Journal of Neural Transmission最新文献

The growing significance of generalization in psychiatric interventions stems from the need for effective and applicable treatments across diverse populations and settings. Addressing psychiatric disorders involves navigating the complex interplay of biological, cognitive, and behavioral factors, making it crucial to assess the transferability of interventions beyond controlled environments. To tackle this challenge, we propose a novel conceptual framework, the FIELD model (Function, Implement, Ecology, Level, and Durability). This model offers a comprehensive exploration of generalization by considering the function and tools used in interventions, the ecological contexts of their application, the various levels of impact, and the durability of effects over time. In this study, we explore the dimensions of the FIELD model, emphasizing the role of assessment tools as valuable indicators and the significance of effect sizes in quantifying the transfer of training effects. The FIELD model stands as a tool to enhance our understanding of psychiatric interventions, providing a systematic and nuanced approach to evaluate their generalization across diverse scenarios.

Aripiprazole is approved for various severe mental disorders in adults and adolescents. However, off-label prescribing is common, especially in children and adolescents (youth) in whom aripiprazole therapeutic serum level reference ranges are lacking for any disorders. The aim of the study was to evaluate the relationship between aripiprazole dose and serum concentrations and provide further knowledge on the use of aripiprazole in order to improve drug safety and effectiveness in the treatment of minors. The clinical course of youth treated with aripiprazole in the multicentre pharmacovigilance study TDM-VIGIL was systematically followed and serum concentrations measured. Sex, age, weight and comedications were analysed to identify possible effect modifiers. A preliminary therapeutic reference range was estimated for youth with schizophrenia-spectrum disorders, affective disorders and behavioural/emotional/tic disorders coded as treatment responders based on a Clinical-Global Impressions-Improvement (CGI-I) score of much or very much improved. In 93 youth (mean age = 15.2 ± 2.6, range = 7.4-18.2 years, females = 53%, CGI-Severity = 4.4 ± 1.1, responders = 64%), a positive, moderate correlation between the weight-normalized daily dose (WNDD) and aripiprazole serum concentration (=0.791, p < 0.0001) was found. The WNDD and co-medications that interact with CYP2D6 and CYP3A4 affected aripiprazole serum levels, explaining 64% of the variance. In patients within the preliminary therapeutic ranges determined by interquartile ranges (IQRs), slightly better outcomes and fewer adverse drug reactions were found versus patients within preliminary therapeutic ranges determined by the mean ± SD. The preliminary reference range for paediatric patients with schizophrenia-spectrum disorders calculated by the IQR showed an identical lower threshold (100-230 ng/ml) compared to adult schizophrenia-spectrum disorders patients (100-350 ng/ml). The preliminary therapeutic ranges for patients with affective disorders was: 60-160 ng/ml and for patients with behavioural/tic disorders 60-140 ng/ml. The therapeutic reference ranges for aripiprazole in youth estimated via the 25th and 75th IQRs may result in more clinically relevant therapeutic windows. Further studies need to confirm these results, especially in patients with affective and behavioural/tic disorder diagnoses.

Dementia with Lewy bodies (DLB), the second most common primary degenerative neurocognitive disorder after Alzheimer disease, is frequently preceded by REM sleep behavior disorders (RBD) and other behavioral symptoms, like anxiety, irritability, agitation or apathy, as well as visual hallucinations and delusions, most of which occurring in 40-60% of DLB patients. Other frequent behavioral symptoms like attention deficits contribute to cognitive impairment, while attention-deficit/hyperactivity disorder (ADHD) is a risk factor for DLB. Behavioral problems in DLB are more frequent, more severe and appear earlier than in other neurodegenerative diseases and, together with other neuropsychiatric symptoms, contribute to impairment of quality of life of the patients, but their pathophysiology is poorly understood. Neuroimaging studies displayed deficits in cholinergic brainstem nuclei and decreased metabolism in frontal, superior parietal regions, cingulate gyrus and amygdala in DLB. Early RBD in autopsy-confirmed DLB is associated with lower Braak neuritic stages, whereas those without RBD has greater atrophy of hippocampus and increased tau burden. αSyn pathology in the amygdala, a central region in the fear circuitry, may contribute to the high prevalence of anxiety, while in attention dysfunctions the default mode and dorsal attention networks displayed diverging activity. These changes suggest that behavioral disorders in DLB are associated with marked impairment in large-scale brain structures and functional connectivity network disruptions. However, many pathobiological mechanisms involved in the development of behavioral disorders in DLB await further elucidation in order to allow an early diagnosis and adequate treatment to prevent progression of these debilitating disorders.

TDCS is one of the most widely used non-invasive neuromodulation techniques, which changes the excitability of local cortical tissue by applying weak continuous direct current to the scalp, effectively improves the attention and concentration of ADHD children, and improves the impulse disorder of patients, but related research is still in its infancy. Based on a review of a large number of existing literatures and an analysis of the pathogenesis and principle of ADHD, this paper summarized the research on tDCS in the treatment of ADHD in recent years from the aspects of treatment mechanism, safety and stimulation parameters, and simply compared the application of tDCS with other non-traumatic neuromodulation techniques in the treatment of ADHD. The future development direction of this technology is further discussed.

Background: Schizophrenia (SCZ) shortens life expectancy, with cardiovascular disease (CVD) as the leading cause of death. The links between psychiatric symptoms, cognitive function and CVD are unclear, and sex differences in this relationship are understudied. This study examined the relationship between clinical characteristics and 10-year cardiovascular risk in males and females with SCZ.

Methods: This study included 802 patients with chronic SCZ. Fasting venous blood samples were collected from all patients to measure relevant glycolipid metabolic indices. The Positive and Negative Syndrome Scale (PANSS) was used to assess psychiatric symptoms. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The Framingham risk score (FRS) was used to estimate the 10-year CVD risk.

Results: The mean 10-year cardiovascular risk for all patients was 11.76 ± 8.99%. Among patients with SCZ, 52.8% exhibited an intermediate-high 10-year cardiovascular risk. Multivariate linear regression analysis showed that FRS increased with higher body mass index, blood pressure, glucose, total cholesterol and triglyceride levels, while it was inversely related to high density lipoprotein levels. The general psychopathological scores were negatively associated with FRS (male: B = - 0.086, P = 0.013; female: B = - 0.056, P = 0.039). Negative symptom (B = - 0.088, P = 0.024) and total PANSS scores (B = - 0.042, P = 0.013) showed a negative association with FRS only in males. Additionally, in patients over 60 years old, general psychopathology (B = - 0.168, P = 0.001) and PANSS total scores (B = - 0.057, P = 0.041) were associated with reduced FRS, while immediate memory (B = 0.073, P = 0.025) was associated with higher FRS.

Conclusion: Patients with SCZ have an elevated risk of developing CVD, with males showing a higher 10-year cardiovascular risk than females. Significant sex differences exist in the relationship between the FRS and psychiatric symptoms, with negative symptoms being negatively related to FRS only in males.

Background: Recently, a network model of cervical dystonia (CD) has been adopted that implicates nodes and pathways involving cerebellar, basal-ganglia and cortico-cortical connections. Although functional changes in the cerebello-thalamo-cortical network in dystonia have been reported in several studies, structural information of this network remain sparse.

Objective: To characterize the structural properties of the cerebellar motor network in isolated CD patients. This includes cerebellar lobules involved in motor processing, the dentate nucleus (DN), the thalamus, and the primary motor cortex (M1).

Methods: Magnetic resonance imaging data of 18 CD patients and 18 healthy control subjects were acquired. In CD patients, the motor part of the Toronto Western Spasmodic Torticollis Rating Scale was assessed to evaluate motor symptom severity. The volume of cerebellar lobules I-VI and VIII, the DN and thalamus, and the cortical thickness (CT) of M1 were determined for a region of interest (ROI)-based quantitative analysis. Volumes/CT of these ROIs were compared between groups and associated with motor symptom severity in patients.

Results: The volume of lobule VI and the CT of M1 were reduced in CD patients. The volumes of the other ROIs were not different between groups. No association was identified between the structural properties of lobule VI or M1 and the severity of CD motor symptoms.

Conclusion: Atrophy within the cerebellum and M1 contributes to CD's complex motor network pathology. Further investigations are needed to ascertain the mechanisms underlying the local volume loss.

Hemifacial spasm (HFS) represents a challenging cranial movement disorder primarily affecting the facial nerve innervated muscles, with significant prevalence among Asians. Botulinum toxin type A (BoNT/A) injections, established as a primary therapeutic intervention since FDA approval, offer considerable effectiveness in alleviating spasms, albeit accompanied by challenges such as temporary effects and potential adverse events including facial asymmetry. This comprehensive review underscores the crucial need for harmonising neurological benefits and aesthetic outcomes in HFS management. The discussion delves into the interplay between facial aesthetics and neurological objectives in BoNT/A injections, emphasising precise techniques, dosages, and site considerations. Distinct aspects in neurological and aesthetic domains are also examined, including detailing the targeted muscles and injection methodologies for optimal therapeutic and aesthetic results. Importantly, evidence regarding various BoNT/A formulations, recommendations, and reconstitution guidelines in both neurology and aesthetics contexts are provided, along with a schematic approach outlining the stepwise process for BoNT/A injection in HFS treatment, addressing critical areas such as orbicularis oculi muscle sites, eyebrow correction strategies, mid- and lower-face considerations, contralateral injection sites, and post-injection follow-up and complication management. By highlighting the culmination of neurological efficacy and facial esthetics in BoNT/A treatment for HFS patients, this review proposes a holistic paradigm to achieve balanced symptomatic relief and natural aesthetic expression, ultimately enhancing quality of life for individuals grappling with HFS.

Early-onset Parkinson's disease (EOPD) occurs during the fertile life, when circulating neuroactive sex hormones might enhance the sexual dimorphism of the disease. Here, we aimed to examine how sex hormones can contribute to sex differences in EOPD patients. A cohort of 34 EOPD patients, 20 males and 14 females, underwent comprehensive clinical evaluation of motor and non-motor disturbances. Blood levels of estradiol, total testosterone, follicle-stimulating hormone, and luteinizing hormone were measured in all patients and correlated to clinical features. We found that female patients exhibited greater non-motor symptoms and a relatively higher rate of dystonia than males. In females, lower estradiol levels accounted for higher MDS-UPDRS-II and III scores and more frequent motor complications, while lower testosterone levels were associated with a major occurrence of dystonia. In male patients, no significant correlations emerged. In conclusion, this study highlighted the relevance of sex hormone levels in the sexual dimorphism and unique phenotype of EOPD.

Fatigue is an extremely common symptom in in people with multiple sclerosis (PwMS) and has a severe impact on quality of life. The purpose of the present study was to verify whether fatigue in PwMS is associated with a selective covert attention impairment, as measured by event-related potentials and to assess whether it is more associated with an impairment of top-down or bottom-up attentional control. Twenty-two PwMS and fatigue-MSF, 17 without fatigue-MSnF and 35 healthy volunteers underwent a three-stimulus P300 novelty task that elicits both the P3a and the P3b components. P3b latency was comparable between groups, but PwMS, independently from the presence of fatigue displayed significantly greater P3b amplitudes. P3a latency was significantly prolonged in MSF alone, while P3a amplitude in MSnF group was greater than controls. MSF were able to categorize the task-relevant target stimulus but the orienting response to a novel salient stimulus was delayed, indicating an impairment in bottom-up attentional control mechanism related to ventral attention network. Fatigue is selectively associated with a covert attentional deficit related to the ability to reallocate attentional resources to salient stimuli, a crucial function of adaptive decision-making behaviour.

Psychotropic drugs are vital in psychiatry, aiding in the management of mental health disorders. Their use requires an understanding of their pharmacological properties, therapeutic applications, and potential side effects. Ongoing research aims to improve their efficacy and safety. Biomarkers play a crucial role in understanding and predicting memory decline in psychotropic drug users. A comprehensive understanding of biomarkers, including neuroimaging, biochemical, genetic, and cognitive assessments, is essential for developing targeted interventions and preventive strategies. In this narrative review, we performed a comprehensive search on PubMed and Google using review-specific terms. Clinicians should use a multifaceted approach, including neurotransmitter analysis, neurotrophic factors, miRNA profiling, and cognitive tasks for early intervention and personalized treatment. Anxiolytics' mechanisms involve various neurotransmitter systems and emerging targets. Research on biomarkers for memory decline in anxiolytic users can lead to early detection and intervention, enhancing clinical practices and aligning with precision medicine. Mood stabilizer users can benefit from early detection of memory decline through RNA, neurophysiological, and inflammatory biomarkers, promoting timely interventions. Performance-enhancing drugs may boost athletic performance in the short term, but their long-term health risks and ethical issues make their use problematic. Long-term use of psychotropic performance enhancers in athletes shows changes in biomarkers of cognitive decline, necessitating ongoing monitoring and intervention strategies. Understanding these genetic influences on memory decline helps pave the way for personalized approaches to prevent or mitigate cognitive deterioration, emphasizing the importance of genetic screening and early interventions based on an individual's genetic profile. Future research should focus on refining these biomarkers and protective measures against cognitive deterioration. Overall, a comprehensive understanding of biomarkers in psychotropic drug users is essential for developing targeted interventions and preventive strategies.