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European Child & Adolescent Psychiatry Jun 2024Previous research has linked attention deficit hyperactivity disorder (ADHD) with an increased risk of all-cause mortality, primarily owing to unnatural causes such as...
BACKGROUND
Previous research has linked attention deficit hyperactivity disorder (ADHD) with an increased risk of all-cause mortality, primarily owing to unnatural causes such as accidents and suicides. This increase may be attributable to the co-occurrence of major psychiatric disorders, including schizophrenia (SCZ), bipolar disorder (BD), major depressive disorder (MDD), autism spectrum disorder (ASD), anxiety disorders, substance use disorders (SUDs), and personality disorders (PDs). This study examined the all-cause and specific-cause mortality rates in individuals with ADHD and the influence of psychiatric comorbidities.
METHODS
Between 2003 and 2017, 1.17 million individuals were enrolled in the study, of which 233,886 received a diagnosis of ADHD from the Taiwan's National Health Insurance Research Database. A 1:4 sex- and birth year-matched control group without ADHD was also included. Hazard ratios (HRs) for mortality rates were estimated between groups after adjusting for demographic data.
RESULTS
During the follow-up period, 781 individuals with ADHD died. The HR for all-cause mortality was 1.45 (95% confidence interval [CI]: 1.30-1.61), largely owing to unnatural causes, particularly suicide. Suicide rates were particularly high in individuals with ADHD and psychiatric comorbidities: the HRs for suicide were 47.06 in ADHD with SUDs (95% CI: 6.12-361.99), 32.02 in ADHD with SCZ (7.99-128.29), 23.60 in ADHD with PDs (7.27-76.66), 10.11 in ADHD with anxiety disorders (5.74-17.82), 9.30 in ADHD with BD (4.48-19.33), 8.36 in ADHD with MDD (5.66-12.35), and 6.42 in ADHD with ASD (1.83-22.53) relative to ADHD only.
DISCUSSION
ADHD was associated with increased mortality rates, primarily owing to suicide. The presence of major psychiatric comorbidities was associated with a further increase in suicide mortality risk.
PubMed: 38916769
DOI: 10.1007/s00787-024-02511-w -
European Archives of Psychiatry and... Jun 2024While most people are right-handed, a minority are left-handed or mixed-handed. It has been suggested that mental and developmental disorders are associated with...
While most people are right-handed, a minority are left-handed or mixed-handed. It has been suggested that mental and developmental disorders are associated with increased prevalence of left-handedness and mixed-handedness. However, substantial heterogeneity exists across disorders, indicating that not all disorders are associated with a considerable shift away from right-handedness. Increased frequencies in left- and mixed-handedness have also been associated with more severe clinical symptoms, indicating that symptom severity rather than diagnosis explains the high prevalence of non-right-handedness in mental disorders. To address this issue, the present study investigated the association between handedness and measures of stress reactivity, depression, mania, anxiety, and positive and negative symptoms in a large sample of 994 healthy controls and 1213 patients with DSM IV affective disorders, schizoaffective disorders, or schizophrenia. A series of complementary analyses revealed lower lateralization and a higher percentage of mixed-handedness in patients with major depression (14.9%) and schizophrenia (24.0%) compared to healthy controls (12%). For patients with schizophrenia, higher symptom severity was associated with an increasing tendency towards left-handedness. No associations were found for patients diagnosed with major depression, bipolar disorder, or schizoaffective disorder. In healthy controls, no association between hand preference and symptoms was evident. Taken together, these findings suggest that both diagnosis and symptom severity are relevant for the shift away from right-handedness in mental disorders like schizophrenia and major depression.
PubMed: 38914850
DOI: 10.1007/s00406-024-01833-9 -
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 -
Molecular Psychiatry Jun 2024There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed...
There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed evidence across mental disorders. We carried out an umbrella review of meta-analyses of randomized controlled trials (RCTs) of biological treatments (pharmacotherapy or neurostimulation) for mental disorders. We explored whether placebo effect size differs across distinct disorders, and the correlates of increased placebo effects. Based on a pre-registered protocol, we searched Medline, PsycInfo, EMBASE, and Web of Knowledge up to 23.10.2022 for systematic reviews and/or meta-analyses reporting placebo effect sizes in psychopharmacological or neurostimulation RCTs. Twenty meta-analyses, summarising 1,691 RCTs involving 261,730 patients, were included. Placebo effect size varied, and was large in alcohol use disorder (g = 0.90, 95% CI [0.70, 1.09]), depression (g = 1.10, 95% CI [1.06, 1.15]), restless legs syndrome (g = 1.41, 95% CI [1.25, 1.56]), and generalized anxiety disorder (d = 1.85, 95% CI [1.61, 2.09]). Placebo effect size was small-to-medium in obsessive-compulsive disorder (d = 0.32, 95% CI [0.22, 0.41]), primary insomnia (g = 0.35, 95% CI [0.28, 0.42]), and schizophrenia spectrum disorders (standardized mean change = 0.33, 95% CI [0.22, 0.44]). Correlates of larger placebo response in multiple mental disorders included later publication year (opposite finding for ADHD), younger age, more trial sites, larger sample size, increased baseline severity, and larger active treatment effect size. Most (18 of 20) meta-analyses were judged 'low' quality as per AMSTAR-2. Placebo effect sizes varied substantially across mental disorders. Future research should explore the sources of this variation. We identified important gaps in the literature, with no eligible systematic reviews/meta-analyses of placebo response in stress-related disorders, eating disorders, behavioural addictions, or bipolar mania.
PubMed: 38914807
DOI: 10.1038/s41380-024-02638-x -
Psychiatry Research Jun 2024Previous research examining bipolar-disorder (BD) and pregnancy/neonatal outcomes yielded mixed results, were mostly derived from Western countries and rarely delineated...
Previous research examining bipolar-disorder (BD) and pregnancy/neonatal outcomes yielded mixed results, were mostly derived from Western countries and rarely delineated effect between disorder and mood-stabilizers. This population-based study identified women age 15-50 years who delivered first/singleton child in 2003-2018 in Hong Kong, utilizing territory-wide medical-record database of public healthcare services. Propensity-score weighted logistic-regression analyses adjusted for confounders were employed to examine risk of adverse pregnancy, delivery and neonatal outcomes associated with BD and mood-stabilizers (lithium, anticonvulsants and antipsychotics). Exploratory unadjusted-analyses were conducted to assess risk for congenital-malformations. Of 465,069 women, 302 had BD-diagnosis, including 168 redeemed ≥ 1 prescription of mood-stabilizers during pregnancy (treated-BD) and 134 gestationally-unexposed to mood-stabilizers (untreated-BD). BD was significantly-associated with increased risk of gestational-diabetes (adjusted-odds-ratio: 1.75 [95 % CI: 1.15-2.70]) and maternal somatic hospitalization ≤ 90 days post-discharge from index-delivery (2.12 [1.19-3.90]). In treatment status-stratified analyses, treated-BD women exhibited significantly-increased rate of gestational-diabetes (2.09 [1.21-3.70]) relative to controls (non-BD and gestationally-unexposed to mood-stabilizers). No significant association of BD or mood-stabilizers with other adverse outcomes was observed. Overall, our findings indicate that BD and mood-stabilizers are not associated with most adverse pregnancy, delivery and neonatal outcomes. Further research clarifying comparative safety of individual mood-stabilizing agents on pregnancy/neonatal outcomes is required.
PubMed: 38914040
DOI: 10.1016/j.psychres.2024.116050 -
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 -
Biological Psychiatry. Cognitive... Jun 2024Schizophrenia (SCZ) and bipolar disorder (BD) are associated with information processing abnormalities, including visual perceptual and cognitive impairments, that...
BACKGROUND
Schizophrenia (SCZ) and bipolar disorder (BD) are associated with information processing abnormalities, including visual perceptual and cognitive impairments, that impact daily functioning. Recent work in healthy samples suggests that peak alpha frequency (PAF) is an electrophysiological index of visual information processing speed that is also correlated with cognitive ability. There is evidence that PAF is slowed in SCZ, but it remains unclear whether PAF is reduced in BD, or if slower PAF is associated with impaired visual perception and cognition in these clinical disorders.
METHODS
The current study recorded resting-state brain activity (both eyes open and closed) with electroencephalography (EEG) in 90 SCZ participants, 62 BD participants, and 69 healthy controls. Most participants also performed a visual perception task (backward masking) and cognitive testing (MATRICS Consensus Cognitive Battery).
RESULTS
We replicated previous findings of reduced PAF in SCZ compared with healthy controls. In contrast, PAF in BD did not significantly differ from healthy controls. Further, PAF was significantly correlated with performance on the perceptual and cognitive measures in SCZ, but not BD. PAF was also correlated with visual perception in the healthy control group, and showed a trend-level correlation with cognition.
CONCLUSIONS
Together, these results suggest that PAF deficits characterize SCZ, but not BD, and that individual differences in PAF relate to abnormalities in visual information processing and cognition in SCZ.
PubMed: 38909899
DOI: 10.1016/j.bpsc.2024.06.004 -
Biological Psychiatry. Cognitive... Jun 2024Risk for Bipolar disorder (BD) is increased among individuals with family history or subthreshold mood symptoms. However, the brain structural developments associated...
BACKGROUND
Risk for Bipolar disorder (BD) is increased among individuals with family history or subthreshold mood symptoms. However, the brain structural developments associated with these BD risks remained unknown.
METHODS
This longitudinal cohort study examined the brain grey matter volume (GMV) developmental features of familial and symptomatic risks for BD, and their associations with participants' global function levels. We recruited unaffected BD offspring with (N=26, age=14.9±2.9 years, 14 females) or without (N=35, age=15.3±2.7 years, 19 females) subthreshold manic or depressive symptoms, and unaffected non-BD offspring with (N=49, age=14.5±2.2 years, 30 females) or without (N=68, age=15.0±2.3 years, 37 females) symptoms. The offspring had no mood disorder diagnosis prior to the study. The average follow-up duration was 2.63±1.63 years.
RESULTS
We found at baseline, significant interactive effects of familial risk and subthreshold symptoms indicated the symptomatic offspring exhibited markedly large GMV in the brain affective and cognitive circuitries. During follow-up, the combined group of BD offspring (symptomatic and non-symptomatic) displayed accelerated GMV decrease than BD non-offspring, in the hippocampus and anterior cingulate cortex. In contrast, the combined group of symptomatic participants (offspring and non-offspring) displayed slower GMV decrease than non-symptomatic participants, in the ventromedial prefrontal cortex. Larger GMV at baseline, and accelerated GMV decrease during follow-up, prospectively and longitudinally predicted positive global function changes. All results survived multiple-testing correction.
CONCLUSIONS
These findings indicated that familial and symptomatic risks of BD are associated with distinct brain structural developments, and unraveled key brain developmental features of particularly vulnerable high-risk individuals to subsequent functional deterioration.
PubMed: 38909895
DOI: 10.1016/j.bpsc.2024.06.005 -
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