The "open" CD4-bound conformation of HIV-1 envelope glycoproteins is the primary target of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies present in HIV-positive (HIV+) sera, such as anti-coreceptor binding site and anti-cluster A antibodies. Here we report that the binding of these two families of antibodies is required to engage FcγRIIIa and mediate ADCC.

Asunto(s)

Epítopos/inmunología , Anticuerpos Anti-VIH/inmunología , Infecciones por VIH/prevención & control , VIH-1/inmunología , Receptores de IgG/metabolismo , Linfocitos T/inmunología , Productos del Gen env del Virus de la Inmunodeficiencia Humana/inmunología , Citotoxicidad Celular Dependiente de Anticuerpos , Sitios de Unión , Anticuerpos Anti-VIH/metabolismo , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Unión Proteica , Receptores de IgG/inmunología , Proteínas Recombinantes/inmunología

RESUMEN

BACKGROUND: Personality disorders (PDs) have been associated with both violent crimes and homicides in many studies. The proportion of PDs among prisoners reaches up to 80%. For male prisoners, the most common PD in the literature is antisocial PD. The aim of this study was to investigate the association between PDs and violent crimes/homicides of male prisoners in Greece. METHODS: A sample of 308 subjects was randomly selected from a population of 1300 male prisoners incarcerated in two Greek prisons, one urban and one rural. The presence of PDs was assessed using the Mini International Neuropsychiatric Interview (MINI) and the Personality Diagnostic Questionnaire-4 (PDQ-4). Using logistic regression models PD types and PD "Clusters" (independent variables) were associated with "violent/non-violent crimes" and "homicides/non homicides" (dependent variables). RESULTS: "Cluster A" PDs (Paranoid, Schizoid, and Schizotypal) were diagnosed in 16.2%, "Cluster B" (Antisocial, Borderline, Histrionic, Narcissistic) in 66.9% and "Cluster C" (Obsessive-Compulsive, Dependent, Avoidant) in 2.9% of the studied population. Violent crimes and homicides were found significantly associated with "Cluster A" PDs (p = 0.022, p = 0.020). The odds ratio of committing violent crimes was 2.86 times higher for patients with "Cluster A" PDs than the ones without PDs. In addition, the odds ratio of committing homicides was 4.25 times higher for patients with "Cluster A" PDs. In separate analyses, the commitment of violent crimes as well as homicides, was significantly associated with Schizoid (p = 0.043, p = 0.020) and Schizotypal PD (p = 0.017, p = 0.030). CONCLUSIONS: The majority of prisoners was found to suffer from a PD, mainly the Antisocial "Cluster B", but the commitment of violent crimes and homicides was significantly associated only with "Cluster A" PDs and specifically with Schizoid and Schizotypal PD.

RESUMEN

OBJECTIVE: Both normative personality and DSM-IV personality disorders have been found to be heritable. However, there is limited knowledge about the extent to which the genetic and environmental influences underlying DSM personality disorders are shared with those of normative personality. The aims of this study were to assess the phenotypic similarity between normative and pathological personality and to investigate the extent to which genetic and environmental influences underlying individual differences in normative personality account for symptom variance across DSM-IV personality disorders. METHOD: A large population-based sample of adult twins was assessed for DSM-IV personality disorder criteria with structured interviews at two waves spanning a 10-year interval. At the second assessment, participants also completed the Big Five Inventory, a self-report instrument assessing the five-factor normative personality model. The proportion of genetic and environmental liabilities unique to the individual personality disorder measures, and hence not shared with the five Big Five Inventory domains, were estimated by means of multivariate Cholesky twin decompositions. RESULTS: The median percentage of genetic liability to the 10 DSM-IV personality disorders assessed at wave 1 that was not shared with the Big Five domains was 64%, whereas for the six personality disorders that were assessed concurrently at wave 2, the median was 39%. Conversely, the median proportions of unique environmental liability in the personality disorders for wave 1 and wave 2 were 97% and 96%, respectively. CONCLUSIONS: The results indicate that a moderate-to-sizable proportion of the genetic influence underlying DSM-IV personality disorders is not shared with the domain constructs of the Big Five model of normative personality. Caution should be exercised in assuming that normative personality measures can serve as proxies for DSM personality disorders when investigating the etiology of these disorders.

Asunto(s)

Enfermedades en Gemelos/genética , Trastornos de la Personalidad/genética , Personalidad/genética , Adulto , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Enfermedades en Gemelos/psicología , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Trastornos de la Personalidad/diagnóstico , Trastornos de la Personalidad/psicología , Inventario de Personalidad , Gemelos Dicigóticos/genética , Gemelos Dicigóticos/psicología , Gemelos Monocigóticos/genética , Gemelos Monocigóticos/psicología

RESUMEN

Antibodies can have an impact on HIV-1 infection in multiple ways, including antibody-dependent cellular cytotoxicity (ADCC), a correlate of protection observed in the RV144 vaccine trial. One of the most potent ADCC-inducing epitopes on HIV-1 Env is recognized by the C11 antibody. Here, we present the crystal structure, at 2.9 Å resolution, of the C11-like antibody N12-i3, in a quaternary complex with the HIV-1 gp120, a CD4-mimicking peptide M48U1, and an A32-like antibody, N5-i5. Antibody N12-i3 recognizes an epitope centered on the N-terminal "eighth strand" of a critical ß sandwich, which our analysis indicates to be emblematic of a late-entry state, after the gp120 detachment. In prior entry states, this sandwich comprises only seven strands, with the eighth strand instead pairing with a portion of the gp120 C terminus. The conformational gymnastics of HIV-1 gp120 thus includes altered ß-strand pairing, possibly to reduce immunogenicity, although nevertheless still recognized by the human immune system.

Asunto(s)

Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Anti-VIH/inmunología , Proteína gp120 de Envoltorio del VIH/química , VIH-1/inmunología , Internalización del Virus/efectos de los fármacos , Secuencia de Aminoácidos , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/farmacología , Anticuerpos Antivirales/química , Anticuerpos Antivirales/farmacología , Citotoxicidad Celular Dependiente de Anticuerpos , Sitios de Unión , Antígenos CD4/química , Antígenos CD4/inmunología , Línea Celular , Cristalografía por Rayos X , Epítopos/química , Epítopos/inmunología , Anticuerpos Anti-VIH/química , Anticuerpos Anti-VIH/farmacología , Proteína gp120 de Envoltorio del VIH/inmunología , VIH-1/genética , Humanos , Inmunidad Innata , Modelos Moleculares , Imitación Molecular , Péptidos/síntesis química , Péptidos/inmunología , Unión Proteica , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de Proteínas , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Linfocitos T/inmunología , Linfocitos T/virología

Asunto(s)

Diagnóstico Precoz , Trastornos de la Personalidad/diagnóstico , Trastornos de la Personalidad/epidemiología , Femenino , Humanos , Masculino , Estados Unidos/epidemiología , Adulto Joven

RESUMEN

From a perspective of conceptual evolution schizoidia was initially considered to describe features both of the premorbid personality of schizophrenic patients and of the personalities of non-psychotic family members (Bleuler, Kahlbaum, Kraepelin). On a psychopatholocial level a close link to the complex basic symptom of autism was stressed. From the very beginnings of modern psychiatry schizoidia was discussed within a conceptual frame of schizophrenia spectrum disorders (Kretschmer, Hoch, Polatin). Approaches to operationalize these conceptual works laid the basis for the cluster A personalities in DSM-III. Due to the prominent concept of schizotypy (Kety, Rado, Meehl) three split up diagnostic categories of schizotypal, schizoid and paranoid personality disorders resulted. Cluster A personality disorders are frequent in community-based epidemiological studies. Health-care seeking behaviour due to primary personality-related problems, however, seems to be less paramount compared to cluster B and C personality disorders. Many family- and twin-based genetic studies convincingly stress a close link between schizotypal personality disorder and schizophrenia. This link is less pronounced for paranoid personality disorder, and even vanishingly low for schizoid personality disorder. From a perspective of schizophrenia spectrum disorders a vast amount of data from molecular genetic, neurobiological, neuropsychological and psychosocial research has impressingly confirmed this link for schizotypal personality disorder. Major research deficits, however, have to be noticed for paranoid and schizoid personality disorder.

Asunto(s)

Trastorno de la Personalidad Esquizotípica/diagnóstico , Enfermedades en Gemelos/diagnóstico , Enfermedades en Gemelos/genética , Enfermedades en Gemelos/psicología , Predisposición Genética a la Enfermedad/genética , Trastorno de Personalidad Paranoide/clasificación , Trastorno de Personalidad Paranoide/diagnóstico , Trastorno de Personalidad Paranoide/genética , Trastorno de Personalidad Paranoide/psicología , Trastorno de Personalidad Esquizoide/clasificación , Trastorno de Personalidad Esquizoide/diagnóstico , Trastorno de Personalidad Esquizoide/genética , Trastorno de Personalidad Esquizoide/psicología , Esquizofrenia/clasificación , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Psicología del Esquizofrénico , Trastorno de la Personalidad Esquizotípica/clasificación , Trastorno de la Personalidad Esquizotípica/genética , Trastorno de la Personalidad Esquizotípica/psicología

RESUMEN

Objective: It is unclear why some individuals reporting psychotic experiences have balanced lives while others go on to develop mental health problems. The objective of this study was to test if the personality traits of harm avoidance, self-directedness, and self-transcendence can be used as criteria to differentiate healthy from unhealthy schizotypal individuals. Methods: We interviewed 115 participants who reported a high frequency of psychotic experiences. The instruments used were the Temperament and Character Inventory (140), Structured Clinical Interview for DSM-IV, and the Oxford-Liverpool Inventory of Feelings and Experiences. Results: Harm avoidance predicted cognitive disorganization (β = 0.319; t = 2.94), while novelty seeking predicted bipolar disorder (β = 0.136, Exp [β] = 1.146) and impulsive non-conformity (β = 0.322; t = 3.55). Self-directedness predicted an overall decrease in schizotypy, most of all in cognitive disorganization (β = -0.356; t = -2.95) and in impulsive non-conformity (β = -0.313; t = -2.83). Finally, self-transcendence predicted unusual experiences (β = 0.256; t = 2.32). Conclusion: Personality features are important criteria to distinguish between pathology and mental health in individuals presenting high levels of anomalous experiences (AEs). While self-directedness is a protective factor, both harm avoidance and novelty seeking were predictors of negative mental health outcomes. We suggest that the impact of AEs on mental health is moderated by personality factors.

Asunto(s)

Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Trastornos Psicóticos/fisiopatología , Trastornos Psicóticos/psicología , Trastorno de la Personalidad Esquizotípica/fisiopatología , Trastorno de la Personalidad Esquizotípica/psicología , Salud Mental , Ansiedad/psicología , Inventario de Personalidad , Escalas de Valoración Psiquiátrica , Religión y Psicología , Temperamento/fisiología , Brasil , Carácter , Factores Sexuales , Estudios Transversales , Encuestas y Cuestionarios , Factores de Edad , Estadísticas no Paramétricas

RESUMEN

Objective: To assess the relationship of biological rhythms, evaluated by the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), with affective temperaments and schizotypy. Methods: The BRIAN assessment, along with the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A) and the Oxford-Liverpool Inventory for Feelings and Experiences (O-LIFE), was administered to 54 patients with remitted bipolar disorder (BD) and 54 healthy control (HC) subjects. Results: The TEMPS-A cyclothymic temperament correlated positively and the hyperthymic temperament correlated negatively with BRIAN scores in both the BD and HC groups, although the correlation was stronger in BD subjects. Depressive temperament was associated with BRIAN scores in BD but not in HC; conversely, the irritable temperament was associated with BRIAN scores in HC, but not in BD. Several positive correlations between BRIAN scores and the schizotypal dimensions of the O-LIFE were observed in both BD and HC subjects, especially with cognitive disorganization and less so with unusual experiences and impulsive nonconformity. A correlation with introversion/anhedonia was found only in BD subjects. Conclusion: Cyclothymic and depressive temperaments predispose to disturbances of biological rhythms in BD, while a hyperthymic temperament can be protective. Similar predispositions were also found for all schizotypal dimensions, mostly for cognitive disorganization.

Asunto(s)

Humanos , Masculino , Femenino , Adulto , Periodicidad , Trastorno de la Personalidad Esquizotípica/psicología , Trastorno Bipolar/psicología , Inventario de Personalidad , Trastorno de la Personalidad Esquizotípica/rehabilitación , Temperamento , Trastorno Bipolar/tratamiento farmacológico , Estudios de Casos y Controles , Compuestos de Litio/uso terapéutico

RESUMEN

BACKGROUND: The reported rates of personality disorder (PD) in subjects with schizophrenia (SZ) are quite varied across different countries, and less is known about the heterogeneity of PD among subjects with SZ. We examined the co-morbidity of PD among patients who are in the stable phase of SZ. METHOD: 850 subjects were randomly sampled from patients diagnosed with SZ in psychiatric and psycho-counseling clinics at Shanghai Mental Health Center. Co-morbidity of PDs was assessed through preliminary screening and patients were administered several modules of the SCID-II. Evidence of heterogeneity was evaluated by comparing patients diagnosed with SZ with those who presented with either affective disorder or neurosis (ADN). RESULTS: 204 outpatients (24.0 %) in the stable phase of SZ met criteria for at least one type of DSM-IV PD. There was a higher prevalence of Cluster-A (odd and eccentric PD) and C (anxious and panic PD) PDs in SZ (around 12.0 %). The most prevalent PD was the paranoid subtype (7.65 %). Subjects with SZ were significantly more likely to have schizotypal PD (4.4 % vs. 2.1 %, p = 0.003) and paranoid PD (7.6 % vs. 5.4 %, p = 0.034), but much less likely to have borderline, obsessive-compulsive, depressive, narcissistic and histrionic PD. CONCLUSIONS: These findings suggest that DSM-IV PD is common in patients with SZ than in the general population. Patterns of co-morbidity with PDs in SZ are different from ADN.

Asunto(s)

Pacientes Ambulatorios/psicología , Trastornos de la Personalidad/epidemiología , Esquizofrenia/epidemiología , Adulto , China/epidemiología , Comorbilidad , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Trastornos de la Personalidad/psicología , Prevalencia , Psicología del Esquizofrénico

RESUMEN

INTRODUCTION: A personality disorder is a pervasive and enduring pattern of behaviors that impacts an individual's social, occupational, and overall functioning. Specifically, the cluster A personality disorders include paranoid personality disorder, schizoid personality disorder, and schizotypal personality disorder. Patients with cluster A personality disorders tend to be isolative and avoid relationships. The quality of life may also be reduced in these individuals, which provokes the question of how to treat patients with these personality disorders. The purpose of this review is to evaluate the current literature for pharmacologic treatments for the cluster A personality disorders. METHODS: A Medline/PubMed and Ovid search was conducted to identify literature on the psychopharmacology of paranoid personality disorder, schizoid personality disorder, and schizotypal personality disorder. There were no exclusions in terms of time frame from article publication or country of publication, in order to provide a comprehensive analysis; however, only articles that contained information on the cluster A disorders were included. RESULTS: Minimal evidence regarding pharmacotherapy in paranoid and schizoid personality disorders was found. Literature was available for pharmacologic treatment of schizotypal personality disorder. Studies evaluating the use of olanzapine, risperidone, haloperidol, fluoxetine, and thiothixene did yield beneficial results; however, treatment with such agents should be considered on a case-by-case basis. DISCUSSION: Most of the literature analyzed in this review presented theoretical ideas of what may constitute the neurobiologic factors of personality and what treatments may address these aspects. Further research is needed to evaluate specific pharmacologic treatment in the cluster A personality disorders. At this time, treatment with pharmacologic agents is based on theory rather than evidence.