When a psychiatric disorder emerges during adolescence, it can affect the daily functioning and well-being of the entire family, including siblings. This study aimed to explore the impact of having a sibling with psychiatric disorders, regardless of the specific diagnosis, on well-being and perceived social support of young adults. A total of 86 participants (mean age 23 ± 2.59 and 80

BackgroundSelf-disorders constitute a core feature of the schizophrenia spectrum, including early stages such as first-episode psychosis (FEP). These disorders impact the minimal Self, or bodily self-consciousness, which refers to the basic, pre-reflective sense of embodied experience. The minimal Self is intrinsically linked to episodic memory, which captures specific past experiences of the Self. However, research on this relationship in the schizophrenia spectrum remains scarce. This pilot study aimed to investigate how the minimal Self modulated episodic memory of naturalistic events in FEP, using immersive virtual reality. A secondary objective was to examine the relationships between sense of Self, embodiment, episodic memory, schizotypal personality traits in healthy participants (CTL), and psychopathology in FEP.MethodsA full-body illusion was induced in 10 FEP and 35 matched CTL, using a first-person avatar, with synchronous or asynchronous visuomotor stimulation (strong or weak embodiment conditions, respectively). Following embodiment induction, participants navigated a virtual city and encountered naturalistic daily life events, which were incidentally encoded. Episodic memory of these events was assessed through a comprehensive recognition task (factual and contextual information, retrieval phenomenology). Sense of Self, schizotypal personality traits, and psychopathology were assessed via self-reported questionnaires or clinical assessments.ResultsSynchronous visuomotor stimulation successfully induced a stronger sense of embodiment in both FEP and CTL. The strong embodiment condition was associated with reduced perceived virtual space occupation by the body in FEP. Under strong embodiment, FEP performed significantly worse than CTL in contextual information recognition, but their ratings for retrieval phenomenology were comparable to CTL. Conversely, under weak embodiment, FEP performed similarly to CTL in contextual information recognition, but they rated retrieval phenomenology significantly lower. For CTL, we observed a slight, though non-significant, enhancement in recognition memory under strong compared to weak embodiment. Additionally, higher schizotypy in CTL correlated with a diminished sense of Self and poorer episodic memory.ConclusionsDisturbances in the minimal Self in FEP are associated with episodic memory impairments. These findings emphasise the importance of targeting minimal Self-disorders in schizophrenia spectrum disorders, since episodic memory impairments may negatively affect patients’ quality of life and psychosocial outcomes. Additionally, they support a fully dimensional model of schizotypy.

INTRODUCTION:Impairments in bottom-up perceptual processing have been associated to the age-related cognitive decline. Digital cognitive training focusing on bottom-up and/or top-down processes have been studied as a tool to remediate age-related cognitive decline. However, the most effective training type and order of application remain unclear. METHODS:One hundred and fifteen older adults were randomly assigned to 40 h of bottom-up then top-down or top-down then bottom-up digital cognitive training or an active control group. We evaluated cognition at baseline, after 20 h and 40 h of training and at follow-up using a mixed-model analysis. RESULTS:Global cognition improved, for the top-down group, after 20 h of training (p = 0.04; d = 0.7) and for all three groups after 40 h. The improvement in global cognition remained five months after the bottom-up/ top-down training (p = 0.009; d = 4.0). There were also improvements in the recall cognitive domain, after 20 h of training, for the bottom-up group and, after 40 h, for all three groups. Gains were observed in verbal fluency after 40 h of training for both therapeutic groups. Processing speed was significantly slower, after 20 h of training, for the control and bottom-up groups and, after 40 h, only for the control group. Emotion recognition improved, after 20 h, for the control group as compared to the therapeutic groups. CONCLUSIONS:These results indicate that the bottom-up/top-down training has the most endurable effects, which reveals the importance of the order of application of the exercises for gains in cognition in older adults.

Background.Cognitive impairment constitutes a prevailing issue in the schizophrenia spec-trum, severely impacting patients'functional outcomes. A global cognitive score, sensitive tothe stages of the spectrum, would benefit the exploration of potential factors involved in thecognitive decline.Methods.First, we performed principal component analysis on cognitive scores from 768individuals across the schizophrenia spectrum, including first-degree relatives of patients,individuals at ultra-high risk, who had a first-episode psychosis, and chronic schizophreniapatients, alongside 124 healthy controls. The analysis provided 10 g-factors as global cognitivescores, validated through correlations with intelligence quotient and assessed for their sensi-tivity to the stages on the spectrum using analyses of variance. Second, using the g-factors, weexplored potential mechanisms underlying cognitive impairment in the schizophrenia spec-trum using correlations with sociodemographic, clinical, and developmental data, and linearregressions with genotypic data, pooled through meta-analyses.Results.The g-factors were highly correlated with intelligence quotient and with each other,confirming their validity. They presented significant differences between subgroups along theschizophrenia spectrum. They were positively correlated with educational attainment and thepolygenic risk score (PRS) for cognitive performance, and negatively correlated with generalpsychopathology of schizophrenia, neurodevelopmental load, and the PRS for schizophrenia.Conclusions.The g-factors appeared as valid estimators of global cognition, enabling discern-ing cognitive states within the schizophrenia spectrum. Educational attainment and geneticsrelated to cognitive performance may have a positive influence on cognitive functioning, whilegeneral psychopathology of schizophrenia, neurodevelopmental load, and genetic liability toschizophrenia may have an adverse impact.

Abstract BackgroundA prosodic profile for people with schizophrenia has been previously empirically suggested. However, evidence remains inconclusive, particularly with regards to the possible links with psychopathology and the scarcity of substantial data on Italian-speaking individuals.MethodsWe quantified a large set of prosodic and voice quality features from a free speech task conducted with Italian-speaking individuals with and without schizophrenia (SCZ – 29; CTR – 29), using a fully automated pipeline. Moreover, in the SCZ group we thoroughly assessed psychopathology using the Thought Language and Communication scale (TLC), the Clinical Language Disorder Rating scale (CLANG), the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Examination of Anomalous Self Experience Scale (EASE) and the Autism Rating Scale (ARS).ResultsRelative to CTR, SCZ showed a different acoustic profile, with reduced speech rate and increased pause duration, fundamental frequency variability and breathy phonation. Temporal profile features were associated with most of the psychopathology tested, in particular with symptoms related to communication atypicalities but also to subjective experiences related to self and others. Other acoustic features related to pitch and intonation were associated with negative symptoms of schizophrenia and subjective experiences related to others.ConclusionsThis study shows for the first time significant differences in prosody and voice quality in Italian speaking people with schizophrenia, as compared to neurotypical controls. Moreover, significant relationships between speech acoustic profile and fine psychopathology were found. Future research should expand this approach to transdiagnostic and cross-linguistic samples, to test the specificity of the investigated patterns. This could pave the way to new therapeutic approaches.

Individuals with schizophrenia generally show difficulties in interpersonal communication. Linguistic analyses shed new light on speech atypicalities in schizophrenia. However, very little is known about conversational interaction management by these individuals. Moreover, the relationship between linguistic features, psychopathology, and patients’ subjectivity has received limited attention to date. We used a novel methodology to explore dyadic conversations involving 58 participants (29 individuals with schizophrenia and 29 control persons) and medical doctors. High-quality stereo recordings were obtained and used to quantify turn-taking patterns. We investigated psychopathological dimensions and subjective experiences using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Examination of Anomalous Self Experience scale (EASE), the Autism Rating Scale (ARS) and the Abnormal Bodily Phenomena questionnaire (ABPq). Different turn-taking patterns of both patients and interviewers characterised conversations involving individuals with schizophrenia. We observed higher levels of overlap and mutual silence in dialogues with the patients compared to dialogues with control persons. Mutual silence was associated with negative symptom severity; no dialogical feature was correlated with anomalous subjective experiences. Our findings suggest that individuals with schizophrenia display peculiar turn-taking behaviour, thereby enhancing our understanding of interactional coordination in schizophrenia.

BACKGROUND:Treatment resistance is a major challenge in psychiatric disorders. Early detection of potential future resistance would improve prognosis by reducing the delay to appropriate treatment adjustment and recovery. Here, we sought to determine whether neurodevelopmental markers can predict therapeutic response. METHODS:Healthy controls (N = 236), patients with schizophrenia (N = 280) or bipolar disorder (N = 78) with a known therapeutic outcome, were retrospectively included. Age, sex, education, early developmental abnormalities (obstetric complications, height, weight, and head circumference at birth, hyperactivity, dyslexia, epilepsy, enuresis, encopresis), neurological soft signs (NSS), and ages at first subjective impairment, clinical symptoms, treatment, and hospitalization, were recorded. A supervised algorithm leveraged NSS and age at first clinical signs to classify between resistance and response in schizophrenia. RESULTS:Developmental abnormalities were more frequent in schizophrenia and bipolar disorder than in controls. NSS significantly differed between controls, responsive, and resistant participants with schizophrenia (5.5 ± 3.0, 7.0 ± 4.0, 15.0 ± 6.0 respectively, p = 3 × 10-10) and bipolar disorder (5.5 ± 3.0, 8.3 ± 3.0, 12.5 ± 6.0 respectively, p < 1 × 10-10). In schizophrenia, but not in bipolar disorder, age at first subjective impairment was three years lower, and age at first clinical signs two years lower, in resistant than responsive subjects (p = 2 × 10-4 and p = 9 × 10-3, respectively). Age at first clinical signs and NSS accurately predicted treatment response in schizophrenia (area-under-curve: 77 ± 8%, p = 1 × 10-14). CONCLUSIONS:Neurodevelopmental features such as NSS and age of clinical onset provide a means to identify patients who may require rapid treatment adaptation.

Background: Digital cognitive training can remediate cognitive deficits present in schizophrenia. However, limited motivation and engagement may impact adherence to training. Therefore, identifying factors that may enhance (facilitators) or decrease (barriers) engagement in digital cognitive training and possibly modulate its effects are of great clinical relevance.Methods: We measured cognition, symptom severity, motivation (semi-structured interview), and engagement (adapted Utrecht Work Engagement Scale -UWES) of 27 patients with schizophrenia after a 40-h digital cognitive training. The interview transcript quotes were coded and categorized into facilitators and barriers. Thereafter, we tested the association of motivation and engagement with changes in cognition and symptoms after training.Results: The facilitator 'good performance' and the barrier 'difficult exercise' were associated with larger gains in attention (p = 0.03) and reasoning and problem solving (p = 0.02), respectively. 'Poor performance' was associated with smaller gains in global cognition (p < 0.01), attention (p = 0.03), and working memory (p = 0.02). The facilitator 'welcoming setting' was associated with larger reductions in the negative (p = 0.01) and total (p = 0.01) symptoms measured by the Positive and Negative Syndrome Scale. The UWES engagement scale was associated with different facilitators and barriers that emerged from the interview, an indication of con-sistency among both qualitative and quantitative assessments.Discussion: Using a mixed quantitative and qualitative research design, we showed associations between moti-vation and engagement and the response to digital cognitive training in schizophrenia. Facilitators and barriers were associated with engagement, gains in cognition, and reduced symptoms after the intervention, providing insights on how to increase engagement in the digital cognitive training delivered to subjects with schizophrenia.

IntroductionFolates, the main actors in one-carbon (C1) metabolism, are involved in synthesising monoamines and maintaining genomic stability. Previous studies support the association between C1 metabolism and schizophrenia. The main purpose of this study was to assess the prevalence of plasma folate, and/or vitamin B12 deficiencies and hyperhomocysteinemia in young patients with psychotic disorders.MethodsWe included young inpatients (15–30 years old) with psychosis between 2014 and 2017 from Sainte-Anne Hospital in Paris. Plasma folate, vitamin B12 deficiency and homocysteinemia dosages were done at admission. Clinical data were extracted retrospectively, and patients diagnosed with a first-episode psychosis (FEP), schizophrenia, schizoaffective disorder, or persistent delusional disorder were retained for the analysis.ResultsAmong the 334 inpatients, 188 (56%) had C1 dosages available (135 males; 53 females). From the 188 patients, 32% had a C1 abnormality. This abnormality reached 38% of FEP patients. The most frequent abnormality was folate deficiency: 21% of all patients and 27% of FEP. Lower levels of folates were found in males compared to females (p = 0.02) and were correlated with more severe disorder, as assessed by Clinical Global Impression – Severity (CGI-S; p = 0.009). Antipsychotic dosage was positively associated with B12 levels (p = 0.013) and negatively with homocysteinemia (p = 0.034).ConclusionOne-carbon metabolism anomalies in young patients with psychotic disorders are highly prevalent, reaching almost half of the patients with FEP. Potential protective effects from females and antipsychotics have emerged. These results spotlight the need for new therapeutic prospects, such as folate supplementation, to achieve personalised medical approaches to the early stages of psychotic disorders.

IntroductionThe locus coeruleus-noradrenaline (LC-NA) system is involved in a wide range of cognitive functions and may be altered in schizophrenia. A non-invasive method to indirectly measure LC activity is task-evoked pupillary response. Individuals with schizophrenia present reduced pupil dilation compared to healthy subjects, particularly when task demand increases. However, the extent to which alteration in LC activity contributes to schizophrenia symptomatology remains largely unexplored. We aimed to investigate the association between symptomatology, cognition, and noradrenergic response in individuals with schizophrenia.MethodsWe assessed task-evoked pupil dilation during a pro- and antisaccade task in 23 individuals with schizophrenia and 28 healthy subjects.ResultsBoth groups showed similar preparatory pupil dilation during prosaccade trials, but individuals with schizophrenia showed significantly lower pupil dilation compared to healthy subjects in antisaccade trials. Importantly, reduced preparatory pupil dilation for antisaccade trials was associated with worse general symptomatology in individuals with schizophrenia.DiscussionOur findings suggest that changes in LC-NA activity – measured by task-evoked pupil dilation – when task demand increases is associated with schizophrenia symptoms. Interventions targeting the modulation of noradrenergic responses may be suitable candidates to reduce schizophrenia symptomatology.

Background: Neuroscience-informed cognitive training has been used to remediate cognitive deficits in schizo-phrenia, but their effect on emotion processing and social cognition deficits, which may involve auditory and visual impairments, remain relatively unknown. In this study, we compared the efficacy of auditory versus visual neuroscience-informed cognitive training on emotion processing and social cognition in individuals with schizophrenia. Methods: In this randomised, double-blind clinical trial, 79 participants with chronic schizophrenia performed 40-hours auditory or visual dynamically equivalent computerised cognitive training. We assessed emotion processing and social cognition using Emotion Recognition, Affective Go-NoGo, Mayer-Salovey-Caruso Emotional-Intelligence, Theory of mind, and Hinting tests before and after 20 h and 40 h of training. Results: After training, participants from both groups decreased their reaction time for facial emotion recognition (p = 3 x 10(-6), d = 0.9). This was more remarkable for the auditory group when analysing individual emotions. Both groups also reduced omissions in the affective go-no go (p = 0.01, d = 0.6), which was also attributed, post hoc, to the auditory group. Trends for improvement were observed in theory of mind (p = 0.06, d = 0.6) for both groups. Improvement in emotion processing was associated with improvement in reasoning and problem solving and global cognition and improvement in theory of mind was associated with improvement in attention and global cognition. Conclusions: Both the auditory and the visual neuroscience-informed cognitive training were efficacious at improving emotion processing and social cognition in individuals with schizophrenia, although improvement was more remarkable for the auditory training group. These improvements were related to cognitive - but not symptom - improvement.

Studies indicate that neuroscience-informed digital cognitive training can remediate cognitive impairments in schizophrenia, but the factors contributing to these deficits and response to treatment remain unclear. Toxoplasma gondii is a neuroinvasive parasite linked to cognitive decline that also presents a higher prevalence in schizophrenia. Here, we compared the cognition and symptom severity of IgG seropositive (TOXO+; n = 25) and seronegative (TOXO−; n = 35) patients who participated in a randomized controlled trial of digital cognitive training. At baseline, TOXO+ subjects presented lower global cognition than TOXO− ( F = 3.78, p = 0.05). Specifically, TOXO+ subjects showed worse verbal memory and learning ( F = 4.48, p = 0.03), social cognition ( F = 5.71, p = 0.02), and higher antibody concentrations were associated with increased negative ( r = 0.42, p = 0.04) and total ( r = 0.40, p = 0.04) schizophrenia symptoms. After training, the TOXO+ group showed higher adherence to the intervention ( X 2 = 9.31, p = 0.03), but there were no differences in changes in cognition and symptoms between groups. These findings highlight the association between seropositivity to T. gondii and deteriorated cognition and symptoms in schizophrenia. Further research is needed to assess the specific efficacy of digital cognitive training on this population.

Carver and White's Behavioral Inhibition System (BIS)/ Behavioral Activation System (BAS) questionnaire is the most commonly used instrument in the domain of motivation. The BIS refers to behaviors associated to punishment avoidance and the BAS refers to behaviors related to reward. The main goal of this study was to translate and validate the BIS/BAS scale to Brazilian Portuguese. First, we translated the questionnaire to Brazilian Portuguese and twelve proficient bilingual volunteers responded to both versions of the questionnaire. Thereafter, we validated the Brazilian Portuguese version of the questionnaire using an online platform that also collected data on sex, age, years of education and occupational status (n = 568). The Confirmatory Factor Analyses showed a better fit with a five- rather than a four-factor model. The eigenvalues of the Principal Component Analysis showed a five-factor solution, grouping factors within the following subscales: BIS anxiety, BIS fear, BAS drive, BAS reward responsiveness and BAS fun seeking. The convergent and discriminant validity was observed as expected: the BIS correlated with Negative affect and the BAS correlated with Positive affect. The relationship between the TIPI and the BIS/BAS questionnaire suggests that the BAS fun seeking has features of impulsivity and the BIS Fear has features of neuroticism (n = 229). The questionnaire showed stability over a period of one month (n = 45). Results demonstrated a good adaptability of the BIS/BAS scale in the Brazilian population and revealed the importance instrument in the field of motivation.

Schizophrenia typically emerges during adolescence, with progression from an ultra-high risk state (UHR) to the first episode of psychosis (FEP) followed by a chronic phase. The detailed pathophysiology of schizophrenia and the factors leading to progression across these stages remain relatively unknown. The current treatment relies on antipsychotics, which are effective for FEP and chronic schizophrenia but ineffective for UHR patients. Antipsychotics modulate dopaminergic and glutamatergic neurotransmission, inflammation, oxidative stress, and membrane lipids pathways. Many of these biological pathways intercommunicate and play a role in schizophrenia pathophysiology. In this context, research of preventive treatment in early stages has explored the antipsychotic effects of omega-3 supplementation in UHR and FEP patients. This review summarizes the action of omega-3 in various biological systems involved in schizophrenia. Similar to antipsychotics, omega-3 supplementation reduces inflammation and oxidative stress, improves myelination, modifies the properties of cell membranes, and influences dopamine and glutamate pathways. Omega-3 supplementation also modulates one-carbon metabolism, the endocannabinoid system, and appears to present neuroprotective properties. Omega-3 has little side effects compared to antipsychotics and may be safely prescribed for UHR patients and as an add-on for FEP patients. This could to lead to more efficacious individualised treatments, thus contributing to precision medicine in psychiatry.

The objective of this study is to determine whether cannabis influences BDNF levels in patients with psychosis (FEP) and healthy volunteers (HV) to help understand the role of BDNF in psychosis. We assessed the association between BDNF and cannabis in a cohort of FEP antipsychotic-naïve patients and HV, whilst controlling for other potential confounding factors. 70 FEP drug-naive patients and 57 HV were recruited. A sociodemographic variable collection, structured clinical interview, weight and height measurement, substance use determination, and blood collection to determine BDNF levels by ELISA analysis were done. In FEP patients, cannabis use was associated with BDNF levels (high cannabis use was associated with lower BDNF levels). Moreover, cannabis use was statistically significantly associated with age (high use of cannabis was associated with younger age). In HV, no relationship between cannabis use and BDNF levels was observed. Otherwise, cannabis use was significantly associated with tobacco use, so that high cannabis users were also high tobacco users. This study showed a different association between cannabis use and BDNF levels in FEP patients compared with HV, particularly, with high doses of cannabis. These findings may help understand the deleterious effects of cannabis in some vulnerable individuals, as well as discrepancies in the literature.