Adult Attention-Deficit/Hyperactivity Disorder and the Risk of Dementia Posted on November 28, 2023 by admin

Abstract

Importance: Evidence that adult attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk of dementia is scarce and inconsistent, and potential sources of bias are untested.

Objective: To examine the association between adult ADHD and the risk of dementia.

Design, setting, and participants: This prospective national cohort study consisted of 109 218 members of a nonprofit Israeli health maintenance organization born between 1933 and 1952 who entered the cohort on January 1, 2003, without an ADHD or dementia diagnosis and were followed up to February 28, 2020. Participants were aged 51 to 70 years in 2003. Statistical analysis was conducted from December 2022 to August 2023.

Exposure: Adult ADHD was a time-varying covariate, classified as present from the age of the first diagnosis (using the International Classification of Diseases, Ninth Revision, and the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision); otherwise, absent.

Main outcome and measures: Cox regression models were fitted to quantify the association between adult ADHD and the risk of incident dementia with hazard ratios (HRs) and their 95% CIs unadjusted and in the primary analysis, using inverse probability weights, adjusted for 18 sources of potential confounding. In 14 complementary analyses, subgroup and sensitivity analyses were implemented.

Results: At the beginning of the follow-up, the sample of 109 218 participants had a mean (SD) age of 57.7 (5.5) years, 56 474 participants (51.7%) were female, and 52 744 (48.3%) were male. During follow-up, 730 participants (0.7%) received a diagnosis of adult ADHD, and 7726 (7.1%) received a diagnosis of dementia. Dementia occurred among 96 of 730 participants (13.2%) with adult ADHD and 7630 of 108 488 participants (7.0%) without adult ADHD. In the primary analysis, compared with the absence of adult ADHD, the presence of adult ADHD was statistically significantly (P < .001) associated with an increased dementia risk (unadjusted HR, 3.62 [95% CI, 2.92-4.49; P < .001]; adjusted HR, 2.77 [95% CI, 2.11-3.63; P < .001]). Twelve of the 14 complementary analyses did not attenuate the conclusions based on the results of the primary analysis. There was, however, no clear increase in the risk of dementia associated with adult ADHD among those who received psychostimulant medication, and evidence of reverse causation was mild.

Conclusions and relevance: In this cohort study of individuals born between 1933 and 1952 and followed up in old age, adult ADHD was associated with an increased risk of dementia. Policy makers, caregivers, patients, and clinicians may wish to monitor reliably for ADHD in old age.

Levine SZ, Rotstein A, Kodesh A, Sandin S, Lee BK, Weinstein G, Schnaider Beeri M, Reichenberg A. Adult Attention-Deficit/Hyperactivity Disorder and the Risk of Dementia. JAMA Netw Open. 2023 Oct 2;6(10):e2338088. doi: 10.1001/jamanetworkopen.2023.38088. PMID: 37847497; PMCID: PMC10582792.

https://pubmed.ncbi.nlm.nih.gov/37847497/

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Sigma-1 Receptor Inhibition Reduces Mechanical Allodynia and Modulate Neuroinflammation in Chronic Neuropathic Pain Posted on November 24, 2023 by admin

Abstract: Neuropathic pain is one of the most debilitating forms of chronic pain, resulting from an injury or disease of the somatosensory nervous system, which induces abnormal painful sensations including allodynia and hyperalgesia. Available treatments are limited by severe side-effects and reduced efficacy in the chronic phase of the disease. Sigma-1 receptor (σ1R) has been identified as a chaperone protein, which modulate opioid receptors activities and the functioning of several ion channels, exerting a role in pain transmission. As such, it represents a druggable target to treat neuropathic pain. This study aims at investigating the therapeutic potential of the novel compound (+)-2R/S-LP2, a σ1R antagonist, in reducing painful behaviour and modulating the neuroinflammatory environment. We showed that repeated administration of the compound significantly inhibited mechanical allodynia in neuropathic rats, increasing the withdrawal threshold as compared to CCI-vehicle rats. Moreover, we found that (+)-2R/S-LP2-mediated effects resolve the neuroinflammatory microenvironment by reducing central gliosis and pro-inflammatory cytokines expression levels. This effect was coupled with a significant reduction of connexin 43 (Cx43) expression levels and gap junctions/hemichannels mediated microglia-to-astrocyte communication. These results suggest that inhibition of σ1R significantly attenuates neuropathic pain chronicization, thus representing a viable effective strategy.

Denaro S, Pasquinucci L, Turnaturi R, Alberghina C, Longhitano L, Giallongo S, Costanzo G, Spoto S, Grasso M, Zappalà A, Li Volti G, Tibullo D, Vicario N, Parenti R, Parenti C. Sigma-1 Receptor Inhibition Reduces Mechanical Allodynia and Modulate Neuroinflammation in Chronic Neuropathic Pain. Mol Neurobiol. 2023 Nov 3. doi: 10.1007/s12035-023-03717-w. Epub ahead of print. PMID: 37922065.

https://pubmed.ncbi.nlm.nih.gov/37922065/

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3-year outcomes of discharged survivors of COVID-19 following the SARS-CoV-2 omicron (B.1.1.529) wave in 2022 in China: a longitudinal cohort study Posted on November 23, 2023 by admin

Summary

Background

There is a paucity of data on the natural trajectory of outcomes in survivors of COVID-19 beyond 2 years after symptom onset, and no evidence exists on the effect of re-infection in people with long COVID symptoms. We aimed to investigate the 3-year health outcomes of COVID-19 survivors and the effect of omicron re-infection.

Methods

In this single-centre, longitudinal cohort study, we recruited participants with confirmed COVID-19 who were discharged from the Jin Yin-tan hospital in Wuhan, China, between Jan 7 and May 29, 2020. Participants completed three follow-up visits at 6 months (June 16 to Sept 13, 2020), 1 year (Dec 16, 2020, to Feb 7, 2021), and 2 years (Nov 16, 2021, to Jan 10, 2022) since symptom onset (reported previously). At 1-year follow-up, community controls without a history of SARS-CoV-2 infection were recruited from two communities in Wuhan and at 2 years were matched (1:1) with survivors of COVID-19 who underwent pulmonary function tests. We did a 3-year follow-up from Feb 23, 2023, to April 20, 2023, after the omicron (B.1.1.529) wave in winter, 2022. All eligible survivors of COVID-19 and community controls matched at 2-year follow-up were invited to the outpatient clinic at the hospital to complete several face-to-face questionnaires, a 6-min walking test (6MWT), and laboratory tests. A subgroup of survivors of COVID-19 identified by stratified sampling on the basis of disease severity scale score during hospitalisation and community controls underwent pulmonary function tests. Survivors of COVID-19 who received high-resolution CT and showed abnormal lung images at 2-year follow-up were invited for another assessment. We identified participants with and without long COVID at 2 years. The primary outcomes were sequelae symptoms, omicron infection, lung function, and chest imaging at the 3-year follow-up.

Findings

Of 1359 COVID-19 survivors who completed 2-year and 3-year follow-up, 728 (54%) had at least one sequelae symptom at 3 years after symptom onset and before omicron infection, mainly mild to moderate severity. During the omicron wave, participants with long COVID at 2 years had a significantly higher proportion of re-infection (573 [76%] of 753 vs 409 [67%] of 606 without long COVID; p=0·0004), pneumonia (27 [5%] of 568 vs seven [2%] of 403; p=0·012). 3 months after omicron infection, 126 (62%) of 204 survivors with long COVID at 2 years had newly occurring or worse symptoms, which was significantly higher than the proportion in the non-long COVID group (85 [41%] of 205; p<0·0001) and community controls (81 [40%] of 205; p<0·0001), and not significantly different between COVID-19 survivors without long COVID and matched community controls (85 [41%] of 205 vs 81 [39%] of 206; p=0·66). Re-infection was a risk factor for dyspnoea (odds ratio 1·36 [95% CI 1·04 to 1·77]; p=0·023), anxiety or depression (OR 1·65 [1·24 to 2·20]; p=0·0007), EuroQol visual analogue scale score (β –4·51 [–6·08 to –2·95]; p<0·0001), but not for reduced daily activity (0·72 [0·38 to 1·37]; p=0·32) at 3 years. Lung function of survivors at 3 years was similar to that of matched community controls. We found irregular line, traction bronchiectasis, subpleural lines and ground glass opacity at 3 years, but the volume ratio of lung lesion to total lung was only 0·2–0·3%.

Interpretation

Most long COVID symptoms at 3 years were mild to moderate, with lung function recovering to levels of matched controls. Survivors with long COVID had a higher proportion of participants with re-infection and newly occurring or worse symptoms 3 months after omicron infection than those without long COVID. Re-infection had increased symptom occurrence but not increased reduced daily activity. Although the organ function of survivors of COVID-19 recovered over time, those with severe long COVID symptoms, abnormal organ function, or limited mobility require urgent attention in future clinical practice and research.
Zhang H et al., 3-year outcomes of discharged survivors of COVID-19 following the SARS-CoV-2 omicron (B.1.1.529) wave in 2022 in China: a longitudinal cohort study. Lancet Respiratory Medicine  (publ. Nov.21,2023) DOI: https://doi.org/10.1016/S2213-2600(23)00387-9

https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(23)00387-9/fulltext

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ISEF Forms for 2023-3024 Posted on November 19, 2023 by admin

https://www.societyforscience.org/isef/forms/

 

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Selenium mediates exercise-induced adult neurogenesis and reverses learning deficits induced by hippocampal injury and aging Posted on November 18, 2023 by admin

https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00005-5

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Characterizing the Shared Genetic Underpinnings of Schizophrenia and Cardiovascular Disease Risk Factors Posted on November 16, 2023 by admin

Abstract:

Objective:

Schizophrenia is associated with increased risk of cardiovascular disease (CVD), although there is variation in risk among individuals. There are indications of shared genetic etiology between schizophrenia and CVD, but the nature of the overlap remains unclear. The aim of this study was to fill this gap in knowledge.

Methods:

Overlapping genetic architectures between schizophrenia and CVD risk factors were assessed by analyzing recent genome-wide association study (GWAS) results. The bivariate causal mixture model (MiXeR) was applied to estimate the number of shared variants and the conjunctional false discovery rate (conjFDR) approach was used to pinpoint specific shared loci.

Results:

Extensive genetic overlap was found between schizophrenia and CVD risk factors, particularly smoking initiation (N=8.6K variants) and body mass index (BMI) (N=8.1K variants). Several specific shared loci were detected between schizophrenia and BMI (N=304), waist-to-hip ratio (N=193), smoking initiation (N=293), systolic (N=294) and diastolic (N=259) blood pressure, type 2 diabetes (N=147), lipids (N=471), and coronary artery disease (N=35). The schizophrenia risk loci shared with smoking initiation had mainly concordant effect directions, and the risk loci shared with BMI had mainly opposite effect directions. The overlapping loci with lipids, blood pressure, waist-to-hip ratio, type 2 diabetes, and coronary artery disease had mixed effect directions. Functional analyses implicated mapped genes that are expressed in brain tissue and immune cells.

Conclusions:

These findings indicate a genetic propensity to smoking and a reduced genetic risk of obesity among individuals with schizophrenia. The bidirectional effects of the shared loci with the other CVD risk factors may imply differences in genetic liability to CVD across schizophrenia subgroups, possibly underlying the variation in CVD comorbidi

Rødevand L. et al., Amer J Psychiatry EPUB ahead of print, 27 Sept. 2023;  https://doi.org/10.1176/appi.ajp.20220660

https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.20220660

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Navigating the complexity of COVID-19 Posted on November 16, 2023 by admin

The COVID-19 pandemic has left an indelible mark on every facet of our existence. In this issue of Acta Neuropsychiatrica, we embark on a comprehensive exploration of the pandemic’s multifaceted impact, drawing on the insights gleaned from four recent research papers. These studies illuminate critical dimensions, including the pivotal role of inflammation management in shaping COVID-19 outcomes, the unexpected neurological manifestations it incites, the potential risk of obsessive-compulsive disorder (OCD), and the pandemic’s toll on the mental health of undergraduate students. Collectively, these findings offer a holistic perspective on the profound and far-reaching effects of COVID-19, providing essential guidance as we continue to navigate this global crisis.

Inflammation Management in COVID-19 Our evolving understanding of COVID-19 has brought the role of inflammation into sharp focus, as underscored by the work of Tang and coworkers (Tang et al., Reference Tang, Helmeste and Leonard2023). This research emphasises the intricate interplay of various factors in COVID-19, highlighting the host’s inflammatory response as a key determinant of disease severity, symptoms, and prognosis. Genetic factors, age, immune status, health, and disease stage all influence this inflammatory response. Effectively managing inflammation has emerged as a vital strategy for reducing morbidity and mortality across all stages of COVID-19.

OCD and Gender Disparities The pandemic’s impact extends to the realm of mental health, including a potential risk of OCD, as elucidated in a systematic review (Jalalifar et al., Reference Jalalifar, Arad, Rastkar and Beheshti2023). This analysis reveals that COVID-19 and its containment measures may heighten the risk of OCD, with females appearing particularly susceptible. Notably, under-18 students, hospital staff, and individuals in the Middle East are among the groups most affected. This insight can inform targeted support and resource allocation to address these vulnerabilities.

Psychological Suffering Among Undergraduate Students One poignant revelation is the psychological toll exacted on undergraduate students during remote learning (Silva et al., 2023). Despite a relatively low prevalence of COVID-19 fear, an alarming 83.0% of students reported symptoms of depression, and 76.1% experienced anxiety. These findings underscore the profound impact of the pandemic on the mental health of young individuals. Vulnerable groups, including female students, those in poor health, and those who lost family members to COVID-19, are particularly affected. Targeted interventions, such as physical activity programmes, hold promise for enhancing students’ well-being.

Surprising Neurological Manifestations in Post-COVID-19 Patients A fourth paper explores the unexpected neurological sequelae in post-COVID-19 patients, revealing marked impairments in fine motor skills, balance, memory, attention, and concentration (Chiminazzo and Kirsten, Reference Chiminazzo and Kirsten2023). This study challenges initial assumptions about COVID-19, which primarily targets the respiratory system. Instead, it unveils a range of neurological manifestations even among young and healthy individuals. These findings underscore the urgency of developing rehabilitation protocols to address the neurological deficits stemming from COVID-19 infection.

Collectively, these research papers offer a comprehensive view of the multifaceted and profound impact of COVID-19. From the critical role of inflammation management to potential OCD risk disparities, surprising neurological consequences, and the psychological toll on students, our understanding of this pandemic continues to evolve. As we navigate the ongoing challenges, these insights must guide our response, offering hope and evidence-based strategies to mitigate COVID-19’s extensive effects on individuals and society as a whole.

Wegener, G. (2023). Navigating the complexity of COVID-19: A multifaceted examination. Acta Neuropsychiatrica, 35(5), 247-247. doi:10.1017/neu.2023.50

https://www.cambridge.org/core/journals/acta-neuropsychiatrica/article/navigating-the-complexity-of-covid19-a-multifaceted-examination/CCD0997DDCA5E1B26DEB74D974112844

 

 

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Brain-body interactions Posted on November 13, 2023 by admin

https://www.nature.com/articles/d41586-023-03435

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Human Herpesviruses 6A and 6B in Brain Diseases: Association versus Causation Posted on November 8, 2023 by admin

Human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B), collectively termed HHV-6A/B, are neurotropic viruses that permanently infect most humans from an early age. Although most people infected with these viruses appear to suffer no ill effects, the viruses are a well-established cause of encephalitis in immunocompromised patients. In this review, we summarize the evidence that the viruses may also be one trigger for febrile seizures (including febrile status epilepticus) in immunocompetent infants and children, mesial temporal lobe epilepsy, multiple sclerosis (MS), and, possibly, Alzheimer’s disease.

Komaroff AL, Pellett PE, Jacobson S. Human Herpesviruses 6A and 6B in Brain Diseases: Association versus Causation. Clin Microbiol Rev. 2020 Nov 11;34(1):e00143-20. doi: 10.1128/CMR.00143-20. PMID: 33177186; PMCID: PMC7667666.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667666/

 

 

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Parkinson’s disease neurons exhibit alterations in mitochondrial quality control proteins Posted on November 7, 2023 by admin

Abstract

Mitochondrial dysfunction has been suggested to contribute to Parkinson’s disease pathogenesis, though an understanding of the extent or exact mechanism of this contribution remains elusive. This has been complicated by challenging nature of pathway-based analysis and an inability simultaneously study multiple related proteins within human brain tissue. We used imaging mass cytometry (IMC) to overcome these challenges, measuring multiple protein targets, whilst retaining the spatial relationship between targets in post-mortem midbrain sections. We used IMC to simultaneously interrogate subunits of the mitochondrial oxidative phosphorylation complexes, and several key signalling pathways important for mitochondrial homoeostasis, in a large cohort of PD patient and control cases. We revealed a generalised and synergistic reduction in mitochondrial quality control proteins in dopaminergic neurons from Parkinson’s patients. Further, protein-protein abundance relationships appeared significantly different between PD and disease control tissue. Our data showed a significant reduction in the abundance of PINK1, Parkin and phosphorylated ubiquitinSer65, integral to the mitophagy machinery; two mitochondrial chaperones, HSP60 and PHB1; and regulators of mitochondrial protein synthesis and the unfolded protein response, SIRT3 and TFAM. Further, SIRT3 and PINK1 did not show an adaptive response to an ATP synthase defect in the Parkinson’s neurons. We also observed intraneuronal aggregates of phosphorylated ubiquitinSer65, alongside increased abundance of mitochondrial proteases, LONP1 and HTRA2, within the Parkinson’s neurons with Lewy body pathology, compared to those without. Taken together, these findings suggest an inability to turnover mitochondria and maintain mitochondrial proteostasis in Parkinson’s neurons. This may exacerbate the impact of oxidative phosphorylation defects and ageing related oxidative stress, leading to neuronal degeneration. Our data also suggest that that Lewy pathology may affect mitochondrial quality control regulation through the disturbance of mitophagy and intramitochondrial proteostasis.

 

Chen, C., McDonald, D., Blain, A. et al. Parkinson’s disease neurons exhibit alterations in mitochondrial quality control proteins. npj Parkinsons Dis. 9, 120 (2023). https://doi.org/10.1038/s41531-023-00564-3

https://www.nature.com/articles/s41531-023-00564-3


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