Journal of Neural Transmission最新文献

This study aims to review clinical trials investigating dietary or nutritional interventions for Parkinson's Disease (PD) and identify potential research gaps. A PubMed search yielded 3378 results, and after applying inclusion and exclusion criteria, 38 studies were selected. Of these, 13 focused on interventions with potential neuroprotective effects against PD, 18 examined symptom improvement, and 7 explored their relationship to antiparkinsonian medication. Most studies were randomized controlled trials (RCTs) and demonstrated promising results. However, they were often limited by small sample sizes and short durations. Large-scale, double-blind, placebo-controlled RCTs are necessary to further investigate the effects of dietary and nutritional interventions in PD. Other nutrients with promising results in preclinical research should be further evaluated in clinical trials. Moreover, research should prioritize dietary pattern interventions, like the Mediterranean and ketogenic diets, while closely monitoring patient adherence to these approaches. Lastly, future research should further explore the role of gut microbiota and its potential pathogenic involvement in PD.

Speech change is a biometric marker for Parkinson's disease (PD). However, evaluating speech variability across diverse languages is challenging. We aimed to develop a cross-language algorithm differentiating between PD patients and healthy controls using a Taiwanese and Korean speech data set. We recruited 299 healthy controls and 347 patients with PD from Taiwan and Korea. Participants with PD underwent smartphone-based speech recordings during the "on" phase. Each Korean participant performed various speech texts, while the Taiwanese participant read a standardized, fixed-length article. Korean short-speech (≦15 syllables) and long-speech (> 15 syllables) recordings were combined with the Taiwanese speech dataset. The merged dataset was split into a training set (controls vs. early-stage PD) and a validation set (controls vs. advanced-stage PD) to evaluate the model's effectiveness in differentiating PD patients from controls across languages based on speech length. Numerous acoustic and linguistic speech features were extracted and combined with machine learning algorithms to distinguish PD patients from controls. The area under the receiver operating characteristic (AUROC) curve was calculated to assess diagnostic performance. Random forest and AdaBoost classifiers showed an AUROC 0.82 for distinguishing patients with early-stage PD from controls. In the validation cohort, the random forest algorithm maintained this value (0.90) for discriminating advanced-stage PD patients. The model showed superior performance in the combined language cohort (AUROC 0.90) than either the Korean (AUROC 0.87) or Taiwanese (AUROC 0.88) cohorts individually. However, with another merged speech data set of short-speech recordings < 25 characters, the diagnostic performance to identify early-stage PD patients from controls dropped to 0.72 and showed a further limited ability to discriminate advanced-stage patients. Leveraging multifaceted speech features, including both acoustic and linguistic characteristics, could aid in distinguishing PD patients from healthy individuals, even across different languages.

Exposure to stress is known to affect biological aging as well as individuals' susceptibility to a wide variety of mental illnesses, such as schizophrenia. There is an established relationship between the onset of schizophrenia spectrum disorders (SSD) and biological aging. On the other hand, epigenetic modifications, such as DNA methylation (DNAm), are used as biomarkers for biological aging and were previously proven to be altered in schizophrenia. However, previous research did not consider the effect of psychosocial resilience to stress and its effect on aging in schizophrenia, which is what our study aims to address. For our pilot study, 65 schizophrenia patients were recruited and stress exposure and perception levels were assessed using the Social Readjustment Rating Scale (SRRS) and Perceived Stress Scale (PSS), respectively. Moreover, DNA was extracted from venous blood samples and 850,000 CpG loci were assessed for DNA methylation analysis. Average age of participants was 43.15 ± 13.32 years (55.4% male, 44.6% female). Linear regression plots showed significant correlation between SRRS and PSS scores as well as between biological and chronological ages (p < 0.05). The residuals from the two regression models were defined as the psychosocial resilience and DNAm age acceleration, respectively. Interestingly, DNAm age acceleration was inversely correlated with resilience to stress (p < 0.05). In conclusion, it appears that epigenetic age acceleration is associated with reduced resilience to stress in schizophrenia patients. Future studies should focus on establishing resilience effect on disease prognosis.

Spasmodic dysphonia (SD) is now generally considered to be a task-specific focal dystonia. For the first time, we wanted to explore the relationship between SD and dystonia from a combined neurological and phoniatric perspective. For this, we studied 115 patients with non-psychogenic SD by a combined neurological and phoniatric evaluation. Onset of SD was 49.7 ± 19.0 (6-68) years. The female/male ratio was 2. 63% had additional dystonia manifestations (cervical dystonia 35%, arm dystonia 15%, blepharospasm 11%, oromandibular dystonia 11%, writer's cramp 11%, pharyngeal dystonia 10%, generalised dystonia 4%, axial dystonia 2%, spasmodic dyspnoea 2% and segmental dystonia 1%). 71% occurred before, 25% after and 4% together with SD. 17% had a family history of dystonia and 6% a history of exposure to dopamine receptor blocking agents. 41% had mixed SD (SD-M), 31% abductor SD (SD-AB) and 28% adductor SD (SD-AD). SD-M was significantly correlated with additional dystonia manifestations and tremulous SD. No patient showed essential tremor or Parkinsonian syndromes. Two third of SD patients have additional dystonia manifestations and one fifth have a family history of dystonia, considerably more than previously described. In half of all patients, SD starts with non-SD dystonia. Our combined approach revealed a high prevalence of SD-M associated with frequent additional dystonia manifestations including dystonic tremor and a family history of dystonia. Patients presenting with SD should be evaluated for additional dystonia manifestations and dystonia patients should be evaluated for SD. Relevant coexistence of essential tremor and Parkinsonian syndromes cannot be confirmed.

Bipolar disorder (BD) frequently coexists with anxiety disorders, creating complex challenges in clinical therapy and management. This study investigates the prevalence, prognostic implications, and treatment strategies for comorbid BD and anxiety disorders. High comorbidity rates, particularly with generalized anxiety disorder, underscore the necessity of thorough clinical assessments to guide effective management. Our findings suggest that anxiety disorders may serve as precursors to BD, especially in high-risk populations, making early detection of anxiety symptoms crucial for timely intervention and prevention. We also found that comorbid anxiety can negatively affect the course of BD, increasing clinical severity, reducing treatment responsiveness, and worsening prognosis. These complexities highlight the need for caution in using antidepressants, which may destabilize mood. Alternatively, cognitive-behavioral therapy presents a promising, targeted approach for managing BD with comorbid anxiety. In summary, this study provides essential insights for clinicians and researchers, enhancing understanding of BD and anxiety comorbidity and guiding more precise diagnostics and tailored interventions to improve overall patient care.

The cerebellum is a structure in the suprasegmental nervous system classically known for its involvement in motor functions such as motor planning, coordination, and motor learning. However, with scientific advances, other functions of the cerebellum, such as cognitive, emotional, and autonomic processing, have been discovered. Currently, there is a body of evidence demonstrating the involvement of the cerebellum in nociception and pain processing. The aim of this review is to present the current literature on the anatomical, physiological, and functional aspects of the cerebellum in pain processing and suggest functional mechanisms of pain processing based on the cerebellum and its connections with other brain structures. To achieve this, searches were conducted in databases to identify relevant studies on the topic. Studies with relevant data and information were collected and summarized. Current literature demonstrates that the cerebellum receives nociceptive afferents from different pathways and exhibits activity in different regions including the vermis, hemispheres, and deep cerebellar nuclei in pain processing. Through its connections with different brain regions, it is possible that the cerebellum participates in the multidimensional processing of pain, which may make it a potential therapeutic target for pain treatment.

As Parkinson's disease (PD) progresses, patients experience motor fluctuations, which may manifest as motor and/or non-motor wearing off symptoms, delayed "ON" time, and/or levodopa-related dyskinesia. Deep brain stimulation (DBS) is an effective therapy but may not be suitable for all patients due to factors such as premorbid conditions age, or accessibility. We review technology-based therapeutic innovations for PD: infusion therapies and novel non-invasive neuromodulation methods using the following databases: PubMed, Cochrane, and Science Direct. Infusion therapies such as percutaneous (LCIG, LECIG) and subcutaneous options (ND0612, foslevodopa-foscarbidopa, CSAI) demonstrate significant benefits in reducing OFF time and enhancing ON time without troublesome dyskinesias. However, vigilance is required for procedural and skin adverse events. Neuromodulation approaches such as auricular, vagus nerve, and galvanic vestibular stimulation, as well as whole-body vibration, showed promising benefits in freezing of gait (FOG) and tremor. Infusion and non-invasive neuromodulation therapies provide additional treatment options for patients with refractory motor and non-motor symptoms and may be an alternative for those who experience limitations of traditional dopaminergic therapies and are not candidates for neurosurgical interventions.

Non-motor symptoms (NMS) occur in 60-97% of Parkinson's disease (PD) patients. NMS show fluctuations over the course of the day referred to as non-motor fluctuations (NMF). To assess the frequency, severity, predictors and effect of the NMF on the quality of life in PD patients. This was a cross-sectional, hospital based, single-centre study. A total of 150 patients with PD were recruited. NMF was assessed using the MDS-Non-motor rating scale (MDS-NMS) and the Non-motor fluctuation assessment questionnaire (NoMoFA). The mean age at presentation and age at onset was 51.3 ± 10.8 years and 44.6 ± 11.1 years respectively and male predominance (75.3%). The mean duration of parkinsonism was 5.3 ± 3.7 years. Motor fluctuations (MF) were seen in 97 patients. A total of 143 patients (95.3%) had at least single NMS. Depression, cognition and pain was the most common NMS domain. NMF was seen in 57 patients (39.8%). NMF occurred in 50.5% in PD patients with MF. Pain was the most frequent NMS which showed NMF followed by fatigue, anxiety and depression. Pain had greater degree of change from ON to OFF period as compared to other NMS domains. NMF was associated with longer disease duration, higher levodopa dose and longer levodopa intake, greater motor severity, MF, higher NMS burden and poor quality of life. NMF is seen in association with MF. Pain, anxiety, depression and fatigue was the common NMS showing NMF. Pain had a large degree of fluctuation in the severity.

This study aimed to analyze the transferability of non-invasive brain stimulation (NIBS) interventions in individuals with major depressive disorder (MDD) based on the FIELD model (Function, Implementation, Ecology, Level, and Duration), encompassing function, implement, ecology, level, and duration. A systematic search of electronic databases yielded a total of 21 eligible studies, comprising 12 transcranial direct current stimulation (tDCS) and 9 transcranial magnetic stimulation (TMS) trials, involving 1029 individuals with MDD. The meta-analysis of effect sizes revealed positive transfer effects across all domains of the FIELD model, suggesting that NIBS interventions have potential efficacy in improving various facets of MDD. The subgroup analysis highlighted that bilateral dlPFC stimulation exhibited the highest effect size for transferability, indicating greater transferability for rTMS, a higher dose of stimulation, and the integration of additional interventions. Additionally, the study discusses the implications of bilateral dorsolateral prefrontal cortex (dlPFC) stimulation and the integration of complementary therapies for optimizing treatment efficacy.