BackgroundThe rs3800779 polymorphism at KCNH2 gene, which encodes for a Voltage-Gated Potassium Channel Subunit, has been associated with the risk for schizophrenia (SZ) and with changes in the expression of a brain isoform with specific electrophysiological characteristics (Huffaker et al., 2009). It has been hypothesized that the KCNH2 gene variability could be involved in SZ by means of modulating the neuronal excitability. Graph-theory parameters applied to electroencephalographic (EEG) activity are useful to assess functional connectivity in the brain and have shown altered patterns of global connectivity in schizophrenia. We aimed to investigate whether KCNH2 contributes to functional connectivity alterations replicated in SZ patients.MethodsEEG data were acquired during the performance of an odd-ball task in 50 schizophrenia patients and 101 matched healthy controls. The rs3800779 at KCNH2 was genotyped. From the EEG activity, the Small World index (SW, a measure of network efficiency) was calculated as the coefficient between clustering coefficient (CLC, a measure of network segregation) and path length (PL, a measure of network integration). SW was calculated in two temporal windows with respect to the target tone (pre-stimulus and response). Functional SW modulation (SWm) was calculated as the difference in SW between pre-stimulus and response windows. Finally, the association between KCNH2 polymorphism and functional connectivity modulation was assessed.ResultsPatients carrying the A allele (AA or AC, n=25) showed smaller SW modulation in comparison with patients with the CC genotype (n=25) (t=-2.84, df=48, p=0.007). Moreover, patients carrying the A allele showed smaller SW modulation than healthy controls with the A allele (n=45) (t=-3.41, df=68, p=0.001) or without the A allele (n=56) (t=-3.87, df=79 p<0.001). There were no significant SW modulation differences between healthy controls carrying or not the A allele. Patients with the AA/AC genotype showed an inverse SW modulation pattern (decreased SW at response) in comparison with patients without the A allele and controls (increased SW at response).DiscussionOur data indicate that, within SZ patients, the A allele is associated with smaller SW modulation and lower SW values at response, which might be interpreted as an altered ability to coordinate the activity of neural assemblies during cognitive tasks (Basar et al 2016). Although replication analyses are needed, our findings suggest that genetic variation at KCNH2 might contribute to the efficiency of brain functional networks in schizophrenia patients.References1. Basar, E., Golbasi, B.T., Tulay, E., Aydin, S., Basar-Eroglu, C., 2016. Best method for analysis of brain oscillations in healthy subjects and neuropsychiatric diseases. Int J Psychophysiol 103, 22–42.2. \Huffaker, S.J., Chen, J., Nicodemus, K.K., Sambataro, F., Yang, F., Mattay, V., Lipska, B.K., Hyde, T.M., Song, J., Rujescu, D., Giegling, I., Mayilyan, K., Proust, M.J., Soghoyan, A., Caforio, G., Callicott, J.H., Bertolino...

BackgroundCognitive deficits are considered core features of schizophrenia (SZ) (Green & Harvey 2014). Subtle variations in the perfectly coupled mechanism that maintains the potential of membrane in neurons may have repercussion on neuronal processing. Therefore, genetic variability related to the functioning of excitable cells and linked to pathways essential for neuronal survival and plasticity may underlie the observed differences in cognitive abilities (Carr et al 2016). CACNA1C and KCNH2 genes encode for calcium and potassium voltage-gated channels, ultimately related to neuronal functioning (Dolmetsch et al 2001, Schwarz et al 2004). These two genes have been previously related with SZ (Atalar et al 2010, Ripke et al 2014). The aim of this study was to evaluate whether the genetic variability of CACNA1C and KCNH2 is associated with: i) the risk for schizophrenia, ii) the cognitive performance of SZ patients and healthy subjects.MethodsOur sample consisted of 348 SZ patients and 387 unrelated healthy controls (HC). DNA was extracted from blood/saliva samples using standard procedures and two Single Nucleotide Polymorphisms (SNPs) were genotyped: rs1006737 (G/A) in CACNA1C gene, rs3800779 (G/A) in KCNH2. A subsample (296 SZ/157 HC) underwent neurocognitive assessment, which included: i) premorbid IQ (Word Accentuation Test - Test de Acentuación de Palabras (TAP)); ii) memory (Wechsler Memory Scale (WMS-III)) and, iii) executive function (Behavioural Assessment of the Dysexecutive Syndrome (BADS)). The association between the SNPs and neurocognitive performance was explored (adjusted by sex and age) separately in patients and in controls groups.ResultsIn our sample, we did not detect an association of CACNA1C and KCNH2 with the risk for SZ. Patients performed significantly worse than controls in all cognitive measures (p<0.005). SZ patients homozygous for the risk allele (A) of the CACNA1C polymorphism showed lower premorbid IQ (TAP scores) than patients carriers of the C allele (rs1006737: B=-1.39 p=0.027). Within HC, the minor allele (A) of KCNH2 was associated with WMS global score (rs3800779: B=3.01 p=0.010): subjects carrying the AA genotype presented better memory performance.DiscussionOur findings add evidence on the role of CACNA1C and KCNH2 on modulating cognitive performance in SZ patients and HC (Huffaker et al 2009, Krug et al 2010, Zhang et al 2012, Hashimoto et al 2013). Our results in patients are in line with previous studies that suggest an association of CACNA1C risk allele on different cognitive domains. As regards to KCNH2, our results are opposite in terms of the direction of the effect observed in previous studies, probably as a consequence of the sample size and heterogeneity in methods used to assess memory. The different direction of the genetic effects among patients and controls reflects the complex relationship between genetic factors and cognitive performance variability. It is suggested that genes that enhance cognitive abilities under normal circumstances turn to be pern...

BackgroundChildhood trauma has been proposed as a risk factor for schizophrenia. Moreover, it has been related to brain abnormalities associated with cognitive functions, including social cognition. Alterations in mentalizing skills are found in both schizophrenia patients and individuals exposed to childhood trauma. We hypothesize that childhood trauma might be related to emotional processing deficits in psychotic patients.MethodsThe present study is ongoing. To date, we have assessed social cognition and childhood trauma in 30 patients with schizophrenia. Social cognition is quantified using Mayer, Salovey and Caruso emotional intelligence test (MSCEIT) with five different categories: i) emotional perception, ii) emotional facilitation, iii) emotional comprehension, iii) emotional management and iv) emotional intellectual quotient dimensions. Early trauma data is collected using Childhood Trauma Questionnaire (CTQ), which yields physical, emotional, sexual abuse and neglect scores. We have assessed the correlation coefficients (Spearman′s rho) between childhood trauma and social cognition scores.ResultsAccording to our preliminary analyses, there are significant inverse correlation coefficients in the patients group between emotional neglect and total trauma scores and, on the other hand, social cognition scores for the facilitation, comprehension, management and emotional intellectual quotient dimensions. Thus, patients with higher scores reflecting more severe emotional neglect and total trauma performed lower in social cognition tests.DiscussionChildhood trauma experiences may contribute to social cognition deficits in schizophrenia.

BackgroundSocial cognition impairments are found in schizophrenia patients and hamper their ability to form social relationships. The biological underpinnings of this social cognition impairment are poorly investigated. We hypothesize that structural disconnectivity, which is replicated in schizophrenia, might has a relevant role in social cognition.MethodsThe study we present here is under development. We have assessed social cognition using the Mayer, Salovey and Caruso emotional intelligence test (MSCEIT) in 30 patients with schizophrenia and 20 healthy controls. Structural connectivity is assessed with anatomical and Diffusion weighted (DWI) images acquired in a 3 Tesla MRI system. Anatomical and DWI images are processed to obtain fractional anisotropy (FA) values in the tracts connecting prefrontal cortex with anterior cingulate, superior temporal gyrus, insula and superior parietal cortex. The following statistics are assessed i) the differences in MSCEIT scores between patients and controls, ii) the differences in FA values between groups, iii) the relation between MSCEIT punctuation and FA values.ResultsIn our preliminary analyses, patients show significantly lower MSCEIT scores. Furthermore, MSCEIT scores are directly related to FA values in the tracts connecting prefrontal cortex to anterior cingulate and superior temporal gyrus in the patients.DiscussionSocial cognition impairments seem to be associated with altered structural connectivity in the patients.

To my friends Tita and Kuba. I feel fortunate to have met you. I will never forget the three great months we were together in Wroclaw. We must keep in touch despite the distance between our homes. A mis amigos Pucelanos, en primer lugar a Clara, compañera de camino desde hace muchos años, sin tu ejemplo y ayuda quizá no habría llegado aquí. Ahora las dos lo hemos conseguido, ¡somos doctoras!. En segundo lugar a Nati, María, David y Sara. Gracias por estar, por las cenas, los bailes, las risas y, en general, los buenos momentos. Qué suerte tengo de teneros cerca. Por último, a Christopher, por su ayuda con las correcciones del inglés. A mis amigos Leoneses "Los Jetas", con los que recorrí las primeras etapas de mi formación universitaria. Porque nuestras pequeñas y grandes escapadas me han dado fuerzas para realizar esta tesis y lo mejor, permiten que sigamos unidos. A mi padre y abuelos, por darme los recursos y el apoyo para poder estudiar. A mi familia no de sangre, pero sí de corazón, por orden de llegada a mi vida: Celia, Santi, Laura, Samuel, Inés y Manolo. Algunos formáis parte de estos artículos como "conejillos de indias". Gracias por vuestro apoyo, por estar a mi lado siempre y porque la vida es mejor teniéndoos cerca. A Julio, porque tú haces que la vida se me vuelva de colores. Esto es un logro compartido, de ambos. A mi madre, por enseñarme a vivir, a ser valiente, a luchar, a levantarme en cada tropiezo. Por transmitirme el amor de la cultura y la educación. Esta tesis es por y para ti. A los controles y pacientes que dieron su tiempo para formar parte de este proyecto. Y en general, a todos los pacientes que sufren o han sufrido enfermedades mentales y a sus familiares. Este es mi pequeño granito de arena.