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Introduction: Subclinical psychotic experiences (PEs) are far more prevalent than psychotic disorders, with an estimated prevalence of 7.2% (Linscott & Van Os. Psychol Med 2013;43(6) 1133-1149). PEs are particularly prevalent in late adolescence and young adulthood, when obtaining academic education is one of the main developmental tasks. University students are at the peak age of onset of mental disorders, and often experience high levels of social and academic stress that may contribute to the onset of psychopathology. Hence, estimating the prevalence and correlates of PEs among university students is particularly important. Objectives: To estimate the prevalence of PEs in a sample of Israeli students; assess whether rates of PEs differ by selected sociodemographic characteristics; and examine the association between PEs and non-specific psychological distress. Methods: 150 students from universities and colleges in Israel participated in a cross-sectional online survey. All students were over the age of 18 and were not diagnosed with psychotic disorders. Participants completed self-report questionnaires, including the Prodromal Questionnaire - Brief Version (PQ-B), Kessler Psychological Distress Scale (K10) and sociodemographic details. The PQ-B yields a score for the total number of items endorsed (range 0–21), and a total distress score (range 0–105). A cutoff of ≥8 distressing symptoms was used to identify participants at high-risk for psychosis. Results: 21 participants (14.0%) reported 8 or more distressing PEs. PEs were more common in males and among those with a psychiatric illness (Table 1). PEs were not associated with marital status, religiosity, or immigrant status. While a greater number of PEs was positively associated with non-specific psychological distress (r=0.589, p<.001), there was no association between distress caused by PEs and non-specific psychological distress (r=0.145, NS). Table 1. Sociodemographic characteristics by group PEs- PEs+ X2, p Sex M 29.5% 52.4% 4.32,.038 F 70.5% 47.6% Marital Status Married 17.1% 23.8% 0.56, NS Unmarried 82.9% 76.2% Immigrant No 89.9% 85.7% 0.34, NS Yes 10.1% 14.3% Religiosity Secular 74.4% 57.1% 2.67, NS Other 25.6% 42.9% Psychiatric illness No 87.6% 61.9% 8.87,.003 Yes 12.4% 38.1% Conclusions: The findings confirm that self-reported PEs are much more prevalent than clinically diagnosed psychotic disorders, particularly among young adults. As PEs were found to be associated with non-specific psychological distress, and as they are known forerunners for severe mental disorders, it is important to address mental health issues in school settings and promote prevention and early intervention programs. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

Objective Data suggest that adherence to religious beliefs is associated with lower rates of suicide. A number of mediating factors have been hypothesized to explain this association, including enhanced social support, less substance abuse, and lower rates of psychopathology. Method We utilized data from a two-phase population-based, epidemiological study of mental disorders among young Jewish Israel born in a 10-year birth-cohort conducted in the 1980s. This study included data on religiosity and suicidal behaviour. Twenty-five years thereafter, mortality data were obtained from a national vital statistics registry. Results Rates of suicidal ideation were similar among secular, partially observant, and religious subjects (9.4%, 6.7%, and 6.2%, respectively; adjusted OR for linear trend: 0.80, 95% CI: 0.58-1.09). Rates of suicide attempts were significantly lower among religious subjects (2.4%, 2.5%, and 0.4% for secular, partially observant, and religious, respectively; adjusted OR for linear trend: 0.62, 95% CI: 0.43-0.88). Of the 4914 subjects, eight died by suicide: Seven of them were secular and one was partially observant (χ2 = 2.52, P = 0.09). There were no differences in social functioning or rates of psychopathology among the study groups. Conclusion Religiosity has a protective effect against suicide attempts, which is independent of social functioning, psychopathology, and substance use. [ABSTRACT FROM AUTHOR]

What is already known about this subject Low IQ is associated with high BMI in childhood., There are inconsistent findings on the association between low SES and high BMI., Youth with low IQ have been reported to have poorer health behaviors, such as poor nutrition and less physical activity., What this study adds Low IQ is significantly associated with obesity for both male and female adolescents, though more strongly for female adolescents., Physical activity has a mediating effect on the association between low IQ and obesity among both male and female adolescents, though more strongly for male adolescents., The association between low IQ and obesity is strongest among adolescents from high SES backgrounds., Background Previous studies have shown an association between low intelligence quotient ( IQ), high body mass index and low socioeconomic status ( SES). Objectives This study examined the cross-sectional association between IQ and obesity, exploring the roles of gender, SES and physical activity in this association. Methods Subjects were 235 663 male and 169 259 female adolescents assessed by the Israeli military draft board. Results Low IQ was significantly associated with increased odds of obesity among male (odds ratio [ OR] = 1.44, 95% confidence interval [ CI] = 1.36-1.52) and female adolescents ( OR = 1.61, 95% CI = 1.51-1.73); this association was significantly stronger among female adolescents. Sobel tests indicated that physical activity had a significant mediating effect on this association for male and female adolescents, although more strongly for male adolescents. Dividing the sample according to SES, the association between low IQ and obesity was strongest in the high SES group (male adolescents: OR = 1.26, 95% CI = 1.10-1.43, female adolescents: OR = 1.61, 95% CI = 1.38-1.89), even when controlling for physical activity. Conclusions The findings suggest that low IQ is associated with increased odds of obesity, particularly in female adolescents and in adolescents with high SES. Physical activity has a mediating effect on this association, although more strongly for male than for female adolescents. Public health measures on decreasing obesity might focus on these groups. [ABSTRACT FROM AUTHOR]

BackgroundPrevious studies have found that patients with schizophrenia are more likely to be violent than the general population. The aim of this study was to investigate the association between schizophrenia and violent crime in the Israeli population.MethodUsing the Israeli Psychiatric Hospitalization Case Registry we identified 3187 patients with a discharge diagnosis of schizophrenia. For each proband we identified parents and siblings, and gender- and age-matched controls for patients, parents and siblings. Information on violent crimes was obtained from police records.ResultsPatients with schizophrenia were at increased risk for violent crimes compared with controls [odds ratio (OR) 4.3, 95% confidence interval (CI) 3.8–4.9], especially women (OR 9.9, 95% CI 6.2–15.7). Risk for violent crimes was higher among patients with co-morbid substance misuse than in patients without such co-morbidity (OR 5.1, 95% CI 4.2–6.3).ConclusionsThe results of this study suggest that increased risk of violence is part of the clinical picture of schizophrenia and needs to be recognized as a legitimate, essential, aspect of clinical management. [ABSTRACT FROM AUTHOR]

Objective: As patients with psychotic illness have fewer offspring than controls, the persistence of psychotic illness is puzzling. We hypothesized that unaffected first-degree relatives of patients have more offspring than controls. Method: Probands were 4904, individuals with non-affective psychotic disorders identified from a hospitalization registry. Unaffected first degree relatives and matched controls were identified from the Israeli Population Registry. The number of offspring of unaffected parents, biological siblings and controls was ascertained. Results: Unaffected parents of psychotic patients had more offspring/person than controls; 4.5 ± 2.7 vs. 3.4 ± 2.2, P = 0.000. Unaffected parents from familial psychosis families (more than one affected family member) had 1.83 more offspring than controls; unaffected parents from non-familial psychosis families had 0.97 more offspring than controls (both P < 0.001). Conclusion: These findings might imply that genes which increase susceptibility for schizophrenia may be associated with increased number of offspring, perhaps supplying a partial explanation for the persistence of psychosis. [ABSTRACT FROM AUTHOR]

Objective: Previous studies indicate that a poor family environment might affect vulnerability for the later manifestation of psychotic illness. The current study aims to examine family functioning prior to the onset of psychosis. Method: Subjects were 42 948, 17-year old males with behavioural disturbances who were asked about the functioning of their family by the Israeli Draft Board. Data on later psychiatric hospitalizations were obtained from a National Psychiatric Hospitalization Registry. Results: Poorer self-reported family functioning was associated with greater risk for later hospitalization for psychosis [adjusted hazard ratio (HR) = 1.16, 95% CI = 1.05–1.27], with a trend in the same direction for schizophrenia (adjusted HR = 1.1, 95% CI = 0.98–1.24). Conclusion: In male adolescents with behavioural disturbances, perceived poorer family functioning is associated with increased risk for non-affective psychotic disorders and schizophrenia. These data do not enable us to determine if perceived familial dysfunction increases vulnerability for psychosis, if premorbid behavioural abnormalities disrupt family life, or neither. [ABSTRACT FROM AUTHOR]

Background. The base rate of transition from subthreshold psychotic experiences (the exposure) to clinical psychotic disorder (the outcome) in unselected, representative and non-help-seeking population-based samples is unknown. Method. A systematic review and meta-analysis was conducted of representative, longitudinal population-based cohorts with baseline assessment of subthreshold psychotic experiences and follow-up assessment of psychotic and non-psychotic clinical outcomes. Results. Six cohorts were identified with a 3-24-year follow-up of baseline subthreshold self-reported psychotic experiences. The yearly risk of conversion to a clinical psychotic outcome in exposed individuals (0.56%) was 3.5 times higher than for individuals without psychotic experiences (0.16%) and there was meta-analytic evidence of dose-response with severity/persistence of psychotic experiences. Individual studies also suggest a role for motivational impairment and social dysfunction. The evidence for conversion to non-psychotic outcome was weaker, although findings were similar in direction. Conclusions. Subthreshold self-reported psychotic experiences in epidemiological non-help-seeking samples index psychometric risk for psychotic disorder, with strong modifier effects of severity/persistence. These data can serve as the population reference for selected and variable samples of help-seeking individuals at ultra-high risk, for whom much higher transition rates have been indicated. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Cognitive impairment, manifested as mild to moderate deviations from psychometric norms, is present in many but not all schizophrenia patients. The purpose of the present study was to compare the effect of haloperidol with that of second-generation antipsychotic drugs on the cognitive performance of patients with schizophreniform disorder or first-episode schizophrenia. METHODS: Subjects were 498 patients with schizophreniform disorder or first-episode schizophrenia who were randomly assigned to open-label haloperidol (1 to 4 mg/day [N=103]), amisulpride (200 to 800 mg/day [N=104]), olanzapine (5 to 20 mg/day [N=105]), quetiapine (200 to 750 mg/day [N=104]), or ziprasidone (40 to 160 mg/day [N=82]). The Rey Auditory Verbal Learning Test, Trail Making Test Part A and Part B, WAIS Digit Symbol Test, and Purdue Pegboard Test were administered at baseline and the 6-month follow-up evaluation. RESULTS: Compared with scores at baseline, composite cognitive test scores improved for all five treatment groups at the 6-month follow-up evaluation. However, there were no overall differences among the treatment groups. In addition, there was a weak correlation between the degree of cognitive improvement and changes in Positive and Negative Syndrome Scale scores. CONCLUSION: Treatment with antipsychotic medication is associated with moderate improvement in the cognitive test performance of patients who have schizophreniform disorder or who are in their first episode of schizophrenia. The magnitude of improvement does not differ between treatment with haloperidol and treatment with second-generation antipsychotics. Moreover, cognitive improvement is weakly related to symptom change. [ABSTRACT FROM AUTHOR]

BACKGROUND: Being a small and culturally different minority, or having a different appearance, has been invoked to account for the increased prevalence of psychotic disorders among immigrants. The majority of the Jewish Israeli population are first- or second-generation immigrants from Europe, North Africa or Asia, and during the late 1980s and 1990s, 885 000 persons immigrated to Israel from the former Soviet Union and 43 000 immigrated from Ethiopia. These Ethiopian immigrants came from a very different culture compared to the rest of the population, and have a distinct appearance. To further understand the association between immigration and schizophrenia, we compared risk for later schizophrenia between adolescents who immigrated from Ethiopia with risk among the other immigrant groups, and with native-born Israelis.MethodOf 661 792 adolescents consecutively screened by the Israeli Draft Board, 557 154 were native-born Israelis and 104 638 were immigrants. Hospitalization for schizophrenia was ascertained using a National Psychiatric Hospitalization Case Registry. All analyses controlled for socio-economic status (SES). RESULTS: Risk for schizophrenia was increased among both first- [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.18-2.22] and second-generation immigrants [HR 1.41, 95% CI 1.01-1.95 (one immigrant parent) and HR 1.49, 95% CI 1.11-2.0 (two immigrant parents)]. When risk for schizophrenia was calculated for each immigrant group separately, immigrants from Ethiopia were at highest risk of later schizophrenia (HR 2.95, 95% CI 1.88-4.65).ConclusionThis comparison between diverse groups of immigrants supports the notion that immigrants who differ in culture and appearance from the host population are at increased risk for schizophrenia. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a leading cause of mortality and morbidity among aging populations worldwide. Despite arduous research efforts, treatment options for this devastating neurodegenerative disease are limited. Sleep disturbances, through their link to changes in neural excitability and impaired clearance of interstitial abnormal protein aggregates, are a key risk factor for the development of AD. Research also suggests that the neuroprotective effects of sleep are particularly active during slow wave sleep. Given the strong link between sleep disturbance and AD, targeting sleep in the prodromal stages of AD, such as in mild cognitive impairment (MCI), represents a promising avenue for slowing the onset of AD-related cognitive decline. In efforts to improve sleep in older individuals, several pharmacologic approaches have been employed, but many pose safety risks, concern for worsening cognitive function, and fail to effectively target slow wave sleep. Trazodone, a safe and widely used drug in the older adult population, has shown promise in inducing slow wave sleep in older adults, but requires more rigorous research to understand its effects on sleep and cognition in the prodromal stages of AD. In this review, we present the rationale and study design for our randomized, double-bind, placebo-controlled, crossover trial (NCT05282550) investigating the effects of trazodone on sleep and cognition in 100 older adults with amnestic MCI and sleep complaints. [ABSTRACT FROM AUTHOR]

Patients receiving palliative care often express a desire to die. Forms and backgrounds of these expressions can be diverse. To contribute to a better understanding of this phenomenon, we analyzed patients' desire to die expressions reported by palliative care providers participating in 11 communication trainings on desire to die. The 102 participants were asked to reproduce related patients' statements from their everyday practice. The 165 reported statements could be assigned to the four topics: "Putting an end to life by ...," "Social death," "Death images," as well as "Specific and unspecific references to life, death and dying." Across these topics, phrasing differs particularly regarding sentence type (interrogative, declarative, propositional, exclamatory), explicitness and (the way of) referencing others (e.g. attribution of power). The compilation of statements reflects a chorus of expressions, which the palliative care providers might hear throughout their professional career as well as during a patient's process(ing) of disease. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is one of the most severe mental disorders, frequently associated with aggression and violence, particularly in male patients. The underlying mechanisms of violent behavior in these patients remain unclear, limiting effective treatment options and highlighting the need for further research into interventions for impulsive behaviors. This study aims to evaluate the clinical efficacy of neurofeedback treatment in hospitalized male schizophrenia patients exhibiting impulsive behaviors. Methods: The study was designed as a single-center, randomized, single-blind, sham-controlled parallel trial. Eighty patients were randomly assigned to either a study group or a control group. The control group received risperidone and sham neurofeedback,while the study group received risperidone and active neurofeedback therapy. Both groups underwent training five timesperweek,with eachsession lasting 20 minutes, over a six-week period. Clinical symptoms were assessed at baseline, threeweeks and six weeks using the Positive andNegative Syndrome Scale (PANSS), theModified Overt Aggression Scale (MOAS), and the Rating Scale for Extrapyramidal Side Effects (RSESE). Statistical analyses were conducted to compare the therapeutic effects between the two groups at the study's conclusion. Results: Initial comparisons showed no significant differences in baseline data, except for the number of prior hospitalizations (P<0.018). By the end of the study, the study group demonstrate significant improvements in MOAS and PANSS scores (including the Excited, Positive, Cognitive, and Depressive/Anxiety Components), with no significant changes in RSESE scores. Discussion: Both time and group interactions were significant across most outcomes, underscoring the efficacy of neurofeedback in reducing the severity of impulsive behaviors and associated schizophrenia symptoms. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to assess the impact of Traditional Chinese Medicine (TCM) on dementia patients, utilizing real-world data. Specifically, it seeks to evaluate how TCM influences clinical outcomes by examining changes in the Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE) scores, as well as its effect on medical expenses over a two-year period. Data from a multi-center research database spanning from 2004 to 2021 will be used to achieve these objectives, addressing the current gap in empirical data concerning intuitive outcomes and cognitive function assessments. Methods: Propensity score matching was adopted to improve comparability among the intervention and control groups. Due to repeated dependent variable measurements, the generalized estimating equation was used to control for socio-demographic characteristics, regional characteristics, and Western medicine treatments for dementia. Results: After propensity score matching, a total of 441 research subjects were included: 90 in the TCM intervention group and 351 in the non-TCM intervention group. The results of multivariate regression analysis showed that compared with the non-TCM intervention group, the MMSE scores in the TCM intervention group increased by 0.608 points each year. The annual change in CDR scores in the TCM intervention group was 0.702 times that of the non-TCM utilization group. After TCM intervention, annual outpatient expenses increased by US$492.2, hospitalization expenses increased by US$324.3, and total medical expenses increased by US$815.9, compared with the non-intervention group. Conclusions: TCM interventions significantly decelerate cognitive decline in dementia patients, evidenced by slower reductions in MMSE scores and mitigated increases in CDR scores. However, these benefits are accompanied by increased medical expenses, particularly for outpatient care. Future healthcare strategies should balance the cognitive benefits of TCM with its economic impact, advocating for its inclusion in dementia care protocols. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to assess the impact of Traditional Chinese Medicine (TCM) on dementia patients, utilizing real-world data. Specifically, it seeks to evaluate how TCM influences clinical outcomes by examining changes in the Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE) scores, as well as its effect on medical expenses over a two-year period. Data from a multi-center research database spanning from 2004 to 2021 will be used to achieve these objectives, addressing the current gap in empirical data concerning intuitive outcomes and cognitive function assessments. Methods: Propensity score matching was adopted to improve comparability among the intervention and control groups. Due to repeated dependent variable measurements, the generalized estimating equation was used to control for socio-demographic characteristics, regional characteristics, and Western medicine treatments for dementia. Results: After propensity score matching, a total of 441 research subjects were included: 90 in the TCM intervention group and 351 in the non-TCM intervention group. The results of multivariate regression analysis showed that compared with the non-TCM intervention group, the MMSE scores in the TCM intervention group increased by 0.608 points each year. The annual change in CDR scores in the TCM intervention group was 0.702 times that of the non-TCM utilization group. After TCM intervention, annual outpatient expenses increased by US$492.2, hospitalization expenses increased by US$324.3, and total medical expenses increased by US$815.9, compared with the non-intervention group. Conclusions: TCM interventions significantly decelerate cognitive decline in dementia patients, evidenced by slower reductions in MMSE scores and mitigated increases in CDR scores. However, these benefits are accompanied by increased medical expenses, particularly for outpatient care. Future healthcare strategies should balance the cognitive benefits of TCM with its economic impact, advocating for its inclusion in dementia care protocols. [ABSTRACT FROM AUTHOR]

Cognitive impairment is a core feature of schizophrenia, playing a pivotal role in the pathogenesis and prognosis of this disorder. Cognitive impairment in schizophrenia encompasses a wide range of domains, including processing speed, episodic memory, working memory, and executive function. These deficits persist throughout the course of the illness and significantly impact functional outcomes and quality of life. Therefore, it is imperative to identify the biological basis of cognitive deficits in schizophrenia and develop effective treatments. The role of N-methyl-D-aspartate (NMDA) receptors in synaptic transmission and plasticity has long been recognized, making them potential targets for schizophrenia treatment. This review will focus on emerging pharmacology targeting NMDA receptors, offering strategies for the prevention and treatment of cognitive deficits in schizophrenia. [ABSTRACT FROM AUTHOR]

Background/Objectives: Patients with schizophrenia have significant challenges in adhering to and complying with oral medicines, resulting in adverse consequences such as symptom worsening and psychotic relapse. Methods: This study aimed to develop clove oil-based bilosomes using definitive screening design (DSD) to maximize the anti-schizophrenic action of clozapine and promote its nose-to-brain delivery. The target was to optimize the physicochemical properties of bilosomes and incorporate them into mucoadhesive intranasal in situ gels, searching for augmented ex vivo and in vivo clozapine delivery. Results: The bilosomes' particle size was decreased by increasing the span, SDC, and clove oil amounts. In addition to using a high lipid amount, the aforementioned components also helped increase the entrapment efficiency values. Increased zeta potential was only observed by increasing surfactant amount and reducing clozapine concentration. After incorporation of optimized liquid clove oil-based bilosomes, which had a spherical nano-sized vesicular shape, into P 407-dependent gels, an HPMC (2% w/w)/P 407 (20% w/w)-containing formulation (G6) was selected as an optimized gel owing to its acceptable gelation time (13.28 s), gel strength (27.72 s), viscosity (12,766.67 cP), and mucoadhesive strength (4273.93 dyne/cm2). The optimized G6 exhibited higher Jss (50.86 μg/cm2·h−1) through the nasal mucosa compared to the control gel (23.03 μg/cm2·h−1). Compared to the control gel, G6 displayed higher relative bioavailability (491.37%) than a commercial tablet (264.46%). Following ELISA analysis, dopamine and serotonin were significantly reduced, while BDNF was remarkably increased after administration of optimized G6 into schizophrenic rats. Conclusion: Our study indicates the potential of intranasal bilosomal gels in upgrading the anti-schizophrenic and neuroprotective activity of clozapine. [ABSTRACT FROM AUTHOR]

Background: Although the co-occurrence of psychotic experiences (PEs) and psychological distress symptoms is growingly recognized in several previous studies, there is still a lack of literature, which clearly outlines how these two psychopathological entities affect each other over time. This study is intended to add to the literature by examining: (a) the longitudinal, bidirectional associations between PEs and psychological distress in a sample of Tunisian adolescents, and (b) whether these associations are moderated by sex. Methods: 510 adolescent students (mean age of 16.05 ± 1.01 years, 61.2% females) took part in a prospective longitudinal study. PEs and psychological distress were measured at three occasions over a one-year period. The cross-lagged panel modeling approach was adopted. Results: The current results showed that the experience of PEs at baseline tended to temporally precede prospective increases in psychological distress (at 6 months), which had in turn led to further exacerbation of psychological distress at 12 months of follow-up. Temporally primary psychological distress symptoms were not a significant predictor for the development of later psychotic symptoms in the whole sample. However, temporal patterns between adolescent distress and psychotic symptoms differed for girls and boys. Endorsing PEs at baseline was followed by greater psychological distress at 6 months, which was in turn associated with a significant increased risk of subsequent exacerbation of PEs at 12 months in boys, whereas psychological distress at 12-month follow-up was significantly predicted by pre-existing PEs in girls. Conclusion: These findings suggest that clinicians and support workers are recommended to take into account different social risk profiles for boys and girls when considering interventions to address PEs and distress in adolescents. [ABSTRACT FROM AUTHOR]

The introduction of the first antipsychotic drug, chlorpromazine, was a milestone for psychiatry. The authors review the history, classification, indications, mechanism, efficacy, side effects, dosing, drug initiation, switching, and other practical issues and questions related to antipsychotics. Classifications such as first-generation/typical versus second-generation/atypical antipsychotics are neither valid nor useful; these agents should be described according to the Neuroscience-based Nomenclature (NbN). Antipsychotic drugs are not specific for treating schizophrenia. They reduce psychosis regardless of the underlying diagnosis, and they go beyond nonspecific sedation. All currently available antipsychotic drugs are dopamine blockers or dopamine partial agonists. In schizophrenia, effect sizes for relapse prevention are larger than for acute treatment. A major unresolved problem is the implausible increase in placebo response in antipsychotic drug trials over the decades. Differences in side effects, which can be objectively measured, such as weight gain, are less equivocal than differences in rating-scale-measured (subjective) efficacy. The criteria for choosing among antipsychotics are mainly pragmatic and include factors such as available formulations, metabolism, half-life, efficacy, and side effects in previous illness episodes. Plasma levels help to detect nonadherence, and once-daily dosing at night (which is possible with many antipsychotics) and long-acting injectable formulations are useful when adherence is a problem. Dose-response curves for both acute treatment and relapse prevention follow a hyperbolic pattern, with maximally efficacious average dosages for schizophrenia of around 5 mg/day risperidone equivalents. Computer apps facilitating the choice between drugs are available. Future drug development should include pharmacogenetics and focus on drugs for specific aspects of psychosis. [ABSTRACT FROM AUTHOR]

Schizophrenia is a chronic psychotic disorder comprising positive symptoms, negative symptoms, and cognitive deficits. Negative symptoms are associated with stigma, worse functional outcomes, and a significant deterioration in quality of life. Clinical diagnosis is challenging despite its significance, and current treatments offer little improvement in the burden of negative symptoms. This article reviews current pharmacological strategies for treating negative symptoms. Dopaminergic, glutamatergic, serotonergic, noradrenergic, cholinergic, anti-inflammatory compounds, hormones, and psychostimulants are explored. Finally, we review pharmacological global treatment guidelines for negative symptoms. In general, switching to a second-generation antipsychotic seems to be most often recommended for patients with schizophrenia on first-generation antipsychotics, and an add-on antidepressant is considered when depression is also present. However, the treatment of negative symptoms remains an unmet need. Future, larger clinical studies and meta-analyses are needed to establish effective pharmacological agents for the effective treatment of negative symptoms. [ABSTRACT FROM AUTHOR]

Introduction: It is unclear whether the risk of suicide differs among individuals with only physical health condition, those with only mental health conditions, and those with both types of conditions (multimorbidity) and how emotional social support modifies these associations. This study aimed to examine differences in the association of suicidal ideation with the presence of only physical health conditions, only mental health conditions, and multimorbidity and the modifying role of emotional social support in these associations. Methods: A cross-sectional survey was conducted between August and September 2023 in a Japanese rural town to collect data. The exposure variable was the health condition, and it was classified into 4 groups: disease-free, only physical health conditions, only mental health conditions, and multimorbidity. The outcome variable was suicidal ideation. The data collected were analyzed using multivariate logistic regression analysis and stratified analysis. Results: Suicidal ideation was found to have a significant positive association with the presence of only mental health conditions and multimorbidity. These associations remained unchanged in the absence of emotional social support. However, the odds ratio for the only mental health conditions group decreased in the presence of emotional social support, while the odds ratio for the multimorbidity group remained significantly higher. Conclusions: Suicidal ideation is positively associated with the presence of only mental health conditions and multimorbidity, but emotional social support modifies only the association between suicidal ideation and the presence of only mental health conditions. These results suggest that it may be important to identify the type of social support one needs based on one's health condition to prevent suicide. [ABSTRACT FROM AUTHOR]

Introduction: The relationship between schizophrenia and violence is heterogeneous and complex. The aim of this study was to explore the characteristics and the potential risk factors for violence crime in patients with schizophrenia. Methodology: We conducted a retrospective case-control study at the Judicial Psychiatric Identification Unit of Xiangya Second Hospital of Central South University from January 1, 2013 to December 31, 2016. The case group included violent offenders diagnosed with schizophrenia, while the control group comprised non-violent individuals with the same diagnosis. Results: There were 308 individuals in the violent group [subdivided into the homicide group (n = 155) and the intentional injury group (n = 153)] and 139 individuals in the non-violent group. A risk model showed that a history of violence (odds ratio (OR) = 2.88, 95% CI [1.79–4.64]), persecutory delusions (OR = 2.57, 95% CI [1.63–4.06]), regular treatment in the previous four weeks (OR = 0.29, 95% CI [0.16–0.51]) and insight (OR = 0.30, 95% CI [0.14-0.62]) were independently associated with violence. Conclusion: This study provided useful clinical information to identify risk factors for violence and develop better strategic programs to manage violence in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

For several decades, the dopamine hypothesis contributed to the discovery of numerous typical and atypical antipsychotics and was the sole hypothesis for the pathophysiology of schizophrenia. However, neither typical nor atypical antipsychotics, other than clozapine, have been effective in addressing negative symptoms and cognitive impairments, which are indices for the prognostic and disability outcomes of schizophrenia. Following the development of atypical antipsychotics, the therapeutic targets for antipsychotics expanded beyond the blockade of dopamine D2 and serotonin 5-HT2A receptors to explore the partial agonism of the D2 receptor and the modulation of new targets, such as D3, 5-HT1A, 5-HT7, and metabotropic glutamate receptors. Despite these efforts, to date, psychiatry has not successfully developed antipsychotics with antipsychotic properties proven to be superior to those of clozapine. The glutamate hypothesis, another hypothesis regarding the pathophysiology/pathomechanism of schizophrenia, was proposed based on clinical findings that N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists, such as phencyclidine and ketamine, induce schizophrenia-like psychotic episodes. Large-scale genome-wide association studies (GWASs) revealed that approximately 30% of the risk genes for schizophrenia (the total number was over one hundred) encode proteins associated with glutamatergic transmission. These findings supported the validation of the glutamate hypothesis, which was inspired by the clinical findings regarding NMDAR antagonists. Additionally, these clinical and genetic findings suggest that schizophrenia is possibly a syndrome with complicated pathomechanisms that are affected by multiple biological and genetic vulnerabilities. The glutamate hypothesis has been the most extensively investigated pathophysiology/pathomechanism hypothesis, other than the dopamine hypothesis. Studies have revealed the possibility that functional abnormalities of the NMDAR play important roles in the pathophysiology/pathomechanism of schizophrenia. However, no antipsychotics derived from the glutamatergic hypothesis have yet been approved for the treatment of schizophrenia or treatment-resistant schizophrenia. Considering the increasing evidence supporting the potential pro-cognitive effects of glutamatergic agents and the lack of sufficient medications to treat the cognitive impairments associated with schizophrenia, these previous setbacks cannot preclude research into potential novel glutamate modulators. Given this background, to emphasize the importance of the dysfunction of the NMDAR in the pathomechanism and/or pathophysiology of schizophrenia, this review introduces the increasing findings on the functional abnormalities in glutamatergic transmission associated with the NMDAR. [ABSTRACT FROM AUTHOR]

Background: The Charlson Comorbidity Index (CCI) is commonly employed for predicting mortality. Nonetheless, its performance has rarely been evaluated in patients with dementia. This study aimed to examine the predictive capability of the CCI-based model for survival prediction in Thai patients diagnosed with dementia. Methods: An external validation study was conducted using retrospective data from adults with dementia who had visited the outpatient departments at Maharaj Nakorn Chiang Mai Hospital between 2006 and 2012. The data obtained from electronic medical records included age, gender, date of dementia diagnosis and death, types of dementia, and comorbidities at the time of dementia diagnosis. The discriminative ability and calibration of the CCI-based model were estimated using Harrell's C Discrimination Index and visualized with calibration plot. As the initial performance did not meet satisfaction, model updating and recalibration were performed. Results: Of 702 patients, 56.9% were female. The mean age at dementia diagnosis was 75.22 (SD 9.75) year-old. During external validation, Harrell's C-statistic of the CCI-based model was 0.58 (95% CI, 0.54–0.61). The model showed poor external calibration. Model updating was subsequently performed. All updated models demonstrated a modest increase in Harrell's C-statistic. Temporal recalibration did not significantly improve the calibration of any of the updated models. Conclusion: The CCI-based model exhibited fair discriminative ability and poor calibration for predicting survival in Thai patients diagnosed with dementia. Despite attempts at model updating, significant improvements were not achieved. Therefore, it is important to consider the incorporation of other influential prognostic factors. [ABSTRACT FROM AUTHOR]

Background: Low health literacy is costly and observed among justice-impacted adults (JIA), a group that often faces numerous barriers in accessing healthcare and a disproportionate burden of illness. Health literacy interventions for JIA are critically needed to improve healthcare access and related outcomes. Methods: This manuscript describes the protocol for a longitudinal mixed-methods randomized clinical trial that assesses the effectiveness of a coach-guided health literacy intervention on JIA's healthcare access. The intervention was previously piloted with justice impacted adults. We will recruit 300 JIA ages 18 + in San Diego, California. Participants will be randomized 1:1 to the Treatment Group (i.e., coach-guided intervention providing 12 sessions of individualized health coaching and service navigation over 6 months) or the Control Group (i.e., self-study of the health coaching program, and brief service navigation support). We will quantitatively assess JIA's healthcare access defined as: use of healthcare, health insurance status, and regular source of care at 6-months as the primary outcomes. Participants will also be surveyed at 12-months. Statistical analyses will incorporate the intent-to-treat (ITT) principle and we will estimate mixed-effects logistic regression for the primary outcomes. We will also conduct qualitative interviews at 6 and 12-months with 40 purposively sampled participants, stratified by study arm, who reported healthcare access barriers at baseline. Interviews will explore participants' satisfaction with the intervention, healthcare attitudes, self-efficacy for and barriers to healthcare access over time, perceived contribution of the intervention to health and well-being, and diffusion of intervention-related information within participants' social networks. We will conduct deductive thematic analyses of qualitative data. Discussion: Low health literacy among JIA is a foundational challenge requiring tailored intervention strategies. Findings from this trial may inform policies and the structure of service delivery models to build health literacy among JIA in institutional and community settings throughout the United States and elsewhere. Trial registration: This study is registered with the United States' ClinicalTrials.gov registry under protocol # 161,903. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: People with serious mental health problems (SMHP) are more likely to be admitted to psychiatric hospital following contact with crisis services. Admissions can have significant personal costs, be traumatic and are the most expensive form of mental health care. There is an urgent need for treatments to reduce suicidal thoughts and behaviours and reduce avoidable psychiatric admissions. Methods: A multi-stage, multi-arm (MAMS) randomised controlled trial (RCT) with four arms conducted over two stages to determine the clinical and cost effectiveness of three psychosocial treatments, compared to treatment as usual (TAU), for people with SMHP who have had recent suicidal crisis. Primary outcome is any psychiatric hospital admissions over a 6-month period. We will assess the impact on suicidal thoughts and behaviour, hope, recovery, anxiety and depression. The remote treatments delivered over 3 months are structured peer support (PREVAIL); a safety planning approach (SAFETEL) delivered by assistant psychologists; and a CBT-based suicide prevention app accessed via a smartphone (BrighterSide). Recruitment is at five UK sites. Stage 1 includes an internal pilot with a priori progression criteria. In stage 1, the randomisation ratio was 1:1:1:2 in favour of TAU. This has been amended to 2:2:3 in favour of TAU following an unplanned change to remove the BrighterSide arm following the release of efficacy data from an independent RCT. Randomisation is via an independent remote web-based randomisation system using randomly permuted blocks, stratified by site. An interim analysis will be performed using data from the first 385 participants from PREVAIL, SAFETEL and TAU with outcome data at 6 months. If one arm is dropped for lack of benefit in stage 2, the allocation ratio of future participants will be 1:1. The expected total sample size is 1064 participants (1118 inclusive of BrighterSide participants). Discussion: There is a need for evidence-based interventions to reduce psychiatric admissions, via reduction of suicidality. Our focus on remote delivery of established brief psychosocial interventions, utilisation of different modalities of delivery that can provide sustainable and scalable solutions, which are also suitable for a pandemic or national crisis context, will significantly advance treatment options. Trial registration: ISRCTN33079589. Registered on June 20, 2022. [ABSTRACT FROM AUTHOR]

Objectives: To explore the care and support received and wanted by United Kingdom (UK) South Asian and White British people affected by dementia and whether access to it is equitable. Design: Semi-structured interviews using a topic guide. Setting: Eight memory clinics across four UK National Health Service Trusts; three in London and one in Leicester. Participants: We purposefully recruited a maximum variation sample of people living with dementia from South Asian or White British backgrounds, their family carers, and memory clinic clinicians. We interviewed 62 participants including 13 people living with dementia, 24 family carers, and 25 clinicians. Measurements: We audio-recorded interviews, transcribed them, and analyzed them using reflexive thematic analysis. Results: People from either background were willing to accept needed care and wanted competence and communication from carers. South Asian people frequently discussed needing care from someone with a shared language, but language differences could also be an issue for White British people. Some clinicians thought South Asian people had a stronger preference to provide care within the family. We found that preferences for who provides care varied across families regardless of ethnicity. Those with more financial resources and English language have more options for care that meets their needs. Conclusions: People of the same background make differing choices about care. Equitable access to care is impacted by people's personal resources, and people from South Asian backgrounds may experience the double disadvantage of having fewer options for care that meets their needs and fewer resources to seek care elsewhere. [ABSTRACT FROM AUTHOR]

Purpose: Community rehabilitation is crucial for the long-term treatment of people with chronic psychotic disorder. Ethnic minorities are less likely to seek care and have accessible treatment. This study examines whether the use of rehabilitation services and the relationship between rehabilitation and number of hospitalization days differ between Arabs and Jews. Methods: Data from the Israel National Psychiatric Case Register on 18,684 adults with schizophrenia/schizoaffective disorders hospitalized in 1963–2016 were merged with data from the national Mental Rehabilitation Register. Associations between the use of rehabilitation services and demographic and clinical characteristics were assessed through logistic regression modeling. Associations between ethnicity and duration of rehabilitation (housing or vocational) and annual hospitalization days during Period1: 2001–2009 and Period2: 2010–2016 were analyzed using ANOVA. Results: Among Jewish patients (N = 2556), 37% and 57% used rehabilitation services during Period1 and Period2, respectively, compared with 18% and 40% among Arab patients (N = 15,145) (p < 0.0001). The use of rehabilitation services was significantly higher among Jews (adjusted OR = 2.26, 95% CI 2.07–2.47). Average duration of housing and vocational rehabilitation services did not differ between Arab and Jewish patients. In both groups, duration of rehabilitation was inversely associated with annual hospitalization days. Conclusions: The ethnic disparity in the use of rehabilitation services has narrowed over time, yet remains. Although fewer Arab patients use rehabilitation, Jewish and Arab benefit similarly from the services with regard to reduced hospitalization days. To further close the ethnic gap, greater efforts must be made to expand the availability of culturally appropriate rehabilitation services for the Arab minority. [ABSTRACT FROM AUTHOR]

Emergent literature suggests that micro- and macro-climates influence criminal behaviour; a complex phenomenon that is still incipient in theory development. This mixed-method research starts with a systematic review of the literature on the theoretical premises that urban heat islands amplify aggressive behaviour and crime. Further, it discusses the potential implications of the relationship between the environment and social outcomes on the design and planning of urban environments. A meta-synthesis was conducted to explain the correlations between patterns of criminal behaviour and thermal (dis)comfort. This correlation is to relate fundamental urban design principles to socially sustainable communities that dissuade violence and crime, and otherwise show poorly designed spaces do propagate criminal behaviour. Cross-validation was undertaken using a case study of Midland, a suburb of Perth, Western Australia. Data involves population demographics, temperature, and crime statistics relating to Offences against the Person. Analysis focused on homicide, assault, threatening behaviour, and robbery. The findings imply a positive correlation between long-term temperature, crime, population density, and green canopy cover. Variables of climate (e.g., short-to-long-term climate-related stressors) and crime types also show non-linear association. Nonetheless, forecasting the future of violence and trends of crime through attributes or potential impacts of heat and urban canopy cover on the built environment will inform sustainable social development policy, environmental planning, development strategy, designers, and planners. Recommendations are made around these in relation to making urban communities adaptive to the impacts of global warming and future densification. [ABSTRACT FROM AUTHOR]

Background: Due to limitations of categorical definitions of mental illness, there is a need for quantitative empirical investigations of the dimensional structure of psychopathology. Using exploratory bifactor methods, this study investigated a comprehensive and representative structure of psychopathology in children to better understand how psychotic‐like experiences (PLEs), autism spectrum disorder (ASD) symptoms, impulsivity, and sensitivity to reward and punishment, may be integrated into extant general factor models of psychopathology. Methods: We used seven child‐report and three parent‐report instruments capturing diverse mental health symptoms in 11,185 children aged 9–10 from the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study. We built on previous modeling frameworks by conducting both split sample and full sample factor analytic approaches that harnessed recent methodological advances in bifactor exploratory structural equation modeling (B‐ESEM) to examine a wide range of psychopathology measures not previously integrated into a single analysis. Validity of psychopathology dimensions was examined by investigating associations with sex, age, cognition, imaging measures, and medical service usage. Results: All four factor analytic models showed excellent fit and similar structure within informant. PLEs loaded most highly onto a general psychopathology factor, suggesting that they may reflect non‐specific risk for mental illness. ASD symptoms loaded separately from attention/hyperactivity symptoms. Symptoms of impulsivity and sensitivity to reward and punishment loaded onto specific factors, distinct from externalizing and internalizing factors. All identified factors were associated with clinically relevant risk factors, providing preliminary evidence for their construct validity. Conclusion: By integrating diverse child‐report and parent‐report psychopathology measures for children in the ABCD sample, we deliver data on the quantitative structure of psychopathology for an exceptionally large set of measurements and discuss implications for the field. [ABSTRACT FROM AUTHOR]

Background: Delusions are a hallmark feature of psychotic disorders and lead to significant clinical and functional impairment. Internalizing symptoms—such as symptoms of depression, anxiety, and trauma exposure—are commonly cited to be related to delusions and delusional ideation and are often associated with deficits in social functioning. While emerging studies are investigating the impact of low social engagement on psychotic-like experiences, little work has examined the relationship between social engagement, internalizing symptoms, and delusional ideation, specifically. Methods: Using general population data from the Nathan Kline Institute-Rockland (NKI-Rockland) database (N = 526), we examined the relationships between self-reported delusional ideation, internalizing symptoms, and social engagement and tested four indirect effect models to understand how these factors interrelate. Results: Delusional ideation was significantly associated with both increased internalizing symptoms (r = 0.41, p < 0.001) and lower social engagement (r = − 0.14, p = 0.001). Within aspects of social engagement, perceived emotional support showed the strongest relationship with delusional ideation (r = − 0.17, p < 0.001). Lower social engagement was also significantly associated with increased internalizing symptoms (r = − 0.29, p < 0.001). Cross-sectional models suggest that internalizing symptoms have a significant indirect effect on the association between delusional ideation and social engagement. Conclusions: These findings reveal that elevated delusional ideation in the general population is associated with lower social engagement. Elevated internalizing symptoms appear to play a critical role in reducing engagement, possibly exacerbating delusional thinking. Future work should examine the causal and temporal relationships between these factors. [ABSTRACT FROM AUTHOR]

Objective: Understanding prognosis is critical to anticipating public health needs and providing care to individuals with psychotic disorders. However, the long-term course of remission and recovery remains unclear. In this study, the most common trajectories of illness course are described for a cohort of individuals followed for 25 years since first admission for psychosis. Methods: Participants are from the Suffolk County Mental Health Project, an epidemiological study of first-admission psychosis. Data for the present study was collected from six follow-ups, with 311 individuals assessed at the 25-year follow-up. Common patterns of remission and recovery were assessed in the baseline cohort of 591 individuals and the subsample from the 25-year follow up. Results: In the baseline cohort and the 25-year subsample, the most common trajectory for individuals with schizophrenia spectrum disorders was no remission and no recovery. Among individuals with other psychotic disorders, in both the baseline and 25-year cohorts, the modal pattern was one of intermittent remission and recovery. Individuals with other psychotic disorders were more likely to experience stable remission (15.1%) and stable recovery (21.1%), outcomes that were rare among individuals with schizophrenia spectrum disorders (0% and 0.6%, respectively). Conclusions: The modal longitudinal pattern for individuals with other psychoses is one of multiple transitions into and out of symptomatic and functional recovery. Engagement in a long-term health care plan may help individuals detect and respond to these changes. Sustained remission and recovery are rare among people with schizophrenia spectrum disorders. Efforts should be directed toward developing more effective treatments for this population. [ABSTRACT FROM AUTHOR]

The present work explored the independent and joint consequences of multiple factors that prior work indicated were central to suicide risk among a sample of public safety personnel. Of key interest relevant to the experience of suicidal thoughts and behaviors were the roles of sleep disturbance, social support, and agency stigma discouraging discussion of mental health. These risk factors and relevant demographic variables were measured in a nationally representative sample of law enforcement and correctional officers at time 1. Their suicidal thoughts and behaviors were assessed one year later at time 2. Officers who reported sleep disturbances at time 1 were more likely to report suicidal thoughts and behaviors at time 2. Mediation analyses indicated that the effect of sleep on the officers' suicidal responses was partially accounted for by their lower social support. For officers, sleep disturbances may contribute to loneliness and interfere with social relationships, which has negative mental health consequences. However, social support was only a partial mediator suggesting that sleep disturbances have additional influences on suicidal responses for officers beyond their impact on social support. Perceived stigma from the agency regarding the discussion of psychological problems was also an independent predictor of suicidal thoughts and behaviors. The stigma that these officers perceived likely exasperated the suicidal reactions because it may have interfered with their tendency to seek help and benefit from any ongoing treatment. The implications of these findings for treatment and future research building on the present work are discussed. [ABSTRACT FROM AUTHOR]

The convergence of smart technologies and predictive modelling in prisons presents an exciting opportunity to revolutionize the monitoring of inmate behaviour, allowing for the early detection of signs of distress and the effective mitigation of suicide risks. While machine learning algorithms have been extensively employed in predicting suicidal behaviour, a critical aspect that has often been overlooked is the interoperability of these models. Most of the work done on model interpretations for suicide predictions often limits itself to feature reduction and highlighting important contributing features only. To address this research gap, we used Anchor explanations for creating human-readable statements based on simple rules, which, to our knowledge, have never been used before for suicide prediction models. We also overcome the limitation of anchor explanations, which create weak rules on highdimensionality datasets, by first reducing data features with the help of SHapley Additive exPlanations (SHAP). We further reduce data features through anchor interpretations for the final ensemble model of XGBoost and random forest. Our results indicate significant improvement when compared with state-of-the-art models, having an accuracy and precision of 98.6% and 98.9%, respectively. The F1-score for the best suicide ideation model appeared to be 96.7%. [ABSTRACT FROM AUTHOR]

There is a lack of robust research investigating the association between neurocognitive impairments and chronic tobacco smoking in adolescents/young adults. Therefore, a systematic review and meta-analysis were conducted to examine this association by pooling cross-sectional studies published from 1980 to 2023. The systematic review assessed the neurocognitive performances between chronic tobacco smokers and nonsmokers in each study. The meta-analysis included six studies that compared chronic tobacco smokers against non-smokers using neuropsychological tests covering three neurocognitive domains. The results showed a cross-sectional association between impairpments in motor impulsivity across two aspects: reaction delay and incongruent errors, with the effect size being (SDM = 0.615, p = 0.000) and (SDM = 0.593, p = 0.000) respectively. However, no significant associations were found for intelligence (SDM = 0.221, p = 0.425) or working memory (SDM = 0.150, p = 0.581). This study highlights the need for further research to explore a greater number of neurocognitive domains in the context of chronic smoking in adolescents/young adults, particularly motor impulsivity, intelligence and working memory, as well as the socioeconomic factors involved. There is also a need to further study the effects of emerging alternative nicotine administration methods in this age group. [ABSTRACT FROM AUTHOR]

Management of negative symptoms is one of the most challenging and important unmet needs of schizophrenia treatment. Negative symptoms together with positive symptoms result in significant psychosocial impairment and poor quality of life. Existing studies on atypical antipsychotics reported limited treatment adherence due to higher prevalence of treatment-emergent adverse events, such as diabetes, weight gain, hyperlipidemia, hyperprolactinemia and hypertension. A compound with greater affinity for dopamine D2/D3 receptors may improve negative symptoms, mood, and cognitive impairment associated with schizophrenia. In 2015, the US FDA has approved cariprazine, a partial D2/D3 agonist for treatment of schizophrenia, mania or mixed episodes. Midlands and Lancashire Commissioning Support Unit, UK (2019) has particularly suggested cariprazine for the treatment of predominant negative symptoms of schizophrenia. India's Central Drugs Standard Control Organization (CDSCO) has approved cariprazine in 2021 for the treatment of schizophrenia, manic or mixed episodes associated with bipolar I disorder. A ten-fold greater affinity for D3 receptors and partial agonism to serotonin receptors, along with longer half-lifemake cariprazine distinct when compared with other atypical antipsychotics. Cariprazine is also reported to have fewer incidents of metabolic and hormonal adverse events, and has been shown to provide better relapse prevention. Recent evidence indicates promising effect of cariprazine in ameliorating negative symptoms as well as psychotic symptoms in patients with schizophrenia. In addition, improved adherence to treatment (adjunctive/monotherapy) with cariprazine in patients having inadequate response to an ongoing antipsychotic treatment has also been clinically established. This review presents the evidence-based safety and efficacy of cariprazine for treatment of predominant negative symptoms of schizophrenia. [ABSTRACT FROM AUTHOR]

Traumatic experiences can have long-lasting negative effects on individuals, organizations, and societies. If trauma is not addressed, it can create unsafe cultures with constant arousal, untrusting relationships, and the use of coercive measures. Trauma-informed care (TIC) can play a central role in mitigating these negative consequences, but it is unknown how and in which way(s) TIC should be implemented. Our objective was to conduct a scoping review that systematically explored and mapped research conducted in this area and to identify existing knowledge about the implementation of TIC. The search was conducted on the CINAHL, Cochrane, Embase, ERIC, Medline, PsycINFO, and Web of Science databases, and more than 3000 empirical papers, published between 2000 and 2022, were identified. Following further screening, we included 157 papers in our review, which were mainly from the USA, Australia, New Zealand, and Canada, focusing on study settings, methodologies, and definitions of TIC, as well as the types of interventions and measures used. This review shows that TIC is a complex and multifaceted framework, with no overarching structure or clear theoretical underpinnings that can guide practical implementations. TIC has been defined and adapted in varied ways across different settings and populations, making it difficult to synthesize knowledge. A higher level of agreement on how to operationalize and implement TIC in international research could be important in order to better examine its impact and broaden the approach. [ABSTRACT FROM AUTHOR]

Multiple genome sequencing studies have identified genetic abnormalities as major causes of severe intellectual disability (ID). However, many children affected by mild ID and borderline intellectual functioning (BIF) lack a genetic diagnosis because known causative ID genetic mutations have not been identified or the role of genetic variants in mild cases is less understood. Genetic variant testing in mild cases is necessary to provide information on prognosis and risk of occurrence. In this study, we report two sibling patients who were 5 years 9 months old and 3 years 3 months old and presented to the hospital due to developmental delay. Clinical assessment and chromosomal microarray analysis were performed. The patients were diagnosed with mild intellectual disability (ID) and borderline intellectual functioning (BIF). Genetic analysis identified a loss of 12p11.22, including the OVCH1-AS1, OVCH1, and TMTC1 genes, which was the only variant that occurred in both sisters. Identical variants were found in their father with probable BIF. Neither patient presented any brain structural abnormalities or dysmorphism, and no exogenous factors or parenting problems were reported. Thus, loss of 12p11.22 may be associated with our patients' cognitive impairment. The OVCH1, OVCH1-AS1 and TMTC1 variants identified in this study are the most likely disease-causing genes in the sisters. Our findings may expand as yet limited knowledge on mild ID and BIF causative variants, which would further support the diagnosis even if the severity is mild. [ABSTRACT FROM AUTHOR]

Background: Violence in schizophrenia (SCZ) is a phenomenon associated with neurobiological factors. However, the neural mechanisms of violence in patients with SCZ are not yet sufficiently understood. Thus, this study aimed to explore the structural changes associated with the high risk of violence and its association with impulsiveness in patients with SCZ to reveal the possible neurobiological basis. Method: The voxel-based morphometry approach and whole-brain analyses were used to measure the alteration of gray matter volume (GMV) for 45 schizophrenia patients with violence (VSC), 45 schizophrenia patients without violence (NSC), and 53 healthy controls (HC). Correlation analyses were used to examine the association of impulsiveness and brain regions associated with violence. Results: The results demonstrated reduced GMV in the right insula within the VSC group compared with the NSC group, and decreased GMV in the right temporal pole and left orbital part of superior frontal gyrus only in the VSC group compared to the HC group. Spearman correlation analyses further revealed a positive correlation between impulsiveness and GMV of the left superior temporal gyrus, bilateral insula and left medial orbital part of the superior frontal gyrus in the VSC group. Conclusion: Our findings have provided further evidence for structural alterations in patients with SCZ who had engaged in severe violence, as well as the relationship between the specific brain alterations and impulsiveness. This work provides neural biomarkers and improves our insight into the neural underpinnings of violence in patients with SCZ. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment is a core symptom of schizophrenia and is associated with functional outcomes. Improving cognitive function is an important treatment goal. Studies have reported beneficial cognitive effects of the second-generation antipsychotic (SGA) ziprasidone. Reducing the dose of first-generation antipsychotics (FGA) might also improve cognitive function. This study compared the cognitive effects in long-stay patients who were randomized to groups who underwent FGA dose reduction or switched to ziprasidone. Methods: High-dose FGA was reduced to an equivalent of 5 mg of haloperidol in 10 patients (FGA-DR-condition), and 13 patients switched to ziprasidone 80 mg b.i.d. (ZIPRA condition). Five domains of cognitive function were assessed before dose reduction or switching (T0) and after 1 year (T1). This study was approved by the ethics committee of the Open Ankh (CCMO number 338) and registered at the Netherlands Trial Register (code 5864). Results: Non-significant deterioration was seen in all cognitive domains studied in the FGA-DR condition, whereas there was a non-significant improvement in all cognitive domains in the ZIPRA condition. The most robust difference between conditions, in favor of ziprasidone, was in executive function. Conclusions: In patients with severe chronic schizophrenia, ziprasidone had a non-significant and very modest beneficial effect on cognitive function compared with FGA dose reduction. Larger trials are needed to further investigate this effect. [ABSTRACT FROM AUTHOR]