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The concept of ultra-high risk for psychosis (UHR) has been at the forefront of psychiatric research for several decades, with the ultimate goal of preventing the onset of psychotic disorder in high-risk individuals. Orygen (Melbourne, Australia) has led a range of observational and intervention studies in this clinical population. These datasets have now been integrated into the UHR 1000+ cohort, consisting of a sample of 1,245 UHR individuals with a follow-up period ranging from 1 to 16.7 years. This paper describes the cohort, presents a clinical prediction model of transition to psychosis in this cohort, and examines how predictive performance is affected by changes in UHR samples over time. We analyzed transition to psychosis using a Cox proportional hazards model. Clinical predictors for transition to psychosis were investigated in the entire cohort using multiple imputation and Rubin's rule. To assess performance drift over time, data from 1995-2016 were used for initial model fitting, and models were subsequently validated on data from 2017-2020. Over the follow-up period, 220 cases (17.7%) developed a psychotic disorder. Pooled hazard ratio (HR) estimates showed that the Comprehensive Assessment of At-Risk Mental States (CAARMS) Disorganized Speech subscale severity score (HR=1.12, 95% CI: 1.02-1.24, p=0.024), the CAARMS Unusual Thought Content subscale severity score (HR=1.13, 95% CI: 1.03-1.24, p=0.009), the Scale for the Assessment of Negative Symptoms (SANS) total score (HR=1.02, 95% CI: 1.00-1.03, p=0.022), the Social and Occupational Functioning Assessment Scale (SOFAS) score (HR=0.98, 95% CI: 0.97-1.00, p=0.036), and time between onset of symptoms and entry to UHR service (log transformed) (HR=1.10, 95% CI: 1.02-1.19, p=0.013) were predictive of transition to psychosis. UHR individuals who met the brief limited intermittent psychotic symptoms (BLIPS) criteria had a higher probability of transitioning to psychosis than those who met the attenuated psychotic symptoms (APS) criteria (HR=0.48, 95% CI: 0.32-0.73, p=0.001) and those who met the Trait risk criteria (a first-degree relative with a psychotic disorder or a schizotypal personality disorder plus a significant decrease in functioning during the previous year) (HR=0.43, 95% CI: 0.22-0.83, p=0.013). Models based on data from 1995-2016 displayed good calibration at initial model fitting, but showed a drift of 20.2-35.4% in calibration when validated on data from 2017-2020. Large-scale longitudinal data such as those from the UHR 1000+ cohort are required to develop accurate psychosis prediction models. It is critical to assess existing and future risk calculators for temporal drift, that may reduce their utility in clinical practice over time.

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OBJECTIVE: The study aimed to determine clinical indicators that could be used to differentiate between patients diagnosed with substance-induced psychotic disorder (SIPD) and patients diagnosed with schizophrenia by comparing their psychotic symptoms and theory of mind (ToM). METHODS: The study included 43 male patients diagnosed with schizophrenia according to DSM-5 criteria and 43 male patients diagnosed with SIPD. The patients were administered the Sociodemographic and Clinical Data Form, Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms (SANS), Psychotic Symptom Evaluation Scale (PSYRATS), and Reading the Mind in the Eyes Test (RMET). RESULTS: In patients diagnosed with schizophrenia, the scores on SAPS subscales for structural thought disorder and bizarre behavior, as well as SANS total scores, were significantly higher compared to patients diagnosed with SIPD (z=2.679, p=0.007; z=2.984, p=0.003; z=6.916, p<0.001). The scores for recognizing negative and neutral expressions on the RMET were significantly higher in patients with SIPD than in patients with schizophrenia (z=3.540; p<0.001; z=4.404, p<0.001). It was found that as the scores on the SANS total and Affect Blunting or Flattening subscale, as well as the scores on the SAPS Bizarre Behavior subscale decrease, the probability of having SIPD increases. CONCLUSION: In patients diagnosed with SIPD, there are fewer disorganized and negative symptoms compared to patients diagnosed with schizophrenia. Patients with SIPD can recognize negative and neutral expressions better than patients with schizophrenia. When making a differential diagnosis between SIPD and schizophrenia, as blunting in affect, total negative symptoms, and severity of bizarre behavior decrease, the probability of being diagnosed with SIPD increases relative to the probability of being diagnosed with schizophrenia.

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We present the case of a 35-year-old female patient admitted to the hospital with symptoms of rapidly increasing disturbances of consciousness and fever for 48 hours. A lumbar puncture, bacteriological and virological examinations, and initial imaging studies did not show abnormalities. Brain magnetic resonance imaging (MRI), repeated several times, showed hyperintense confluent lesions in both temporal lobes and atrophy of both hippocampi. General examination, cerebrospinal fluid culture, the panel of antineuronal antibodies, and tumor markers remained negative on subsequent repeats. Despite several laboratory and imaging studies, the etiology of the disease could not be established, infections were excluded, and no autoantibodies were found. A diagnosis of probable limbic encephalitis, amnestic syndrome resulting from organic brain damage, and drug-resistant epilepsy was made. The patient, with limbic encephalitis complicated by drug-resistant status epilepticus, was treated with cycles of immunoglobulin and subsequent plasmapheresis. She was then transferred to the Department of Psychiatry for diagnosis and treatment of intermittent psychotic disorders. During hospitalization, the patient was observed to have multiple epileptic seizures with temporal and frontal morphology, amnestic syndrome with confabulations, and periodic psychotic disorders with the occurrence of visual hallucinations. Antiepileptic treatment was escalated by including cenobamate in increasing doses. To control the mental disorders, duloxetine, tiapride, and cognitive function exercises were introduced. There was a slight improvement in memory, a cessation of confabulations, and an emergence of the patient's criticism of the symptoms presented. The psychotic symptoms subsided, and the number of epileptic seizures decreased. The described case portrays a unique co-occurrence of disease symptoms that are difficult to treat. It shows the therapeutic difficulties that can occur in patients with suspected autoimmune encephalitis. Furthermore, it shows the need for multispecialty care of a patient with psychotic symptoms in the course of epilepsy accompanied by amnestic syndrome.

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BACKGROUND: Psychotic experiences are thought to emerge from various interrelated patterns of disrupted belief updating, such as overestimating the reliability of sensory information and misjudging task volatility. Yet, these substrates have never been jointly addressed under one computational framework and it is not clear to what degree they reflect trait-like computational patterns. METHODS: We introduced a novel hierarchical Bayesian model that describes how individuals simultaneously update their beliefs about the task volatility and noise in observation. We applied this model to data from a modified Predictive inference task in a test-retest study with healthy volunteers (N=45, 4 sessions) and examined the relationship between model parameters and schizotypal traits in a larger online sample (N = 437) and in a cohort of patients with schizophrenia (N = 100). RESULTS: The interclass correlations were moderate to high for model parameters and excellent for averaged belief trajectories and precision-weighted learning rates estimated through hierarchical Bayesian inference. We found that uncertainty about the task volatility was related to schizotypal traits and to positive symptoms in patients, when learning to gain rewards. In contrast, negative symptoms in patients were associated with more rigid beliefs about observational noise, when learning to avoid losses. CONCLUSION: These findings suggest that individuals with schizotypal traits across the psychosis continuum are less likely to learn or utilize higher-order statistical regularities of the environment and showcase the potential of clinically relevant computational phenotypes for differentiating symptom groups in a transdiagnostic manner.

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This review focuses on late-onset schizophrenia and schizophrenia-like psychosis with very late onset (VLOSLP) with focus on their psychopathologic, neuropsychologic, and neurobiologic aspects. A literature review on late-onset schizophrenia and VLOSLP was conducted based on publications from PubMed, Scopus, and Google Scholar databases up to December 2023. It may be noted that research into schizophrenia has largely focused on early-onset patients, and research into the mental health of older people has focused primarily on dementia and depression, with relatively little information on late-onset schizophrenia and VLOSLP. The nosology of late-onset functional psychoses is still poorly understood. There is currently no consensus on the diagnostic framework for psychosis labeled by the term VLOSLP. These deficiencies need to be addressed in order to understand the background of VLOSLP, the course and prognosis of the illness, and to develop successful management and treatment strategies for these patients, as older adults are more susceptible to the adverse effects of psychotropic medications. Therapy should be holistic, including not only medication but also psychotherapy, and the key role of caregivers of elderly schizophrenia patients should be taken into account. There should be judicious use of pharmacotherapy with an assessment of its risks and benefits.

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Background and Hypothesis: When occurring in adolescence, psychotic experiences (PE), subclinical psychotic symptoms, can be an early marker of mental illnesses. Studies with high-risk populations for psychosis show that anxiety symptoms often precede the onset of psychosis. Although anxiety symptoms are frequently experienced across the continuum of psychosis, no previous study has analyzed this association using a cross-lagged panel model (CLPM) longitudinally to identify if anxiety can be a predictor of PE over time or vice versa. The aim of the current study was to investigate whether one symptom domain predicts the other over time. Study Design: 2194 children from the Brazilian High-Risk Cohort (BHRC) were evaluated at baseline (T 0), and 76.5% completed a 3-year follow-up (T 1) interview. Childhood anxiety symptoms and PE were assessed using a standardized self-report questionnaire at both time points. Cross-lagged panel models evaluated time-lagged associations between PE and anxiety longitudinally. Study Results: Higher levels of anxiety in childhood predicted an increase in PE levels in adolescence. The cross-lagged effect of anxiety scores at T 0 on PE scores at T 1 was significant (ß = .03, SE = 0.01, P ≤ .001) and PE in childhood did not increase levels of anxiety in adolescence, when controlling for sociodemographic and clinical characteristics. Conclusions: Our findings reinforce that anxiety may represent an early marker of psychosis proneness, not a consequence of already presenting PE, which can help to develop better screening approaches. Therefore, future studies should focus on identifying biological or other clinical markers to increase prediction accuracy.

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Substance use disorders (SUDs) are complex biopsychosocial diseases that cause neurocognitive deficits and neurological impairments by altering the gene expression in reward-related brain areas. Repeated drug use gives rise to alterations in DNA methylation, histone modifications, and the expression of microRNAs in several brain areas that may be associated with the development of psychotic symptoms. The first section of this review discusses how substance use contributes to the development of psychotic symptoms via epigenetic alterations. Then, we present more evidence about the link between SUDs and brain epigenetic alterations. The next section presents associations between paternal and maternal exposure to substances and epigenetic alterations in the brains of offspring and the role of maternal diet in preventing substance-induced neurological impairments. Then, we introduce potential therapeutic agents/approaches such as methyl-rich diets to modify epigenetic alterations for alleviating psychotic symptoms or depression in SUDs. Next, we discuss how substance use-gut microbiome interactions contribute to the development of neurological impairments through epigenetic alterations and how gut microbiome-derived metabolites may become new therapeutics for normalizing epigenetic aberrations. Finally, we address possible challenges and future perspectives for alleviating psychotic symptoms and depression in patients with SUDs by modulating diets, the epigenome, and gut microbiome.

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BACKGROUND AND HYPOTHESIS: Young people (YP) with psychotic experiences (PE) have an increased risk of developing a psychiatric disorder. Therefore, knowledge on continuity of care from child and adolescent (CAMHS) to adult mental health services (AMHS) in relation to PE is important. Here, we investigated whether the self-reported trajectories of persistent PE were associated with likelihood of transition to AMHS and mental health outcomes. STUDY DESIGN: In this prospective cohort study, interviews and questionnaires were used to assess PE, mental health, and service use in 763 child and adolescent mental health service users reaching their service's upper age limit in 8 European countries. Trajectories of self-reported PE (3 items) from baseline to 24-month follow-up were determined using growth mixture modeling (GMM). Associations were assessed with auxiliary variables and using mixed models. Study results. At baseline, 56.7% of YP reported PE. GMM identified 5 trajectories over 24 months: medium increasing (5.2%), medium stable (11.7%), medium decreasing (6.5%), high decreasing (4.2%), and low stable (72.4%). PE trajectories were not associated with continuity of specialist care or transition to AMHS. Overall, YP with PE reported more mental health problems at baseline. Persistence of PE or an increase was associated with poorer outcomes at follow-up. CONCLUSIONS: PE are common among CAMHS users when reaching the upper age limit of CAMHS. Persistence or an increase of PE was associated with poorer mental health outcomes, poorer prognosis, and impaired functioning, but were less discriminative for continuity of care.

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BACKGROUND: The ability to value rewards is crucial for adaptive behavior and is influenced by the time and effort required to obtain them. Impairments in these computations have been observed in patients with schizophrenia and may be present in individuals with subclinical psychotic symptoms (PS). METHODS: In this study, we employed delay and effort-discounting tasks with food rewards in thirty-nine participants divided into high and low levels of PS. We investigated the underlying mechanisms of effort-discounting through computational modelling of dopamine prefrontal and subcortical circuits and the electrophysiological biomarker of both delay and effort-discounting alterations through resting-state frontal alpha asymmetry (FAA). RESULTS: Results revealed greater delay discounting in the High PS group compared to the Low PS group but no differences in the effort discounting task. However, in this task, the same levels of estimated dopamine release were associated with a lower willingness to exert effort for high-calorie food rewards in High PS participants compared to Low PS participants. Although there were no significant differences in FAA between the High PS and Low PS groups, FAA was significantly associated with the severity of participants' negative symptoms. CONCLUSIONS: Our study suggests that the dysfunction in temporal and effort cost computations, seen in patients with schizophrenia, may be present in individuals with subclinical PS. These findings provide valuable insight into the early vulnerability markers (behavioral, computational, and electrophysiological) for psychosis, which may aid in the development of preventive interventions. These findings are preliminary and warrant further investigation.

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Psychosis can be considered a dimension that in its most severe extreme can be expressed with alterations in sensory perception, mainly hallucinations. Their presence is a fact that is frequently observed in severe psychiatric pathologies such as schizophrenia (EZQ) and bipolar disorder (BD) where they can be markers of severity. However, sensory-perceptual disturbances are not pathognomonic of these disorders, nor do they signal any of these illnesses as an isolated event. Such symptomatology can be described in a variety of situations both within and outside psychopathology. In this sense, proposing a direct line between hallucinations and diseases such as CZS or TB disregards their occurrence in other pathologies, as is the case of Borderline Personality Disorder (BPD). It is feasible that we may find the expression of pseudo hallucinations or hallucinations in patients with this disorder and their presence may have etiological, clinical and therapeutic connotations that should be reviewed and taken into account in our clinical practice.

La psicosis puede ser considerada una dimensión que en su extremo de mayor gravedad puede expresarse con alteraciones en la sensopercepción, principalmente alucinaciones. Su presencia es un hecho que se constata con frecuencia en patologías psiquiátricas severas como la esquizofrenia (EZQ) y el trastorno bipolar (TB) donde pueden ser marcadores de gravedad. No obstante, las alteraciones sensoperceptivas no son patognomónicas de estos trastornos ni señalan ninguna de estas enfermedades como un hecho aislado. Dicha sintomatología puede ser descripta en diversas situaciones dentro y fuera de la psicopatología. En este sentido, proponer una línea directa entre las alucinaciones con enfermedades tales como la EZQ o el TB desestima su ocurrencia en otras patologías, como es el caso del Trastorno límite de la personalidad (TLP). Es factible que constatemos la expresión de alucinaciones en pacientes con este trastorno y su presencia puede tener connotaciones etiológicas, clínicas y terapéuticas que deben ser revisadas para tener en cuenta en nuestra práctica clínica.

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Cross-sectional research suggests an association between loneliness and psychotic symptoms, but the causal direction of this association is still unclear. Even though loneliness has been proposed as a potential treatment target to improve psychotherapy for psychosis, not much is known about its role in the treatment process. In this study, we re-analyzed data from a therapy process study to investigate the temporal dynamics between loneliness and psychotic symptoms throughout therapy and to explore whether state-of-the-art CBT for psychosis (CBTp) decreases loneliness. Over the course of up to 45 weekly sessions of CBTp, 57 patients reported their feelings of loneliness and current positive, negative and depressive symptom levels at each session. Multilevel regression revealed a reduction in all symptoms over time, but no reduction in loneliness. Time-lagged multilevel regression showed that loneliness predicted subsequent negative and depressive symptoms, whereas positive symptom levels predicted subsequent loneliness. Thus, changes in loneliness seem to be both cause and consequence of psychotic symptom changes. These findings highlight the importance of loneliness as a treatment target, particularly in patients with negative symptoms and depression. Future research should address loneliness-specific interventions as an augmentation of state-of-the-art CBTp.

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BACKGROUND: Coercive measures have been applied in mental health fields throughout history, denying people with mental illness the ability to decide, even though there is increasing evidence that these measures bring few benefits to these individuals. OBJECTIVE: The objective of this study was to analyse the sociodemographic and clinical characteristics most likely associated with the use of mechanical restraints (MRs) in psychiatric hospital settings. DESIGN, SETTINGS AND PARTICIPANTS: This was a descriptive, comparative and analytical cross-sectional study in people with mental disorders who were hospitalized in two hospitals in the Autonomous Valencian Community (Spain). We included a total of 91 participants who completed the Scale to Assess Unawareness of Mental Disorder (SUMD), Positive and Negative Syndrome Scale (PANSS), Barrat's Impulsiveness Scale and the Hamilton Anxiety Scale. RESULTS: The results we collected indicated that the patients most likely to be mechanically restrained were younger people with less awareness of their symptoms and disease, previous admissions to a psychiatric hospital and cohabitation with parents and/or family. In addition, having been admitted involuntarily, previously having had MRs applied, presenting more positive psychotic symptoms and habitual caffeine consumption all predicted the use of MRs. CONCLUSIONS: The variables that were able to predict MR were involuntary admission, previous use of MR, the presence of positive psychotic symptoms and caffeine consumption. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Evaluation of the sociodemographic and clinical characteristics of patients can help health professionals, especially nurses, to recognize patients who are at risk of requiring MR. This allows mental health practitioners to take these factors into account during interventions or when implementing programmes designed to reduce the use of coercive measures in psychiatric hospital settings. IMPACT: What problem did the study address? Coercive measures have been applied in mental health fields throughout history, with no benefits to these patients. What were the main findings? There are studies that relate some variables to MR in psychiatric settings, but we have been able to find variables capable of predicting MR such as involuntary admission, previous use of MR, the presence of positive psychotic symptoms and caffeine consumption. Where and on whom will the research have an impact? The findings of this study allow for the reduction of MRs in psychiatric units. The sociodemographic and clinical characteristics found to be related to MR will help professionals identify when a patient is admitted in order to use specific interventions aimed at preventing the use of MRs during admission. This is the first study to indicate a relationship between caffeine consumption and the use of MRs. Further studies will be necessary to verify if controlled caffeine supplementation during admission to psychiatric units could become an additional strategy contributing to preventing the application of MR specifically in individuals who habitually consume coffee or caffeine-containing beverages daily. REPORTING METHOD: We have adhered to relevant EQUATOR guidelines using the STROBE reporting method. PATIENT CONTRIBUTION: No patient or public contribution.

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OBJECTIVE: To evaluate the association between cannabis use during pregnancy and the risk for long-term neuropsychiatric pathology in the offspring. DATA SOURCES: MEDLINE, EMBASE, and Cochrane library databases were systematically searched until January 22, 2024, with no language or date restrictions. STUDY ELIGIBILITY CRITERIA: Studies were eligible for inclusion if they reported quantitative data on any long-term neuropsychiatric outcome in offspring whose mothers used cannabis during pregnancy for medical or recreational use, by any route and at any trimester, in comparison to offspring of women who abstained from cannabis use during pregnancy. All observational study designs were included in the analysis. STUDY APPRAISAL AND SYNTHESIS METHODS: A systematic review and meta-analysis were performed according to the PRISMA and MOOSE guidelines. The data was extracted independently by 2 reviewers. The following offspring outcomes were of interest: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), depression, anxiety, psychotic disorders, as well as cannabis and other substance use. Odds ratios (OR) and 95% confidence intervals (CI) were pooled for each neuropsychiatric outcome in the offspring of women exposed to cannabis during pregnancy compared with nonexposed. Data were pooled using random-effects models. RESULTS: Eighteen eligible observational studies were included in the systematic review, and 17 were included in the final quantitative analysis, representing 534,445 participants. After adjusting for confounders, the pooled OR for ADHD was 1.13 (95% CI 1.01-1.26); for ASD, the pooled OR was 1.04 (95% CI 0.74-1.46); for psychotic symptoms, the pooled OR was 1.29 (95% CI 0.97-1.72); for anxiety, the pooled OR was 1.34 (95% CI 0.79-2.29); for depression, the pooled OR was 0.72 (95% CI 0.11-4.57); and for offspring's cannabis use, the pooled OR was 1.20 (95% CI 1.01-1.42). CONCLUSION: Prenatal cannabis exposure is not associated with an increased risk of ASD, psychotic symptoms, anxiety, or depression in offspring. However, it may slightly elevate the risk of ADHD and predispose offspring to cannabis consumption. Despite these findings, caution is warranted regarding cannabis use during pregnancy. Further research is imperative, especially given the increasing potency of cannabis in recent years.

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BACKGROUND: Neurocognitive impairment is a core feature of schizophrenia spectrum disorders (SSDs), and the relationship between cognition and symptoms in SSDs has been widely researched. Negative symptoms are related to a wide range of cognitive impairments; however, the aspects of negative symptoms that underpin this relationship have yet to be specified. STUDY DESIGN: We used iterative Constrained Principal Component Analysis (iCPCA) to explore the relationship between 18 cognitive measures (including processing speed, attention, working, spatial and verbal memory and executive functions) and 46 symptoms in schizophrenia at the individual item level while minimizing the risk of Type I errors. ICPCA was conducted on a sample of SSD patients in the early stages of psychiatric treatment (n = 121) to determine the components of cognition overlapping with symptoms measured by the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS). RESULTS: We found that a verbal memory component was associated with items from SANS and SAPS related to impoverished and disorganized emotional communication, language, and thought. In contrast, a working memory component was associated with SANS items related to motor system impoverishment. CONCLUSIONS: The iCPCA allowed us to explore the associations between individual items, optimized to understand the overlap between symptoms and cognition. The specific symptoms linked to verbal and working memory impairments imply distinct brain networks, which further investigation may lead to our deeper understanding of the illness and the development of treatment methods.

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PURPOSE: to study sex differences in self-reported symptoms measured with the Scale of Patient-Reported Impact of Symptoms in Schizophrenia (PRISS), to investigated sex differences in the degree of agreements between self-reported symptoms and clinical symptoms assessed by professionals, and to identify which clinical and sociodemographic variables predicted a greater presence of self-reported symptoms split by sex. METHODS: 161 patients (37 females; 124 males), aged between 18 and 65 years, with a diagnosis of schizophrenia assisted in non-acute mental health services at four mental health catchment areas in Andalucia and Catalonia were included. The PRISS scale was administered to asses self-reported symptoms. RESULTS: males reported higher presence of excitement, grandiosity, motor retardation and poor attention) than women. There was less agreement in the presence of psychotic symptoms in men than in women when comparing self-reported symptoms and clinical symptoms assessed by professionals. Finally, in men the predictors variables for the greater presence of self-perceived symptoms were greater psychotic symptomatology and more disability, while in women were greater presence of alogia and higher doses of chlorpromazine. CONCLUSIONS: Assessing and being aware of the self-perceived symptoms of patients with schizophrenia should be considered in the clinic, especially in men, as there appears to be a lack of agreement on certain items. This would allow treatments to be more focused on patients' need by sex, and would make them feel part of the therapeutic process, improving their therapeutic adherence, evolution and quality of life.

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Depressive episodes with psychotic symptoms are prevalent among the older adults, emphasizing the need to differentiate them from dementia with Lewy bodies (DLB), in which depressive and psychotic symptoms commonly coexist. In contrast, psychotic symptoms occur more frequently in depressive episodes of bipolar disorder (BD) than in major depressive disorder (MDD). Although MDD is a significant risk factor for dementia, studies exploring the relationship between BD and dementia are lacking. This report details the case of a 74-year-old female who experienced severe psychotic depression that led to suicide attempts during a long-term course of young-onset BD. Ultimately, she was diagnosed with DLB based on her neurocognitive symptoms and results of the neuroimaging examination. She had experienced multiple relapses in the past, predominantly characterized by depressive episodes in her old age. Notably, she had never undergone lithium treatment, which is known for its potential efficacy in preventing relapse and dementia. Recent systematic reviews and meta-analyses have suggested that patients with BD have a higher risk of dementia than the general population, and that lithium usage is associated with a reduced risk. Moreover, patients with BD have been suggested to have an elevated risk of developing Parkinson's disease (PD), and the pathophysiological relationship between BD and PD may be attributed to dopamine dysregulation resulting from multiple relapses. Future research is imperative to identify strategies for preventing dementia in patients with BD and to develop interventions for the comorbidities of BD and DLB.

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Although it is well established that individuals living with psychosis are at increased risk for suicidal ideation, attempts, and death by suicide, several gaps in the literature need to be addressed to advance research and improve clinical practice. This Call-to-Action highlights three major gaps in our understanding of the intersection of psychosis and suicide as determined by expert consensus. The three gaps include research methods, suicide risk screening and assessment tools used with persons with psychosis, and psychosocial interventions and therapies. Specific action steps to address these gaps are outlined to inform research and practice, and thus, improve care and prognoses among persons with psychosis at risk for suicide.

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BACKGROUND: Psychotic symptoms and elevated fasting blood glucose (FBG) are frequently observed in people with major depressive disorder (MDD), but there is a lack of research into this relationship within this cohort. AIMS: This study aimed to preliminarily explore the prevalence of psychotic symptoms and their predictors among patients with MDD and elevated FBG. METHOD: This study enrolled 1718 patients with first-episode and drug-naïve (FEDN) MDD. Sociodemographic data and physical and biochemical indicators were collected. Clinical symptoms were assessed with tools such as the Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression (HRSD) and Positive and Negative Syndrome Scale positive subscale. RESULTS: The odds ratio for psychotic symptoms in those with MDD and elevated FBG (18.7%) was 2.33 times higher than those with MDD without elevated FBG. Presence of psychotic symptoms was significantly correlated with HRSD score, suicide attempts, and total cholesterol and thyroid-stimulating hormone levels. The combination of HRSD score, suicide attempts and thyroid-stimulating hormone levels among patients with MDD and elevated FBG effectively distinguished between individuals with and without psychotic symptoms, achieving an area under the curve of 0.87. CONCLUSIONS: Psychotic symptoms are frequently observed among FEDN MDD patients with elevated FBG, and depressive symptoms, suicide attempts and thyroid-stimulating hormone levels are related to psychotic symptoms in this cohort.

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BACKGROUND AND HYPOTHESIS: The Structured Interview for Psychosis-Risk Syndromes (SIPS) and other assessments of psychosis risk define clinical high risk for psychosis (CHR) by the presence of attenuated psychotic symptoms. Despite extensive research on attenuated psychotic symptoms, substantial questions remain about their internal psychometric structure and relationships to comorbid non-psychotic symptoms. STUDY DESIGN: Hierarchical and bifactor models were developed for the SIPS in a large CHR sample (NAPLS-3, N = 787) and confirmed through preregistered replication in an independent sample (NAPLS-2, N = 1043). Criterion validity was tested through relationships with CHR status, comorbid symptoms/diagnoses, functional impairment, demographics, neurocognition, and conversion to psychotic disorders. STUDY RESULTS: Most variance in SIPS items (75%-77%) was attributable to a general factor. Hierarchical and bifactor models included a general factor and five specific/lower-order factors (positive symptoms, eccentricity, avolition, lack of emotion, and deteriorated thought process). CHR participants were elevated on the general factor and the positive symptoms factor. The general factor was associated with depressive symptoms; functional impairment; and mood, anxiety, and schizotypal personality diagnoses. The general factor was the best predictor of psychotic disorders (d ≥ 0.50). Positive symptoms and eccentricity had specific effects on conversion outcomes. The deteriorated thought process was least meaningful/replicable. CONCLUSIONS: Attenuated psychotic symptoms, measured by the SIPS, have a complex hierarchical structure with a strong general factor. The general factor relates to internalizing symptoms and functional impairment, emphasizing the roles of general psychopathological distress/impairment in psychosis risk. Shared symptom variance complicates the interpretation of raw symptom scores. Broad transdiagnostic assessment is warranted to model psychosis risk accurately.

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BACKGROUND: The relationship between childhood trauma (CT) and psychotic symptoms in patients with schizophrenia (SCZ), and subthreshold psychotic experiences in non-clinical populations is well-established. However, little is known about the relationship between subtypes of trauma and specific symptoms in patients, their siblings, and controls. It is also not clear which variables mediate the relationship between trauma and psychotic symptoms. METHODS: Seven hundred and forty-two patients with SCZ, 718 of their unaffected siblings and 1039 controls from three EU-GEI sites were assessed for CT, symptom severity, and cognitive schemas about self/others. CT was assessed with the Childhood Trauma Questionnaire, and cognitive schemas were assessed by The Brief Core Schema Scale. RESULTS: Patients with psychosis were affected by CT more than their siblings and controls in all domains. Childhood emotional abuse and neglect were more common in siblings than controls. CT was related to negative cognitive schemas toward self/others in patients, siblings, and controls. We found that negative schemas about self-mediated the relationship between emotional abuse and thought withdrawal and thought broadcasting. Approximately 33.9% of the variance in these symptoms was explained by the mediator. It also mediated the relationship between sexual abuse and persecutory delusions in SCZ. CONCLUSIONS: Our findings suggest that childhood abuse and neglect are more common in patients with schizophrenia than their siblings and healthy controls, and have different impacts on clinical domains which we searched. The relationship between CT and positive symptoms seems to be mediated by negative cognitive schemas about self in schizophrenia.