Deterioro funcional y neurocognitivo en pacientes con esquizofrenia deficitaria en Perú y confiabilidad de la estructura bidimensional de la sintomatología negativa / Functional and neurocognitive impairment in deficit schizophrenia patients in Peru and reliability of the bidimensional structure of negative symptomatology

Resumen La mayoría de los estudios sugieren que los pacientes con esquizofrenia deficitaria presentan un deterioro funcional y neurocognitivo más grave en comparación con los pacientes con esquizofrenia no deficitaria. Sin embargo, existen pocos estudios al respecto en América Latina. Examinar las diferencias entre el funcionamiento y el deterioro neurocognitivo en pacientes con y sin esquizofrenia deficitaria; y analizar la validez de la estructura bifactorial de los síntomas negativos en una muestra de pacientes peruanos. Se reclutó a un total de 53 pacientes peruanos con esquizofrenia. Se utilizó la versión en español del Schedule for the Deficit Syndrome (SDS) para diagnosticar el síndrome deficitario, el Functioning Assessment Short Test (FAST) para evaluar el funcionamiento global, y el Screen for Cognitive Impairment in Psychiatry (SCIP) para evaluar el funcionamiento neurocognitivo. La prevalencia de esquizofrenia deficitaria fue del 62,3 %. Los pacientes con esquizofrenia deficitaria presentan un mayor deterioro en la memoria de trabajo (p = 0,003), fluidez verbal (p = 0,002), aprendizaje verbal retardado (p = 0,039) y velocidad de procesamiento (p = 0,004). En cuanto al funcionamiento global, los pacientes con esquizofrenia deficitaria muestran un rendimiento inferior en las dimensiones de autonomía (p = 0,002), laboral (p = 0,001), cognitiva (p = 0,010), finanzas (p = 0,015), relaciones interpersonales (p < 0,001) y tiempo de ocio (p < 0,001). Los pacientes con esquizofrenia deficitaria muestran un mayor deterioro en el funcionamiento global y cognitivo. La replicación de la estructura bidimensional de los síntomas negativos en una muestra peruana contribuye a la hipótesis de la universalidad del modelo de «déficit expresivo¼ y «apatía-abulia¼.

ABSTRACT Many studies suggest that patients with deficit schizophrenia exhibit a more severe functional and neurocognitive impairment than those with non-deficit schizophrenia. However, there are few studies on this topic in Latin America. To examine the differences in functioning and neurocognitive impairment between patients with and without deficit schizophrenia, and to analyze the validity of the bifactorial structure of negative symptoms in a sample of Peruvian patients. A total of 53 Peruvian patients with schizophrenia were recruited. The Spanish version of the Schedule for the Deficit Syndrome (SDS) was used to diagnose the syndrome under study. The Functioning Assessment Short Test (FAST) was employed to assess global functioning, and the Screen for Cognitive Impairment in Psychiatry (SCIP), to evaluate neurocognitive functioning. The prevalence of deficit schizophrenia was 62.3%. Patients with deficit schizophrenia exhibited greater impairment in working memory (p = 0.003), verbal fluency (p = 0.002), delayed verbal learning (p = 0.039), and processing speed (p = 0.004). Regarding global functioning, patients with deficit schizophrenia demonstrated poorer performance in the domains of autonomy (p = 0.002), occupational functioning (p = 0.001), cognitive functioning (p = 0.010), financial functioning (p = 0.015), interpersonal relationships (p < 0.001), and leisure time (p < 0.001). Patients with deficit schizophrenia display greater impairment in global and cognitive functioning. The replication of the bidimensional structure of negative symptoms in a Peruvian sample contributes to the hypothesis of the universality of the "expressive deficit" and "apathy-abulia" model.

Validación de las propiedades psicométricas de la Escala de Personalidad Tipo D en adultos colombianos

La personalidad tipo D se refiere a la vulnerabilidad frente al estrés psicológico, la cual se expresa en dos componentes: la afectividad negativa (AN) y la inhibición social (is), que pueden desencadenar un estado de estrés psicosocial que afecta la salud. El objetivo de este estudio fue analizar las propiedades psicométricas de la Escala de Personalidad Tipo D (DS-14) en población adulta colombiana. La muestra estuvo conformada por 456 adultos (41.7 % hombres y 58.3 % mujeres) colombianos entre los 18 y 86 años. El coeficiente de fiabilidad para las dos subescalas de la DS-14 fue de .73 (AN) y .72 (IS), y .79 para el puntaje total. Se analizó la validez concurrente con medidas de estrategias de afrontamiento resiliente y afrontamiento religioso. Los resultados evidencian validez interna y externa, dados los índices del análisis factorial exploratorio y confirmatorio.

Type D personality refers to vulnerability to psychological stress, which is expressed in two components: negative affectivity (NA) and social inhibition (si), which can trigger a state of psychosocial stress that affects health. The aim of this study was to analyze the psychometric properties of the Type D Personality Scale (DS-14) in the Colombian adult population. The sample consisted of 456 colombian adults (41.7 °% men and 58.3 °% women) between 18 and 86 years of age. The reliability coefficient for the two subscales of the DS-14 was .73 (NA) and .72 (SI), and .79 for the total score. Concurrent validity was analyzed with measures of resilient coping strategies and religious coping. The results show internal and external validity given the indices of the exploratory and confirmatory factor analysis.

Longitudinal Investigation of Auditory Dynamic Range Deficits in Early Psychosis and its Relationship to Negative Symptoms.

BACKGROUND AND HYPOTHESIS: Despite accounting for significant disease morbidity in schizophrenia, the neuropathological basis of negative symptoms remains poorly understood and options for treatment limited. Our recent study identified robust associations between diminished auditory cortex (AC) dynamic range and social functioning impairments and negative symptoms in first episode psychosis (FESz). The current investigation examined the progression of these relationships 4-8 months from baseline testing. STUDY DESIGN: Twenty-six FESz and 38 healthy controls (HC) were tested at baseline and follow-up. Magnetoencephalography (MEG) was recorded during binaural presentation of tones (75, 80, and 85 dB). Assessments included the MATRICS cognitive consensus battery (MCCB) and Global Functioning: Role and Social scales (GFR/GFS) and the Positive and Negative Syndrome Scale. STUDY RESULTS: Overall, FESz exhibited a blunted response to increasing tone intensity relative to HC. While this deficit did not change over time at the group level, recovery of right hemisphere AC dynamic range (85-75 dB response) among FESz individuals was associated with reductions in negative symptoms (ρ = -0.50). Diminished dynamic range was also associated with impaired GFS (ρ = 0.65), GFR (ρ = 0.51), and MCCB (ρ = 0.49) at baseline and increased negative symptoms at baseline (ρ = -0.53) and follow-up (ρ = -0.51). CONCLUSION: Despite persistent dynamic range impairment in FESz as a group, individual recovery of this AC response property was associated with significant reduction in negative symptoms. Identification of a functional neural deficit that tracts progression of negative symptoms during a critical period for disease modification is essential to the management of these devastating and historically treatment refractory symptoms.

Longitudinal invariance of the positive and negative syndrome scale negative dimension in antipsychotic naïve first-episode schizophrenia.

AIM: Construct stability over time is required for reliable inference, but evidence regarding the longitudinal invariance of negative symptoms is still limited. Thus, we examined the longitudinal invariance of the negative dimension using the positive and negative syndrome scale (PANSS) in an antipsychotic-naïve first-episode schizophrenia sample at baseline and after 10 weeks. METHODS: Our study was conducted at a specialized early intervention service. PANSS ratings were analysed for 138 patients, and two different models were specified and tested: a unidimensional and a two-correlated factor solution. RESULTS: The unidimensional model fulfilled criteria for longitudinal invariance, whilst the two-correlated did not. CONCLUSION: Our study provides support for the PANSS negative unidimensional model use to evaluate negative symptoms' longitudinal change following first-episode schizophrenia.

What is the Best Latent Structure of Negative Symptoms in Schizophrenia? A Systematic Review.

BACKGROUND: Determining the best latent structure of negative symptoms in schizophrenia could benefit assessment tools, neurobiological research, and targeted interventions. However, no review systematically evaluated studies that assessed and validated latent models of negative symptoms. OBJECTIVE: To identify and evaluate existing latent structure models in the literature of negative symptoms and to determine the best model. METHOD: Systematic search of MEDLINE, EMBASE, and Scopus on July 19, 2020, for confirmatory factor analysis models of negative symptoms in patients with schizophrenia. The available evidence was assessed through 2 sets of criteria: (1) study design quality-based on negative symptoms assessment and modeling strategy and (2) psychometric quality and model fit-based on fit indices and factor definition quality. RESULTS: In total, 22 studies (n = 17 086) from 9 countries were included. Studies differed greatly regarding symptom scales, setting, and sample size (range = 86-6889). Dimensional models included 2-6 factors (median = 4). Twelve studies evaluated competing models and adopted appropriate instruments to assess the latent structure of negative symptoms. The 5-factor and hierarchical models outperformed unitary, 2-factor, and 3-factor models on all direct comparisons, and most of the analyses derived from the Brief Negative Symptom Scale. Considering the quality criteria proposed, 5-factor and hierarchical models achieved excellent fit in just one study. CONCLUSIONS: Our review points out that the 5-factor and hierarchical models represent the best latent structure of negative symptoms, but the immaturity of the relevant current literature may affect the robustness of this conclusion. Future studies should address current limitations regarding psychometric properties and also address biological and clinical validity to refine available models.

Psychosis in Huntington´s Disease. a rare and Under-Investigated Psychiatric Manifestation / Psychosis in Huntington's Disease: uma manifestação psiquiátrica rara e pouco investigada

Introduction: Psychotic symptoms are among the least prevalent and under-investigated psychiatric manifestations (PM) of Huntington's disease (HD). Case report: We herein report a case of a 31-year-old male patient who presented PM with a predominance of negative symptoms, without any significant abnormal movement. HD was diagnosed based on positive DNA analysis and family history. HD imposes longitudinal follow-up through a multidisciplinary approach in order to improve the quality of life and prognosis. Conclusion: This case report highlights the importance of comprehending the PM in the initial presentation of HD so that the diagnosis is not delayed until the onset of motor symptoms.

Introdução: Os sintomas psicóticos estão entre as manifestações psiquiátricas (MP) menos prevalentes e pouco investigadas da doença de Huntington (DH). Relado de caso: Relatamos o caso de um paciente do sexo masculino, 31 anos, que apresentou MP com predomínio de sintomas negativos, sem qualquer movimento anormal significativo. A DH foi diagnosticada com base em uma análise de DNA positiva e na história familiar. A DH impõe um acompanhamento longitudinal por meio de uma abordagem multidisciplinar, a fim de melhorar a qualidade de vida e o prognóstico. Conclusão: Este relato de caso destaca a importância da compreensão das MPs na apresentação inicial da DH, para que o diagnóstico não seja atrasado até ao aparecimento dos sintomas motores

Dance promotes positive benefits for negative symptoms in autism spectrum disorder (ASD): A systematic review.

BACKGROUND: Autism spectrum disorder (ASD) is characterized as a neurodevelopmental disorder with stereotyped and repetitive behaviors. Dance practice can elicit esthesia to stimulate the communication process through the notion of the phenomenal body that is recognized in an expressive and symbolic space. OBJECTIVE: To conduct a systematic review to identify how dance promotes positive benefits for the negative symptoms in ASD. METHOD: We formulated the research question based on PICO: "What is the influence of dance on negative symptoms in individuals with autism spectrum disorder?". Databases were searched in March 2019 and included PubMed, Science Direct, Scopus, PsycInfo and Web of Science. RESULTS: We identified 9,350 studies of which five were selected for our review (a total of 266 individuals). All included studies showed an influence of dance on negative symptoms, including empathy, emotional expression, body awareness, behavior, and psychological wellbeing that impact on social reciprocity, and consequently the communication process, in ASD. CONCLUSIONS: Dance practice may contribute to body awareness and social involvement using techniques that provide mirroring, synchronization, rhythm, and reciprocity in adults with normal to high-functioning ASD.

Cross-cultural adaptation, reliability, and content validity of the Brief Negative Symptom Scale (BNSS) for use in Brazil

Abstract Background The Brief Negative Symptom Scale (BNSS) assesses the presence and intensity of negative symptoms in schizophrenia. Objectives This study aimed to carry out the BNSS cross-cultural adaptation to the Brazilian Portuguese language and verify its content validity and reliability. Methods This is a methodological study that followed these steps: (1) implementation of the cross-cultural adaptation and translation protocol, (2) BNSS adapted content validation, and (3) reliability assessment. Six experts participated in the adaptation process. The sample consisted of 30 individuals diagnosed with schizophrenia and assisted at the Brazilian Psychosocial Care Center (CAPS), in João Pessoa, Paraíba, Brazil, which was the research setting. Results The cross-cultural adaptation was successful due to the values obtained for each aspect evaluated, such as semantic (0.922), idiomatic (0.910), experiential (0.961), and conceptual equivalence (0.974). The same happened with content validity regarding clarity of language (0.935), practical relevance (0.974), and theoretical relevance (0.948). Cronbach's alpha coefficient was 0.884 for the entire instrument, and the items ranged from 0.865 to 0.882. Discussion The BNSS adaptation process has shown to be satisfactory for use in the Brazilian context, constituting a useful clinical tool for teaching and research.

Schizophrenia, Not a Psychotic Disorder: Bleuler Revisited.

Current diagnostic criteria delineate schizophrenia as a discrete entity essentially defined by positive symptoms. However, the role of positive symptoms in psychiatry is being questioned. There is compelling evidence that psychotic manifestations are expressed in the population in a continuum of varying degrees of severity, ranging from normality to full-blown psychosis. In most cases, these phenomena do not persist, but they constitute risk factors for psychiatric disorders in general. Psychotic symptoms are also present in most non-psychotic psychiatric diagnoses, being a marker of severity. Research revealed that hallucinations and delusions appear to have distinct, independent biological underpinnings-in the general population, in psychotic, and in non-psychotic disorders as well. On the other hand, negative symptoms were seen to be far more restricted to schizophrenia, have other underlying pathophysiology than positive symptoms, predict outcome and treatment response in schizophrenia, and start before the first psychotic outbreak. The current work discusses the concept of schizophrenia, suggesting that a greater emphasis should be put on cases where psychotic symptoms emerge in a premorbid subtly increasing negative/cognitive symptoms background. In those cases, psychosis would have a different course and outcome while psychosis occurring in the absence of such background deterioration would be more benign-probably having no, or a milder, underlying degenerative process. This reformulation should better drive psychopathological classification, face positive symptoms as epiphenomenon of the schizophrenia process, and dishevel stigma from schizophrenia and from delusions and hallucinations.

Metacognition in schizophrenia disorders: Comparisons with community controls and bipolar disorder: Replication with a Spanish language Chilean sample.

Metacognition refers to the activities which allow for the availability of a sense of oneself and others in the moment. Research mostly in North America with English-speaking samples has suggested that metacognitive deficits are present in schizophrenia and are closely tied to negative symptoms. Thus, replication is needed in other cultures and groups. The present study accordingly sought to replicate these findings in a Spanish speaking sample from Chile. Metacognition and symptoms were assessed among 26 patients with schizophrenia, 26 with bipolar disorder and 36 community members without serious mental illness. ANCOVA controlling for age and education revealed that the schizophrenia group had greater levels of metacognitive deficits than the bipolar disorder and community control groups. Differences in metacognition between the clinical groups persisted after controlling for symptom levels. Spearman correlations revealed a unique pattern of associations of metacognition with negative and cognitive symptoms. Results largely support previous findings and provide added evidence of the metacognitive deficits present in schizophrenia and the link to outcome cross culturally. Implications for developing metacognitively oriented interventions are discussed.

Effects of transcranial direct current stimulation on working memory and negative symptoms in schizophrenia: a phase II randomized sham-controlled trial.

BACKGROUND: The lack of efficacy of pharmacological treatments for cognitive and negative symptoms in schizophrenia highlights the need for new interventions. We investigated the effects of tDCS on working memory and negative symptoms in patients with schizophrenia. METHOD: Double-blinded, randomized, sham-controlled clinical trial, investigating the effects of 10 sessions of tDCS in schizophrenia subjects. Stimulation used 2 mA, for 20 min, with electrodes of 25 cm2 wrapped in cotton material soaked in saline solution. Anode was positioned over the left DLPFC and the cathode in the contralateral area. Twenty-four participants were assessed at baseline, after intervention and in a three-months follow-up. The primary outcome was the working memory score from MATRICS and the secondary outcome the negative score from PANSS. Data were analyzed using generalized estimating equations. RESULTS: We did not find group ∗ time interaction for the working memory (p = 0.720) score or any other cognitive variable (p > 0.05). We found a significant group ∗ time interaction for PANSS negative (p < 0.001, d = 0.23, CI.95 = -0.59-1.02), general (p = 0.011) and total scores (p < 0.001). Exploratory analysis of PANSS 5 factors suggests tDCS effect on PANSS negative (p = 0.012), cognitive (p = 0.016) and depression factors (p = 0.029). CONCLUSION: The results from this trial highlight the therapeutic effects of tDCS for treatment of persistent symptoms in schizophrenia, with reduction of negative symptoms. We were not able to confirm the superiority of active tDCS over sham to improve working memory performance. Larger sample size studies are needed to confirm these findings.

Is Forced Swimming Immobility a Good Endpoint for Modeling Negative Symptoms of Schizophrenia? - Study of Sub-Anesthetic Ketamine Repeated Administration Effects

ABSTRACT Immobility time in the forced swimming has been described as analogous to emotional blunting or apathy and has been used for characterizing schizophrenia animal models. Several clinical studies support the use of NMDA receptor antagonists to model schizophrenia in rodents. Some works describe the effects of ketamine on immobility behavior but there is variability in the experimental design used leading to controversial results. In this study, we evaluated the effects of repeated administration of ketamine sub-anesthetic doses in forced swimming, locomotion in response to novelty and novel object recognition, aiming a broader evaluation of the usefulness of this experimental approach for modeling schizophrenia in mice. Ketamine (30 mg/kg/day i.p. for 14 days) induced a not persistent decrease in immobility time, detected 24h but not 72h after treatment. This same administration protocol induced a deficit in novel object recognition. No change was observed in mice locomotion. Our results confirm that repeated administration of sub-anesthetic doses of ketamine is useful in modeling schizophrenia-related behavioral changes in mice. However, the immobility time during forced swimming does not seem to be a good endpoint to evaluate the modeling of negative symptoms in NMDAR antagonist animal models of schizophrenia.

Crack cocaine inhalation induces schizophrenia-like symptoms and molecular alterations in mice prefrontal cortex.

Crack cocaine (crack) addiction represents a major social and health burden, especially seeing as users are more prone to engage in criminal and violent acts. Crack users show a higher prevalence of psychiatric comorbidities - particularly antisocial personality disorders - when compared to powder cocaine users. They also develop cognitive deficits related mainly to executive functions, including working memory. It is noteworthy that stimulant drugs can induce psychotic states, which appear to mimic some symptoms of schizophrenia among users. Social withdraw and executive function deficits are, respectively, negative and cognitive symptoms of schizophrenia mediated by reduced dopamine (DA) tone in the prefrontal cortex (PFC) of patients. That could be explained by an increased expression of D2R short isoform (D2S) in the PFC of such patients and/or by hypofunctioning NMDA receptors in this region. Reduced DA tone has already been described in the PFC of mice exposed to crack smoke. Therefore, it is possible that behavioral alterations presented by crack users result from molecular and biochemical neuronal alterations akin to schizophrenia. Accordingly, we found that upon crack inhalation mice have shown decreased social interaction and working memory deficits analogous to schizophrenia's symptoms, along with increased D2S/D2L expression ratio and decreased expression of NR1, NR2A and NR2B NMDA receptor subunits in the PFC. Herein we propose two possible mechanisms to explain the reduced DA tone in the PFC elicited by crack consumption in mice, bringing also the first direct evidence that crack use may result in schizophrenia-like neurochemical, molecular and behavioral alterations.

La terapia cognitivo conductual y los síntomas negativos en la esquizofrenia / Cognitive behavioral therapy and negative symptoms in schizophrenia

INTRODUCCIÓN: La esquizofrenia constituye un problema sanitario y social de grandes dimensiones que afecta no sólo al paciente sino a su entorno familiar y social. Dentro de las aproximaciones psicoterapéuticas dirigidas a pacientes con esquizofrenia, las terapias cognitivo conductuales (TCC) son las que cuentan con mayor evidencia de efectividad para diferentes propósitos y etapas del trastorno. OBJETIVO: Analizar las técnicas y efectos específicos sobre síntomas negativos de las principales TCC para pacientes con esquizofrenia: Psicoeducación, Entrenamiento en Habilidades Sociales, Rehabilitación Cognitiva, TCC para Síntomas Positivos y TCC orientada a la Recuperación (TCC-R). MÉTODO: Se llevó a cabo una búsqueda y análisis de literatura científica en PSYCLIT, MEDLINE, EBSCO-HOST y PROQUEST publicada entre 1990 y 2014 en revistas indexadas en inglés y español, utilizando como palabras clave los nombres de las diferentes TCC para la esquizofrenia que se cruzaron en todos los casos con el diagnóstico. Se recopiló también la literatura relevante citada en estos artículos, sobre todo en las revisiones de literatura antecedentes. RESULTADOS: A pesar de los avances que han presentado las TCC en la recuperación de pacientes con diagnóstico de esquizofrenia, los problemas generados por la sintomatología negativa no han sido resueltos por completo. DISCUSIÓN Y CONCLUSIÓN: La TCC-R se considera un estilo terapéutico prometedor para alcanzar los objetivos de recuperación de los pacientes con bajo funcionamiento psicosocial y predominio de sintomatología negativa.

INTRODUCTION: Schizophrenia is a health and social problem of great dimensions, affecting not only the patient but their family and social environment. Within the psychotherapeutic approaches for patients with schizophrenia, Cognitive Behavioral Therapy (CBT) has most evidence of effectiveness for different porpoises and stages of the disorder. OBJECTIVE: Analyze the specific techniques and outcome on negative symptoms of the major CBT for patients with schizophrenia: Psychoeducation, Social Skills Training, Cognitive Remediation, CBT for positive symptoms and Cognitive Behavioral Recovery Oriented Therapy (CBT-R). METHOD: A searching and analysis of scientific literature published in English and Spanish between 1990 and 2014 were performed in PSYCLIT, MEDLINE, EBSCO-HOST and PROQUEST, employing as key words the names of the different CBT for schizophrenia and the diagnosis. Relevant literature included in review articles was also included. RESULTS: Despite the advances of CBT, the problems generated by negative symptoms of patients with schizophrenia are not completely solved. DISCUSSION AND CONCLUSION: CBT-R is considered a promising therapeutic style to achieve the objectives of recovery in patients with low psychosocial functioning and predominance of negative symptomatology.

Experiencias perceptuales inusuales, experiencias anómalo/paranormales y propensión a la esquizotipia / Unusual perceptual experiences, anomalous/paranormal experiences and proneness to schizotypy

Parece haber similitudes entre el trastorno esquizotípico de personalidad (TEP) y las experiencias paranormales. De hecho, algunos de los síntomas en el TEP en el Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) coinciden con un número de experiencias anómalo/paranormales. La esquizotipia positiva, que incluye pensamiento mágico, alucinaciones y otras experiencias perceptuales inusuales, también ha estado relacionada con experiencias y creencias paranormales. Sin embargo, las experiencias paranormales difieren de las experiencias psicóticas en la población no clínica. Para examinar diferencias en síntomas positivos y negativos de esquizotipia se comparó un grupo de individuos interesados en temas paranormales (N = 121) con uno de estudiantes universitarios (N = 588). Como estaba previsto en las hipótesis, las personas interesadas en temas paranormales puntuaron más alto en el subtotal de síntomas positivos de esquizotipia en comparación con los estudiantes, sin diferencias en síntomas negativos. Los síntomas positivos se presentan también en estudiantes que indican tener experiencias paranormales en comparación con aquellos sin experiencias, con una diferencia marginalmente significativa en los síntomas negativos entre ambos grupos.

There seems to be similarities between schizotypal personality and paranormal experiences, in fact, some of the symptoms of PTSD in The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) match a number of anomalous/paranormal experiences. Positive schizotypy, including magical thinking, hallucinations and other unusual perceptual experiences, has also been associated with paranormal experiences and beliefs. However, paranormal experiences differ from psychotic experiences in nonclinical populations. In order to establish differences between positive and negative symptoms of schizotypy, we compared a group of believers in the paranormal (N = 121) and a sample of undergraduate students (N = 588). The hypothesis that believers would have higher scores in schizotypy positive symptoms was confirmed. There was a significant difference in positive symptoms of schizotypy among the group of students with and no experiences, although not significant for negative symptoms.

Estimulación magnética transcraneal para síntomas negativos en la esquizofrenia: una revisión / The transcraneal magnetic stimulation for the negative symptoms in schizofrenia: a review

Schizophrenia is one of the most studied diseases in psychiatry and different dysfunctions of thinking, emotions, perception, movement, and behavior converge in it. These dysfunctions affect the quality of life of the patients in different ways. It is a disease that has been observed in the whole world, with a 0.5 to 1.5% prevalence among adults. Although the biological basis of schizophrenia is not clear enough, the dopaminergic hypothesis is preponderant in our understanding of the symptoms of the disease. A mesolimbic pathway hyperactivity is related to a positive symptomathology, while a prefrontal dopaminergic hypofunction relates to negative symptoms. It has been observed that using serotoninergic antagonists, which promote dopaminergic activity in the prefrontal cortex, translates in to a reduction of the intensity of negative symptoms. This negative syndrome includes a difficulty to initiate new activities (apathy), speech and creativity impoverishment (alogia), alterations in emotional expression, and a lack of capacity to experiment joy. Patients with negative symptoms present gray and white matter loss in left-sided cerebral structures, including temporal lobe, anterior cingulated, and medial frontal cortex. Such a loss seems to be more evident in prefrontal regions, such as the dorsolateral prefrontal region, which connects with anterior temporal structures. Persistent negative symptomathology is a concept proposed by Buchanan, which must fulfill the following criteria: symptoms are primary to the disease or secondary but have not responded to current treatment; interfere with the patient's capacity to accomplish normal functioning; persist during periods of clinical stability, and represent an unresolved therapeutic need. They must be measurable by clinical scales and persist, at least, six months. The Food and Drug Administration has recently considered negative symptoms as an investigation target or new treatments due to their prevalence and high negative impact in the life of the schizophrenic population. Nowadays, the current treatments available for such an entity are second generation antipshycotics and glutamatergic agents -such as d-cycloserine and glicine-, amisulpiride and seleginine, even though their efficacy is limited. Dysfunction of the human prefrontal cortex is considered to be implicated in the pathophisiology of negative symptoms. This cerebral region is essential in the regulation of emotions and cognition. Multiple neural networks begin in the prefrontal cortex and go towards other cortical association areas, to insular region, thalamic structures, basal ganglia and limbic system. It regulates dopaminergic mesencephalic activity through activating and inhibitory pathways, allowing a precise regulation of dopaminergic activity. This double modulation model of dopaminergic pathways has been recently sustained by studies which prove that extracellular dopaminergic concentration in nucleus accumbens increases or reduces after a high or low frequency stimulation of the prefrontal cortex, respectively. A prefrontal cortex lesion causes a syndrome similar to the negative symptomathology in schizophrenia. Transcraneal magnetic stimulation (TMS) could be effective in the treatment of negative symptoms by activating the prefrontal cortex, maybe by stimulating the liberation of dopamine in the mesolimbic and mesoestriatal pathways which have a crucial role in the pathogenesis of negative symptoms such as apathy and anhedonia. TMS was introduced in 1985 and since the early 90's its potential as a treatment has been tested in numerous neurological and psychiatric conditions. It is a noninvasive means of stimulating nervous cells in superficial areas of the brain. During a TMS procedure, an electrical current passes through a wire coil placed over the scalp. This induces a magnetic field that can produce a substantive electrical field in the brain. This electrical field produces in turn a depolarization of nervous cells resulting in the stimulation or disruption of brain activity. TMS may be applied as a single stimulus or repeated many times per second (repetitive TMS), with variations in the intensity, site, and orientation of the magnetic field. Most research and interest has focused on the potential application of repetitive TMS (rTMS) in the treatment of depression. In addition, in recent years an increasing number of open and double-blinded studies of rTMS were conducted in patients with schizophrenia. Most investigators have chosen to focus on the treatment of specific refractory symptoms or syndromes within the disorder such as refractory auditory hallucinations or persistent negative symptoms. TMS has become widely used in research, especially as a method to probe normal and abnormal brain function, motor cortical physiology, and cognition. Regarding negative symptoms in schizophrenia, eleven studies using TMS were carried out until 2006, with a total of 172 patients studied. These studies are difficult to compare because they used different stimulation parameters and the symptoms described were heterogenic. Six studies were blind and five were open, using high frequency TMS in all of them (frequencies above 1 Hz), which is the type of stimulation most commonly used in treatment studies. Six of these studies found a reduction in the severity of the symptoms, but the reduction was not significant in two of them. Ten were the maximum number of sessions included in every study, except for one, in which 20 sessions of TMS were given. In this study, the score of negative subscale of the PANSS was reduced in 33%, which is considered a significant response, and this result was sustained within the next month. In one of these studies, researchers compared 3- and 20-Hz stimulation with sham stimulation and stimulation provided at the patient's individual alpha frequency. Alpha-frequency stimulation was calculated as the patient's peak alpha frequency from five frontal EEG leads. Stimulation of alpha frequency resulted in a significantly greater reduction in negative symptoms than the other conditions. This finding could suggest that negative symptoms may specifically relate to alpha EEG oscillations, which is interesting and requires further exploration and confirmation. Another two studies were conducted in 2007; in the first one, no improvement in negative, positive of affective symptoms was found. The second one, which was a double-blinded clinical trial, found a significant reduction in the intensity of negative, positive, and general symptoms with the active TMS. We should remark that TMS produces changes in the cortical activity in ventral and dorsoestratial regions, but other cerebral regions could be stimulated too, since some activation abnormalities in the left globus palidus, bilateral caudate nucleus, prefrontal, and temporal right cortex have been found and are associated with the etiology of the negative syndrome. In addition, it will be interesting to see whether changes in subcortical dopamine release, which were shown with rTMS in normal volunteers, can be demonstrated in clinical populations, such as patients with schizophrenia, and how this may relate to response to treatment. There is still a need for a larger number of controlled studies, with larger samples, longer periods of evaluation, and constant stimulation parameters, so they can be compared between them and the exact efficacy of TMS as a treatment for negative symptoms can be established.

La estimulación magnética transcraneal (EMT) es un método no invasivo que utiliza campos magnéticos alternantes para inducir corrientes eléctricas en el tejido cortical en diferentes áreas cerebrales. Se considera una forma de tratamiento para diferentes trastornos psiquiátricos, especialmente en la depresión, adicciones y esquizofrenia. Está técnica terapéutica ofrece una vía innovadora para estudiar la excitabilidad de la corteza, la conectividad regional cortical, la plasticidad de las respuestas cerebrales y las funciones cognitivas en el estado del enfermo. Aunque se han documentado resultados positivos en la estimulación de la CPF izquierda y en la CPF derecha, se sugiere que puede ejercer su acción beneficiosa a través de diversos mecanismos de acción aún no comprendidos en su totalidad. La corteza prefrontal humana es esencial en el control e integración de las emociones, la cognición y la regulación del Sistema Nervioso Autónomo. Numerosas conexiones neuronales bidireccionales se originan en la CPF y se extienden al resto de las áreas de asociación cortical, región insular, sistema límbico y los ganglios basales. La CPF modula la actividad dopaminérgica mesencefálica mediante una vía activadora y otra inhibidora, lo que permite una regulación sumamente fina de la actividad dopaminérgica. La vía activadora funciona por medio de proyecciones glutamatérgicas directas e indirectas a las células dopaminérgicas. La vía inhibitoria hace lo propio mediante eferencias glutamatérgicas prefrontales a las interneuronas GABAérgicas mesencefálicas y a las neuronas GABAérgicas estriatomesencefálicas. El modelo de la doble modulación del sistema dopaminérgico mesolímbico demuestra que la concentración dopaminérgica extracelular en el núcleo accumbens disminuye o aumenta después de la estimulación de la corteza prefrontal a baja o alta frecuencia, respectivamente. Dentro de los estudios que utilizan la EMT en la esquizofrenia, se ha encontrado que, tras una EMT de alta frecuencia (>1Hz) o repetititiva (EMTr), hay un aumento de la excitabilidad en varias áreas cerebrales, mientras que la excitabilidad cortical disminuye tras una EMT de baja frecuencia (<1Hz). La excitabilidad cortical también depende de la intensidad y duración de la estimulación, lo que quiere decir que a intensidades más altas habrá mayor actividad cortical y a trenes prolongados habrá cambios duraderos en la excitabilidad cortical. Una gama de síntomas de difícil tratamiento en la esquizofrenia son los síntomas negativos persistentes, donde se ha demostrado una disminución de la actividad en la CPF, por lo que la EMT se ha utilizado para revertir dicha hipoactividad y disminuir los síntomas. De forma contraria, los síntomas positivos, como las alucinaciones, se asocian con una hiperactividad de las áreas témporo-parietales y por tanto debería resultar beneficiosa la aplicación de EMT de baja frecuencia en dichas áreas. La EMT de alta frecuencia también se ha utilizado para tratar a sujetos con síntomas catatónicos prominentes y se ha logrado una mejoría con el tratamiento. El objetivo de esta revisión es que se comprendan mejor la EMT y el uso que se le puede dar para tratar diversos síntomas en la esquizofrenia.

Scale for assessing perceptual anomalies: validation of a Spanish version of the SIAPA scale in a sample of Cuban schizophrenic patients

INTRODUCTION: Perceptual-attentional disorders other than hallucinations in schizophrenic patients have been studied little. In this work, the results of the Spanish version of the SIAPA scale to detect perceptual-attentional anomalies to real stimuli other than hallucinations in a sample of schizophrenic patients in a community study in Cuba are presented. METHODS: 329 subjects were studied: 129 schizophrenic patients and 200 controls. Patients were diagnosed by psychiatrists according to DSM-IV criteria. The SIAPA and PANSS scales were used for the study. Cronbach's alpha coefficient was determined to analyze internal consistency. Reliability, validity of current criterion and structural validity were measured. Comparisons between groups were made using the ANOVA. RESULTS: Schizophrenic patients had more perceptual anomalies than healthy controls. Auditory and visual perceptual anomalies were more frequent. The scale showed high internal consistency (Cronbach's alpha: 0.84). Using a PANSS scale cut-off score of 60, validity had a sensitivity of 56 percent and specificity of 79 percent All modalities of SIAPA scales showed good kappa coefficients (0.72-0.85). CONCLUSIONS: This scale showed similar internal validity and test-retest reliability to those reported in the English version. The results showed that this scale can differentiate the presence of perceptual anomalies in schizophrenic patients from healthy controls. Therefore, we suggest that the SIAPA scale may be useful for assessing perceptual anomalies in clinical researching for cognitive impairment evaluations(AU)

Introducción. Las alteraciones perceptuales-atencionalesdiferentes de las alucinaciones en los pacientes esquizofrénicos han sido poco estudiadas. En este trabajo se presentan los resultados de la versión al español de la escala SIAPA para detectar anomalías perceptuales-atencionalesa estímulos reales diferentes de las alucinaciones en una muestra de pacientes esquizofrénicos en unestudio comunitario en Cuba. Métodos. Se estudiaron 329 sujetos: 129 esquizofrénicos y 200 controles. Para el diagnóstico se usaron los criterios diagnósticos del DSM IV. Para el estudio se aplicó la escala SIAPA y la escala PANSS. Se determinó el coeficiente alpha de Cronbach para analizar la consistencia interna. Se determinó la fiabilidad, la validez de criterio concurrente y la validez estructural. La comparación entre los grupos se realizó con el test de análisis de varianza ANOVA. Resultados. Los pacientes presentaron más alteracionesperceptuales-atencionales diferentes de las alucinaciones que los sujetos normales, principalmente en las modalidades auditivas y visuales. La consistencia interna fue de 0,84. Se obtuvo una sensibilidad del 56 por ciento y una especificidad del 79 por ciento. Se obtuvo índices de fiabilidad(Kappa) adecuados (0,72-0,85) en las diferentes subescalas del SIAPA Conclusiones. En este estudio se obtuvieron valores de confiabilidad y validez de la escala similares a los obtenidos con la versión inglesa. Esta escala permite diferenciar la presencia de alteraciones perceptuales atencionales diferentes de las alucinaciones en pacientes esquizofrénicos en comparación con la población general. Esta escala puede ser utilizada en investigaciones clínicasy epidemiológicas para la evaluación de alteraciones perceptuales-atencionales(AU)