A new role for erythropoietin in the homeostasis of red blood cells.

The regulation of red blood cell (RBC) homeostasis is widely assumed to rely on the control of cell production by erythropoietin (EPO) and the destruction of cells at a fixed, species-specific age. In this work, we show that such a regulatory mechanism would be a poor homeostatic solution to satisfy the changing needs of the body. Effective homeostatic control would require RBC lifespan to be variable and tightly regulated. We suggest that EPO may control RBC lifespan by determining CD47 expression in newly formed RBCs and SIRP-α expression in sinusoidal macrophages. EPO could also regulate the initiation and intensity of anti-RBC autoimmune responses that curtail RBC lifespan in some circumstances. These mechanisms would continuously modulate the rate of RBC destruction depending on oxygen availability. The control of RBC lifespan by EPO and autoimmunity emerges as a key mechanism in the homeostasis of RBCs.

Knowledge of the treatment in schizophrenia and schizoaffective disorder and its relationship with nonadherence.

Despite its potential impor- tance for adherence, knowledge of the treatment has been little studied in patients with psychosis. We performed this study to assess the possible association between knowledge of the treatment and nonadherence, unintentional nonad- herence (UNA) and intentional nonadherence (INA).

Conocimiento del tratamiento en esquizofrenia y trastorno esquizoafectivo y su relación con la no adherencia / Knowledge of the treatment in schizophrenia and schizoaffective disorder and its relationship with nonadherence

Introducción. El conocimiento del tratamiento ha sidoescasamente estudiado en pacientes con psicosis, a pesar de su potencial importancia para la adherencia. Evaluamos la posible asociación entre el conocimiento del tratamiento y la no adherencia, no adherencia no intencional (NANI) y no adherencia intencional (NAI). Metodología. Se incluyeron 106 pacientes con diagnóstico de esquizofrenia o trastorno esquizoafectivo que ingresaron consecutivamente. Las evaluaciones se realizaron durante la hospitalización y a los seis meses de seguimiento. Se incluyeron variables sociodemográficas, clínicas, psicopatológicas y relacionadas con el tratamiento. La adherencia se definió como la concurrencia de adherencia al tratamiento antipsicótico y adherencia al seguimiento ambulatorio durante ese periodo de seis meses. Establecimos dos subtipos de no adherencia dependiendo del motivo principal de no adherencia: NANI y NAI. Resultados. El 45,3% de los pacientes mostraron un inadecuado conocimiento del tratamiento. Los pacientes adherentes, comparados con los no adherentes, no mostraron diferencias en el conocimiento del tratamiento (mediana 77 vs. 77, respectivamente; p = 0,232). Sin embargo, los pacientes NANI presentaron peor conocimiento del tratamiento comparados con los pacientes adherentes (mediana 62 vs. 77 respectivamente; p < 0,001), mientras que los pacientes NAI presentaron mejor conocimiento del tratamiento comparados con los pacientes adherentes (mediana 86 vs. 77, respectivamente; p = 0,026). Conclusión. Un alto porcentaje de los pacientes con esquizofrenia y trastorno esquizoafectivo no tienen un adecuado conocimiento del tratamiento. Además, nuestros resultados sugieren que un inadecuado conocimiento del tratamiento puede contribuir a la no adherencia en pacientescon no adherencia no intencional. (AU)

Background and objectives. Despite its potential importance for adherence, knowledge of the treatment has been little studied in patients with psychosis. We performed this study to assess the possible association between knowledge of the treatment and nonadherence, unintentional nonadherence (UNA) and intentional nonadherence (INA). Methods. We assessed 106 consecutively admitted patients diagnosed with schizophrenia or schizoaffective disorder. Evaluations were carried out during hospitalization and after six-months of follow-up. This included sociodemographic, clinical, psychopathologic variables and those related to treatment. Adherence was interpreted as the concurrence of adherence to antipsychotic treatment and adherence to outpatient follow-up over the course of the six-month period. We established two subtypes according to the main reason for nonadherence: unintentional and intentional nonadherence. Results. Inadequate knowledge of the treatment was detected in 45.3% of patients. Adherent patients, as compared to nonadherent patients, showed no difference regarding knowledge of the treatment (median 77 vs. 77, respectively; p = 0.232). Nevertheless, UNA patients showed worse knowledge of the treatment as compared to adherent patients (median 62 vs. 77 respectively; p < 0.001), whereas INA patients showed better knowledge of the treatment as compared to adherent patients (median 86 vs. 77, respectively; p = 0.026). Conclusions. A large number of patients with schizophrenia or schizoaffective disorder did not have an appropriate knowledge of their treatment. More importantly, our results suggest that inadequate knowledge of the treatment may contribute to nonadherence in patients with unintentional nonadherence. (AU)

Brain IGF-I regulates LTP, spatial memory, and sexual dimorphic behavior.

Insulin-like growth factor-I (IGF-I) exerts multiple actions, yet the role of IGF-I from different sources is poorly understood. Here, we explored the functional and behavioral consequences of the conditional deletion of Igf-I in the nervous system (Igf-I Δ/Δ), and demonstrated that long-term potentiation was impaired in hippocampal slices. Moreover, Igf-I Δ/Δ mice showed spatial memory deficits in the Morris water maze, and the significant sex-dependent differences displayed by Igf-I Ctrl/Ctrl mice disappeared in Igf-I Δ/Δ mice in the open field and rota-rod tests. Brain Igf-I deletion disorganized the granule cell layer of the dentate gyrus (DG), and it modified the relative expressions of GAD and VGLUT1, which are preferentially localized to inhibitory and excitatory presynaptic terminals. Furthermore, Igf-I deletion altered protein modules involved in receptor trafficking, synaptic proteins, and proteins that functionally interact with estrogen and androgen metabolism. Our findings indicate that brain IGF-I is crucial for long-term potentiation, and that it is involved in the regulation of spatial memory and sexual dimorphic behaviors, possibly by maintaining the granule cell layer structure and the stability of synaptic-related protein modules.

The coordination of anti-phage immunity mechanisms in bacterial cells.

Bacterial cells are equipped with a variety of immune strategies to fight bacteriophage infections. Such strategies include unspecific mechanisms directed against any phage infecting the cell, ranging from the identification and cleavage of the viral DNA by restriction nucleases (restriction-modification systems) to the suicidal death of infected host cells (abortive infection, Abi). In addition, CRISPR-Cas systems generate an immune memory that targets specific phages in case of reinfection. However, the timing and coordination of different antiviral systems in bacterial cells are poorly understood. Here, we use simple mathematical models of immune responses in individual bacterial cells to propose that the intracellular dynamics of phage infections are key to addressing these questions. Our models suggest that the rates of viral DNA replication and cleavage inside host cells define functional categories of phages that differ in their susceptibility to bacterial anti-phage mechanisms, which could give raise to alternative phage strategies to escape bacterial immunity. From this viewpoint, the combined action of diverse bacterial defenses would be necessary to reduce the chances of phage immune evasion. The decision of individual infected cells to undergo suicidal cell death or to incorporate new phage sequences into their immune memory would be determined by dynamic interactions between the host's immune mechanisms and the phage DNA. Our work highlights the importance of within-cell dynamics to understand bacterial immunity, and formulates hypotheses that may inspire future research in this area.

Morphological Diversity of Calretinin Interneurons Generated From Adult Mouse Olfactory Bulb Core Neural Stem Cells.

Neural stem cells (NSCs) in the olfactory bulb (OB) core can generate mature interneurons in the adult mice brain. The vast majority of these adult generated cells express the calcium-binding protein Calretinin (CalR), and they migrate towards different OB layers. However, these cells have yet to be fully characterized and hence, to achieve this we injected retroviral particles expressing GFP into the OB core of adult animals and found that the CalR+ neurons generated from NSCs mainly migrate to the granule cell layer (GCL) and glomerular layer (GL) in similar proportions. In addition, since morphology and function are closely related, we used three-dimensional imaging techniques to analyze the morphology of these adult born cells, describing new subtypes of CalR+ interneurons based on their dendritic arborizations and projections, as well as their localization in the GCL or GL. We also show that the migration and morphology of these newly generated neurons can be altered by misexpressing the transcription factor Tbr1 in the OB core. Therefore, the morphology acquired by neurons located in a specific OB layer is the result of a combination of both extrinsic (e.g., layer allocation) and intrinsic mechanisms (e.g., transcription factors). Defining the cellular processes and molecular mechanisms that govern adult neurogenesis might help better understand brain circuit formation and plasticity, as well as eventually opening the way to develop strategies for brain repair.

Killing the competition: a theoretical framework for liver-stage malaria.

The first stage of malaria infections takes place inside the host's hepatocytes. Remarkably, Plasmodium parasites do not infect hepatocytes immediately after reaching the liver. Instead, they migrate through several hepatocytes before infecting their definitive host cells, thus increasing their chances of immune destruction. Considering that malaria can proceed normally without cell traversal, this is indeed a puzzling behaviour. In fact, the role of hepatocyte traversal remains unknown to date, implying that the current understanding of malaria is incomplete. In this work, we hypothesize that the parasites traverse hepatocytes to actively trigger an immune response in the host. This behaviour would be part of a strategy of superinfection exclusion aimed to reduce intraspecific competition during the blood stage of the infection. Based on this hypothesis, we formulate a comprehensive theory of liver-stage malaria that integrates all the available knowledge about the infection. The interest of this new paradigm is not merely theoretical. It highlights major issues in the current empirical approach to the study of Plasmodium and suggests new strategies to fight malaria.

Nonadherence after hospital discharge in patients with schizophrenia or schizoaffective disorder: A six-month naturalistic follow-up study.

BACKGROUND: Despite a wealth of studies seeking to identify factors associated with nonadherence few consistent predictors have been determined, and several gaps still exist in the literature. METHOD: We assessed 110 consecutively admitted patients diagnosed with schizophrenia or schizoaffective disorder according to ICD-10 criteria. Assessments were performed during hospitalization and at six-months follow-up. Evaluation included sociodemographic, clinical, psychopathologic and treatment-related variables. Prevalence of nonadherence, associated variables, reasons for nonadherence and possible subtypes were explored. Adherence was defined as the concurrence of adherence to antipsychotic treatment and adherence to outpatient follow-up, during the six-month period. RESULTS: Nonadherence was detected in 58.2% of patients. An identifiable profile was found in nonadherent patients. After multivariate logistic regression analysis, low socio-economic level (OR = 3.68; 95% CI = 1.42-9.53), current cannabis use or abuse (OR = 2.79; 95% CI = 1.07-7.28), nonadherence as a reason for relapse and admission (OR = 5.46; 95% CI = 2.00-14.90), and greater overall severity of symptoms at six months follow-up (OR = 2.00; 95% CI = 1.02-3.95) remained independently associated with nonadherence. Believing that medication is unnecessary was the most reported reason for nonadherence. For nonadherent patients (N = 64), two distinguishable subtypes were found: intentional nonadherence (N = 32; 50%), and unintentional nonadherence (N = 32; 50%). CONCLUSIONS: A large percentage of patients with schizophrenia or schizoaffective disorder did not adhere to their treatment in the post-discharge follow-up period. The profile identified may enable better prevention of this problem. Specific reasons for nonadherence should also be explored to provide individualized strategies.

Testing the hypothesis of subtypes of nonadherence in schizophrenia and schizoaffective disorder: A prospective study.

BACKGROUND: Nonadherence is a major problem in the treatment of psychotic disorders. It has been hypothesized that nonadherent patients with schizophrenia are not a homogeneous population and subtypes of nonadherence might exist, but this hypothesis has not been specifically tested. AIM: To test the hypothesis of subtypes of nonadherence in schizophrenia and schizoaffective disorder. METHODS: This prospective study included 110 consecutively admitted patients diagnosed with schizophrenia or schizoaffective disorder. Assessments were performed at baseline and at 6 mo follow-up after discharge. Sociodemographic, clinical, psychopathological and treatment-related variables were evaluated. Adherence was defined as the concurrence of adherence to antipsychotic treatment and outpatient follow-up during the six-month period. Adherence to antipsychotic treatment was defined as the concurrence of objective and subjective adherence. Sixty-four patients (58%) fulfilled nonadherence criteria at the end of the follow-up period and were categorized according to their subtype of nonadherence. RESULTS: In nonadherent patients (n = 64), 32 (50%) fulfilled criteria of intentional nonadherence, and 32 (50%) of unintentional nonadherence (UNA). Unintentional nonadherent patients, as compared to intentional nonadherent patients, are characterized by older age, lower educational level, worse cognitive and negative symptoms, greater severity, worse knowledge of their treatment regimen, greater prevalence of supervision of the treatment, lower number of prior hospitalizations and greater use of nonpsychiatric treatment, anticholinergics and hypnotics. Low educational level (OR = 26.1; 95%CI: 2.819-241), worse treatment knowledge at six months (OR per unit = 0.904; 95%CI: 0.853-0.957) and nonpsychiatric treatment at six months (OR = 15.8; 95%CI: 1.790-139) were independently associated to UNA. CONCLUSION: Differentiated subtypes of nonadherence according to intentionality seem to exist in patients with schizophrenia and schizoaffective disorder. Our findings suggest the need for differentiated approach, both in future research and in clinical practice.

Narcolepsia y psicosis, a propósito de un caso / Narcolepsy and psychosis, a case report

La narcolepsia es trastorno neurológico infrecuente, incluido dentro del catálogo de enfermedades raras. Pese a la existencia de criterios diagnósticos precisos, se encuentra infradiagnosticada. Se caracteriza por una excesiva somnolencia diurna asociada a cataplejías, y en algunos casos puede aparecer alucinaciones hipnagógicas e hipnopómpicas, alucinaciones auditivas y/o ideación delirante. La presencia de síntomas psicóticos dificulta enormemente el diagnóstico diferencial (narcolepsia, esquizofrenia o la concomitancia de ambas). Además, el manejo terapéutico puede resultar complejo, ya que el tratamiento de una patología puede empeorar la otra. El siguiente caso clínico corresponde a una paciente con esta infrecuente comorbilidad entre ambos trastornos, en el que quedan patentes las importantes dificultades tanto en el diagnóstico diferencial como en el manejo terapéutico, una vez alcanzado el diagnóstico de certeza

Narcolepsy is an infrequent neurological disorder, included in the catalog of rare diseases. Despite the existence of precise diagnostic criteria, this entity remains underdiagnosed. It is characterized by excessive daytime sleepiness associated with cataplexy; in some cases, hypnagogic or hypnopompic hallucinations, auditory hallucinations, and/or delusional ideation may appear. The occurrence of psychotic symptoms makes differential diagnosis extremely difficult (narcolepsy, schizophrenia, or both). Furthermore, therapeutic management may be complex, since the treatment of one of the disorders may worsen the other. Here we describe the case of a patient with this rare comorbidity, which illustrates the major difficulties associated to both differential diagnosis and therapeutic management once a definitive diagnosis has been reached

Painful insight vs. usable insight in schizophrenia. Do they have different influences on suicidal behavior?

BACKGROUND: Suicidal behavior is highly prevalent in schizophrenia. Among the risk factors, insight has been little studied and has yielded contradictory results. In addition, it has been studied neglecting relevant psychological aspects, such as beliefs about illness and coping styles. METHOD: We assessed 133 outpatients diagnosed with schizophrenia according to ICD-10 criteria. Evaluation included sociodemographic, general clinical, psychopathological, psychological and suicidal behavior variables. RESULTS: Neither insight nor insight coupled with negative beliefs and/or coping styles were associated with suicidal behavior. Nevertheless, insight coupled with negative beliefs and/or coping styles was associated with greater hopelessness and depression, internalized stigma, worse control over illness and greater global severity as compared to insight coupled with positive beliefs and coping styles. Suicide attempt and suicidal ideation groups showed greater depression and hopelessness, worse global beliefs and worse control over illness, higher socio-economic level, and greater number of previous psychiatric admissions compared to the non-suicidal group. CONCLUSIONS: Insight coupled with negative beliefs and/or coping style was not associated with suicidal behavior. Nevertheless, it was associated with greater depression and hopelessness, both of which are firmly established risk factors for suicide in schizophrenia. Prospective studies with long-term follow-up and large samples are needed to clarify this issue. Clinicians should assess these psychological features associated with insight, both in patients with insight and in those with poor insight when promoting it.

Narcolepsy and psychosis; case report.

Narcolepsy is an infrequent neurological disorder, included in the catalog of rare diseases. Despite the existenceof precise diagnostic criteria, this entity remains underdiagnosed. It is characterized by excessive daytime sleepiness associated with cataplexy; in some cases, hypnagogic or hypnopompic hallucinations, auditory hallucinations, and/or delusional ideation may appear. The occurrence of psychotic symptoms makes differential diagnosis extremely difficult (narcolepsy, schizophrenia, or both). Furthermore, therapeutic management may be complex, since the treatment of one of the disorders may worsen the other. Here we describe the case of a patient with this rare comorbidity, which illustrates the major difficulties associated to both differential diagnosis and therapeutic management once a definitive diagnosis has been reached.

Suicide Coverage in the Digital Press Media: Adherence to World Health Organization Guidelines and Effectiveness of Different Interventions Aimed at Media Professionals.

This study evaluated the characteristics of suicide news articles in the digital press, their adherence to World Health Organization (WHO) recommendations, and the effectiveness of interventions. We assessed adherence, avoidability, frequency and typology of suicide news over a six-month period in the four main digital media outlets of the Canary Islands (Spain). A brief training and information package intervention to the Canary Islands media outlets was carried out. We compared the quality of media reporting at both the pre-intervention and post-intervention timepoints, and compared the quality of reporting at the post-intervention timepoint in Victoria (Australia), where media interventions have been well-resourced and running for several years. We evaluated 339 suicide news articles: 38 from the pre-intervention period, 64 from the post-intervention period, and 237 from Victoria. News articles showed a very low degree of adherence to WHO recommendations, especially to those recommendations thought to have a protective effect. Post-intervention news articles showed better adherence than pre-intervention ones, but lower than those of Victoria, where constant interventions have been developed for years. We conclude that adherence to WHO recommendations is low. Simple interventions aimed at media professionals can improve adherence. However, constant and complex interventions seem to be more effective.

Prospective study of variables associated with nonadherence to psychotherapy.

Background: The identification of factors associated with nonadherence to psychotherapy would allow a better prevention of this problem.Aim: To investigate factors associated with nonadherence in psychotherapy, its possible effect on outcomes, and reasons for therapy dropout.Method: Prospective analytic observational study of patients who initiated psychotherapy (N = 144). Sociodemographic, general clinical, treatment-related, subjective, psychological, psychopathologic, and outcome variables were evaluated at baseline and 1, 3, 6, and 12 months later. Objective nonadherence (dropout and irregularity), subjective nonadherence (poor patient engagement), and global nonadherence (combination of both) were analyzed.Results: Global nonadherence was 66%. Global nonadherence was associated with substance use or abuse (OR = 2.64) and younger age (OR = 0.97). Objective nonadherence was associated with active working status (OR = 4.11), younger age (OR = 1.04) and substance use or abuse (OR = 2.35). Subjective nonadherence was associated with worse insight in psychotherapy (OR = 0.95) and poor pharmacologic adherence (OR = 0.55). Contextual reasons (25.8%) were the most commonly reported cause of dropout. Time in psychotherapy was associated with outcome variables.Conclusions: Nonadherence to psychotherapy is frequent. To reduce nonadherence in psychotherapy, specific interventions for reducing substance use and abuse, measures aimed at facilitating access to Community Mental Health Units, and enhancing insight in psychotherapy should be implemented.

Suicidal risk, hopelessness and depression in patients with schizophrenia and internalized stigma.

BACKGROUND: Internalized stigma has negative consequences on subjective and objective aspects of the recovery in people diagnosed with mental disorders. Despite its relevance, it has been poorly studied in patients with schizophrenia. METHODS: A sample of 71 outpatients with a diagnosis of schizophrenia who attended Psychosocial Rehabilitation Centers of Gran Canaria, Spain, were evaluated. We assessed the prevalence of internalized stigma and its possible association with sociodemographic, clinical, psychological and psychopathological variables, as well as suicidal behaviour and suicidal ideation. RESULTS: 21.1% of the patients had internalized stigma. Internalized stigma was associated with higher prevalence of suicidal ideation during the last year, higher number of suicide attempts, higher current suicidal risk, worse self-compassion, higher self-esteem, higher scores on depression, higher prevalence of depression and higher hopelessness. After multivariate analysis, hopelessness and the existence of depression were independently associated with internalized stigma, although depression showed trend towards significance. CONCLUSIONS: The association between internalized stigma and higher hopelessness, depression and higher suicidal risk suggests the necessity to systematically assess internalized stigma in patients with schizophrenia, and to intervene to reduce it.

Riesgo suicida, desesperanza y depresión en pacientes con esquizofrenia y autoestigma / Suicidal risk, hopelessness and depression in patients with schizophrenia and internalized stigma

Introducción. El autoestigma tiene efectos negativos en aspectos subjetivos y objetivos de la recuperación en las personas con trastornos mentales. A pesar de su importancia, ha sido poco estudiado en la esquizofrenia. Metodología. Evaluamos el autoestigma en 71 pacientes diagnosticados de esquizofrenia, en Centros de Día de Rehabilitación Psicosocial de Gran Canaria. Se evaluó su prevalencia y su posible asociación con variables sociodemográficas, clínicas generales, psicopatológicas y aspectos psicológicos, así como la conducta suicida e ideación suicida. Resultados. El 21,1% de los pacientes presentaron autoestigma. El autoestigma se asoció a mayor prevalencia de ideación suicida en el último año, mayor número total de tentativas suicidas, mayor riesgo suicida actual, peor autocompasión, mayor autoestima y peores puntuaciones en depresión, mayor prevalencia de depresión y mayor desesperanza. En el análisis multivariante, la desesperanza y la existencia de depresión se asociaron de manera independiente con el autoestigma, si bien la depresión lo hizo con tendencia a la significación. Conclusiones. La asociación entre autoestigma y mayor desesperanza, depresión y riesgo suicida sugiere la necesidad de evaluar sistemáticamente el autoestigma en los pacientes con esquizofrenia, e intervenir para su reducción

Background. Internalized stigma has negative consequences on subjective and objective aspects of the recovery in people diagnosed with mental disorders. Despite its relevance, it has been poorly studied in patients with schizophrenia. Methods. A sample of 71 outpatients with a diagnosis of schizophrenia who attended Psychosocial Rehabilitation Centers of Gran Canaria, Spain, were evaluated. We assessed the prevalence of internalized stigma and its possible association with sociodemographic, clinical, psychological and psychopathological variables, as well as suicidal behavior and suicidal ideation. Results. 21.1% of the patients had internalized stigma. Internalized stigma was associated with higher prevalence of suicidal ideation during the last year, higher number of suicide attempts, higher current suicidal risk, worse self-compassion, higher self-esteem, higher scores on depression, higher prevalence of depression and higher hopelessness. After multivariate analysis, hopelessness and the existence of depression were independently associated with internalized stigma, although depression showed trend towards significance. Conclusions. The association between internalized stigma and higher hopelessness, depression and higher suicidal risk suggests the necessity to systematically assess internalized stigma in patients with schizophrenia, and to intervene to reduce it

Modeling the effect of boost timing in murine irradiated sporozoite prime-boost vaccines.

Vaccination with radiation-attenuated sporozoites has been shown to induce CD8+ T cell-mediated protection against pre-erythrocytic stages of malaria. Empirical evidence suggests that successive inoculations often improve the efficacy of this type of vaccines. An initial dose (prime) triggers a specific cellular response, and subsequent inoculations (boost) amplify this response to create a robust CD8+ T cell memory. In this work we propose a model to analyze the effect of T cell dynamics on the performance of prime-boost vaccines. This model suggests that boost doses and timings should be selected according to the T cell response elicited by priming. Specifically, boosting during late stages of clonal contraction would maximize T cell memory production for vaccines using lower doses of irradiated sporozoites. In contrast, single-dose inoculations would be indicated for higher vaccine doses. Experimental data have been obtained that support theoretical predictions of the model.

Population mechanics: A mathematical framework to study T cell homeostasis.

Unlike other cell types, T cells do not form spatially arranged tissues, but move independently throughout the body. Accordingly, the number of T cells in the organism does not depend on physical constraints imposed by the shape or size of specific organs. Instead, it is determined by competition for interleukins. From the perspective of classical population dynamics, competition for resources seems to be at odds with the observed high clone diversity, leading to the so-called diversity paradox. In this work we make use of population mechanics, a non-standard theoretical approach to T cell homeostasis that accounts for clone diversity as arising from competition for interleukins. The proposed models show that carrying capacities of T cell populations naturally emerge from the balance between interleukins production and consumption. These models also suggest remarkable functional differences in the maintenance of diversity in naïve and memory pools. In particular, the distribution of memory clones would be biased towards clones activated more recently, or responding to more aggressive pathogenic threats. In contrast, permanence of naïve T cell clones would be determined by their affinity for cognate antigens. From this viewpoint, positive and negative selection can be understood as mechanisms to maximize naïve T cell diversity.

Variables asociadas a la no adherencia en pacientes con trastorno bipolar en estabilidad clínica / Variables associated with nonadherence in clinically stable patients with bipolar disorder

Introducción. La no adherencia es un problema altamente prevalente en el trastorno bipolar y puede conllevar importantes consecuencias. Sorprendentemente apenas existen estudios sobre factores de riesgo en pacientes en estado de estabilidad clínica. Metodología. La adherencia se evaluó en 76 pacientes con trastorno bipolar en estabilidad clínica, mediante métodos objetivos y subjetivos, abarcando el momento transversal y un periodo retrospectivo de 3 años. Se evaluó su posible asociación con variables sociodemográficas, clínicas, relacionadas con el tratamiento, psicopatológicas, psicológicas y de aspectos subjetivos, y de resultado. Resultados. Un 36,8% de los pacientes fueron no adherentes. Estos mostraron mayor preocupación sobre la medicación, peor funcionalidad, mayor número de episodios, episodios depresivos, y mayores prevalencias de comorbilidad con otros trastornos psiquiátricos, consumo de tóxicos actual y/o pasado y de antecedentes de episodios con síntomas psicóticos. Tras el análisis multivariante, la preocupación por la medicación, el consumo actual y/o pasado de tóxicos y la comorbilidad con otros trastornos psiquiátricos se asociaron de manera independiente con la no adherencia. Conclusiones. La no adherencia en el trastorno bipolar es un fenómeno frecuente, incluso en pacientes en estabilidad. El clínico debería explorar las creencias y actitudes del paciente hacia la medicación, y ayudarle a reevaluarlas desde un punto de vista más realista. Por su parte, deben realizarse intervenciones para evitar el consumo de tóxicos. La identificación de factores de riesgo asociados a la no adherencia en estabilidad añade información al perfil de riesgo disponible para el trastorno bipolar

Introduction. Nonadherence is an important and highly prevalent issue in bipolar disorder, which may have serious consequences. Surprisingly, few studies have been carried out in patients with clinical stability to explore risk factors for nonadherence. Method. Adherence was assessed in 76 bipolar disorder patients with clinical stability using objective and subjective methods, both with a cross-sectional approach and a 3-year retrospective period. Possible associations between nonadherence and sociodemographic, clinical, treatment-related, psychopathological, psychological-subjective and result variables were also assessed. Results. 36.8% of patients were nonadherent. These patients showed greater concerns about medicines, worse functionality, a greater number of episodes and depressive episodes, higher prevalence of psychiatric comorbidities, present and/or past substance use or abuse and a history of depressive episodes with psychotic symptoms. A multivariate analysis revealed that concern about medicines, present and/or past substance use or abuse and psychiatric comorbidities were independently associated with nonadherence. Conclusions. Nonadherence is a frequent phenomenon in bipolar disorder, even in patients with clinical stability. Clinicians should assess patients’ beliefs and attitudes towards medicines and help them reevaluate those issues with a more realistic perspective. Clinicians should also take actions to prevent substance use or abuse. Identification of nonadherence risk profile in bipolar disorder patients in clinical stability, adds complementary information to the identified risk profile in acute phases of the disease

Variables associated with nonadherence in clinically stable patients with bipolar disorder.

INTRODUCTION: Nonadherence is an important and highly prevalent issue in bipolar disorder, which may have serious consequences. Surprisingly, few studies have been carried out in patients with clinical stability to explore risk factors for nonadherence. METHOD: Adherence was assessed in 76 bipolar disorder patients with clinical stability using objective and subjective methods, both with a cross-sectional approach and a 3-year retrospective period. Possible associations between nonadherence and sociodemographic, clinical, treatment-related, psychopathological, psychological-subjective and result variables were also assessed. RESULTS: 36.8% of patients were nonadherent. These patients showed greater concerns about medicines, worse functionality, a greater number of episodes and depressive episodes, higher prevalence of psychiatric comorbidities, present and/or past substance use or abuse and a history of depressive episodes with psychotic symptoms. A multivariate analysis revealed that concern about medicines, present and/or past substance use or abuse and psychiatric comorbidities were independently associated with nonadherence. CONCLUSIONS: Nonadherence is a frequent phenomenon in bipolar disorder, even in patients with clinical stability. Clinicians should assess patients’ beliefs and attitudes towards medicines and help them reevaluate those issues with a more realistic perspective. Clinicians should also take actions to prevent substance use or abuse. Identification of nonadherence risk profile in bipolar disorder patients in clinical stability, adds complementary information to the identified risk profile in acute phases of the disease.