Psychotherapies for comorbid anxiety in bipolar spectrum disorders

Background

Comorbid anxiety disorders are highly prevalent in bipolar disorder and have been shown to have serious negative impacts on the course of illness. The pharmacological treatment of anxiety can interact with the bipolar disorder and has not been proven effective. As such, many have recommended the psychological treatment of anxiety. This paper reviews the literature on psychological treatments for anxiety comorbid to bipolar disorder.

Method

The Medline, PsychInfo and Web of Science databases were thoroughly examined for relevant treatment studies.

Results

Despite frequent recommendations in the literature, surprisingly few have studied the psychological treatment of comorbid anxiety in bipolar disorders. Nevertheless, preliminary results suggest that comorbid anxiety disorders can be effectively treated in a bipolar clientele using cognitive-behavioral therapy, mindfulness-based cognitive-behavioral therapy or relaxation training. In contrast, interpersonal, family therapy and psychoeducation alone would not seem to be beneficial treatment alternatives for anxiety. Cognitive-behavioral therapy appears to reduce the symptoms of obsessive-compulsive disorder, generalized anxiety disorder, panic disorder, post-traumatic stress disorder and general symptoms of anxiety among patients with bipolar disorder. However, the long-term maintenance of anxiety treatment effects may be somewhat reduced and adaptations may be called for to augment and sustain benefits.

Conclusions

There is an urgent need for randomized controlled trials of different forms of psychotherapy for anxiety disorders comorbid to bipolar disorder. Until such trials are available, the most promising approach would appear to be the sequential or modular CBT-based treatment of the anxiety disorder.     

The neurochemistry of mania. The effect of lithium on catecholamines, indoleamines and calcium mobilization

In an attempt to elucidate the chemical pathology of mania one has to consider the pharmacology of the two most effective treatments for this illness: lithium and the neuroleptics. Some of the possible mechanisms of action of these drugs on catecholamine and indoleamine mechanisms are discussed. The majority of this article is based on my and my colleagues' work which has been carried out in this MRC Laboratory on the effect of lithium on biological variates in bipolar patients and the effects of the administration of antidepressant treatments in these patients. It is concluded that lithium has a similar action on these mechanisms in both unipolar and bipolar patients which might suggest a common pathology in both unipolar and bipolar illness. It is suggested that in order to maintain an euthymic state in a bipolar patient one should maintain a certain degree of sensitivity of 5-HT2 receptors. This sensitivity may be related to the activity of calcium channels and to the polyphosphoinositide system. The former system can be regulated by the administration of calcium channel antagonists which have been shown to be effective in the treatment of mania. The polyphosphoinositide system is one that can be regulated by therapeutic concentrations of lithium. It is concluded that co-administration of a calcium channel antagonist and lithium may be a very effective treatment for mania.     

Brain-derived neurotrophic factor serum levels before and after treatment for acute mania

Accumulating evidence suggests that reduced levels of brain-derived neurotrophic factor (BDNF) in acute mood episodes may play an important role in the pathophysiology of bipolar disorder (BD). In order to assess changes in BDNF serum levels in BD patients before and after treatment for acute mania, ten bipolar patients were prospectively examined at inpatient unit admission and discharge. Diagnoses were made using the Structured Clinical Interview for DSM-IV, SCID-I. Serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF levels were decreased in BD patients during mania when compared to controls (p = 0.013) but this difference was no longer significant after treatment (p = 0.126). A sharp increase in BDNF levels was found after treatment of the episode of acute mania (p = 0.010). These findings suggest that the changes in BDNF serum levels may be associated with treatment response in acute mania. Further studies designed to validate the use of BDNF as a marker of treatment response in bipolar disorder are warranted.     

A meta-analysis of the influence of comorbidity on treatment outcome in the anxiety disorders

Although psychiatric comorbidity is common among patients with anxiety disorders, its impact on treatment outcome remains unclear. The present study used meta-analytic techniques to examine the relationship between diagnostic comorbidity and treatment outcome for patients with anxiety disorders. One hundred forty-eight anxiety-disordered treatment samples (combined N = 3534) were examined for post-treatment effects from the PsychINFO database. Samples consisted of those exposed to both active (CBT, dynamic therapy, drug treatment, CBT + drug treatment, mindfulness) and inactive treatments (placebo/attention control, wait-list). All treatments were associated with significant improvement at post-treatment, and active treatments were associated with greater effects than were inactive treatments. However, overall comorbidity was generally unrelated to effect size at post-treatment or at follow-up. A significant negative relationship between overall comorbidity and treatment outcome was found for mixed or “neurotic” anxiety samples when examining associations between comorbidity and specific diagnoses. Conversely, there was a significant positive relationship between overall comorbidity and treatment outcome for panic disorder and/or agoraphobia and PTSD or sexual abuse survivors. These findings suggest that while diagnostic comorbidity may not impact the effects of specific anxiety disorder treatments, it appears to differentially impact outcome for specific anxiety disorder diagnoses.     

Difference in Temperament and Character Inventory scores between depressed patients with bipolar II and unipolar major depressive disorders

Background

Although some core personality variables are known to be characteristic of unipolar or bipolar depression, few studies have compared the personality profile between these two disorders.

Methods

Temperament and Character Inventory (TCI) was employed to assess the personality of 36 depressed patients with bipolar II disorder (BPII), 90 patients with unipolar major depressive disorder (UP), and 306 healthy controls. The TCI was administered during the depressive episode in BPII and UP patients so that the results can be applied in a clinical setting.

Results

Significantly higher scores in harm avoidance (p < 0.0001) and lower scores in self-directedness (p < 0.0001) and cooperativeness (p < 0.05) were observed in both BPII and UP patients compared to controls. Lower novelty seeking in UP patients compared to BPII patients and controls was observed in females (p < 0.0001, p < 0.01, respectively). A significant difference in self-transcendence score was observed between BPII and UP patients in females (p < 0.0005), with higher scores in BPII (p = 0.009) and lower scores in UP (p = 0.046) patients compared to controls. A logistic regression model predicted BPII in depressed females based on novelty seeking and self-transcendence scores with a sensitivity of 89% and a specificity of 73%, but did not accurately predict BPII in males.

Limitations

Patients in our study were limited to those receiving outpatient treatments, and bipolar patients were limited to those with BPII.

Conclusions

Novelty seeking and self-transcendence scores of TCI might be useful in the differentiation of UP and BPII in female patients.     

Heterogeneity in EEG sleep findings in adolescent depression: unipolar versus bipolar clinical course

Background: EEG sleep measures in child and adolescent subjects with depression have shown considerable variability regarding group differences between depressed and control subjects. This investigation was designed to assess whether some of the observed variability is related to undifferentiated unipolar and bipolar disorders in a sample that was reported previously. Methods: Twenty-eight adolescents who met criteria for unipolar major depression and 35 controls with no lifetime psychiatric disorder participated in a cross-sectional sleep polysomnography study. Approximately 7 years later, follow-up clinical evaluations were conducted in 94% of the original cohort. Clinical course during the interval period was assessed without knowledge of subjects’ initial diagnostic and psychobiological status. Re-analysis of the original sleep data were performed with the added information of longitudinal clinical course. Results: Depressed subjects who had a unipolar course showed reduced REM latency, higher REM density, and more REM sleep (specifically in the early part of the night) compared with depressed adolescents who converted to bipolar disorder and controls who remained free from psychopathology at follow-up. In contrast to the unipolar group, depressed subjects who would later switch to bipolar disorder had demonstrated more stage 1 sleep and diminished stage 4 sleep. Conclusions: These preliminary results indicate that some of the observed variability in EEG sleep measures in adolescent depression appear to be confounded by latent bipolar illness. The findings also suggest that sleep regulatory changes associated with unipolar versus bipolar mood disorders may be different.     

A conceptual review of the comorbidity of attention-deficit/hyperactivity disorder and anxiety: implications for future research and practice

Although approximately 25% of children with attention-deficit/hyperactivity disorder (ADHD) exhibit an anxiety disorder, the comorbidity of ADHD and anxiety has been given less attention than comorbidity of ADHD and oppositional or conduct disorders. While it is true that comorbidity between ADHD and these externalizing disorders is more prevalent (approximately 50%), the comorbidity of ADHD and anxiety deserves careful scrutiny in its own right in as much as this comorbidity may have important implications for etiology, assessment, and treatment. The primary purpose of the current review is to examine the methodological and substantive reasons for the comorbidity of ADHD and anxiety. Methodological areas include definitional issues and informant characteristics, while substantive areas include genetics, temperament, neurobiological and neuropsychological functioning, family influences, and temporal relations between ADHD and anxiety. The study of the comorbidity of ADHD and anxiety will be advanced through a more precise phenotypic classification of ADHD and the integration of research in adjacent fields such as temperament and genetics with current research on the psychopathology of ADHD.     

Axis I and II comorbidity in a large sample of patients with obsessive-compulsive disorder

Background: No study has reported yet on the prevalence of both comorbid DSM-IV axis I and personality disorders in a large cohort of OCD patients, and little is known about differences in clinical characteristics between OCD patients with and without comorbid symptoms. Objective: To examine the cross-sectional prevalence of comorbid DSM-IV axis I, and personality disorders in a population of patients with primary obsessive–compulsive disorder (OCD). Method: 420 outpatients with OCD were evaluated for comorbid pathology, demographic, and clinical characteristics. Results: Forty-six percent of the patients were diagnosed with a comorbid disorder. Twenty-seven percent met the criteria for at least one comorbid axis I disorder, 15.6 percent for a comorbid personality disorder, and 20.4 percent for both a comorbid axis I disorder and a personality disorder. Limitations: A limitation of the current study is that the sample was drawn from a psychiatric department specialised in anxiety disorders, which might have underestimated the rate of comorbid diagnoses. Conclusion: Comorbid diagnoses occur less frequently than would be expected on the basis of comparable comorbidity studies in OCD. Associated axis I comorbidity did not affect clinical severity of OCD, but was related to higher levels of depression and anxiety, whereas axis II comorbidity impaired to a higher extent the overall functioning.     

Childhood anxiety: An early predictor of mood disorders in offspring of bipolar parents

Background

Anxiety disorders are common among the offspring of parents with bipolar disorder (BD). This study investigated the nature of the association between anxiety disorders and mood disorders in a prospectively studied high-risk cohort.

Methods

High-risk offspring were identified from families in which one parent had confirmed BD based on SADS-L interviews and best estimate diagnostic procedures. All agreeable offspring aged 8–25 years were enrolled in a longitudinal study involving repeated KSADS-PL format clinical assessments. Control (C) offspring from families in which neither parent met lifetime criteria for a psychiatric disorder were similarly assessed. All DSM-IV diagnoses in the offspring were confirmed on blind consensus review. Cumulative incidence and adjusted Cox Proportional Hazards models were used to calculate the risk of anxiety disorders and the predictive association with mood disorders.

Results

The cumulative incidence of anxiety disorders was higher (23.40% vs. 10.42%; HR=2.136; p=.0382) and occurred earlier (9.79 vs. 14.84 years; p=.0125) in high-risk compared to C offspring. In high-risk offspring generalized anxiety disorders (GAD) followed by social phobia were the most incident anxiety subtypes; while high emotionality (HR 1.111; p=.0096) and shyness (HR 1.144; p=.0053) increased the risk of anxiety disorders. Anxiety disorders increased the adjusted risk of mood disorders (HR 2.166; p=.0004), on average 8.49 years later (SD 5.97).

Limitations

The cumulative incidence of BD is relatively low, as the cohort is still in the period of risk.

Conclusions

Findings highlight the need for longitudinal surveillance of symptomatic high-risk children and suggest anxiety disorders are an important early intervention target.     

癫痫共病精神障碍住院患者的临床特征分析

目的对我院近两年来住院的癫痫患者进行回顾性研究,为规范治疗方案,改善预后提供循证依据。方法采用一般资料量表对50例患者住院资料进行整理,根据诊断与统计手册第五版(DSM-5).诊断系统对这类患者的病例记录资料进行规范诊断,分析临床特征。结果根据DSM-5诊断标准,癫痫脑病的比例明显下降(χ2=21.93,P0.01),癫痫共病双相情感障碍的比例明显增加(χ2=23.51,P0.01)。癫痫起病年龄越晚,共病双相情感障碍的可能性越大,差异有统计学意义(χ2=9.28,P0.05);难治性癫痫共病双相情感障碍所占比例较非难治性癫痫共病双相情感障碍比例低(χ2=12.78,P0.05);癫痫全面性发作共病双相情感障碍比例与部分性发作共病双相情感障碍比例无明显差异(χ2=11.67,P0.05)。结论临床实践中癫痫脑病诊断过多,癫痫共病双相情感障碍诊断不足。癫痫患者共病双相情感障碍与癫痫的发作特征、发病年龄及抗癫痫治疗的效果有关。     

Juvenile and late onset forms of depressive disorder: Genetic and biological characterization of bipolar and unipolar illness — A review

The age of onset of depressive illness may have an association with the genetic character and clinical course of the disorder. There are several genetic models of depressive disorder that are based on differences in age of onset. According to a multifactorial model, for example, a late onset would indicate a smaller genetic and greater environmental component. A correlation has been found between positive family history of affective illness and early age of the first episode. The presence or absence of a family history of affective illness has also been found to be distinguished by pharmacology, physiology, symptomatology, and severity. It is therefore recommended, for purposes of diagnosis and treatment, that a family history be gathered for patients with depressive illness.     

Co-occurring anxiety and disruptive behavior disorders: The roles of anxious symptoms, reactive aggression, and shared risk processes

The current review uses a developmental perspective to examine processes that may underlie and partially account for the association between anxiety disorders and disruptive behavior disorders among children and adolescents. We propose that one way to understand development of comorbid anxiety and disruptive behavior disorders is to examine symptoms that are precursors for or part of these syndromes, such as anxious symptoms and reactive aggression. We use a framework that considers these issues first at the syndrome or disorder level (e.g., anxiety disorders, disruptive behavior disorders), then at the symptom level (e.g., anxious symptoms and reactive aggression), and finally at the risk factor level (e.g., factors associated with anxious symptoms and/or reactive aggression). We apply various frameworks that have been put forth for understanding comorbidity of psychological syndromes to the co-occurrence of anxiety and disruptive behavior disorders and to the co-occurrence of reactive aggression and anxious symptoms where possible. We then identify gaps in the literature with regard to anxiety and reactive aggression, as well as anxiety and disruptive behavior disorders more generally. Finally, we provide a conceptual model describing how the relation of anxiety and reactive aggression may develop into clinically identifiable, comorbid anxiety and disruptive behavior disorders.     

Cognitive correlates of mania risk: are responses to success,positive moods,and manic symptoms distinct or overlapping?

Several measures of cognitive style have been shown to be elevated among persons diagnosed with bipolar disorder and those at risk for bipolar disorder. Several of these scales capture responses to positive affect, success, and hypomanic symptoms. We had two goals: (a) to use factor analyses to assess whether the constructs within these scales were statistically independent and (b) to examine whether the factors identified uniquely related to mania risk. A cross‐national sample of 638 participants completed measures of cognitive style, including the Responses to Positive Affect scale, the Positive Overgeneralization Scale, and the Hypomanic Interpretations Questionnaire. To assess whether these measures might simply reflect more impulsive reactions to positive mood states, participants also completed the Barratt Impulsivity Scale. To measure risk of mania, participants completed the Hypomanic Personality Scale (HPS). Factor analyses suggested seven factors of cognitive style and impulsivity. Four factors uniquely correlated with HPS. That is, risk for mania related to higher scores on separable factors of acting before thinking, being overly positive in interpreting manic symptoms, being overly confident in response to success, and tendencies to dampen positive affect. Current findings suggest the need to consider multifaceted aspects of cognition in refining psychological treatments of bipolar disorder. © 2009 Wiley Periodicals, Inc. J Clin Psychol 65:1–15, 2009.     

Psychostimulants for managing unipolar and bipolar treatment-resistant melancholic depression: A medium-term evaluation of cost benefits

Background

We earlier reported an open study of 50 unipolar and bipolar treatment resistant depressed patients indicating that psychostimulants may have differential superiority for the melancholic depressive sub-type. We designed an extension study to examine cost benefits of psychostimulants more closely for those only with melancholic depression.

Method

The sample comprised patients clinically diagnosed with melancholic depression who had failed to respond to and/or experienced significant side-effects with at least two antidepressants. Data were collected for 61 unipolar and 51 bipolar II patients receiving a psyschostimulant for a mean interval of 69 weeks. Benefits and side-effects were assessed.

Results

Effectiveness ratings were similar across unipolar and bipolar sub-sets. Psychostimulants were judged as ‘very’ effective for 20% of patients and ‘somewhat’ effective for 50%. Forty percent judged the psychostimulant as being ‘as effective’ or as ‘superior’ to previously prescribed antidepressants, and worthy of being maintained. Significant side-effects were experienced by 40% of patients, requiring medication to be ceased in 12%. Twenty percent of the bipolar patients experienced a worsening of highs.

Limitations

The study was uncontrolled and retrospective, no formal rater-completed or patient-completed interval measures of severity were completed, while diagnostic judgments about melancholic depression and bipolar disorder were clinically judged.

Conclusions

This open study suggests that psychostimulants may be efficacious antidepressant options for managing unipolar and bipolar melancholia, often seemingly having very rapid onset and generally requiring only low doses, and arguing the need for controlled studies in melancholic patients.     

The co-occurrence of attention-deficit/hyperactivity disorder and unipolar depression in children and adolescents: A meta-analytic review

This paper reviews the empirical literature on the association between attention-deficit/hyperactivity disorder (ADHD) and depression (i.e., unipolar depressive disorders and symptoms) among children and adolescents. Findings from cross-sectional and longitudinal studies published on the co-occurrence of ADHD and depression were summarized and subjected to a meta-analysis. Results (k = 29, N = 8755; rbar = 0.22) indicated that ADHD and depression were positively related, but substantial variability existed across the studies. Subgroup analyses indicated medium positive effects for cross-sectional studies, studies that operationalized ADHD based on DSM-III or DSM-IV diagnostic criteria, and studies that did not include teacher report in the assessment of ADHD. Subgroup analyses showed a large positive effect for studies that operationalized ADHD based on DSM-III-R criteria and studies using clinic referred samples. In contrast, subgroup analyses indicated a small negative and/or unreliable association between ADHD and depression for longitudinal studies, studies using DSM-II diagnostic criteria for hyperkinetic reaction of childhood or used a dichotomous motor hyperactivity criterion, studies that used nonreferred samples, and studies including teacher report in the assessment of ADHD. When studies that used DSM-II diagnostic criteria were removed, a reliable medium effect was found for studies that included teacher report. Similarly when the study that used idiosyncratic methods of diagnosing ADHD was excluded, a reliable medium effect was found for studies that used nonreferred samples. Potential explanations for the findings are discussed, including explanations based on sampling and base rates, artifacts of diagnostic criteria, inaccurate diagnostic boundaries, and etiological relationships. Directions for future research and clinical implications are discussed.     

Validation study of tripartite model of anxiety and depression in children and adolescents: clinical sample in Korea

Although the currently available literature has provided some empirical support for a tripartite model of child and adolescent anxiety and depression, one of the limitations of these studies was that they have been conducted in America, primarily with Caucasians. In order to make this model more applicable to diverse ethnic and cultural groups, this study used a tripartite model for child and adolescent anxiety and depression in Korea, using confirmatory factor analysis with logically selected items from the Revised Children's Manifest Anxiety Scale (RCMAS), as well as the Children's Depression Inventory (CDI). The results indicated that the model fit of a three-factor model was superior to one- and two-factor models. In addition, the findings of discriminant analysis demonstrated that the correct classification rate with three factors of the tripartite model was superior to the classification rate achievable using CDI and RCMAS. In a departure from Clark and Watson's hypothesis, however, the correlations of three factors were significantly higher than had been expected. The results are discussed on the basis of cultural background.     

Overlapping clusters of gray matter deficits in paranoid schizophrenia and psychotic bipolar mania with family history

The purpose of this study was to assess volumetric abnormalities of gray matter throughout the entire brain in patients with paranoid schizophrenia or with bipolar mania compared with control groups. We obtained weighted 3D T1 magnetic resonance images from 23 patients with paranoid schizophrenia, 24 patients with psychotic bipolar mania, and 36 healthy controls. Gray matter volume differences were assessed using optimized volumetric voxel-based morphometry (VBM). Both paranoid schizophrenia and bipolar mania group showed reduction of gray matter volume in the superior temporal gyrus (STG) (Brodmann Area, BA 22 areas), and the inferior parietal lobule, and enlargement of putamen, although different sides of the inferior parietal lobule and putamen were affected in the groups. Our findings showed the presence of overlapping clusters of gray matter deficits in paranoid-type schizophrenia and psychotic bipolar mania. The overlap in gray matter pathology between the two disorders may be attributed to risk factors common to both disorders.     

The role of somatic health problems in the recognition of depressive and anxiety disorders by general practitioners

Background

Recognition of depression and anxiety by general practitioners (GPs) is suboptimal and there is uncertainty as to whether particular somatic health problems hinder or facilitate GP recognition. The objective of this study was to investigate the associations between somatic health problems and GP recognition of depression and anxiety.

Methods

We studied primary care patients with a DSM-IV based psychiatric diagnosis of depressive or anxiety disorder during a face-to-face interview (n=778). GPs′ registrations of depression and anxiety diagnoses, based on medical file extractions, were compared with the DSM-IV based psychiatric diagnoses as reference standard. Somatic health problems were based on self-report of several chronic somatic diseases and pain symptoms, using the Chronic Pain Grade (CPG), during the interview.

Results

Depression and anxiety was recognized in sixty percent of the patients. None of the health problems were negatively associated with recognition. Greater severity of pain symptoms (OR=1.18, p=.02), and chest pain (OR=1.56, p=.02), in particular, were associated with more GP recognition of depression and anxiety. Mediation analyses showed that depression and anxiety in these patients were better recognized through the presence of more severe psychiatric symptoms.

Limitations

Some specific chronic diseases had low prevalence.

Conclusions

This study shows that the presence of particular chronic diseases does not influence GP recognition of depression and anxiety. GPs tend to recognize depression and anxiety better in patients with pain symptoms, partly due to more severe psychiatric symptoms among those with pain.     

丁螺环酮治疗焦虑症30例临床分析

目的 评价丁螺环酮治疗焦虑症的疗效及副反应。方法 应用丁螺环酮治疗30例焦虑症，应用焦虑自评量表(SAS)及汉密尔顿焦虑量表(HAMA)评定疗效，并作临床疗效评定。结果 治疗后SAS、HAMA分值均明显下降，临床疗效评定显示痊愈率为33．3%，总有效率为90%，除出现口干5例(16．67%)、头昏及眩晕3例(10％)、嗜睡1例(3.33％)外，未见其它不良反应，且症状轻微，勿须作特殊处理。结论 丁螺环酮治疗焦虑症疗效肯定，且副作用轻微。