Brain and Behavior最新文献

Background

Spinal muscular atrophy (SMA) is a motor neuron disease caused by mutations in the SMN1 gene. Nusinersen, an antisense oligonucleotide, has been shown to improve motor function in SMA patients. However, concerns regarding its renal safety remain as previous studies have linked similar treatments to renal toxicity.

Objective

The aim of this study was to evaluate the effects of the nusinersen treatment on platelet counts and renal functions, specifically urine protein excretion, in SMA patients and to estimate safe urinary protein levels before administration of each intrathecal injection.

Methods

This retrospective study examined data from 33 patients with SMA to assess the effects of nusinersen on motor functions and laboratory parameters including platelet count, serum creatinine, urine protein, and urine creatinine. Measurements were taken at baseline andprior to each maintenance dose, after the completion of four initial loading doses. The baseline values were compared between SMA Type 1 and Type 2 patients, while the changes in these values over time were analyzed within each group.

Results

No significant adverse effects on platelet counts or renal functions were observed. Urine creatinine and protein levels were significantly higher in SMA Type 2 patients compared to SMA Type 1 at baseline; these parameters remained stable in SMA Type 2 but increased significantly after the loading doses in SMA Type 1. Motor function improvements were observed in both groups, with the most significant gains in SMA Type 1 after the loading doses. Thus, improvement in motor functions was associated with increase in urine creatinine.

Conclusion

Nusinersen treatment did not cause significant renal toxicity or affect platelet counts. Urine creatinine levels may serve as a potential biomarker for assessing treatment response in SMA Type 1.

Introduction

The cognitive side-effects of medication are common, but often overlooked in practice, and not routinely considered in interventional trials or post-market surveillance. The cognitive footprint of a medication seeks to quantify the impact of its cognitive effects based on magnitude, duration, and interaction with other factors, evaluated across the exposed population.

Methods

Bayesian multivariable regression analysis of retrospective population-based cross-sectional cohorts.

Results

We replicate positive and negative cognitive effects of commonly used medications in UK Biobank, and extend observed associations to two additional cohorts, the EPIC Norfolk, and the Caerphilly Prospective Cohort. We quantify the resultant cumulative impact at the population level given known patterns of prescribing and compare it with exemplar common diseases.

Conclusion

The cognitive side-effects of commonly used drugs may have significant impact at the population level. Consideration should be given to a routine structured assessment of cognition in interventional trials and post-market surveillance.

Background

Immune system modulation has been shown to have a significant impact on attention deficit hyperactivity disorder (ADHD). Mendelian randomization (MR) analysis was used in this study to investigate the potential role of different immune cells in the development of ADHD to provide therapy and preventative alternatives.

Methods

In this study, 731 immune cells and the risk of ADHD were examined using publicly accessible genetic data and a two-sample MR analysis. Included were four different types of immunological profiles: determinate cells (DC), proportional cells (PC), median brightness level (MBL), and morphological characteristics (MA). It was discovered that single-nucleotide polymorphisms (SNPs) are linked to ADHD. To evaluate the dependability of the results, we conducted sensitivity analysis (heterogeneity and pleiotropy) and employed supplementary MR techniques, such as the inverse variance weighted (IVW) and MR-Egger. Graphs are used to display the final findings of the pertinent analyses.

Results

Following MR analysis, immune cells associated with a few low p value phenotypes may influence ADHD, and these immune cells may serve as an inspiration for clinical treatment practices that aim to prevent and cure ADHD. Immune cell phenotypes that may both increase and worsen the likelihood of having ADHD were identified by IVW results. These included CD27 on memory B cells (OR = 1.066, 95% CI = 1.024–1.109, p = 2E−3) and CD27 on IgD⁻CD38⁻ (OR = 1.059, 95% CI = 1.018–1.103, p = 5E−3), among others. Immune cell phenotypes that may act as a safeguard against ADHD included CD3 on resting Treg (OR = 0.925, 95% CI = 0.888–0.963, p = 1.5E−4) and SSC-A on monocytes (OR = 0.951, 95% CI = 0.924–0.980, p = 8.5E−4), among others. The primary findings and the outcomes of the sensitivity analysis matched.

Conclusions

This study provides a broad theoretical foundation for the development of immune-oriented therapeutic strategies in future clinical practice by demonstrating a potential genetic relationship between immune cells and ADHD. This study also advances our understanding of how to use the immune pathway to prevent and treat ADHD.

Background

While automated methods for differential diagnosis of parkinsonian syndromes based on MRI imaging have been introduced, their implementation in clinical practice still underlies considerable challenges.

Objective

To assess whether the performance of classifiers based on imaging derived biomarkers is improved with the addition of basic clinical information and to provide a practical solution to address the insecurity of classification results due to the uncertain clinical diagnosis they are based on.

Methods

Retro- and prospectively collected data from multimodal MRI and standardized clinical datasets of 229 patients with PD (n = 167), PSP (n = 44), or MSA (n = 18) underwent multinomial classification in a benchmark study comparing the performance of nine machine learning methods. A predictor space of imaging variables, either with or without clinical information, was investigated. Classification results were assessed using multiclass AUCs. Individual predicted probabilities were visualized to address diagnostic uncertainty.

Results

Clinical diagnosis was accurately confirmed using machine learning models with only small differences when using imaging and clinical signs versus imaging variables only (expected multiclass AUC of 0.95 vs. 0.92). Still, multinomial classification is hampered by imbalanced class frequencies. The most discriminatory variables were responsiveness to levodopa, vertical gaze palsy, and the volumes of subcortical structures, including the red nucleus.

Conclusion

Machine-learning-assisted classification of MR-imaging biomarkers gathered in routine care can assist in the diagnosis of parkinsonian syndromes as part of the diagnostic workup. We provide a visual method that aids the interpretation of neuroimaging-based classification results of the three main parkinsonian syndromes, improving clinical interpretability.

Background

Psychotherapeutic memory plays an important role in maintaining therapeutic effects; however, the neural mechanisms of therapeutic metaphor promoting long-term memory were still unknown.

Objective

This study used metaphorical micro-counseling dialog scenarios to investigate the memory effect of therapeutic metaphor and correlated neural mechanisms.

Methods

At first, 31 participants read a mental distress problem, followed by a metaphorical or a literal solution, while undergoing functional magnetic resonance imaging scanning during the encoding phase. One week later, a recognition memory test was performed outside the scanner.

Results

The results revealed that metaphorical solutions were associated with higher insight experiences and better memory performance than literal solutions. Greater activations were observed in the multiple memory systems, including episodic (parahippocampal gyrus, hippocampus, and thalamus), emotional (amygdala), and procedural/implicit (caudate, putamen, and cerebellum), in contrast to later remembered versus later forgotten based on the gap between metaphorical and literal solutions. Insightfulness and activities of the hippocampus, caudate, and cerebellum could predict memory performance.

Conclusions

These findings indicated that multiple memory systems are involved in successful memory encoding of therapeutic metaphors; this suggested that incorporating metaphors into psychotherapy practices could lead to better retention of therapeutic information and improve clinical outcomes compared to literal psychotherapy.

Introduction

This study describes epidemiology of attention deficit hyperactivity disorder (ADHD) and use of ADHD medication across all age groups in Finland.

Methods

This retrospective study is based on nationwide registers in Finland. The study population included individuals with ADHD diagnosis and/or an ADHD medication record at least once during 2015–2020.

Results

The yearly prevalence of ADHD was higher in males than in females and was highest in the age groups of 6- to 12- and 13- to 17-year-old males. In 2020, the yearly prevalence was 4.2% in ≤12-year-old, 6.7% in 13- to 17-year-old, 0.7% in ≥18-year-old males, and 1.1%, 2.6%, and 0.6%, respectively, in females. The gender-related differences were greatest among 6- to 12- and 13- to 17-year-olds, after which the differences evened out. During the study period from 2015 to 2020, the yearly prevalence more than doubled in each of the five Finnish administrative university hospital areas. The prevalence was higher in males, but the relative growth was higher in females compared to males. The incidence per 100,000 inhabitants was the highest in ≤12-year-old males and increased in all age groups and in both genders. The use of medication was more common in males than in females, and the overall proportion of prevalent ADHD patients on medication remained around 80%. Decrease in medication use was observed in connection with the transition from adolescence to adulthood, in both genders.

Conclusion

Both prevalence and incidence of ADHD more than doubled in Finland during the study period 2015–2020. This study presents the most comprehensive analysis of national register data at personal-level linkage in Finland, since it included all age groups, and both diagnosed ADHD patients and individuals receiving medication, not limited to reimbursed medication.

Aim

The aim of the study was to survey the observed incidence of adverse effects (AEs) related to electroconvulsive therapy (ECT) in Finnish neuromodulation units, as well as to explore what medical interventions are used to prevent and treat them in those units.

Methods

An electronic survey was conducted among Finnish neuromodulation units at the end of 2022. The survey included 35 questions related to AEs and their prevention and/or treatment in the responding units’ ECT patient populations.

Results

Our survey reached 19 out of 26 units in Finland, with 17 units completing the full questionnaire. Headache, myalgia and postictal confusion (PIC) emerged as the most frequently reported AEs. Nausea and high blood pressure were reported less often. Only a few units reported AEs known to be rare, such as accidental awareness during general anesthesia and the aspiration of gastric contents.

However, there was considerable variation in the recognition and treatment of those ECT-related AEs the diagnosis of which depends more on patients’ self-reporting, including headache, myalgia or nausea. Five units (29%) reported frequent or occasional headache or myalgia and four units (24%) reported occasional nausea experienced by their patients, but these AEs were addressed pharmacologically in those units neither by prophylaxis nor by treatment. This raises concern about whether these AEs are perceived as an insignificant issue in delivering ECT treatment, thus requiring no intervention, or if those AEs should be better recognized and and managed more actively.

Conclusions

AEs related to ECT treatment are common, but some still appear poorly recognized and treated. Regarding treatment adherence, minimizing potential AEs whenever feasible can be considered important. A thorough preoperative assessment of patients is required to identify possible risk factors for AEs. An objective and structured evaluation tool for recognizing adverse effects in patients undergoing ECT treatment would be useful.

Introduction

The interplay between emotional disorders and thyroid disorders has been subject to numerous observational studies, which have consistently reported associations but have failed to establish clear causal links due to the multifactorial etiology and influences. We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to explore the genetic causal association between emotional disorders and thyroid disorders.

Methods

We employed several methods, including inverse-variance weighted (IVW), weighted median, weighted mode, and MR Egger regression. Additionally, sensitivity analyses were conducted using MR-Egger, MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), Cochran's Q, and leave-one-out methods.

Results

IVW results showed negative causal relationships between bidirectional emotional disorders and hypothyroidism, toxic single thyroid nodules in thyrotoxicosis, and hyperthyroidism/toxicity. Additionally, there was a positive causal relationship between anxiety disorders and hypothyroidism. IVW results of reverse MR analysis estimates revealed a positive causal relationship between hypothyroidism, autoimmune thyroiditis, and recurrent or chronic depression. Additionally, there was a negative causal relationship between hyperthyroidism/toxicity and bipolar disorder.

Conclusion

This bidirectional two-sample MR study preliminarily reveals a complex, bidirectional causal relationship between emotional disorders and thyroid disorders, particularly highlighting the role of thyroid dysfunction in the development of certain emotional disorders and vice versa.

Introduction

Acute encephalopathy (AE) in childhood due to a viral infection causes convulsions and altered consciousness, leading to severe sequelae and death. Among the four types of AE, cytokine storm–induced AE is the most severe and causes serious damage to the brain. Moreover, a fundamental treatment for AE has not been established yet. Recently, it has been shown that the administration of multilineage-differentiating stress-enduring (Muse) cells, a population of mesenchymal stem cells, improves symptoms in various types of brain injuries when administered in the subacute phase (1–7 days after brain damage). We aimed to examine the effects of Muse cells in a cytokine storm–induced AE animal model using immunocompromised nonobese diabetic/severe combined immunodeficiency (NOD/SCID) neonatal mice.

Methods

We established a modified protocol to induce AE-like symptoms in NOD/SCID. Then, Muse cells were injected at an acute phase (2–4 h after hyperthermia treatment).

Results

Injection of Muse cells significantly improved body weight gain 1 day after treatment and the survival ratio for 3 weeks.

Conclusion

These effects could be a result of the direct and/or indirect upregulation of IL-10, an anti-inflammatory cytokine, in the Muse cell–treated brain. Although non-Muse cells, a residual cell population in the bone marrow after isolating Muse cells, also improved some symptoms, their effects were weaker than those of Muse cells. Our results indicate that the injection of Muse cells in the acute phase has an effect on AE, suggesting that they exert their therapeutic effects not only in the subacute phase but also in the acute phase.