Cross-cultural differences in somatic presentation in patients with generalized anxiety disorder

Little is known about cultural differences in the expression of distress in anxiety disorders. Previous cross-cultural studies of depression have found a greater somatic focus in Asian populations. We examined anxiety symptoms in patients with generalized anxiety disorder (GAD) in urban mental health settings in Nepal (N = 30) and in the United States (N = 23). Participants completed the Beck Anxiety Inventory (BAI). The overall BAI score and somatic and psychological subscales were compared. While there was no difference in total BAI scores, the Nepali group scored higher on the somatic subscale (i.e. "dizziness" and "indigestion," t[df] = -2.63[50], p < 0.05), while the American group scored higher on the psychological subscale (i.e. "scared" and "nervous," t[df] = 3.27[50], p < 0.01). Nepali patients with GAD had higher levels of somatic symptoms and lower levels of psychological symptoms than American patients with GAD. Possible explanations include differences in cultural traditions of describing distress and the mind-body dichotomy.     

Overview and clinical presentation of generalized anxiety disorder.

1. To distinguish GAD from panic disorder is not difficult if a patient has frequent, spontaneous panic attacks and agoraphobic symptoms, but many patients with GAD have occasional anxiety attacks or panic attacks. Such patients should be considered as having GAD. An even closer overlap probably exists between GAD and social phobia. Patients with clear-cut phobic avoidant behavior may be distinguished easily from patients with GAD, but patients with social anxiety without clear-cut phobic avoidant behavior may overlap with patients with GAD and possibly should be diagnosed as having GAD and not social phobia. The cardinal symptoms of GAD commonly overlap with those of social phobia, particularly if the social phobia is more general and not focused on a phobic situation. For example, free-floating anxiety may cause the hands to perspire and may cause a person to be shy in dealing with people in public, and thus many patients with subthreshold social phobic symptoms have, in the authors' opinion, GAD and not generalized social phobia. The distinction between GAD and obsessive-compulsive disorder, acute stress disorder, and posttraumatic stress disorder should not be difficult by definition. At times, however, it may be difficult to distinguish between adjustment disorder with anxious mood from GAD or anxiety not otherwise specified, particularly if the adjustment disorder occurs in a patient with a high level of neuroticism or trait anxiety or type C personality disorder. Table 2 presents features distinguishing GAD from other psychiatric disorders. 2. Lifetime comorbid diagnoses of other anxiety or depression disorders, not active for 1 year or more and not necessitating treatment during that time period, should not effect a diagnosis of current GAD. On the other hand, if concomitant depressive symptoms are present and if these are subthreshold, a diagnosis of GAD should be made, and if these are full threshold, a diagnosis of MDD should be made. 3. If GAD is primary and if no such current comorbid diagnosis, such as other anxiety disorders or MDD, is present, except for minor depression and dysthymia, or if only subthreshold symptoms of other anxiety disorders are present, GAD should be considered primary and treated as GAD; however, patients with concurrent threshold anxiety or mood disorders should be diagnosed according to the definitions of these disorders in the DSM-IV and ICD-10 and treated as such. 4. Somatization disorders are now classified separately from anxiety disorders. Some of these, particularly undifferentiated somatization disorder, may overlap with GAD and be diagnostically difficult to distinguish. The authors believe that, as long as psychic symptoms of anxiety are present and predominant, patients should be given a primary diagnosis of GAD. 5. Two major shifts in the DSM diagnostic criteria for GAD have markedly redefined the definition of this disorder. One shift involves the duration criterion from 1 to 6 months, and the other, the increased emphasis on worry and secondary psychic [table: see text] symptoms accompanied by the elimination of most somatic symptoms. This decision has had the consequence of orphaning a large population of patients suffering from GAD that is more transient and somatic in its focus and who typically present not to psychiatrists but to primary care physicians. Therefore, clinicians should consider using the ICD-10 qualification of illness duration of "several months" to replace the more rigid DSM-IV criterion of 6 months and to move away from the DSM-IV focus on excessive worry as the cardinal symptom of anxiety and demote it to only another important anxiety symptom, similar to free-floating anxiety. One also might consider supplementing this ICD-10 criterion with an increased symptom severity criterion as, for example, a Hamilton Anxiety Scale of 18. Finally, the adjective excessive, not used in the definition of other primary diagnostic criteria, such as depressed mood for MDD, should be omitted (Table 3). 6. One may want to consider the distinction of trait (chronic) from state (acute) anxiety, but whether the presence of some personality characteristics, particularly anxious personality or Cluster C personality and increased neuroticism, as an indicator of trait [table: see text] anxiety is a prerequisite for anxiety disorders; occurs independently of anxiety disorders; or is a vulnerability factor that, in some patients, leads to anxiety symptoms and, in others, does not, is unknown. 7. Symptoms that some clinicians consider cardinal for a diagnosis of GAD, such as extreme worry, obsessive rumination, and somatization, also are present in other disorders, such as MDD. (ABSTRACT TRUNCATED)     

Sertraline in generalized anxiety disorder: efficacy in treating the psychic and somatic anxiety factors

OBJECTIVE: The objective was to study the efficacy of sertraline on symptoms of psychic and somatic anxiety in patients suffering from moderate-to-severe generalized anxiety disorder (GAD). METHOD: Out-patients with DSM-IV GAD were randomized to 12 weeks of double-blind treatment with placebo. The psychic and somatic anxiety factors of the Hamilton Anxiety Rating Scale (HAM-A) and the Quality of Life, Enjoyment, and Satisfaction Questionnaire were analyzed. RESULTS: Treatment with sertraline resulted in significantly greater last observation carried forward (LOCF)-endpoint improvement than placebo on both the HAM-A psychic and somatic anxiety factors. At LOCF-endpoint, all items on the HAM-A psychic factor were more improved on sertraline than placebo, as were three of seven items on the somatic factor. Reduction of secondary depressive symptoms was more correlated with endpoint improvement in quality of life than either psychic- or somatic anxiety. CONCLUSION: Sertraline treatment demonstrated efficacy for both the psychic and somatic anxiety symptoms of GAD.     

Cognitive processes of generalized anxiety disorder in comorbid generalized anxiety disorder and major depressive disorder

This study examines how cognitive variables, which play a central role in the development and maintenance of generalized anxiety disorder (GAD), manifest themselves when GAD and major depressive disorder (MDD) are comorbid. Thirty-two participants were divided into two groups, a group of individuals with a principal diagnosis of comorbid GAD and MDD and a group of people with a principal diagnosis of GAD without MDD. Groups were compared using four cognitive variables: intolerance of uncertainty, poor problem orientation, cognitive avoidance, and beliefs about worry. Our results show that the group of individuals with a principal diagnosis of comorbid GAD and MDD were more intolerant of uncertainty, presented poorer problem orientation, and displayed more cognitive avoidance. The cognitive implications of these results are discussed, and diagnostic criteria are presented to facilitate the differential diagnosis between both groups.     

PET in generalized anxiety disorder

Positron emission tomography (PET) measurements of cerebral glucose use were made in 18 patients with generalized anxiety disorder (GAD) during a passive viewing task off medication, and an active vigilance viewing task before and after medication or placebo treatment. In the passive viewing task, patients with GAD were compared with 15 normal controls. A significant difference in pattern of absolute brain metabolism was found. Patients showed lower absolute metabolic rates in basal ganglia and white matter. Relative metabolism was increased in the left inferior area 17 in the occipital lobe, right posterior temporal lobe, and the right precentral frontal gyrus. Significant left-right asymmetry of the parahippocampal gyri was not found in patients with GAD. An active vigilance task resulted in activation of relative basal ganglia metabolism in patients. Benzodiazepine therapy resulted in decreases in absolute metabolic rates for cortical surface, limbic system, and basal ganglia and was not associated with normalization of patterns of glucose metabolism. Change in anxiety scores was significantly correlated with change in limbic system and basal ganglia for the placebo group. The normal-anxious difference in the basal ganglia and the change seen in this region after benzodiazepine treatment are suggestive of a role in anxiety for this structure.     

Treating generalized anxiety disorder

Generalized anxiety disorder (GAD) is characterized by chronically persistent worry and therefore requires effective long-term treatment. This article reviews the benefits and risks associated with various pharmacologic and psychological therapies to assess their ability to achieve the elimination of GAD symptomatology and restoration of normal function. Psychotherapeutic approaches such as applied relaxation, cognitive therapy, and cognitive-behavioral therapy have all been shown to be effective when used as monotherapies and may be beneficial when used adjunctively. Current effective pharmacotherapies for patients with GAD include anxiolytic benzodiazepines, buspirone, and antidepressants including venlafaxine and paroxetine. Benzodiazepines have long been used to treat anxiety and are particularly appropriate in short-term treatment situations; however, their adverse side-effect profile and their inability to treat depression commonly comorbid with GAD renders them less than ideal in many situations. Buspirone has demonstrated anxiolytic benefits but, like benzodiazepines, shows negligible antidepressant action. Antidepressants like paroxetine and venlafaxine are not only effective antidepressants but also effective anxiolytics, thus implying their special ability to treat GAD and concurrent depression, even over the long-term.     

Differential effects of alprazolam and imipramine in generalized anxiety disorder: somatic versus psychic symptoms

Some researchers have recently suggested that antidepressants may be superior to benzodiazepines in the alleviation of generalized anxiety. In a 6-week, double-blind, parallel-design study with flexible dosage scheduling, the authors compared the effects of alprazolam with those of imipramine in 60 patients who had generalized anxiety disorder. On rating scales that contained both psychic and somatic symptoms, patients in both treatment groups improved to a similar degree after 2 weeks. However, alprazolam was more effective in attenuating somatic symptoms, and imipramine was more effective in attenuating psychic symptoms such as dysphoria and negative anticipatory thinking. The authors' results suggest that, in generalized anxiety, somatic symptoms and hyperarousal selectively respond to drugs acting on the gamma-aminobutyric acid system, whereas psychic symptoms respond to treatments affecting the noradrenergic or serotonergic systems.     

Patients with generalized anxiety disorder and a history of trauma: somatic symptom endorsement

The authors investigated the types and rates of trauma exposure and differences in symptom endorsement in a clinical sample of patients diagnosed with generalized anxiety disorder (GAD). Fifty-eight patients with GAD were assessed using the Structured Clinical Interview (SCID) and Trauma Assessment for Adults. In order to explore the relationship between specific traumatic event(s) and clinical presentation, the presence of somatic symptoms associated with GAD, including muscle tension, autonomic hyperactivity, and vigilance/scanning clusters (using DSM-III-R criteria), were examined. Patients with a history of sexual assault before 18 years (25.9%) endorsed fewer somatic symptoms, specifically fewer motor tension and autonomic GAD symptoms, than patients with other types of trauma. These findings indicate that early exposure to serious trauma, specifically childhood sexual assault, may lead to a different clinical presentation in GAD patients.     

Pooled analysis of venlafaxine XR efficacy on somatic and psychic symptoms of anxiety in patients with generalized anxiety disorder

We evaluated the relative efficacy of venlafaxine XR on the psychic versus somatic symptoms of anxiety in patients with generalized anxiety disorder as determined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Data were pooled and analyzed from 1,841 patients with generalized anxiety disorder who participated in five short-term (8-week) double-blind, multicenter, placebo-controlled studies, two of which had long-term (6-month) extensions. Somatic and psychic anxieties were studied using the Hamilton rating scale for anxiety (HAM-A) factor scores. We examined response rates (> or =50% improvement over baseline severity score) in the overall population and in patients with mainly somatic symptomatology at baseline (somatizers). Venlafaxine XR significantly reduced factor scores for both psychic and somatic HAM-A factors compared with placebo, from the first and second weeks of treatment, respectively. Patients treated with venlafaxine XR had significantly higher rates of response than patients receiving placebo on the psychic (58% vs. 38%, P<.001 at week 8; 66% vs. 35% at week 24, P<.001) and somatic (56% vs. 43%, P<.001 at week 8; 67% vs. 47% at week 24, P<.001) factors of the HAM-A. There was a TreatmentxFactor interaction (P<.027) in response rates: Patients treated with venlafaxine showed similar somatic and psychic anxiety response rates, whereas placebo-treated patients showed higher somatic compared with psychic response rates. Somatizers showed similar rates of response to the total population for the somatic factor of the HAM-A in either treatment group. Patients with generalized anxiety disorder treated with venlafaxine XR showed similar absolute rates of response on somatic and psychic symptoms, but relative to patients treated with placebo, more improvement in psychic than somatic symptoms.     

Comorbidity in generalized anxiety disorder.

GAD has rates of comorbidity that equal or exceed those of other anxiety disorders, and it is one of the most common comorbid conditions with other disorders. Depressive disorders, especially MDD, and other anxiety disorders, especially panic disorder, most commonly co-occur. The pattern of comorbidity is consistent in community and clinical populations and in children and elderly people. Comorbidity is associated with greater impairment, more treatment seeking, and worse outcome among persons with GAD compared with pure GAD. Likewise, patients with panic disorder and MDD who have coexisting GAD tend to have more severe symptoms and less favorable outcome. The relationship between GAD and MDD seems especially close, and data from twin studies suggest that these conditions share a genetic diathesis. Patients with GAD and coexisting conditions respond less well to psychological and pharmacologic treatment, but, for those who do respond, treatment for the primary disorder often also produces improvement in comorbid conditions. Thus, research continues to show that GAD is important as a primary and a comorbid disturbance.     

Treatments for generalized anxiety disorder

Generalized anxiety disorder is characterized by excessive chronic anxiety in association with many somatic symptoms. The disorder has pervasive effects on quality of life, including work, social and educational aspects and requires long-term therapy. Available studies in patients are the Diagnostic and Statistical Manual of Mental Disorders, third edition-revised and fourth edition, which have defined generalized anxiety disorder and demonstrate the efficacy of benzodiazepines, azapirones, some antidepressants and psychotherapy. Benzodiazepines are effective anxiolytics for short-term use but are accompanied by many adverse events. The antidepressants, paroxetine and venlafaxine (Efexor), have demonstrated efficacy in patients with generalized anxiety disorder with mild side-effect profiles. They have the additional benefit of efficacy in depression, which frequently occurs comorbidly in these patients. Long-term efficacy has been shown with venlafaxine in the treatment of this chronic condition, confirming that as in depression, the goal must not just be remission beyond simple symptom resolution but also on to improved functioning and quality of life. Psychotherapy with applied relaxation, cognitive therapy and cognitive behavioral therapy show the most promise in resolving and maintaining treatment gains in the long-term. These approaches may be useful alone or in combination with adjunctive pharmacotherapy to achieve remission. Based on current evidence, the recommended approach to achieving long-term benefits for patients with generalized anxiety disorder is antidepressant therapy with paroxetine or venlafaxine in combination with cognitive behavioral therapy.     

Medical conditions and depressive,anxiety, and somatic symptoms in older adults with and without generalized anxiety disorder

Objective: The objective of this study was to examine medical illness and anxiety, depressive, and somatic symptoms in older medical patients with generalized anxiety disorder (GAD).

Method: A case-control study was designed and conducted in the University of California, San Diego (UCSD) Geriatrics Clinics. A total of fifty-four older medical patients with GAD and 54 matched controls participated.

Measurements: The measurements used for this study include: Brief Symptom Inventory–18, Mini International Neuropsychiatric Interview, and the Anxiety Disorders Interview Schedule.

Results: Older medical patients with GAD reported higher levels of somatic symptoms, anxiety, and depression than other older adults, as well as higher rates of diabetes and gastrointestinal conditions. In a multivariate model that included somatic symptoms, medical conditions, and depressive and anxiety symptoms, anxiety symptoms were the only significant predictors of GAD.

Conclusion: These results suggest first, that older medical patients with GAD do not primarily express distress as somatic symptoms; second, that anxiety symptoms in geriatric patients should not be discounted as a byproduct of medical illness or depression; and third, that older adults with diabetes and gastrointestinal conditions may benefit from screening for anxiety.     

Long-term follow-up of generalized anxiety disorder

The diagnostic stability and long-term prognosis of generalized anxiety disorder (GAD) remain the subjects of considerable controversy. We report the results of an investigation of the long-term outcome of an original sample of 44 subjects who participated in a medication trial. Subjects were reinterviewed approximately 16 months after completion of the study, using structured interviews. Fifty percent continued to fulfill criteria for GAD. Other concurrent axis I diagnoses were as follows: dysthymia, 11%; major depression, 7%; and social phobia, 7%. Regarding axis II comorbidity, subjects with chronic GAD were more likely to fulfill criteria for one or more personality disorders, especially in clusters B and C. In addition, follow-up subjects with GAD and with remitted GAD reported a statistically equivalent number of recent life events, although subjects with chronic GAD were more likely to report significant dissatisfaction with life. The findings indicate that although many subjects with GAD do not follow a chronic course, many others remain symptomatic. The results also suggest that GAD symptoms are not simple the result of a subject's recent negative experiences, and that life satisfaction measures are an accurate reflection of GAD outcome.     

Event-related potentials in panic disorder and generalized anxiety disorder

To evaluate the neurophysiological differences between panic disorder (PD) and generalized anxiety disorder (GAD), 52 patients with PD and 34 with GAD were investigated using event-related potentials (ERP). The ERP were recorded using a tone discrimination task, and peak latencies for N1, P2, N2, and P3 at a Pz electrode site were measured. In addition to analyzing the peak latencies of the ERP, the interpeak latencies (IPL; N1-P2, P2-N2, and N2-P3) were also analyzed. The same analysis was performed in 28 age-matched healthy volunteers (controls). When compared to those of the GAD and control groups, the mean latencies of P2, N2, and P3 were shorter in the PD patients. With regard to the IPL in the PD patients, the N1-P2 IPL was shorter than that in the other groups, and no individual with PD had a longer N1-P2 IPL than 1 SD above the mean of the controls. These findings suggest that certain attention-related processes in the cerebrum that affect ERP data are accelerated in PD patients. These findings demonstrate that it may be useful to neurophysiologically distinguish PD from GAD by measuring ERP peak latencies and IPL.     

Neurobiology of generalized anxiety disorder.

On reviewing the literature on GAD and trying to summarize the various developments in the field of neurobiology of GAD, we see that a range of hypotheses try to explore and integrate the observations found into potentially meaningful theories. Abnormal serotonergic and GABAergic function occur in many patients with GAD. Functional imaging data have shown increased cortical activity and decreased basal ganglia activity in patients with GAD, which reverses with treatment, but it is apparent that no one theory is sufficiently comprehensive to propose a unitary hypothesis for the development of GAD and other anxiety disorders. GAD is a relatively new diagnosable condition, first introduced into the classification system of psychiatric disorders in 1980, and since then has undergone a series of changes in its conceptualization, with some investigators questioning the existence of the condition as a distinct entity. Any inferences that may be drawn from various studies must be guarded, and it is appropriate to compare studies using the same diagnostic criteria. Significant research has been done and may lead to exciting new discoveries in the treatment of anxiety disorders in general and GAD in particular. Gray's model of behavioral inhibition, in which the septohippocampal system acts by assessing stimuli for the presence of danger and, when that is detected, activates the behavioral-inhibition circuit, provides a neuroanatomic conceptualization that has been expanded by preclinical research. Some exciting work has been done on CRF and the concept of development, vulnerability, and kindling and some investigators have contributed to this area of interest. This concept supports the hypothesis that a genetic predisposition, coupled with early stress, in the crucial phases of development may result in a phenotype that is neurobiologically vulnerable to stress and may lower an individual's threshold for developing anxiety or depression on additional stress exposure. The pharmaceutical industry is exploring treatment options using CRF antagonists, and research on other neuropeptides, especially NPY, will be of interest. Research on neurosteroids also may bring the opportunity for pharmacologic treatment approaches. Future research on the startle reflex and on the NMDA and the metabotropic glutamate receptors is important. Future studies of a more homogenous patient population and using more sophisticated techniques, such as molecular genetic strategies and better imaging techniques, may answer some of the outstanding questions.