焦虑和抑郁动物模型的研究方法和策略

焦虑和抑郁障碍是严重威胁人们健康的精神疾病。焦虑和抑郁动物模型是通过一定的心理社会应激使动物产生明显的焦虑和抑郁情绪,模拟人类焦虑和抑郁障碍,以探讨其细胞、分子和基因水平机制。情绪障碍动物模型通常通过表面效度、结构效度和预测效度进行评价。目前的动物模型虽然存在一定的缺点,但已经为临床和科研提供了巨大帮助。     

To be sure, to be sure: intolerance of uncertainty mediates symptoms of various anxiety disorders and depression

The Intolerance of Uncertainty Model was initially developed as an explanation for worry within the context of generalized anxiety disorder. However, recent research has identified intolerance of uncertainty (IU) as a possible transdiagnostic maintaining factor across the anxiety disorders and depression. The aim of this study was to determine whether IU mediated the relationship between neuroticism and symptoms related to various anxiety disorders and depression in a treatment-seeking sample (N=328). Consistent with previous research, IU was significantly associated with neuroticism as well as with symptoms of social phobia, panic disorder and agoraphobia, obsessive-compulsive disorder, generalized anxiety disorder, and depression. Moreover, IU explained unique variance in these symptom measures when controlling for neuroticism. Mediational analyses showed that IU was a significant partial mediator between neuroticism and all symptom measures, even when controlling for symptoms of other disorders. More specifically, anxiety in anticipation of future uncertainty (prospective anxiety) partially mediated the relationship between neuroticism and symptoms of generalized anxiety disorder (i.e. worry) and obsessive-compulsive disorder, whereas inaction in the face of uncertainty (inhibitory anxiety) partially mediated the relationship between neuroticism and symptoms of social anxiety, panic disorder and agoraphobia, and depression. Sobel's test demonstrated that all hypothesized meditational pathways were associated with significant indirect effects, although the mediation effect was stronger for worry than other symptoms. Potential implications of these findings for the treatment of anxiety disorders and depression are discussed.     

Childhood Anxiety/Withdrawal, Adolescent Parent–Child Attachment and Later Risk of Depression and Anxiety Disorder

Previous research has shown that children with high levels of early anxiety/withdrawal are at increased risk of later anxiety and depression. It has also been found that positive parent–child attachment reduces the risk of these disorders. The aim of this paper was to examine the extent to which positive parent–child attachment acted to mitigate the risk of later internalising disorders amongst children with high levels of early anxiety/withdrawal using data from a 30 years longitudinal study of a New Zealand birth cohort. The findings of this study showed that: (a) increasing rates of early anxiety/withdrawal were associated with an increased risk of later anxiety and depression; (b) positive parent–child attachment in adolescence was associated with a decline in the risk of later anxiety and depression; and (c) these associations persisted even after controlling for confounding factors. The implications of these findings for the role of parent–child attachment in mitigating the adverse effects of early anxiety/withdrawal are discussed. It is concluded that positive parent–child attachment in adolescence may act as a compensatory factor which buffers the adverse effects of childhood anxiety/withdrawal on risks of developing later anxiety and depression.     

Improving prevention of depression and anxiety disorders: Repetitive negative thinking as a promising target

Prevention of depression and anxiety disorders is widely acknowledged as an important health care investment. However, existing preventive interventions have only shown modest effects. In order to improve the efficacy of prevention of depression and anxiety disorders, a number of authors have suggested that it is promising to focus on selective prevention programs that are offered to individuals scoring high on clearly established risk factors, whereby the preventive intervention then specifically targets these risk variables. This review presents repetitive negative thinking (worry and rumination) as a promising target for the prevention of depression and anxiety disorders.     

Partial replication of two rumination-related candidate gene studies

Two recent papers associated candidate genes with brooding rumination, a possible cognitive endophenotype for depression, in children ages 8–14 years. Stone et al. reported that BDNF val66met polymorphism predicted brooding in adolescence. Woody et al. reported that children carrying at least one copy of a CRHR1 TAT haplotype reported less brooding than their peers in the presence of maternal depression. We attempted to replicate and extend these findings in a sample of twins aged 12–16 years. We analyzed the BDNF val66met (rs6265) polymorphism and two (rs242924 and rs7209436) out of three single nucleotide polymorphisms (SNPs) that Woody et al. used to create a CRHR1 haplotype. We controlled for maternal history of depression and clustering within families. Unlike Stone et al., we found higher brooding among BDNF Met carriers. This main effect was qualified by an interaction with pubertal status, with the effect driven by more physically mature participants. Similar to Woody et al., we found an interaction between CRHR1 SNPs and maternal depression, with the homozygous minor genotype acting as a protective factor against brooding in the presence of maternal depression. Findings provide partial support for the influence of candidate genes in two environmentally sensitive systems on brooding.     

Thought suppression and psychopathology.

Wegner's seminal investigations of effects of thought suppression on later thought frequency have had a significant impact on recent approaches to understanding emotional disorders characterized by the occurrence of persistent, repetitive, unwanted thoughts. Thought suppression has now been implicated as a etiological and/or maintaining factor in depression, generalized anxiety disorder, specific phobia, posttraumatic stress disorder and obsessive-compulsive disorder. These developments are fairly new, and it has not been until recently that studies have investigated the effects of suppressing thoughts that are actually analogous to problematic thoughts characteristic of emotional disorder. This paper provides a review of this body of work, including the findings and their relevance for existing models of specific disorders. Directions for future research are suggested.     

Interactive Effects of Looming Cognitive Style and Maladaptive Perfectionism on Trait Anxiety

Perfectionism is suggested as a transdiagnostic factor, related to development and maintenance of many psychological disorders. Looming Cognitive Style (LCS), on the other hand, is unique to anxiety disorders, acting as a specific a cognitive vulnerability for anxiety disorders. The present study aims to assess the association of anxiety with two cognitive vulnerability factors, LCS and maladaptive perfectionism. It was hypothesized that maladaptive perfectionism will have moderator role in the relationship between LCS and anxiety. A similar relationship is not expected for depression. Data were collected from 326 university students through self-report measures of LCS, perfectionism, anxiety, and depression. Results indicated the significant moderator roles of maladaptive perfectionism in the relationship of LCS with anxiety, even when the symptoms of depression are controlled. That is, maladaptive perfectionism was associated with higher levels of anxiety especially in individuals who had higher levels of looming vulnerability. A similar moderating effect of maladaptive perfectionism was not observed for depression. The results altogether emphasize the importance of examining the interactive effects of different vulnerability factors in understanding the mechanisms through which the risk factors operate.     

手机成瘾与抑郁：社交焦虑和负性情绪信息注意偏向的多重中介作用

为考察手机成瘾与抑郁的关系, 研究同时整合情绪和认知两方面因素, 探讨了社交焦虑和负性情绪信息注意偏向在手机成瘾和抑郁之间的多重中介作用。研究1共有545名大学生完成了大学生手机成瘾倾向量表、贝克抑郁量表和社会交往焦虑量表。研究2选取51名大学生采用问卷法和2(配对面孔表情的情绪类型: 负性、中性) × 2(探测点位置: 与负性情绪面孔表情同侧、与负性情绪面孔表情异侧)的被试内实验设计。结果表明: (1)手机成瘾、社交焦虑和抑郁两两间存在显著正相关, 且社交焦虑在手机成瘾和抑郁之间起完全中介作用; (2)社交焦虑和负性情绪信息注意偏向在手机成瘾与抑郁的关系中起链式中介作用, 而负性情绪信息注意偏向在手机成瘾与抑郁间的单独中介效应不显著。具体而言, 手机成瘾通过两条路径影响抑郁: 一是社交焦虑的单独中介作用; 二是社交焦虑→负性情绪信息注意偏向的链式中介作用。     

Involvement of 5-HT1A receptors in animal tests of anxiety and depression: evidence from genetic models

Clinical studies have suggested the involvement of 5-HT1A receptors in anxiety and depressive disorders because partial 5-HT1A receptor agonists such as buspirone are therapeutic. The present review considers evidence from genetic animal models that support a role for 5-HT1A receptors in anxiety-like and depressed-like behavior in animals. Selective breeding for differential hypothermic responses to a selective 5-HT1A receptor agonist led to the development of the high DPAT sensitive (HDS) and low DPAT sensitive (LDS) lines of rats. The HDS rats differ from the LDS rats on several behavioral measures reflective of anxiety or depression, including reduced social interaction, reduced responding in a conflict task and exaggerated immobility in the forced swim test. However, they do not differ from the LDS rats in the elevated plus maze task, which is a commonly used test of anxiety. Nor do the HDS rats exhibit a typical anxiogenic response to the hippocampal administration of the 5-HT1A agonist. Although the HDS rats do exhibit elevations in 5-HT1A receptors in regions of the limbic cortex, it is not clear whether these increases account for the behavioral differences. Paradoxically, 5-HT1A receptor knockout mice also exhibit anxiety-like behavior in the plus maze, open field and conflict tests compared to wild type mice. However, the knockouts exhibited less immobility in the forced swim test than wild type control mice. Recent studies using selective regional reinstatement of the receptor have implicated the postsynaptic 5-HT1A receptors in these changes in anxiety-like behavior. Thus, preliminary evidence from two different types of genetic animal models suggests that anxiety-like behavior can arise if the 5-HT1A receptor function is eliminated or overexpressed. Further study with additional tests of anxiety are needed to confirm this intriguing relationship.     

Trajectory of change in anxiety sensitivity in relation to anxiety,depression, and quality of life among persons living with HIV/AIDS following transdiagnostic cognitive-behavioral therapy

ABSTRACT

Persons living with HIV/AIDS (PLHIV) disproportionately suffer from anxiety and depressive symptoms and disorders. Although past work has examined the efficacy of cognitive-behavioral therapy (CBT) for depression, and to a lesser extent anxiety, among PLHIV, little is known regarding potential mechanisms underlying improvement in anxiety/depression among this group. Anxiety sensitivity is a well-established risk/maintenance factor for anxiety and depressive disorders and is hypothesized to play an important role in maintaining anxiety among PLHIV. Past work has identified anxiety sensitivity as a mechanism of action underlying changes in various anxiety domains yet it is unknown whether changes in anxiety sensitivity relate to changes in anxiety symptoms among PLHIV undergoing transdiagnostic CBT for anxiety. The current study sought to examine treatment-related changes in anxiety sensitivity and how the trajectory of change relates to anxiety and depressive symptoms as well as overall quality of life. Individuals (n = 35) with HIV/AIDS and elevated anxiety symptoms received CBT for anxiety. Results indicated that reductions in anxiety sensitivity were significantly related to changes in anxiety, depression, and quality of life. Together, these data suggest that changes in anxiety sensitivity are significantly related to changes in anxiety/depression and quality of life among PLHIV seeking treatment.     

The future is here: A review of foresight systems in anxiety and depression

Cognitive models of anxiety and depression have long suggested a central role for future-oriented thinking in these disorders. Experimental studies suggest that anxiety and depression are characterised by distinct future-oriented thinking profiles, and that these profiles are markedly different from those of asymptomatic adults. In this paper, we review these profiles and propose two explanatory models marked by two different neurocognitive systems. The Reconstructive Memory Model emphasises a role for emotionally driven learning and retrieval in episodic foresight (i.e., the construction of future-oriented scenarios), and the Valuation Model proposes that an overweighing of risk and uncertainty estimates can be invoked to explain the future-oriented thought patterns. We consider the effectiveness of interventions aimed at altering such thought patterns. We suggest that future research aimed at elucidating the neurobiological underpinnings of future-oriented thinking in anxiety and depression can play an important role in advancing development of effective biological and psychosocial interventions for these disorders.     

Influence of maternal depression on children's brooding rumination: Moderation by CRHR1 TAT haplotype

There is growing evidence that brooding rumination plays a key role in the intergenerational transmission of major depressive disorder (MDD) and may be an endophenotype for depression risk. However, less is known about the mechanisms underlying this role. Therefore, the goal of the current study was to examine levels of brooding in children of mothers with a history of MDD (n = 129) compared to children of never depressed mothers (n = 126) and to determine whether the variation in a gene known to influence hypothalamic-pituitary-adrenal axis functioning—corticotropin-releasing hormone receptor 1 (CRHR1) —would moderate the link between maternal MDD and children's levels of brooding. We predicted children of mothers with a history of MDD would exhibit higher levels of brooding than children of mothers with no lifetime depression history but that this link would be stronger among children carrying no copies of the protective CRHR1 TAT haplotype. Our results supported these hypotheses and suggest that the development of brooding among children of depressed mothers, particularly children without the protective CRHR1 haplotype, may serve as an important mechanism of risk for the intergenerational transmission of depression.     

Specificity of autonomic arousal to DSM-IV panic disorder and posttraumatic stress disorder

Although research on the hierarchical model of anxiety and depression has confirmed that autonomic arousability (AA) is more germane to panic disorder with or without agoraphobia (PD/A) than other DSM-IV anxiety and mood disorders, studies have not evaluated the differential relevance of AA to posttraumatic stress disorder (PTSD). This issue was addressed in multivariate analytic models using 295 outpatients with anxiety and mood disorders. Consistent with prediction, the presence of current DSM-IV PTSD and PD/A was significantly predictive of AA, even when other forms of anxiety disorder comorbidity were held constant. Moreover, latent structural analyses indicated that PTSD and PD/A were the only DSM-IV anxiety disorder constructs to have significant direct effects on AA (in accord with previous findings, the DSM-IV constructs of generalized anxiety disorder, social phobia, and obsessive-compulsive disorder did not have significant structural relationships with AA). The current findings, which attest to the specificity of AA to PTSD and PD/A, are discussed in context of other clinically salient shared features of these disorders and their relevance to treatment and diagnostic classification.     

冠心病患者的抑郁和焦虑

许多临床研究表明,冠心病患者常发生抑郁及焦虑。而在严重精神症状（如抑郁或/和焦虑）者中有较高的冠心病发生率。抑郁增加冠心病患者的不良心血管事件发生率,影响预后。其机制有如下几个方面：对医疗措施及生活方式改变的依从性差、血小板功能异常、血管内皮功能紊乱以及心率变异性降低。选择性5-羟色胺再摄取抑制剂由于其较好的耐受性且无明显的心血管副作用而应用于冠心病合并抑郁及焦虑的药物治疗并改善患者的生活质量。但仍需要更大规模的临床研究以确定抑郁及焦虑对冠心病预后的影响。临床上应更加关注焦虑对冠心病的影响,进一步探讨焦虑能否作为冠心病的危险因素。     

The direct and interactive effects of neuroticism and life stress on the severity and longitudinal course of depressive symptoms

The direct and interactive effects of neuroticism and stressful life events (chronic and episodic stressors) on the severity and temporal course of depression symptoms were examined in 826 outpatients with mood and anxiety disorders, assessed on 3 occasions over a 1-year period (intake and 6- and 12-month follow-ups). Neuroticism, chronic stress, and episodic stress were uniquely associated with intake depression symptom severity. A significant interaction effect indicated that the strength of the effect of neuroticism on initial depression severity increased as chronic stress increased. Although neuroticism did not have a significant direct effect on the temporal course of depression symptoms, chronic stress significantly moderated this relationship such that neuroticism had an increasingly deleterious effect on depression symptom improvement as the level of chronic stress over follow-up increased. In addition, chronic stress (but not episodic stress) over follow-up was uniquely predictive of less depression symptom improvement. Consistent with a stress generation framework, however, initial depression symptom severity was positively associated with chronic stress during follow-up. The results are discussed in regard to diathesis-stress conceptual models of emotional disorders and the various roles of stressful life events in the onset, severity, and maintenance of depressive psychopathology.     

Anxiety and depression as correlates of self-reported behavioural inhibition in normal adolescents

In a previous study, Muris, Merckelbach, Wessel, and Van de Ven [Psychopathological correlates of self-reported behavioural inhibition in normal children. Behav. Res. Ther. 37 (1999) 575-584] found that children who defined themselves as high on behavioural inhibition displayed elevated levels of psychopathological symptoms compared to children who defined themselves as low or middle on behavioural inhibition. The present study further examined the relationship between self-reported behavioural inhibition and anxiety disorders and depression symptoms in a large sample of adolescents aged 12-18 years (N=968). Adolescents completed a measure of behavioural inhibition and questionnaires of anxiety and depression. Results indicated that adolescents who classified themselves as high on behavioural inhibition had higher scores of anxiety and depression than adolescents who classified themselves as low or middle on behavioural inhibition. Structural equations modelling was employed to test hypothetical models on the role of behavioural inhibition in childhood anxiety and depression. It was found that a pathway in which behavioural inhibition results in anxiety, which in turn leads to depression, provided the best fit for the data.     

Effects of age on symptoms of anxiety and depression in a sample of retired police officers

This study addressed the effects of age on anxiety and depressive symptoms. The analysis was based on the responses of 1,334 retired male Scottish police officers (34-94 years old) to the Hospital Anxiety and Depression Scale. Multiple regression analysis was used to determine the partialed linear and curvilinear effects of symptoms of, separately, anxiety and depression on age and retirement variables. Significant partialed effects of retirement type and present age were found. Early retirement was a vulnerability factor for both disorders. The authors found a consistent linear reduction in anxiety across age and a U-shaped function for depression across age. The differing profiles and independent effects of age on anxiety and depression are consistent with their status as separate entities. Respondents were increasingly susceptible to depression from the mid-50s onward, whereas susceptibility to anxiety was reduced with age.     

Internet-delivered transdiagnostic and tailored cognitive behavioral therapy for anxiety and depression: a systematic review and meta-analysis of randomized controlled trials

Anxiety and depressive disorders are often comorbid. Transdiagnostic and tailored treatments seem to be promising approaches in dealing with comorbidity. Although several primary studies have examined the effects of Internet-delivered cognitive behavior therapy (iCBT) for anxiety and depression, no meta-analysis including different types of iCBT that address comorbidity has been conducted so far. We conducted systematic searches in databases up to 1 July 2016. Only randomized trials comparing transdiagnostic/tailored iCBT for adult anxiety and/or depression with control groups were included. Nineteen randomized trials with a total of 2952 participants that met inclusion criteria were analyzed. The quality of the studies was high, however the blinding criteria were not fulfilled. The uncontrolled effect size (Hedges’ g) of transdiagnostic/tailored iCBT on anxiety and depression outcomes was large and medium for quality of life. The controlled effect size for iCBT on anxiety and depression outcomes was medium to large (anxiety: g = .82, 95% CI: .58–1.05, depression: g = .79, 95% CI: .59–1.00) and medium on quality of life (g = .56, 95% CI: .37–.73). Heterogeneity was small (quality of life) to moderate (anxiety, depression). There was a large effect on generic outcome measures and a moderate effect on comorbidities. When compared to disorder-specific treatments there were no differences on anxiety and quality of life outcomes, however there were differences in depression outcomes. Transdiagnostic and tailored iCBT are effective interventions for anxiety disorders and depression. Future studies should investigate mechanisms of change and develop outcome measures for these interventions.     

Association between anxiety and depression in children and adolescents with anxiety disorders

The relationship between anxiety and depression was examined in a sample of 106 children and adolescents referred to an outpatient anxiety disorder clinic for children. Twenty-eight percent of patients with DSM-III diagnoses of anxiety disorders displayed a concurrent major depression. Children with anxiety disorders plus major depression were found (1) to be older, (2) to demonstrate more severe anxiety symptomatology, and (3) to be diagnosed with different rates of certain anxiety-disorder subtypes, when compared to anxious patients without major depression. Nondepressed anxious children and adolescents did not differ from a psychopathological control group in severity of either anxiety or depression symptoms.