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Immunity & Ageing : I & A Jun 2024Neutrophils play an essential role in Alzheimer's disease (AD) pathology. However, the extent of their heterogeneity remains poorly explored, particularly in the context...
BACKGROUND
Neutrophils play an essential role in Alzheimer's disease (AD) pathology. However, the extent of their heterogeneity remains poorly explored, particularly in the context of developing novel therapies targeting these cells.
RESULTS
We investigate the population structure of neutrophils purified from peripheral blood samples of AD mice. Utilizing single cell RNA sequencing, we comprehensively map neutrophil populations into six distinct clusters and find that the Neu-5 subset is specially enriched in AD mice. This subset exhibits fewer specific granules and a lower mature score. Gene ontology (GO) analysis reveals that genes involved in cytokine-mediated signaling are downregulated in the Neu-5 cluster. Furthermore, we identify the Ccrl2 gene is specifically upregulated in this subgroup, which is confirmed by flow cytometry in AD mice. Finally, immunohistochemical staining indicates that CCRL2 protein is increased in the brains of AD mice.
CONCLUSIONS
We identify a unique CCRL2 positive neutrophil cluster, that is specifically enriched in the peripheral blood of AD mice.
PubMed: 38918830
DOI: 10.1186/s12979-024-00448-x -
Journal of Neurodevelopmental Disorders Jun 2024Minor physical anomalies (MPAs) are congenital morphological abnormalities linked to disruptions of fetal development. MPAs are common in 22q11.2 deletion syndrome...
BACKGROUND
Minor physical anomalies (MPAs) are congenital morphological abnormalities linked to disruptions of fetal development. MPAs are common in 22q11.2 deletion syndrome (22q11DS) and psychosis spectrum disorders (PS) and likely represent a disruption of early embryologic development that may help identify overlapping mechanisms linked to psychosis in these disorders.
METHODS
Here, 2D digital photographs were collected from 22q11DS (n = 150), PS (n = 55), and typically developing (TD; n = 93) individuals. Photographs were analyzed using two computer-vision techniques: (1) DeepGestalt algorithm (Face2Gene (F2G)) technology to identify the presence of genetically mediated facial disorders, and (2) Emotrics-a semi-automated machine learning technique that localizes and measures facial features.
RESULTS
F2G reliably identified patients with 22q11DS; faces of PS patients were matched to several genetic conditions including FragileX and 22q11DS. PCA-derived factor loadings of all F2G scores indicated unique and overlapping facial patterns that were related to both 22q11DS and PS. Regional facial measurements of the eyes and nose were smaller in 22q11DS as compared to TD, while PS showed intermediate measurements.
CONCLUSIONS
The extent to which craniofacial dysmorphology 22q11DS and PS overlapping and evident before the impairment or distress of sub-psychotic symptoms may allow us to identify at-risk youths more reliably and at an earlier stage of development.
Topics: Humans; DiGeorge Syndrome; Psychotic Disorders; Female; Male; Adolescent; Child; Craniofacial Abnormalities; Young Adult; Adult; Machine Learning; Image Processing, Computer-Assisted
PubMed: 38918700
DOI: 10.1186/s11689-024-09547-8 -
Systematic Reviews Jun 2024Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a...
BACKGROUND
Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia.
METHODS
We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel-Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach.
DISCUSSION
Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO-ID CRD42023410645.
Topics: Humans; Systematic Reviews as Topic; Network Meta-Analysis; Schizophrenia, Treatment-Resistant; Transcranial Direct Current Stimulation; Antipsychotic Agents; Transcranial Magnetic Stimulation; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 38915121
DOI: 10.1186/s13643-024-02585-2 -
Frontiers in Psychiatry 2024The psychic structure of people with psychosis has been the subject of theoretical and qualitative considerations. However, it has not been sufficiently studied...
INTRODUCTION
The psychic structure of people with psychosis has been the subject of theoretical and qualitative considerations. However, it has not been sufficiently studied quantitatively. Therefore, the aim of this study was to explore the structural abilities of people diagnosed with schizophrenia and schizoaffective psychosis using the Levels of Structural Integration Axis of the Operationalized Psychodynamic Diagnosis System (OPD-2-LSIA). The study aimed to determine possible associations between the OPD-2-LSIA and central parameters of illness. Additionally, possible structural differences between people diagnosed with schizophrenia and schizoaffective psychosis were tested.
METHODS
This cross-sectional study included 129 outpatients with schizophrenia or schizoaffective disorders. Measures of structural integration, symptom load, severity of illness, cognition, and social functioning were obtained. Descriptive statistics were used to analyze the overall structural level and the structural dimensions. Correlation coefficients were computed to measure the associations between OPD-2-LSIA and variables regarding the severity of illness and psychosocial functioning. Regression models were used to measure the influence of illness-related variables on OPD-2-LSIA, and the influence of OPD-2-LSIA on psychosocial functioning. Participants diagnosed with schizophrenia and schizoaffective disorders were examined with regard to possible group differences.
RESULTS
The results of the OPD-2-LSIA showed that the overall structural level was between 'moderate to low' and 'low level of structural integration'. Significant correlations were found between OPD-2-LSIA and psychotic symptoms (but not depressive symptoms), as well as between OPD-2-LSIA and psychosocial functioning. It was found that variables related to severity of illness had a significant impact on OPD-2-LSIA, with psychotic, but not depressive symptoms being significant predictors. OPD-2-LSIA was found to predict psychosocial functioning beyond symptoms and cognition. No significant differences were found between participants with schizophrenia and schizoaffective psychosis. There was also no correlation found between OPD-2-LSIA and depressive symptomatology (except for the subdimension Internal communication).
DISCUSSION
Contrary to theoretical assumptions, the results of the study show a heterogenous picture of the psychic structure of people with psychosis. The associations between OPD-2-LSIA and severity of illness, particularly psychotic symptomatology, as well as the influence of OPD-2-LSIA on psychosocial functioning, are discussed.
PubMed: 38911709
DOI: 10.3389/fpsyt.2024.1388478 -
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 -
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 -
BMC Psychiatry Jun 2024Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Psychotic disorders have long been considered neurodevelopmental disorders where excessive synaptic pruning and cortical volume loss are central to disease pathology. We conducted a systematic review of the literature to identify neuroimaging studies specifically examining synaptic density across the psychosis spectrum.
METHODS
PRISMA guidelines on reporting were followed. We systematically searched MEDLINE, Embase, APA PsycINFO, Web of Science and The Cochrane Library from inception to December 8, 2023, and included all original peer-reviewed articles or completed clinical neuroimaging studies of any modality measuring synaptic density in participants with a diagnosis of psychosis spectrum disorder as well as individuals with psychosis-risk states. The NIH quality assessment tool for observational cohort and cross-sectional studies was used for the risk of bias assessment.
RESULTS
Five studies (k = 5) met inclusion criteria, comprising n = 128 adults (psychotic disorder; n = 61 and healthy volunteers; n = 67 and specifically measuring synaptic density via positron emission tomography (PET) imaging of the synaptic vesicle glycoprotein 2 A (SV2A). Three studies were included in our primary meta-analysis sharing the same outcome measure of SV2A binding, volume of distribution (V). Regional SV2A V was reduced in psychotic disorder participants in comparison to healthy volunteers, including the occipital lobe (Mean Difference (MD)= -2.17; 95% CI: -3.36 to -0.98; P < 0.001 ), temporal lobe (MD: -2.03; 95% CI: -3.19 to -0.88; P < 0.001 ), parietal lobe (MD:-1.61; 95% CI: -2.85 to -0.37; P = 0.01), anterior cingulate cortex (MD= -1.47; 95% CI: -2.45 to -0.49; P = 0.003), frontal cortex (MD: -1.16; 95% CI: -2.18 to -0.15; P = 0.02), amygdala (MD: -1.36; 95% CI: -2.20 to -0.52, p = 0.002), thalamus (MD:-1.46; 95% CI:-2.46 to -0.46, p = 0.004) and hippocampus (MD= -0.96; 95% CI: -1.59 to -0.33; P = 0.003).
CONCLUSIONS
Preliminary studies provide in vivo evidence for reduced synaptic density in psychotic disorders. However, replication of findings in larger samples is required prior to definitive conclusions being drawn.
PROSPERO
CRD42022359018.
Topics: Humans; Psychotic Disorders; Neuroimaging; Synapses; Positron-Emission Tomography; Brain; Nerve Tissue Proteins; Membrane Glycoproteins
PubMed: 38898401
DOI: 10.1186/s12888-024-05788-y -
Psychiatry Research Jun 2024The impact of traumatic brain injury (TBI) on subsequent risk of schizophrenia (SCZ) or bipolar disorder (BD) remains contested. Possible genetic and environmental...
The impact of traumatic brain injury (TBI) on subsequent risk of schizophrenia (SCZ) or bipolar disorder (BD) remains contested. Possible genetic and environmental confounding effects have also been understudied. Therefore, we aim to investigate the impact of TBI on the risk of SCZ and BD and whether the effect varies by injury severity, age at injury, and sex. We identified 4,184 SCZ and 18,681 BD cases born between 1973 and 1998 in the Swedish National Registers. Case-control samples matched (1:5) on birth year, sex, and birthplace were created along with a family design study, with cases matched to non-case full siblings. TBI was associated with higher risk of SCZ and BD (IRR=1.33 for SCZ, IRR=1.78 for BD). The association remained significant in the sibling comparison study. Moderate or severe TBI was associated with higher risk for both SCZ and BD compared to mild TBI. Older age at injury was associated with higher risk of SCZ and BD, and the effect of TBI was stronger in women than men. Findings indicate that TBI is a risk factor for both SCZ and BD with differential impact by age, severity and sex and that this association cannot be explained by familial confounding alone.
PubMed: 38896929
DOI: 10.1016/j.psychres.2024.115990 -
BioRxiv : the Preprint Server For... Jun 2024Haloperidol is used to manage psychotic symptoms in several neurological disorders through mechanisms that involve antagonism of dopamine D2 receptors that are highly...
Haloperidol is used to manage psychotic symptoms in several neurological disorders through mechanisms that involve antagonism of dopamine D2 receptors that are highly expressed in the striatum. Significant side effects of haloperidol, known as extrapyramidal symptoms, lead to motor deficits similar to those seen in Parkinson's disease and present a major challenge in clinical settings. The underlying molecular mechanisms responsible for these side effects remain poorly understood. Parkinson's disease-associated LRRK2 kinase has an important role in striatal physiology and a known link to dopamine D2 receptor signaling. Here, we systematically explore convergent signaling of haloperidol and LRRK2 through pharmacological or genetic inhibition of LRRK2 kinase, as well as knock-in mouse models expressing pathogenic mutant LRRK2 with increased kinase activity. Behavioral assays show that LRRK2 kinase inhibition ameliorates haloperidol-induced motor changes in mice. A combination of electrophysiological and anatomical approaches reveals that LRRK2 kinase inhibition interferes with haloperidol-induced changes, specifically in striatal neurons of the indirect pathway. Proteomic studies and targeted intracellular pathway analyses demonstrate that haloperidol induces a similar pattern of intracellular signaling as increased LRRK2 kinase activity. Our study suggests that LRRK2 kinase plays a key role in striatal dopamine D2 receptor signaling underlying the undesirable motor side effects of haloperidol. This work opens up new therapeutic avenues for dopamine-related disorders, such as psychosis, also furthering our understanding of Parkinson's disease pathophysiology.
PubMed: 38895420
DOI: 10.1101/2024.06.06.597594