Lithium (Li) concentrations in drinking-water supplies are not regulated in the United States; however, Li is included in the 2022 U.S. Environmental Protection Agency list of unregulated contaminants for monitoring by public water systems. Li is used pharmaceutically to treat bipolar disorder, and studies have linked its occurrence in drinking water to human-health outcomes. An extreme gradient boosting model was developed to estimate geogenic Li in drinking-water supply wells throughout the conterminous United States. The model was trained using Li measurements from similar to 13,500 wells and predictor variables related to its natural occurrence in groundwater. The model predicts the probability of Li in four concentration classifications, <= 4 mu g/L, >4 to <= 10 mu g/L, >10 to <= 30 mu g/L, and >30 mu g/L. Model predictions were evaluated using wells held out from model training and with new data and have an accuracy of 47-65%. Important predictor variables include average annual precipitation, well depth, and soil geochemistry. Model predictions were mapped at a spatial resolution of 1 km(2) and represent well depths associated with public- and private-supply wells. This model was developed by hydrologists and public-health researchers to estimate Li exposure from drinking water and compare to national-scale human-health data for a better understanding of dose-response to low (<30 mu g/L) concentrations of Li.
We report a Group A streptococcal (GAS) outbreak in a geriatric mental health in-patient unit. Communication with cognitively impaired patients, limitations in adherence to hygiene practices and communal dining may have facilitated transmission. Settle plates aided in identifying a colonized patient. Rapid access to whole genome sequencing facilitated assessment and management.
Background:Attention-deficit/hyperactivity disorder (ADHD), a common neurodevelopmental condition now recognized to persist into older adulthood, has been postulated to be a risk factor for neurocognitive disorders given the overlap in clinical features and neurobiology, as well as the complex interplay between ADHD and known risk factors for dementia. Studies have emerged assessing this relationship, but there has not yet been a comprehensive systematic review addressing this topic. Objective:To assess whether ADHD is a risk factor for neurocognitive disorders and to explore possible mechanisms for such an association. Methods:A systematic review of the literature was conducted using Medline, Embase, and PsycINFO from inception until June 4, 2023. Studies were included if they assessed whether or how ADHD may be a risk factor for neurocognitive disorders. Studies were excluded if they were not primary literature, not published in a peer-reviewed journal, not in English, and/or used non-human subjects. Study quality was assessed using the QualSyst tool. Results:Sixteen studies met inclusion criteria. Seven studies found a positive association between ADHD and neurocognitive disorders (all-cause dementia in four studies, Alzheimer's disease in three studies, Lewy body dementia in two studies, and mild cognitive impairment in one study). Four studies did not find an association. Five studies pertained to possible mechanisms for an association, including genetics, with minimal significant findings. Conclusions:ADHD may be a risk factor for certain neurocognitive disorders, although the evidence base is limited, and the absolute risk is small. Possible explanations include genetic and lifestyle factors.
AIMS:This systematic review aims to identify and synthesise the publicly available research testing treatments for mental health, cognition and psychological well-being in long COVID. METHODS:The following databases and repositories were searched in October-November 2023: Medline, Embase, APA PsycINFO, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Internet, WANFANG Data, Web of Science's Preprint Citation Index, The Cochrane Central Register of Controlled Trials, Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform. Articles were selected if they described participants with long COVID symptoms at least 4 weeks after SAR-CoV-19 infection, reported primary outcomes on mental health, cognition and/or psychological well-being, and were available with at least an English-language summary. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for systematic reviews were followed. RESULTS:Thirty-three documents representing 31 studies were included. Seven tested psychosocial interventions, five pharmaceutical interventions, three natural supplement interventions, nine neurocognitive interventions, two physical rehabilitation interventions and five integrated interventions. While some promising findings emerged from randomised controlled trials, many studies were uncontrolled; a high risk of bias and insufficient reporting were also frequent. CONCLUSIONS:The published literature on treatments for mental health, cognition and psychological well-being in long COVID show that the interventions are highly heterogeneous and findings are inconclusive to date. Continued scientific effort is required to improve the evidence base. Regular literature syntheses will be required to update and educate clinicians, scientists, interventionists and the long COVID community.
Introduction Governments and public health authorities across many jurisdictions implemented social (physical) distancing measures to contain the spread of the 2019 novel coronavirus disease (COVID-19). Adherence to these measures is variable and likely influenced by various factors. This study aimed to 1) identify the individual sociodemographic, COVID-19 and social distancing related, and psychological determinants of social distancing adherence, and 2) explore regional differences in social distancing adherence in the United States (U.S.) and English-speaking Canada based on each region's discrepant response to social distancing restrictions. Methods A web-based repeated cross-sectional survey was conducted in 4,942 English-speaking participants from the four most populous U.S. states, specifically New York, California, Texas, and Florida, and Canada ( www.covid19-database.com ). The study was conducted at two timepoints, from May 1 to 5, 2020 ( n = 1,019, Canadian participants only) and from July 6 to 10, 2020 ( n = 3,923). Separate univariate models were computed for individual sociodemographic, COVID-19 and social distancing related, and psychological determinants of social distancing adherence. To determine the total variance explained, a univariate analysis including all of the determinants was performed. Regional differences in social distancing were compared between the four U.S. states and Canada, and between the U.S. as a whole and Canada. Results Adherence to social distancing was higher in May (mean = 4.4/5.0±0.7) compared to July (mean = 4.3/5.0±0.7) [ t (4940) = 6.96, p < 0.001], likely a reflection of relaxing restrictions. There were no regional differences in adherence. Sociodemographic, COVID-19 and social distancing related, and psychological determinants explained 10, 36, and 23% of the variance of social distancing adherence, respectively. Higher perceived seriousness of COVID-19 [β (SE) = 0.39 (0.01), p < 0.001, partial η 2 = 0.22], lower risk propensity [β (SE) = −0.15 (0.01), p < 0.001, partial η 2 = 0.06], germ aversion [β (SE) = 0.12 (0.01), p < 0.001, partial η 2 = 0.03], age [β (SE) = 0.01 (0.00), p < 0.001, partial η 2 = 0.02], and greater social support [β (SE) = 0.03 (0.00), p < 0.001, partial η 2 = 0.02] had the largest effects on social distancing adherence. Conclusion Public service initiatives to emphasize the serious consequences of infection and targeted interventions toward certain sociodemographic groups, such as younger adults and vulnerable individuals in greater need of social support, may help enhance the public's adherence to social distancing measures during subsequent waves of COVID-19 and future pandemics.
Impaired insight into illness is a common element of schizophrenia that contributes to treatment nonadherence and negative clinical outcomes. Previous studies suggest that impaired insight may arise from brain abnormalities. However, interpretations of these findings are limited due to small sample sizes and inclusion of patients with a narrow range of illness severity and insight deficits. In a large sample of patients with schizophrenia, the majority of which were designated as treatment-resistant, we investigated the associations between impaired insight and cortical thickness and subcortical volumes. A total of 94 adult participants with a schizophrenia spectrum disorder were included. Fifty-six patients (60%) had treatment-resistant schizophrenia. The core domains of insight were assessed with the VAGUS insight into psychosis scale. We obtained 3T MRI T1-weighted images, which were analysed using CIVET and MAGeT-Brain. Whole-brain vertex-wise analyses revealed impaired insight, as measured by VAGUS average scores, was related to cortical thinning in left frontotemporoparietal regions. The same analysis in treatment-resistant patients showed thinning in the same regions, even after controlling for age, sex, illness severity, and chlorpromazine antipsychotic dose equivalents. No association was found in non-treatment-resistant patients. Region-of-interest analyses revealed impaired general illness awareness was associated with cortical thinning in the left supramarginal gyrus when controlling for covariates. Reduced right and left thalamic volumes were associated with VAGUS symptom attribution and awareness of negative consequences subscale scores, respectively, but not after correction for multiple testing. Our results suggest impaired insight into illness is related to cortical thinning in left frontotemporoparietal regions in patients with schizophrenia, particularly those with treatment resistance where insight deficits may be more chronic.
The COVID-19 Behavior Determinants Database (http://covid19-database.com) is a research project that examined the sociodemographic and psychological determinants of COVID-19 related attitudes and behaviors. It is a comprehensive web-based survey that was administered to adults ages 18 or older (total n=8070) from the United States of America (n = 5326), including the four most populous states, specifically New York, California, Florida, and Texas, and Canada (n = 2744), including all provinces, except Quebec. The survey was collected at three timepoints, May 2020 (n=1019), July 2020 (n=4027), and March 2021 (n=3024). Participants provided detailed sociodemographic information and completed a battery of psychological assessments. Participants also provided information about prior testing for COVID-19 and perceived seriousness of COVID-19 and the need for current physical (social) distancing restrictions. The database is helpful to researchers and public health policy decision-makers who are interested in investigating and identifying the determinants of COVID-19 related attitudes and behaviors in North America.
IntroductionFor some people, COVID-19 infection leads to negative health impacts that can last into the medium or long term. The long-term sequelae of COVID-19 infection, or ‘long COVID’, negatively affects not only physical health, but also mental health, cognition or psychological well-being. Complex, integrated interventions are recommended for long COVID, including psychological components; however, the effectiveness of such interventions has yet to be critically evaluated. This protocol describes a systematic review to be conducted of scientific literature reporting on clinical trials of interventions to promote mental health, cognition or psychological well-being among individuals with long COVID.Methods and analysisThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed. A health sciences librarian will identify the relevant literature through comprehensive systematic searches of Medline, Embase, APA PsycINFO, Cumulative Index to Nursing and Allied Health Literature, medRxiv, PsyArXiv, China National Knowledge Internet and WANFANG Data databases, as well as The Cochrane Central Register of Controlled Trials, clinicaltrials.gov and the WHO International Clinical Trials Registry Platform. Studies will be selected through a title and abstract review, followed by a full-text review using inclusion and exclusion criteria. Data extracted will include intervention descriptions and efficacy metrics. Data will be narratively synthesised; if the data allow, a meta-analysis will be conducted. Risk of bias assessment will be conducted using the Cochrane Risk of Bias 2.0 tool.Ethics and disseminationEthical approval for systematic reviews is not required. As researchers and clinicians respond to the new clinical entity that long COVID represents, this review will synthesise a rapidly emerging evidence base describing and testing interventions to promote mental health, cognition or psychological well-being. Results will therefore be disseminated through an open-access peer-reviewed publication and conference presentations to inform research and clinical practice.Prospero registration numberCRD42022318678
Gamma-Aminobutyric Acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABAergic dysfunction has been implicated in the pathophysiology of schizophrenia. Clozapine, the only approved drug for treatment-resistant schizophrenia (TRS), involves the GABAergic system as one of its targets. However, no studies have investigated the relationship between brain GABA levels, measured by proton magnetic resonance spectroscopy (1H-MRS), and clozapine response in patients with TRS.
The radiotracers [11C]‐raclopride and [11C]‐(+)‐PHNO are commonly used to measure differences in amphetamine‐induced dopamine release between healthy persons and persons with neuropsychiatric diseases. As an agonist radiotracer, [11C]‐(+)‐PHNO should theoretically be roughly 2.7 times more sensitive to displacement by endogenous dopamine than [11C]raclopride. To date, only one study has been published comparing the sensitivity of these two radiotracers to amphetamine‐induced dopamine release in healthy persons. Unfortunately, conflicting findings in the literature suggests that the dose of amphetamine they employed (0.3 mg/kg, p.o.) may not reliably reduce [11C]‐raclopride binding in the caudate. Thus, it is unclear whether the preponderance of evidence supports the theory that [11C]‐(+)‐PHNO is more sensitive to displacement by amphetamine in humans than [11C]‐raclopride. In order to clarify these issues, we conducted a comparative meta‐analysis summarizing the effects of amphetamine on [11C]‐raclopride and [11C]‐(+)‐PHNO binding in healthy humans. Our analysis indicates that amphetamine given at 0.3 mg/kg, p.o. does not reliably reduce [11C]‐raclopride binding in the caudate. Second, the greater sensitivity of [11C]‐(+)‐PHNO is evidenced at 0.5 mg/kg, p.o., but not at lower doses of amphetamine. Third, our analysis suggests that [11C]‐(+)‐PHNO may be roughly 1.5 to 2.5 times more sensitive to displacement by amphetamine than [11C]‐raclopride in healthy persons. We recommend that future displacement studies with these radiotracers employ 0.5 mg/kg, p.o. of amphetamine with a dose, post‐scan interval of at least 3 hr. Using this dose of amphetamine, [11C]‐raclopride studies should employ at least n = 34 participants per group, while [11C]‐(+)‐PHNO studies should employ at least n = 6 participants per group, in order to be sufficiently powered (80%) to detect changes in radiotracer binding within the caudate.
Introduction: Racial minority groups have been disproportionately affected by the 2019 novel coronavirus disease (COVID-19). Vaccine hesitancy may be a major barrier to achieving equitable herd immunity and must be addressed to reduce the excess morbidity and mortality of COVID-19 in disproportionately affected communities. This study aimed to determine if COVID-19 vaccine hesitancy, and its factors vaccine complacency and confidence, are more prominent among disproportionately affected racial minority groups. Methods:We collected data from participants aged 18 years or older from the four most populous U.S. states, including New York, California, Florida, and Texas, and Canada. Data were collected using a web-based survey platform. Data are available at http://www.covid19-database.com. Results:Data from 4,434 participants were included [mean (SD) age = 48.7 (17.2) and 50.4% women]. Vaccine hesitancy was higher in Black, Indigenous (Native American and Indigenous People of Canada, including First Nations, Inuit and Métis), and Latinx compared to White participants, while no difference was found between East Asian and White participants. The group differences in vaccine hesitancy for Indigenous and Black compared to White participants remained after controlling for sociodemographic factors. Determinants of vaccine complacency were equivalent between disproportionately affected racial groups and white participants. Vaccine confidence (i.e., trust in vaccine benefit) was generally lower in all racial groups compared to White participants. Differences in vaccine mistrust comparing Black and East Asian to White participants remained after controlling for sociodemographic factors. Discussion:Disproportionately affected racial minorities may have higher vaccine hesitancy and lower confidence in COVID-19 vaccines. Public health and other relevant government services should address vaccine hesitancy among racial minorities using a culturally sensitive, community-centered approach to attain equitable herd immunity.
The regulation of the serotonin transporter (SERT) by guanine nucleotide-binding protein alpha (Gα) q was investigated using Gαq knockout mice. In the absence of Gαq, SERT-mediated uptake of 5-hydroxytryptamine (5HT) was enhanced in midbrain and frontal cortex synaptosomes, but only in female mice. The mechanisms underlying this sexual dimorphism were investigated using quantitative western blot analysis revealing brain region-specific differences. In the frontal cortex, SERT protein expression was decreased in male knockout mice, seemingly explaining the sex-dependent variation in SERT activity. The differential expression of Gαi1 in female mice contributes to the sex differences in the midbrain. In fact, Gαi1 levels inversely correlate with 5HT uptake rates across both sexes and genotypes. Likely due to differential SERT regulation as well as sex differences in the expression of tryptophan hydroxylase 2, Gαq knockout mice also displayed sex- and genotype-dependent alterations in total 5HT tissue levels as determined by high-performance liquid chromatography. Gαq inhibitors, YM-254890 and BIM-46187, differentially affected SERT activity in both, synaptosomes and cultured cells. YM-254890 treatment mimicked the effect of Gαq knockout in the frontal cortex. BIM-46187, which promotes the nucleotide-free form of Gα proteins, substantially inhibited 5HT uptake, prompting us to hypothesise that Gαq interacts with SERT similarly as with G-protein-coupled receptors and inhibits SERT activity by modulating transport-associated conformational changes. Taken together, our findings reveal a novel mechanism of SERT regulation and impact our understanding of sex differences in diseases associated with dysregulation of serotonin transmission, such as depression and anxiety.
Objective: Since apathy increases in prevalence with severity of dementia pathology, we sought to distinguish concomitant neurodegenerative processes from brain differences associated with apathy in persons with mild cognitive impairment (MCI) and Alzheimer's Disease (AD). We examined relative structural brain differences between case-control matched cognitively impaired patients with and without apathy. Design: Cross-sectional case-control study. Setting: Fifty-eight clinical sites in phase 2 of the AD Neuroimaging Initiative across the United States and Canada. Participants: The >= 55 years of age with MCI or AD dementia and no major neurological disorders aside from suspected incipient AD dementia. Participants with apathy (n = 69) were age-, sex-, apolipoprotein E epsilon 4 allele carrier status-, Mini-Mental State Exam score-, and MCI or AD dementia diagnosis-matched to participants without apathy (n = 149). Interventions: The 3-tesla T1-weighted MRI scan and neurocognitive assessments. Using the Neuropsychiatric Inventory apathy domain scores, participants were dichotomized into a with-apathy group (score >= 1) and a without-apathy group (score = 0). Measurements: Cortical thicknesses from 24 a priori regions of interest involved in frontostriatal circuits and frontotemporal association areas. Results: False-discovery rate adjusted within-group comparisons between participants with apathy and participants without apathy showed thinner right medial orbitofrontal (mOFC; mean difference (MD) +/- standard error of MD (SE) = -0:0879 +/- 0:0257 mm; standardized MD (d) = -0:4456) and left rostral anterior cingulate (rACC; MD +/- SE = -0:0905 +/- 0:0325 mm; d = -0:3574) cortices and thicker left middle temporal cortices (MTC; MD +/- SE = 0:0688 +/- 0:0239 mm; d = 0:3311) in those with apathy. Conclusion: Atrophy of the right mOFC and left rACC and sparing of atrophy in the left MTC are associated with apathy in cognitively impaired persons.
Apathy increases the risk of developing dementia, is prevalent among cognitively impaired (CI) older adults, and is associated with worse outcomes. It is also associated with deficits in frontostriatal circuits and frontotemporal association areas. However, the specific brain regions that mediate apathy remain unclear given concomitant neurodegenerative processes involved in dementias.
Background Novel coronavirus disease 2019 (COVID-19) vaccine hesitancy is a barrier to achieving herd immunity, and thus, a prominent public health concern. This study aimed to identify the determinants of COVID-19 vaccine hesitancy based on the World Health Organization’s ‘3Cs’ model (i.e., confidence, complacency, and convenience) in the United States (U.S.) and Canada. Methods Data from 7678 adults ages 18 or older were collected from the four most populous U.S. States, specifically New York, California, Florida, and Texas, and from English-speaking Canada at three timepoints, in May and July 2020, and March 2021 using a web-based survey (www.covid19-database.com). Sociodemographic information was collected, and comprehensive psychological assessments were administered. Univariate analyses were performed to identify the individual determinants of vaccine hesitancy, which were categorized as: 1) vaccine confidence, 2) vaccine complacency, 3) sociodemographic, and 4) other psychological factors. A series of models were computed using these categorizations. Results Mistrust of vaccine benefit (β(SE) = 0.67(0.01), p<0.001, partial η2 = 0.26) and lower perceived seriousness of COVID-19 (β(SE) = 0.68(0.02), p<0.001, partial η2 = 0.12) were the principal determinants of vaccine hesitancy. Right-wing political affiliation (β(SE) = 0.32(0.02), p<0.001, partial η2 = 0.03), higher risk propensity (β(SE) = 0.24(0.02), p<0.001, partial η2 = 0.03), and less negative mental health effects of the COVID-19 pandemic (β(SE) = 0.20(0.01), p<0.001, partial η2 = 0.03) were the main sociodemographic and psychological determinants. Other sociodemographic determinants included younger age, women, race, and employment status. Lack of vaccine confidence and complacency explained 38% and 21% of the variance in vaccine hesitancy, respectively; whereas, sociodemographic and psychological determinants explained 13% and 11% of the variance in vaccine hesitancy, respectively. Discussion Targeted and tailored public health interventions that enhance the public’s confidence in vaccines and emphasize the risk and seriousness of COVID-19 may address COVID-19 vaccine hesitancy. Efforts directed toward specific marginalized and underserved groups may be required to promote vaccine confidence.