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Objective: This study was aimed at identifying sex differences in patients presenting a first episode mania (FEM) or psychosis (FEP) to help shaping early treatment strategies focused on sex differences., Methods: Patients with a FEM or FEP underwent a clinical, neuropsychological (neurocognitive functions and emotional intelligence) and functional assessment. Performance on those variables was compared between groups through general linear model, with sex and group (FEM vs FEP) as main effects and group by sex interactions., Results: The total sample included 113 patients: FEM = 72 (45.83 % females) and FEP = 41 (46.34 % females). There were significant main effects for group (not for sex) for most of the clinical features (depressive, negative and positive symptoms) and psychosocial functioning (χ 2  = 8.815, p = 0.003). As for neuropsychological performance, there were significant main effects for sex and group. Females performed better than males in verbal memory (χ 2  = 9.038, p = 0.003) and obtained a higher emotional intelligence quotient (χ 2  = 13.20, p < 0.001). On the contrary, males obtained better results in working memory (χ 2  = 7.627, p = 0.006). FEP patients significantly underperformed FEM patients in most cognitive domains. There were significant group by sex interactions for few neuropsychological variables, namely processing speed (χ 2  = 4.559, p = 0.033) and verbal fluency (χ 2  = 8.913, p = 0.003)., Limitations: Differences between sexes were evaluated, but the influence of gender was not considered. Retrospective evaluation of prodromes and substance use. No healthy control group comparator., Conclusion: The main finding is the presence of significant sex effect and group by sex interaction on specific neurocognitive cognition and emotional intelligence measures. Tailored sex-based early treatment strategies might be implemented., Competing Interests: Declaration of competing interest RPG has received financial support for CME activities and travel funds the following entities (unrelated to the present work): Angelini, Janssen, Lundbeck, Rovi and Otsuka. SA has been a consultant to and/or has received honoraria/grants from Otsuka-Lundbeck, with no financial or other relationship relevant to the subject of this article. MG has received grants and served as consultant or advisor for Ferrer, Lundbeck, and Janssen-Cilag. MSV has received financial support for CME activities and travel funds from Janssen-Cilag and Lundbeck, and reports no financial or other relationship relevant to the subject of this article. JARQ was on the speakers' bureau and/or acted as consultant for Eli-Lilly,Janssen-Cilag, Novartis, Shire, Takeda, Bial, Shionogui, Lundbeck, Almirall, Braingaze, Sincrolab, Medice, Rubió and Raffo in the last 5 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen-Cilag, Rubió, Shire, Takeda, Shionogui, Bial, Medice and Eli-Lilly. The Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 5 years: Eli-Lilly, Lundbeck, Janssen-Cilag, Actelion, Shire, Ferrer, Oryzon, Roche, Psious and Rubió. VSG has received financial support for CME activities and travel funds the following entities (unrelated to the present work): Angelini, Janssen, Lundbeck, Otsuka. GM served as speaker/consultant or received travel funds from Angelini, Janssen and Labor Est. AMA has received funding for research projects and/or honoraria as a consultant or speaker for the following companies and institutions (work unrelated to the topic of this manuscript): Otsuka, Pfizer, AstraZeneca, Bristol-Myers Squibb, Lundbeck, the Spanish Ministry of Economy and Competitiveness and Instituto de Salud Carlos III. IP has received CME-related honoraria or consulting fees from ADAMED, Janssen-Cilag and Lundbeck. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Janssen, Lundbeck, Medincell, Merck, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, outside the submitted work. NV has received financial support for CME activities and travel funds from the following entities (unrelated to the present work): Angelini, Janssen, Lundbeck, Otsuka. The rest of authors report no biomedical financial interests or potential conflicts of interest related to the present article., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Given the shared ectodermal origin and integrated development of the face and the brain, facial biomarkers emerge as potential candidates to assess vulnerability for disorders in which neurodevelopment is compromised, such as schizophrenia (SZ) and bipolar disorder (BD). The sample comprised 188 individuals (67 SZ patients, 46 BD patients and 75 healthy controls (HC)). Using a landmark-based approach on 3D facial reconstructions, we quantified global and local facial shape differences between SZ/BD patients and HC using geometric morphometrics. We also assessed correlations between facial and brain cortical measures. All analyses were performed separately by sex. Diagnosis explained 4.1 % - 5.9 % of global facial shape variance in males and females with SZ, and 4.5 % - 4.1 % in BD. Regarding local facial shape, we detected 43.2 % of significantly different distances in males and 47.4 % in females with SZ as compared to HC, whereas in BD the percentages decreased to 35.8 % and 26.8 %, respectively. We detected that brain area and volume significantly explained 2.2 % and 2 % of facial shape variance in the male SZ - HC sample. Our results support facial shape as a neurodevelopmental marker for SZ and BD and reveal sex-specific pathophysiological mechanisms modulating the interplay between the brain and the face., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Few studies have examined the functional brain correlates of the performance of the Stroop task in bipolar disorder (BD). It is also not known whether it is associated with failure of de-activation in the default mode network, as has been found in studies using other tasks., Methods: Twenty-four BD patients and 48 age, sex and educationally estimated intellectual quotient (IQ) matched healthy subjects (HS) underwent a functional MRI during performance of the counting Stroop task. Task-related activations (incongruent versus congruent condition) and de-activations (incongruent versus fixation) were examined using whole-brain, voxel-based methodology., Results: Both the BD patients and the HS showed activation in a cluster encompassing the left dorsolateral and ventrolateral prefrontal cortex and the rostral anterior cingulate cortex and supplementary motor area, with no differences between them. The BD patients, however, showed significant failure of de-activation in the medial frontal cortex and the posterior cingulate cortex/precuneus., Conclusions: The failure to find activation differences between BD patients and controls suggests that the 'regulative' component of cognitive control remains intact in the disorder, at least outside episodes of illness. The failure of de-activation found adds to evidence documenting trait-like default mode network dysfunction in the disorder., Competing Interests: Conflict of interest Dr. R. Rodriguez-Jimenez has been a consultant for, spoken in activities of, or received grants from: Instituto de Salud Carlos III, Fondo de Investigación Sanitaria (FIS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid Regional Government (S2010/BMD-2422 AGES; S2017/BMD-3740), Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Ferrer, Juste, Takeda, Exeltis, Angelini, Casen-Recordati. Dr. N. Verdolini has received financial support for CME activities and travel funds from the following entities (unrelated to the present work): Angelini, Janssen-Cilag, Lundbeck, Otsuka. The other authors declare no financial or other conflicts of interest related to this study., (Copyright © 2023. Published by Elsevier B.V.)

The psychosocial functioning of individuals suffering from bipolar disorder (BD) has a significant impact on prognosis and quality of life. The aim of this study was to assess brain functional correlates of psychosocial functioning in BD individuals during the performance of a working memory task. Sixty-two subjects (31 euthymic BD individuals and 31 matched healthy controls) underwent structural and functional magnetic resonance imaging scanning while performing the 1- and 2-back versions of the n-back task (1-back and 2-back). The Functional Assessment Short Test (FAST) and its subdomains were used to assess functioning. Whole brain analysis revealed only overall activation differences between BD patients and healthy controls, but the patients showed failure of de-activation in the medial frontal cortex. Six clusters of significant inverse correlation with the FAST scores were found in the dorsolateral prefrontal cortex, the superior parietal cortex, and temporo-occipital regions bilaterally, and in the left inferior frontal cortex. Cognitive and occupational functioning were the subdomains most significantly associated with brain activation in these clusters. The results suggest that poor psychosocial functioning in BD individuals is associated with hypoactivation in a range of cortical regions, including the fronto-parietal working memory network and inferior temporo-occipital regions., Competing Interests: Declaration of competing interest Dr. Vieta has received grants and served as consultant, advisor or CME speaker for the following entities (unrelated to the present work): AB-Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka, Sage, Sanofi-Aventis, and Takeda. Dr. Verdolini has received financial support for CME activities and travel funds from the following entities (unrelated to the present work): Angelini, Janssen, Lundbeck, Otsuka. The other authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Relapse prevention is an important goal in the clinical management of psychosis. Cognitive deficits/deterioration can provide useful insights for monitoring relapse in psychosis patients., Methods: This was a prospective, naturalistic 1-year follow-up study involving 110 psychosis patients with full clinical remission. Relapse, defined as the recurrence of psychotic symptoms, was monitored monthly along with digital tracking of verbal and visual working memory using a mobile app developed for this study. Cognitive deterioration was defined as worsening performance over 2 months prior to relapse or study termination, whichever was earlier. Other clinical, cognitive, functioning, and psychosocial variables were also collected., Results: At 1 year, 18 (16.36%) patients relapsed, of which 6 (33.33%) required hospitalization. Relapse was predicted by verbal working memory deterioration 2 months prior to relapse (p = 0.029), worse medication adherence (p = 0.018), and less resilience (p = 0.014)., Conclusions: Verbal working memory deterioration is a novel early sign of relapse. It is a clearly defined, objectively measurable, and reproducible marker that can help clinicians and healthcare workers identify patients at risk of relapse and make decisions about maintenance therapy. Moreover, digital monitoring is a viable tool in the management of relapse., Competing Interests: Declaration of Competing Interest EYHC reports having received speaker honoraria from Otsuka and DSK BioPharma; received research funding from Otsuka; participated in paid advisory boards for Jansen and DSK BioPharma; and received funding to attend conferences from Otsuka and DSK BioPharma. The remaining authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Sex differences influence the clinical characteristics and course of illness of bipolar disorder (BD)., Objective: Therefore, the aim of the present study was to examine the role of sex differences in neurocognitive performance and psychosocial functioning in a large sample of euthymic patients suffering from BD., Methods: The sample included 462 individuals, 347 patients with BD (148 males and 199 females) and 115 healthy controls (HC) (45 males and 70 females). Performance on a comprehensive neuropsychological battery assessing six cognitive domains and psychosocial functioning was compared between groups using linear mixed models, with sex and group as main effects, group by sex interactions and center as a random effect., Results: Males performed better than females in working memory (p < 0.001), whereas females outperformed males in the verbal learning (p = 0.03) and memory recognition (p = 0.03) tasks. No significant group by sex interactions were detected in cognitive performance. There were no overall sex differences or group by sex interactions in psychosocial functioning., Limitations: Lack of assessment of visuo-spatial working memory., Conclusions: There were no overall sex differences in neurocognition and psychosocial functioning. However, small sex differences in some measures of working memory and verbal memory were found. Individual differences of each patient, including sex perspective, should be considered in order to perform a tailored intervention plan adjusted to specific needs in the context of personalized treatment., (Copyright © 2021. Published by Elsevier B.V.)

The ability of attributing mental states to oneself and to the others (theory of mind, ToM) is impaired in schizophrenia. ToM is not a monolithic function, it includes different capacities: some implies the decoding of affective states, others the reasoning about mental states. We have developed the BAT, a Battery to Assess Theory of mind abilities in adult psychotic subjects in an ecological audiovisual format. The performance on the BAT and three other test of social cognition was compared in a sample of schizophrenic patients with a control group. The samples were matched in terms of age and premorbid IQ. The BAT was sensitive to detect the ToM impairments in schizophrenia, showed good internal consistency and concurrent validity. The area under the ROC curves established a cutoff point that would correctly classify controls and patients in a 96.6% of cases. The factorial analysis isolated two factors: empathy and reasoning, with a good adjustment. Our results showed that the BAT could be a valid, ecological and usable tool to assess ToM in psychotic patients, with good psychometric properties, that would allow obtaining a more complete profile of their impairment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Neuritin-1 is a neurotrophic factor involved in synaptic plasticity that has been associated with depressive disorders, schizophrenia and cognitive performance. The study of genotype-phenotype relationships in healthy individuals is a useful framework to investigate the etiology of brain dysfunctions. We therefore aimed to investigate in a non-clinical sample whether NRN1 gene contributes to the psychopathological profile, with a particular focus on the clinical dimensions previously related to the NRN1 gene (i.e. depressive and psychotic). Furthermore, we aimed to analyze: i) the role of NRN1 on executive functions, ii) whether the association between either NRN1-psychopathological profile or NRN1-cognitive performance is moderated by the BDNF gene., Methods: The sample comprised 410 non-clinical subjects who filled in the self-reported Brief Symptom Inventory (BSI) and were assessed for executive performance (Verbal Fluency, Wisconsin Card Sorting Test (WCST) and Letter-Number subscale (WAIS-III)). Genotyping included nine SNPs in NRN1 and one in BDNF., Results: i) GG homozygotes (rs1475157-NRN1) showed higher scores on BSI depressive dimension and on total scores compared to A carriers (corrected p-values: 0.0004 and 0.0003, respectively). ii) a linear trend was detected between GG genotype of rs1475157 and a worse cognitive performance in WCST total correct responses (uncorrected p-value: 0.029). iii) Interaction between rs1475157-NRN1 and Val66Met-BDNF was found to modulate depressive symptoms (p=0.001, significant after correction)., Limitations: Moderate sample size; replication in a larger sample is needed., Conclusions: NRN1 is associated with depressive symptoms and executive function in a non-clinical sample. Our results also suggest that the role of NRN1 seems to be modulated by BDNF., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Midline brain abnormalities might increase susceptibility to both first-episode and chronic mental disorder. Evidence of cavum vergae (CV) abnormality in mental disorders is scarce., Methods: The presence of CV was assessed by a researcher blind to clinical information in a cross-disorder sample of 639 patients with mood and psychotic disorders and in 223 healthy controls. Homogeneous magnetic resonance imaging methods of acquisition and assessment were applied., Results: Seven out of 639 patients with mood or psychotic disorders were detected with CV which corresponds to a prevalence of 1.1%. There were no concurrent cases of CV in the healthy control group. Identified cases which are briefly described were diagnosed from bipolar I disorder (n=2), delusional disorder (n=1), brief psychotic disorder (n=1) and schizoaffective disorder (n=3). Patients with CV had descriptively lower current IQ, executive functioning and memory scores in relation to patients without CV but this was not statistically significant., Limitations: Effects of medication and lack of statistical power of the CV patient group., Conclusions: Midline brain abnormalities, such as CV, might represent an unspecific risk factor for the development of severe mental disorders., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The Bipolar Depression Rating Scale (BDRS) arguably better captures symptoms in bipolar depression especially depressive mixed states than traditional unipolar depression rating scales. The psychometric properties of the Spanish adapted version, BDRS-S, are reported., Methods: The BDRS was translated into Spanish by two independent psychiatrists fluent in English and Spanish. After its back-translation into English, the BDRS-S was administered to 69 DSMI-IV bipolar I and II patients who were recruited from two Spanish psychiatric hospitals. The Hamilton Depression Rating Scale (HDRS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Young Mania Rating Scale (YMRS) were concurrently administered. 42 patients were reviewed via video by four psychiatrists blind to the psychopathological status of those patients. In order to assess the BDRS-S intra-rater or test-retest validity, 22 subjects were assessed by the same investigator performing two evaluations within five days., Results: The BDRS-S had a good internal consistency (Cronbach׳s α=0.870). We observed strong correlations between the BDRS-S and the HDRS (r=0.874) and MADRS (r=0.854) and also between the mixed symptom cluster score of the BDRS-S and the YMRS (r=0.803). Exploratory factor analysis revealed a three factor solution: psychological depressive symptoms cluster, somatic depressive symptoms cluster and mixed symptoms cluster., Limitations: A relatively small sample size for a 20-item scale., Conclusions: The BDRS-S provides solid psychometric performance and in particular captures depressive or mixed symptoms in Spanish bipolar patients., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The aim of this study was to compare serum BDNF levels of chronic schizophrenic patients, with or without deficit syndrome, and healthy controls. A comparative study of serum BDNF levels, determined by ELISA, was performed in 47 chronic patients with schizophrenia matched with 47 healthy controls. A part of the chronic schizophrenic sample was further divided into patients with a deficit (n=14) and a nondeficit syndrome (n=20), according to the Proxy for the Deficit Syndrome Scale. A significant difference was observed in decreased serum BDNF levels between chronic schizophrenia and healthy controls. No statistical significant differences in BDNF levels between deficit and nondeficit chronic schizophrenic patients were found. Our study confirms differences of serum BDNF levels of chronic schizophrenia and healthy controls, which correspond to the clinical progression of the disease. Our results do not support a relation between deficit profile in chronic schizophrenia and lower serum BDNF levels., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Traumatic events are frequent in bipolar patients and can worsen the course of the disease. Psychotherapeutic interventions for these events have not been studied so far. Twenty DSM-IV bipolar I and II patients with subsyndromal mood symptoms and a history of traumatic events were randomly assigned to Eye Movement Desensitization and Reprocessing therapy (n=10) or treatment as usual (n=10). The treatment group received between 14 and 18 Eye Movement Desensitization and Reprocessing sessions during 12 weeks. Evaluations of affective symptoms, symptoms of trauma and trauma impact were carried out by a blind rater at baseline, 2 weeks, 5 weeks, 8 weeks, 12 weeks and at 24 weeks follow-up. Patients in the treatment group showed a statistically significant improvement in depressive and hypomanic symptoms, symptoms of trauma and trauma impact compared to the treatment as usual group after intervention. This effect was only partly maintained in trauma impact at the 24 weeks follow-up visit. One patient dropped from Eye Movement Desensitization and Reprocessing group whereas four from the treatment as usual group. This pilot study suggests that Eye Movement Desensitization and Reprocessing therapy may be an effective and safe intervention to treat subsyndromal mood and trauma symptoms in traumatized bipolar patients., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Bipolar depression has been found to be associated with changes in prefrontal cortex activity during performance of cognitive tasks. However, the role of task-related de-activations has been little investigated., Method: Forty-one bipolar depressed patients and 41 matched normal controls underwent fMRI scanning while performing baseline, 1-back and 2-back versions of the n-back task. Linear models were used to obtain maps of within-group activations and areas of differential activation between the groups., Results: The bipolar depressed patients showed reduced activation in the dorsolateral prefrontal cortex (DLPFC) bilaterally and several other regions. After controlling for differences in task performance only differences in the DLPFC and cerebellum remained. Left DLPFC activation was inversely correlated with Hamilton and MADRS scores. The patients showed failure to de-activate in the medial prefrontal cortex, an area corresponding to the anterior medial node of the default mode network., Limitations: To confirm default mode network dysfunction demonstration of resting-state connectivity abnormalities would also be required. The study was carried out on treated patients, and did not assess for presence of depressive symptoms in the healthy controls., Conclusions: Both prefrontal cortical and default mode network dysfunction appear to characterise bipolar depression. The former, but not the latter, is associated with symptom severity., (Copyright © 2012 Elsevier B.V. All rights reserved.)