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Auditory hallucinations (AH) are clinical hallmarks of schizophrenia, however little is known about molecular genetics of these symptoms. In this study, gene expression profiling of postmortem brain samples from prefrontal cortex of schizophrenic patients without AH (SNA), patients with AH (SA) and control subjects were compared. Genome-wide expression analysis was conducted using samples of three individuals of each group and the Affymetrix GeneChip Human-Gene 1.0 ST-Array. This analysis identified the Axon Guidance pathway as one of the most differentially expressed network among SNA, SA and CNT. To confirm the transcriptome results, mRNA level quantification of seventeen genes involved in this pathway was performed in a larger sample. PLXNB1, SEMA3A, SEMA4D and SEM6C were upregulated in SNA or SA patients compared to controls. PLXNA1 and SEMA3D showed down-regulation in their expression in the patient's samples, but differences remained statistically significant between the SNA patients and controls. Differences between SNA and SA were found in PLXNB1 expression which is decreased in SA patients. This study strengthens the contribution of brain plasticity in pathophysiology of schizophrenia and shows that non-hallucinatory patients present more alterations in frontal regions than patients with hallucinations concerning neural plasticity.

The number of large collaborative research networks in mental health is increasing. Training programs are an essential part of them. We critically review the specific implementation of a research training program in a translational Centre for Biomedical Research in Mental Health in order to inform the strategic integration of basic research into clinical practice to have a positive impact in the mental health system and society. Description of training activities, specific educational programs developed by the research network, and challenges on its implementation are examined. The Centre for Biomedical Research in Mental Health has focused on training through different activities which have led to the development of an interuniversity master's degree postgraduate program in mental health research, certified by the National Spanish Agency for Quality Evaluation and Accreditation. Consolidation of training programs within the Centre for Biomedical Research in Mental Health has considerably advanced the training of researchers to meet competency standards on research. The master's degree constitutes a unique opportunity to accomplish neuroscience and mental health research career-building within the official framework of university programs in Spain.

BACKGROUND Despite a growing interest in the use of technology in order to support the treatment of psychotic disorders, limited knowledge exists about the viability and acceptability of these eHealth interventions in relation to the clinical characteristics of patients. OBJECTIVE The objective of this study was to assess the access and use of, as well as experiences and interest in, new technologies using a survey of patients diagnosed with early psychosis compared with a survey of patients diagnosed with chronic psychotic disorders. METHODS We designed a structured questionnaire. This questionnaire was divided into five parts: (1) clinical and demographic information, (2) access and use of the internet, (3) use of the internet in relation to mental health, (4) experiences with technology, and (5) patients’ interest in eHealth services. In total, 105 patients were recruited from early psychosis units (n=65) and recovery units (n=40). RESULTS In this study, 84.8% (89/105) of the patients had access to the internet and 88.6% (93/105) owned an electronic internet device. In total, 71.3% (57/80) of patients who owned a mobile phone were interested in eHealth systems and 38.2% (37/97) reported negative experiences related to the internet usage. We observed differences between the groups in terms of device ownership (P=.02), the frequency of internet access (P CONCLUSIONS The availability and use of technology for the participants in our survey were equivalent to those for the general population. The differences found between the groups in relation to the access or use of technology seemed to due to age-related factors. The use of technology involving mental health and the interest in eHealth interventions were mainly positive and equivalent between the groups. Accordingly, this group of patients is a potential target for the emerging eHealth interventions, regardless of their clinical status. However, 28.7% (23/80) of the studied patients rejected the use of internet interventions and 38.2% (37/97) had unpleasant experiences related to its usage; thus, more in-depth studies are needed to better define the profile of patients with psychosis who may benefit from eHealth treatments.

[EN] Background: Despite a growing interest in the use of technology in order to support the treatment of psychotic disorders, limited knowledge exists about the viability and acceptability of these eHealth interventions in relation to the clinical characteristics of patients. Objective: The objective of this study was to assess the access and use of, as well as experiences and interest in, new technologies using a survey of patients diagnosed with early psychosis compared with a survey of patients diagnosed with chronic psychotic disorders. Methods: We designed a structured questionnaire. This questionnaire was divided into five parts: (1) clinical and demographic information, (2) access and use of the internet, (3) use of the internet in relation to mental health, (4) experiences with technology, and (5) patients¿ interest in eHealth services. In total, 105 patients were recruited from early psychosis units (n=65) and recovery units (n=40). Results: In this study, 84.8% (89/105) of the patients had access to the internet and 88.6% (93/105) owned an electronic internet device. In total, 71.3% (57/80) of patients who owned a mobile phone were interested in eHealth systems and 38.2% (37/97) reported negative experiences related to the internet usage. We observed differences between the groups in terms of device ownership (P=.02), the frequency of internet access (P, This study was supported by Generalitat Valenciana (PROMETEO/2016/082 grant) and CIBERSAM and Fondo de Investigacion Sanitaria (PI01399, PI13/00447; PI17/00402, Cofunded FEDER).

Structural and functional imaging of the brain language structures, regions, and circuits has revealed the association between brain anomalies and hallucinations in psychosis (see Chaps. 9, 10, and 11). Similarly genetic investigations have demonstrated the effect of gene variations on the severity of hallucination (see Chap. 7).

Background Many studies having shown significant improvements in non-social and social cognitive performance in smoking FEP patients compared to non-smoking FEP patients. The findings are controversial. This study analyzed the effects of tobacco use on non-social and social cognitive function in a large group of FEP patients and a matched healthy control group. Methods A sample of 335 patients with FEP and 253 healthy controls was divided into four subgroups: control tobacco users (CTU), control non-tobacco users (CNTU), patient tobacco users (PTU) and patient non-tobacco users (PNTU). Demographic variables, tobacco use variables (presence or absence, frequency and duration of tobacco use), neurocognitive (non-social) performance and social cognition were assessed. Results Comparison of 4 subgroups in non-social cognitive function revealed significant differences after controlling for covariables in executive functions (F = 13.45; p ≤0.001) and working memory domains (F = 4.30; p = 0.005). CTU and CNTU subgroups scored higher in all the domains compared to the PTU and the PNTU subgroups respectively. Social cognitive function was also significantly different within the four subgroups, with control subgroups showing better social cognition than patient subgroups. Significant differences in the executive functions domain were observed when comparing PTU and CTU groups (F = 19.60; p ≤0.001). No significant differences were revealed in the comparison between the patient groups. Conclusions This large study suggests that tobacco use in FEP patients is not related to better non-social or social cognitive performance.

Background and objectives: Neurofeedback treatments have shown successful results in anxiety disorders. Thus, the effectiveness of a beta1 Neurofeedback protocol was tested in a longitudinal clinical case study. Design and methods: A participant suffering from an anxiety syndrome was treated with 10 sessions of Neurofeedback, which protocol consisted in uptraining beta1 rhythm (16-21 Hz) while downtraining theta (4-8 Hz) band. For each of the 10 sessions the state anxiety and salivary cortisol levels were measured in a pre/post design. Initial and final examinations of anxiety symptoms and sustained attention performance were taken in addition. Results: The final evaluation showed that levels of anxiety fell within normative range and sustained attention improved. A t-test for related samples disclosed a significant improvement of beta1 amplitude across sessions, without modifications in untrained bands. A significant inverse correlation between beta1 amplitude and salivary cortisol appeared, suggesting that brain activity could be considered a marker of anxiety. The validation of the beta1 Neurofeedback protocol was assessed by independence, trainability and interpretability criteria. Conclusions: We showed an effective Neurofeedback protocol on anxiety and sustained attention, the success of which could consist on the reestablishment of an optimal cortical arousal capable of inhibiting the elevated amygdalar activity. (English)

Brain volume and thickness abnormalities have been reported in first-episode psychosis (FEP). However, it is unclear if and how they are modulated by brain developmental stage (and, therefore, by age at FEP as a proxy). This is a multicenter cross-sectional case-control brain magnetic resonance imaging (MRI) study. Patients with FEP (n = 196), 65.3% males, with a wide age at FEP span (12-35 y), and healthy controls (HC) (n = 157), matched for age, sex, and handedness, were scanned at 6 sites. Gray matter volume and thickness measurements were generated for several brain regions using FreeSurfer software. The nonlinear relationship between age at scan (a proxy for age at FEP in patients) and volume and thickness measurements was explored in patients with schizophrenia spectrum disorders (SSD), affective psychoses (AFP), and HC. Earlier SSD cases (ie, FEP before 15-20 y) showed significant volume and thickness deficits in frontal lobe, volume deficits in temporal lobe, and volume enlargements in ventricular system and basal ganglia. First-episode AFP patients had smaller cingulate cortex volume and thicker temporal cortex only at early age at FEP (before 18-20 y). The AFP group also had age-constant (12-35-y age span) volume enlargements in the frontal and parietal lobe. Our study suggests that age at first episode modulates the structural brain abnormalities found in FEP patients in a nonlinear and diagnosis-dependent manner. Future MRI studies should take these results into account when interpreting samples with different ages at onset and diagnosis.

Projections from the nucleus incertus (NI) to the septum have been implicated in the modulation of hippocampal theta rhythm. In this study we describe a previously uncharacterized projection from the septum to the NI, which may provide feedback modulation of the ascending circuitry. Fluorogold injections into the NI resulted in retrograde labeling in the septum that was concentrated in the horizontal diagonal band and areas of the posterior septum including the septofimbrial and triangular septal nuclei. Double-immunofluorescent staining indicated that the majority of NI-projecting septal neurons were calretinin-positive and some were parvalbumin-, calbindin-, or glutamic acid decarboxylase (GAD)-67-positive. Choline acetyltransferase-positive neurons were Fluorogold-negative. Injection of anterograde tracers into medial septum, or triangular septal and septofimbrial nuclei, revealed fibers descending to the supramammillary nucleus, median raphe, and the NI. These anterogradely labeled varicosities displayed synaptophysin immunoreactivity, indicating septal inputs form synapses on NI neurons. Anterograde tracer also colocalized with GAD-67-positive puncta in labeled fibers, which in some cases made close synaptic contact with GAD-67-labeled NI neurons. These data provide evidence for the existence of an inhibitory descending projection from medial and posterior septum to the NI that provides a "feedback loop" to modulate the comparatively more dense ascending NI projections to medial septum and hippocampus. Neural processes and associated behaviors activated or modulated by changes in hippocampal theta rhythm may depend on reciprocal connections between ascending and descending pathways rather than on unidirectional regulation via the medial septum.

Georg Juckel,1 Andrea de Bartolomeis,2 Philip Gorwood,3 Sergey Mosolov,4 Luca Pani,5 Alessandro Rossi,6 Julio Sanjuan7 1Department of Psychiatry, LWL-University Hospital, Ruhr-University Bochum, Bochum, Germany; 2Laboratory of Molecular Psychiatry and Unit of Treatment Resistant Psychosis, University School of Medicine of Naples Federico II, Napoli, Italy; 3Groupe Hospitalier Sainte-Anne (CMME), Paris-Descartes University, Paris, France; 4Moscow Research Institute of Psychiatry, Moscow, Russia; 5Institute of Translational Pharmacology, Italian National Research Council, Rome, Italy; 6Università de L’Aquila, L’Aquila, Italy; 7Clinic Hospital, Spanish Mental Health Network (CIBERSAM), University of Valencia, Valencia, Spain Introduction: Prompt administration of antipsychotic treatment that is adhered to is essential for the optimal treatment of schizophrenia. Many patients have benefited from the advent of second-generation antipsychotics, which can offer good symptomatic control with reduced incidence of extrapyramidal symptoms, although with higher risk of metabolic side effects. It is unsurprising that accounts as to whether first- and second-generation antipsychotics differ in their efficacy vary, since treatment effectiveness is a broad notion and difficult to define. Objectives: Numerous factors may be used to gauge treatment effectiveness and, while it has largely been defined in terms of improvements in four domains (symptoms of disease, treatment burden, disease burden, and health and wellness), the real-world clinical utility of this consensus is unclear. Therefore, this article aims to provide a framework that can aid psychiatrists in making assessments about treatment effectiveness. Methods and results: A panel of 12 psychiatrists and psychopharmacologists convened to develop and propose an accessible and globally-applicable framework for assessing the effectiveness of antipsychotic treatments in patients with schizophrenia. Following presentation of a preliminary proposal to a wider group of psychiatrists from across Europe, it was refined into a framework comprising five domains: symptomatic remission and retention of treatment; affective symptoms; cognitive functioning; treatment satisfaction; and personal and social functioning – each of which is discussed in this article. Conclusions: This article provides a framework that can aid psychiatrists in making assessments about treatment effectiveness. It is anticipated that the framework outlined here may contribute to improving clinical practice through the promotion of a patient-centered approach to the assessment of treatment effectiveness, using five specified domains, in patients with schizophrenia. Keywords: antipsychotic, assessment scales, functioning, mental illness, satisfaction

Introduction and objective By using appropriate instrumentation, we have found that cochlear microphonics (CM) advance or delay their appearance, depending on the sound pressure that generates them. This time variation is on the order of microseconds. We have not found any reference to this behaviour, which is why we make the finding known. Materials and method We used the standard instrumentation specified for the study of CM. The method was based on the phase shift function of the CM according to the intensity of the stimulus. Results Latency was observed in CM, and we determined that latency time diminishes as the intensity of the stimulus increases. Conclusions From the sound stimulus to the bioelectric potential transduction, there is a time period of microseconds, the shorter the more powerful the stimulus. This suggests that electromechanical transduction is not a simple mechanical process.

Resumen Introduccion y objetivo Empleando la instrumentacion adecuada, venimos constatando que los microfonicos cocleares (MC) evocados adelantan o retrasan su aparicion en funcion de la presion sonora que los genera. Esta variacion en el tiempo es del orden de microsegundos. No hemos encontrado referencia alguna de este comportamiento, razon por la cual damos conocer el hallazgo. Material y metodo Se emplea instrumentacion especifica para el estudio de los MC. El metodo se basa en el desplazamiento de fase de los MC en funcion de la intensidad del estimulo. Resultados Se constata la latencia en los MC y se observa que la misma disminuye a medida que se incrementa la intensidad del estimulo. Conclusiones Desde el estimulo sonoro a la traduccion en potencial bioelectrico encontramos un periodo de tiempo en microsegundos, menor a mayor potencia. Esto sugiere que traduccion mecano-electrica no es un simple proceso de naturaleza mecanica.

Background Some studies of first psychotic episodes have suggested the association between childhood trauma, such as sexual abuse, and the risk of hallucinations.1 Furthermore, other studies indicated that environment can alter the phenomenological presentation of first psychotic episodes.2 However, there are no studies about the association between hallucinations in first psychotic episodes and the prognosis of the disease. This is the main objective of this study. We also compared the phenomenological differences between hallucinations in first episode psychosis and persistent hallucinations in patients with chronic psychosis. Methods Naturalistic, longitudinal follow-up study in a sample of 173 patients of first psychotic episode attending public mental health service in Area 5 of Valencia region (Spain) in a period between 2010–2017. We compared first-episode patients with hallucinations (N=38) with two samples: A) First-episode patients without hallucinations (N=137). B) Chronic patients with persistent hallucinations (N=45) from a previous study.3 In the first comparison we used the following variables: sociodemographic data, risk factors (such as cannabis consume and immigration), psychiatric pathology (CIE-10), psicopathology (including clinical scales GAF, CGI and PANSS), number of emercengy visits and number of hospitalization after the first psychotic episode. In the second one, we use the PSYRATS scale to compare both groups. Results In the first comparison, First Episode Psychotic patients with and without hallucinations,we only found significant differences in the number of hospital income, with more hospitalizations in the non hallucinating group (P= 0.001). In the second comparison, First Episode Hallucinations versus Chronic Persistent Hallucinations, significant differences were only found in the duration of the hallucinations, which was much higher in chronic persistent hallucinations group (P= 0.001) Discussion Consequently, it seems that first psychotic episode patients without hallucinations have more hospitalizations than first-episode patients with hallucinations. Moreover, we can conclude that the duration of voices is higher in chronic patients with persistent hallucinations than in first psychotic episode hallucinations. Both results have practical implications in the prognostic importance of hallucinations in first psychotic episodes. References 1. Misiak, B. et al “Childhood traumatic events and types of auditory verbal hallucinations in first-episode schizophrenia patients”, Comprehensive Psychiatry 66 (2016) 17–22. 2. Oher, F.J. et al “The effect of the environment on symptom dimensions in the first episode of psychosis: a multilevel study”, Psychological Medicine 44 (2014) 2419–2430. 3. González, J.C. et al J., “Persistent Auditory Hallucinations”, Psychopathology 39 (2006) 120–125.

BACKGROUND: In spite of promising results of mobile Health (mHealth) interventions for patients with psychosis, integration of these appliances into clinical practice remains a significant challenge (Bonet et al. 2017). Moreover, some studies have pointed out that percentages between 19–38% of patients have had negative experiences related to internet or cell phone usage, which may increase the risk of psychotic relapses (Bonet et al. 2018). In order to address these issues, we have developed an app called “ReMindCare” whose main objective is being simple, useful and automatically integrated into clinical practice. METHODS: ReMindCare is an app that collects the following information: a) Three daily questions regarding anxiety, sadness and irritability b) 18 weekly questions about: 1. level of adherence to medication, 2. presence of medication side-effects, 3. prodromal psychotic symptoms and 4. attitude towards medication. Answers to these questions are displayed following a Likert scale (1 to 5). In addition, patients are able to contact clinicians by clicking an “urgent consultation” tab. All this information is summarized in a clinical report which is given to patients and uploaded at their electronic medical record at the hospital database, being accessible for consultation for any clinician involved in treatment of the patient. Exclusion criteria are: presence of severe mental disability, language barriers and not to sign the informant consent. All patients from the First Episode of Psychosis Unit are being offered the use of ReMindCare as a part of their usual treatment. RESULTS: 56 patients have been offered the app (from 26 September to 26 November). Mean age 32.96 (SD=8.82), 78.6% are male, 87,5% Caucasian, 80.4% single, 80% have medium education level (until 16 years old) or more and 98.2% are taking antipsychotic medication. From this sample, 38 patients (67.9%) accepted using the app. Significant differences were found between users and no-users regarding: previous suicidal attempts (None of no-users have had previous suicidal attempts while 37.8% of users have) (χ2= 8.23 p=.004), years of illness (65.8% of users have less than 3 years of illness compared to 38.9% of no-users) (χ2= 3.61 p=.005) and in GAF punctuations (50% of users have punctuations between 100–60 in GAF compared to 33.3% of no users, and 13.2% have punctuations lower than 50 compared 50% of no-users) (χ2=9.03 p=.01). No differences were found in other clinical and demographic factors. DISCUSSION: To our knowledge, this is the first attempt to integrate the use of mHealth technologies into daily practice and electronic clinical records. Rate of acceptance is high, however some clinical differences regarding years of illness and GAF punctuations, may indicate that chronic patients are less willing to use ReMindCare. On the contrary, patients who have had previous suicide attempts are very interested in using the app. This can be due to the “urgent consultation” function which would allow them to contact clinicians in case of mood aggravation. ReMindCare is being especially useful in order to detect deception into medication intake in some patients. Encouraging feedback is being received for patients and clinicians, especially in regards of improvement of quality of interview and clinical alliance. References: Bonet L, Izquierdo C, Escartí MJ, Sancho JV, Arce D, Blanquer I et al. Utilización de tecnologías móviles en pacientes con psicosis: una revisión sistemática. Rev Psiquiatr Salud Ment 2017 Jul-Sept; 10(3): 168–78. Bonet L, Llácer B, Hernandez-Viadel M, Arce D, Blanquer I, Cañete C et al. Differences in the Use and Opinions About New eHealth Technologies Among Patients with Psychosis: Structured Questionnaire. JMIR Ment Health. 2018 Jul;5(3):e51.

NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia. ? 2013 Published by Elsevier B.V. and ECNP.

Auditory hallucinations (AH) are the most frequent positive symptoms in patients with schizophrenia. Hallucinations have been related to emotional processing disturbances, altered functional connectivity and effective connectivity deficits. Previously, we observed that, compared to healthy controls, the limbic network responses of patients with auditory hallucinations differed when the subjects were listening to emotionally charged words. We aimed to compare the synchrony patterns and effective connectivity of task-related networks between schizophrenia patients with and without AH and healthy controls. Schizophrenia patients with AH (n = 27) and without AH (n = 14) were compared with healthy participants (n = 31). We examined functional connectivity by analyzing correlations and cross-correlations among previously detected independent component analysis time courses. Granger causality was used to infer the information flow direction in the brain regions. The results demonstrate that the patterns of cortico-cortical functional synchrony differentiated the patients with AH from the patients without AH and from the healthy participants. Additionally, Granger-causal relationships between the networks clearly differentiated the groups. In the patients with AH, the principal causal source was an occipital–cerebellar component, versus a temporal component in the patients without AH and the healthy controls. These data indicate that an anomalous process of neural connectivity exists when patients with AH process emotional auditory stimuli. Additionally, a central role is suggested for the cerebellum in processing emotional stimuli in patients with persistent AH., Graphical abstract, Highlights • Schizophrenia is thought to reflect subtle dysfunctions in connectivity. • We analyze differences in functional and effective connectivity among groups. • The patterns of cortico-cortical functional synchrony are different among groups. • Granger-causal relationships between networks also clearly differentiated the groups. • These data implicate an anomalous process of neural connectivity.

To date, no study has evaluated the effects on brain function of cognitive behavior therapy (CBT) for persistent auditory hallucinations. This study explored the changes in brain activation associated with an emotional auditory paradigm when patients with schizophrenia and auditory hallucinations were treated with CBT. Functional magnetic resonance (fMR) imaging data were obtained from 55 subjects (17 patients with schizophrenia in the therapy group, 24 patients with schizophrenia in the control patient group, and 14 healthy control subjects). The patients in the experimental group were treated with 16-20 bi-weekly sessions of CBT, whereas the patients in the control group received treatment as usual. fMR images were obtained at baseline, 9 and 14 months after enrollment. Patients who received CBT showed significant decrease in brain activation in right and left amygdalae, and the left middle temporal gyrus, compared to both control groups. Significantly reductions in the brain activation of therapy patients were found in both amygdalae, but also in the left superior temporal gyrus and the right superior frontal gyrus at 14-month follow-up. Significant and stable reductions in the abnormal activation of key limbic regions appear to be attributable to the CBT during an emotional auditory paradigm in patients with schizophrenia and persistent auditory hallucinations. These results point to the availability of a biological imaging biomarker for CBT effects in patients with persistent auditory hallucinations. (c) 2017 Elsevier B.V. All rights reserved.

[EN] There is a growing interest in mobile Health interventions (m-Health) in patients with psychosis. The aim of this study is to conduct a systematic review in order to analysethe current state of research in this area. The search of articles was carried out following the PRISMA criteria, focusing on those studies that used mobile technologies in patients with psychosis during the period from 1990 to 2016. A total of 20 articles were selected from the 431 studies found. Three types of studies are distinguished: 1) Analysis of quality and usability, 2) Improving treatment adherence and reducing hospital admissions, and 3) Analysisof patient symptoms. CONCLUSIONS: m-Health interventions are feasible, and are easy to use for patients with psychosis. They evaluate the evolution of psychotic symptoms more efficiently, and improve adherence to treatment, as well as symptoms and hospital admissions. However, a particular strategy does not stand out over the rest, because differences in methodology make them difficult to compare., [ES] Introducción: Hay un creciente interés en las intervenciones mobile Health (m-Health) en pacientes con psicosis. El objetivo de este estudio es realizar una revisión sistemática para analizar el estado actual de la investigación en este ámbito. Metodología: Búsqueda en las bases de datos PsycINFO, PubMED, SCOPUS, Medline, ISI Web of Knowledge e IME del CSIC. Intervenciones con tecnologías móviles en pacientes con psicosis. Resultados: De un total de 431 artículos se seleccionaron 20. Se diferencian tres tipos de intervenciones: (1) Análisis de calidad y usabilidad, (2) Mejora de la adherencia, síntomas y reducción de hospitalizaciones, (3) Análisis de la sintomatología del paciente. Conclusiones: Las intervenciones m-Health son viables y resultan fáciles de utilizar para los pacientes con psicosis. Evalúan de forma más eficiente la evolución de los síntomas psicóticos y mejoran la adherencia al tratamiento, síntomas y hospitalizaciones. No se puede destacar una estrategia sobre las demás debido a que las diferencias en la metodología las hace difícilmente comparables., A ‘‘Prometeo’’ support grant from the Conselleria de Sanidad de la Comunidad Valenciana.

Introduction: Recent research demonstrates the heterogeneous etiology of psychotic disorders, where gen-environment (GxE) interaction plays a key role. Large genetic studies have linked many genetic variants with schizophrenia, but each variant is only associated with a small effect and the GxE interaction contribution has not been evaluated. Methods: The PEPs Project was designed to carefully collect a large amount of genetic and environmental exposure data of 335 FEP patients and 253 matched healthy controls. 780 single-nucleotide polymorphisms (from 159 candidate genes) and 16 environmental variables previously reported as the main psychosis non-genetic risk factors were analyzed together using entropy-based measures of information gain. Results: Our analyses identified an interaction between nine SNPs and the exposition to the environmental risk factors of psychosis, showing a clear enrichment of genes linked to serotonin neurotransmission and neurodevelopmental processes. Conclusions: This study has allowed the identification of several GxE-environment interactions involved in the risk of presenting a FEP. Our results highlight the importance of serotonin neurotransmission interacting with certain environmental stimuli. The serotoninergic system may be playing a key role in the regulatory network of stress and other systems implicated in the emergence and development of psychotic disorders. (C) 2017 Elsevier B.V. All rights reserved.

Resumen PEPs es un estudio multicentrico, naturalistico, prospectivo y longitudinal disenado para evaluar las variables clinicas, neuropsicologicas, de neuroimagen, bioquimicas, ambientales y geneticas en una muestra de casi 350 pacientes con un primer episodio psicotico y 250 controles sanos. El proyecto PEPs ha sido realizado en Espana desde enero de 2009 hasta diciembre de 2011. En este articulo se describe la justificacion de los metodos de evaluacion adoptados, proporcionando una breve descripcion de las medidas clinicas y funcionales seleccionadas. Los objetivos principales son: a) el examen clinico y la caracterizacion neuropsicologica de una muestra de primeros episodios de psicosis, y b) el estudio de las interacciones entre las variables geneticas y ambientales seleccionadas para predecir los resultados clinicos y de estructura cerebral y determinar la relacion de polimorfismos geneticos implicados en la farmacocinetica y la farmacodinamica, y la respuesta en los efectos adversos del tratamiento.

Schizophrenia is a clinically heterogeneous syndrome affecting multiple dimensions of patients' life. Therefore, its treatment might require a multidimensional approach that should take into account the efficacy (the ability of an intervention to get the desired result under ideal conditions), the effectiveness (the degree to which the intended effect is obtained under routine clinical practice conditions or settings) and the efficiency (value of the intervention as relative to its cost to the individual or society) of any therapeutic intervention. In a first step of the process, a group of 90 national experts from different areas of health-care and with a multidimensional and multidisciplinary perspective of the disease, defined the concepts of efficacy, effectiveness and efficiency of established therapeutic interventions within 7 key dimensions of the illness: symptomatology; comorbidity; relapse and adherence; insight and subjective experience; cognition; quality of life, autonomy and functional capacity; and social inclusion and associated factors. The main conclusions and recommendations of this stage of the work are presented herein.

Background Childhood and adolescence represent the periods during which hallucinatory experiences occur at the greatest prevalence, and also constitute a critical window of vulnerability for the pathogenesis of psychotic disorders. The longitudinal course of hallucinatory experiences during late childhood and adolescence, as well as their relationship to psychotic disorders, has never been the subject of review. Methods We followed the PRISMA guidelines for conducting systematic reviews and combined the use of electronic and manual systematic search methods. Data were extracted upon pre-defined requested items and were analyzed using several epidemiological measures. The interpretation of the results was conducted in relation to the study design variables. Results A total of 11 datasets (6 epidemiological and 5 clinical) were reviewed. The baseline prevalence of hallucinatory experiences ranged from 4.9% to 9%. Discontinuation occurred in between 58.7% and 94.5% of the cases, and person–year discontinuation rates ranged from 3% to 40.7% and appeared to be related to the duration of follow-up. Despite low person–year incidence rate, incident cases constituted between 27.7% and 83.3% of outcome samples. 2 of 3 studies showed evidence to predict transition to psychosis with likelihood ratios of 2.5 and 6.6. Conclusions Hallucinatory experiences are a common experience during childhood and adolescence. A review of the current literature suggests that there is a considerable turnover of incident-discontinuing cases and that most cases discontinue in the short term. A subset of the cases was at risk for persistence or transition to psychosis, probably related to indicators of severity of the hallucinatory experience.

Resumen Fundamento y objetivo La experiencia subjetiva de los pacientes psicoticos con el tratamiento neuroleptico es un factor clave en la adherencia terapeutica, calidad de vida y pronostico. El objetivo de este trabajo fue realizar la adaptacion cultural al castellano de la Escala del Bienestar Subjetivo con Neurolepticos (SWN-K) y analizar sus propiedades psicometricas en pacientes con esquizofrenia. Pacientes y metodo Se realizo un estudio transversal en dos fases (adaptacion cultural y validacion psicometrica) en el que se incluyo a 97 pacientes mayores de 18 anos en tratamiento antipsicotico. Se valoraron la factibilidad, fiabilidad y validez de la escala. Resultados Se demostro una buena aceptabilidad de la escala SWN-K. El coeficiente α de Cronbach de la puntuacion total de la escala SWN-K fue de 0,86. La fiabilidad test-retest fue de 0,88 (intervalo de confianza del 95% [IC 95%] 0,84 y 0,93). La SWN-K discrimino entre los niveles de gravedad de la ICG-G (p Conclusiones La version adaptada al castellano de la SWN-K muestra propiedades psicometricas adecuadas como instrumento autoadministrado de evaluacion del bienestar subjetivo en esquizofrenia.

Introduction Lack of insight is a common clinical problem in psychiatric patients, but few times has been properly studied until recently. Patients with good insight tend to show a better treatment adherence with a better prognosis and show less hostility. This study aims to investigate whether there is a relationship between the hostility degree and insight or not and to analyse if there are insight quantitative differences between the patients regarding their diagnoses. Method One hundred and sixty-eight psychotic patients were studied (including 86 patients with schizophrenia and 43 with bipolar disorder). PANNS P7 (hostility) item and G14 (poor impulse control) were analysed in order to assess patients’ violence and G12 in order to assess insight. All these data were correlated. It was also analysed the PANSS results of schizophrenic vs bipolar patients regarding insight and hostility separately looking for a more homogenic pull of patients. Results Patients with greater hostility showed a worse impulse control and poorer insight than the rest. Schizophrenic patients showed a greater hostility and lower insight than bipolar patients. Discussion Lack of insight may lead to a greater hostility and worse impulse control. Therapeutic interventions addressed to improve insight could indirectly lower hostility and gain a better impulse control for psychotic patients.

Genome-wide association studies using several hundred thousand anonymous markers present limited statistical power. Alternatively, association studies restricted to common nonsynonymous single nucleotide polymorphisms (nsSNPs) have the advantage of strongly reducing the multiple testing problem, while increasing the probability of testing functional single nucleotide polymorphisms (SNPs).We performed a case-control association study of common nsSNPs in Galician (northwest Spain) samples using the Affymetrix GeneChip Human 20k cSNP Kit, followed by a replication study of the more promising results. After quality control procedures, the discovery sample consisted of 5100 nsSNPs at minor allele frequency5% analyzed in 476 schizophrenia patients and 447 control subjects. The replication sample consisted of 4069 cases and 15,128 control subjects of European origin. We also performed multilocus analysis, using aggregated scores of nsSNPs at liberal significance thresholds and cross-validation procedures.The 5 independent nsSNPs with false discovery rate q ≤ .25, as well as 13 additional nsSNPs at p.01 and located in functional candidate genes, were genotyped in the replication samples. One SNP, rs13107325, located at the metal ions transporter gene SLC39A8, reached significance in the combined sample after Bonferroni correction (trend test, p = 2.7 × 10(-6), allelic odds ratio = 1.32). This SNP presents minor allele frequency of 5% to 10% in many European populations but is rare outside Europe. We also confirmed the polygenic component of susceptibility.Taking into account that another metal ions transporter gene, SLC39A3, is associated to bipolar disorder, our findings reveal a role for brain metal homeostasis in psychosis.

Resumen Introduccion En pacientes con trastornos psiquiatricos el deficit en la capacidad de introspeccion o insight es frecuentemente un problema clinico importante, pero ha sido pocas veces objeto de estudio formal. Los pacientes psicoticos con buen insight suelen cumplir mejor las pautas de medicacion siendo un factor de buen pronostico y muestran menor hostilidad. Con este estudio se pretende valorar si existe una relacion entre el grado de hostilidad del paciente y la conciencia de enfermedad ademas de analizar si el grado de conciencia de enfermedad varia segun el diagnostico del paciente (esquizofrenia vs. trastorno bipolar). Metodologia Se estudiaron en 168 pacientes psicoticos (entre ellos 86 con esquizofrenia y 43 con trastorno bipolar) los items de la PANSS P7 (hostilidad) y G14 (control deficiente de impulsos) para valorar el grado de violencia y el item G12 (ausencia de juicio e introspeccion) correlacionandolos entre ellos. Para observar si habia diferencias en cuanto a insight y hostilidad segun el diagnostico, se estudiaron los datos utilizando una muestra mas reducida y homogenea comparando los pacientes diagnosticados de esquizofrenia con los diagnosticados de trastorno bipolar. Resultados Los pacientes con mayor hostilidad presentaban un peor control de impulsos y una pobre conciencia de enfermedad. Los pacientes diagnosticados de esquizofrenia presentan una mayor hostilidad y un peor insight comparados con los diagnosticados de trastorno bipolar. Discusion La ausencia de introspeccion supondria un mayor nivel de hostilidad y mayor deficit de control de impulsos. Las estrategias terapeuticas encaminadas a aumentar el grado de insight del paciente podrian disminuir indirectamente el grado de hostilidad y proporcionar un mejor control de los impulsos.

Genetic studies on human personality have provided little satisfactory results to date mainly because of the complexity of this trait. Neonatal temperament using observational measures is an alternative phenotype to approach genetics to human behavior. An association study was conducted on 117 Caucasian newborns. Their temperament was evaluated using the Neonatal Behavior Assessment Scale 48 h after birth. Thirteen polymorphisms in the SLC6A4, DRD4 and TFAP2B genes were genotyped. Linear regression was performed to analyze data, and Bonferroni correction was applied. To check the functional effect of the TFAP2B Indel Intron 2 polymorphism, reporter gene luciferase assays using a mouse cortical neural progenitor cell line and quantitative polymerase chain reaction (qPCR) studies in human post-mortem brain samples were performed. A significant association was found between 5-HTTLPR, 5-HTTLPR + rs25531 and TFAP2B Indel Intron 2 with Range of State cluster as well as an interaction between rs25531 and TFAP2B Indel Intron 2 with Range of State. DRD4 variable number tandem repeat exon 3 was associated with orientation. A 30% increase in the luciferase levels of the TFAP2B 5-repeat alleles compared with the 6-repeat alleles (P-value = 0.03) was found using the pGL3 promoter vector. The qPCR experiments showed the same trend as the in vitro studies, although no significant results were obtained. This study supports a role of the SLC6A4, DRD4 and TFAP2B genes in the temperament, including a gene-gene interaction between SLC6A4 and TFAP2B. It also provides evidence about an effect of the TFAP2B polymorphism in TFAP2B gene transcription.

Cannabis use is one of the environmental factors with more solid evidence contributing to schizophrenia risk, especially in genetically susceptible individuals. One of the genes that may interact with cannabis is COMT, although available data are scarce. Here, we present a case-only study of the putative COMT-cannabis interaction in schizophrenia. Two Spanish samples from Santiago de Compostela and Valencia were screened for cannabis use. One hundred and fifty five individuals from a total of 748 patients were identified as cannabis users. Five SNPs in COMT, defining three common functional haplotypes with different enzymatic activities, were genotyped and analyzed for association at the SNP, haplotype and genotype levels. An association was detected between cannabis use and low activity variants (P

Poor insight in psychosis has been described as a seeming lack of awareness of the deficits, consequences of the disorder, and of the need for treatment. The aim of this study is to investigate whether patients with auditory hallucinations have less insight than those without hallucinations, and to determine which hallucination characteristics are related to patient insight. Using the PANSS and PSYRATS, the authors have evaluated the lack of insight data corresponding to 168 psychotic patients divided into three groups: patients with a history of nonpersistent hallucinations, patients with persistent hallucinations, and patients without hallucinations. Patients with persistent hallucinations showed significantly less insight than patients without persistent hallucinations and patients without hallucinations, the farther away the hallucination is located, the greater the lack of patient insight. Patients who hear the hallucination inside their head rather than outside show better insight, possibly because such patients can understand the voice as being created by their own mind.

Catechol-O-methyltransferase (COMT) has been largely studied in relation to schizophrenia susceptibility. Most studies focused on the functional single nucleotide polymorphism (SNP) rs4680 that causes a substitution of Val by Met at codon 158 of the COMT protein. Recent meta-analyses do not support an association between allelic variants at rs4680 and schizophrenia. However, the putative role of overdominance has not been tested in meta-analyses, despite its biological plausibility. In this work, we tested the overdominant model in two Spanish samples (from Valencia and Santiago de Compostela), representing a total of 762 schizophrenic patients and 1042 controls, and performed a meta-analysis of the available studies under this model. A total of 51 studies comprising 13,894 schizophrenic patients and 16,087 controls were included in the meta-analysis, that revealed a small but significant protective effect for heterozygosity at rs4680 (pooled OR = 0.947, P = 0.023). Post-hoc analysis on southwestern European samples suggested a stronger effect in these populations (pooled OR = 0.813, P = 0.0009). Thus, the COMT functional polymorphism rs4680 contributes to schizophrenia genetic susceptibility under an overdominant model, indicating that both too high and too low levels of dopamine (DA) signalling may be risk factors. This effect can be modulated by genetic background

Brain connectivity is a key concept for understanding brain function. Current methods to detect and quantify different types of connectivity with neuroimaging techniques are fundamental for understanding the pathophysiology of many neurologic and psychiatric disorders. This article aims to present a critical review of the magnetic resonance imaging techniques used to measure brain connectivity within the context of the Human Connectome Project. We review techniques used to measure: a) structural connectivity b) functional connectivity (main component analysis, independent component analysis, seed voxel, meta-analysis), and c) effective connectivity (psychophysiological interactions, causal dynamic models, multivariate autoregressive models, and structural equation models). These three approaches make it possible to combine and use different statistical techniques to elaborate mathematical models in the attempt to understand the functioning of the brain. The findings obtained with these techniques must be validated by other techniques for analyzing structural and functional connectivity. This information is integrated in the Human Connectome Project where all these approaches converge to provide a representation of all the different models of connectivity.

Physiological changes during gestation and after delivery are associated with postpartum thyroid dysfunction, which is due to thyroid autoimmunity in some cases. Postpartum thyroid dysfunction, in turn, has been associated with postpartum depression (PPD). The aim of the present study was to evaluate whether thyroid function immediately after delivery can predict postpartum depression at 8 weeks and 32 weeks after delivery. This study examined 1053 postpartum Spanish women without a previous history of depression. We evaluated depressive symptoms at 48h, 8 weeks and 32 weeks postpartum and used a diagnostic interview to confirm major depression for all probable cases. Free thyroxin (fT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb) and C-reactive protein (CRP) were assayed at 48h postpartum. Binary and multivariate logistic regression analyses were performed to determine independent risk factors for PPD. Although 152 women (14.4%) had high TPOAb (>27IU/mL) and slightly elevated TSH concentrations with normal fT4, we did not find any association between thyroid function and PPD. This thyroid dysfunction was not associated with CRP concentrations that were outside of the normal range (>3mg/L). We conclude that thyroid function at 48h after delivery does not predict PPD susceptibility.

Background Some naturalistic longitudinal studies of first psychotic episodes of the last 50 years have suggested associations between psychopathology and the remission of symptoms and the clinical course of disease.1 A recent study in a large sample of patients with schizophrenia has obtained significant results using the number of hospitalizations as outcome variable.2 The main objective of this study is to know if clinical and sociodemographic variables predict the number of hospitalizations after the first psychotic episode Methods Naturalistic, longitudinal follow-up study in a sample of 212 patients of first-episode psychosis attending public mental health service in Area 5 of Valencia (Spain) in a period between 2010–2017. Of 212 patients, a total of135 were included, excluding patients lost due to abandonment and death. The study included a) baseline variables: sociodemographic, risk factors (Cannnabis use), clinical scales; PANSS, CGI (clinical global impression) and GAF (global assessment of functioning scale) and kind of treatment (oral versus injectable). b) outcome variables: number of visits to the emergency room, hospitalizations, and outpatient consultations. Results None of the psychopathological or treatment variables at baseline were significantly associated with the outcome variables. The younger patients have a significant (p < 0.01) higher number of emergencies room visit in the follow up. Discussion In contrast with previous reports1,2 Tihonen J et al2017)) we were not able to find any relationship between severity of illness (at baseline) or the kind of treatment (oral versus injectable) with the emergency rooms visits or number of hospitalizations. The only significant result was related with the age of the patients. Younger patients have more probability of having more visit to the emergency room. References 1. Capdeville D. A multi-dimensional approach to insight and its evolution in first- episode psychosis: a 1 -year outcome naturalistic study. Psychiatry Res. 2013 dec 30;210(3):835–41 2. Tihonen J.Real-World effectiveness of antipsychotic treatments in a Nation wide Cohort of 29.823 patients with schizophrenia. Jamapsych.2017;74(7)686–693

A fundamental difficulty in human genetics research is the identification of the spectrum of genetic variants that contribute to the susceptibility to common/complex disorders. We tested here the hypothesis that functional genetic variants may confer susceptibility to several related common disorders. We analyzed five main psychiatric diagnostic categories (substance-abuse, anxiety, eating, psychotic, and mood disorders) and two different control groups, representing a total of 3,214 samples, for 748 promoter and non-synonymous single nucleotide polymorphisms (SNPs) at 306 genes involved in neurotransmission and/or neurodevelopment. We identified strong associations to individual disorders, such as growth hormone releasing hormone (GHRH) with anxiety disorders, prolactin regulatory element (PREB) with eating disorders, ionotropic kainate glutamate receptor 5 (GRIK5) with bipolar disorder and several SNPs associated to several disorders, that may represent individual and related disease susceptibility factors. Remarkably, a functional SNP, rs945032, located in the promoter region of the bradykinin receptor B2 gene (BDKRB2) was associated to three disorders (panic disorder, substance abuse, and bipolar disorder), and two additional BDKRB2 SNPs to obsessive-compulsive disorder and major depression, providing evidence for common variants of susceptibility to several related psychiatric disorders. The association of BDKRB2 (odd ratios between 1.65 and 3.06) to several psychiatric disorders supports the view that a common genetic variant could confer susceptibility to clinically related phenotypes, and defines a new functional hint in the pathophysiology of psychiatric diseases.

The ancestral susceptibility hypothesis has been proposed to explain the existence of susceptibility alleles to common diseases. Some ancestral alleles, reflecting ancient adaptations, may be poorly adapted to the more contemporary environmental conditions giving rise to an increased risk to suffer some common disorders. In order to test this hypothesis in schizophrenia, we focused on the monoamine oxidase B gene (MAOB). This gene is involved in deamination of several monoamines, including both xenobiotic amines present in several foods, as well as neurotransmitters such as dopamine. In addition, preliminary analysis based on phase I HapMap data suggested that recent natural selection has acted on this locus. We further explored the existence of this recent positive selection using a test based on extension of linkage disequilibrium (LD) to large distance at the specific selected haplotype taking data from HapMap phase II, and searched for association of the ancestral haplotypes with schizophrenia in a sample of 532 schizophrenic patients and 597 controls from Spain. Our analysis suggested the existence of a haplotype of MAOB subject to recent selection. In agreement with the ancestral susceptibility hypothesis, the ancestral haplotypes were significantly over-represented in patients (P = 0.047). These haplotypes conferred an increased risk to schizophrenia, restricted to males (P = 0.024, OR = 1.41, 95% CI 1.01-1.90). Thus, pending on replication studies, MAOB seems to fit the ancestral susceptibility model, validating a new strategy to search for common schizophrenia susceptibility genes by focusing in those functional candidate genes subject to recent positive selection.

Objective Previous studies have found neurochemical abnormalities in thalamic nuclei in patients with schizophrenia. These abnormalities have been associated with information processing deficiencies and symptom formation. There are no metabolic spectroscopy studies in patients with schizophrenia attending to auditory hallucinations. The aim of the present study is to explore metabolic Magnetic Resonance Spectroscopy (MRS) ratio differences in the thalamus between schizophrenic patients with and without auditory hallucinations and control subjects. Methods MRS studies (MRI 1.5 T unit) were performed in 49 patients with schizophrenia (30 with auditory hallucinations and 19 without auditory hallucinations) and 37 controls. 1 H MRS imaging was used to acquire 2 transverse slices (TR/TE 2700/272 ms, region of interest 110 × 100 × 23 mm). In the quantitative analysis four elements of volume (9.2 × 9.2 × 23 × 4 mm), added into one spectrum representative of each thalamus, were chosen in the slice passing through the main body of the thalamus. The areas of metabolites were integrated with the jMRUI program. Results The patients with schizophrenia had significantly lower bilateral NAA/Cho ratios when compared with healthy subjects. There was also a lower NAA/Cho ratio in the right thalamus in patients with auditory hallucinations compared to patients without auditory hallucinations and control subjects. Significant correlations were found between metabolic ratios and BPRS, PANSS and PSYRATS scores, age of onset of auditory hallucinations, and age of subjects. Conclusions Choline and NAA ratio abnormalities determined by thalamic spectroscopy may be related to the pathogenesis of auditory hallucinations in patients with schizophrenia.

Objetivo Aportar un procedimiento objetivo para la obtencion del factor de reclutamiento (recruitment). En la actualidad todos los metodos estan basados en la respuesta subjetiva del paciente. La relacion entre el aumento del potencial microfonico coclear (MC) y el incremento del estimulo es la base de esta aportacion. El sistema permite la apreciacion de decimas de decibelio, precision necesaria para determinar el poder diferencial de amplitud auditiva en los pacientes. Metodo Se ha empleado un equipo especifico para el estudio de los potenciales MC. Hemos comparado los resultados obtenidos con esta nueva tecnica con los determinados subjetivamente por el metodo de Luscher. Se presenta a 10 adultos sin proposito estadistico. Previamente se comprobo la precision fisica del equipo, y luego se practicaron determinaciones en animales de experimentacion y, por ultimo, en humanos. Resultados Obtenemos mediante MC una desviacion maxima de 0,3 dB respecto a la apreciacion subjetiva de los pacientes. En la repeticion de la prueba objetiva se obtienen identicos resultados en el mismo paciente, mientras que en el estudio subjetivo se observan discrepancias en las repeticiones. Conclusiones La posibilidad de estudiar el reclutamiento objetivamente abre nuevas perspectivas en diagnostico precoz y nos capacita para optar mas acertadamente respecto a la colocacion de un implante o la adaptacion de un audifono, con un control automatico de volumen correcto unido al ajuste de la ganancia selectiva en frecuencia, ya que obtenemos simultaneamente el perfil audiometrico umbral.

Objective To present an objective procedure for recruitment measure. Nowadays all recruitment methods are based on the patients’ subjective responses. This procedure is based on the ratio between an increase in the cochlear microphonic potential and the increase in stimuli intensity. The system allows recruitment to be measured down to one tenth of a decibel; the precision necessary to differentiate the auditory capacity of patients Method We used a specific technique to detect cochlear microphonic potentials. We have compared the results obtained with this new technique with those determined by the Luscher method. We present 10 adults with no statistic aim. We first tested the physical accuracy followed by measures with laboratory animals and humans Results We obtained a maximum deviation of 0.3 dB with respect to the patients’ subjective appreciation. During the repetition of the objective measure with the same patients, we obtained identical results, whereas significant differences were observed with the repetitions in the subjective study Conclusions The possibility of an objective measurement for recruitment opens up new perspectives for early diagnosis. This technique may be of assistance in the decision to place an implant or how to adapt a hearing aid. Through automatic volume control as well as the correct adjustment of the selective gain in frequency, we can also obtain the threshold audiometric profile simultaneously

Many studies have shown widespread but subtle pathological changes in gray matter in patients with schizophrenia. Some of these studies have related specific alterations to the genesis of auditory hallucinations, particularly in the left superior temporal gyrus, but none has analysed the relationship between morphometric data and a specific scale for auditory hallucinations. The present study aims to define the presence and characteristics of structural abnormalities in relation with the intensity and phenomenology of auditory hallucinations by means of magnetic resonance voxel-based morphometry (MR-VBM) method applied on a highly homogeneous group of 18 persistent hallucinatory patients meeting DSM-IV criteria for schizophrenia compared to 19 healthy matched controls. Patients were evaluated using the PSYRATS scale for auditory hallucinations. Reductions of gray matter concentration in patients to controls were observed in bilateral insula, bilateral superior temporal gyri and left amygdala. In addition, specific relationships between left inferior frontal and right postcentral gyri reductions and the severity of auditory hallucinations were observed. All these areas might be implicated in the genesis and/or persistence of auditory hallucinations through specific mechanisms. Precise morphological abnormalities may help to define reliable MR-VBM biomarkers for the genesis and persistence of auditory hallucinations.

[Objective]: Previous studies on a possible association between CCK-AR polymorphisms and schizophrenia have been controversial. The aim of the present study was to assess a potential association between schizophrenic patients with auditory hallucinations and polymorphisms of the CCK-AR gene., [Methods]: A set of single nucleotide polymorphisms mainly located in the regulatory region of the CCK-AR gene was analysed in a sample of 163 Diagnostic and statistical manual of mental disorders-IV-diagnosed schizophrenic patients and 162 healthy controls, [Results]: Significant differences in the genotype (P=0.011) and allele (P=0.0009) frequencies of the +121C/G SNP (located in the 5' regulatory region) were found between patients and controls. The excess of the C allele in the patient group remained significant after Bonferroni correction (P=0.03). However, functional in vitro assays, did not reveal significant differences on gene expression between +121G and +121C alleles of this SNP. Further investigations revealed two risk haplotypes: +121C/+978A/+984T (P=0.01) and +121C/+978T/+984C (P=0.0091) as well as a protective haplotype: +121G/+978T/+984T (P=0.0001)., [Conclusion]: Our data support a possible role of the CCK-AR gene in the vulnerability to schizophrenia in patients with auditory hallucinations, and suggest remarkable allele heterogeneity.

Objetivo Actualmente el estudio de la audicion mediante el registro y el procesamiento de los potenciales microfonicos cocleares esta en fase de validacion definitiva respecto a los resultados que se obtienen mediante otros procedimientos objetivos. El proposito de esta aportacion es contribuir a esa validacion. Material y metodo Se ha empleado equipo destinado exclusivamente al registro de los microfonicos cocleares realizando el estudio en adultos para poder comparar los resultados audiometricos subjetivos con los obtenidos mediante microfonicos cocleares. Resultados Presentamos una concordancia estadistica entre la audiometria subjetiva y la audiometria microfonicococlear. Conclusiones Dada la equidad de resultados, el procedimiento resulta valido muy especialmente en el diagnostico precoz, en el que se consigue un perfil identico al del audiograma subjetivo en las frecuencias audiometricas 250, 500, 1.000, 2.000 y 4.000 Hz.

Objective The recording and processing of cochlear microphone potentials in hearing studies is currently in the definitive validation phase against results obtained with other objective procedures. The purpose of this work is to contribute to its validation. Material and method The equipment used was exclusively designed for recording cochlear microphone potentials. The study has been carried out in adults to compare subjective audiometric results with those obtained from cochlear microphones. Results We present a statistical concordance study between subjective audiometry and cochlear microphone audiometry. Conclusions In view of the results obtained, this method is particularly valid for early diagnosis. We obtained an identical profile to the subjective audiogram at audiometric frequencies of 250, 500, 1000, 2000, and 4000 Hz.

A mother’s emotional state is a well-known environmental factor that relates to the development of infant temperament. However, some relevant issues have not yet been fully explored. The current study examines the influence of determined maternal, contextual and perinatal variables on infant temperament and the mother’s confidence in caregiving during the first weeks of life. A prospective study was carried out in three-hundred and seventeen newborns and their mothers. Perinatal and socio-demographic variables were recorded. The mother’s anxiety and mood were measured in the first days after childbirth and again at 8 weeks. Infant temperament and the mother’s confidence in caregiving were measured at 8 weeks. A mother’s postpartum anxiety following delivery was the best predictor for most of the variables of infant temperament, including infant irritability (p= .001), and other child variables like infant sleep (p= .0003) and nursing difficulty (p= .001). Contextual-family variables, such as the number of people at home (p= .0024) and whether they were primiparous (p= .001), were the best predictors for a mother´s confidence in caregiving. Support was found for an early effect of maternal anxiety on infant temperament. The results have clinical implications for postnatal psychological interventions.

The transition to motherhood is stressful as it requires several important changes in family dynamics, finances, and working life, along with physical and psychological adjustments. This study aimed at determining whether some forms of coping might predict postpartum depressive symptomatology. A total of 1626 pregnant women participated in a multi-centric longitudinal study. Different evaluations were performed 8 and 32 weeks after delivery. Depression was assessed using the Edinburgh Postnatal Depression Scale (EPDS) and the structured Diagnostic Interview for Genetic Studies (DIGS). The brief Coping Orientation for Problem Experiences (COPE) scale was used to measure coping strategies 2–3 days postpartum. Some coping strategies differentiate between women with and without postpartum depression. A logistic regression analysis was used to explore the relationships between the predictors of coping strategies and major depression (according to DSM-IV criteria). In this model, the predictor variables during the first 32 weeks were self-distraction (OR 1.18, 95 % CI 1.04–1.33), substance use (OR 0.58, 95 % CI 0.35–0.97), and self-blame (OR 1.18, 95 % CI 1.04–1.34). In healthy women with no psychiatric history, some passive coping strategies, both cognitive and behavioral, are predictors of depressive symptoms and postpartum depression and help differentiate between patients with and without depression.

Objetivo Valorar la aceptabilidad, efectividad y cumplimiento terapeutico de una nueva formulacion bucodispersable de mirtazapina en pacientes con depresion (segun criterios del DSM-IV). Metodo Estudio clinico multicentrico, prospectivo, abierto, no controlado, en 49 pacientes provenientes de consultas externas de 7 servicios de psiquiatria, durante 6 semanas. Se realizaron evaluaciones mediante la escala de Hamilton para la Depresion de 17 items y la escala de Impresion Clinica Global, subescalas de gravedad y de cambio (ICG-G, ICG-C), y se valoraron los efectos adversos, el cumplimiento terapeutico de los pacientes y el Cuestionario de aceptabilidad y preferencia (Soltab Patient Preference Survey). Resultados La puntuacion media total de la escala Hamilton para la Depresion de 17 items (HAMD-17) fue de 23,27 en la visita basal y disminuyo a 12,84 el dia 15 (p Conclusion Este es el primer estudio realizado en Espana en el que se valora la aceptabilidad de la nueva formulacion bucodispersable de mirtazapina, ademas de la eficacia, la seguridad, la tolerabilidad y el cumplimiento terapeutico en pacientes con depresion.

Background: There is still a significant proportion of psychotic patients who suffer from persistent auditory hallucinations (PAH) in spite of treatment. The objective of our study was to analyze those clinical dimensions that characterize persistent hallucinators in comparison with episodic hallucinators. Sampling and Methods: Ninety-one outpatients with AH were assessed through semistructured interviews. The interviews included the Psychotic Symptom Rating Scales for AH and the Krawiecka scale. They elicited descriptions about the persistence of AH, existence of pleasurable hallucinations and other types of hallucinations. Results: Forty-five patients fulfilled criteria for reported PAH. Persistent hallucinators showed greater scores in frequency and duration of hallucinations, Krawiecka total score and incoherence of speech. Moreover, pleasurable experiences were more frequent in this group of patients. Logistic regression analysis rendered a model with the following variables: duration of voices, degree of control and pleasurable hallucinations. Conclusion: Specific dimensions of AH can predict the possibility of treatment resistance.

ResumenEstudios recientes han propuesto que variaciones del ADN en el gen del receptor A de la pancreocimina (CCK-RA) podrían predisponer a los individuos a la esquizofrenia y particularmente a las alucinaciones auditivas’ (AA). El propósito de este estudio es evaluar la asociación entre las AA, utilizando una escala específica para ellas en la esquizofrenia (PSYRATS), y el polimorfismo del RA-CCK en 779 en una muestra española. Se estudió un total de 105 pacientes esquizofrénicos del DSM-IV con AA y 93 controles no relacionados. Se consideró que 22 pacientes tenían alucinaciones auditivas persistentes, y mostraban características clínicas y demográficas similares a los pacientes con AA episódicas, con la excepción de los valores de la PSYRATS. El grupo de AA persistentes mostró una mayor cantidad de alelo Al cuando se comparó con los grupos de alucinaciones episódicas o de control. Nuestros datos apoyan el posible papel del gen del RA-CCK en el desarrollo de AA persistentes en los pacientes esquizofrénicos.