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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 -
Schizophrenia Research Jun 2024The utilization of atypical antipsychotics (AAPs) often leads to metabolic syndrome (MetS) in schizophrenia (SZ) patients. Macrophage migration inhibitory factor (MIF)...
The utilization of atypical antipsychotics (AAPs) often leads to metabolic syndrome (MetS) in schizophrenia (SZ) patients. Macrophage migration inhibitory factor (MIF) is an important MetS-related cytokine. To investigate the potential association between the MIF-794 CATT polymorphism and AAP-induced MetS in SZ patients, data from 375 chronic SZ patients who received AAP treatment for a minimum of one year were included. MIF-794 CATT polymorphism genotyping and plasma MIF quantification was performed. The metabolism status of all patients was assessed according to the NCEP-ATP III criteria. Individuals who displayed at least three of the five risk factors (waist circumference, high-density lipoprotein cholesterol, triglycerides, fasting glucose levels, and blood pressure) were diagnosed with MetS. The prevalence of MetS in SZ patients with MIF CATT >5/6 was significantly higher than in those with CATT 5/5-5/6. In female patients, MIF CATT >5/6 was associated with an elevated risk of AAP-induced MetS after adjusting for covariates, particularly regarding abdominal obesity, and the mediating effect of plasma MIF levels was significant. In conclusion, MIF CATT >5/6 increased the risk of AAP-induced MetS among females with chronic SZ. The MIF-794 CATT microsatellite polymorphism may be a unique indicator for AAP-induced metabolic adverse effects in female SZ patients.
PubMed: 38889656
DOI: 10.1016/j.schres.2024.05.017 -
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 -
JAMA Psychiatry Jun 2024Characterizing mental health service use trajectories preceding diagnosis of a psychotic disorder may help identify individuals at highest risk and in which settings...
IMPORTANCE
Characterizing mental health service use trajectories preceding diagnosis of a psychotic disorder may help identify individuals at highest risk and in which settings they are at highest risk.
OBJECTIVE
To examine mental health service use and diagnostic trajectories before first diagnosis of psychotic disorder and identify utilization and diagnostic patterns.
DESIGN, SETTING, AND PARTICIPANTS
This population-based, retrospective cohort study used linked provincial health administrative data. The sample included individuals aged 15 to 29 years diagnosed with a psychotic disorder in Ontario, Canada, between April 1, 2012, and March 31, 2018. These individuals were matched to individuals with a diagnosis of a mood disorder. Data were analyzed from November 2108 to November 2019.
MAIN OUTCOMES AND MEASURES
The main outcomes were rates, timing, and setting of mental health-related service use and associated diagnoses in the 3 years before the index disorder among individuals first diagnosed with a psychotic disorder compared with those first diagnosed with a mood disorder.
RESULTS
A total of 10 501 individuals with a first diagnosis of psychotic disorder were identified (mean [SD] age, 21.55 [3.83] years; 72.1% male). A total of 72.2% of individuals had at least 1 mental health service visit during the 3 years before their first psychotic disorder diagnosis, which was significantly more than matched controls with a first mood disorder diagnosis (66.8%) (odds ratio [OR], 1.34; 95% CI, 1.26-1.42). Compared with individuals diagnosed with a mood disorder, individuals diagnosed with a psychotic disorder were significantly more likely to have had mental health-related hospital admissions (OR, 3.98; 95% CI, 3.43-4.62) and emergency department visits (OR, 2.27; 95% CI, 2.12-2.43) in the preceding 3 years. Those with psychotic disorders were more likely to have had prior diagnoses of substance use disorders (OR, 2.57; 95% CI, 2.35-2.81), other disorders (personality disorders, developmental disorders) (OR, 1.75; 95% CI, 1.61-1.90), and self-harm (OR, 1.64; 95% CI, 1.36-1.98) in the past 3 years compared with those diagnosed with mood disorders.
CONCLUSIONS AND RELEVANCE
This study found that in the 3 years prior to an index diagnosis, individuals with a first diagnosis of psychotic disorder had higher rates of mental health service use, particularly emergency department visits and hospitalizations, compared with individuals with a first diagnosis of a mood disorder. Individuals with psychotic disorders also had a greater number of premorbid diagnoses. Differences in health service utilization patterns between those with a first psychotic disorder diagnosis vs a first mood disorder diagnosis suggest distinct premorbid trajectories that could be useful for next steps in prediction and prevention research.
PubMed: 38888908
DOI: 10.1001/jamapsychiatry.2024.1467 -
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 -
Psychopathology Jun 2024This study aimed to investigate the influence of familial predisposition on substance-induced psychosis among healthy siblings of patients diagnosed with...
OBJECTIVE
This study aimed to investigate the influence of familial predisposition on substance-induced psychosis among healthy siblings of patients diagnosed with substance-induced psychotic disorder, who themselves lack any family history of psychotic disorders. Additionally, the study aimed to explore clinical high-risk states for psychosis, schizotypal features, and neurocognitive functions in comparison to a healthy control group.
METHOD
The study compared healthy siblings of 41 patients diagnosed with substance-induced psychotic disorder with 41 healthy volunteers without a family history of psychotic disorders, matching age, gender, and education. Sociodemographic and clinical characteristics of participants were obtained using data collection forms. The Comprehensive Assessment of At-Risk Mental States (CAARMS) and the Structured Interview for Schizotypy-Revised Form (SIS-R) scales were utilized to assess clinical high risk for psychosis. Neurocognitive functions were evaluated with digit span test (DST), trail making test part A-B (TMT), verbal fluency test (VFT), and Stroop test (ST).
RESULTS
Analysis using the CAARMS scale revealed that 39% of siblings and 7.3% of the control group were at clinically high risk for psychosis, indicating a significant difference in rates of psychotic vulnerability. Comparison between siblings and the control group showed significant differences in mean SIS-R subscale scores, including social behavior, hypersensitivity, referential thinking, suspiciousness, illusions, and overall oddness, as well as in mean neurocognitive function scores, including errors in TMT-A, TMT-B, and VFT out-of-category errors, with siblings exhibiting poorer performance.
CONCLUSION
Our study suggests that healthy siblings of patients with substance-induced psychosis exhibit more schizotypal features and have a higher risk of developing psychosis compared to healthy controls. Additionally, siblings demonstrate greater impairment in attention, response inhibition, and executive functions compared to healthy controls, indicating the potential role of genetic predisposition in the development of substance-induced psychotic disorder.
PubMed: 38885619
DOI: 10.1159/000538478 -
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 -
Journal of Clinical Sleep Medicine :... Jun 2024Brunner syndrome is a recessive X-linked disorder characterized by intellectual disability and impulsive aggressiveness associated with Monoamine Oxidase-A (MAOA)...
Brunner syndrome is a recessive X-linked disorder characterized by intellectual disability and impulsive aggressiveness associated with Monoamine Oxidase-A (MAOA) deficiency leading to increased monoaminergic activity. We report the presence of REM sleep behavior disorder (RBD) in a 46-year-old patient with Brunner syndrome due to a c.1438A>G/iVS14-2 A>G mutation of the gene. He suffered from mild intellectual disability and psychotic disturbances. He presented a 15-year history of nightmares (chase, attacks and fights), sleep-related vocalizations and motor behaviors characterized by talking, screaming, crying, gesturing, punching, and kicking. Video-polysomnography showed RBD characterized by excessive tonic and phasic muscle activity in the mentalis and limb muscles with dream enacting behaviors during REM sleep. Clonazepam achieved a significant reduction of RBD symptomatology. We conclude that RBD can be a manifestation of Brunner syndrome probably due to an increased monoaminergic neurotransmission occurring in this rare genetic disorder.
PubMed: 38881510
DOI: 10.5664/jcsm.11230