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Neural Regeneration Research Jun 2024In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may...
In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.
PubMed: 38934398
DOI: 10.4103/NRR.NRR-D-23-01878 -
Journal of Clinical Medicine Jun 2024Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder frequently co-occurring with attention-deficit/hyperactivity disorder (ADHD) and... (Review)
Review
Treatment of Aggressive Behavior and Agitation in an 11-Year-Old Boy with Co-Occurring Autism and ADHD: A Case Report and Literature Review on the Use of Intravenous Valproate in Emergency Psychiatry.
Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder frequently co-occurring with attention-deficit/hyperactivity disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage the core symptoms of ASD, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend the use of neuroleptics to reduce psychomotor agitation in patients with ASD. However, as children with ASD are often drug-resistant, alternative treatments are often justified. Reports from the literature have indicated that intravenous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with a lower frequency of adverse events compared to conventional treatments. However, as the related findings are occasionally inconsistent, IV-VPA is not yet an approved option in the context of clinical psychiatry. We aim to improve knowledge of the IV-VPA treatment option for emergency psychiatric treatment in pediatric patients. We report the case of an 11-year-old boy suffering from a complex neurodevelopmental condition who experienced a psychotic episode with severe aggressive and disruptive behaviors and was successfully treated with IV-VPA. Furthermore, we provide an updated literature review on this topic. In our case, first-line therapies proved to be ineffective. To the contrary, IV-VPA led to safe and prompt clinical success, which is in line with other reports. Based on our literature review, IV-VPA can be highly effective and reduces the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.
PubMed: 38930101
DOI: 10.3390/jcm13123573 -
Medicina (Kaunas, Lithuania) Jun 2024: Radicalization, a complex and multifaceted phenomenon, has been a subject of increasing concern in recent years, particularly due to its potential connection to acts... (Review)
Review
: Radicalization, a complex and multifaceted phenomenon, has been a subject of increasing concern in recent years, particularly due to its potential connection to acts of mass violence and terrorism. This systematic review examines the intricate link between radicalization and psychotic disorders, utilizing various sources such as observational studies, case reports, and series. It aims to highlight the prevalence of schizophrenia spectrum and other psychotic disorders among radicalized individuals and to define the role of mental health professionals in dealing with this issue, contributing to the development of prevention and treatment strategies. : The methodology involved an extensive literature search across PubMed, Scopus, and APA PsycINFO up to 1 February 2024, adhering to PRISMA guidelines. The study focused on radicalization and psychotic disorders as defined by DSM-5 criteria, excluding other mental disorders. A population sample of 41 radicalized individuals diagnosed with psychotic disorders was selected, among which schizophrenia was identified as the predominant condition. : It was observed that 24% of these individuals passed away soon after committing their crimes, leading the researchers to rely on retrospective data for their diagnoses. The use of diverse assessment tools for psychiatric diagnosis and the lack of a standardized method for diagnosing or assessing involvement in the radicalization process were also noted. Despite limitations like reliance on observational studies and case reports, which result in low evidence quality and varied methodologies, our work provides a valuable contribution to clarifying the relationship between radicalization and psychotic disorders. However, further clinical studies are needed to delve deeper into these aspects. : In conclusion, our review points out that individuals with psychotic disorders do not have a higher crime rate than the general population and warns against associating crimes with mental illness due to the stigma it creates. The lack of uniform psychiatric diagnostic tools and radicalization assessment highlights the need for more standardized risk assessment tools and validated scales in psychiatric diagnosis to better understand the relationship between radicalization and psychotic disorders and to develop integrated protocols.
Topics: Humans; Psychotic Disorders; Schizophrenia; Terrorism
PubMed: 38929543
DOI: 10.3390/medicina60060926 -
Antioxidants (Basel, Switzerland) Jun 2024Psychosis, defined as a set of symptoms that results in a distorted sense of reality, is observed in several psychiatric disorders in addition to schizophrenia. This... (Review)
Review
Psychosis, defined as a set of symptoms that results in a distorted sense of reality, is observed in several psychiatric disorders in addition to schizophrenia. This paper reviews the literature relevant to the underlying neurobiology of psychosis. The dopamine hypothesis has been a major influence in the study of the neurochemistry of psychosis and in development of antipsychotic drugs. However, it became clear early on that other factors must be involved in the dysfunction involved in psychosis. In the current review, it is reported how several of these factors, namely dysregulation of neurotransmitters [dopamine, serotonin, glutamate, and γ-aminobutyric acid (GABA)], neuroinflammation, glia (microglia, astrocytes, and oligodendrocytes), the hypothalamic-pituitary-adrenal axis, the gut microbiome, oxidative stress, and mitochondrial dysfunction contribute to psychosis and interact with one another. Research on psychosis has increased knowledge of the complexity of psychotic disorders. Potential new pharmacotherapies, including combinations of drugs (with pre- and probiotics in some cases) affecting several of the factors mentioned above, have been suggested. Similarly, several putative biomarkers, particularly those related to the immune system, have been proposed. Future research on both pharmacotherapy and biomarkers will require better-designed studies conducted on an all stages of psychotic disorders and must consider confounders such as sex differences and comorbidity.
PubMed: 38929148
DOI: 10.3390/antiox13060709 -
Brain Sciences Jun 2024Positive symptoms of schizophrenia have been proposed to be an intrusion of dreaming in wakefulness; conversely, psychotic patients' abnormal cognitive and behavioral...
Positive symptoms of schizophrenia have been proposed to be an intrusion of dreaming in wakefulness; conversely, psychotic patients' abnormal cognitive and behavioral features could overflow into sleep, so that their dreams would differ from those of healthy people. Here we assess this hypothesis by comparing dream features of 46 patients affected by schizophrenic spectrum disorders to those of 28 healthy controls. In patients, we also investigated correlations of dream variables with symptom severity and verbal fluency. Overall, patients reported fewer and shorter dreams, with a general impoverishment of content (including characters, settings, interactions) and higher spatiotemporal bizarreness. The number of emotions, mainly negative ones, was lower in patients' reports and correlated inversely with symptom severity. Verbal fluency correlated positively with dream report length and negatively with perceptive bizarreness. In conclusion, our data show a significant impoverishment of dream reports in psychotic patients versus controls. Future research should investigate to what extent this profile of results depends on impaired verbal fluency or on impaired mechanisms of dream generation in this population. Moreover, in line with theories on the role of dreaming in emotion regulation, our data suggest that this function could be impaired in psychoses and related to symptom severity.
PubMed: 38928568
DOI: 10.3390/brainsci14060568 -
Genes Jun 2024Recent research has highlighted associations between sleep and microbial taxa and pathways. However, the causal effect of these associations remains unknown. To...
Recent research has highlighted associations between sleep and microbial taxa and pathways. However, the causal effect of these associations remains unknown. To investigate this, we performed a bidirectional two-sample Mendelian randomization (MR) analysis using summary statistics of genome-wide association studies (GWAS) from 412 gut microbiome traits (N = 7738) and GWAS studies from seven sleep-associated traits (N = 345,552 to 386,577). We employed multiple MR methods to assess causality, with Inverse Variance Weighted (IVW) as the primary method, alongside a Bonferroni correction (( < 2.4 × 10) to determine significant causal associations. We further applied Cochran's Q statistical analysis, MR-Egger intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) for heterogeneity and pleiotropy assessment. IVW estimates revealed 79 potential causal effects of microbial taxa and pathways on sleep-related traits and 45 inverse causal relationships, with over half related to pathways, emphasizing their significance. The results revealed two significant causal associations: genetically determined relative abundance of pentose phosphate decreased sleep duration ( = 9.00 × 10), and genetically determined increase in fatty acid level increased the ease of getting up in the morning ( = 8.06 × 10). Sensitivity analyses, including heterogeneity and pleiotropy tests, as well as a leave-one-out analysis of single nucleotide polymorphisms, confirmed the robustness of these relationships. This study explores the potential causal relationships between sleep and microbial taxa and pathways, offering novel insights into their complex interplay.
Topics: Humans; Mendelian Randomization Analysis; Gastrointestinal Microbiome; Genome-Wide Association Study; Sleep; Polymorphism, Single Nucleotide; Causality
PubMed: 38927705
DOI: 10.3390/genes15060769 -
BMJ Open Jun 2024Evidence-based psychological treatments for people with personality disorder usually involve attending group-based sessions over many months. Low-intensity psychological...
Clinical effectiveness and cost-effectiveness of Structured Psychological Support for people with probable personality disorder in mental health services in England: study protocol for a randomised controlled trial.
INTRODUCTION
Evidence-based psychological treatments for people with personality disorder usually involve attending group-based sessions over many months. Low-intensity psychological interventions of less than 6 months duration have been developed, but their clinical effectiveness and cost-effectiveness are unclear.
METHODS AND ANALYSIS
This is a multicentre, randomised, parallel-group, researcher-masked, superiority trial. Study participants will be aged 18 and over, have probable personality disorder and be treated by mental health staff in seven centres in England. We will exclude people who are: unwilling or unable to provide written informed consent, have a coexisting organic or psychotic mental disorder, or are already receiving psychological treatment for personality disorder or on a waiting list for such treatment. In the intervention group, participants will be offered up to 10 individual sessions of Structured Psychological Support. In the control group, participants will be offered treatment as usual plus a single session of personalised crisis planning. The primary outcome is social functioning measured over 12 months using total score on the Work and Social Adjustment Scale (WSAS). Secondary outcomes include mental health, suicidal behaviour, health-related quality of life, patient-rated global improvement and satisfaction, and resource use and costs. The primary analysis will compare WSAS scores across the 12-month period using a general linear mixed model adjusting for baseline scores, allocation group and study centre on an intention-to-treat basis. In a parallel process evaluation, we will analyse qualitative data from interviews with study participants, clinical staff and researchers to examine mechanisms of impact and contextual factors.
ETHICS AND DISSEMINATION
The study complies with the Helsinki Declaration II and is approved by the London-Bromley Research Ethics Committee (IRAS ID 315951). Study findings will be published in an open access peer-reviewed journal; and disseminated at national and international conferences.
TRIAL REGISTRATION NUMBER
ISRCTN13918289.
Topics: Humans; Cost-Benefit Analysis; England; Mental Health Services; Personality Disorders; Quality of Life; Treatment Outcome; Multicenter Studies as Topic; Adult; Psychosocial Intervention
PubMed: 38925701
DOI: 10.1136/bmjopen-2024-086593 -
Behavioral Sciences (Basel, Switzerland) Jun 2024Improving social functioning deficits-a core characteristic of schizophrenia-spectrum disorders-is often listed by patients as a key recovery goal. Evidence suggests...
Improving social functioning deficits-a core characteristic of schizophrenia-spectrum disorders-is often listed by patients as a key recovery goal. Evidence suggests that social deficits also extend to people with schizotypy, a group at heightened risk for psychotic and other psychopathological disorders. One challenge of social functioning research in schizotypy is understanding whether social deficits arise from receiving less pleasure from social activities or from participating less in high-pleasure activities. However, limited information exists on what constitutes highly pleasurable, common social activities. In this study, 357 college students rated the frequency and enjoyment of 38 social activities. Our aims were to categorize activities based on their frequency and enjoyment, and whether these correlated with validated social functioning and schizotypy measures. We found that social activities could be characterized based on their frequency and enjoyment and created a frequency-enjoyment matrix that could be useful for future studies. Activities were correlated with social functioning, generally reaching a small effect size level, with increasing frequency and enjoyment showing associations with greater social functioning. Further, negative and disorganized-but not positive-traits were associated with less engagement and pleasure. Although follow-up studies in community samples are needed, our findings have the potential to help researchers and clinicians better understand which activities participants are more likely to engage in and derive pleasure from. The findings may also illustrate the extent to which social deficits may be due to less engagement or less pleasure from social activities, as well as which aspects of schizophrenia-spectrum disorders are associated with these facets of social functioning.
PubMed: 38920806
DOI: 10.3390/bs14060474 -
Frontiers in Psychology 2024Metacognitive Training (MCT) is widely used and effective in reducing positive symptoms in psychosis. Physical exercise, such as Water Aerobics (WA), improves general...
Efficacy of the combination of water aerobics and metacognitive training on psychological and physical health variables and their relationship with SP1 and SP4 biomarkers in people with psychosis: a study protocol.
BACKGROUND
Metacognitive Training (MCT) is widely used and effective in reducing positive symptoms in psychosis. Physical exercise, such as Water Aerobics (WA), improves general health, quality of life and symptoms as a low impact activity that allows social interactions. Preliminary results suggest a relationship between dopamine and psychotic symptoms, through SP transcription factors, SP1 and SP4 biomarkers. The aims of the project are to evaluate the efficacy of a combined intervention (WA and MCT) for psychosis to improve psychotic symptoms, physical health, and transcription levels of SP biomarkers.
MATERIALS AND METHODS
This is a unicentric randomized controlled trial of three parallel intervention groups: MCT, WA and combined intervention. The estimated sample will be 48 patients with a psychotic spectrum disorder diagnosis. The assessment will be performed at baseline and at 2-months' follow-up. Instruments used in the assessment will include clinical, cognitive, metacognitive, social cognitive and psychosocial variables.
DISCUSSION
This will be the first study investigating the impact of the combination of MCT and WA in psychosis. Moreover, it will be the first study analyzing changes in the transcriptional biomarkers SP1 and SP4 after interventions. The results of this study may have clinical implications contributing to the improvement of treatment selection.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/, identifier: NCT05455593.
PubMed: 38919799
DOI: 10.3389/fpsyg.2024.1360004 -
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