Neuropsychological profiles in first-episodes psychosis and their relationship with clinical, metacognition and social cognition variables.

An increasing interest in the assessment of neuropsychological performance variability in people with first-episode psychosis (FEP) has emerged. However, its association with clinical and functional outcomes requires further study. Furthermore, FEP neuropsychological subgroups have not been characterized by clinical insight or metacognition and social cognition domains. The aim of this exploratory study was to identify specific groups of patients with FEP based on neuropsychological variables and to compare their sociodemographic, clinical, metacognition and social cognition profiles. A sample of 149 FEP was recruited from adult mental health services. Neuropsychological performance was assessed by a neuropsychological battery (WAIS-III; TMT; WSCT; Stroop Test; TAVEC). The assessment also included sociodemographic characteristics, clinical, functional, metacognition and social cognition variables. Two distinct neuropsychological profiles emerged: one neuropsychological impaired cluster (N = 56) and one relatively intact cluster (N = 93). Significant differences were found between both profiles in terms of sociodemographic characteristics (age and level of education) (p = 0.001), clinical symptoms (negative, positive, disorganized, excitement and anxiety) (p = 0.041-0.001), clinical insight (p = 0.038-0.017), global functioning (p = 0.014), as well as in social cognition domains (emotional processing and theory of mind) (p = 0.001; p = 0.002). No significant differences were found in metacognitive variables (cognitive insight and 'jumping to conclusions' bias). Relationship between neurocognitive impairment, social cognition and metacognition deficits are discussed. Early identifying of neuropsychological profiles in FEP, characterized by significant differences in clinical and social cognition variables, could provide insight into the prognosis and guide the implementation of tailored early-intervention.

The influence of gender in cognitive insight and cognitive bias in people with first-episode psychosis: an uncontrolled exploratory analysis.

PURPOSE: Previous studies have investigated the role of gender in clinical symptoms, social functioning, and neuropsychological performance in people with first-episode psychosis (FEP). However, the evidence of gender differences for metacognition in subjects with FEP is still limited and controversial. The aim of the present study was to explore gender differences in cognitive insight and cognitive biases in this population. METHODS: Cross-sectional study was carried out in a sample of 104 patients with FEP (35 females and 69 males) recruited from mental health services. Symptoms were assessed with the Positive and Negative Syndrome Scale, cognitive insight with the Beck Cognitive Insight Scale, and cognitive bias by the Cognitive Biases Questionnaire for Psychosis. The assessment also included clinical and sociodemographic characteristics. RESULTS: After controlling for potential confounders (level of education, marital status, and duration of psychotic illness) analysis of covariance revealed that males presented greater self-reflectiveness (p = 0.004) when compared to females. However, no significant differences were found in self-certainty and composite index of the cognitive insight scale, as in the cognitive biases assessed. CONCLUSIONS: Gender was an independent influence factor for self-reflectiveness, being better for males. Self-reflectiveness, if shown to be relatively lacking in women, could contribute to the design of more gender-sensitive and effective psychotherapeutic treatments, as being able to self-reflect predicts to better treatment response in psychosis.

Positive and Useful Voices in Patients With Schizophrenia: Prevalence, Course, Characteristics, and Correlates.

Auditory verbal hallucinations (AVHs) in schizophrenia have been characterized by their negative emotional valence. However, positive hallucinations have also been described. The objective of the current study is to explore the prevalence, course, characteristics, and associations of positive and useful voices. The Positive and Useful Voices Inquiry and some clinical and functioning instruments were administered to a sample of 68 patients with schizophrenia or schizoaffective disorder presenting with AVHs. Both the lifetime and current prevalences of positive and useful voices were high. Although AVHs tended to remain stable, there was a trend to decrease over time. The strongest positive attributions of such voices were that they help patients to feel important, amuse them, and help them to conduct their studies and carry out their profession. They seem to be mainly related to more grandiosity and to worse general functioning. Interference with biological and psychological treatments and the need for personalized formulations in patients with auditory hallucinations are discussed.

Validation of a Spanish version of the Schizotypal Personality Questionnaire (SPQ): Psychometric characteristics and underlying factor structure derived from a healthy university student sample.

OBJECTIVE: The need for early detection, prevention and intervention in psychosis has prompted the study of prodromal and threshold syndromes. One strategy involves the assessment of schizotypy, a personality construct involving unusual perceptual experiences, magical thinking or bizarre behavior. Sensitive measurement instruments could potentially allow detection of signs heralding transition to psychosis in high-risk individuals, or risk of relapse in patients after a first psychotic episode. The Schizotypal Personality Questionnaire (SPQ) is a self-report scale, originally developed for English speakers, that covers the nine DSM-IV criteria for schizotypal personality disorder (SPD). Our aim was to validate a Spanish version of the SPQ and assess its psychometric properties. METHODS: The original SPQ was back-translated and administered to university students (n=250). We assessed the internal consistency, the convergent, discriminant and criterion validity of the instrument, and analyzed its factor structure. RESULTS: Our version of the SPQ showed good internal consistency, and convergent (O-LIFE), discriminant (P-scale of EPQ) and criterion validity (SCID-II). Factor analyses supported a four-factor structure in fitting SPQ data. CONCLUSIONS: Our Spanish version of the SPQ questionnaire preserved the psychometric properties of the original questionnaire. This adaptation will provide a useful tool for the early detection of prodromal schizophrenia symptoms and clinical relapse in Spanish-speaking populations.

Predictors of clinical insight in first-episode psychosis: Different patterns in men and women.

BACKGROUND: We aimed to explore gender-related differences in the associations of insight impairment with clinical symptoms, metacognition, and social cognition in psychosis. METHODS: Regression analysis of several clinical insight dimensions was conducted on the data from 116 men and 56 women with first-episode psychosis. Various clinical symptoms and measures of metacognition and social cognition were entered as predictors. RESULTS: In both men and women, delusions emerged as a strong predictor of all insight dimensions, and verbal hallucinations as a strong predictor of symptom relabelling. In men, certain negative symptoms as well as self-certainty, lack of self-reflectiveness, impaired theory of mind, attributional biases, and a jumping-to-conclusions bias were additional predictors of poor insight, while good insight was associated with depression, anxiety, avolition, blunted affect, and impaired emotional recognition. In women, poor insight was associated with a self-serving/externalising bias, impaired emotional recognition, and attention disorders. CONCLUSIONS: Poor insight in first-episode psychosis is strongly linked to deficits in metacognition and social cognition, with marked differences between men and women with respect to the specific skills involved in the impairment. Meanwhile, good insight is linked to a variety of affective manifestations in men. These findings suggest new avenues for more targeted cognitive interventions to improve clinical insight in psychosis.

Alterations in the volume and shape of the basal ganglia and thalamus in schizophrenia with auditory hallucinations.

Different lines of evidence indicate that the structure and physiology of the basal ganglia and the thalamus is disturbed in schizophrenia. However, it is unknown whether the volume and shape of these subcortical structures are affected in schizophrenia with auditory hallucinations (AH), a core positive symptom of the disorder. We took structural MRI from 63 patients with schizophrenia, including 36 patients with AH and 27 patients who had never experienced AH (NAH), and 51 matched healthy controls. We extracted volumes for the left and right thalamus, globus pallidus, putamen, caudate and nucleus accumbens. Shape analysis was also carried out. When comparing to controls, the volume of the right globus pallidus, thalamus, and putamen, was only affected in AH patients. The volume of the left putamen was also increased in individuals with AH, whereas the left globus pallidus was affected in both groups of patients. The shapes of right and left putamen and thalamus were also affected in both groups. The shape of the left globus pallidus was only altered in patients lacking AH, both in comparison to controls and to cases with AH. Lastly, the general PANSS subscale was correlated with the volume of the right thalamus, and the right and left putamen, in patients with AH. We have found volume and shape alterations of many basal ganglia and thalamus in patients with and without AH, suggesting in some cases a possible relationship between this positive symptom and these morphometric alterations.

Cognitive insight in first-episode psychosis: Exploring the complex relationship between executive functions and social cognition.

Social cognition (SC) and executive function (EF) have been described as important variables for social functioning and recovery of patients with psychosis. However, the relationship between SC and EF in first-episode psychosis (FEP) deserves further investigation, especially focusing on gender differences. AIMS: To investigate the relationship between EF and different domains of SC in FEP patients and to explore gender differences in the relationship between these domains. METHODS: A cross-sectional study of 191 patients with new-onset psychosis recruited from two multicenter clinical trials. A comprehensive cognitive battery was used to assess SC (Hinting Task, Face Test and IPSAQ) and EF (TMT, WSCT, Stroop Test and digit span - WAIS-III). Pearson correlations and linear regression models were performed. RESULTS: A correlation between Theory of Mind (ToM), Emotional Recognition (ER) and EF was found using the complete sample. Separating the sample by gender showed different association profiles between these variables in women and men. CONCLUSIONS: A relationship between different domains of SC and EF is found. Moreover, women and men presented distinct association profiles between EF and SC. These results should be considered in order to improve the treatment of FEP patients and designing personalized interventions by gender.

Direct experience and the course of eating disorders in patients on partial hospitalization: a pilot study.

Awareness of sensory experience in the present moment is central to mindfulness practice. This type of information processing, in contrast to an analytical evaluative style of processing, could be more beneficial for the course of those psychiatric disorders characterized by ruminative and content-centred processing, such as eating disorders (EDs). We performed a pilot study to assess the relation between patients' approach to information processing and the duration and severity of EDs. Fifty-seven patients with a diagnosed ED were included in the study and participated in a self-guided eating activity to asses the primary information processing mode based on mindfulness concepts of 'Direct Experience' and 'Thinking About'. Additionally, dispositional mindfulness was assessed by the Five Factors Mindfulness Questionnaire, and anxiety during the experiment was determined by means of a 10-point visual analogue scale. We found that a higher level of self-reported Direct Experience was inversely associated with several severity variables and with anxiety levels. Direct Experience was predicted by a low anxiety level, less severe illness, and higher scores on one mindfulness facet (Observing). Our results suggest that a Direct Experience processing approach is associated with better ED outcomes. Future studies should be carried out to clarify the repercussion of mindfulness training on EDs.

Volume alterations of the hippocampus and amygdala in patients with schizophrenia and persistent auditory hallucinations.

INTRODUCTION: Auditory hallucinations (AH) are one of the most prevalent symptoms of schizophrenia. They might cause several brain alterations, especially changes in the volumes of hippocampus and amygdala, regions related to the relay and processing of auditory cues and emotional memories. MATERIAL AND METHODS: We have recruited 41 patients with schizophrenia and persistent AH, 35 patients without AH, and 55 healthy controls. Using their MRIs, we have performed semiautomatic segmentations of the hippocampus and amygdala using Freesurfer. We have also performed bilateral correlations between the total PSYRATS score and the volumes of affected subregions and nuclei. RESULTS: In the hippocampus, we found bilateral increases in the volume of its hippocampal fissure and decreases in the right fimbria in patients with and without AH. The volume of the right hippocampal tail and left head of the granule cell layer from the dentate gyrus were decreased in patients with AH. In the amygdala, we found its left total volume was shrunk, and there was a decrease of its left accessory basal nucleus in patients with AH. CONCLUSIONS: We have detected volume alterations of different limbic structures likely due to the presence of AH. The volumes of the right hippocampal tail and left head of the granule cell layer from the dentate gyrus, and total volume of the amygdala and its accessory basal nucleus, were only affected in patients with AH. Bilateral volume alterations in the hippocampal fissure and right fimbria seem inherent of schizophrenia and due to traits not contemplated in our research.

Relationship between cognition and suicidal behavior in recent-onset psychosis.

Suicidal behavior (SB) is common in first-episode psychosis (FEP), and cognitive impairment has also been described in psychosis. Despite well-established risk factors for SB in psychosis, the role of cognition and insight remains unclear. This study aimed to explore the relationship between history of SB and cognition in recent-onset FEP, distinguishing between neurocognition, social cognition, and metacognition, and including cognitive insight (CI) as a metacognitive variable. The sample consisted of 190 participants with recent-onset FEP recruited from two multicentric studies. Two groups were formed based on presence/absence of a history of SB. Demographic, clinical, and cognitive data were compared by group, including significance level adjustments and size effect calculation. No differences were found regarding demographic, clinical, neurocognitive, social cognition, and metacognitive variables except for CI (18.18 ± 4.87; t = -3.16; p = 0.0020; d = -0.635), which showed a medium effect size. Small to medium effect size were found for attributional style (externalizing bias) (1.15 ± 3.94; t = 2.07; d = 0.482), theory of mind (ToM) (1.73 ± 0.22; t = 2.04; d = -0.403), jumping to conclusions bias (JTC) (23.3 %; X2 = 0.94; V = 0.178). In recent-onset psychosis, neurocognitive functioning was not related to the history of SB. As novelty, individuals with previous SB showed higher CI. Also, regarding social cognition and metacognition, individuals with prior SB tended to present extremely low externalizing bias, better ToM, and presence of JTC.

m-RESIST, a Mobile Therapeutic Intervention for Treatment-Resistant Schizophrenia: Feasibility, Acceptability, and Usability Study.

BACKGROUND: In the European Union, around 5 million people are affected by psychotic disorders, and approximately 30%-50% of people with schizophrenia have treatment-resistant schizophrenia (TRS). Mobile health (mHealth) interventions may be effective in preventing relapses, increasing treatment adherence, and managing some of the symptoms of schizophrenia. People with schizophrenia seem willing and able to use smartphones to monitor their symptoms and engage in therapeutic interventions. mHealth studies have been performed with other clinical populations but not in populations with TRS. OBJECTIVE: The purpose of this study was to present the 3-month prospective results of the m-RESIST intervention. This study aims to assess the feasibility, acceptability, and usability of the m-RESIST intervention and the satisfaction among patients with TRS after using this intervention. METHODS: A prospective multicenter feasibility study without a control group was undertaken with patients with TRS. This study was performed at 3 sites: Sant Pau Hospital (Barcelona, Spain), Semmelweis University (Budapest, Hungary), and Sheba Medical Center and Gertner Institute of Epidemiology and Health Policy Research (Ramat-Gan, Israel). The m-RESIST intervention consisted of a smartwatch, a mobile app, a web-based platform, and a tailored therapeutic program. The m-RESIST intervention was delivered to patients with TRS and assisted by mental health care providers (psychiatrists and psychologists). Feasibility, usability, acceptability, and user satisfaction were measured. RESULTS: This study was performed with 39 patients with TRS. The dropout rate was 18% (7/39), the main reasons being as follows: loss to follow-up, clinical worsening, physical discomfort of the smartwatch, and social stigma. Patients' acceptance of m-RESIST ranged from moderate to high. The m-RESIST intervention could provide better control of the illness and appropriate care, together with offering user-friendly and easy-to-use technology. In terms of user experience, patients indicated that m-RESIST enabled easier and quicker communication with clinicians and made them feel more protected and safer. Patients' satisfaction was generally good: 78% (25/32) considered the quality of service as good or excellent, 84% (27/32) reported that they would use it again, and 94% (30/32) reported that they were mostly satisfied. CONCLUSIONS: The m-RESIST project has provided the basis for a new modular program based on novel technology: the m-RESIST intervention. This program was well-accepted by patients in terms of acceptability, usability, and satisfaction. Our results offer an encouraging starting point regarding mHealth technologies for patients with TRS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03064776; https://clinicaltrials.gov/ct2/show/record/NCT03064776. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2017-021346.

The role of striatal dopamine D2 receptors in the occurrence of extrapyramidal side effects: iodine-123-iodobenzamide single photon emission computed tomography study.

Levels above 75% of striatal dopamine 2 receptor occupancy (D2RO) have been associated with extrapyramidal symptoms (EPS). The aim of the present study is to investigate the relationship between D2RO and EPS in a sample of psychotic patients in current treatment with both typical and atypical antipsychotics. Brain iodine-123-iodobenzamide single photon emission computed tomography ((123)I-IBZM SPECT) was performed in 81 patients taking stable doses of haloperidol, risperidone, olanzapine, quetiapine, clozapine or ziprasidone. First, the degree of D2RO and Positive and Negative Syndrome Scale (PANSS) scores was compared between the group of patients who presented EPS and the group free of EPS. Afterwards, these variables were compared among the different antipsychotic medications. The group with EPS presented means of D2RO significantly higher than the group free of EPS. Significant differences in D2RO were found in clozapine, quetiapine and ziprasidone groups compared with the haloperidol group. No differences were observed between either olanzapine or risperidone and haloperidol. No quetiapine- or clozapine-treated patients developed EPS. Haloperidol and risperidone demonstrated a relationship between striatal D2RO and EPS. The findings suggest that higher D2RO is related to appearance of EPS. Occupancy in the group with EPS was in agreement with previous studies that suggested a high degree of D2RO is necessary for the occurrence of EPS.

Alterations in the volume of thalamic nuclei in patients with schizophrenia and persistent auditory hallucinations.

The thalamus is a subcortical structure formed by different nuclei that relay information to the neocortex. Several reports have already described alterations of this structure in patients of schizophrenia that experience auditory hallucinations. However, to date no study has addressed whether the volumes of specific thalamic nuclei are altered in chronic patients experiencing persistent auditory hallucinations. We have processed structural MRI images using Freesurfer, and have segmented them into 25 nuclei using the probabilistic atlas developed by Iglesias and collaborators (Iglesias et al., 2018). To homogenize the sample, we have matched patients of schizophrenia, with and without persistent auditory hallucinations, with control subjects, considering sex, age and their estimated intracranial volume. This rendered a group number of 41 patients experiencing persistent auditory hallucinations, 35 patients without auditory hallucinations, and 55 healthy controls. In addition, we have also correlated the volume of the altered thalamic nuclei with the total score of the PSYRATS, a clinical scale used to evaluate the positive symptoms of this disorder. We have found alterations in the volume of 8 thalamic nuclei in both cohorts of patients with schizophrenia: The medial and lateral geniculate nuclei, the anterior, inferior, and lateral pulvinar nuclei, the lateral complex and the lateral and medial mediodorsal nuclei. We have also found some significant correlations between the volume of these nuclei in patients experiencing auditory hallucinations, and the total score of the PSYRATS scale. Altogether our results indicate that volumetric alterations of thalamic nuclei involved in audition may be related to persistent auditory hallucinations in chronic schizophrenia patients, whereas alterations in nuclei related to association cortices are evident in all patients. Future studies should explore whether the structural alterations are cause or consequence of these positive symptoms and whether they are already present in first episodes of psychosis.

Different measures for auditory hallucinations in populations with psychosis. The Validation of the Spanish versions of the Auditory Vocal Hallucination Rating Scale (AVHRS) and the Positive and Useful Voices Inquiry (PUVI).

INTRODUCTION: An updated summary of the most used instruments assessing auditory hallucinations in population with psychosis, allows us to underline the scarceness and need of Spanish versions of important instruments. The aim of the study is to examine the psychometric characteristics of two different and complementary instruments for assessing auditory hallucinations, the Spanish version of the Auditory Vocal Hallucination Scale (AVHRS) and the Spanish version of the Positive and Useful Voices Inquiry (PUVI). MATERIALS AND METHODS: A sample of 68 patients from four different centres, with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder presenting with auditory hallucinations were included. Apart from the AVHRS and the PUVI, the Psychotic Symptom Rating Scales-Auditory Hallucinations subscale (PSYRATS-AH) and the Positive and Negative Syndrome Scale (PANSS) were also administered to all patients, plus an acceptability questionnaire. RESULTS: The Spanish version of the AVHRS showed a good internal consistency, a moderate to high inter-rater reliability, a medium to moderate test-retest reliability, and a good convergent and discriminant validity. The Spanish version of the PUVI showed a good internal consistency and a heterogeneous, but in general moderate, test-retest reliability. CONCLUSIONS: The Spanish versions of the AVHRS and the PUVI have good psychometric properties and are well accepted among patients.

Clinical insight in first-episode psychosis: Clinical, neurocognitive and metacognitive predictors.

OBJECTIVE: Poor insight is a major problem in psychosis, being detrimental for treatment compliance and recovery. Previous studies have identified various correlates of insight impairment, mostly in chronic samples. The current study aimed to determine clinical, neurocognitive, metacognitive, and socio-cognitive predictors of insight in first-episode psychosis. METHODS: Regression analyses of different insight dimensions were conducted in 190 patients with first-episode psychosis. Measures of clinical symptoms, neurocognition, metacognition, social cognition, and 'jumping to conclusions' bias were entered as predictors. RESULTS: Delusions, disorganisation, and certain negative symptoms were associated with unawareness in various domains, while depression was associated with greater awareness of illness. Deficit in theory of mind and self-reflective processes, as well as a 'jumping to conclusions' bias, contributed to poor insight. Several neuropsychological scores also contributed to this but their contribution was no longer observed in regression analyses that included all the previously identified clinical and cognitive predictors. A measure of perseverative errors was still associated with unawareness and misattribution of symptoms. CONCLUSION: In models that account for 28 % to 50 % of the variance, poor insight in first-episode psychosis is mainly associated with delusions and certain negative symptoms. At the cognitive level it does not appear to result from neuropsychological impairment but rather from altered reasoning bias and dysfunction in metacognitive processes. Therapeutic strategies specifically directed at these mechanisms could help improve the evolution of insight in first episode psychosis.

Is Metacognitive Training effective for improving neurocognitive function in patients with a recent onset of psychosis?

The aims are to assess improvements in memory, attention and executive function in first-episode psychosis after Metacognitive Training (MCT). A multicenter randomized clinical trial was performed with two arms: MCT and psychoeducational intervention. A total of 126 patients with a diagnosis of psychosis, less than 5 years from the onset of the disease, were included. Patients were assessed two or three moments (baseline, post-treatment, 6 months follow-up) depending on the test, with a battery of neurocognitive tests (TAVEC, TMTA-B, CPT, WCST, Stroop and premorbid IQ). General linear models for repeated measures were performed.  A better improvement in the MCT was found by an interaction between group and time in CPT Hit index, TMTB, Stroop, recent memory and number of perseverations of the TAVEC. Considering three assessments, a better improvement was found in non-perseverative, perseverative and total errors of the WCST and TMTB. The MCT is an effective psychological intervention to improve several cognitive functions.

The relationship between jumping to conclusions and social cognition in first-episode psychosis.

Jumping to conclusions (JTC) and impaired social cognition (SC) affect the decoding, processing, and use of social information by people with psychosis. However, the relationship between them had not been deeply explored within psychosis in general, and in first-episode psychosis (FEP) in particular. Our aim was to study the relationship between JTC and SC in a sample with FEP. We conducted a cross-sectional study with 121 patients with FEP, with measures to assess JTC (easy, hard, and salient probability tasks) and SC (emotional recognition, attributional style, and theory of mind). We performed Student's t-test and logistic regression in order to analyse these associations.We found a statistically significant and consistent relationship of small-moderate effect size between JTC (all three tasks) and impaired emotional recognition. Also, our results suggest a relationship between JTC and internal attributions for negative events. Relationships between JTC and theory of mind were not found. These results highlight the importance of psychological treatments oriented to work on a hasty reasoning style and on improving processing of social information linked to emotional recognition and single-cause attributions.

Heterogeneity in Response to MCT and Psychoeducation: A Feasibility Study Using Latent Class Mixed Models in First-Episode Psychosis.

Metacognitive training (MCT) is an effective treatment for psychosis. Longitudinal trajectories of treatment response are unknown but could point to strategies to maximize treatment efficacy during the first episodes. This work aims to explore the possible benefit of using latent class mixed models (LCMMs) to understand how treatment response differs between metacognitive training and psychoeducation. We conducted LCMMs in 28 patients that received MCT and 34 patients that received psychoeducation. We found that MCT is effective in improving cognitive insight in all patients but that these effects wane at follow-up. In contrast, psychoeducation does not improve cognitive insight, and may increase self-certainty in a group of patients. These results suggest that LCMMs are valuable tools that can aid in treatment prescription and in predicting response to specific treatments.

Influence of Maternal and Paternal History of Mental Health in Clinical, Social Cognition and Metacognitive Variables in People with First-Episode Psychosis.

This study investigates, for the first time, clinical, cognitive, social cognitive and metacognitive differences in people diagnosed with first-episode of psychosis (FEP) with and without a family history of mental disorder split by maternal and paternal antecedents. A total of 186 individuals with FEP between 18 and 45 years old were recruited in community mental-health services. A transversal, descriptive, observational design was chosen for this study. Results suggest that there is a higher prevalence of maternal history of psychosis rather than paternal, and furthermore, these individuals exhibit a specific clinical, social and metacognitive profile. Individuals with a maternal history of mental disorder scored higher in delusional experiences, inhibition of the response to a stimulus and higher emotional irresponsibility while presenting a poorer overall functioning as compared to individuals without maternal history. Individuals with paternal history of mental disorder score higher in externalizing attributional bias, irrational beliefs of need for external validation and high expectations. This study elucidates different profiles of persons with FEP and the influence of the maternal and paternal family history on clinical, cognitive, social and metacognitive variables, which should be taken into account when offering individualized early treatment.

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

OBJECTIVE: 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. METHODS: Single oral morning doses of olanzapine (5 mg) were administered to 10 men and 10 women. Sleep variables were evaluated using traditional polysomnography Rechstschaffen and Kales criteria and all-night sleep electroencephalogram spectral analysis. Drug plasma concentrations were also measured. RESULTS: Significant sex-by-drug interactions were obtained in slow-wave sleep. After olanzapine, women showed an increase in slow-wave sleep, whereas men showed a decrease. We did not observe sex differences in olanzapine-induced hypnotic effects. Neither did we find any significant differences in pharmacokinetic parameters between sexes. Significant sex effects were observed in deep sleep, with women showing longer periods than men. CONCLUSION: Our results showed significant pharmacodynamic differences in olanzapine sleep effects between men and women. Further studies in clinical populations are needed to assess if these sex-based differences suggest that optimal treatment and doses should differ between men and women.