不同焦虑程度青少年首发广泛性焦虑障碍患者血清NPY、5-HT、BDNF的变化及其与生活应激、炎症因子和记忆功能的相关性分析

摘要 目的：探讨不同焦虑程度青少年首发广泛性焦虑障碍（GAD）患者血清神经肽Y（NPY）、5-羟色胺（5-HT）、脑源性神经营养因子（BDNF）的变化及其与生活应激、炎症因子和记忆功能的相关性。方法：选择2019年1月至2021年12月成都市精神卫生中心收治的147例青少年首发GAD患者,根据广泛性焦虑量表（GAD-7）分为轻度焦虑组（5-9分,50例）、中度焦虑组（10-14分,65例）、重度焦虑组（15-21分,32例）。检测血清NPY、5-HT、BDNF、C反应蛋白（CRP）、白细胞介素（IL）-1α、IL-6水平,采用学生生活应激问卷（SLSI）、延迟匹配测验（DMS）评估生活应激水平和记忆功能。比较组间血清NPY、5-HT、BDNF、CRP、IL-1α、IL-6水平以及SLSI、DMS差异,分析血清NPY、5-HT、BDNF水平与血清CRP、IL-1α、IL-6水平及SLSI、DMS的相关性。结果：重度焦虑组血清NPY、5-HT、BDNF水平低于中度焦虑组和轻度焦虑组（P＜0.05）,且中度焦虑组低于轻度焦虑组（P＜0.05）,重度焦虑组CRP、IL-1α、IL-6水平以及SLSI评分高于中度焦虑组和轻度焦虑组（P＜0.05）,且中度焦虑组高于轻度焦虑组（P＜0.05）。重度焦虑组总延迟反应时间、无延迟反应时间长于中度焦虑组和轻度焦虑组（P＜0.05）,且中度焦虑组长于轻度焦虑组（P＜0.05）;重度焦虑组总延迟正确数、无延迟正确数少于中度焦虑组和轻度焦虑组（P＜0.05）,且中度焦虑组少于轻度焦虑组（P＜0.05）。青少年首发GAD患者血清NPY、5-HT、BDNF水平与SLSI评分、CRP、IL-1α、IL-6、总延迟反应时间、无延迟反应时间呈负相关（P＜0.05）,与总延迟正确数、无延迟正确数呈正相关（P＜0.05）。结论：青少年首发GAD患者随着焦虑程度加重,其生活应激强度增强、炎症因子水平升高,记忆功能减弱,且均与患者血清NPY、5-HT、BDNF水平降低有关。     

Effects of paced respiration on anxiety reduction in a clinical population

The purpose of this study was to examine the effects of paced respiration on autonomic and self-report indices of affect within a clinical population. Thirty-six alcohol-dependent inpatients scoring high in trait anxiety were randomly assigned to either a pacing or attention control group. The paced subjects received 10 minutes of slow-breathing training during the first experimental session, while control subjects simply counted the pacing tones. In a second session, paced subjects were asked to breathe at the same lowered rate (10 cycles per minute) on their own, while the remaining subjects were instructed to relax. Prior to and following each session, self-ratings of tension level and state anxiety were collected. As expected, paced subjects evidenced greater reductions in self-rated tension, state anxiety, and skin conductance levels compared to the control subjects. It was concluded that respiratory pacing is an easily learned self-control strategy and potentially may be a useful therapeutic tool.This project was supported by Veterans Administration Medical Health Services Research and Development funds awarded to the first author.     

<Emphasis Type="Italic">Ataques De Nervios</Emphasis> In Relation to Anxiety Sensitivity Among Island Puerto Ricans

This study investigated the symptom profile of ataques de nervios (ADN) among Puerto Rican volunteers from the community who self-identified as having experienced at least one ataque. As expected, the most commonly reported ataques-specific symptoms were crying, anger, nervousness, and becoming hysterical. Comparing the responses of those with ADN to those with no history of ADN but who reported elevated anxiety sensitivity (AS) indicated that both groups were comparable on measures of depression, state and trait anxiety, and associated panic symptoms. As expected, both groups scored significantly higher on all measures than did participants with no history of ADN and low AS with the exception of the measure of state anxiety. It is unclear, however, whether the overlap in symptom severity between those with ADN and those with elevated anxiety sensitivity indicates that ADN and AS are the same or distinct conditions.     

UK patients with primary Sjögren's syndrome are at increased risk from clinical depression

Objective: This study was undertaken to assess the presence and degree of anxiety and depression in a group of UK patients with primary Sjögren's syndrome (1°SS). Design: Cross‐sectional. Setting: Department of Oral Medicine, Liverpool University Dental Hospital. Subjects: Eighty adult patients; 40 diagnosed with 1°SS according to the revised European Criteria and 40 age/gender‐matched controls with no history of chronic illness. Intervention: Hospital Anxiety and Depression Scale (HADS), a self‐administered questionnaire designed to evaluate the presence and degree of anxiety and depression in a clinical setting. Main outcome measures: Age, gender, Hospital Anxiety and Depression Scale (HADS). Results: Forty patients with 1°SS and 40/age/gender‐matched controls completed the HADS. Scores for anxiety in both the 1°SS and control groups showed no statistically significant difference. Patients with 1°SS had statistically significant higher, mean HADS scores for depression than the controls. There was an increased prevalence of ‘definite’ clinical depression in the 1°SS group. Conclusion: Patients with 1°SS appear to be at increased risk from clinical depression. Early recognition and appropriate intervention is therefore essential to reduce the negative impact of depression on the patient's quality of life and outcome of their disease.     

Sub-neurotoxic neonatal anoxia induces subtle behavioural changes and specific abnormalities in brain group-I metabotropic glutamate receptors in rats

Anoxia in the first week of life can induce neuronal death in vulnerable brain regions usually associated with an impairment of cognitive function that can be detected later in life. We set-up a model of subneurotoxic anoxia based on repeated exposures to 100% nitrogen during the first 7 days of post-natal life. This mild post-natal exposure to anoxia specifically modified the behaviour of the male adult rats, which showed an attention deficit and an increase in anxiety, without any impairment in spatial learning and any detectable brain damage (magnetic resonance imaging and histological analysis). Post-anoxic rats showed a reduction in the expression of group-I metabotropic glutamate receptors (i.e. mGlu1 and mGlu5 receptors) in the hippocampus and cerebral cortex, whereas expression of the mGlu 2/3 receptors, the NR1 subunit of NMDA receptors, and the GluR1 subunit of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors was unchanged. mGlu1 and mGlu5 receptor signalling was also impaired in postanoxic rats, as revealed by a reduced efficacy of the agonist (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) to stimulate polyphosphoinositide hydrolysis in hippocampal slices. We conclude that rats subjected to subneurotoxic doses of anoxia during the early post-natal life develop behavioural symptoms that are frequently encountered in the inattentive subtype of the attention deficit hyperactivity disorder, and that group-I mGlu receptors may be involved in the pathophysiology of these symptoms.     

Long-term individual housing in C57BL/6J and DBA/2 mice: assessment of behavioral consequences

The aim of the present study was to investigate the effects of individual housing on mouse behavior. The male mice of the C57BL/6J and DBA/2 strains were separated at the age of 4 weeks and kept in individual housing for 7 weeks until behavioral testing began. Their behavior was compared to the group-housed mice in a battery of tests during the following 7 weeks. The single-housed mice were hyperactive and displayed reduced habituation in the tests assessing activity and exploration. Reduced anxiety was established in the elevated plus-maze, but an opposite effect was observed in the dark-light (DL) and hyponeophagia tests. Immobility in the forced swimming test was reduced by social isolation. The DBA mice displayed higher anxiety-like behavior than the B6 mice in the plus-maze and DL exploration test, but hyponeophagia was reduced in the DBA mice. Moreover, all effects of individual housing on the exploratory and emotional behavior were more evident in the DBA than in the B6 mice. Novel object recognition and fear conditioning (FC) were significantly impaired in the single-housed mice, whereas water-maze (WM) learning was not affected. Marked strain differences were established in all three learning tests. The B6 mice performed better in the object recognition and FC tasks. Initial spatial learning in the WM was faster and memory retention slightly enhanced in the B6 mice. The DBA mice displayed lower preference to the new and enhanced preference to the old platform location than the B6 mice after reversal learning in the WM. We conclude that individual housing has strong strain- and test-specific effects on emotional behavior and impairs memory in certain tasks.     

Molecular correlates of emotional learning using genetically selected rat lines

The genetic contributions to active avoidance learning in rodents have been well established, yet the molecular basis for genetically selected line differences remains poorly understood. To identify candidate genes influencing this active avoidance paradigm, we utilized the bidirectionally selected Syracuse high- and low-avoidance (SHA and SLA) rat lines that markedly differ in their two-way active avoidance behavior. Rats were phenotyped, rested to allow recovery from testing stress and then hippocampi were dissected for gene expression profiling (Affymetrix U34A chips; approximately 7000 known genes), comparing SLA to SHA. Next, a subset of differentially expressed genes was confirmed by real-time PCR (RT-PCR) in hippocampi. Additional studies at the protein level were performed for some genes. Using triplicate arrays on pooled hippocampal samples, differentially expressed genes were identified by microarray suite 5.0 and robust multi-array average analyses. By RT-PCR analysis in hippocampi, eight genes were nominated as potential candidate genes consistent with the differential expression from the microarray data. Four genes, Veli1 (mlin-7B), SLC3a1, Ptpro and Ykt6p, showed higher expression in SHA hippocampi than SLA. Four genes, SLC6A4, Aldh1a4, Id3a and Cd74, showed higher expression in SLA hippocampi than SHA. The active avoidance behavioral difference between lines probably emerges from 'many small things'. These potential candidate genes generate hypotheses for future testing in human association and rodent studies. Differences in levels of a pleiotropic gene like Ptpro and SLC6A4 suggest that small differences over a lifespan may contribute to large behavioral differences.     

Eph家族蛋白在阿尔茨海默症等神经精神疾病中的作用

促红细胞生成素产生肝细胞(erythropoietin-producing hepatomocellular, Eph)受体是受体酪氨酸激酶家族中数量最多的成员。Eph受体与其配体肝配蛋白(Eph receptor-interacting proteins, ephrin)被统称为Eph家族蛋白,通过独特的双向信号传递在调控正常学习和记忆中扮演重要角色。近年大量的研究发现,Eph家族蛋白在多种神经精神疾病中发挥复杂而又重要的作用,主要是通过改变突触效能,参与神经元形态发生和调控基因表达等方式影响上述疾病的进程。然而,目前靶向Eph家族蛋白对阿尔茨海默症(Alzheimer’s disease, AD)、焦虑症及恐惧症等疾病进行治疗的研究却为数甚微。同时,单纯以β样淀粉蛋白为靶点的抗AD药物开发均遭遇瓶颈。因此,探索Eph家族蛋白在上述疾病中的具体作用变得十分迫切。本文综述了Eph家族蛋白在AD、焦虑症和恐惧症中的最新研究进展,旨在为靶向Eph家族蛋白治疗相关疾病提供新的思路。     

The ICD‐11 developmental field study of reliability of diagnoses of high‐burden mental disorders: results among adult patients in mental health settings of 13 countries

Reliable, clinically useful, and globally applicable diagnostic classification of mental disorders is an essential foundation for global mental health. The World Health Organization (WHO) is nearing completion of the 11th revision of the International Classification of Diseases and Related Health Problems (ICD‐11). The present study assessed inter‐diagnostician reliability of mental disorders accounting for the greatest proportion of global disease burden and the highest levels of service utilization – schizophrenia and other primary psychotic disorders, mood disorders, anxiety and fear‐related disorders, and disorders specifically associated with stress – among adult patients presenting for treatment at 28 participating centers in 13 countries. A concurrent joint‐rater design was used, focusing specifically on whether two clinicians, relying on the same clinical information, agreed on the diagnosis when separately applying the ICD‐11 diagnostic guidelines. A total of 1,806 patients were assessed by 339 clinicians in the local language. Intraclass kappa coefficients for diagnoses weighted by site and study prevalence ranged from 0.45 (dysthymic disorder) to 0.88 (social anxiety disorder) and would be considered moderate to almost perfect for all diagnoses. Overall, the reliability of the ICD‐11 diagnostic guidelines was superior to that previously reported for equivalent ICD‐10 guidelines. These data provide support for the suitability of the ICD‐11 diagnostic guidelines for implementation at a global level. The findings will inform further revision of the ICD‐11 diagnostic guidelines prior to their publication and the development of programs to support professional training and implementation of the ICD‐11 by WHO member states.