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Frontiers in Psychiatry 2024Psychotic symptoms are among the most debilitating and challenging presentations of severe psychiatric diseases, such as schizophrenia, schizoaffective, and bipolar...
UNLABELLED
Psychotic symptoms are among the most debilitating and challenging presentations of severe psychiatric diseases, such as schizophrenia, schizoaffective, and bipolar disorder. A pathophysiological understanding of intrinsic brain activity underlying psychosis is crucial to improve diagnosis and treatment. While a potential continuum along the psychotic spectrum has been recently described in neuroimaging studies, especially for what concerns absolute and relative amplitude of low-frequency fluctuations (ALFF and fALFF), these efforts have given heterogeneous results. A transdiagnostic meta-analysis of ALFF/fALFF in patients with psychosis compared to healthy controls is currently lacking. Therefore, in this pre-registered systematic review and meta-analysis PubMed, Scopus, and Embase were searched for articles comparing ALFF/fALFF between psychotic patients and healthy controls. A quantitative synthesis of differences in (f)ALFF between patients along the psychotic spectrum and healthy controls was performed with Seed-based d Mapping, adjusting for age, sex, duration of illness, clinical severity. All results were corrected for multiple comparisons by Family-Wise Error rates. While lower ALFF and fALFF were detected in patients with psychosis in comparison to controls, no specific finding survived correction for multiple comparisons. Lack of this correction might explain the discordant findings highlighted in previous literature. Other potential explanations include methodological issues, such as the lack of standardization in pre-processing or analytical procedures among studies. Future research on ALFF/fALFF differences for patients with psychosis should prioritize the replicability of individual studies.
SYSTEMATIC REVIEW REGISTRATION
https://osf.io/, identifier (ycqpz).
PubMed: 38895037
DOI: 10.3389/fpsyt.2024.1378439 -
Frontiers in Psychiatry 2024Depressive episodes with psychotic symptoms are prevalent among the older adults, emphasizing the need to differentiate them from dementia with Lewy bodies (DLB), in...
Depressive episodes with psychotic symptoms are prevalent among the older adults, emphasizing the need to differentiate them from dementia with Lewy bodies (DLB), in which depressive and psychotic symptoms commonly coexist. In contrast, psychotic symptoms occur more frequently in depressive episodes of bipolar disorder (BD) than in major depressive disorder (MDD). Although MDD is a significant risk factor for dementia, studies exploring the relationship between BD and dementia are lacking. This report details the case of a 74-year-old female who experienced severe psychotic depression that led to suicide attempts during a long-term course of young-onset BD. Ultimately, she was diagnosed with DLB based on her neurocognitive symptoms and results of the neuroimaging examination. She had experienced multiple relapses in the past, predominantly characterized by depressive episodes in her old age. Notably, she had never undergone lithium treatment, which is known for its potential efficacy in preventing relapse and dementia. Recent systematic reviews and meta-analyses have suggested that patients with BD have a higher risk of dementia than the general population, and that lithium usage is associated with a reduced risk. Moreover, patients with BD have been suggested to have an elevated risk of developing Parkinson's disease (PD), and the pathophysiological relationship between BD and PD may be attributed to dopamine dysregulation resulting from multiple relapses. Future research is imperative to identify strategies for preventing dementia in patients with BD and to develop interventions for the comorbidities of BD and DLB.
PubMed: 38895028
DOI: 10.3389/fpsyt.2024.1409027 -
International Journal of Molecular... May 2024For the past 70 years, the dopamine hypothesis has been the key working model in schizophrenia. This has contributed to the development of numerous inhibitors of... (Review)
Review
For the past 70 years, the dopamine hypothesis has been the key working model in schizophrenia. This has contributed to the development of numerous inhibitors of dopaminergic signaling and antipsychotic drugs, which led to rapid symptom resolution but only marginal outcome improvement. Over the past decades, there has been limited research on the quantifiable pathological changes in schizophrenia, including premature cellular/neuronal senescence, brain volume loss, the attenuation of gamma oscillations in electroencephalograms, and the oxidation of lipids in the plasma and mitochondrial membranes. We surmise that the aberrant activation of the aryl hydrocarbon receptor by toxins derived from gut microbes or the environment drives premature cellular and neuronal senescence, a hallmark of schizophrenia. Early brain aging promotes secondary changes, including the impairment and loss of mitochondria, gray matter depletion, decreased gamma oscillations, and a compensatory metabolic shift to lactate and lactylation. The aim of this narrative review is twofold: (1) to summarize what is known about premature cellular/neuronal senescence in schizophrenia or schizophrenia-like disorders, and (2) to discuss novel strategies for improving long-term outcomes in severe mental illness with natural senotherapeutics, membrane lipid replacement, mitochondrial transplantation, microbial phenazines, novel antioxidant phenothiazines, inhibitors of glycogen synthase kinase-3 beta, and aryl hydrocarbon receptor antagonists.
Topics: Humans; Antipsychotic Agents; Schizophrenia; Psychotic Disorders; Animals; Brain; Cellular Senescence
PubMed: 38892092
DOI: 10.3390/ijms25115904 -
BMC Psychiatry Jun 2024Adjustment and stress-related disorders are prevalent among psychiatric service users. Despite their prevalence, little is known about their prognosis. To reduce that...
BACKGROUND
Adjustment and stress-related disorders are prevalent among psychiatric service users. Despite their prevalence, little is known about their prognosis. To reduce that gap, the present article documents the service use and diagnostic outcomes of people with adjustment or stress-related disorders presenting at Singapore's largest psychiatric emergency department.
METHODS
Administrative data from 2014 to 2021 was retrieved to follow a group of 683 service users whose first-ever psychiatric presentation in 2014 warranted a diagnosis of adjustment or stress-related disorder. People were grouped a priori depending on whether different diagnoses were recorded within 7 days, 9 months, after 9 months or not at all. Survival curves characterized conversion to other diagnoses and engagement with healthcare services. Service use outcomes include the number of hospitalizations, outpatient appointments, emergency department visits, and prescriptions.
RESULTS
Sixty-one percent (n = 417) never received another diagnosis over the 8-year period. This group used emergency services most and received the most pharmacotherapy shortly after their first visit. Of those who received another diagnosis, depression, personality disorders, and psychotic disorders were the most common. Those who received another diagnosis within 7 days (n = 70, 10%) received it on their first day of hospitalization (IQR 1-1), making the most use of inpatient services. The group who received another diagnosis within 9 months (n = 105, 15%) did so after 42 days (IQR 26-84) and had the highest relative number of deaths. Those who received another diagnosis after 9 months (n = 91, 13%) did so after 1,134 days (IQR 613-1,823) and had the longest period of engagement but made the least use of any psychiatric service, potentially suggesting a group whose early index diagnosis heralded vulnerability to future disorders.
CONCLUSIONS
A large group of service users with acute stress or adjustment disorders will likely never be given another psychiatric diagnosis and appear to disengage following an initial period of high-intensity service use. The group that received a different diagnosis after the 9-month mark had prolonged contact with services but low intensity of service use and may represent a target for preventative intervention to help them improve their stress-managing skills and avoid developing other disorders.
Topics: Humans; Male; Female; Adult; Middle Aged; Adjustment Disorders; Singapore; Longitudinal Studies; Hospitalization; Emergency Service, Hospital; Patient Acceptance of Health Care; Young Adult; Emergency Services, Psychiatric; Mental Health Services
PubMed: 38890697
DOI: 10.1186/s12888-024-05904-y -
PloS One 2024There is a treatment gap for those living with severe mental illnesses in low- and middle-income countries, yet not enough is known about those who are currently... (Clinical Trial)
Clinical Trial
BACKGROUND
There is a treatment gap for those living with severe mental illnesses in low- and middle-income countries, yet not enough is known about those who are currently accessing clinical services. A better understanding of potentially modifiable factors associated with functioning and quality of life will help inform policies and programming.
AIMS
To describe the functioning and quality of life for a psychiatric treatment-engaged population living with psychotic disorders in two urban areas of Tanzania, and to explore their respective correlates.
METHODS
This study analyzed cross-sectional data from 66 individuals enrolled in the Kuwezeshana Kupata Uzima (KUPAA) pilot clinical trial who had a diagnosis of schizophrenia or schizoaffective disorder, recent relapse, and who were receiving outpatient treatment. Baseline functioning (WHO Disability Assessment Schedule 2.0) and quality of life (WHO Quality of Life BREF scale) were measured. Univariable and multivariable regression analyses were conducted to determine correlates of functioning and quality of life.
RESULTS
Adjusted analyses indicated that higher disability was associated with higher food insecurity, more symptomatology, more self-stigma, less instrumental support, less hope, lower self-efficacy, and/or lower levels of family functioning. Higher quality of life was associated with higher levels of self-efficacy, more hopefulness, more instrumental support, less self-stigma, and better family functioning.
CONCLUSIONS
Identification of factors associated with disability and quality of life can help clinicians and policymakers, as well as consumers of mental health services, to better co-design and target psychosocial interventions to optimize their impact in low-resource settings.
TRIAL REGISTRATION
Trial registration: ClinicalTrials.gov # NCT04013932, July 10, 2019.
Topics: Humans; Quality of Life; Male; Tanzania; Psychotic Disorders; Female; Adult; Cross-Sectional Studies; Urban Population; Middle Aged; Schizophrenia; Young Adult
PubMed: 38889160
DOI: 10.1371/journal.pone.0304367 -
Clinical Case Reports Jun 2024The case highlights an unusual presentation where sleep issues preceded psychotic symptoms, implying link between disrupted sleep and psychosis onset. Earlier symptoms...
KEY CLINICAL MESSAGE
The case highlights an unusual presentation where sleep issues preceded psychotic symptoms, implying link between disrupted sleep and psychosis onset. Earlier symptoms were viewed as depression but may have signaled psychosis exacerbated by insomnia.
ABSTRACT
Sleep disorders, prevalent yet frequently overlooked in individuals with psychotic disorders, have significant associations with the onset and severity of psychosis. Here we describe the case of a patient who first presented with insomnia, but whose condition improved with the use of risperidone and was diagnosed with first-episode psychosis. Multiple studies emphasize the critical relationship between sleep disturbances and psychosis, particularly in the lead-up to first-episode psychosis. Structural abnormalities in the brain, notably the thalamus, combined with neurotransmitter imbalances involving dopamine and acetylcholine, seem pivotal in this interrelation. The connection between dopamine, sleep disturbances, and psychosis, specifically the role of D2 dopamine receptors, highlights a potential pathway bridging sleep irregularities with psychosis. The study underscores the need for further research to delineate the relationship between sleep disturbances and psychosis and to assess the efficacy of various therapeutic interventions targeting both conditions.
PubMed: 38887308
DOI: 10.1002/ccr3.9108 -
BMJ Mental Health Jun 2024Individuals with psychiatric disorders have an increased risk of developing dementia. Most cross-sectional studies suffer from selection bias, underdiagnosis and poor...
BACKGROUND
Individuals with psychiatric disorders have an increased risk of developing dementia. Most cross-sectional studies suffer from selection bias, underdiagnosis and poor population representation, while there is only limited evidence from longitudinal studies on the role of anxiety, bipolar and psychotic disorders. Electronic health records (EHRs) permit large cohorts to be followed across the lifespan and include a wide range of diagnostic information.
OBJECTIVE
To assess the association between four groups of psychiatric disorders (schizophrenia, bipolar disorder/mania, depression and anxiety) with dementia in two large population-based samples with EHR.
METHODS
Using EHR on nearly 1 million adult individuals in Wales, and from 228 937 UK Biobank participants, we studied the relationships between schizophrenia, mania/bipolar disorder, depression, anxiety and subsequent risk of dementia.
FINDINGS
In Secure Anonymised Information Linkage, there was a steep increase in the incidence of a first diagnosis of psychiatric disorder in the years prior to the diagnosis of dementia, reaching a peak in the year prior to dementia diagnosis for all psychiatric diagnoses. Psychiatric disorders, except anxiety, were highly significantly associated with a subsequent diagnosis of dementia: HRs=2.87, 2.80, 1.63 for schizophrenia, mania/bipolar disorder and depression, respectively. A similar pattern was found in the UK Biobank (HRs=4.46, 3.65, 2.39, respectively) and anxiety was also associated with dementia (HR=1.34). Increased risk of dementia was observed for all ages at onset of psychiatric diagnoses when these were divided into 10-year bins.
CONCLUSIONS
Psychiatric disorders are associated with an increased risk of subsequent dementia, with a greater risk of more severe disorders.
CLINICAL IMPLICATIONS
A late onset of psychiatric disorders should alert clinicians of possible incipient dementia.
Topics: Humans; Dementia; Female; Male; Middle Aged; Aged; Adult; Mental Disorders; Wales; Electronic Health Records; Bipolar Disorder; United Kingdom; Schizophrenia; Risk Factors; Aged, 80 and over; Incidence
PubMed: 38886095
DOI: 10.1136/bmjment-2024-301097 -
JAMA Network Open Jun 2024Long-acting injectable antipsychotics (LAIs) can help decrease the rate of nonadherence to medications in patients with schizophrenia, but these drugs are underutilized...
IMPORTANCE
Long-acting injectable antipsychotics (LAIs) can help decrease the rate of nonadherence to medications in patients with schizophrenia, but these drugs are underutilized in clinical practice, especially in Asian countries. One strategy for the early prescription of LAIs is to administer the drugs during patients' first admission, when they have more time to absorb medication-related knowledge.
OBJECTIVE
To estimate the prevalence of and risk factors for in-hospital use of LAIs among first-admission patients with schizophrenia in Taiwan and to examine the association of early discontinuation with readmission risk among patients receiving LAIs.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study included data from a claims database for patients with a first admission for schizophrenia at psychiatric wards in Taiwan from 2004 to 2017. Eligible patients were diagnosed with schizophrenia or schizoaffective disorder at discharge and aged between 15 and 64 years. Data analysis was performed from April to September 2022.
EXPOSURE
In-hospital use of LAIs with or without early discontinuation.
MAIN OUTCOME AND MEASURES
Readmission for any psychotic disorder following discharge from first admission, with risk estimated via multivariable survival regression analysis, including the Cox proportional hazards (CPH) model and accelerated failure time (AFT) model.
RESULTS
Of the 56 211 patients with a first admission for schizophrenia (mean [SD] age, 38.1 [12.1] years; 29 387 men [52.3%]), 46 875 (83.4%) did not receive any LAIs during admission, 5665 (10.1%) received LAIs with early discontinuation, and 3671 (6.5%) received LAIs without early discontinuation. The prevalence of receiving LAIs increased by 4%, from 15.3% (3863 of 25 251 patients) to 19.3% (3013 of 15 608 patients) between 2004-2008 and 2013-2017. After controlling for sex, year, prior antipsychotic use, age at first admission, and length of stay, the CPH regression analysis revealed that the readmission risk increased among patients receiving LAIs with early discontinuation (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.21-1.30) but decreased among patients receiving LAIs without early discontinuation (aHR, 0.88; 95% CI, 0.84-0.92) compared with patients not receiving LAIs. Results remained similar for the AFT model.
CONCLUSIONS AND RELEVANCE
The incidence of in-hospital use of LAIs among patients with a first admission for schizophrenia has remained low. In this study, early discontinuation of LAIs was associated with readmission risk-specifically, early discontinuation with a higher risk while the lack of early discontinuation with a lower risk compared with treatment with oral antipsychotics alone-which suggests our results have implications for improving the efficacy of LAI administration among patients with a first admission for schizophrenia.
Topics: Humans; Schizophrenia; Antipsychotic Agents; Patient Readmission; Male; Taiwan; Female; Adult; Middle Aged; Delayed-Action Preparations; Risk Factors; Adolescent; Young Adult; Cohort Studies; Medication Adherence; Hospitalization; Injections; Proportional Hazards Models
PubMed: 38884998
DOI: 10.1001/jamanetworkopen.2024.17006 -
Consciousness and Cognition Jun 2024The phenomenon of "hearing voices" can be found not only in psychotic disorders, but also in the general population, with individuals across cultures reporting auditory...
The phenomenon of "hearing voices" can be found not only in psychotic disorders, but also in the general population, with individuals across cultures reporting auditory perceptions of supernatural beings. In our preregistered study, we investigated a possible mechanism of such experiences, grounded in the predictive processing model of agency detection. We predicted that in a signal detection task, expecting less or more voices than actually present would drive the response bias toward a more conservative and liberal response strategy, respectively. Moreover, we hypothesized that including sensory noise would enhance these expectancy effects. In line with our predictions, the findings show that detection of voices relies on expectations and that this effect is especially pronounced in the case of unreliable sensory data. As such, the study contributes to our understanding of the predictive processes in hearing and the building blocks of voice hearing experiences.
PubMed: 38880020
DOI: 10.1016/j.concog.2024.103718 -
Scientific Reports Jun 2024Smooth pursuit eye movements are considered a well-established and quantifiable biomarker of sensorimotor function in psychosis research. Identifying psychotic syndromes...
Smooth pursuit eye movements are considered a well-established and quantifiable biomarker of sensorimotor function in psychosis research. Identifying psychotic syndromes on an individual level based on neurobiological markers is limited by heterogeneity and requires comprehensive external validation to avoid overestimation of prediction models. Here, we studied quantifiable sensorimotor measures derived from smooth pursuit eye movements in a large sample of psychosis probands (N = 674) and healthy controls (N = 305) using multivariate pattern analysis. Balanced accuracies of 64% for the prediction of psychosis status are in line with recent results from other large heterogenous psychiatric samples. They are confirmed by external validation in independent large samples including probands with (1) psychosis (N = 727) versus healthy controls (N = 292), (2) psychotic (N = 49) and non-psychotic bipolar disorder (N = 36), and (3) non-psychotic affective disorders (N = 119) and psychosis (N = 51) yielding accuracies of 65%, 66% and 58%, respectively, albeit slightly different psychosis syndromes. Our findings make a significant contribution to the identification of biologically defined profiles of heterogeneous psychosis syndromes on an individual level underlining the impact of sensorimotor dysfunction in psychosis.
Topics: Humans; Male; Female; Pursuit, Smooth; Psychotic Disorders; Adult; Biomarkers; Young Adult; Bipolar Disorder; Middle Aged; Case-Control Studies; Adolescent
PubMed: 38879556
DOI: 10.1038/s41598-024-64487-6