Efficacy of a cognitive and behavioural psychotherapy applied by primary care psychologists in patients with mixed anxiety-depressive disorder: a research protocol

Background: In contrast with the recommendations of clinical practice guidelines, the most common treatment for anxiety and depressive disorders in primary care is pharmacological. The aim of this study is to assess the efficacy of a cognitive-behavioural psychological intervention, delivered by primary care psychologists in patients with mixed anxiety-depressive disorder compared to usual care. Methods/Design: This is an open-label, multicentre, randomized, and controlled study with two parallel groups. A random sample of 246 patients will be recruited with mild-to-moderate mixed anxiety-depressive disorder, from the target population on the lists of 41 primary care doctors. Patients will be randomly assigned to the intervention group, who will receive standardised cognitive-behavioural therapy delivered by psychologists together with usual care, or to a control group, who will receive usual care alone. The cognitive-behavioural therapy intervention is composed of eight individual 60-minute face-to face sessions conducted in eight consecutive weeks. A follow-up session will be conducted over the telephone, for reinforcement or referral as appropriate, 6 months after the intervention, as required. The primary outcome variable will be the change in scores on the Short Form-36 General Health Survey. We will also measure the change in the frequency and intensity of anxiety symptoms (State-Trait Anxiety Inventory) and depression (Beck Depression Inventory) at baseline, and 3, 6 and 12 months later. Additionally, we will collect information on the use of drugs and health care services. Discussion: The aim of this study is to assess the efficacy of a primary care-based cognitive-behavioural psychological intervention in patients with mixed anxiety-depressive disorder. The international scientific evidence has demonstrated the need for psychologists in primary care. However, given the differences between health policies and health services, it is important to test the effect of these psychological interventions in our geographical setting.

Integrated treatment of first episode psychosis with online training (e-learning): study protocol for a randomised controlled trial

Background: The integrated treatment of first episode psychosis has been shown to improve functionality and negative symptoms in previous studies. In this paper, we describe a study of integrated treatment (individual psychoeducation complementary to pharmacotherapy) versus treatment as usual, comparing results at baseline with those at 6-month re-assessment (at the end of the study) for these patients, and online training of professionals to provide this complementary treatment, with the following objectives: 1) to compare the efficacy of individual psychoeducation as add-on treatment versus treatment as usual in improving psychotic and mood symptoms; 2) to compare adherence to medication, functioning, insight, social response, quality of life, and brain-derived neurotrophic factor, between both groups; and 3) to analyse the efficacy of online training of psychotherapists. Methods/design: This is a single-blind randomised clinical trial including patients with first episode psychosis from hospitals across Spain, randomly assigned to either a control group with pharmacotherapy and regular sessions with their psychiatrist (treatment as usual) or an intervention group with integrated care including treatment as usual plus a psychoeducational intervention (14 sessions). Training for professionals involved at each participating centre was provided by the coordinating centre (University Hospital of Alava) through video conferences. Patients are evaluated with an extensive battery of tests assessing clinical and sociodemographic characteristics (Positive and Negative Syndrome Scale, State-Trait Anxiety Inventory, Liebowitz Social Anxiety Scale, Hamilton Rating Scale for Depression, Scale to Assess Unawareness of Mental Disorders, Strauss and Carpenter Prognostic Scale, Global Assessment of Functioning Scale, Morisky Green Adherence Scale, Functioning Assessment Short Test, World Health Organization Quality of Life instrument WHOQOL-BREF (an abbreviated version of the WHOQOL-100), and EuroQoL questionnaire), and brain-derived neurotrophic factor levels are measured in peripheral blood at baseline and at 6 months. The statistical analysis, including bivariate analysis, linear and logistic regression models, will be performed using SPSS. Discussion: This is an innovative study that includes the assessment of an integrated intervention for patients with first episode psychosis provided by professionals who are trained online, potentially making it possible to offer the intervention to more patients.

Antsietate asaldura orokorraren tratamenduaren hausnarketa eta erizaintzaren esku hartzea : berrikuspen bibliografikoa

Antsietate asaldurak gaixotasun mentalen artean ugarienak dira; hau horrela izanik, Antsietate Asaldura Orokorraren tratamenduak aztertu beharrekoak dira gaur egun. Lehenik eta behin, ikerketa askoren arabera dependentzia, tolerantzia eta bigarren mailako efektu asko ematen baitira epe luzeko antsietatearen aurkako farmakoetan. Bentzodiazepinak eragiten dituzten arazoak direla eta, garrantzitsua da tratamendu psikologikoaren eraginkortasuna aztertzea. Helburua: Tratamendu farmakologiko eta ez-farmakologikoaren eraginkortasunaren hausnarketa egitea eta patologiaren kudeaketan Erizaintzaren funtzioa baloratzea dira. Metodologia: Scopus, Pubmed, Cochrane library, Trip database, Science Direct, Ministerio de Sanidad Servicios Sociales e Igualdad eta Cuiden bezalako datu baseetan azkeneko 10 urteetako bilaketa bibliografikoaz gain, eskuzko bilaketa ere gauzatu da gaztelaniaz zein ingelesez . Emaitzak: Nahiz eta gidek bentzodiazepinen epe laburrerako erabilpena gomendatu, epe luzerako tratamendu moduan erabiltzen dira bigarren mailako efektu ugari eta dependentzia garatuz. Psikoterapiaren eraginkortasuna, farmakoena baino geldoagoa izaten da baina epe luzera iraupen luzeagoa du. Ondorioak: Bentzodiazepinen eraginkortasuna epe laburrean ezin da ukatu, Terapia Kognitibo-Konduktuala hasteko momentuan erabilgarria izanik bere eraginkortasun sintomatologikoagatik. Erizainaren funtzioa baliagarria da asaldura mental honen balorazioan, beharrezko tratamenduak jasotzea ahalbidetuz eta bideraketa on bat eginez.

Terapias cognitivo-conductuales en la fobia social, en adultos

La fobia social es una enfermedad psiquiátrica que causa costes socioeconómicos significativos y que presenta una alta comorbilidad. Las terapias cognitivo-conductuales (TCC) pueden ser una alternativa de tratamiento efectiva, ya que buscan el cambio de pensamientos y comportamientos adquiridos en una enfermedad con un alto componente de aprendizaje. Objetivo: Verificar la efectividad de las terapias cognitivo-conductuales (TCC) con respecto a otros tratamientos empleados en la fobia social, en adultos (farmacoterapia y otras técnicas de psicoterapia). Metodología: Revisión bibliográfica de estudios de los últimos 10 años, en bases de datos (Pumed etc...). Se seleccionan 12 artículos, 10 ensayos clínicos y 2 meta-análisis. Resultados: Los estudios muestran una respuesta positiva de los pacientes (en términos de reducción de síntomas según escalas de medida estandarizadas para la fobia social) al tratamiento con terapias cognitivo-conductuales (TCC), en sus distintas modalidades de aplicación (individual, grupal y por internet). Estos ratios de respuesta son similares a los que se obtienen en otros tratamientos (farmacoterapia y terapia psicodinámica). Las TCC presentan como ventaja la ausencia de efectos secundarios; como desventaja, su efecto se produce a más largo plazo Conclusiones: No hay resultados concluyentes en relación al beneficio de estas terapias respecto de otras; los factores que determinan fundamentalmente el éxito de las mismas son la situación y la predisposición individual de cada paciente. Dadas las implicaciones de esta patología en la sociedad actual, sería conveniente invertir más medios en el desarrollo de nuevas técnicas.

The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers

Background: The aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT) gene (polymorphism Val158 Met) as a risk factor for Alzheimer's disease (AD) and mild cognitive impairment of amnesic type (MCI), and its synergistic effect with the apolipoprotein E gene (APOE). A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups. The DNA Bank of the University of the Basque Country (UPV-EHU) (Spain) determined COMT Val158 Met and APOE genotypes using real time polymerase chain reaction (rtPCR) and polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLPs), respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI. Results: Neither COMT alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG) showed a synergistic effect with APOE epsilon 4 allele, increasing the risk of AD (OR = 5.96, 95% CI 2.74-12.94, p < 0.001 and OR = 6.71, 95% CI 3.36-13.41, p < 0.001 respectivily). In AD patients this effect was greater in women. In MCI patients such as synergistic effect was only found between AG and APOE epsilon 4 allele (OR = 3.21 95% CI 1.56-6.63, p = 0.02) and was greater in men (OR = 5.88 95% CI 1.69-20.42, p < 0.01). Conclusion: COMT (Val158 Met) polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE epsilon 4 allele that proves greater in women with AD.

Self-Organized Criticality, Plasticity and Sensorimotor Coupling. Explorations with a Neurorobotic Model in a Behavioural Preference Task

During the last two decades, analysis of 1/f noise in cognitive science has led to a considerable progress in the way we understand the organization of our mental life. However, there is still a lack of specific models providing explanations of how 1/f noise is generated in coupled brain-body-environment systems, since existing models and experiments typically target either externally observable behaviour or isolated neuronal systems but do not address the interplay between neuronal mechanisms and sensorimotor dynamics. We present a conceptual model of a minimal neurorobotic agent solving a behavioural task that makes it possible to relate mechanistic (neurodynamic) and behavioural levels of description. The model consists of a simulated robot controlled by a network of Kuramoto oscillators with homeostatic plasticity and the ability to develop behavioural preferences mediated by sensorimotor patterns. With only three oscillators, this simple model displays self-organized criticality in the form of robust 1/f noise and a wide multifractal spectrum. We show that the emergence of self-organized criticality and 1/f noise in our model is the result of three simultaneous conditions: a) non-linear interaction dynamics capable of generating stable collective patterns, b) internal plastic mechanisms modulating the sensorimotor flows, and c) strong sensorimotor coupling with the environment that induces transient metastable neurodynamic regimes. We carry out a number of experiments to show that both synaptic plasticity and strong sensorimotor coupling play a necessary role, as constituents of self-organized criticality, in the generation of 1/f noise. The experiments also shown to be useful to test the robustness of 1/f scaling comparing the results of different techniques. We finally discuss the role of conceptual models as mediators between nomothetic and mechanistic models and how they can inform future experimental research where self-organized critically includes sensorimotor coupling among the essential interaction-dominant process giving rise to 1/f noise.

Altered expression of Alzheimer's disease-related genes in the cerebellum of autistic patients: a model for disrupted brain connectome and therapy

Autism and Alzheimer's disease (AD) are, respectively, neurodevelopmental and degenerative diseases with an increasing epidemiological burden. The AD-associated amyloid-beta precursor protein-alpha has been shown to be elevated in severe autism, leading to the 'anabolic hypothesis' of its etiology. Here we performed a focused microarray analysis of genes belonging to NOTCH and WNT signaling cascades, as well as genes related to AD and apoptosis pathways in cerebellar samples from autistic individuals, to provide further evidence for pathological relevance of these cascades for autism. By using the limma package from R and false discovery rate, we demonstrated that 31% (116 out of 374) of the genes belonging to these pathways displayed significant changes in expression (corrected P-values <0.05), with mitochondria- related genes being the most downregulated. We also found upregulation of GRIN1, the channel-forming subunit of NMDA glutamate receptors, and MAP3K1, known activator of the JNK and ERK pathways with anti-apoptotic effect. Expression of PSEN2 (presinilin 2) and APBB1 (or F65) were significantly lower when compared with control samples. Based on these results, we propose a model of NMDA glutamate receptor-mediated ERK activation of alpha-secretase activity and mitochondrial adaptation to apoptosis that may explain the early brain overgrowth and disruption of synaptic plasticity and connectome in autism. Finally, systems pharmacology analyses of the model that integrates all these genes together (NOWADA) highlighted magnesium (Mg2+) and rapamycin as most efficient drugs to target this network model in silico. Their potential therapeutic application, in the context of autism, is therefore discussed.