Update on the use and management of lithium in neuropsychiatry / Actualización en el uso y el manejo del litio en neuropsiquiatría.

Lithium is an alkaline metal, used for more than 60 years in psychiatry, and currently considered the gold standard in the treatment of bipolar disorder (BD). According to recent evidence, this active ingredient is useful for the treatment of a wide spectrum of clinical varieties of affective disorders. In addition, it is estimated that lithium reduces the risk of suicide and suicidal behavior in people with mood disorders. On the other hand, some novel studies have shown that the cation has a potential efficacy for the treatment of other neuropsychiatric processes, such as the likelihood of reducing the risk of dementia and slowing down the development of neurodegenerative diseases. Despite the enormous evidence in favor of the use of lithium, it is known that, in Argentina, medications containing it are prescribed less than expected. In view of all this, the Asociación Argentina de Psiquiatría Biológica (Argentine Association of Biological Psychiatry) (AAPB or AABP) convened a group of experts to review the available scientific literature and prepare an updated document on the management and use of lithium in neuropsychiatry. In addition to the use of the ion in daily clinical practice, the scope of this review includes other contents that have been considered of interest for the psychiatrist, such as certain pharmacological and pharmacogenetic aspects, possible clinical predictors of response to treatment with lithium, management of ion during perinatal period, management of lithium in child and adolescent population, management of adverse effects linked to cation and interactions with drugs and other substances.

El litio es un metal alcalino, usado hace más de 60 años en psiquiatría, y actualmente es considerado el estándar de oro en el tratamiento del trastorno bipolar (TB). De acuerdo con la evidencia reciente, este principio activo es útil para el tratamiento de un amplio espectro de variedades clínicas de los trastornos afectivos. Además, se estima que desde hace tiempo el litio reduce el riesgo de suicidio y de comportamiento suicida en personas con trastornos del estado de ánimo. Por otro lado, algunos estudios novedosos han demostrado que el catión posee una potencial eficacia para el tratamiento de otros procesos neuropsiquiátricos, tales como la probabilidad de disminuir el riesgo de demencia y la de ralentizar el desarrollo de enfermedades neurodegenerativas. A pesar de la enorme evidencia a favor de la utilización del litio, se sabe que, en la Argentina, las especialidades medicinales que lo contienen se prescriben menos de lo esperado. En virtud de todo lo mencionado, la Asociación Argentina de Psiquiatría Biológica (AAPB) convocó a un grupo de expertos para revisar la literatura científica disponible y elaborar un documento actualizado sobre el manejo y el uso del litio en neuropsiquiatría. Además de la utilización del ion en la práctica clínica diaria, el alcance de esta revisión incluye otros contenidos que se han considerado de interés para el médico psiquiatra, tales como ciertos aspectos farmacológicos y farmacogenéticos, posibles predictores clínicos de la respuesta al tratamiento con litio, el manejo del ion durante el período perinatal, el manejo de litio en la población infantojuvenil, el manejo de los efectos adversos vinculados con el catión y las interacciones con medicamentos y otras sustancias.

Third Argentine Consensus statement on management Bipolar Disorders. Section3: Bipolar Disorder in the context of special situations / Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares. Tercera parte: Manejo de los Trastornos Bipolares en el contexto de situaciones especiales.

This document constitutes the third and last part of the Third Argentine Consensus on the Management of Bipolar Disorders carried out by the Argentine Association of Biological Psychiatry (AAPB). Continuing with the initial objective, this section of the Consensus on the Management of Bipolar Disorders is focused on the management of bipolar disorders in special populations. This section constitutes a comprehensive review and expert consideration of the scientific evidence on: a) the management of bipolar disorders in treatment-resistant patients; b) the management of bipolar disorder in childhood and adolescence; c) the management of bipolar disorders in women during their perinatal period and, d) the management of bipolar disorders in older adults.

Este documento constituye la tercera y última parte del Tercer Consenso Argentino sobre el Manejo de los Trastornos Bipolares llevada a cabo por la Asociación Argentina de Psiquiatría Biológica (AAPB). Siguiendo con el objetivo propuesto por el comité de expertos, en la actual versión del Consenso sobre el manejo de los trastornos bipolares, esta sección está enfocada al abordaje de los Trastornos Bipolares en situaciones especiales. Esto configura una revisión exhaustiva de la evidencia científica  sobre: a) el manejo de los trastornos bipolares en pacientes resistentes al tratamiento, b) el manejo de los trastornos bipolares en la mujer en el período perinatal, c) el manejo del trastorno bipolar en la etapa infantojuvenil y d) el manejo de los trastornos bipolares en los adultos mayores.

Third Argentine Consensus statement on management Bipolar Disorders. Section 2 B / Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares. Segunda Parte B.

This document constitutes the second section B of the Third Argentine Consensus on the Management of Bipolar Disorders, focused on synthesizing the most updated evidence on therapeutic approaches for adult patients. The scope of this section is to provide therapeutic recommendations for managing bipolar disorders in adults, (i) acute mania (ii) bipolar depression (iii) mixed stated (iv) suicidality and (vi) psychological interventions. In addition, the current manuscript outlines the assessment and management of side effects of pharmacotherapeutic treatments.

Este documento constituye la segunda parte B del Tercer Consenso Argentino sobre el Manejo de los Trastornos Bipolares llevada a cabo por la Asociación Argentina de Psiquiatría Biológica (AAPB). Siguiendo con el direccionamiento iniciado en el parte 2A sobre el tratamiento integral de los trastornos bipolares, esta sección se ha enfocado en sintetizar la evidencia más actualizada sobre abordajes terapéuticos para pacientes adultos. El alcance de esta sección es proporcionar recomendaciones terapéuticas para el manejo de los trastornos bipolares en adultos, (i) manía aguda, (ii) depresión bipolar, (iii) estado mixto, (iv) el suicidio en el trastorno bipolar, (v) intervenciones psicológicas. Además, el presente manuscrito aborda la evaluación y el manejo de los efectos secundarios de los tratamientos farmacoterapéuticos.

Third Argentine Consensus statement on management Bipolar Disorders. Section 2 A: Comprehensive treatment of the bipolar disorders in adults / Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares. Segunda Parte A: Tratamiento integral de los trastornos bipolares en el adulto.

This document constitutes the second section A of the Third Argentine Consensus on the Management of Bipolar Disorders, focused on synthesizing the most updated evidence on therapeutic approaches for adult patients. The aim of this section (2A) is to provide therapeutic recommendations for managing bipolar disorders in adults. In addition, the scope of this current manuscript outlines recommendations on the use of treatment guidelines, levels of evidence available to support these recommendations, general considerations for the treatment of bipolar disorders, the so-called pseudoresistance and adherence to treatment, general considerations on psychological therapies, as well as long term treatment of bipolar disorders.

Este documento corresponde a la segunda parte del Tercer Consenso Argentino sobre el manejo de los trastornos bipolares, enfocada en sintetizar la evidencia actualizada sobre los abordajes terapéuticos de esta patología en los pacientes adultos. Siguiendo la metodología descripta en la primera parte del Consenso, el panel de expertos realizó una exhaustiva revisión de la bibliografía y, como consecuencia de un posterior debate sobre la información disponible, se generó esta sección A del segundo documento que abarca el tratamiento integral de las personas adultas que padecen este trastorno. Durante la etapa de debate y discusión de estas guías, se decidió incorporar algunos puntos que estimamos serán de gran utilidad para el equipo interdisciplinario encargado del manejo de pacientes con trastornos bipolares.  En tal sentido, en la sección A de la segunda parte de este documento, se podrán encontrar las recomendaciones generales para el uso de las guías de tratamiento, los niveles de evidencia disponibles para sustentar las recomendaciones, las consideraciones generales del tratamiento de los trastornos bipolares, el fenómeno de pseudorresistencia y adherencia al tratamiento, las consideraciones generales sobre el abordaje psicológico, así como el tratamiento a largo plazo de los trastornos bipolares.

Third Argentine Consensus statement on management Bipolar Disorders. Section1: introduction and general concepts / Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares. Primera Parte: introducción, método de trabajo y generalidades.

The Third Argentine Consensus on the management of bipolar disorders (TB) is an initiative of the Argentine Association of Biological Psychiatry (AAPB). As a reference document, this consensus pursues two main objectives: on the one hand, to summarize and systematize the best available evidence on the comprehensive management of this pathology; on the other, to provide a useful, up-to-date instrument for psychiatrists, multidisciplinary teams dedicated to mental health, and government agencies. During a period of approximately six months of work -that is, from May to October 2022- a committee of experts made up of 18 professionals and representatives of the three most important Psychiatry and Mental Health associations in Argentina (that is, the AAPB, the Argentine Association of Psychiatrists, AAP, and the Association of Argentine Psychiatrists, APSA) have focused on updating the information regarding TB. Finally, this document was prepared as a result of an exhaustive review of the bibliography published to date, which was strategically divided into three parts: the first deals with the generalities of TB; the second deals with the comprehensive treatment of the pathology; finally, the third analyzes TB in the context of special situations.

El Tercer Consenso Argentino sobre el manejo de los Trastornos Bipolares (TB) es una iniciativa de la Asociación Argentina de Psiquiatría Biológica (AAPB). Como documento de referencia, este consenso persigue dos objetivos principales: por un lado, resumir y sistematizar la mejor evidencia disponible sobre el manejo integral de esta patología; por el otro, proporcionar un instrumento útil y actualizado a psiquiatras, a equipos multidisciplinarios abocados a la salud mental y a organismos gubernamentales. Durante un período de aproximadamente seis meses de trabajo -desde mayo a octubre de 2022- un comité de expertos integrado por 18 profesionales y por representantes de las tres asociaciones de Psiquiatría y Salud Mental más importantes de la Argentina: la AAPB, la Asociación Argentina de Psiquiatras, (AAP) y la Asociación de Psiquiatras Argentinos (APSA), se abocaron a actualizar la información respecto de los TB. Finalmente, y como resultado de una exhaustiva revisión de la bibliográfica publicada hasta la actualidad, se confeccionó este documento que fue dividido estratégicamente en tres partes: la primera versa acerca de las generalidades del TB; la segunda aborda el  tratamiento integral de la patología; y, por último, la tercera analiza los TB en el contexto de situaciones especiales.

Endometriosis: current challenges in modeling a multifactorial disease of unknown etiology.

Endometriosis is a chronic inflammatory hormone-dependent condition associated with pelvic pain and infertility, characterized by the growth of ectopic endometrium outside the uterus. Given its still unknown etiology, treatments usually aim at diminishing pain and/or achieving pregnancy. Despite some progress in defining mode-of-action for drug development, the lack of reliable animal models indicates that novel approaches are required. The difficulties inherent to modeling endometriosis are related to its multifactorial nature, a condition that hinders the recreation of its pathology and the identification of clinically relevant metrics to assess drug efficacy. In this review, we report and comment endometriosis models and how they have led to new therapies. We envision a roadmap for endometriosis research, integrating Artificial Intelligence, three-dimensional cultures and organ-on-chip models as ways to achieve better understanding of physiopathological features and better tailored effective treatments.

Episodic density, subsyndromic symptoms, and mood instability in late-life bipolar disorders: A 5-year follow-up study.

OBJECTIVES: Characterization of clinical course in old age bipolar disorder (OABD) is scarce and based solely on episode density (ED). The aim of this study was to explore mood instability (MI) and subsyndromal symptomatology (SS) in a prospective cohort of OABD. Further, we contrasted these measures with a cohort of young age bipolar disorder (YABD). METHODS: Life charts from weekly mood ratings were used to compute the number of weeks spent with subsyndromal symptoms (SD), the ED, and the MI during follow-up for a cohort of OABD (N = 38) that excluded late onset BD. Linear and logistic regression models were fitted to compare the clinical course of OABD with a cohort of YABD (N = 52) and to explore the relationship between these measures and functional outcomes. RESULTS: Median follow-up was 5 years (IQR: 3.6-7.9). OABD (61.6 years, SD: 8.3) spent 15%, 6%, and 3% of their follow-up with depressive, manic, and mixed symptoms, respectively, and suffered 4.2 mood changes per year (SD: 2.6). No significant differences between OABD and YABD regarding ED or MI emerged in multivariate analysis, while a higher subsyndromal manic symptom burden was observed in OABD (ß coefficient: 3.79, 95%CI: 0.4-7.2). Both SS and MI were associated with functional outcomes in OABD. CONCLUSIONS: The course of illness throughout OABD was similar to the one observed in YABD except for a higher subsyndromal manic burden. This study extended the association of MI and SD with global functioning to the late-life BD.

Functional Outcome in the Middle Course of Bipolar Disorder: A Longitudinal Study.

The aim of this study was to assess the long-term functional outcome of patients with bipolar disorder (BD). At baseline and after a follow-up period of at least 48 months, three measures of functioning were administered: psychosocial functioning (GAF), employment status (full-time, part-time, and unemployment/disability), and a self-reported measure of functional recovery. At baseline, patients with more than five previous affective episodes exhibited poorer outcomes on all measures of functioning than patients with less than five previous episodes. However, along a mean follow-up period of 77 months, measures of functioning tended to remain stable or improved slightly. These results highlight the limitation of studies comparing measures of functioning between patients with many and few episodes to evaluate functional outcome. Likewise, these preliminary results do not support the hypothesis that functional outcome deteriorates over the course of BD.

Accuracy of the number of previous episodes reported by patients with bipolar disorder.

BACKGROUND: The number of previous episodes in patients with BD is a variable widely used for both clinical and research purposes. The aim of this study was to compare the number of episodes retrospectively reported by euthymic BD subjects with that registered by their psychiatrists during a follow-up period. METHODS: Fifty euthymic patients with BD and more than 2years of follow-up were retrospectively asked in a standardized fashion about the number of hypomanic/manic and depressive episodes suffered during that period. Patient-reported outcomes were compared with the number of episodes registered by psychiatrists in a life chart during the same period. RESULTS: The mean follow-up of patients was 66.70months. There was a mean difference of 2.74 episodes between reports of patients' and psychiatrists' reports during the complete follow-up period; Intraclass correlation coefficient was 0.40 (CI95%=0.15-0.61). This difference increased with the duration of the follow-up period (R=0.33, p=0.023) and with the number of episodes occurred during that (R=0.32, p=0.023). The difference between patient-reported and clinician-rated in the number of depressive during the follow-up period was more pronounced in BDII than in BDI (Z=-2.47, p=0.014), and it correlated with the number of previous depressive episodes at baseline (R=0.28, p=0.047) and subclinical depressive symptoms (R=0.41, p=0.003). CONCLUSIONS: The number of previous episodes referred by patients with BD is not an accurate measure of the true number of episodes suffered. The theoretical and practical implications of these findings are discussed.

Mycobacterium leprae Hsp65 administration reduces the lifespan of aged high antibody producer mice.

BACKGROUND: Aging process may result in immune modifications that lead to disruption of innate and acquired immunity mechanisms that may induce chronic-degenerative events. The heat shock proteins (Hsp), phylogeneticaly conserved among organisms, present as main function the ability of folding and refolding proteins, but they also are associated with chronic-degenerative disorders. Here were evaluated the role of M. leprae native Hsp65 (WT) and its point-mutated (K409A) on survival and anti-DNA and anti-Hsp65 antibody production of aged genetically selected mice for high (HIII) and low (LIII) antibody production; data from 120- and 270-days old mice (named "adult" or "aged", respectively) were compared. RESULTS: WT Hsp65 administration induces reduction in the mean survival time of adult and aged female HIII mice, this effect being stronger in aged individuals. Surprisingly, the native protein administration increased the survival of aged female LIII when compared to K409A and control groups. No survival differences were observed in aged male mice after Hsp65 proteins inoculation. We observed increase in IgG1 anti-Hsp65 in WT and K409A aged HIII female mice groups and no marked changes in the anti-DNA (adult and aged HIII) and anti-Hsp65 IgG1 or IgG2a isotypes production in adult HIII female and aged male mice. LIII male mice presented increased anti-DNA and anti-Hsp65 IgG2a isotype production after WT or K409A injection, and LIII female groups showed no alterations. CONCLUSIONS: The results revealed that the WT Hsp65 interferes with survival of aged HIII female mice without involvement of a remarkable IgG1 and IgG2a anti-DNA and anti-Hsp65 antibodies production. The deleterious effects of Hsp65 on survival time in aged HIII female mice could be linked to a gender-effect and are in agreement with those previously reported in lupus-prone mice.

[Pregnancy in bipolar disorders. Concepts for clinical and therapeutic management]. / Embarazo en mujeres afectadas por trastornos bipolares: conceptos para el manejo clínico-terapéutico.

Pregnancy in women affected with bipolar disorders supposes a complex clinical decision making process for those women affected and their clinicians. On one hand, a careful weighing of potential consequences of maintains pharmacologic treatment for obstetric health and embryo-fetal development is essential. On the other, a thorough consideration of risks of discontinuing treatment for pregnant women and fetal health is needed. In this paper, critical items to discuss with women that make informed decisions regarding their mood stabilizing treatment in these complex circumstances are described. Likewise, some clinical recommendations for psychiatric management of pregnancy in this population are presented.

Can we predict a "tsunami"? Symptomatic and syndromal density, mood instability and treatment intensity in people with bipolar disorders under a strict and long lockdown.

BACKGROUND: Converging evidence supports the involvement of circadian rhythm disturbances in the course and morbidity of bipolar disorders (BD). During 2020, lockdown measures were introduced worldwide to contain the health crisis caused by the COVID-19 pandemic. As a result, chronobiological rhythms were critically disrupted and illness outcomes were expected to worsen. The current study aimed to explore changes in morbidity among BD patients living under lockdown. METHODS: Ninety BD outpatients under naturalistic treatment conditions were followed from March to September 2020 using a mood chart technique. Different treatment and illness variables, including mood instability, were assessed and compared with the outcomes obtained during the same 28-week period in 2019. RESULTS: For most clinical variables, no significant differences were observed between time periods. A slight decrease was found in symptom intensity (from 15.19 ± 20.62 to 10.34 ± 15.79, FDR-adjusted p = 0.04) and in the number of depressive episodes (from 0.39 ± 0.74 to 0.22 ± 0.63, FDR-adjusted p = 0.03), whereas the intensity of pharmacological treatment remained unchanged. Previous illness course predicted mood outcomes during the confinement. LIMITATIONS: Follow-up periods were relatively short. Further, actigraphy or other methods capable of ensuring significant changes in physical activity were not used. CONCLUSIONS: In line with other studies, our findings show no worsening in the clinical morbidity of BD patients during lockdown. This conspicuous contrast between our initial predictions and the observed findings highlights the fact that we are still far from being able to provide accurate predictive models for BD.

Autolytic Mycobacterium leprae Hsp65 fragments may act as biological markers for autoimmune diseases.

Investigating the proteolytic activity of the recombinant Mycobacterium leprae Heat Shock Protein of 65 kDa (rHsp65), chaperonin 2 (cpn2), we observed that it displays high instability. The fragmentation process starts at the C-terminus followed by progressive degradation of the N-terminus, which leads to a stable fragment comprising the middle region of the molecule. Urea was able to prevent autolysis, probably due to its denaturing action, while EDTA increased degradation levels indicating the need for metal ions. Peptides originated from autolysis were purified and analyzed by mass spectrometry, generating a continuous map. Since the bacteria and mammalian Hsp60 are known to be targets of the immune response and have been implicated in autoimmune diseases and chronic inflammation, the in vivo effect of rHsp65 peptides was evaluated in the spontaneous Systemic Lupus Erythematosus (SLE) model developed by the (NZB/NZW)F(1) mouse hybrids, and their individual anti-rHsp65 IgG2a/IgG1 antibody titer ratio was determined. The results showed orientation toward a T(H)1 responsiveness, and the treatment with the rHsp65 peptides diminished the environmental variance of the survival time of treated animals. These results outline the fact that environmental factors may also act through the modified stability expression of Heat Shock Proteins intervening during autoimmune processes.

Long-term worsening of bipolar disorder related with frequency of antidepressant exposure.

BACKGROUND: The aim of this study of 53 persons with bipolar disorder (BD) was to evaluate the relationship between history of exposure to antidepressants (AD) and mood stabilizers (MS) and the percentage of time spent ill. METHODS: BD outpatients with more than 12 months of prospective follow-up were included. Outcome was documented using a life charting technique. Current and previous exposure to AD and MS were assessed using a scale that provides a quantitative measure of exposure to psychotropic medications. Regression models were used to correct for possible confounders. RESULTS: Previous treatment with AD was an independent predictor of polarity changes (P < .001) and mixed symptoms (P = .01). In contrast, "years of exposure to MS" was an independent predictor of time spent asymptomatic (P = .019). The ratio between exposure to AD vs MS was associated with less weeks asymptomatic (P = .03), more mixed symptomatology (P = .019), and more polarity changes (P = .001). CONCLUSIONS: Antidepressant exposure was a major predictor of mood instability in the long-term outcome of BD. The ratio used of previous exposure to AD vs MS was associated with poor outcomes, suggesting that the harmful effect of AD may be additive and related to how much they are used.

Theory of mind and facial emotion recognition in euthymic bipolar I and bipolar II disorders.

The main aim of this study was to compare patients with euthymic bipolar I (BDI) and bipolar II (BDII) disorders and healthy controls in measures of social cognition. Additional aims were to explore the association between social cognition performance with neurocognitive impairments and psychosocial functioning. Eighty one euthymic patients with BDI or BDII and 34 healthy controls were included. All subjects completed tests to assess verbal memory, attention, and executive functions. Additionally theory of mind (ToM) and facial emotion recognition measures were included. Psychosocial functioning was assessed with the GAF. Both groups of patients had lower performance than healthy controls in ToM, and a lower recognition of fear facial expression. When neurocognitive impairments and exposure to medications were controlled, performance in ToM and recognition of fear facial expression did not allow predicting if a subject was patient or healthy control. Social cognition measures not enhance variance beyond explained by neurocognitive impairments and they were not independent predictors of psychosocial functioning. Impairments in facial emotion recognition and ToM are mediated, at least partly, by attention-executive functions deficits and exposure to psychotropic medications. Likewise, social cognition measures did not contribute to variance beyond neurocognitive impairments.

Neurocognitive impairments and their relationship with psychosocial functioning in euthymic bipolar II disorder.

The aim of this study was to compare neurocognitive functioning between euthymic patients with bipolar I disorder (BDI), bipolar II disorder (BDII), and healthy controls. An additional aim was to estimate the relationship between neurocognitive impairments and psychosocial functioning. Eighty-seven patients with BDI (n = 48) or BDII (n = 39) and 39 healthy controls were included. All subjects completed an extensive neurocognitive battery. Psychosocial functioning was assessed using the General Assessment of Functioning. Patients with BDII performed more poorly than did the controls in measures of psychomotor speed, verbal memory, and executive functioning. Patient groups did not show differences in any of the cognitive measures assessed. The performance in trail-making test B was the only independent predictor of psychosocial functioning in both patient groups. Patients with BDII have cognitive impairments, and this has a negative influence on their functional outcome. Our results bring additional support to the notion that BDII disorder is not a merely mild type of BDI.

[Clinical concepts associated with lithium underutilization in the treatment of bipolar disorder]. / Conceptos clínicos asociados a la subestimación del litio en el tratamiento del Trastorno Bipolar.

OBJECTIVES: Bipolar Disorders are among the ten leading causes of morbity and lithium is considered first-line treatment and the most cost-effective. Nevertheless, its use takes a back seat to other treatment options less effective, safe and more expensive; and the reasons for this remains unclear. The present study investigates clinical concepts related to its underutilization. METHOD: An anonymous questionnaire concerning different aspects of lithium clinical use (compared efficacy, adverse effects, practical aspects regarding its use, use in special populations) was administered during the XXV Congress of the Argentinean Psychiatrist Association. RESULTS: 164 questionnaires were analyzed. Less than one-third of the sample referred lithium as their most frequent treatment option, although almost 60% qualified it as effective. Almost two-thirds considered its utilization as more complex and ill-ascribed adverse effects to it. One third referred not to use it in youth and senior populations. CONCLUSIONS: Contrary to current recommendations, lithium is under utilized. This is the first report on the possible causes leading to such phenomena, which can be related to ill concepts regarding its safety, clinical use and adverse effects; although not to its effectiveness.

Cloning, expression and characterisation of an HtrA-like serine protease produced in vivo by Mycobacterium leprae.

Members of the high temperature requirement A (HtrA) family of chaperone proteases have been shown to play a role in bacterial pathogenesis. In a recent report, we demonstrated that the gene ML0176, which codes for a predicted HtrA-like protease, a gene conserved in other species of mycobacteria, is transcribed by Mycobacterium leprae in human leprosy lesions. In the present study, the recombinant ML0176 protein was produced and its enzymatic properties investigated. M. lepraerecombinant ML0176 was able to hydrolyse a variety of synthetic and natural peptides. Similar to other HtrA proteins, this enzyme displayed maximum proteolytic activity at temperatures above 40 degrees C and was completely inactivated by aprotinin, a protease inhibitor with high selectivity for serine proteases. Finally, analysis of M. leprae ML0176 specificity suggested a broader cleavage preference than that of previously described HtrAs homologues. In summary, we have identified an HtrA-like protease in M. lepraethat may constitute a potential new target for the development of novel prophylactic and/or therapeutic strategies against mycobacterial infections.

Cognitive and motor features in elderly people with bipolar disorder.

BACKGROUND: Although elderly people will represent one third of the bipolar population in a few years, data about cognitive and motor features in these patients are very scarce. The aim of this study was to compare the cognitive and motor functioning between elderly euthymic patients with bipolar disorder (BD) and healthy controls, as well as to determine the degree of correlation with psychosocial functioning. METHODS: Euthymic older adults with BD (n=20) and healthy controls (n=20) were evaluated with traditional clinical instruments and measures of exposure to psychotropic drugs and extrapyramidal symptoms. All subjects completed an extensive neuropsychological battery. RESULTS: Patients with BD had more extrapyramidal symptoms and worse performance than healthy controls in psychomotor speed, verbal memory, and executive functions even after controlling sub-clinical symptomatology. These findings were not associated with age at onset or length of illness or with current pharmacological exposure. Psychosocial functioning correlated negatively with performance in psychomotor speed and executive function, and with extrapyramidal symptoms. LIMITATIONS: The small sample size and cross-sectional design. CONCLUSIONS: Older adult patients with BD in a euthymic state could have a similar cognitive and motor profile to that described in younger euthymic bipolar patients. Cognitive-motor disturbances may help to explain impairments in daily functioning among elderly patients with bipolar disorder during remission.

Heterogeneity in cognitive functioning among patients with bipolar disorder.

BACKGROUND: Nowadays it is not clear if in bipolar disorders (BD) cognitive impairments are heterogeneous and if so which are the variables that determine it. METHODS: Fifty patients with BD and thirty healthy controls were clinically evaluated including measures of obstetric complications history. All subjects completed an extensive neuropsychological battery selected to asses premorbid IQ and different cognitive domains. RESULTS: Compared with standardized norms, 38% of patients had none cognitive domain affected, while 40% had 1 to 2, and 22% had 3 to 5. Patients with cognitive functioning within normal limits had higher psychosocial functioning and premorbid IQ, and lower history of obstetric complications. LIMITATIONS: The small sample size could limit the generalizability of the results; since these data should be taken as preliminaries. CONCLUSIONS: The extension and severity of cognitive impairments may be heterogeneous in patients with BD, and it might contribute to explain the variability in functional outcome. Bipolar patients with low premorbid IQ and history of obstetric complications may represent a subgroup with lower cognitive performance and psychosocial functioning.