Journal of Neural Transmission最新文献

Schizophrenia spectrum disorders (SSD) are a complex group of illnesses, and their pathophysiology remains unclear. Recent developments in neuroimaging techniques provided useful quantitative measures, such as quantitative T1 mapping (qT1) that is susceptible to tissue-level, microscopic changes. However, it is important to identify the most sensitive, accurate, and reliable imaging protocol, given the complex nature of SSD. We compared structural brain changes in a pilot sample of 15 SSD patients and 7 healthy controls, cross-sectionally, and using two different qT1 mapping protocols. Our findings showed a global elevation in qT1 values in SSD patients, that was statistically significant in the lateral ventricles, thalamus, caudate, and hippocampus (p < 0.01). Moreover, the two acquisition protocols were differently modulated by demographic factors, such as age, sex, and education, which further illustrates the importance of protocol selection. In conclusion, this investigation revealed microstructural tissue changes in subcortical regions in SSD patients, providing further insights into the pathophysiology of the illness.

Anorexia nervosa (AN) represents an eating disorder, which features the highest rate of mortality among all psychiatric disorders. The disease prevalence is increasing steadily, and an effective cure is missing. The neurobiology of the disease is largely unknown, and only a few studies were designed to disclose specific brain areas, where altered neural transmission may occur. In AN behavioral alterations surpassing altered feeding are present, which often involve archaic behaviors finalized to the survival of the species. In fact, alterations of sleep and reward-driven behavior accompany the eating disorder, where a disruption of peripheral and central circadian rhythms occurs along with effortful behaviors, aberrant learning and mild cognitive impairment. Abnormal behavior often co-exists with a number of metabolic alterations in peripheral organs. The present article wishes to analyze the potential role of altered brain circuitry within the brainstem reticular formation during AN. In fact, this brain area contains neuronal nuclei and pathways, which are pivotal in connecting eating pattern with archaic behaviorsand autonomic activity within peripheral organs. A number of reticular nuclei releasing catecholamine and non-catecholamine neurotransmittersare evidenced in relationship with altered behavioral states and vegetative control to produce this psycho-metabolic disorder. The relevance of the reticular formation in sustaining the disorder is discussed in the light of developing effective therapeutic strategies.

Multiple system atrophy (MSA), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are the most common atypical parkinsonisms. These adult-onset and lethal neurodegenerative disorders of unknown etiology are clinically characterized by varying combinations of autonomic, levodopa-poorly responsive parkinsonsm, motor, non-motor, cerebellar syndromes, behavioral, cognitive and other neuropsychiatric disorders. Although their pathological hallmarks are different-MSA α-synucleinopathy, CBD and PSP 4-repeat (4R) tauopathies-their neuropsychiatric disturbances include anxiety, depression, agitations, attention-executive dysfunctions, less often compulsive and REM sleep behavior disorders (RBD), which may contribute to disease progression and reduced quality of life (QoL) of patients and caregivers. The present paper reviews the prevalence and type of neuropsychiatric profile in these atypical parkinsonian syndromes, their neuroimaging, and pathogenic backgrounds based on extensive literature research. MSA patients show anxiety, apathy (depression), initial RBD, attentional and executive dysfunction; PSP patients present with apathy, depression, disinhibition, and to a lesser extent, anxiety and agitation; CBD patients are featured by executive and visuospatial dysfunctions, irritability, alien limb phenomena, sleep and language disorders. Neuropsychiatric disorders in these syndromes are often similar, due to disruption of prefronto-subcortical (limbic) and striato-thalamo-cortical circuitries or default mode and attention network disorder. This supports the concept that they are brain network disorders due to complex pathogenic mechanisms related to the basic proteinopathies that are still poorly understood. Psychotic symptoms, hallucinations and delusions are rare. Neuropsychiatric changes in these disorders are often premature and anticipate motor dysfunctions; their assessment and further elucidation of their pathogenesis are warranted as a basis for early diagnosis and adequate treatment of these debilitating comorbidities.

Amyotrophic Lateral Sclerosis(ALS) has traditionally been managed as a neuromuscular disorder. However, recent evidence suggests involvement of non-motor domains. This study aims to evaluate the impact of APOE and MAPT genotypes on the cognitive features of ALS. We included confirmed ALS cases from the Neurology department at Razi University Hospital, Tunisia. APOE and MAPT screening were conducted with Sanger sequencing validation, and preliminary screening for four main ALS genes was performed. Clinical phenotypes and genotypes were analyzed using appropriate tests, with healthy controls (HC) representing the Tunisian population. Two-hundred-seventy ALS patients were included, stratified as 213 spinal cases,49 with bulbar onset and 8 patients with generalized form with 140 HC. Regarding APOE, we reported high frequency of ALS cases carrier of APOE-ε4 isoform compared to controls(p < 0.0001).We found a significant association between APOE-ɛ4 and ALS onset site (p = 0.05,r = 0.33),with higher frequencies in bulbar onset patients. Cognitive signs were more frequent in ɛ4 carriers (r = 0.43,p < 0.01),and a significant link was observed between dysexecutive functions and the APOE risk allele (p = 0.0495).Concerning the MAPT haplotypes, we reported high frequency of ALS cases carrier of MAPT H1-haplotype HC (94.45% and 72.14% respectively, p < 0.001).Among ALS cases,MAPT-H1 showed a stronger positive correlation with the presence of oculomotor signs(p = 0.05,r = 0.28).As well as significant positive association between cognitive impairments(p = 0.039,r = 0.59). Our findings emphasize the correlation between APOE and MAPT genotypes and the cognitive features in our ALS patients. We also observed other interesting, though weak, significant correlations (with coefficients not exceeding 0.20),which require further validation in a larger cohort to confirm our results.

Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by both motor and non-motor symptoms that necessitate ongoing clinical evaluation and medication adjustments. Home-based wearable sensor monitoring offers a detailed and continuous record of patient symptoms, potentially enhancing disease management. The EmPark-PKG study aims to evaluate the effectiveness of the Parkinson's KinetoGraph (PKG), a wearable sensor device, in monitoring and tracking the progression of motor symptoms over 12 months in Emirati and non-Emirati PD patients. Fifty PD patients (32% Emirati, 68% non-Emirati) were assessed at baseline and a 12-month follow-up. Clinical evaluations included levodopa equivalent daily dosage (LEDD) and motor and non-motor assessments. Concurrently, the PKG provided metrics such as bradykinesia score (BKS) and dyskinesia score (DKS). Statistical analyses were conducted to determine changes from baseline to six months, differences between Emirati and non-Emirati groups, and correlations between PKG metrics and clinical assessments. Significant reductions in LEDD and improvements in both motor and non-motor scores were observed from baseline to six months (p < 0.05). PKG-guided medication adjustments were associated with enhanced motor and non-motor outcomes (p < 0.05). Specifically, non-Emirati patients exhibited a significant reduction in LEDD (Z = - 2.010, p = 0.044), whereas Emirati patients did not (Z = - 0.468, p = 0.640). Both groups showed significant improvements in motor scale scores and motor complication scores. Spearman correlation analysis revealed strong relationships between PKG metrics and subjective clinical assessments (p < 0.001). The EmPark-PKG study demonstrates the potential benefits of remote PKG monitoring for personalised motor symptom management in PD. PKG supports a stepped care paradigm by enabling bespoke medication titration based on objective data, facilitating tailored and effective patient care.

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.

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.

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.

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.

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.