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Schizophrenia Research Jun 2024
PubMed: 38909487
DOI: 10.1016/j.schres.2024.04.011 -
Psychiatry Research Jun 2024Although HCV cure after direct-acting antiviral (DAA) treatment is associated with hepatic and extrahepatic benefits, few studies have assessed the impact of HCV...
BACKGROUND AND AIMS
Although HCV cure after direct-acting antiviral (DAA) treatment is associated with hepatic and extrahepatic benefits, few studies have assessed the impact of HCV treatment in people with mental disorders (PWMDs). Using quasi-exhaustive national data from the French administrative health care databases (SNDS), we explored whether DAA treatment in PWMDs affected hospitalizations in both psychiatric and non-psychiatric settings.
METHODS
All adult PWMDs identified in the SNDS with DAA treatment initiation between 2015 and 2018 and 12 months of data pre- and post-treatment were included. Individuals were algorithmically classified into one or several subgroups: "addictive disorders", "neurotic and mood disorders", "psychotic disorders" and "other psychiatric disorders". A longitudinal approach was used to compare the frequency and duration of hospitalizations one year before and one year after DAA treatment.
RESULTS
In total, 17,203 individuals met the inclusion criteria. The number of patients with at least one hospitalization (any type) decreased by 28% after HCV cure. The mean numbers of hospitalizations in non-psychiatric units per patient per year were 1·2 during the pre-DAA period and 0·8 during the post-DAA period (p < 0·0001). Similarly, the number of hospitalizations in psychiatric wards decreased from 1·4 to 1·2 (p = 0.006). The duration of hospital stays decreased from 20·2 days to 16·7 days in non-psychiatric settings (p < 0·0001). These results were also homogeneous and significant across all subgroups.
CONCLUSIONS
HCV cure significantly lowered the frequency and duration of hospitalizations during the year following treatment in all PWMDs subgroups, including the psychotic disorders subgroup.
FUNDING
This study was funded by Gilead Sciences.
PubMed: 38909413
DOI: 10.1016/j.psychres.2024.116032 -
Biological Psychiatry Jun 2024Early Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence...
BACKGROUND
Early Psychosis patients (EP, within 3 years after psychosis onset) show significant variability, making outcome predictions challenging. Currently, little evidence exists for stable relationships between neural microstructural properties and symptom profiles across EP diagnoses, limiting the development of early interventions.
METHODS
A data-driven approach, Partial Least Squares (PLS) correlation, was used across two independent datasets to examine multivariate relationships between white matter (WM) properties and symptomatology, to identify stable and generalizable signatures in EP. The primary cohort included EP patients from the Human Connectome Project-Early Psychosis (n=124). The replication cohort included EP patients from the Feinstein Institute for Medical Research (n=78). Both samples included individuals with schizophrenia, schizoaffective disorder, and psychotic mood disorders.
RESULTS
In both cohorts, a significant latent component (LC) corresponded to a symptom profile combining negative symptoms, primarily diminished expression, with specific somatic symptoms. Both LCs captured comprehensive features of WM disruption, primarily a combination of subcortical and frontal association fibers. Strikingly, the PLS model trained on the primary cohort accurately predicted microstructural features and symptoms in the replication cohort. Findings were not driven by diagnosis, medication, or substance use.
CONCLUSIONS
This data-driven transdiagnostic approach revealed a stable and replicable neurobiological signature of microstructural WM alterations in EP, across diagnoses and datasets, showing a strong covariance of these alterations with a unique profile of negative and somatic symptoms. This finding suggests the clinical utility of applying data-driven approaches to reveal symptom domains that share neurobiological underpinnings.
PubMed: 38908657
DOI: 10.1016/j.biopsych.2024.06.011 -
American Journal of Obstetrics and... Jun 2024To evaluate the association between cannabis use during pregnancy and the risk for long-term neuropsychiatric pathology in the offspring. (Review)
Review
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 two 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 non-exposed. Data were pooled using random-effects models.
RESULTS
Eighteen eligible observational studies were included in the systematic review, and seventeen 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).
CONCLUSIONS
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.
PubMed: 38908654
DOI: 10.1016/j.ajog.2024.06.014 -
Spanish Journal of Psychiatry and... Jun 2024Approximately 20-30% of patients with schizophrenia fail to respond to antipsychotic treatment and are considered treatment resistant (TR). Although clozapine is the...
BACKGROUND
Approximately 20-30% of patients with schizophrenia fail to respond to antipsychotic treatment and are considered treatment resistant (TR). Although clozapine is the treatment of choice in these patients, in real-world clinical settings, clinicians often delay clozapine initiation, especially in first-episode psychosis (FEP).
AIM
The main aim of this study was to describe prescription patterns for clozapine in a sample of patients diagnosed with FEP and receiving specialized treatment at a university hospital. More specifically, we aimed to determine the following: (1) the proportion of patients who received clozapine within two years of disease onset, (2) baseline predictors of clozapine use, (3) time from starting the first antipsychotic to clozapine initiation, (4) concomitant medications, and (5) clozapine-related adverse effects.
METHODS
All patients admitted to a specialized FEP treatment unit at our hospital between April 2013 and July 2020 were included and followed for two years. The following variables were assessed: baseline sociodemographic characteristics; medications prescribed during follow-up; clozapine-related adverse effects; and baseline predictors of clozapine use. We classified the sample into three groups: clozapine users, clozapine-eligible, and non-treatment resistant (TR).
RESULTS
A total of 255 patients were consecutively included. Of these, 20 (7.8%) received clozapine, 57 (22.4%) were clozapine-eligible, and 178 (69.8%) were non-TR. The only significant variable associated with clozapine use at baseline was the Global Assessment of Functioning (GAF) score (R=0.09, B=-0.07; OR=0.94; 95% CI: 0.88-0.99; p=0.019). The median time to clozapine initiation was 55.0 (93.3) days. The most common side effect was sedation.
CONCLUSIONS
A significant proportion (30.2%) of patients in this cohort were treatment resistant and eligible for clozapine. However, only 7.8% of the sample received clozapine, indicating that this medication was underprescribed. A lower baseline GAF score was associated with clozapine use within two years, suggesting that it could be used to facilitate the early identification of patients who will need treatment with clozapine, which could in turn improve treatment outcomes.
PubMed: 38908404
DOI: 10.1016/j.sjpmh.2024.06.001 -
Microbiome Jun 2024
PubMed: 38907261
DOI: 10.1186/s40168-024-01846-5 -
Evaluation of the neuroprotective effect of antipsychotics by serum quantification of protein S100B.Farmacia Hospitalaria : Organo Oficial... Jun 2024This research delves into the intricate interplay between antipsychotic medications and neuroprotection focusing on the S100B protein-a central player in the regulation...
OBJECTIVE
This research delves into the intricate interplay between antipsychotic medications and neuroprotection focusing on the S100B protein-a central player in the regulation of neuroapoptotic activity.
METHOD
Blood samples were collected to assess serum S100B protein levels using an immunoassay of immunoelectrochemiluminescence. The first two samples were collected with a 3-month interval between each, and the third sample was obtained 6 months after the previous one. Changes in S100B protein levels throughout the study were assessed using Friedman's ANOVA test. This was followed by the Wilcoxon signed-rank test with Bonferroni correction to account for multiple comparisons.
RESULTS
This study involved 40 patients diagnosed with severe mental disorders (34 schizophrenia, 4 schizoaffective disorder, 1 bipolar disorder, and 1 borderline personality disorder). These patients had been receiving antipsychotic treatment for an average duration of 17 years. The results revealed that the S100B protein remained within physiological levels (median values 39.0 ng/L for the first sample, median values 41.0 ng/L for the second sample, and median values 40.5 ng/L for the third sample) with no significant changes (p = 0.287), with all anti-psychotic medicaments values consistently below 50 ng/L, a lower value compared to maximum range of 105 ng/L. Importantly, there were no significant differences in S100B protein levels between patients on monotherapy and those on combination antipsychotic therapy (p = 0.873), suggesting that combination therapy did not increase neuroapoptotic activity.
CONCLUSIONS
These findings provide compelling evidence for the potential neuroprotective effects of long-term antipsychotic treatment in individuals with severe mental disorders. By maintaining physiological levels of the S100B protein, antipsychotic medications may help protect against neuronal damage and dysfunction. This research contributes valuable insights into the neuroprotective mechanisms of antipsychotic drugs, enhancing our understanding of their potential benefits in the treatment of severe mental disorders.
PubMed: 38906717
DOI: 10.1016/j.farma.2024.05.013 -
Biochemical Pharmacology Jun 2024For nearly fifty years, the dopamine hypothesis has dominated our understanding of the pathophysiology of schizophrenia and provided the lone target for drug... (Review)
Review
For nearly fifty years, the dopamine hypothesis has dominated our understanding of the pathophysiology of schizophrenia and provided the lone target for drug development. However, with the exception of clozapine, the dopamine D2 receptor antagonizing anti-psychotic drugs have little impact on the negative symptoms and cognitive deficits, aspects of the disorder that robustly predict outcome. Pathologic studies reveal cortical atrophy and wide-spread loss of glutamatergic synaptic spines, unexplained by dopaminergic malfunction. Recent genome-wide association studies indicate that at least thirty risk genes for schizophrenia encode proteins localized to the glutamatergic synapse and inhibit glutamate neurotransmission, especially at the NMDA receptor. To function, the NMDA receptor requires the binding of glycine (primarily in the cerebellum and brainstem) or D-serine (in forebrain) to the NR1 channel subunit of the NMDA receptor. Genetically silencing the gene (srr) encoding serine racemase, the biosynthetic enzyme for D-serine, results in forebrain NMDA receptor hypofunction. The srr-/- mice have 90 % loss of endogenous D-serine and approximately 70 % decrease in NMDA receptor function. Several animal models of schizophrenia are based on behavioral and pharmacologic strategies, which have negligible validity with regard to the fundamental etiology of schizophrenia. We summarize here the results of a mouse model, in which srr, one of the two dozen or more risk gene for schizophrenia that affect NMDA receptor function, has been inactivated. The srr-/- mice exhibit striking similarities to schizophrenia including cortical atrophy, loss of cortico-limbic glutamatergic synapses, increased sub-cortical dopamine release, EEG abnormalities, and cognitive impairments. The limited efficacy of drugs targeting the glutamatergic synapse on DSM-5 diagnosed criteria for schizophrenia used in clinical trials may reflect the fact that only 30 % of the patients have impaired glutamatergic neurotransmission, resulting from the genetic heterogeneity of the disorder.
PubMed: 38906225
DOI: 10.1016/j.bcp.2024.116376 -
Comprehensive Psychiatry Jun 2024Psychotic-like experiences (PLEs) during adolescence can lead to psychotic disorders. Digital media usage has been suggested to link to PLEs, but research is limited on...
INTRODUCTION
Psychotic-like experiences (PLEs) during adolescence can lead to psychotic disorders. Digital media usage has been suggested to link to PLEs, but research is limited on how different types of screen exposure may differentially relate to PLEs over time. This study aimed to examine longitudinal associations between screen usage patterns and PLEs in adolescents.
METHODS
Participants comprised 11,876 adolescents assessed annually from ages 9-12 years as part of the Adolescent Brain Cognitive Development study (ABCD). Screen usage (TV, video games, online video, social media, texting, video chat) and PLEs were assessed via self-report. Longitudinal network analysis models were estimated to examine connections between screen usage types and PLEs across three time points.
RESULTS
Two clusters were formed, including digital media for socializing (e.g., social media/texting/video chat) and digital media for entertainment (e.g., online video/video games/TV). Texting and online video(s) had the highest centrality at each time point, suggesting importance in the network. PLE symptoms of hallucinations and concentration difficulties exhibited higher centrality than other symptoms. Online video and TV were influential bridges between screen usage and PLEs. Network structure significantly differed between ages 9-10 and 10-12 years, but global strength was unchanged over time.
DISCUSSION
Results highlight the importance of understanding the associations between specific screen usage types and PLE symptoms. Texting and online video usage appear most influential in the development of adolescent PLEs over time. Findings can inform targeted interventions to promote healthy screen habits and reduce PLEs in at-risk youth.
PubMed: 38905775
DOI: 10.1016/j.comppsych.2024.152509 -
Nordic Journal of Psychiatry Jun 2024The Positive and Negative Syndrome Scale (PANSS) is one of the most commonly used assessment tools for measuring psychotic symptoms. The Psychotic Symptom Rating Scales...
Measuring the concurrent validity of the norwegian versions of the psychotic symptom rating scales (PSYRATS) and the positive scale from the positive and negative syndrome scale (PANSS).
PURPOSE
The Positive and Negative Syndrome Scale (PANSS) is one of the most commonly used assessment tools for measuring psychotic symptoms. The Psychotic Symptom Rating Scales (PSYRATS) is another instrument created specifically to assess delusions and auditory hallucinations. However, research on the concurrent validity of PSYRATS with PANSS is limited. There are also inconsistent findings regarding the association between the PSYRATS scales and the PANSS positive scale. The present study aims to add to the understanding of the concurrent validity of these measures, while also incorporating a broader measure of psychiatric symptoms (the symptom scale from the Global Assessment of Functioning Scale - split version, GAF-S).
MATERIALS AND METHODS
Spearman's Rank Order Correlations (rho) were calculated for scores from the PANSS positive scale, PSYRATS and GAF-S in a sample of 148 participants with psychotic disorders at three time points.
RESULTS
The findings indicate concurrent validity between PSYRATS and PANSS, while the PSYRATS scales were not consistently correlated with GAF-S.
CONCLUSIONS
PSYRATS may be a valid assessment tool for evaluating psychotic symptoms. The utility of PSYRATS in research and clinical practice should be investigated further.
PubMed: 38905132
DOI: 10.1080/08039488.2024.2367638