BACKGROUND: Schizophrenia is a disorder associated with neurocognitive deficits that adversely affect daily functioning and impose an economic burden. Cognitive rehabilitation interventions, particularly during the early phases of illness, have been shown to improve cognition, functionality, and quality of life. The Feuerstein Instrumental Enrichment (FIE) program, based on the Mediated Learning Experience and the Structural Cognitive Modifiability theory, has been applied in various disorders, but its applicability in schizophrenia has not yet been clarified.
OBJECTIVE: This study aims to investigate the effects of the FIE program on the functionality of patients with first-episode schizophrenia.
METHODS: In total, 17 patients will be recruited for an open-label intervention consisting of twice-weekly sessions for 10 weeks. The primary outcome measure will be changes in the Goal Achievement Scale score. Maze task performance from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery will serve as a secondary outcome measure. At the same time, changes in Positive and Negative Syndrome Scale scores and other MATRICS domains will be analyzed as exploratory outcomes. Assessments will be administered before and after the intervention, with a follow-up period of 6 months.
RESULTS: This trial was preregistered in The Brazilian Registry of Clinical Trials (RBR-4gzhy4s). By February 2024, 11 participants were enrolled in the training. Recruitment is expected to be completed by May 2024. Data analysis will be conducted between May and September 2024. The results are expected to be published in January 2025.
CONCLUSIONS: This study may establish a protocol for the FIE program that uses mediation techniques for individuals in the early stages of schizophrenia. The results will add to the knowledge about strategies to promote cognitive skills and functional impairment in daily life.
UNASSIGNED: DERR1-10.2196/57031.

OBJECTIVE: Functional Management and Recovery is a standardized Psychoeducational Intervention, derived from \"Integro\", an effective salutogenic-psychoeducational intervention for people in recovery journey, designed to improve recovery and functioning of individuals with psychotic disorders in Psychiatric Residential Facilities (PRFs). The aim of this study is to evaluate the primary and secondary outcomes of this intervention elaborated specifically for PRFs where evidence based structured interventions seem rare and desirable.
METHODS: 66 individuals with psychotic disorders were recruited in 9 PRFs dislocated in the North, Center and South Italy and 63 underwent a multicenter follow-up study with a two time-point evaluation (t0, pre-treatment and t1, 6 months; ). At each time point, social functioning was assessed as primary outcome by the Personal and Social Performance scale (PSP); furthermore, psychopathological status was assessed by Brief Psychiatric Rating Scale (BPRS), Recovery by Recovery Assessment Scale (RAS), Cognitive Functioning by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Stress management by Stress-Scale, Cognitive Flexibility by Modified Five-Point Test (M-FPT), Emotional Intelligence by Emotional Intelligence Index (EI-I), the PRF Atmosphere and the Opinion of users about the PFR by an ad hoc questionnaire. The Abilities Knowledge, the Utility and Pleasantness of sessions were measured by an ad hoc list of items.
RESULTS: 63 individuals out of 66, 52 (82,5%) affected by schizophrenia and 11 (17,5%) by bipolar I disorder with psychotic symptoms according to DSM-5-TR completed the study. At the end of the study, 43 (68,3%) were male, 57 (90.5%) were single, 5 (7.9%) engaged, 1 (1.6%) married; 45 (71.4%) unemployed. The total scores of PSP, RAS, BPRS, BANS, Stress management, Abilities Knowledge, Utility and Pleasantness of sessions showed a statistically significant improvement at t1 vs. t0. Two sub-scales out of 5 of M-FPT showed a statistically significant improvement. The Emotional Intelligence, the Unit Atmosphere and the Opinion of Users about PFR improved without statistical significance. Six months after the end of the follow-up study 22 individuals of the sample were dismissed with a very high turnover.
CONCLUSIONS: After a six-month follow-up (a short period of time), these results showed improvement in functioning, the primary outcome, as well as in the following secondary outcome variables: RAS, BPRS, BANS, Stress management, Abilities Knowledge, two sub-scales out of 5 of M-FPT, Utility and Pleasantness of sessions. Overall, a remarkable impact of psychoeducational structured intervention on the key Recovery variables is observed. Further studies are needed to address extent and duration of these improvements.

Little is known about the individual course of suicidal ideations and attempts (i.e., suicidality) after treatment initiation. We examined the trajectories of suicidality and associated risk factors over a 2-year early intervention program for first-episode psychosis in 450 patients (age range 18-35 years at admission) consecutively admitted from 2003 to 2017. Suicidality was assessed via systematic file review, while sociodemographic and clinical variables were assessed at admission. Latent class growth modelling identified three trajectories: low (69.6 %), initially high (22.9 %), and persistently high (7.6 %) suicidality. Patients who were younger, lived alone and were diagnosed with affective psychosis were significantly more likely to follow the initially high trajectory. Patients who attempted suicide up to 3 months before admission, lived alone and presented lower levels of the PANSS excited factor were significantly more likely to follow the persistently high trajectory. Attempting suicide up to 3 months before admission distinguished persistently high and initially high suicidality trajectories. Suicide risk during early intervention program for first-episode psychosis is heterogenous, with acute and enduring suicidal risk, suggesting the need to adapt suicide prevention strategies to these different risk profiles.

BACKGROUND: Methamphetamine use and related direct and indirect problems are increasing all over the world. The coexistence of lifetime marijuana use (LMU) and methamphetamine use disorder (MUD) may also be accompanied by psychotic symptoms (MAP). Methamphetamine and marijuana use are known to pose risks for cardiovascular diseases (CVDs). However, ten-year CVD risk and inflammation markers of LMU-MUD (non-psychosis group) and LMU-MAP (psychosis group) subjects and the relationship of various sociodemographic and clinical variables with these markers have not yet been examined.
METHODS: Thirty-two male subjects were included in non-psychosis group and 72 male subjects in psychosis group. Sociodemographic and clinical characteristics were recorded. Psychotic symptom severity of psychosis group subjects was measured. The ten-year CVD risk was calculated using QRISK®3 model.
RESULTS: Age, cigarettes/pack-years, alcohol use onset age, drug use onset age, methamphetamine use onset age, duration of methamphetamine use, education and marital status of the groups were similar (p > 0.05). There was a statistical difference between the non-psychosis and psychosis groups in terms of self-mutilation history (p < 0.001), suicidal attempt history (p = 0.007), homicidal attempt history (p = 0.002), psychiatric hospitalization history (p = 0.010). Ten-year QRISK®3 score was 4.90 ± 9.30 in the psychosis group, while it was 1.60 ± 1.43 in the non-psychosis group (p = 0.004). The mean heart age of the psychosis group was 14 years higher than their chronological age, while the mean heart age of the non-psychosis group was 8 years higher. Neutrophil to lymphocyte ratio (NLR) (p = 0.003) was higher in the psychosis group. A significant correlation was detected between ten-year QRISK®3 and positive psychotic symptoms in the psychosis group (r = 0.274, p = 0.020). Regression analysis showed that self-mutilation history, NLR and relative risk obtained from QRISK®3 can be used to distinguish non-psychosis group and psychosis group subjects (sensitivity = 91.7; Nagelkerke R2 0.438; p = 0.001).
CONCLUSIONS: This study is important as it demonstrates for the first time that among the subjects using marijuana and methamphetamine, those with psychotic symptoms have a higher NLR and ten-year CVD risk.

BACKGROUND: A longer duration of untreated psychosis (DUP) is associated with poorer treatment outcomes. Screening for psychosis spectrum disorders in the primary care setting could help support the earlier detection and treatment of individuals in need. However, the acceptability of screening for psychosis in this setting as part of routine care is currently unknown.
METHODS: We conducted a qualitative interview study with providers and service users who participated in an early psychosis screening program conducted in an integrated behavioral health primary care (IBH-PC) setting. Interviews were recruited from one of eight WellSpace Federally Qualified Health Center IBH-PC clinics in the Sacramento, CA area. Transcripts of the recorded interviews were analyzed using thematic analysis.
RESULTS: In total, 12 providers and eight service users participated in the interviews. Most service user and provider participants were supportive of psychosis screening in an IBH-PC setting, but not as part of the general practitioner consultation due to the brief, non-behavioral health nature of many of the appointments, and the expected low prevalence of psychosis in this population. The support of leadership, adequate training and support, staff turnover, and organizational changes were all seen to impact the successful implementation of the program. Different barriers and facilitators were considered important at each stage of the process from introducing the screening procedures to service users; to determining when, where, and how to screen; and how to effectively manage the referral and post-referral stages.
CONCLUSIONS: Despite the additional challenges of screening in an IBH-PC setting relative to secondary mental health services, the process was considered acceptable and feasible to providers and service users. Services that plan to conduct psychosis screening in their clinics need to consider the challenges and their potential solutions to implementation at each stage of the screening process.

BACKGROUND: Psychosis involves a distortion of thought content, which is partly reflected in anomalous ways in which words are semantically connected into utterances in speech. We sought to explore how these linguistic anomalies are realized through putative circuit-level abnormalities in the brain\'s semantic network.
METHODS: Using a computational large-language model, Bidirectional Encoder Representations from Transformers (BERT), we quantified the contextual expectedness of a given word sequence (perplexity) across 180 samples obtained from descriptions of 3 pictures by patients with first-episode schizophrenia (FES) and controls matched for age, parental social status, and sex, scanned with 7 T ultra-high field functional magnetic resonance imaging (fMRI). Subsequently, perplexity was used to parametrize a spectral dynamic causal model (DCM) of the effective connectivity within (intrinsic) and between (extrinsic) 4 key regions of the semantic network at rest, namely the anterior temporal lobe, the inferior frontal gyrus (IFG), the posterior middle temporal gyrus (MTG), and the angular gyrus.
RESULTS: We included 60 participants, including 30 patients with FES and 30 controls. We observed higher perplexity in the FES group, indicating that speech was less predictable by the preceding context among patients. Results of Bayesian model comparisons showed that a DCM including the group by perplexity interaction best explained the underlying patterns of neural activity. We observed an increase of self-inhibitory effective connectivity within the IFG, as well as reduced self-inhibitory tone within the pMTG, in the FES group. An increase in self-inhibitory tone in the IFG correlated strongly and positively with inter-regional excitation between the IFG and posterior MTG, while self-inhibition of the posterior MTG was negatively correlated with this interregional excitation.
CONCLUSIONS: Our design did not address connectivity in the semantic network during tasks that selectively activated the semantic network, which could corroborate findings from this resting-state fMRI study. Furthermore, we do not present a replication study, which would ideally use speech in a different language.
CONCLUSIONS: As an explanation for peculiar speech in psychosis, these results index a shift in the excitatory-inhibitory balance regulating information flow across the semantic network, confined to 2 regions that were previously linked specifically to the executive control of meaning. Based on our approach of combining a large language model with causal connectivity estimates, we propose loss in semantic control as a potential neurocognitive mechanism contributing to disorganization in psychosis.

OBJECTIVE: Catatonia is a neuropsychiatric disorder that can occur in patients of any age, but it is uncertain whether patient demographics or underlying diagnoses differ between pediatric and adult patients. This study investigates patients of all ages diagnosed with catatonia during acute care hospitalizations in the United States over a 5-year period.
METHODS: The National Inpatient Sample, an all-payors database of acute care hospital discharges, was queried for patients with a discharge diagnosis of catatonia between 2016 and 2020 with patients stratified by age as pediatric (≤18 years) or adult (>18 years).
RESULTS: Among 174,776,205 hospitalizations recorded in the NIS from 2016 to 2020, 61,990 (95% CI: 60,257 to 63,723; 0.035%) involved a diagnosis of catatonia. Of these, 3255 were for pediatric patients and 58,735 were for adult patients. Compared with adult patients, pediatric catatonia patients were more likely to be male and non-White. Diagnostically, psychotic disorders, encephalitis, and neurodevelopmental disorders were more common primary discharge diagnoses in pediatric patients, while adult patients more frequently were diagnosed with mood disorders. Length of stay was not significantly different between pediatric and adult catatonia hospitalizations. Physical restraints were commonly applied for patients with catatonia.
CONCLUSIONS: Pediatric and adult catatonia patients differed in sex, race, and diagnosis, although hospital length of stay was not different between pediatric and adult catatonia hospitalizations. These results may inform catatonia diagnosis in the hospital setting and point to disparities that could be targets of quality improvement efforts.

OBJECTIVE: Sleep problems are common in patients with psychotic disorders, especially schizophrenia. Although pharmacological methods are at the forefront of treatment, this method has some drawbacks. Cognitive behavioral therapy for insomnia (CBT-I) is an option for the treatment of individuals with insomnia. In recent years, there has been an increasing interest in its use in patients with psychotic disorders. This meta-analysis aims to evaluate the effectiveness of CBT-I on sleep problems in patients with psychotic disorders.
METHODS: A systematic search was conducted using PubMed, Scopus, and EBSCO (MEDLINE) databases to identify relevant studies. The study included RCTs and uncontrolled studies that focused on participants diagnosed with schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, bipolar disorders, or unipolar depression with psychotic features, who had sleep problems for at least one month, and who were receiving treatment. The initial search yielded 246 studies, and eight studies were selected for the meta-analysis after screening and applying inclusion and exclusion criteria.The statistical analysis was conducted using the R software.
RESULTS: CBT-I significantly ameliorates insomnia and sleep quality in patients with psychotic disorders during short and long-term periods. In addition to this, CBT-I leads to a significant improvement in psychotic symptoms in the short-term period and contributes significantly to the improvement in mental well-being in both short and long-term periods.
CONCLUSIONS: CBT-I is an effective and valuable method for sleep problems in patients with psychotic disorders and its use is recommended to be widespread.

BACKGROUND: Ongoing psychiatric follow-up and medication adherence improve outcomes for patients with psychotic disorders. Due to COVID-19, outpatient care may have been disrupted, impacting healthcare utilization.
METHODS: A retrospective population-wide study was conducted for adults in Manitoba, Canada. Medication adherence and healthcare utilization were examined from 2019 to 2021. The presence of a diagnosed psychotic disorder was identified in the five years before the index date in each year. The LAI and clozapine cohorts consisted of those who received at least two prescriptions in each year 180 days before the March 20th index date. The change in adherence was measured using the average Medication Possession Ratio. Healthcare utilization rates were compared using Generalized Estimating Equation models.
RESULTS: There were no significant differences between LAI and clozapine discontinuation rates before and during the pandemic. In the LAI cohort, general practitioner visits decreased significantly (-3.5 %, p = 0.039) across four quarters of 2021 versus 2019. All-cause hospitalizations decreased by 16.8 % in 2020 versus 2019 (p = 0.0055), while psychiatric hospitalizations decreased by 18.7 % across four quarters in 2020 (p = 0.0052) and 13.7 % in 2021 (p = 0.0425), versus 2019 in the LAI cohort. There was a significant transition to virtual care during the first wave of COVID-19 (71 % in clozapine, 51 % in LAI cohorts). Trends in total outpatient visits and non-psychiatric hospitalizations remained stable.
CONCLUSIONS: COVID-19 had no substantial impact on LAI and clozapine discontinuation rates for patients previously adherent. Outpatient care remained stable, with a significant proportion of visits being done virtually at the outset of the pandemic.

Monozygotic (MZ) twins are often thought to have identical genomes, but recent work has shown that early post-zygotic events can result in a spectrum of DNA variants that are different between MZ twins. Such variants may explain phenotypic discordance and contribute to disease etiology. Here we performed whole genome sequencing in 17 pairs of MZ twins discordant for a psychotic disorder (schizophrenia, schizoaffective disorder or bipolar disorder). We examined various classes of rare variants that are discordant within a twin pair. We identified four genes harboring rare, predicted deleterious missense variants that were private to an affected individual in the cohort. Variants in FOXN1 and FLOT2 would have been categorized as damaging from recent schizophrenia and bipolar exome sequencing studies. Additionally, we identified four rare genic copy number variants (CNVs) private to an affected sample, two of which overlapped genes that have shown evidence for association with schizophrenia or bipolar disorder. One such CNV was a 3q29 duplication previously implicated in autism and developmental delay. We have performed the largest MZ twin study for discordant psychotic phenotypes to date. These findings warrant further investigation using other analytical approaches.