Predictors of outcome in outpatients with anxiety disorders: The Leiden routine outcome monitoring study

Little is known about the predictors of outcome in anxiety disorders in naturalistic outpatient settings. We analyzed 2-year follow-up data collected through Routine Outcome Monitoring (ROM) in a naturalistic sample of 917 outpatients in psychiatric specialty care in order to identify factors predicting outcome. We included patients with panic disorder with or without agoraphobia, agoraphobia without panic, social phobia, or generalized anxiety disorder. Main findings from Cox regression analyses demonstrated that several socio-demographic variables (having a non-Dutch ethnicity [HR = 0.71)], not having a daily occupation [HR = 0.76]) and clinical factors (having a diagnosis of agoraphobia [HR = 0.67], high affective lability [HR = 0.80] and behavior problems [HR = 0.84]) decreased chances of response (defined as 50% reduction of anxiety severity) over the period of two years. Living with family had a protective predictive value [HR = 1.41]. These results may imply that factors that could be thought to limit societal participation, are associated with elevated risk of poor outcome. A comprehensive ROM screening process at intake may aid clinicians in the identification of patients at risk of chronicity.     

Predictors of outcome in outpatients with anxiety disorders: The Leiden routine outcome monitoring study

Little is known about the predictors of outcome in anxiety disorders in naturalistic outpatient settings. We analyzed 2-year follow-up data collected through Routine Outcome Monitoring (ROM) in a naturalistic sample of 917 outpatients in psychiatric specialty care in order to identify factors predicting outcome. We included patients with panic disorder with or without agoraphobia, agoraphobia without panic, social phobia, or generalized anxiety disorder. Main findings from Cox regression analyses demonstrated that several socio-demographic variables (having a non-Dutch ethnicity [HR = 0.71)], not having a daily occupation [HR = 0.76]) and clinical factors (having a diagnosis of agoraphobia [HR = 0.67], high affective lability [HR = 0.80] and behavior problems [HR = 0.84]) decreased chances of response (defined as 50% reduction of anxiety severity) over the period of two years. Living with family had a protective predictive value [HR = 1.41]. These results may imply that factors that could be thought to limit societal participation, are associated with elevated risk of poor outcome. A comprehensive ROM screening process at intake may aid clinicians in the identification of patients at risk of chronicity.     

Well that changes everything! The genesis of memory bias for threat with implications for delayed onset in anxiety disorders

Background and Objectives

A number of aetiological pathways have been proposed in the development of anxiety disorders, including those associated with stressful triggering situations. Life events can provide new meaning to past situations, potentially leading to the delayed onset of a disorder. Whether or not a disorder will emerge is theoretically related to one's appraisal and memory of prior events, and memory biases are proposed to exist for threat-related information in association with anxiety. Given that new events may change the meaning of past experiences, threatening information may change one's memory for once-neutral events.

Methods

The current study aimed to examine the effect of threatening information on memory for previously encoded (neutral) stimuli. Undergraduate participants (n = 81) interacted with 30 neutral objects (displayed in two boxes) and completed a recall memory test for these objects. They were then randomly assigned to receive either new threatening or new neutral information about half (one box) of the already-learned objects; a second recall test was then administered.

Results

Individuals given threatening information showed a greater proportion of memory for items that were manipulated to total items recalled than did individuals given new non-threatening information.

Limitations

A nonclinical sample reported relatively low ratings of disgust and anxiety. Additionally, the time between the two memory tests was brief, likely differing from the actual occurrence of delayed onset disorders.

Conclusions

Results showed the genesis of a memory bias for threat in the presumed absence of an attentional bias, and are discussed in terms of the delayed onset of anxiety disorders.     

Association between age of onset and mood in bipolar disorder: Comparison of subgroups identified by cluster analysis and clinical observation

Background

This study compared subgroups identified by cluster analysis and clinical observation by evaluating the association between the age of onset of bipolar disorder and self-reported daily mood ratings.

Methods

Two hundred and seventy patients with bipolar disorder provided daily self-reported mood ratings for about 6 months returning 55,188 days of data. The age of onset subgroups were determined both using previously defined cutoff values based upon clinical observation (≤12 years, 13–19 years, 20–29 years, >29 years), and model-based cluster analysis. Demographic characteristics were compared in the age of onset subgroups. Univariate general linear models with age of onset subgroups and other demographic variables as fixed factors and covariates were used to analyze the percent of days depressed, euthymic and hypomanic/manic.

Results

Using the predetermined subgroups, demographic differences were found between the four subgroups in the diagnosis of bipolar I/II, years of illness, age and use of lamotrigine. Post-hoc pairwise comparison found that patients with an age of onset less ≤ 12 years spent more days hypomanic/manic: 16.4 percent versus 8.0 for patients with an age of onset between 13 and 19 years (p = 0.006) and 8.2 percent for patients with an age of onset between 20 and 29 years (p = 0.031). The majority of the additional days of hypomania/mania occurred outside of an episode. Model-based cluster analysis found a mixture of 2 distributions of onset with peaks at age 15.1 years (SD = 4.7) and 27.5 years (SD = 10.2). Analysis of these two subgroups detected no significant differences in demographic characteristics or mood ratings.

Conclusion

Age of onset subgroups arising from clinical observation may be more useful than those determined by cluster analysis.     

Orexin A in adolescents with anxiety disorders

Abstract

Objectives: The relationships between orexins and stress-related conditions have been well documented in animal studies. However, human studies confirming this relationship are limited. The aim of this study was to investigate the association between orexin-A and anxiety disorders in adolescents. Additionally, we aimed to examine the relationship between orexin-A and cortisol levels in those with anxiety disorders.

Methods: A total of 56 medication-free adolescents diagnosed with any anxiety disorder, except for specific phobias, and 32 healthy controls were included in this study. Depression, state and trait anxiety levels of the participants were measured using self-report scales. Orexin-A and cortisol levels were measured by an enzyme-linked immunosorbent assay (ELISA).

Results: Analysis of covariance (ANCOVA) indicated that serum orexin-A levels were significantly higher in the anxiety disorder group than in the control group while controlling for age, sex and depression levels. After controlling for age and sex, orexin-A levels were positively and negatively correlated to depression and cortisol levels, respectively. In addition, a positive correlation trend between trait anxiety and orexin-A was found.

Conclusions: Orexin-A levels are higher in adolescents with anxiety disorder; however, depressive symptoms should be considered when investigating this relationship.     

Cognitive functioning in a population-based sample of young adults with anxiety disorders

Objective

Cognitive functioning in anxiety disorders has received little investigation, particularly among young adults and in non-clinical samples. The present study examined cognitive functioning in a population-based sample of young adults with anxiety disorders in comparison to healthy peers.

Methods

A population-based sample of 21–35-year-olds with a lifetime history of anxiety disorders (n = 75) and a random sample of healthy controls (n = 71) derived from the same population were compared in terms of performance in neuropsychological tests measuring verbal and visual short-term memory, verbal long-term memory, attention, psychomotor processing speed, and executive functioning.

Results

In general, young adults with anxiety disorders did not have major cognitive impairments when compared to healthy peers. When participants with anxiety disorder in remission were excluded, persons with current anxiety disorder scored lower in visual working memory tests. Current psychotropic medication use and low current psychosocial functioning associated with deficits in executive functioning, psychomotor processing speed, and visual short-term memory.

Conclusion

Lifetime history of anxiety disorders is not associated with cognitive impairment among young adults in the general population. However, among persons with anxiety disorders, current psychotropic medication use and low psychosocial functioning, indicating more severe symptoms, may associate with cognitive impairments.     

昆明市焦虑障碍现况调查及相关因素分析

目的 调查昆明市焦虑障碍的患病情况.方法 2005年11月至2006年1月采用分层容量比例概率随机抽样法,应用中文版复合性国际诊断交谈检查2.1版(CIDI-2.1)对昆明市≥15岁的居民5033人进行访谈,调查焦虑障碍的患病率,分析影响焦虑障碍的相关因素、起病年龄及共病情况.结果 (1)焦虑障碍的加权终生患病率为7.05%(324例),其中,男性为5.34%(100例),女性为8.89%(224例);城镇人口为7.81%(189例),农村人口为5.33%(135例);以特殊恐怖障碍患病率最高(5.64%,236例),惊恐障碍患病率最低(0.14%,6例).(2)女性患病风险[相对危险度(OR)=1.00]高于男性(OR=0.61;P<0.01);各类焦虑障碍的起病年龄中位数为16岁;焦虑障碍与美国精神障碍诊断与统计手册第4版诊断的物质使用障碍,情感障碍及疼痛障碍存在共病情况.结论 昆明市焦虑障碍患病率较高,焦虑障碍是一类起病年龄早、呈慢性病程且普遍存在与其他精神障碍共病状况的精神障碍,有必要加强对焦虑障碍的防治.     

上海某综合性医院内科门诊患者焦虑与抑郁症状调查

目的调查综合性医院内科门诊患者的焦虑和抑郁症状的发生率及不同性别、年龄、文化程度和职业间的差异。方法采用综合性医院焦虑抑郁量表（HADS）在上海某三级综合性医院4个普通内科门诊按10∶1随机调查6117例患者,有效回收完整量表6104例。HADS每个亚量表评分大于等于8分即表示存在焦虑或抑郁症状。结果调查对象中焦虑和抑郁的检出率分别为9.5%（95%CI=8.8%～10.2%）和23.0%（21.9%～24.1%）。其中30岁以下、文化程度高、职业为学生或无业者的人群,焦虑检出率较高;男性、60岁及以上、文化程度低、职业为农民或学生的人群抑郁检出率较高。结论上海三级综合性医院内科门诊患者焦虑和抑郁的发生率较高,应提高识别率,给予有效的预防和干预。     

氯氟(艹卓)乙酯治疗焦虑障碍的不良反应

目的观察氯氟(艹卓)乙酯治疗焦虑障碍的不良反应.方法采用双盲双模拟、多中心、随机、平行对照研究.共观察患者163例,其中试验组(氯氟(艹卓)乙酯组)82例,对照组(地西泮组)81例.试验组早、午餐后同时服用一片氯氟(艹卓)乙酯安慰剂片衣一片地西泮安慰剂片,晚餐后同时服用一片氯氟(艹卓)乙酯片2 mg及一片地西泮安慰剂片;对照组早、午、晚餐后同时服用一片氯氟(艹卓)乙酯安慰剂片及一片地西泮片2.5 mg,疗程为4 wk. 结果治疗4 wk后,试验组出现至少1项不良反应的病例数为25例,总的不良反应发生率为30.5%,可能与药物有关的病例数为10例,主要的不良反应为头昏、困倦、厌食、口干等;对照组出现至少1项不良反应的病例数为27例,总的不良反应发生率为33.3%,可能与药物有关的病例数为7例,主要的不良反应为头昏、困倦、衰弱、口干等. 结论氯氟(艹卓)乙酯治疗焦虑障碍有明显疗效,无明显不良反应.     

Personality disorders and the persistence of anxiety disorders: Evidence of a time-of-measurement effect in NESARC

Recent studies using data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) have found that some personality disorders (PDs) increase the persistence of several Axis I disorders. However, these effects are potentially confounded with the data collection wave in which PDs were assessed. Our aim was to extend published analyses to the case of anxiety disorders and to determine the robustness of the associations to analyses examining time-of-measurement effects. Persistence of anxiety disorders was defined either as follow-up diagnosis among participants diagnosed at baseline (“prediction”) or baseline diagnosis among participants diagnosed at follow-up (“post-diction”). Results revealed a robust pattern of higher odds ratios for post-diction among PDs assessed at baseline, and lower odds ratios for post-diction among PDs assessed at follow-up, suggesting a time of measurement artifact. Although only 4% of associations were robust to both predictive and post-dictive analyses, these were consistent with previous research.     

Locus of control in chronic anxiety disorders

The relationship between psychopathology and the personality trait, locus of control, was examined in 116 adult outpatients diagnosed as having chronic anxiety disorder. Measures consisted of state and trait scales, a measure of social adjustment, and a measure of disturbance during childhood. Patients with an external locus of control were more depressed, had higher levels of state anxiety, and exhibited more indecisiveness, fatigue and agoraphobia than those with an internal locus of control. Externally oriented patients also scored higher on neuroticism and trait anxiety and scored lower on social adjustment. On the somatic scales, externally oriented patients rated themselves, in contrast to physician's rating, as being more symptomatic than internal patients, suggesting the presence of a help-seeking attitude. Locus of control may be of importance in the formulation of therapy and prognosis in patients with anxiety disorders.     

Examining determinants of early and late age at onset in panic disorder: An admixture analysis

Past research demonstrated that age at onset might account for different clinical and etiological characteristics in panic disorder (PD). However, prior research relied on arbitrary choices of age cut-offs. Using a data-driven validated method, this study aimed to examine differences between early and late onset PD in various determinants. Admixture analysis was used to determine the best fitting model of age at onset distribution in PD. Data was collected from 511 individuals (ages 18–65) with PD diagnoses, who participated in the Netherlands Study of Depression and Anxiety (NESDA). DSM-IV comorbidities and various measures of childhood adversities, suicidal behavior, anxiety and depressive symptoms were assessed. The best fitting cut-off score between early and late age at onset groups was 27 years (early age at onset ≤ 27 years). Univariate tests showed that participants with early onset PD were younger and more likely to be female. Early onset PD was associated with agoraphobia, higher frequency of childhood trauma and life events, and higher rates of suicide attempts as compared to late onset PD. Multivariate logistic regression analysis demonstrated that only current age, childhood trauma and agoraphobia remained significantly associated with early onset PD. Findings suggest that 27 years marks two onset groups in PD, which are slightly distinct. Early onset PD is independently associated with exposure to childhood trauma and increased avoidance. This highlights the importance of subtyping age of onset in PD. Clinical implications are further discussed.     

A comparison of gains after treatment at a psychiatric outpatient clinic in patients with cluster A+B,or cluster C personality disorders,and non-psychotic axis I disorders

Few studies exist on the outcome of patients with personality disorders (PDs) treated at ordinary outpatient clinics. This study examines the gains of such patients 2?years after treatment start at an outpatient clinic. Three patient groups were sampled: cluster A?+?B PDs, cluster C PDs and axis I disorders. Fifty-eight patients (53%) were amenable to follow-up, and they did not show less psychopathology than the non-compliers. All patients had structured interviews and filled in questionnaires. Patients in the PDs cluster A?+?B group showed considerable gains, while that was not found for the PDs cluster C and Axis I disorder groups. Since almost all patients received long-term psychotherapy sometimes combined with antidepressant drugs, the finding that such a treatment mainly shows gains in more severely disturbed PDs patients should be replicated in larger samples at ordinary psychiatric outpatient clinics.     

Attentional bias towards angry faces in childhood anxiety disorders

Objective

To examine attentional bias towards angry and happy faces in 8-12 year old children with anxiety disorders (n = 29) and non-anxious controls (n = 24).

Method

Children completed a visual-probe task in which pairs of angry/neutral and happy/neutral faces were displayed for 500 ms and were replaced by a visual probe in the spatial location of one of the faces.

Results

Children with more severe anxiety showed an attentional bias towards angry relative to neutral faces, compared with anxious children who had milder anxiety and non-anxious control children, both of whom did not show an attentional bias for angry faces. Unexpectedly, all groups showed an attentional bias towards happy faces relative to neutral ones.

Conclusions

Anxiety symptom severity increases attention to threat stimuli in anxious children. This association may be due to differing threat appraisal processes or emotion regulation strategies.     

儿童青少年焦虑与抑郁障碍共病的临床研究

目的了解焦虑和抑郁障碍患儿中焦虑与抑郁共病的发生率和行为特点。方法在门诊收集符合中国精神障碍分类与诊断标准第3版中焦虑障碍和抑郁障碍诊断标准的5～17岁儿童青少年,其中单纯焦虑障碍41例(焦虑组),单纯抑郁障碍31例(抑郁组),焦虑与抑郁共病31例(共病组)。由父母、儿童、医师分别采用自编一般资料表、Achenbach儿童行为量表(CBCL)、儿童焦虑性情绪障碍筛查表(SCARED)、儿童抑郁障碍自评量表和儿童大体评定量表,评定三组儿童。结果(1)焦虑障碍患儿有16%(8例)合并抑郁;抑郁障碍患儿有42%(23例)合并焦虑。(2)CBCL焦虑组的活动情况及社会能力总分[(15.74±3.65)分]优于共病组[(12.98±4.00)分]和抑郁组[(14.02±3.67)分],均P<0.01和<0.05;共病组行为问题总分[(61.74±28.96)分]高于焦虑组[(43.44±22.54)分]和抑郁组[(47.74±25.99)分;F=4.62,P<0.05]。(3)SCARED共病组的总分高于焦虑组和抑郁组(P<0.05)。(4)儿童抑郁障碍自评量表抑郁组和共病组总分高于焦虑组(P<0.01)。(5)儿童大体评定量表焦虑组[(67.71±9.54)分]优于抑郁组[(58.55±8.08)分]和共病组[(61.16±7.60)分;F=11.10,P<0.001]。结论儿童焦虑、抑郁共病现象常见,共病患儿比单纯焦虑或抑郁患儿的内化性问题、外化性问题更严重,社会功能损害更明显。     

Assessing excessive reassurance seeking in the anxiety disorders

Reassurance seeking has long been hypothesized to be a key factor in the maintenance of anxiety within contemporary cognitive-behavioral approaches to the conceptualization and treatment of anxiety disorders. However, empirical studies have lagged due to the absence of a reliable and valid measure of reassurance seeking. The present study sought to develop and examine the psychometric properties of a theoretically derived measure of reassurance seeking in treatment-seeking participants with DSM-IV-TR (American Psychiatric Association, 2000) social phobia (n = 116), generalized anxiety disorder (n = 75), panic disorder with or without agoraphobia (n = 50), and obsessive compulsive disorder (n = 42). Participants (N = 283) completed the Reassurance Seeking Scale (RSS), Depression Anxiety Stress Scale, Beck Anxiety Inventory, and Beck Depression Inventory-II. An exploratory factor analysis resulted in a coherent three factor solution reflecting the need to seek excessive reassurance regarding: (1) uncertainty about decisions, (2) attachment and the security of relationships, and (3) perceived general threat and anxiety. The RSS was found to possess good internal consistency and was moderately correlated with measures of anxiety, stress, and depression. The psychometric properties of the RSS appear promising for the promotion of programmatic research on reassurance seeking and its treatment in the anxiety disorders.     

抑郁症焦虑症患者心率变异性特点的对比研究

目的探讨抑郁症、焦虑症患者自主神经功能的特点。方法随机选择42例抑郁症患者,10例焦虑症患者和17例健康对照者分别接受短时心率变异性分析,记录相关考察指标,进行统计学分析。结果心率变异性分析的各项考察指标中,各观察组均有一项或多项低于正常对照组（P〈0．05）;且各组之间互相对比分析P〈0．05。结论抑郁症、焦虑症患者均存在心率变异性的降低,其自主神经功能活性降低。抑郁症患者因伴或不伴有焦虑症状,其心率变异指标不同,可以指导治疗。     

Elements of the therapeutic relationship in CBT for anxiety disorders: A systematic review

To optimise the effects of cognitive behaviour therapy (CBT) for anxiety disorders, research has increasingly focussed on understanding mechanisms of change. Specifically, the therapeutic relationship has been identified as a potential “active ingredient” of therapy. The evidence for the effects of eleven elements of the therapeutic relationship (alliance, collaboration, goal consensus, group cohesion, empathy, positive regard, feedback, emotional expression, outcome expectations, treatment credibility, alliance rupture-repair) on treatment outcomes in CBT for anxiety disorders was systematically reviewed. Fifty unique studies were included, and findings were qualitatively reviewed and summarised. Results revealed consistent and sizeable evidence for the cohesion-outcome and expectation-outcome relationships. There was emerging evidence for the effects of collaboration, empathy, and alliance rupture-repair on outcomes. However, the evidence for goal consensus and credibility on outcomes was limited. Notably, review of the alliance literature revealed substantial inconsistencies across studies. No studies were identified for positive regard, feedback, and emotional expression. Overall, further research is needed to clarify the role of the therapeutic relationship in CBT for anxiety disorders. These findings will contribute to the conceptual integration of therapeutic relationship constructs in cognitive behavioural models, and help to improve treatments and outcomes for individuals.     

Internet-based Cognitive Bias Modification of Interpretations in patients with anxiety disorders: A randomised controlled trial

Background and objectives

Previous research suggests that negative interpretation biases stimulate anxiety. As patients with an anxiety disorder tend to interpret ambiguous information negatively, it was hypothesised that training more positive interpretations reduces negative interpretation biases and emotional problems.

Methods

In a randomised, double-blind placebo-controlled trial, patients with different anxiety disorders were trained online over eight days to either generate positive interpretations of ambiguous social scenarios (n = 18) or to generate 50% positive and 50% negative interpretations in the placebo control condition (n = 18) (Study 1).

Results

Positively trained patients made more positive interpretations and less negative ones than control patients. This training was followed by a decrease in anxiety, depression, and general psychological distress, but this effect was also observed in the control group. To get a better understanding of these unexpected results, we tested a 100% neutral placebo control group (Study 2, n = 19); now the scenarios described neutral, non-emotional situations and no valenced interpretations were generated. The results from this neutral group were comparable to the effects from the other control group.

Limitations

An advantage, but potentially also a disadvantage of the study is that CBM-I training was performed online with less control over the procedures and setting. In addition, the scenarios were not matched to the specific concerns of each patient and the training sessions were performed in close proximity to one another.

Conclusions

Compared to both control conditions, CBM-I had superior effects on interpretations, but not on emotions. The current findings showed the boundary conditions for CBM-I.     

Admixture analysis of age at onset in schizophrenia: evidence of three subgroups in a first-episode sample

Objective

The objective was to assess the presence of different subgroups, via age-at-onset (AAO) analysis, in a schizophrenia population consecutively recruited through an Early Psychosis Service in London, Canada.

Method

Admixture analysis was applied in order to identify a model of separate normal distribution of AAO characterized by different means, variances and population proportions to allow for evaluation of different subgroups in a sample of 187 unrelated patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of schizophrenia.

Results

The best-fitting model suggested three subgroups with means and standard deviations of 16.8±1.9, 22.3±2.1 and 32.7±5.9 years comprising 41%, 30% and 29% of the schizophrenia sample, respectively. These three subgroups were categorized as early, intermediate and late onset with cutoffs determined by admixture analysis to be 19 and 26 years of age, respectively. In our investigation, the definition of early-onset schizophrenia is the main outcome. We considered the clinical variables mainly related to the heritability and neurobiology of schizophrenia. Single status was strongly associated with early onset (P< .001). The male gender (P= .023), as well as a history of drug abuse (P= .004), was significantly associated with early onset. Interestingly, lower academic achievement was also associated with early-onset schizophrenia (P< .001).

Conclusion

Overall, our study showed that a typical early-onset schizophrenia patient is more likely to be a single male, with a history of drug abuse and birth complications, and lower academic achievement as compared to the late-onset subgroup.