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Indian Journal of Psychiatry May 2024Bipolar disorder is one of the severe mental disorders that are associated with significant morbidity of the patients. Despite advancements in our understanding about... (Review)
Review
BACKGROUND
Bipolar disorder is one of the severe mental disorders that are associated with significant morbidity of the patients. Despite advancements in our understanding about the disorder, it remains a challenging proposition to treat bipolar disorder, largely since the prophylactic treatment of the disorder requires assessment of complex clinical algorithms. The revisions of the classificatory systems have also changed the conceptualization of the disorder. In this background, we conducted a review of the Indian studies conducted on the clinical aspects of bipolar disorder.
METHODS
A narrative review was conducted with focus on the literature published from India. The databases searched included PubMed, Scopus, and Google Scholar, and articles published over the last 15 years by Indian authors were included for this review.
RESULTS
In our review, we could access a substantial volume of research published from India. We could identify studies that catered to most of the relevant themes in bipolar disorder including epidemiology, etiology, comorbidities, stigma, disability, clinical course, cognitive profile, pathways to care, and recovery.
CONCLUSION
The research trajectory was in line with the research conducted elsewhere in the world. However, certain dissimilarities in terms of focus could also be observed. The possible reason behind this deviation could be the difference in clinical need and unique challenges faced in the management and rehabilitation of patients in bipolar disorder in Indian scenario.
PubMed: 38919568
DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_698_23 -
Database : the Journal of Biological... Jun 2024Major depressive disorder (MDD) is a pressing global health issue. Its pathogenesis remains elusive, but numerous studies have revealed its intricate associations with...
Major depressive disorder (MDD) is a pressing global health issue. Its pathogenesis remains elusive, but numerous studies have revealed its intricate associations with various biological factors. Consequently, there is an urgent need for a comprehensive multi-omics resource to help researchers in conducting multi-omics data analysis for MDD. To address this issue, we constructed the MDDOmics database (Major Depressive Disorder Omics, (https://www.csuligroup.com/MDDOmics/), which integrates an extensive collection of published multi-omics data related to MDD. The database contains 41 222 entries of MDD research results and several original datasets, including Single Nucleotide Polymorphisms, genes, non-coding RNAs, DNA methylations, metabolites and proteins, and offers various interfaces for searching and visualization. We also provide extensive downstream analyses of the collected MDD data, including differential analysis, enrichment analysis and disease-gene prediction. Moreover, the database also incorporates multi-omics data for bipolar disorder, schizophrenia and anxiety disorder, due to the challenge in differentiating MDD from similar psychiatric disorders. In conclusion, by leveraging the rich content and online interfaces from MDDOmics, researchers can conduct more comprehensive analyses of MDD and its similar disorders from various perspectives, thereby gaining a deeper understanding of potential MDD biomarkers and intricate disease pathogenesis. Database URL: https://www.csuligroup.com/MDDOmics/.
Topics: Depressive Disorder, Major; Humans; Databases, Genetic; Polymorphism, Single Nucleotide; Genomics; DNA Methylation; Multiomics
PubMed: 38917209
DOI: 10.1093/database/baae042 -
International Journal of Bipolar... Jun 2024Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of... (Review)
Review
BACKGROUND
Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium's clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations.
CONTENT
This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors' preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections.
CONCLUSIONS
Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium's ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately.
PubMed: 38914810
DOI: 10.1186/s40345-024-00345-8 -
Cureus May 2024Violent deaths, including suicides and homicides, pose a significant public health challenge in the United States. Understanding the trends and identifying associated...
BACKGROUND
Violent deaths, including suicides and homicides, pose a significant public health challenge in the United States. Understanding the trends and identifying associated risk factors is crucial for targeted intervention strategies.
AIM
To examine the trends in suicides and homicides over the past two decades and identify demographic and contextual predictors using the Center for Disease Control and Prevention's Web-based Injury Statistics Query and Reporting System online database.
METHODS
A retrospective analysis of mortality records from 2000 to 2020 was conducted, utilizing multivariate regression analyses. Covariates included age, race, sex, education, mental health conditions, and time period. Age-adjusted rates were employed to assess trends.
RESULTS
Over the 20 years, there was an upward trajectory in suicide rates, increasing from approximately 10/100,000 to over 14/100,000 individuals, which is a notable increase among American Indians (100.8% increase) and individuals aged 25 years and younger (45.3% increase). Homicide rates, while relatively stable, exhibited a significant increase in 2019-2020, with African Americans consistently having the highest rates and a significant increase among American Indians (73.2% increase). In the multivariate regression analysis, Individuals with advanced education (OR= 1.74, 95% CI= 1.70 - 1.78), depression (OR = 13.47, 95% CI = 13.04 - 13.91), and bipolar disorder (OR = 2.65, 95% CI = 2.44 - 2.88) had higher odds of suicide. Risk factors for homicide include African Americans (OR = 4.15, 95% CI = 4.08 - 4.23), Latinx (OR = 2.31, 95% CI = 2.26 - 2.37), people aged 25 years and younger, and those with lower educational attainment.
CONCLUSION
This study highlights the changing demographic pattern in suicides and homicides in the United States and the need for targeted public health responses. Means restriction, universal suicide screening, addressing mental health stigma, and implementing broad interventions that modify societal attitudes toward suicide and homicides are essential components of a comprehensive strategy.
PubMed: 38910703
DOI: 10.7759/cureus.61010 -
Annals of General Psychiatry Jun 2024Migraine has been associated with mental disorders, however whether parental migraine is associated with an increased risk of major mental disorders (MMDs) in offspring...
BACKGROUND
Migraine has been associated with mental disorders, however whether parental migraine is associated with an increased risk of major mental disorders (MMDs) in offspring has not been investigated. We aimed to examine the risk of the development of MMDs in the offspring of parents with migraine compared with those of parents without migraine.
METHODS
This study used data derived from the Taiwan National Health Insurance Research Database. Offspring of parents with migraine and a control group consisting of offspring of parents without migraine matched for demographic and parental mental disorders were included. Cox regression was used to estimate the risk of MMDs, including schizophrenia, depressive disorder, bipolar disorder, autistic spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Sub-analyses stratified by the fathers and mothers were further performed to separately clarify the risks of MMDs among the offspring.
RESULTS
We included 22,747 offspring of parents with migraine and 227,470 offspring of parents without migraine as the controls. Parental migraine was significantly associated with an increased risk of ADHD (reported as hazard ratios with 95% confidence intervals: 1.37, 1.25-1.50), bipolar disorder (1.35, 1.06-1.71), and depressive disorder (1.33, 1.21-1.47) compared to the offspring of parents without migraine. Importantly, sub-analyses showed that only maternal migraine was significantly associated with these risks.
CONCLUSIONS
Due to the heavy burden of MMDs, healthcare workers should be aware of the risk of MMDs in the offspring of parents with migraine, particular in mothers.
PubMed: 38909222
DOI: 10.1186/s12991-024-00508-y -
BMJ Open Jun 2024Clinical practice guidelines (CPGs) are essential for standardising patient care based on evidence-based medicine. However, the presence of financial conflicts of...
OBJECTIVE
Clinical practice guidelines (CPGs) are essential for standardising patient care based on evidence-based medicine. However, the presence of financial conflicts of interest (COIs) among CPG authors can undermine their credibility. This study aimed to examine the extent and size of COIs among authors of psychiatry CPGs in Japan.
METHODS
This cross-sectional analysis of disclosed payments from pharmaceutical companies assesses the prevalence and magnitude of personal payments for lecturing, consulting and writing to CPGs for bipolar disorder and major depressive disorder in Japan between 2016 and 2020.
RESULTS
This study found that 93.3% of authors received payments over a 5-year period, with total payments exceeding US$4 million. The median payment per author was US$51 403 (IQR: US$9982-US$111 567), with a notable concentration of payments among a small number of authors, including the CPG chairperson. Despite these extensive financial relationships, only a fraction of authors disclosed their COIs in the CPGs. These large amounts of personal payments were made by pharmaceutical companies manufacturing new antidepressants and sleeping aids listed in the CPGs.
CONCLUSIONS
This study found that more than 93% of authors of CPGs for major depressive disorder and bipolar disorder in Japan received considerable amounts of personal payments from the pharmaceutical industry. The findings highlight deviations from international COI management standards and suggest a need for more stringent COI policies for psychiatry CPGs in Japan.
Topics: Humans; Japan; Depressive Disorder, Major; Cross-Sectional Studies; Drug Industry; Conflict of Interest; Bipolar Disorder; Practice Guidelines as Topic; Disclosure; Authorship
PubMed: 38908845
DOI: 10.1136/bmjopen-2024-086396 -
Ultrasonics Sonochemistry Jun 2024Bipolar disorder is commonly treated with lithium carbonate. The concentration of lithium in the blood serum should be closely monitored in patients who require...
Bipolar disorder is commonly treated with lithium carbonate. The concentration of lithium in the blood serum should be closely monitored in patients who require long-term lithium therapy. To date, no colorimetric method of detecting lithium ions has been reported using nanosensors. We have developed a novel chemosensor based on nanozyme (NZ) to address this clinical need. The GO-AgO NZs were synthesized by a sonochemical method and used as a colorimetric nanosensor to detect lithium ions in human blood serum (Li (I)). To characterize NZs, various techniques were employed, including XRD, FTIR, TEM, FESEM, EDX, Raman spectroscopy, BET, DLS, Zeta potential, and ICP-OES. According to TEM and FESEM images of GO-AgO, the nanoparticles (NPs) of AgO are uniformly distributed on the surface of 2D graphene oxide sheets. In addition, silver oxide nanoparticles exhibited a cubic morphology with an average size of 3.5 nm. We have examined the performance of the NZs in an aqueous medium and in human blood serum that contains Li (I). A colorimetric test revealed that NZs synthesized in the presence of ultrasound were more sensitive to Li (I). According to the linearity of the calibration curves' ranges, Li (I) has a limit of detection (LOD) of 0.01 µg/mL. Furthermore, it displayed a linear range between 0 and 12 µg/mL. GO-AgO NZs showed noticeable color changes from green to orange after exposure to Li (I). An incubation time of two minutes was found to be the most effective for sensing. This innovative approach provides a reliable method for monitoring lithium levels and ensuring patient safety during long-term lithium therapy for bipolar disorder.
PubMed: 38908076
DOI: 10.1016/j.ultsonch.2024.106960 -
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 -
PloS One 2024This study addresses the challenge of differentiating between bipolar disorder II (BD II) and borderline personality disorder (BPD), which is complicated by overlapping...
This study addresses the challenge of differentiating between bipolar disorder II (BD II) and borderline personality disorder (BPD), which is complicated by overlapping symptoms. To overcome this, a multimodal machine learning approach was employed, incorporating both electroencephalography (EEG) patterns and cognitive abnormalities for enhanced classification. Data were collected from 45 participants, including 20 with BD II and 25 with BPD. Analysis involved utilizing EEG signals and cognitive tests, specifically the Wisconsin Card Sorting Test and Integrated Cognitive Assessment. The k-nearest neighbors (KNN) algorithm achieved a balanced accuracy of 93%, with EEG features proving to be crucial, while cognitive features had a lesser impact. Despite the strengths, such as diverse model usage, it's important to note limitations, including a small sample size and reliance on DSM diagnoses. The study suggests that future research should explore multimodal data integration and employ advanced techniques to improve classification accuracy and gain a better understanding of the neurobiological distinctions between BD II and BPD.
Topics: Humans; Borderline Personality Disorder; Bipolar Disorder; Machine Learning; Electroencephalography; Adult; Female; Male; Diagnosis, Differential; Young Adult; Cognition; Algorithms
PubMed: 38905185
DOI: 10.1371/journal.pone.0303699 -
Frontiers in Endocrinology 2024Epidemiologic studies have suggested co-morbidity between hypothyroidism and psychiatric disorders. However, the shared genetic etiology and causal relationship between...
BACKGROUND
Epidemiologic studies have suggested co-morbidity between hypothyroidism and psychiatric disorders. However, the shared genetic etiology and causal relationship between them remain currently unclear.
METHODS
We assessed the genetic correlations between hypothyroidism and psychiatric disorders [anxiety disorders (ANX), schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP)] using summary association statistics from genome-wide association studies (GWAS). Two disease-associated pleiotropic risk loci and genes were identified, and pathway enrichment, tissue enrichment, and other analyses were performed to determine their specific functions. Furthermore, we explored the causal relationship between them through Mendelian randomization (MR) analysis.
RESULTS
We found significant genetic correlations between hypothyroidism with ANX, SCZ, and MDD, both in the Linkage disequilibrium score regression (LDSC) approach and the high-definition likelihood (HDL) approach. Meanwhile, the strongest correlation was observed between hypothyroidism and MDD (LDSC: rg=0.264, =7.35×10; HDL: rg=0.304, =4.14×10). We also determined a significant genetic correlation between MDD with free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels. A total of 30 pleiotropic risk loci were identified between hypothyroidism and psychiatric disorders, of which the 15q14 locus was identified in both ANX and SCZ ( values are 6.59×10 and 2.10×10, respectively) and the 6p22.1 locus was identified in both MDD and SCZ ( values are 1.05×10 and 5.75×10, respectively). Sixteen pleiotropic risk loci were identified between MDD and indicators of thyroid function, of which, four loci associated with MDD (1p32.3, 6p22.1, 10q21.1, 11q13.4) were identified in both FT4 normal level and Hypothyroidism. Further, 79 pleiotropic genes were identified using Magma gene analysis (<0.05/18776 = 2.66×10). Tissue-specific enrichment analysis revealed that these genes were highly enriched into six brain-related tissues. The pathway analysis mainly involved nucleosome assembly and lipoprotein particles. Finally, our two-sample MR analysis showed a significant causal effect of MDD on the increased risk of hypothyroidism, and BIP may reduce TSH normal levels.
CONCLUSIONS
Our findings not only provided evidence of a shared genetic etiology between hypothyroidism and psychiatric disorders, but also provided insights into the causal relationships and biological mechanisms that underlie their relationship. These findings contribute to a better understanding of the pleiotropy between hypothyroidism and psychiatric disorders, while having important implications for intervention and treatment goals for these disorders.
Topics: Humans; Hypothyroidism; Genome-Wide Association Study; Mendelian Randomization Analysis; Genetic Predisposition to Disease; Mental Disorders; Polymorphism, Single Nucleotide; Schizophrenia; Bipolar Disorder; Depressive Disorder, Major; Linkage Disequilibrium; Anxiety Disorders
PubMed: 38904036
DOI: 10.3389/fendo.2024.1370019