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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 -
Journal of Huntington's Disease Jun 2024Huntington's disease (HD) is an autosomal dominant disorder that affects the basal ganglia, caused by CAG repeats in the huntingtin gene. Delusional infestation (DI)...
Huntington's disease (HD) is an autosomal dominant disorder that affects the basal ganglia, caused by CAG repeats in the huntingtin gene. Delusional infestation (DI) is a rare psychotic manifestation of the disease. This report presents two cases of HD patients with DI, both middle-aged females. The first patient achieved remission of DI with olanzapine, later cross-tapered to risperidone, but had spontaneous relapses. The second experienced gradual resolution of DI with risperidone in the setting of iron repletion and amantadine discontinuation, although her other psychotic symptoms remained. These cases shed light on an uncommon condition and may help guide understanding of the most effective treatment for it.
PubMed: 38905053
DOI: 10.3233/JHD-240013 -
International Journal of Obesity (2005) Jun 2024As the second most risky environmental pollution, noise imposes threats to human health. Exposure to high-intensity noise causes hearing impairment, psychotic disorders,...
BACKGROUND
As the second most risky environmental pollution, noise imposes threats to human health. Exposure to high-intensity noise causes hearing impairment, psychotic disorders, endocrine modifications. The relationship among low-intensity noise, obesity and lipid-regulating nuclear factor PPARα is not yet clear.
METHODS
In this study, male wild-type (WT) and Pparα-null (KO) mice on a high-fat diet (HFD) were exposed to 75 dB noise for 12 weeks to explore the effect of low-intensity noise on obesity development and the role of PPARα. 3T3-L1 cells were treated with dexamethasone (DEX) and sodium oleate (OA) to verify the down-stream effect of hypothalamic-pituitary-adrenal (HPA) axis activation on the adipose tissues.
RESULTS
The average body weight gain (BWG) of WT mice on HFD exposed to noise was inhibited, which was not observed in KO mice. The mass and adipocyte size of adipose tissues accounted for the above difference of BWG tendency. In WT mice on HFD, the adrenocorticotropic hormone level was increased by the noise challenge. The aggravation of fatty liver by noise exposure occurred in both mouse lines, and the transport of hepatic redundant lipid to adipose tissues were similar. The lipid metabolism in adipose tissue driven by HPA axis accorded with the BWG inhibition in vivo, validated in 3T3-L1 adipogenic stem cells.
CONCLUSION
Chronic exposure to low-intensity noise aggravated fatty liver in both WT and KO mice. BWG inhibition was observed only in WT mice, which covered up the aggravation of fatty liver by noise exposure. PPARα mediates the activation of HPA axis by noise exposure in mice on HFD. Elevated adrenocorticotropic hormone (ACTH) promoted lipid metabolism in adipocytes, which contributed to the disassociation of BWG and fatty liver development in male WT mice. Summary of PPARα suppresses noise-induced body weight gain in mice on high-fat-diet. Chronic exposure to low-intensity noise exposure inhibited BWG by PPARα-dependent activation of the HPA axis.
PubMed: 38902386
DOI: 10.1038/s41366-024-01550-2 -
The British Journal of General Practice... Jun 2024Early Intervention in Psychosis (EIP) services offer treatment to people experiencing a first episode of psychosis. Service users may be referred from primary care and...
BACKGROUND
Early Intervention in Psychosis (EIP) services offer treatment to people experiencing a first episode of psychosis. Service users may be referred from primary care and discharged directly back at the end of their time in an EIP service.
AIM
To explore the role of primary care in supporting EIP service users (SUs) and to understand how to improve collaboration between primary and specialist care.
METHOD
Qualitative study comprising semi-structured interviews with SUs, carers, healthcare professionals (HCPs), managers, and commissioners. Interviews were conducted either online or by telephone. Thematic analysis was carried out using principles of constant comparison. Patient and public involvement were key to all stages, including data analysis.
RESULTS
In total, 55 interviews were conducted with SUs ( = 13), carers ( = 10), and GPs, EIP HCPs, managers, and commissioners ( = 33). GPs reported difficulties in referring people into EIP services and little contact with SUs while in EIP services, even about physical health. GPs suggested they were not included in planning discharge from EIP to primary care. SUs and carers reported that transition from EIP can lead to uncertainty, distress, and exacerbation of symptoms. GPs reported only being made aware of patients on or after discharge, with no contact for 3 years. GPs described difficulty managing complex medication regimes, and barriers to re-referral to mental health services.
CONCLUSION
GPs have a key role in supporting people within EIP services, specifically monitoring and managing physical health. Inclusion of GPs in planning discharge from EIP services is vital.
Topics: Humans; Primary Health Care; Psychotic Disorders; Qualitative Research; Early Medical Intervention; Referral and Consultation; Male; Female; Mental Health Services; Attitude of Health Personnel; Adult; Caregivers
PubMed: 38902097
DOI: 10.3399/bjgp24X737541 -
The British Journal of General Practice... Jun 2024It is estimated 20-70% of those living with a dementia diagnosis experience dementia-related psychosis (D-RP). D-RP results in decreased quality of life, increased carer...
BACKGROUND
It is estimated 20-70% of those living with a dementia diagnosis experience dementia-related psychosis (D-RP). D-RP results in decreased quality of life, increased carer burden, increased rapid cognitive decline, increased need for primary care support, and earlier care/nursing home admission, all which come at a considerable cost to the NHS. Antipsychotic medications prescribed by primary care services are typically used as treatment but have short-term efficacy and dangerous side effects. Effective management with the use of non-pharmacological interventions could safely improve the quality of life of those living with dementia, as well as reduce burden on primary care services and GPs.
AIM
To evaluate the effectiveness of non-pharmacological interventions in the management of D-RP. Studies that measure the effect of non-pharmacological interventions on patient or caregiver quality of life or determine the cost-effectiveness and safety of non-pharmacological interventions against antipsychotic medications will also be included.
METHOD
A global systematic literature review was conducted in Medline, Embase, PsychInfo, CINAHL, Web of Science, and CENTRAL. Included studies were analysed using meta-analysis and narrative synthesis. The protocol is registered with PROSPERO (ID: CRD42022294750).
RESULTS
Data extraction of 18 included papers revealed 4 interventions to show evidence of efficacy in improving D-RP in older adults. Person-centred care, robot pets, cognitive rehabilitation, and music therapy significantly decreased psychosis in care homes and in participants living at home. These results are discussed, and implications noted.
CONCLUSION
Future RCTs should focus on specifically improving D-RP, as this was not the primary aim for many interventions.
Topics: Humans; Dementia; Psychotic Disorders; Quality of Life; Caregivers; Primary Health Care; Antipsychotic Agents; Cost-Benefit Analysis
PubMed: 38902088
DOI: 10.3399/bjgp24X737445 -
Progress in Neuro-psychopharmacology &... Jun 2024Schizophrenia is a prevalent mental disorder, leading to severe disability. Currently, the absence of objective biomarkers hinders effective diagnosis. This study was...
BACKGROUND
Schizophrenia is a prevalent mental disorder, leading to severe disability. Currently, the absence of objective biomarkers hinders effective diagnosis. This study was conducted to explore the aberrant spontaneous brain activity and investigate the potential of abnormal brain indices as diagnostic biomarkers employing machine learning methods.
METHODS
A total of sixty-one schizophrenia patients and seventy demographically matched healthy controls were enrolled in this study. The static indices of resting-state functional magnetic resonance imaging (rs-fMRI) including amplitude of low frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated to evaluate spontaneous brain activity. Subsequently, a sliding-window method was then used to conduct temporal dynamic analysis. The comparison of static and dynamic rs-fMRI indices between the patient and control groups was conducted using a two-sample t-test. Finally, the machine learning analysis was applied to estimate the diagnostic value of abnormal indices of brain activity.
RESULTS
Schizophrenia patients exhibited a significant increase ALFF value in inferior frontal gyrus, alongside significant decreases in fALFF values observed in left postcentral gyrus and right cerebellum posterior lobe. Pervasive aberrations in ReHo indices were observed among schizophrenia patients, particularly in frontal lobe and cerebellum. A noteworthy reduction in voxel-wise concordance of dynamic indices was observed across gray matter regions encompassing the bilateral frontal, parietal, occipital, temporal, and insular cortices. The classification analysis achieved the highest values for area under curve at 0.87 and accuracy at 81.28% when applying linear support vector machine and leveraging a combination of abnormal static and dynamic indices in the specified brain regions as features.
CONCLUSIONS
The static and dynamic indices of brain activity exhibited as potential neuroimaging biomarkers for the diagnosis of schizophrenia.
PubMed: 38901758
DOI: 10.1016/j.pnpbp.2024.111066