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.     

Block the light and sleep well: Evening blue light filtration as a part of cognitive behavioral therapy for insomnia

ABSTRACT

The objective of the present study was to assess the effect of combining CBT-I with wearing blue-light blocking glasses 90 min prior to bedtime on subjective and objective sleep parameters and daily symptoms (anxiety, depression, hyperarousal). Thirty patients (mean age 48.1 ± 16.13 years, range 21–71, 15 men/15 women) completed a CBT-I group therapy program, with groups randomly assigned to either “active” (blue-light filtering glasses) condition or “placebo” (glasses without filtering properties) condition. Patients were continually monitored by wristwatch actigraphy, kept their sleep diaries and completed a standard questionnaire battery at admission and after the end of the program. Statistical analyses showed a greater reduction of BAI score in “active” (4.33 ± 4.58) versus “placebo” (?0.92 ± 3.68) groups of patients [F = 6.389, p = .019, Cohen’s d = 1.26] and significant prolongation of subjective total sleep time in “active” (?36.88 ± 48.68 min.) versus “placebo” (7.04 ± 47.50 min.) [F = 8.56, p < .01, d = 0.91] group. When pre- and post-treatment results were compared in both groups separately, using paired-samples t-tests, significant differences were observed also in the active group for BDI-II score (t = 3.66, p = .003, Cohen’s d = 0.95) and HAS score (t = 2.90, p = .012, Cohen’s d = 0.75). No significant differences were found in the placebo group. In active group, there was also a significant reduction of subjective sleep latency (t = 2.65, p = .021, d = 0.73) and an increase of subjective total sleep time (t = ?2.73, p = .018, d = ?0.76) without change in objective sleep duration which was significantly shortened in the placebo group. We provide further evidence that blocking short-wavelength light in the evening hours may be beneficial for patients suffering from insomnia.     

Changing time and emotions

In this paper, we consider that our experience of time (to come) depends on the emotions we feel when we imagine future pleasant or unpleasant events. A positive emotion such as relief or joy associated with a pleasant event that will happen in the future induces impatience. Impatience, in our context, implies that the experience of time up to the forthcoming event expands. A negative emotion such as grief or frustration associated with an unpleasant event that will happen in the future triggers anxiety. This will give the experience of time contraction. Time, therefore, is not exogeneously given to the individual and emotions, which link together events or situations, are a constitutive ingredient of the experience of time. Our theory can explain experimental evidence that people tend to prefer to perform painful actions earlier than pleasurable ones, contrary to the predictions yielded by the standard exponential discounting framework.     

Behavioural studies of MHC‐congenic mice

Behavioural studies of MHC‐congenic mice and rats have focused primarily on mate choice and the ability to discriminate between strains by their urine odours, but these strains may differ in other behaviours, such as activity and ultrasonic vocalizations. Ivanyi (1978, Proc. Roy. Soc. Lord. 202, 117–158) has reviewed the physiological differences associated with the MHC, many of which could influence behaviour. We have started a systematic study of behavioural development and adult behaviour in MHC‐congenic mice. A developmental test battery (growth, rate, locomotion, grooming, eye opening, ultrasonic vocalizations, etc.) was used to examine differences between C57BL/6J vs. B6‐H‐2^bm1 and C57BL/10SnJ vs. B10.BR/sgSnJ mice. A test battery of spontaneous behaviours (activity, exploration, ultrasonic vocalizations, etc.) was used to examine behavioural differences between adult C57BL/6J vs. B6‐H‐2^bm1 and C57BL/10SnJ vs. B10.BR/sgSnJ mice. Differences in development and in adult behaviours between these MHC-congenic strains is discussed in relation to possible neural, endocrine and immune system differences. Future studies will compare MHC-congenic mice on levels of anxiety, sociosexual behaviour and on learning paradigms. This revised version was published online in July 2006 with corrections to the Cover Date.     

Sialyltransferase ST3Gal IV deletion protects against temporal lobe epilepsy

Temporal lobe epilepsy (TLE) often becomes refractory, and patients with TLE show a high incidence of psychiatric symptoms, including anxiety and depression. Therefore, it is necessary to identify molecules that were previously unknown to contribute to epilepsy and its associated disorders. We previously found that the sialyltransferase ST3Gal IV is up‐regulated within the neural circuits through which amygdala‐kindling stimulation propagates epileptic seizures. In contrast, this study demonstrated that kindling stimulation failed to evoke epileptic seizures in ST3Gal IV‐deficient mice. Furthermore, approximately 80% of these mice failed to show tonic–clonic seizures with stimulation, whereas all littermate wild‐type mice showed tonic–clonic seizures. This indicates that the loss of ST3Gal IV does not cause TLE in mice. Meanwhile, ST3Gal IV‐deficient mice exhibited decreased acclimation in the open field test, increased immobility in the forced swim test, enhanced freezing during delay auditory fear conditioning, and sleep disturbances. Thus, the loss of ST3Gal IV modulates anxiety‐related behaviors. These findings indicate that ST3Gal IV is a key molecule in the mechanisms underlying anxiety – a side effect of TLE – and may therefore also be an effective target for treating epilepsy, acting through the same circuits.

     

Sex‐specific behavioral traits in the Brd2 mouse model of juvenile myoclonic epilepsy

Idiopathic generalized epilepsy represents about 30–35% of all epilepsies in humans. The bromodomain BRD2 gene has been repeatedly associated with the subsyndrome of juvenile myoclonic epilepsy (JME). Our previous work determined that mice haploinsufficient in Brd2 (Brd2+/?) have increased susceptibility to provoked seizures, develop spontaneous seizures and have significantly decreased gamma‐aminobutyric acid (GABA) markers in the direct basal ganglia pathway as well as in the neocortex and superior colliculus. Here, we tested male and female Brd2+/? and wild‐type littermate mice in a battery of behavioral tests (open field, tube dominance test, elevated plus maze, Morris water maze and Barnes maze) to identify whether Brd2 haploinsufficiency is associated with the human behavioral patterns, the so‐called JME personality. Brd2+/? females but not males consistently displayed decreased anxiety. Furthermore, we found a highly significant dominance trait (aggression) in the Brd2+/? mice compared with the wild type, more pronounced in females. Brd2+/? mice of either sex did not differ from wild‐type mice in spatial learning and memory tests. Compared with wild‐type littermates, we found decreased numbers of GABA neurons in the basolateral amygdala, which is consistent with the increase in aggressive behavior. Our results indicate that Brd2+/? haploinsufficient mice show no cognitive impairment but have behavioral traits similar to those found in patients with JME (recklessness, aggression). This suggests that either the BRD2 gene is directly responsible for influencing many traits of JME or it controls upstream regulators of individual phenotypes.