Eva Grasa

Density of striatal D2 receptors in untreated first-episode psychosis: an I123-IBZM SPECT study.

There is as yet no definite prognostic marker to determine whether a first-episode psychosis will become schizophrenia or not. The aim of the present study is to address whether the mechanism of sensitization of the subcortical dopaminergic pathway - yielding to an increase of the postsynaptic D2 receptors - may serve as a prognostic marker of clinical outcome in drug naïve patients with a first-episode psychosis, by means of a prospective and multicentric study with untreated first-episode psychosis patients (n=37). 123I-IBZM SPECT was performed at the time of the inclusion in the study, before antipsychotic medication was initiated. One year later, patients were assessed again so as to determine their diagnosis. There was a significant group effect at baseline in D2 Striatal/Frontal (S/F) ratios (F=10.2, p<0.001). Bonferroni posthoc comparisons attested significant differences between diagnosis (p=0.006), and between schizophrenia and control groups (p<0.001) but no differences between non-schizophrenia and control groups (p=0.9). The logistic regression model showed that D2R binding (p=0.02) and PAS (Premorbid Adjustment Scale) adulthood score (p=0.03) were predictive of the final diagnosis (schizophrenia/non-schizophrenia; Nagelkerke R(2)=0.59; X(2)=11.08, p=0.001). These findings replicate previous results on the usefulness of D2R binding as an objective prognostic parameter, together with the evaluation of premorbid adjustment, of the evolution of first-episode psychosis. In this regard, the results may provide a new view in the approach of early and personalized treatment in the debut of a psychosis.

Pharmacogenetic study of antipsychotic induced acute extrapyramidal symptoms in a first episode psychosis cohort: role of dopamine, serotonin and glutamate candidate genes

This study investigated whether the risk of presenting antipsychotic (AP)-induced extrapyramidal symptoms (EPS) could be related to single-nucleotide polymorphisms (SNPs) in a naturalistic cohort of first episode psychosis (FEP) patients. Two hundred and two SNPs in 31 candidate genes (involved in dopamine, serotonin and glutamate pathways) were analyzed in the present study. One hundred and thirteen FEP patients (43 presenting EPS and 70 non-presenting EPS) treated with high-potency AP (amisulpride, paliperidone, risperidone and ziprasidone) were included in the analysis. The statistical analysis was adjusted by age, gender, AP dosage, AP combinations and concomitant treatments as covariates. Four SNPs in different genes (DRD2, SLC18A2, HTR2A and GRIK3) contributed significantly to the risk of EPS after correction for multiple testing (P<1 × 10−4). These findings support the involvement of dopamine, serotonin and glutamate pathways in AP-induced EPS.

Neurophysiological evidence of impaired self-monitoring in schizotypal personality disorder and its reversal by dopaminergic antagonism.

Background Schizotypal personality disorder (SPD) is a schizophrenia-spectrum disorder characterized by odd or bizarre behavior, strange speech, magical thinking, unusual perceptual experiences, and social anhedonia. Schizophrenia proper has been associated with anomalies in dopaminergic neurotransmission and deficits in neurophysiological markers of self-monitoring, such as low amplitude in cognitive event-related brain potentials (ERPs) like the error-related negativity (ERN), and the error positivity (Pe). These components occur after performance errors, rely on adequate fronto-striatal function, and are sensitive to dopaminergic modulation. Here we postulated that analogous to observations in schizophrenia, SPD individuals would show deficits in self-monitoring, as measured by the ERN and the Pe. We also assessed the capacity of dopaminergic antagonists to reverse these postulated deficits. Methods We recorded the electroencephalogram (EEG) from 9 SPD individuals and 12 healthy controls in two separate experimental sessions while they performed the Eriksen Flanker Task, a classical task recruiting behavioral monitoring. Participants received a placebo or 1 mg risperidone according to a double-blind randomized design. Results After placebo, SPD individuals showed slower reaction times to hits, longer correction times following errors and reduced ERN and Pe amplitudes. While risperidone impaired performance and decreased ERN and Pe in the control group, it led to behavioral improvements and ERN amplitude increases in the SPD individuals. Conclusions These results indicate that SPD individuals show deficits in self-monitoring analogous to those in schizophrenia. These deficits can be evidenced by neurophysiological measures, suggest a dopaminergic imbalance, and can be reverted by dopaminergic antagonists.

Sex differences in sleep after a single oral morning dose of olanzapine in healthy volunteers

Polysomnography abnormalities are frequent in schizophrenia and have been correlated with clinical variables. Because women with schizophrenia present a general better clinical outcome than men, we aimed to determine whether sex differences in antipsychotic‐induced effects on sleep could contribute to this difference.

Randomized control trial to assess the efficacy of metacognitive training compared with a psycho-educational group in people with a recent-onset psychosis

BACKGROUND Aims were to assess the efficacy of metacognitive training (MCT) in people with a recent onset of psychosis in terms of symptoms as a primary outcome and metacognitive variables as a secondary outcome. METHOD A multicenter, randomized, controlled clinical trial was performed. A total of 126 patients were randomized to an MCT or a psycho-educational intervention with cognitive-behavioral elements. The sample was composed of people with a recent onset of psychosis, recruited from nine public centers in Spain. The treatment consisted of eight weekly sessions for both groups. Patients were assessed at three time-points: baseline, post-treatment, and at 6 months follow-up. The evaluator was blinded to the condition of the patient. Symptoms were assessed with the PANSS and metacognition was assessed with a battery of questionnaires of cognitive biases and social cognition. RESULTS Both MCT and psycho-educational groups had improved symptoms post-treatment and at follow-up, with greater improvements in the MCT group. The MCT group was superior to the psycho-educational group on the Beck Cognitive Insight Scale (BCIS) total (p = 0.026) and self-certainty (p = 0.035) and dependence self-subscale of irrational beliefs, comparing baseline and post-treatment. Moreover, comparing baseline and follow-up, the MCT group was better than the psycho-educational group in self-reflectiveness on the BCIS (p = 0.047), total BCIS (p = 0.045), and intolerance to frustration (p = 0.014). Jumping to Conclusions (JTC) improved more in the MCT group than the psycho-educational group (p = 0.021). Regarding the comparison within each group, Theory of Mind (ToM), Personalizing Bias, and other subscales of irrational beliefs improved in the MCT group but not the psycho-educational group (p < 0.001-0.032). CONCLUSIONS MCT could be an effective psychological intervention for people with recent onset of psychosis in order to improve cognitive insight, JTC, and tolerance to frustration. It seems that MCT could be useful to improve symptoms, ToM, and personalizing bias.

Estudio farmacogenético del tratamiento a largo plazo con antipsicóticos de segunda generación y sus efectos adversos metabólicos (Estudio SLiM): justificación, objetivos, diseño y descripción de la muestra

AIM Weight gain is an important and common side effect of second generation antipsychotics (SGAs). Furthermore, these drugs can induce other side effects associated with higher cardiovascular morbidity and mortality, such as insulin resistance, diabetes or metabolic syndrome. Preliminary studies show that inter-individual genetic differences produce varying degrees of vulnerability to the different SGA-induced side effects. The Second-generation antipsychotic Long-term treatment Metabolic side effects (SLiM) study aims to identify clinical, environmental and genetic factors that explain inter-individual differences in weight gain and metabolic changes in drug-naïve patients after six months of treatment with SGAs. MATERIALS AND METHODS The SLIM study is a multicenter, observational, six-month pharmacogenetic study where a cohort of 307 drug-naïve paediatric and adult patients (age range 8.8-90.1 years) and a cohort of 150 age- and sex- matched healthy controls (7.8-73.2 years) were recruited. RESULTS This paper describes the rationale, objectives and design of the study and provides a description of the sample at baseline. CONCLUSIONS Results from the SLiM study will provide a better understanding of the clinical, environmental, and genetic factors involved in weight gain and metabolic disturbances associated with SGA treatment.

S121. JUMPING TO CONCLUSIONS, SOCIAL COGNITION AND METACOGNITION IN PEOPLE WITH A RECENT-ONSET OF PSYCHOSIS

Abstract Background The reasoning bias of jumping to conclusions (JTC) consists of a tendency to have an impaired decision process in which assumptions are made having little information. JTC is one of the most widely studied cognitive biases in psychosis (Freeman, 2007; Garety and Freeman, 1999; Moritz and Woodward, 2005) due to its higher prevalence in people with psychosis in comparison to healthy participants as found by So et al. (2016) in her meta-analyses and by Dudley et al. (2016) in his systematic review and meta-analysis. Social cognition(sc) is the best defined as a set of neurocognitive processes related to understanding, recognizing, processing, and appropriately using social stimuli in one′s environment (Adolphs, 1999). The domains are: emotion processing, theory of mind, attributional style and social perception. Methods One hundred and twenty patients with a recent onset of a psychotic disorder were assessed. Jumping to conclusions (JTC) was assessed with the beads task in which the subject must take a decision regarding the probability of the extracted bead belonging to one of two jars. In task 1 a jar is presented with a ratio of 85% black beads and 15% orange beats and another jar with inverse proportion. Task 2 is the same but the probability is 60%-40%. Task 3 has the same probability 60%-40& but instead of beads, the jars contain negative and positive adjectives. JTC was considered as taking a decision after extracting one or two beads (Brett-Jones et al. 1987). A battery of questionnaires regarding social cognition was included: The Hinting Task, was used to assess ToM. (Corcoran et al. 1995; Gil et al. 2012); Emotional perception was assessed with the Emotional Recognition Test Faces (Baron-Cohen et al. 1997), and the attributional style was assessed with the Internal, Personal and Situational Attributions Questionnaire (IPSAQ; Kinderman & Bentall, 1996). Irrational beliefs were assessed with the irrational Belief Test (TCI; Calvete & Cardeñoso, 2001). The scale is composed of ten subscales: needing acceptance from others, high expectations, guilt, intolerance to frustration, worry and anxiety, emotional irresponsibility, avoidance of problems, dependence, helplessness, and perfectionism. Results Patients who performed JTC in Task 1 scored higher levels of worry and anxiety (p=0.026), perfectionism (p=0.01) and internal attribution for negative events (p=0.034) and lower in externalizing bias (p=0.042) and emotional recognition (p=0.042). Patients who performed JTC in Task 2 scored higher levels of worry and anxiety (p=0.016) and lower in emotional recognition (p=0.031). And finally, patients who performed JTC in Task 3 scored higher in internal attribution for negative events (p=0.029) and worry and anxiety (p=0.002) whereas that lower in situational attribution for negative events (p=0.004) and emotional recognition (p=0.017). ToM is not related with any of the JTC tasks. Discussion JTC is related to some aspects of social cognition, specifically with attributional style and emotional recognition. Moreover, JTC is related with perfectionism and worry and anxiety irrational beliefs.

F49. EFFECTIVENESS OF THE META-COGNITIVE TRAINING IN PEOPLE WITH FIRST-EPISODE PSYCHOSIS: DOES GENDER MATTER?

Abstract Background The Meta-Cognitive Training (MCT) is a psychological intervention that combines psychoeducational components and cognitive behavioural therapies with a meta-cognitive approach. The MCT (Moritz and Woodward, 2007) focuses on different cognitive biases, theory of mind and attribution bias, as well as on the predictive value of depressed mood and low self-esteem on paranoid ideation. The MCT has result effective for people with schizophrenia in order to improve symptoms, cognitive insight, jumping to conclusions, memory and quality of life. However, less information is regarding the effectiveness of MCT in first episode psychosis. On the other hand, gender has an important role in psychosis, nevertheless the effect of gender in the effectiveness of MCT has not been proved. The aim of the study is to assess the effectiveness of MCT regarding symptoms and cognitive insight in people with first episode psychosis, considering the effect of gender. Methods A multicenter, randomized, controlled clinical trial was performed. A total of 122 patients were randomized to an MCT or a psycho-educational intervention. The sample was composed of people with a recent onset of psychosis, recruited from 9 public centers in Spain. The treatment consisted of 8 weekly sessions for both groups. Patients were assessed at three time-points: baseline, post-treatment, and at six months of follow-up. The evaluator was blinded to the condition of the patient. Symptoms were assessed with the PANSS and cognitive insight with the BCIS. A regression model for repeated measures was performed with the SPSS by gender. Results The sample was composed by 85 men and 37 women, although 53 men and 21 women completed the treatment and the follow-up. Both psychoeducational and MCT group improved in positive symptoms at post-treatment and follow-up (p<0.05-0.001) with higher effect sizes in the MCT group (0.53 versus 0.38). Regarding negative symptoms the MCT group improved in the follow-up (p<0.001) and general symptoms MCT improved in the post-treatment and follow-up (p<0.001). Cognitive insight was higher in people who attended the MCT, in self-certainty in the post-treatment (p<0.05), self-reflectiveness in the follow-up (p<0.05) and the composite index in both assessments (p<0.05). Considering the results by gender, men of both groups improve more in positive, negative and disorganized symptoms of the PANSS (p<0.001- 0.046) while women improve in positive symptoms. A tendency of interaction between group and affective symptoms was found only in women (p=0.062), improving more women of the MCT group. Regarding cognitive insight, women of the MCT group improve more in self certainty and total BCIS compared with the psychoeducational group (p<0.001–0.022). Discussion MCT could be an effective psychological intervention for people with a recent-onset of psychosis for the improvement of cognitive insight and psychotic symptoms. It seems that women could benefit more from the MCT intervention than men in reduction of affective symptoms and in the improvement of cognitive insight.

F243. INFLUENCE OF METACOGNITION AND IRRATIONAL BELIEFS ON SOCIAL FUNCTIONING IN PSYCHOSIS OF RECENT ONSET

Abstract Background Social functioning is affected in early psychosis stages. This affection has multiple domains, such as vocational functioning or performance of independent living skills. These different domains are also linked; so elucidating differential or generalized determinants on specific areas and global outcomes is thus a critical step in case conceptualization and the development planning of effective early interventions. The aim of this study was to test the influence of specific domains of metacognition in different and global areas of social functioning. Methods A cross-sectional study was performed based on baseline data from a main multicenter clinical trial. The sample was composed of 122 patients with psychosis of recent onset treated at one of the nine participating mental health centers from diverse regions of Spain. The order of assessment was a sociodemographic questionnaire, the Positive and Negative Syndrome Scale (PANSS), the Social Functioning Scale (SFS), the Hinting Task (Theory of Mind, ToM), the Beck Cognitive Insight Scale (BCIS), the Internal, Personal and Situational Attributions Questionnaire (IPSAQ), the Irrational Belief Test (TCI) and the Emotional Recognition Test Faces. Pearson correlations and multiple regression analysis were performed. Results In the first models, results showed that social engagement/withdrawal was explained by Helplessness (9.2% of the variance). Interpersonal communication was explained by Emotional Irresponsibility, internal attribution of negative events, affective JTC and emotion recognition (17.5% of variance). Independence-competence was explained by Helplessness, Emotional Irresponsibility and ToM (16% of variance). Independence-performance was explained by Helplessness (8.2% of variance). Employment/occupation was explained Emotional Irresponsibility (12.4% of variance). Prosocial Activities was explained by Helplessness and Emotional Irresponsibility (14.4% of variance). Finally, the total score of the SFS was explained by Helplessness and self-reflectiveness (16% of variance). Subsequently, in a second analysis, negative symptoms emerged as a significant mediator for most domains of social functioning. Discussion In our results, two kind of irrational beliefs, one of the main axes of cognitive therapy, emerged as relevant for social functioning in psychosis of recent onset. However, classic social cognition and metacognition measures were less significant, only ToM and self-reflecteness influenced some aspects of social functioning. Further analysis of determinants of social functioning in psychosis should explore the role of irrational beliefs and consider them for treatment strategy, along social cognition and negative symptoms.

T241. INTERPERSONAL COGNITIVE RIGIDITY AFFECTS SOCIAL FUNCTIONING IN PSYCHOSIS MORE THAN THEORY OF MIND: A STUDY WITH THE REPERTORY GRID TECHNIQUE

Abstract Background Social functioning impairment is one of the core features for schizophrenia diagnosis and are also present in other psychotic spectrum disorders, being determinant for disability. This impairment has multiple domains, which are linked but separate. Previous research has shown that social functioning is multiply determined by neurocognition, social cognition and symptoms, being social cognition the domain that accounts for more of the variance in daily functioning. However, cognitive rigidity in interpersonal perception has received less attention and much variance remains unexplained. The aim of this study was to test the role of interpersonal cognitive rigidity, as measured with the Repertory Grid Technique (RGT) in social functioning in psychosis. Methods Sample of 40 out-patients with a psychotic spectrum diagnosis from the network of mental health services of Parc Sanitari Sant Joan de Déu (Barcelona, Spain). Cross-sectional study, assessment was carried out by a predoctoral researcher (GMH), using a sociodemographic questionnaire, the Social Functioning Scale (SFS), the Hinting Task (Theory of Mind, ToM), the Beck Cognitive Insight Scale (BCIS), and the RGT (to measure interpersonal cognitive rigidity, two indices were selected: Percentage of Variance Accounted for the First Factor, PVAFF, and Polarization). Pearson correlations and multiple regression analysis were performed. Results Results showed that social engagement/withdrawal was explained by PVAFF, accounting for 16% of the variance. Independence-competence was explained by polarization, explaining 14.6% of the variance and by sex, which accounted for 11.1% of the variance. Independence-performance was explained by theory of mind, explaining 22.5% of variance. Employment/occupation was explained by years of illness accounting for 21.6% of variance, and by polarization (beta=-0.318, p=0.026) which explained 10% of variance. Finally, the total score of the SFS was explained by polarization, explaining 14.4% of variance, and sex, which accounted for 12.6% of variance. For prosocial activities and interpersonal communication, none of the variables entered for the linear regression analysis. Discussion Despite ToM and cognitive insight are common variables reported in the research literature, in our study the cognitive rigidity measures of the RGT, based on the patients’ own terms (personal constructs) in rating their significant others, were better predictors of social functioning. These findings support the importance and utility of an idiographic instrument like the RGT to investigate cognitive processes related to social perception and their impact on functioning. Regarding PVAFF, a higher tendency to perceive the interpersonal world from a unidimensional manner predicted a worse outcome in social relationships/withdrawal. Regarding interpersonal polarized thinking, it was the best cognitive predictor of social functioning measures. Our results suggest that a dichotomous thinking style in interpersonal perception might also be relevant for elucidating the dysfunction in social adjustment domains. These findings are still preliminary, and form part of an ongoing study.