Subcortical Volume Changes in Schizophrenia and Bipolar Disorder: A Quantitative MRI Study

SUMMARY: Volume abnormalities in subcortical structures, including the hippocampus, amygdala, thalamus, caudate, putamen, and globus pallidus have been observed in schizophrenia (SZ) and bipolar disorder (BD), not all individuals with these disorders exhibit such changes. In addition, the specific patterns and severity of volume changes may vary between individuals and at different stages of the disease. The study aims to compare the volumes of these subcortical structures between healthy subjects and individuals diagnosed with SZ or BD. Volumetric measurements of lateral ventricle, globus palllidus, caudate, putamen, hippocampus, and amygdale were made by MRI in 52 healthy subjects (HS), 33 patients with SZ, and 46 patients with BD. Automatic segmentation methods were used to analyze the MR images with VolBrain and MRICloud. Hippocampus, amygdala and lateral ventricle increased in schizophrenia and bipolar disorder patients in comparison with control subjects using MRIcloud. Globus pallidus and caudate volume increased in patients with schizophrenia and bipolar disorder compared control subjects using Volbrain. We suggested that our results will contribute in schizophrenia and bipolar disorder patients that assessment of the sub-cortical progression, pathology, and anomalies of subcortical brain compositions. In patients with psychiatric disorders, VolBrain and MRICloud can detect subtle structural differences in the brain.

Se han observado anomalías de volumen en las estructuras subcorticales, incluidos el hipocampo, la amígdala, el tálamo, el núcleo caudado, el putamen y el globo pálido, en la esquizofrenia (SZ) y el trastorno bipolar (BD); no todos los individuos con estos trastornos presentan tales cambios. Además, los patrones específicos y la gravedad de los cambios de volumen pueden variar entre individuos y en diferentes etapas de la enfermedad. El estudio tuvo como objetivo comparar los volúmenes de estas estructuras subcorticales entre sujetos sanos e individuos diagnosticados con SZ o BD. Se realizaron mediciones volumétricas del ventrículo lateral, globo pálido, núcleo caudado, putamen, hipocampo y amígdala mediante resonancia magnética en 52 sujetos sanos (HS), 33 pacientes con SZ y 46 pacientes con BD. Se utilizaron métodos de segmentación automática para analizar las imágenes de resonancia magnética con VolBrain y MRICloud. El hipocampo, la amígdala y el ventrículo lateral aumentaron en pacientes con esquizofrenia y trastorno bipolar en comparación con sujetos de control que utilizaron MRIcloud. El globo pálido y el núcleo caudado aumentaron en pacientes con esquizofrenia y trastorno bipolar en comparación con los sujetos control que utilizaron Volbrain. Sugerimos que en pacientes con esquizofrenia y trastorno bipolar, nuestros resultados contribuirán a la evaluación de la progresión subcortical, la patología y las anomalías de las composiciones cerebrales subcorticales. En pacientes con trastornos psiquiátricos, VolBrain y MRICloud pueden detectar diferencias estructurales sutiles en el cerebro.

Smaller left anterior cingulate cortex in non-bipolar relatives of patients with bipolar disorder

Objective: Bipolar disorder (BD) is highly heritable. The present study aimed at identifying brain morphometric features that could represent markers of BD vulnerability in non-bipolar relatives of bipolar patients. Methods: In the present study, structural magnetic resonance imaging brain scans were acquired from a total of 93 subjects, including 31 patients with BD, 31 non-bipolar relatives of BD patients, and 31 healthy controls. Volumetric measurements of the anterior cingulate cortex (ACC), lateral ventricles, amygdala, and hippocampus were completed using the automated software FreeSurfer. Results: Analysis of covariance (with age, gender, and intracranial volume as covariates) indicated smaller left ACC volumes in unaffected relatives as compared to healthy controls and BD patients (p = 0.004 and p = 0.037, respectively). No additional statistically significant differences were detected for other brain structures. Conclusion: Our findings suggest smaller left ACC volume as a viable biomarker candidate for BD.

White matter volume is decreased in bipolar disorder at early and late stages / O volume da substância branca está reduzido tanto nos estágios iniciais quanto nos estágios avançados do transtorno bipolar

Abstract Introduction: Bipolar disorder (BD) is a debilitating mood condition that affects approximately 1.3% of people worldwide, although some studies report up to 3.9% lifetime prevalence and 4-6% in adults when broad diagnostic criteria are applied. Objective: To compare differences in total white matter (WM), corpus callosum (CC) and total gray matter (GM) volumes in patients with type I BD at early and late stages compared with controls. Methods: Fifty-five subjects were enrolled in this study protocol. The double case-control design included 14 patients with BD at early stage; 15 patients at late stage; and their respective matched controls (14 and 12 subjects). Results: CC and total WM volumes were significantly smaller in patients with BD at early and late stages vs. controls. There was no difference for total GM volume in the early stage group, but in patients at late stage total GM volume was significantly smaller than in controls. The total GM volume reduction in patients at late stage is in agreement with the neuroprogression theory of BD. The reduction of WM volumes in total WM and in the CC at early and late stages supports the possibility that an early demyelination process could occur underlying the clinical manifestation of BD. Conclusion: Our findings may direct to the investigation of WM abnormalities in populations at high risk to develop BD, perhaps as early biomarkers before the overt syndrome.

Resumo Introdução: O transtorno do humor bipolar (THB) é uma condição debilitante que afeta aproximadamente 1,3% das pessoas em todo o mundo, embora alguns estudos relatem uma prevalência acumulada de até 3,9% e de 4-6% em adultos quando os critérios diagnósticos mais abrangentes são aplicados. Objetivo: Comparar as diferenças nos volumes totais de substância branca (SB), corpo caloso (CC) e volume total de substância cinzenta (SC) em pacientes com THB tipo I em estágios iniciais e tardios em comparação com controles. Métodos: Cinquenta e cinco sujeitos foram incluídos neste protocolo de estudo. O desenho de caso com duplo controle incluiu 14 pacientes com THB em estágio inicial; 15 pacientes com THB em fase tardia; e seus respectivos controles correspondentes (14 e 12 sujeitos). Resultados: Os volumes do CC e total de SB foram significativamente menores nos pacientes com THB nos estágios iniciais e tardios vs. controles. Não houve diferença para o volume total de SC no grupo em estágio inicial, mas em pacientes em fase tardia o volume total de SC foi significativamente menor do que nos controles. A redução do volume total de SC em pacientes em fase tardia está de acordo com a teoria da neuroprogressão do THB. A redução dos volumes de SB em SB total e no CC em fases precoces e tardias suporta a possibilidade de que um processo de desmielinização precoce poderia ocorrer subjacente à manifestação clínica de THB. Conclusão: Nossos achados podem direcionar a investigação de anormalidades da SB em populações de alto risco para o desenvolvimento de THB, talvez como biomarcadores precoces antes da síndrome aberta.

Early stages of bipolar disorder: characterization and strategies for early intervention

Objective: To characterize the early stages of bipolar disorder (BD), defined as the clinical prodrome/subsyndromal stage and first-episode phase, and strategies for their respective treatment. Methods: A selective literature search of the PubMed, Embase, PsycINFO, and ISI databases from inception until March 2014 was performed. Included in this review were articles that a) characterized prodromal and first-episode stages of BD or b) detailed efficacy and safety/tolerability of interventions in patients considered prodromal for BD or those with only one episode of mania/hypomania. Results: As research has only recently focused on characterization of the early phase of BD, there is little evidence for the effectiveness of any treatment option in the early phase of BD. Case management; individual, group, and family therapy; supportive therapy; and group psychoeducation programs have been proposed. Most evidence-based treatment guidelines for BD do not address treatment specifically in the context of the early stages of illness. Evidence for pharmacotherapy is usually presented in relation to illness polarity (i.e., manic/mixed or depressed) or treatment phase. Conclusions: Although early recognition and treatment are critical to preventing unfavorable outcomes, there is currently little evidence for interventions in these stages of BD.

Association of interleukin-10 levels with age of onset and duration of illness in patients with major depressive disorder

Objective: To investigate peripheral levels of interleukin-10 (IL-10) in patients with major depressive disorder (MDD) and bipolar disorder (BD) and evaluate the relationship between IL-10, age of disease onset, and duration of illness. Methods: Case-control study nested in a population-based cohort of 231 individuals (age 18-24 years) living in Pelotas, state of Rio Grande do Sul, Brazil. Participants were screened for psychopathology using the Mini-International Neuropsychiatric Interview (MINI) and the Structured Clinical Interview for DSM-IV (SCID-I). Serum IL-10 was measured using commercially available immunoassay kits. Results: Peripheral levels of IL-10 were not significantly different in individuals with MDD or BD as compared to controls. However, higher IL-10 levels were found in MDD patients with a later disease onset as compared with controls or early-onset patients. In addition, IL-10 levels correlated negatively with illness duration in the MDD group. In the BD group, age of onset and duration of illness did not correlate with IL-10 levels. Conclusion: Higher levels of IL-10 are correlated with late onset of MDD symptoms. Moreover, levels of this cytokine might decrease with disease progression, suggesting that an anti-inflammatory balance may be involved in the onset of depressive symptoms and disease progression in susceptible individuals.

Biomarkers and staging of bipolar disorder: a systematic review / Dos biomarcadores ao estadiamento do transtorno bipolar: uma revisão sistemática

INTRODUCTION: A growing body of evidence suggests that bipolar disorder (BD) is a progressive disease according to clinical, biochemical and neuroimaging findings. This study reviewed the literature on the relationship between specific biomarkers and BD stages. METHODS: A comprehensive literature search of MEDLINE and PubMed was conducted to identify studies in English and Portuguese using the keywords biomarker, neurotrophic factors, inflammation, oxidative stress, neuroprogression and staging models cross-referenced with bipolar disorder. RESULTS: Morphometric studies of patients with BD found neuroanatomic abnormalities, such as ventricular enlargement, grey matter loss in the hippocampus and cerebellum, volume decreases in the prefrontal cortex and variations in the size of the amygdala. Other studies demonstrated that serum concentrations of neurotrophic factors, inflammatory mediators and oxidative stress may be used as BD biomarkers. CONCLUSIONS: The analysis of neurobiological changes associated with BD progression and activity may confirm the existence of BD biomarkers, which may be then included in staging models that will lead to improvements in treatment algorithms and more effective, individually tailored treatment regimens. Biomarkers may also be used to define early interventions to control disease progression. .

INTRODUÇÃO: Níveis crescentes de evidência sugerem que o transtorno bipolar (TB) exibe um caráter progressivo, em nível tanto clínico, quanto bioquímico e neuroimagiológico. Este estudo revisa a literatura existente sobre a relação entre biomarcadores específicos e estágios do TB. MÉTODOS: Uma busca extensa da literatura nas bases de dados MEDLINE e PubMed foi conduzida para identificar estudos publicados em inglês e em português utilizando as palavras-chave biomarker (biomarcador), neurotrophic factors (fatores neurotróficos), inflammation (inflamação), oxidative stress (estresse oxidativo), neuroprogression (neuroprogressão) e staging models (modelos de estadiamento), em referência cruzada com o termo bipolar disorder (transtorno bipolar). RESULTADOS: Estudos morfométricos em doentes bipolares mostraram a existência de alterações neuroanatômicas, tais como o alargamento dos ventrículos, a perda de substância cinzenta no hipocampo e no cerebelo, a diminuição do volume de determinadas áreas do córtex pré-frontal e variações no tamanho da amígdala. Além disso, outros estudos apontam para a potencialidade do uso dos valores séricos dos fatores neurotróficos, de mediadores inflamatórios e de estresse oxidativo como biomarcadores do TB. CONCLUSÕES: O conhecimento das alterações neurobiológicas, associadas à progressão e atividade do TB, é fundamental para a identificação de biomarcadores. A incorporação de biomarcadores nos modelos de estadiamento do TB poderá permitir um aperfeiçoamento dos algoritmos terapêuticos, possibilitando a elaboração de esquemas de tratamento mais personalizados e eficazes, com destaque para a importância da intervenção precoce na atenuação da progressão da doença. .

Monitoreo del litio / Lithium monitoring

Objetivo: El litio continúa siendo un fármaco de primera línea para el tratamiento de las distintas fases y tipos de enfermedad bipolar, muy posiblemente debido a su eficacia. El monitoreo es necesario para su prescripción segura debido a su rango terapéutico estrecho, su perfil de eventos adversos y su uso durante extensos períodos de tiempo. Se realiza una revisión bibliográfica sobre el monitoreo del litio y las recomendaciones que de allí se derivan para su aplicación en el ámbito de la asistencia clínica de pacientes con patología bipolar. Método: Búsqueda en biblioteca electrónica (medline) desde 1998 hasta la actualidad de los siguientes términos: monitoreo litio, estudio clínico SILENT (neurotoxicidad inducida por litio), tiroides, tiroiditis de Hashimoto, encefalopatía de Hashimoto y litio, interacciones farmacológicas y eventos adversos. Fueron consultadas la guía de tratamiento canadiense, Canadian Network for Mood and Anxiety (CANMAT actualización 2009) (1)), la National Institute for Health and Clinical Excellence (NICE) (2), aprobaciones de la FDA (Food and Drug Administation, EE.UU.) y la International Society for Bipolar Disorders (ISBD). Resultados: El monitoreo de la concentración plasmática de litio estaría indicado cada 3 meses, o cada cambio de dosis o ante comorbilidad con otra enfermedad (2). Evitar la intoxicación aguda para disminuir el riesgo renal y la neurotoxicidad. Es conveniente tener en cuenta el tiempo de prescripción del fármaco y la edad del paciente, debido a la declinación de la función renal a partir de los 50 años. A los 5 años el daño estructural en el túbulo renal puede convertir a la diabetes insípida en irreversible. A los 10 años la prevalencia de falla renal progresiva ocurre en aproximadamente el 20 % de los pacientes (3, 4). La evaluación clínica del paciente es lo que permite hacer un diagnóstico precoz de neurotoxicidad inducida por litio, los factores de riesgo requieren mayor alerta: edad avanzada...

Objective: Lithium remains a first-line drug for the treatment of the different phases and types of bipolar disorder, most likely due to its effectiveness despite its adverse events. Monitoring is necessary for the safe prescription of lithium, given its narraw therapeutic range, the adverse event profile, and its use for extended periods of time. We revise the literature on lithium monitoring and the recommendations that derive from it, for use in the field of the clinical care of patients with bipolar disorder. Method: From 1998 to the present i serched the following terms in Medline: lithium monitoring, SILENT (lithium-induced neurotoxicity), thyroid, Hashimoto's thyroiditis, Hashimoto's encephalopathy and lithium, drug interactions and adverse events. We consulted the Canadian treatment guidelines, the Canadian Network for Mood and Anxiety (update CANMAT 2009), the National Institute for Health and Clinical Excellence (NICE) and the approvals of the FDA (Food and Drug Administration, USA, and the International Society for Bipolar Disorders (ISBD). Results: the monitoring of lilthium plasma concentration would be indicated every 3 months, or every dose change, or when there is comorbidity with other diseases. It is useful to prevent acute toxicity in order to reduce kidney risk and neurotoxicity. The length of prescription and the patients's age should be taken into account, due to the decline in the renal function past the age of 50. At 5 years, the structural damage in the renal tubule can turn diabetes from insipid to irreversible. At 10 years, progressive renal failure occurs in approximately 20 % of the patients. The clinical evaluation of the patient is what allows an early diagnosis of lithium-induced neurotoxicity; the risk factors demand a higher alert: advanced age, prior neurological disease, medical...

Fundamentos neurobiológicos del abordaje psicofarmacológico del trastorno por déficit atencional con/sin hiperquinesia. Riesgo evolutivo y responsabilidad profesional / Neurological basis of the attention deficit disorder with hyperkinesia psychopharmacological treatment-evolution risk and professional liability

El objetivo del presente trabajo es evaluar los riesgos resultantes de no realizar el abordaje psicofarmacológico adecuado al trastorno de déficit atencional con hiperquinesia en niños. Se analiza el riesgo evolutivo y en especial, las comorbilidades que presumiblemente podrían haberse neutralizado de haberse operado un tratamiento médico precoz. El estudio de las disfunciones neurobiológicas, en especial los aspectos derivados de las neuroimágenes y de la afectación de la neurotransmisión dan un soporte neurocientífico a la necesidad de un correcto abordaje médico del trastorno. Se apela finalmente a la responsabilidad profesional para no defeccionar de actuar y no caer en la negligente inacción terapéutica.

The aim of this study is to evaluate the risks resulting from not using the appropriate psychotropic approach to Attention Deficit Disorder with hyperkinesia in children. It analyzes the evolutionary risks, especially comorbidity, which presumably could neutralize itself should it be subjetct to early medical treatment. The study of neurobiological dysfunctions, especially those aspects derived from neuroimaging and neurotransmission involvement, provide neuroscientific support to the need for a correct medical approach to this disorder. Finally, this study stresses the respnsibility of all professionals in not failing to act, and not falling to the negligence of therapeutic inaction.

Rol del sistema de genes CLOCK en las alteraciones del ritmo circadiano en pacientes con Trastorno Bipolar. Estudio de asociación genómica amplia / Role of CLOCK Genes in Circadian Rhythm Alterations, in Patients with Bipolar Disorder. Genome-wide Association Study

Introducción: Las anomalías del ritmo circadiano en el transcurso del TB ha motivado la búsqueda de anomalías en los genes CLOCK asociados a la génesis de ritmos circadianos que podrían estar involucrados en este aspecto de la compleja patología del TB. A pesar de ingentes búsquedas, no se han registrado hallazgos significativos en estudios de asociación amplia de genoma (GWAS/genome-wide association studies). Hay por lo menos 3 razones para explicar estos resultados negativos. En primer lugar el hecho de que los rasgos genéticos de patologías complejas, como es el caso del TB, son habitualmente poligénicos. En segundo término, la organización del reloj/es circadiano/s es bastante más compleja de lo que habitualmente se está dispuesto a admitir; y en tercer lugar, el riesgo genético para TB podría ser compartido entre varias patologías diferentes. Objetivos. Investigar la posibilidad de una asociación entre anomalías en las agrupaciones genéticas responsables de la generación de ritmos circadianos y TB, para lo cual se analizaron las redes constitutivas de los genes CLOCK en por lo menos tres niveles: 1) los genes CLOCK centrales, 2) los genes moduladores de genes CLOCK centrales y 3) los genes controlados por los genes CLOCK centrales. Método: Mediante el uso de método de asociación amplia de genoma con umbrales permisivos se intentó establecer asociaciones significativas entre genes CLOCK y TB comparados con genes control, ademas de incluir asociaciones significativas entre genes CLOCK y TB comparados con genes control, además de incluir asociaciones con otras enfermedades que comparten rasgos clínicos y/o genéticos con el TB, como la Depresión Mayor (DM), Esquizofrenia (E), Trastorno por Déficit de Atención e Hiperactividad (TDAH). Luego de establecer estas asociaciones se compararon los resultados con un conjunto de genes sensibles al litio (Li) y otro grupo sensible a valproato (VPO). Las asociaciones entre TEB y respuesta al litio y/o valproato ...

Introduction. Circadian rythm abnormalities during bipolar disoder has prompetd the search for alterations in CLOCK genes responible for generating circadian rythms, which could be envolved with this complex issue of biipolar disorder. In spite of urgent search, no sinificative results ave been reached in genome wide association scales studies (GWAS). At least three rehaznos could account for this fact: first, genetic traits of complex pathology are usually poligenic, second circadian clock organization is far more complex than usually admitted, and third bipolar disorder genetic risk could be shared with other different diseases. Goals. Search for the possibiity of an association between genetic assemblies anormalies responsible for circadian clock rhythm generation and bipolar disorder. Whith that objective, CLOCK genes networks were analyzed n at least three levels: 1) central CLOCK genes, 2) central CLOCK genes modulators and 3) central CLOCK controlled genes. Method. Using GWAS with permissive tresholds and control comparison, a significative association between CLOCK genes and bipolar disorder was searched, including involvement with other diseases that share common (ADHD). After establishing these associations, results were compared for Lithium and valproate sensitive genes associations. Associations between bipolar disorder, CLOCK genes, lithium and valproate sensitive genes were enriched through comparisons with rhythmic, weakly rhythmic and arrhythmic genes. Results. Significative enrichments were found between CLOCK central genes, bipolar disorder and lithium and valproate sensitive genes, not incluiding CLOCK genes modulators. Associations between bipolar disorder, lithium and valproate sensitive genes and rhythmic genes also were significative, excluding weakly rhythmic and arrhythmic genes. GWAS analysis with flexible tresholds made possible the regognition of association between central CLOCK genes and bipolar disorder, identifying candidate ..

Detection of prodromal symptoms of relapse in mania & unipolar depression by relatives & patients.

Background & objectives: Detection of prodromal symptoms among patients with mania by their immediate relatives has been seldom examined. We carried out this study to examine the ability to detect and report prodromol symptoms of manic relapses by patients themselves and their relatives. Methods: The ability of patients and their relatives to detect prodromal symptoms was examined among 60 remitted patients, 30 each with DSM-IV diagnoses of bipolar disorder and recurrent depressive disorder, with recent manic/depressive relapses, and their 60 immediate relatives, using an instrument composed of items from common symptom-scales, as well as by unstructured interview. Results: Seventy per cent of patients with mania reported prodromes prior to relapse. This was significantly (P<0.01) less than the proportion of their relatives (97%), as well as the proportion of patients with unipolar depression (93%), reporting prodromal symptoms (P<0.05) among patients. Mean duration of the prodromal period reported by patients with mania was about 20 days (median-10 days); relatives reported durations which were longer by about 5 days. Prodromes of unipolar depression (mean 42.7 days; median- 21 days), were significantly longer than of mania, when reported by patients, but not by their relatives. Differences in reporting of prodromes, between relatives and patients seen in mania, were not observed in unipolar depression. The number and type of prodromal symptoms of mania reported was similar among patients and relatives. Interpretation & conclusions: Our findings showed that relatives of patients with mania were better at detecting prodromes of relapse; thus, input from relatives can improve the early detection of prodromal symptoms to prevent relapses of bipolar disorder.

Bipolaridad: monitoreo terapéutico de drogas antiepilépticas / Bipolarity: Therapeutic monitoring of antiepileptic drugs

Objetivo: Revisión bibliográfica del monitoreo de los fármacos utilizados en el tratamiento de la bipolaridad y las recomendaciones que de allí se derivan para su aplicación en el ámbito de la asistencia clínica de pacientes con patología bipolar. Método: Búsqueda en medline y medscape desde 1998 hasta mayo 2011 de los siguientes términos: monitoreo, valproato, lamotrigina, carbamacepina, gabapentina, topiramato, antiepilépticos, trastornos bipolares, interacciones farmacológicas y eventos adversos. Fueron consultadas las guías de tratamiento (CANMAT: Canadian Network for Mood and Anxiety Treatments, update 2009), aprobaciones de la FDA (Food and Drug Administation, EEUU) y recomendaciones de la Asociación Americana de Psiquiatría (APA). Resultados: Los fármacos para los cuales se halló evidencia documentada en bipolaridad, hasta el momento son: valproato, lamotrigina y carbamacepina; no habiendo evidencia que avale el uso de gabapentina o topiramato. Los principales eventos adversos de los antiepilépticos son los del sistema nervioso; requieren evaluación clínica, ya que carecen de un laboratorio específico. Constituye una excepción la hiperamoniemia producida por valproato que puede medirse en el laboratorio y ser causa de encefalopatía o asociarse, con más frecuencia, a trastornos cognitivos. El monitoreo de valproato está recomendado, así como el de amonio. El monitoreo de lamotrigina podría ser útil. La titulación debe ser lenta, para disminuir riesgo de rash potencialmente fatal. Considerar el inicio del tratamiento con monodroga. Se recomienda el monitoreo de carbamacepina y en caso de polifarmacia: el monitoreo del epóxido de carbamacepina. En los tres fármacos considerar interacciones y la posibilidad de toxicidad aún dentro del rango terapéutico

Objective: Literature review of monitoring of AEDs used in the treatment of bipolarity and the recommendations arising from there for use in the field of clinical care of patients with bipolar disease. Method: Search Medscape and medline from 1998 to May 2011 of the following terms: monitoring, valproate, lamotrigine, carbamazepine, gabapentin, topiramate, antiepileptics, bipolar disorders, drug interactions and adverse events. having consulted in addition to treatment guidelines Canadian Network for Mood and Anxiety Treatments, update 2009 (CANMAT), approvals of the Food and Drug Administration, USA (FDA) and recommendations of the American Psychiatric Association (APA). Results: Drugs with documented evidence for use in bipolar disorder are: valproate, lamotrigine and carbamazepine, there being no evidence to support the use of gabapentin or topiramate. It is important to consider that the main adverse effects of antiepileptic drugs (AEDs) develop in the Nervous System. These symptoms require clinical evaluation, since they lack a specific laboratory, except hyperammonemia: a parameter measurable in the laboratory, produced by valproate that is associated with encephalopathy and cognitive disorders. Valproate monitoring is recommended, as well as ammonium. Monitoring of lamotrigine may be useful. The titration should be slow always, to avoid risk of potentially fatal rash. Consider, where possible, the beginning of treatment with single drug. Carbamazepine monitoring is recommended and in case of polypharmacey: the monitoring of carbamazepine epoxide becomes useful. In all cases should be evaluated possible interactions and their mechanisms to have in mind the possibility of toxicity symptoms even with plasma dosages within the therapeutic range

Trastornos neurocognitivos en la hiperamonemia inducida por ácido valproico / Neurocognitive disorders of Valpoic Acid-Induced Hyperammonemia

El objetivo de este trabajo se orienta a dar cuenta de los trastornos neurocognitivos debidos al uso del ácido valproico, por su capacidad de inducir hiperamonemias, las que en muy pocos casos pueden implicar cuadros clínicos severos, y en otros, los más comunes, ocasionar síntomas cognitivos leves pero que pueden revestir importancia en la vida cotidiana de un paciente. Resulta necesario diferenciarlos de aquellos síntomas cognitivos que son una consecuencia de la enfermedad bipolar en sí misma, cuando dicho fármaco se lo usa como estabilizador del ánimo

The aim of this paper is oriented to account for neurocognitive disorders due to use of valproic acid, their ability to induce hyperammonemias, which in rare cases can lead to severe clinical symptoms, and in others, the most common, cause mild cognitive symptoms but of potential importance in the daily life of a patient. It is necessary to differentiate them from those cognitive symptoms wich are a consequence of bipolar disorder itself, when the drug is used as a mood stabilizer

Comorbilidad, trastorno psiquiátrico y consumo de sustancias psicoactivas (patología dual) / Comorbility, psichiatric disorder and psychoactive substance consumption (dual pathology)

La patología dual es una problemática en la que se observa la coexistencia de un trastorno psiquiátrico y el consumo de sustancias psicoactivas, simultáneamente. Es de difícil diagnóstico y tratamiento. Se observa en los estados depresivos, los trastornos de ansiedad, la esquizofrenia, el trastorno bipolar y los trastornos de conducta. El abordaje debe ser integral e incluir tratamiento psicofarmacológico, psicoterapéutico cognitivo-conductual, psicoterapia grupal y orientación a la familia, asimismo, lograr un compromiso del paciente, los familiares y los amigos en el cumplimiento estricto del tratamiento. El tratamiento puede realizarse en forma ambulatoria, en hospital de día, con internación breve para la desintoxicación o en comunidades terapéuticas, la elección dependerá del tipo de patología psiquiátrica y del nivel bajo, medio o alto de consumo de sustancias concomitante.

Dual pathology is a problem in which a psychiatric disorder and the consumption of psychoactive substances coexist at the same time. It is difficult to diagnose and to treat. This pathology is observed in depressive states, anxiety disorders, shizophrenia, bipolar disorder and behavior disorders. Its approach should be integral and include psychopharmacological, psychotherapeutic, cognitive-behavioral treatment, group psychotherapy and family guidance, and it should achieve commitment on the part of the patient, relatives and friends, in the strict compliance of such treatment. Treatment can be performed externally, at a day hospital, through brief hospitalization for desintoxication or in therapeutic communities, the choice will depend on the type of psychiatric pathology and on the low, medium or high concomitant level of consumption of substances.

Alteraciones cognitivas en el trastorno bipolar: posibles etilogías / Cognitive alterations in bipolar disorder: possible etiologies

Diversos estudios científicos sugieren la posibilidad de cambios estructurales y/o funcionales en el cerebro de los sujetos con diagnóstico de trastorno bipolar (TBP). A su vez, estos individuos presentan déficits en un alto rango de pruebas neuropsicológicas, tanto durante los episodios agudos como en autimia, que se correlacionan también con el número de episodios y con la duración de la enfermedad. Las alteraciones halladas más frecuentemente consisten en déficits atencionales, en aprendizaje y memoria y en funciones ejecutivas. Esta revisión se propone estudiar 6 causas que potencialmente podrían estar implicadas en la aparición de las deficiencias cognitivas en los sujetos con TBP: 1) iatrogénica y/o abuso de sustancias, 2)cambios funcionales agudos asociados con depresión y/o manía, 3) lesiones estructurales permanentes de origen neurodegenerativo, 4) lesiones estructurales permanentes de origen en el neurodesarrollo, 5) cambios funcionales permanentes de origen genético, y 6) cambios funcionales permanentes secundarios a influencias del entorno. Se concluye que las diversas alteraciones cognitivas presentes en los individuos con TBP serían consecuencia de la interacción y la combinación aleatoria de los distintos factores mencionados.

Different scientific studies suggest the possibility of structural and/or functional changes in the brain of people whit diagnosis of Bipolar Disorder. Besides that, these people show deficits in a large number of neuro psychological test, both in acute episodes and in eutimia. Deficits are also correlated with the number of episodes and the duration of the illness. The most frequent alterations founded were deficits in attention, learning and memory and executive functions. This review proposes the study of six causes that potentially could be implicated in the emergence of the cognitive deficits in people whit bipolar disorder: 1) iatrogenic and/or substance abuse; 2) acute functional changes related to depression and/or mania; 3) permanent structural injuries neurodegenertive in origin; 4) permanent structural injuries neurodevelopmental in origin; 5) permanent functional changes of genetic origin; 6) permanent functional changes as a consequence of environmental influence. Our conclusion is that different cognitive alterations in people with bipolar disorder are the consequence of the interaction and random combination of different factors mentioned above.

[Comparing the SSR changes in patients with depression, mania and healthy persons]

Skin sympathetic response [SSR] is an electrophysiological techniques and a central polysynaptic process. In mood disorders there are some changes in the cortex, hypothalamus activity, limbic system and basalganglia. Therefore, we compare the SSR changes in the patients with depression, mania and healthy persons. The patients with depression and mania were chosen based on DSM IV criterion by the psychiatrist. In cross-sectional analytic study, control group was selcted away healthy men and women. The SSR was written by physiograph. The stimulat electrod was fixed on the middle finger of the left hand and 5 sympathetic responses were recored for every sample. The mean of amplitude, duration and latency time were computed and compared among three groups. The mean of latency in control, mania and depressed groups were not statistically difference [p=.8]. There were no difference between mean of duration in latency time in three groups. The mean of amplitude were not significant in three groups. It seems hypothalamus has not direct effect balance of sympathy skin responses

Is brain banking of psychiatric cases valuable for neurobiological research?: [review]

It is widely accepted that neurobiological abnormalities underlie the symptoms of psychiatric disorders such as schizophrenia and unipolar or bipolar affective disorders. New molecular methods, computer-assisted quantification techniques and neurobiological investigation methods that can be applied to the human brain are all used in post-mortem investigations of psychiatric disorders. The following article describes modern quantitative methods and recent post-mortem findings in schizophrenia and affective disorders. Using our brain bank as an example, necessary considerations of modern brain banking are addressed such as ethical considerations, clinical work-up, preparation techniques and the organization of a brain bank, the value of modern brain banking for investigations of psychiatric disorders is summarized.

Anormalidades neuropatológicas e neuroquímicas no transtorno afetivo bipolar / Neuropatological and neurochemical abnormalities in bipolar disorder

OBJETIVOS: Estudos pós-mortem, farmacológicos, de neuroimagem e em modelos animais têm demonstrado uma possível associação de mecanismos de sinalização intracelular na fisiopatologia do transtorno afetivo bipolar (TAB). Esse trabalho tem como objetivo revisar os achados em neuropatologia e bioquímica celular. MÉTODOS: Foi realizada uma pesquisa ao MEDLINE, entre 1980 e 2003, tendo sido utilizados os unitermos: bipolar disorder, signaling, second messengers e postmortem, além de referências cruzadas dos artigos selecionados. RESULTADOS: uropatológicos demonstraram uma diminuição do número de células neuronais e gliais, principalmente no córtex pré-frontal de pacientes bipolares. Estudos neuroquímicos demonstraram alterações nas vias do AMPc, fosfatidilinositol, Wnt/GSK-3beta e Ca++ intracelular nesses pacientes. CONCLUSÃO: Os achados de alterações neuropatológicas e neuroquímicas no TAB podem estar relacionados com a fisiopatologia deste transtorno e com os efeitos dos estabilizadores de humor. No entanto, mais estudos são necessários para esclarecer o papel das cascatas de sinalização intracelular na patogênese deste transtorno.

Avanços no diagnóstico do transtorno do humor bipolar / Advances in the diagnosis of bipolar mood disorder

Atualmente, vemos transformações no diagnóstico do Transtorno de Humor Bipolar (THB). A prática clínica exige conhecimento mais detalhado da correlação THB - outras doenças psiquiátricas. Nessa revisão não-sistemática, foram abordados aspectos diagnósticos do THB: a) histórico, b) Espectro Bipolar, c) Depressão Atípica (DeA) e Disforia Histeróide, d) Estados Mistos, e) relação THB-Transtornos de Ansiedade, f) relação com o diagnóstico de Transtorno de Personalidade Borderline (TPB), g) contraponto ao conceito de espectro bipolar. A doença é conhecida desde a Grécia Antiga. Os estudos baseados nas publicações de Hagop Akiskal expandem o diagnóstico para além dos critérios usualmente utilizados, criando o conceito de espectro bipolar. A alta prevalência de comorbidade entre THB e Transtornos de Ansiedade corroboram que ambos compartilham o mesmo substrato neurobiológico. O debate demonstra que não há consenso, expondo a fragilidade dos nossos métodos diagnósticos. Entretanto, a revisão mostra a utilidade de sempre considerar o THB como diagnóstico diferencial.

Lítio, Carbamazepina e Acido Valpróico: eficácia na fase de manutençäo / Lithium, carbamazepine and valproate: efficacy in the prophylaxis of bipolar disorder

Neste artigo, foi feita uma revis