Cognitive Anxiety Research Articles

Melatonin attenuates scopolamine-induced cognitive dysfunction through SIRT1/IRE1α/XBP1 pathway.

The prevalence of dementia around the world is increasing, and these patients are more likely to have cognitive impairments, mood and anxiety disorders (depression, anxiety, and panic disorder), and attention deficit disorders over their lifetime. Previous studies have proven that melatonin could improve memory loss, but its specific mechanism is still confused. In this study, we used invivo and invitro models to examine the neuroprotective effect of melatonin on scopolamine (SCOP)-induced cognitive dysfunction. The behavioral tests were performed. 18F-FDG PET imaging was used to assess the metabolism of the brain. Protein expressions were determined through kit detection, Western blot, and immunofluorescence. Nissl staining was conducted to reflect neurodegeneration. MTT assay and RNAi transfection were applied to perform the invitro experiments. We found that melatonin could ameliorate SCOP-induced cognitive dysfunction and relieve anxious-like behaviors or HT22 cell damage. 18F-FDG PET-CT results showed that melatonin could improve cerebral glucose uptake in SCOP-treated mice. Melatonin restored the cholinergic function, increased the expressions of neurotrophic factors, and ameliorated oxidative stress in the brain of SCOP-treated mice. In addition, melatonin upregulated the expression of silent information regulator 1 (SIRT1), which further relieved endoplasmic reticulum (ER) stress by decreasing the expression of phosphorylate inositol-requiring enzyme (p-IRE1α) and its downstream, X-box binding protein 1 (XBP1). These results indicated that melatonin could ameliorate SCOP-induced cognitive dysfunction through the SIRT1/IRE1α/XBP1 pathway. SIRT1 might be the critical target of melatonin in the treatment of dementia.

Effects of 12 weeks of head-down strong abdominal breathing on motor and cognitive performance during dual-tasking in patients with chronic obstructive pulmonary disease: Study protocol for a randomised controlled trial

ObjectiveHead-down training can affect behavioural and neurocognitive control while performing dual tasks (DT). Breathing training improves motor and cognitive performance in patients with chronic obstructive pulmonary disease (COPD). As a neurorehabilitation tool, functional near-infrared spectroscopy (fNIRS) has been demonstrated to be an effective method for detecting changes in brain activation during motor recovery, as well as monitoring patients' long-term progress during DT in motor and cognitive performance. However, no studies have examined the combined effect of head-down position and breathing exercises on motor and cognitive performance during DT. This study will employ a novel intervention involving head-down strong abdominal breathing training to investigate its effects on motor and cognitive performance during DT in patients with COPD aiming to inform future training modalities in the community and at home. MethodsWe will recruit participants from Anqing, China, through community announcements, bulletin board postings, WeChat, and offline visits and screen 72 patients with stable COPD, classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-II, by pulmonologists at the university hospital. All participants will be randomly assigned to the head-down strong abdominal breathing (tilt angle 0–30° on the inversion apparatus, respiratory rate 20–30 breaths/min), head-down training, and strong abdominal breathing training groups in a 1:1:1 ratio. The intervention will last 12 weeks, with sessions performed thrice weekly for 1 h. ResultsThe primary outcomes will be motor-cognitive DT time, dual-task effects, correct responses to cognitive tasks, and gait characteristics assessed at baseline, 6 and 12 weeks of intervention. The patient’s dorsolateral prefrontal cortex (PFC) will also be stimulated with fNIRS at wavelengths of 730 and 850 nm, with a sampling rate of 11 Hz, to record oxy-haemoglobin (oxy-Hb), deoxy-haemoglobin (deoxy-Hb), and total oxyhaemoglobin (total-Hb). Secondary outcomes will include pre- and post-intervention scales for dyspnoea, overall cognitive function, balance, and anxiety and depression. ConclusionAlterations in the PFC involved in attentional control, planning, and decision-making may partially explain cognitive and motor deficits (such as impaired balance and slower walking speed) in patients with COPD. This study may help to understand the effects of head-down strong abdominal breathing training on cognitive and motor performance under DT in patients with COPD and compare it with head-down training and breathing training alone. It may also help to determine whether it is a simple and effective form of exercise at home and in the community.

Aberrant functional hubs and related networks attributed to cognitive impairment in patients with anti‑N‑methyl‑D‑aspartate receptor encephalitis.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis results in severe neuropsychiatric symptoms and persistent cognitive impairment; however, the underlying mechanism is still not fully understood. The present study utilized the degree centrality (DC), functional connectivity (FC) and multivariate pattern analysis (MVPA) to further explore neurofunctional symptoms in patients with anti-NMDAR encephalitis. A total of 29 patients with anti-NMDAR encephalitis and 26 healthy controls (HCs) were enrolled for neuropsychological assessment and resting-state functional MRI (rs-fMRI) scans. DC, FC and MVPA were examined to investigate cerebral functional activity and distinguish neuroimaging characteristics between the patient and HC groups based on the rs-fMRI data. Compared with the HCs, the patients exhibited cognitive deficits, anxiety and depression. In the DC analysis, the patients exhibited significantly decreased DC strength in the left rectus gyrus, left caudate nucleus (LCN) and bilateral superior medial frontal gyrus, as well as increased DC strength in the cerebellar anterior lobe, compared with the HCs. In the subsequent FC analysis, the LCN showed decreased FC strength in the bilateral middle frontal gyrus and right precuneus. Furthermore, correlation analysis indicated that disrupted cerebral functional activity was significantly correlated with the alerting effect and Hamilton Depression Scale score. Using DC maps and receiver operating characteristic curve analysis, the MVPA classifier exhibited an area under curve of 0.79, and the accuracy classification rate was 76.36%, with a sensitivity of 79.31% and a specificity of 78.18%. The present study revealed that the disrupted functional activity of hub and related networks in the cerebellum, including the default mode network and executive control network, contributed to deficits in cognition and emotion in patients with anti-NMDAR encephalitis. In conclusion, the present study provided imaging evidence and primary diagnostic markers for pathological and compensatory mechanisms of anti-NMDAR encephalitis, with the aim of improving the understanding of this disease.

Cognitive emotional regulation, depression, anxiety and anger in Mexican children during the COVID-19 pandemic

Cognitive emotional regulation, depression, anxiety and anger in Mexican children during the COVID-19 pandemic

Fecal microbiota transplantation of patients with anorexia nervosa did not alter flexible behavior in rats.

Patients with anorexia nervosa (AN) are often anxious, display inflexible behavior and disrupted reward processing. Emerging evidence suggests that gut dysbiosis in patients contributes to the disease phenotype and progression. In a preclinical study, we explored whether AN-derived microbiota impacts cognitive flexibility, anxiety, and dopamine signaling using fecal microbiota transplantation (FMT) in tyrosine hydroxylase-cre rats. We performed probabilistic reversal learning task (PRLT) at the baseline, after antibiotic treatment, and following FMT from patients with AN and controls. We assessed flexible behavior, task engagement, and ventral tegmental area (VTA) dopamine signaling during and in the absence of reward. Furthermore, anxiety-like behavior was evaluated with open field (OF) and elevated plus maze (EPM) tests. Neither antibiotic-induced dysbiosis nor AN FMT led to significant alterations in the number of reversals or lever press strategies after reinforced or nonreinforced lever presses (win and lose-stay) in the PRLT. However, the number of initiated trials decreased after antibiotic treatment while remaining unchanged after FMT. No significant differences were observed in VTA dopamine activity, anxiety measures in the OF and EPM tests. Microbiome analysis revealed limited overlap between the microbiota of the donors and recipients. No evidence was found that the microbiota of patients compared to controls, nor a depleted microbiome impacts cognitive flexibility. Nonetheless, antibiotic-induced dysbiosis resulted in reduced task engagement during the PRLT. The relatively low efficiency of the FMT is a limitation of our study and highlights the need for improved protocols to draw robust conclusions in future studies. While our study did not reveal direct impacts of AN-associated gut microbiota on cognitive flexibility or anxiety behaviors in our preclinical model, we observed a decrease in task engagement after antibiotic-induced dysbiosis, underscoring that the presence of a gut microbiome matters. Our findings underscore the need for further refinement in FMT protocols to better elucidate the complex interplay between gut microbiota and behaviors characteristic of anorexia nervosa.

Clinical Evaluation of Effectiveness and Safety of Combined Use of Dietary Supplements Amberen® and SmartB® in Women with Climacteric Syndrome in Perimenopause.

Perimenopause is a time of transition in a woman's life that links her reproductive years to the cessation of ovulation, or menopause. For many women, this time is characterized by a variety of physiological and lifestyle changes, including increasing irregularity in menstrual bleeding, frequency and severity of vasomotor symptoms, etc. Therapies evaluated specifically for the perimenopausal women are very limited. This study aimed to evaluate the effectiveness and safety of Amberen® (a succinate-based non-hormonal supplement) combined with a SmartB® (vitaminB) complex in women with typical (without complications) mild to moderate climacteric syndrome during perimenopause. Women up to 50years of age, in perimenopause, with vasomotor and psychosomatic symptoms of the climacteric syndrome were enrolled for the study. The trial was randomized, double-blinded, placebo-controlled, comparative, and prospective. A total of 106 participants were enrolled in the trial and, per protocol, 105 completed the trial. We observed statistically significant improvements in most of the Greene Climacteric Scale symptoms, State-Trait Anxiety Inventory (STAI), Hospital Anxiety and Depression Scale (HADS), and Well-being, Activity, and Mood (WAM) scores. The intervention was well tolerated with few adverse effects reported to be mild and transient. The use of this dietary supplement is safe and eliminates or improves vasomotor and psychosomatic symptoms of climacteric symptoms in perimenopausal women: it improves sleep and cognitive abilities, lowers depression and anxiety, improves mood and well-being, and positively affects quality of life. NCT03897738.

Second Language Writing Anxiety among Faculty Scholars of a State University in the Philippines and Its Sex-Disaggregated Data

The study investigated the causes and the nature of writing anxiety specifically in the use of English as the second official language of the Philippines. Further, it accounted and analyzed its sex-disaggregated data. This was done among faculty scholars of Central Luzon State University. The respondents were randomly chosen from among the purposively identified faculty scholars of the university pursuing their graduate degrees - master’s and doctorate, in the different graduate curricular offerings in various universities in the Philippines and abroad, that require a thesis or dissertation as the final requirement for obtaining a graduate degree. The Second Language Writing Anxiety Inventory (SLWAI) of Cheng (2004), a questionnaire composed of 22 items with three open-ended questions was used to collect responses. The responses were scored and measured on a five-point Likert response scale. The differences in Second Language Writing Anxiety (SLWA) between male and female participants were analyzed using the Mann-Whitney Test, which is ideal for analyzing statistically the difference between the distributions of data of unparalleled groups with the comparison of ranks and scores. Based on the study findings, the most prominent nature of SLWA among participants is cognitive anxiety. Other sources of anxiety include the availability of external and internal resources and environmental elements. In relation to sex, males scored higher in terms of the level of anxiety compared to females. Lastly, it is forwarded that educators and the pedagogical approach may utilize a positive feedback mechanism as negative evaluation promotes anxiety even in composing in a second language.

THE COGNITIVE COMPONENTS OF ANXIETY DURING SPEAKING TESTS AMONG OMANI LEARNERS

To find out the components and levels of cognitive anxiety among Omani learners, 110 participants were selected in three proficiency levels: elementary, pre-intermediate, and intermediate. To collect the data, a questionnaire adapted from Thomas et al. (2017) Cognitive Test Anxiety Scale (CTAS-2) was used and some statistical analysis was run to measure other variables including gender and English proficiency levels on the amount of cognitive anxiety that students experience during speaking examinations. The results of the study revealed that lack of confidence and sleep, fear of failure, and immediate feedback were the primary sources of anxiety at either average or high levels during the speaking examination sessions. In addition, the study could not find any effect of gender on anxiety. The elementary English proficiency level students suffer more during the speaking examination. The results suggest that teachers provide a comfortable examination environment by fostering some jokes and laughter. Punctuality of examiners, and giving one or two minutes extra to exceptional cases assist in stress reduction during speaking examinations. In addition, the findings suggest that institutions and curriculum developers prepare semi-authentic speaking examination situations to reduce the cognitive elements of test anxiety by designing game-based speaking tasks.

Developing a Cognitive Behavioral Intervention for Gynecologic Cancer Survivors Undergoing Pelvic Exams

Regular pelvic exams after completing cancer treatment are critical for detecting endometrial and cervical cancer recurrence. Patients report high levels of distress and pain during exams. We conducted in-depth individual interviews with patients (N = 13) and providers (N = 10) to explore patients’ pelvic exam experiences and intervention preferences. Findings suggested that most patients experience exam-related distress and pain, and a telemedicine cognitive behavioral intervention targeting anxiety and pain would be acceptable and feasible for most patients. Findings informed PEACE (Pelvic Examination and Anxiety Coping skills for Empowerment) intervention development. Formative work is described, including a conceptual model, qualitative data collection and analysis, and session content.

Emotional Experiences During Completion of Daily Occupations in Individuals With Anxiety

The present study examined the frequency with which individuals with anxiety experienced positive and negative emotions during the completion of daily occupations. Participants were 89 individuals with a self-reported diagnosis of anxiety who completed the Emotional Experiences in Activities of Daily Living Scale (EEADLs) and State-Trait Inventory for Cognitive and Somatic Anxiety (STICSA). Individuals with high anxiety demonstrated more negative emotions but no differences in positive emotions during completion of personal care and household tasks with high physical and cognitive demands. Assessing emotions experienced during occupations can help inform recommendations to improve occupational balance and engagement in individuals with anxiety.

Pre and post-competitive anxiety and self-confidence and their relationship with technical-tactical performance in high-level men's padel players.

This study aimed to analyze the variations in pre- and post-competitive anxiety and self-confidence considering match outcomes, the performance according to the result and the correlation among performance and psychological variables. The sample consisted on 12 matches in which 11 high-level padel players from Finland (top 24) voluntarily participated. CSAI-2R and STAI-S were used to assess psychological variables and technical-tactical performance was evaluated by a certified padel coach. Losing players presented higher cognitive (p = .004), somatic (p = .020) and state (p = .001) anxiety and lower selfconfidence (p = .014), and winning players showed higher state anxiety (p = .022), after than before the matches. Post-match, winning players exhibited higher self-confidence (p = .015) than losing players. Winning players made more winners (p = .010) than losing players. There are direct correlations between unforced errors and post-state anxiety (p = .015), unforced errors and state anxiety (p = .009) and winners and cognitive anxiety (p = .033), in winning players; between generators of forced error and post-cognitive anxiety (p = .034), forced errors and cognitive anxiety in losing players (p = .001). There are indirect correlations between forced errors and pre-cognitive anxiety (p = .009), winners and somatic anxiety (p = .046), unforced errors and state anxiety (p = .042) in losing players. The outcomes imply the need for intervention programs to equip players, especially those facing defeat, with tools for anxiety management and self-confidence enhancement. Likewise, coaches are advised to incorporate exercises that promote the occurrence of winners.

The mediating role of cognitive test anxiety on the relationship between academic procrastination and subjective wellbeing and academic performance.

Promoting wellness as a predictor of sustainable development empowers schools to model healthy behavior. The multiple interactions in real and virtual environments that today's youth are subjected to force schools to explore effective educational strategies to provide a quality education for students and their families. This study examines the relationship between academic procrastination, assessment anxiety, subjective wellbeing, and academic performance. A convenience sample of 322 undergraduate students () was used, and questionnaires were administered to students measuring academic procrastination, cognitive test anxiety, and subjective wellbeing. For the same target group, the level of academic performance was identified using personal reports. The questionnaires were administered between May and June 2023 in an online format. For the data analysis, we applied correlational analysis and path analysis using. Both test anxiety and academic procrastination negatively correlate with performance and subjective wellbeing, leading to decreased performance and subjective wellbeing. Procrastination correlates positively with test anxiety. Cognitive test anxiety partially mediated the relationship between academic procrastination and subjective wellbeing and fully mediated the relationship between academic procrastination and academic performance. Thus, high procrastination leads to decreased performance and subjective wellbeing both directly and indirectly through increased test anxiety, leading to decreased performance and subjective wellbeing. As a result of theoretical and practical investigations, it emerges that joint action of educational actors is required in the generation of effective educational strategies for the prevention and control of procrastination and evaluation anxiety, given the fact that both a high level of procrastination as well as assessment anxiety led to the decrease of students' wellbeing, to the registration of low academic performances. In the long term, disruptive behavior (procrastination and anxious behavior) could generate low social and professional performance, which is a research question for a future longitudinal study.

Evaluating Perceptions of Test Anxiety Among Student Pharmacists and Faculty Members: A Pilot Study

ObjectiveThe purpose of this study was to determine student perceptions versus actual level of test anxiety, as measured by the Cognitive Test Anxiety Scale-2 (CTAS-2), and student and faculty perceptions of test anxiety with regard to prevalence, impact, ease of treatment, and importance in pharmacy education. MethodsTwo independent Qualtrics questionnaires were distributed via email to all students and faculty in the professional pharmacy program (years 1–4) at the University of Mississippi. The first questionnaire evaluated pharmacy students’ perceptions of test anxiety and self-awareness of personal test anxiety. The second questionnaire evaluated faculty members’ perceptions of student test anxiety. The questionnaires had 50 and 21 questions, respectively, and were developed from validated, reliable questionnaires used in Cognitive Test Anxiety (CTA) research. ResultsQuestionnaires were completed by 123 students and 19 faculty. Overall, 46 % of students had a self-perception of “high test anxiety”, with 28 % having a CTAS-2 score that correlated to severe test anxiety. A majority of faculty respondents (84 %) believed severe test anxiety affects 30 % or less of pharmacy students and may be associated with poor academic performance. ConclusionStudent pharmacists’ self-perception of test anxiety and perception of difficulty mitigating test anxiety may be overestimated. Overall, faculty accurately estimated the degree of test anxiety, felt confident in being able to help students, and believed it should receive attention from both faculty and the university.

Neuropsychology intervention for managing invisible symptoms of MS (NIMIS-MS) group: A pilot effectiveness and acceptability study

BackgroundPeople with MS (pwMS) commonly experience a range of hidden symptoms, including cognitive impairment, anxiety and depression, fatigue, pain, and sensory difficulties. These “invisible” symptoms can significantly impact wellbeing, relationships, employment and life goals. We developed a novel bespoke online group neuropsychological intervention combining psychoeducation and cognitive rehabilitation with an Acceptance and Commitment Therapy (ACT)-informed approach for pwMS in an acute tertiary hospital. This ‘Neuropsychological Intervention for Managing Invisible Symptoms’ in MS (NIMIS-MS) consisted of 6 sessions, each with a psychoeducation and ACT component. The content included psychoeducation around managing cognitive difficulties, fatigue, pain, sleep and other unpleasant sensations in MS with the general approach of understanding, monitoring, and recognising patterns and potential triggers. Specific cognitive rehabilitation and fatigue management strategies were introduced. The ACT-informed component focussed on three core ACT areas of the ‘Triflex’ of psychological flexibility (Harris, 2019): Being Present, Opening Up, and Doing What Matters. Methods118 pwMS attended the NIMIS-MS group intervention which was delivered 14 times in six-week blocks over an 18-month period. To evaluate the effectiveness and acceptability, participants completed measures of depression and anxiety (HADS), functional impairment (WSAS), Values- Progress (VQ) and Values- Obstruction (VQ), and Acceptance of MS (MSAS) pre and post NIMIs-MS group intervention. Qualitative feedback was obtained during focus groups after the final session and via online feedback questionnaires ResultsPre-post analysis showed that symptoms of depression and anxiety were significantly lower and acceptance of MS was significantly higher following completion of the NIMIS-MS group. Qualitative feedback showed that participants reported that they felt more equipped to manage the “invisible” symptoms of MS following completion of the group, and benefited from using ACT-based strategies and techniques. Participants highly valued the peer support that evolved during the NIMIS-MS groups. The online format was considered more accessible than in-person groups, due to less concerns of travel time, cost, fatigue, and comfort and infection. ConclusionEvaluation suggests that our novel NIMIS-MS groups is an acceptable, beneficial and feasible approach for providing neuropsychological interventions to individuals with MS.

Absence of the Peptide Transporter 1 Induces a Prediabetic and Depressive-Like Phenotype in Mice.

Protein-enriched diets improve glycemic control in diabetes or emotional behavior in depressive patients. In mice, these benefits depend on intestinal gluconeogenesis activation by di-/tripeptides. Intestinal di-/tripeptides absorption is carried out by the peptide transporter 1, PEPT1. The lack of PEPT1 might thus alter glucose and emotional balance. To determine the effects of PEPT1 deficiency under standard dietary conditions or during a dietary challenge known to promote both metabolic and cognitive dysfunction, insulin sensitivity, anxiety, and depressive-like traits, hippocampal serotonin (5-HT) and insulin signaling pathway were measured in wild-type (WT) and Pept1-/- mice fed either a chow or a high-fat high-sucrose (HF-HS) diet. Pept1-/- mice exhibited slight defects in insulin sensitivity and emotional behavior, which were aggravated by an HF-HS diet. Pept1-/- mice fed a chow diet had lower hippocampal 5-HT levels and exhibited cerebral insulin resistance under HF-HS diet. These defects were independent of intestinal gluconeogenesis but might be linked to increased plasma amino acids levels. Pept1-/- mice develop prediabetic and depressive-like traits and could thus be used to develop strategies to prevent or cure both diseases.

EFL University Student’s Writing Anxiety in Essay Development

<p class="8Abstractcontent"><span lang="EN-US">Among the numerous research of writing anxiety in EFL writing instruction, the investigation of writing anxiety during the creation of argumentative essay remains limited. This current research, therefore, was purposed to examine the levels and specific manifestations of writing anxiety for the development of argumentative essay. Guided by descriptive quantitative research framework, 53 university students in writing course were asked to fill out the Second Language Writing Anxiety Inventory (SLWAI) in a small-scale survey. The results shows that 78% of students experienced moderate levels of anxiety when engaged in the development of argumentative essays, with only a small percentage reporting high or low level of anxiety (11%). An analysis of the anxiety levels across all respondents revealed a prevailing trend of moderate anxiety. Moreover, cognitive anxiety was the predominant category, followed by somatic anxiety and avoidance behavior respectively.</span></p>

Cognitive profile, neuroimaging and fluid biomarkers in post-acute COVID-19 syndrome

We aimed to characterize the cognitive profile of post-acute COVID-19 syndrome (PACS) patients with cognitive complaints, exploring the influence of biological and psychological factors. Participants with confirmed SARS-CoV-2 infection and cognitive complaints ≥ 8 weeks post-acute phase were included. A comprehensive neuropsychological battery (NPS) and health questionnaires were administered at inclusion and at 1, 3 and 6 months. Blood samples were collected at each visit, MRI scan at baseline and at 6 months, and, optionally, cerebrospinal fluid. Cognitive features were analyzed in relation to clinical, neuroimaging, and biochemical markers at inclusion and follow-up. Forty-nine participants, with a mean time from symptom onset of 10.4 months, showed attention-executive function (69%) and verbal memory (39%) impairment. Apathy (64%), moderate-severe anxiety (57%), and severe fatigue (35%) were prevalent. Visual memory (8%) correlated with total gray matter (GM) and subcortical GM volume. Neuronal damage and inflammation markers were within normal limits. Over time, cognitive test scores, depression, apathy, anxiety scores, MRI indexes, and fluid biomarkers remained stable, although fewer participants (50% vs. 75.5%; p = 0.012) exhibited abnormal cognitive evaluations at follow-up. Altered attention/executive and verbal memory, common in PACS, persisted in most subjects without association with structural abnormalities, elevated cytokines, or neuronal damage markers.

Impact of Cognitive Impairment on Quality of Life in Multiple Sclerosis Patients-A Comprehensive Review.

Multiple sclerosis (MS) is characterized by a variety of symptoms that have a major impact on quality of life (QoL) even in early stages. In addition to individual motor, sensory, visual disturbances, and brainstem and sphincter disorders, which are expressed through the widely used Expanded Disability Status Scale (EDSS), other manifestations of MS have a detrimental effect on overall functioning and quality of life, such as cognitive impairment, depression, anxiety, fatigue, and pain. However, when talking about QoL, categorical definitions cannot be used because although the concept is generally understood, it is highly nuanced. Suffering from MS can significantly reduce QoL. Numerous research studies have focused on trying to identify and assess which are the elements that most affect the loss of QoL in MS people. However, in addition to the fact that the measurement of QoL can be subjective, it is very difficult to consider these elements in isolation, as they are interrelated. One such limiting factor of QoL that has been investigated is cognitive impairment (CI). This has been shown to have an impact on the lives of MS people, although the different approaches that have been taken to assess CI have evident limitations.

Exploring serum α‑synuclein and its autoantibodies in essential tremor: implications for diagnosis and symptom correlations.

There is no definite biomarker for confirming the diagnosis of essential tremor (ET) or differentiating it from other diseases, particularly Parkinson's disease. The present study aimed to investigate the serum levels of the α-synuclein protein (α-syn) and its autoantibodies in patients with ET compared with healthy controls and its relation to motor and non-motor symptoms in patients with ET. Serum α-syn and its autoantibodies were measured in 32 patients with ET and 32 age- and sex-matched controls. Both groups were assessed using the non-motor symptoms scale, MoCA, Beck Depression Inventory, Hamilton Anxiety Rating Scale, and the Short Form 36 Health Survey Questionnaire. Tremor was assessed using the Fahn-Tolosa-Marin Tremor Rating Scale. The serum α-syn concentration in patients with ET was significantly lower than that in healthy controls (P<0.001), with a positive predictive value of 0.81 and a negative predictive value of 0.75, while the serum anti-a-syn autoantibody concentration was not significantly different between the two groups. There were no correlations between serum α-syn or its autoantibodies and patients' clinical characteristics. Furthermore, patients with ET had worse cognitive impairment, depression, anxiety, non-motor symptoms and quality of life. The serum α-syn concentration was lower in patients with ET than in controls, with favorable predictive values, suggesting that it could serve as a biomarker for ET diagnosis.

The 5-HT1A receptor biased agonists, NLX-204 and NLX-101, like ketamine, elicit rapid-acting antidepressant activity in the rat chronic mild stress model via cortical mechanisms.

The highly selective 5-HT1A serotonin receptor "biased" agonists NLX-101 and NLX-204 display, like ketamine, potent and efficacious rapid-acting antidepressant (RAAD) activity in the rat chronic mild stress (CMS) model with systemic (i.p.) administration. They rapidly (within 1 day) reverse anhedonia (i.e., CMS-induced sucrose consumption deficit), attenuate working memory deficit (novel object recognition: NOR), and decrease anxiety behavior in the elevated-plus maze (EPM). Here, we sought to explore the contribution of prefrontal cortex (PFC) 5-HT1A receptor activation in the RAAD activity of NLX compounds. In male Wistar rats, unilateral PFC microinjections of NLX-204 and NLX-101 (16 µg), like ketamine (10 µg), reproduced the effects of their systemic administration: they reversed CMS-induced sucrose consumption deficit, attenuated anxiety (EPM), and reduced working memory deficits (NOR). In addition, unilateral PFC microinjections of the selective 5-HT1A antagonist, WAY-100,635 (2 µg), attenuated the beneficial effects of systemic NLX-204 and NLX-101 (0.16 mg/kg i.p.) in the sucrose intake and NOR models, indicating that these compounds exert their RAAD activity specifically through activation of PFC 5-HT1A receptors. These data indicate that 5-HT1A receptor biased agonists share with ketamine a common neuroanatomical site for RAAD activity, which can be obtained not only by targeting glutamatergic/NMDA neurotransmission (ketamine's primary mechanism of action) but also by activating 5-HT1A receptors, as is the case for the NLX compounds. The present observations also reinforce the notion that biased agonism at 5-HT1A receptors constitutes a promising strategy to achieve RAAD effects, with additional benefits against cognitive deficits and anxiety in depressed patients, without ketamine's troublesome side effects.