The influence of risk factors on the onset and outcome of psychosis: What we learned from the GAP study.

The GAP multidisciplinary study carried out in South London, recruited 410 first episode of psychosis patients and 370 controls; the aim was to elucidate the multiple genetic and environmental factors influencing the onset and outcome of psychosis. The study demonstrated the risk increasing effect of adversity in childhood (especially parental loss, abuse, and bullying) on onset of psychosis especially positive symptoms. Adverse life events more proximal to onset, being from an ethnic minority, and cannabis use also played important roles; indeed, one quarter of new cases of psychosis could be attributed to use of high potency cannabis. The "jumping to conclusions" bias appeared to mediate the effect of lower IQ on vulnerability to psychosis. We confirmed that environmental factors operate on the background of polygenic risk, and that genetic and environment act together to push individuals over the threshold for manifesting the clinical disorder. The study demonstrated how biological pathways involved in the stress response (HPA axis and immune system) provide important mechanisms linking social risk factors to the development of psychotic symptoms. Further evidence implicating an immune/inflammatory component to psychosis came from our finding of complement dysregulation in FEP. Patients also showed an upregulation of the antimicrobial alpha-defensins, as well as differences in expression patterns of genes involved in NF-κB signaling and Cytokine Production. Being of African origin not only increased risk of onset but also of a more difficult course of illness. The malign effect of childhood adversity predicted a poorer outcome as did continued use of high potency cannabis.

Predicting suicidal behaviour after first episode of non-affective psychosis: The role of neurocognitive functioning.

BACKGROUND: Suicide has been recognised as one of the major causes of premature death in psychosis. However, predicting suicidal behaviour (SB) is still challenging in the clinical setting and the association of neurocognition with SB in psychosis remains poorly understood. This study aimed to investigate the role of neurocognitive performance as predictor of SB. Also, we sought to explore differences in the evolution of clinical and neurocognitive functioning between participants with/without history of suicide attempts (SA) over follow-up period. METHODS: The sample of the study is composed by 517 patients. Sociodemographic, clinical, functional and neurocognitive measures were evaluated at baseline as well as 1-year and 3 years after first episode of psychosis. Bivariate and multivariate analyses explored the influence of these variables as putative baseline predictors of SB. Repeated measures analyses of variance tested differences in clinical and neurocognitive outcomes at 1- and 3-year follow-up. RESULTS: Global cognitive functioning (GCF) (OR = 1.83, 95% CI = 1.25-2.67) and severe depressive symptoms (OR = 1.17, 95% CI = 1.07-1.28) predicted SB. Longitudinal analyses revealed that patients with SB at follow-up presented with higher levels of remission in terms of positive psychotic symptoms and depression. In addition, those with a history of SB had worse GCF and visual memory than those without such antecedents. CONCLUSIONS: GCF was found to be the most robust predictor of SB along with severe depressive symptomatology. Hence, poorer cognitive performance in FEP appears to emerge as a risk factor for suicidal behaviour from early stages of the illness and a comprehensive neurocognitive assessment may contribute to risk assessment.

The role of premorbid personality and social cognition in suicidal behaviour in first-episode psychosis: A one-year follow-up study.

BACKGROUND: High suicide attempt (SA) rates have been reported in first-episode psychosis (FEP) patients, particularly during the first year after the illness onset. Despite previous studies establishing several risk factors for suicidal behaviour in FEP, premorbid personality and social cognition have not been sufficiently investigated to date. OBJECTIVE: To test whether personality traits and social cognition are associated with SAs in FEP over a 12-month follow-up. METHOD: Sixty-five FEP patients were evaluated at first contact with mental health services. The presence of SAs was recorded at six and twelve months after first presentation. Bivariate and multivariate analyses explored the influence of a range of sociodemographic and clinical variables, including premorbid personality and social cognition-related Theory of Mind (ToM) measures, on SAs. RESULTS: SAs were associated with greater severity of symptoms at first hospitalization with psychotic symptoms (OR = 2.18, 95% CI = 1.25-3.82), schizoid personality traits (OR = 1.62, 95% CI = 1.02-2.57) and impairment in a first-order false belief task (OR = 4.26, 95% CI = 1.05-17.31) in the multivariate models. CONCLUSIONS: Symptom severity at illness onset, premorbid schizoid personality traits and ToM impairment emerged as predictors of SA in this FEP sample, which, if replicated, may be useful in identifying high-risk groups and implementing more targeted suicide prevention programs in FEP.

La estimulación magnética transcraneal para el tratamiento de alucinaciones auditivas refractarias en niños y adolescentes / Transcranial magnetic stimulation for treating refractory auditory hallucinations in children and adolescents

La estimulación magnética transcraneal (EMT) es una técnica novedosa, no invasiva, que utiliza la fuerza electromagnética para alterar la excitabilidad neuronal. De manera que al contrario que el TEC (terapia electroconvulsiva) no requiere anestesia y el paciente permanece despierto y monitorizado clínicamente; y al contrario que en la estimulación del nervio vago o que en la estimulación cerebral profunda los electrodos no se insertan en el cerebro. Hasta la fecha se ha utilizado en el tratamiento de distintos trastornos neuropsiquiátricos y desde el 2008 ha sido aprobada por la FDA para el tratamiento de la depresión resistente sin síntomas psicóticos. La experiencia en esquizofrenia y otras psicosis es menor y como siempre hay muchos menos estudios en la población infantil y juvenil, pero como clínicos sabemos que el inicio de la patología psiquiátrica más grave ocurre en la infancia y la adolescencia y que la mitad de todos los trastornos mentales se inician antes de la mitad de la adolescencia. En pacientes tan jóvenes es especialmente importante encontrar tratamientos más efectivos y menos dañinos. La EMT representaría una alternativa interesante, ya que puede activar algunas regiones mientras que al mismo tiempo inhibe otras; de manera que hay estudios que explican mejoría de la sintomatología negativa de la esquizofrenia mediante la estimulación del córtex frontal dorsolateral. La eficacia en el tratamiento de las alucinaciones auditivas mediante la inhibición del córtex temporal izquierdo será revisada en este artículo

Transcranial magnetic stimulation (TMS) is a novel, non-invasive neuromodulatory technique that utilices electromagnetic force to alter neuronal excitability. Hence, unlikely ECT (electroconvulsive therapy) anaesthesia is not required and the individual remains awake and clinically monitored; and in contrast with vagus nerve stimulation and deep brain stimulation, electrodes will not be placed in the brain. To date, it has been applied to a range of neuropsychiatric disorders and since 2008 it has been approved by FDA for the management of resistant depression without psychotic symptoms. Experience in schizophrenia and other psychosis is lesser and as always there are fewer studies in children and adolescentes, but as clinicians we know that the first onset of the most serious mental disorders occurs in childhood or adolescence and half of all lifetime disorders start by the mid-teens. In so young patients is specially important finding more effective treatments and less harmful. TMS would represent an interesting therapeutic alternative since it can activate some regions while at the same time it can inhibit others: for example there are studies that explain improvent in negative symptoms through dorsolateral prefrontal cortex stimulation. Efficacy on auditory hallucinations by inhibition of left temporal cortex will be reviewed below

Enfermedad de Parkinson y espectro obsesivo-compulsivo / Parkinson´s disease and obsessive-compulsive spectrum

Introducción. La descripción de la asociación de síntomas obsesivos con trastornos neurológicos ha sentado las bases de los modelos neuroanatómicos del trastorno obsesivo-compulsivo y ha involucrado a los ganglios basales y lóbulos frontales en su etiopatogenia. En la última década se han comunicado frecuentemente en pacientes con enfermedad de Parkinson fenómenos obsesivo-compulsivos –ya sean rasgos o síntomas– y trastornos del control de impulsos –en el otro extremo del espectro–. Se ha postulado que esta asociación constituiría una prueba más del hipotético papel de los ganglios de la base en los circuitos implicados en la aparición de los fenómenos característicos de los trastornos del espectro obsesivo-compulsivo. Objetivos. Se realiza una revisión en Medline con las expresiones ‘obsessive compulsive Parkinson’ e ‘impulse control Parkinson’, con la finalidad de comprobar las evidencias existentes sobre dichas asociaciones. Desarrollo. Parecen existir suficientes datos como para no considerar casual la aparición de novo de trastornos del control de impulsos en enfermos parkinsonianos. Esto se ha relacionado sobre todo con el tratamiento con agonistas dopaminérgicos. Mayor desacuerdo existe sobre la presentación de síntomas obsesivo-compulsivos en la enfermedad de Parkinson, al encontrarse estudios con resultados dispares y con importantes diferencias metodológicas, incluso en la definición del fenómeno obsesivo. Conclusiones. Actualmente son necesarios más estudios que profundicen en esta cuestión y que sean lo más rigurosos posible, por los avances que podría suponer para el conocimiento de la neurobiología de estas entidades (AU)

Introduction. The description of obsessive symptoms associated with neurological diseases are in the basis of the neuroanatomical models of obsessive-compulsive disorder, with participation of basal ganglia and frontal lobes in its ethiopathogenesis. In the last years, the growth of obsessive-compulsive phenomena –including personality features or symptoms– and impulse control disorders –at the other extreme of the spectrum– in patients with Parkinson’s disease were frequently reported. It was proposed that this association could be other proof of the role of basal ganglia in the characteristic features of the obsessive-compulsive spectrum disorders. Aims. A review in Medline was conduced using the expressions ‘obsessive compulsive Parkinson’ and ‘impulse control Parkinson’. The purpose of this review was to compile the current evidence about these associations. Development. There are sufficient data to support that the growth of impulse control disorders in parkinsonian patients are not produced by chance. It was mainly related with the dopaminergic agonist treatments. More controversial is the growth of obsessive-compulsive symptoms in Parkinson’s disease. The studies found have shown contradictory results and important methodological disparities that included even the definition of obsessive phenomenon. Conclusions. Further and more rigorous studies about these topics are needed, because they could produce and important advance in the knowledge of the neurobiology of these entities (AU)

[Parkinson's disease and obsessive-compulsive spectrum]. / Enfermedad de Parkinson y espectro obsesivo-compulsivo.

INTRODUCTION: The description of obsessive symptoms associated with neurological diseases are in the basis of the neuroanatomical models of obsessive-compulsive disorder, with participation of basal ganglia and frontal lobes in its ethiopathogenesis. In the last years, the growth of obsessive-compulsive phenomena -- including personality features or symptoms -- and impulse control disorders -- at the other extreme of the spectrum -- in patients with Parkinson's disease were frequently reported. It was proposed that this association could be other proof of the role of basal ganglia in the characteristic features of the obsessive-compulsive spectrum disorders. AIMS: A review in Medline was conduced using the expressions 'obsessive compulsive Parkinson' and 'impulse control Parkinson'. The purpose of this review was to compile the current evidence about these associations. DEVELOPMENT: There are sufficient data to support that the growth of impulse control disorders in parkinsonian patients are not produced by chance. It was mainly related with the dopaminergic agonist treatments. More controversial is the growth of obsessive-compulsive symptoms in Parkinson's disease. The studies found have shown contradictory results and important methodological disparities that included even the definition of obsessive phenomenon. CONCLUSIONS: Further and more rigorous studies about these topics are needed, because they could produce and important advance in the knowledge of the neurobiology of these entities.