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Comprehensive Psychiatry 53 (2012) 1056–1062www.elsevier.com/locate/comppsych

Generalized anxiety disorder: is there any specific symptom?Carlo Faravelli a,⁎, Giovanni Castellinib, Laura Bennib, Andrea Brugneraa, Monica Landib,

Carolina Lo Sauroa, Francesco Pietrinib, Francesco Rotellab, Valdo RiccabaDepartment of Psychology, University of Florence, 50135 Florence, Italy

bPsychiatric Unit, Department of Neuropsychiatric Sciences, Florence University School of Medicine, Florence, Italy

Abstract

Objective: The main aim of the present research was to evaluate the coherence of generalized anxiety disorder (GAD) psychopathologicalpattern, the robustness of its diagnostic criteria, and the clinical utility of considering this disorder as a discrete condition rather than assigningit a dimensional value.Method: The study was designed in a purely naturalistic setting and carried out using a community sample; data from the Sesto FiorentinoStudy were reanalyzed.Results: Of the 105 subjects who satisfied the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria forthe diagnosis of GAD, only 18 (17.1%) had no other comorbid DSM-IV disorder. The most frequent comorbid condition was majordepressive disorder (70.4 %). Only 2 of the GAD diagnostic symptoms (excessive worry and muscle tension) showed a specific associationwith the diagnosis itself, whereas the others, such as feeling wound up, tense, or restless, concentration problems, and fatigue, were found tobe more prevalent in major depressive disorder than in GAD.Conclusion: Our study demonstrates that GAD, as defined by DSM-IV criteria, shows a substantial overlap with other DSM-IV diagnoses(especially with mood disorders) in the general population. Furthermore, GAD symptoms are frequent in all other disorders included in themood/anxiety spectrum. Finally, none of the GAD symptoms, apart from muscle tension, distinguished GAD from patients without GAD.© 2012 Elsevier Inc. All rights reserved.

1. Introduction

Generalized anxiety disorder (GAD) was introduced as aseparate diagnosis in the third edition of the Diagnostic andStatistical Manual of Mental Disorders (DSM) [1]. Since itsintroduction, GAD has been criticized based on thefollowing considerations:

- A clear clinical prototype has not been identified [2].- Comorbidity is extremely frequent; GAD is frequentlycomorbid with major depressive disorder (MDD),panic disorder (PD), social anxiety disorder, andspecific phobia, and it is often associated with chronicpain conditions, medically unexplained somatic symp-toms, and sleep disorders [3,4].

⁎ Corresponding author. Tel.: +39 055 6237811; fax: +39 0556236047.

E-mail address: carlo.faravelli@unifi.it (C. Faravelli).

0010-440X/$ – see front matter © 2012 Elsevier Inc. All rights reserved.doi:10.1016/j.comppsych.2012.04.002

- The specificity of the symptoms of GAD is poor; infact, 4 of the 6 associated physical symptoms of GAD(ie, restlessness, fatigue, difficulty concentrating, sleepdifficulties, obsessive rumination, and somatization)are also part of the diagnostic criteria for MDD [2,5].Conversely, 4 of the symptoms required for MDD (ie,sleep difficulties, psychomotor agitation, fatigue, anddifficulty concentrating) overlap with GAD ones [2].Moreover, symptoms required for the diagnosis ofGAD are also present in other anxiety disordersbecause closer overlaps probably exist between GADand PD or social anxiety disorder [6].

In the subsequent editions of DSM (viz, DSM-III-R andDSM-IV) [7,8], the American Psychiatric Associationchanged substantially the diagnostic criteria of GAD, butnone of the above issues were solved. Reasonably, thecontinuous changes of the diagnostic criteria seem to reflectthe difficulties in defining a stable constellation ofinterrelating symptoms associated to a specific population.

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Therefore, many authors challenged that GAD, as anindependent disorder, may represent the best conceptualiza-tion for organizing and explaining the complexity of aheterogeneous cluster of psychopathologic conditions [2]. Ithas been proposed that GAD should be considered as aprodromal condition, a residual form, a severity marker forother psychiatric disorders (such as MDD), or simply anindicator of general distress rather than a syndrome [9-17].

On the other hand, other authors claim that GAD shouldbe considered as an independent disorder [4,15,16,18-20].

According to the first definition stated by Sydenham in1742, a syndrome consists of several interrelated symptomsshowing a stable characteristic structure and a peculiarprognosis [21]. Patients affected by a specific syndromeshould share a sufficiently pathognomonic (specific) clusterof symptoms that should be more frequent in these subjectscompared with patients having other morbid conditions. Theconcept of discontinuity among different syndromes wasconceptualized by Sneath [22], who introduced the termpoint of rarity, which referred to precise clinical boundariesamong disorders, and was later revised by Kendell [23] andKendell and Jablensky [24], who preferred the concept ofzone of rarity. According to this definition, if a syndromecorresponds to a natural entity, then we should find a naturalboundary or a discontinuity between this condition and itsclinical “neighbors.” Mixed conditions can exist, but theyhave to be less common than the pure forms [25].

According to this construct, a cluster of proposed criteria(eg, symptoms, laboratory markers, exclusion criteria,course, and outcome) [26-28] should be associated with aspecific population of patients to establish the validity of adiagnosis [21,23,29].

Moreover, individuals included into a diagnostic categoryshould share other distinctive features in addition to thoseused to include them in that category.

In line with previous observations, Brown and Barlow[30] have recently considered the problem of sensitivity andspecificity of GAD and have concluded that DSM-IV criteriafor GAD do not differentiate a patient with GAD from apatient with clinical depression [31] because the exclusion ofthe autonomic symptoms from DSM-IV criteria for GADmight obfuscate the boundary between MDD and GAD. Infact, muscle tension appeared to be uniquely related toworry, whereas difficulty concentrating appeared to have avery strong relationship with depression [2].

Moving from these concepts, the main aim of the presentresearch was to evaluate the coherence of GAD psychopath-ological pattern, the robustness of its diagnostic criteria, andthe clinical utility of considering this disorder as a discretecondition rather than assigning it a dimensional value. Theapproach we adopted resembled similar researches in thisfield, attempting to corroborate the validity of the constructsof different diagnoses, such as major depression [32].

The study was designed in a purely naturalistic setting,using a community sample (the Sesto Fiorentino Study,Faravelli et al [33]) with a “bottom-up” design in which

symptoms were assessed by clinical psychiatrists accordingwith a nosographic system of reference, unlike most largecommunity surveys.

2. Methods

Data from the Sesto Fiorentino Study, which has beendescribed in detail elsewhere [33], were reanalyzed. Briefly,a representative sample of 2500 subjects aged older than14 years and living in the municipality of Sesto Fiorentino(close to Florence, central Italy) has been interviewed bytheir own general practitioners. A total of 609 subjects whoresulted positive at a first screening with the Mini-International Neuropsychiatric Interview [34] as well as asubsample of the cases who resulted negative werereassessed by interviewers with clinical experience bymeans of the Florence Psychiatric Interview (FPI) [35].The FPI is a fully validated instrument that combines severalwell-established and validated assessment procedures (ratingscales and semistructured interviews) into a single interview,aimed at exploring the psychopathology and its connectedfactors in nonclinical samples. Because the FPI is a typicalbottom-up procedure where symptoms are explored regard-less of any predefined diagnostic system, the study of thenatural relationship of symptoms and/or sets of symptoms iswell suited. Because all questions of the Structured ClinicalInterview for DSM-IV [36] are included in the FPI, the DSM-IV diagnoses generated by computerized diagnostic algo-rithms, using these data, were totally coherent to thosederived by the Structured Clinical Interview for DSM-IV[33]. The FPI is primarily centered on the episode:first, itattempts to isolate a period of illness, and then, it explores theaspects of that episode. The FPI was built without relying onany predefined classifications, and one of its goals is tocollect ample sets of data to test, verify, and hypothesizedifferent proposal for classifying cases.

A total of 121 symptoms, including most of those listed inthe DSM-IV, are explored independently of their diagnosticvalue. All subjects were asked to provide written, informedconsent, and the Sesto Fiorentino Study was approved by thelocal ethical committee. For the present study, all patientswho reported at least 1 of the symptoms of GAD during thelast 2 years were selected: (1) feeling wound up, tense, orrestless; (2) easily becoming fatigued; (3) difficulty concen-trating; (4) irritability; (5) muscle tension; and (6) sleepdisturbance (difficulty falling or staying asleep or restlessand unsatisfying sleep). The final sample was composed by375 subjects (201 women, or 53.6%) with a mean age of47.2 ± 14.7 years (years ± SD).

3. Results

Of the 375 subjects considered, 105 met the DSM-IVdiagnosis of GAD. The other diagnoses were MDD (n =130), dysthymia (n = 24), depression not otherwise specified

Table 1Generalized anxiety disorder symptoms and different DSM-IV diagnoses (anxiety and mood disorders)

GAD(n = 105)

PD(n = 32)

Social phobia(n = 55)

Anxiety NOS(n = 126)

Major depression(n = 130)

Dysthymia(n = 24)

Depression NOS(n = 131)

n (%) n (%) n (%) n (%) n (%) n (%) n (%)

At least 1 GAD symptom 105 (100)⁎⁎ 27 (84.4)⁎⁎ 48 (87.3)⁎⁎ 126 (100)⁎⁎ 129 (99.2)⁎⁎ 22 (91.7) 128 (97.7)Sleep disturbance 82 (78.1) 23 (71.9) 34 (61.8)⁎ 91 (72.2) 117 (90.0)⁎⁎ 15 (62.5) 96 (73.3)Feeling wound up, tense, or restless 38 (36.2) 10 (31.3) 19 (34.5) 36 (28.6) 54 (41.5)⁎⁎ 2 (8.3)⁎ 37 (28.2)Concentration problems 59 (56.2) 12 (37.5)⁎ 26 (47.3) 62 (49.2) 107 (82.7)⁎⁎ 2 (8.3)⁎⁎ 75 (57.3)Easily becoming fatigued or worn-out 55 (52.4) 10 (31.3)⁎⁎ 24 (43.6) 60 (47.6) 101 (77.7)⁎⁎ 6 (25)⁎⁎ 71 (54.2)Irritability 15 (14.3) 1 (3.1) 2 (3.6)⁎ 15 (11.9) 18 (13.8) – 13 (9.9)Generalized anxiety 105 (100)⁎⁎ 19 (59.4) 37 (67.3) 126 (100)⁎⁎ 72 (55.4) 19 (79.2) 76 (58)Significanttension in muscles 82 (78.1)⁎⁎ 14 (43.8) 29 (52.7)⁎ 68 (54)⁎⁎ 46 (35.4) 14 (58.3) 47 (35.9)

⁎ P b .05.⁎⁎ P b .01.

0,111000

Restless and Unsatisfying Sleep1.29 [0.75-2.21]

Significant tension in muscles10.18 [5.95-17.42]

Irritability1.33 [0.68-2.59]

Concentration problems1.05 [0.67-1.66]

Easily becoming fatigued or worn-out 0.96 [0.61-1.51]

Feeling wound-up, tense, or restless1,56 [0.96-2.52]

Generalized Anxiety1.82 [1.62-2.04]

igure. Associations of DSM-IV GAD symptoms and GAD diagnosis. Note:dds ratios reported with log scale express the associations of GADymptoms with different diagnostic conditions.

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(NOS) (n = 131), PD (n = 32), social phobia (n = 55), anxietyNOS (n = 126), obsessive-compulsive disorder (n = 33),bipolar disorder (n = 4), nonaffective psychosis (n = 7),somatoform disorder (n = 37), eating disorder (n = 5), andimpulsive disorder (n = 17). The association of more than1 diagnosis in the same case was common, and the meannumber of DSM-IV diagnosis was 1.88 per person.

Of the 105 cases that satisfied the DSM-IV diagnosis forGAD, only 18 (17.1%) had the disorder in the absence of othercomorbid DSM-IV diagnoses. The most frequent comorbidcondition was MDD (n = 74, or 70.4 %). In particular, 38subjects (51.3%) reported an Major Depressive Episode;24 (32.4%), MDD NOS; and 12 (16.2%), dysthymia.

Compared with patients without GAD, patients withGAD were older (mean age ± SD [years], 40.88 ± 15.04 vs35.21 ± 15.4; t = 3.21; P b .01) and did not show significantdifferences in terms of sex, education, marital status, numberof children, family history for any psychiatric disorder, andsocial functioning (data not shown).

3.1. Symptom analyses

The prevalence of DSM-IV diagnostic symptoms of GADin the different diagnostic subgroups is reported in Table 1.Two symptoms seem to have a specific association withGAD: excessive worry and muscle tension. Other symptomsincluded in the diagnostic requirements for GAD, such asfeeling wound up, tense, or restless, concentration problems,and fatigue, are more prevalent in MDD than in GAD. Theseobservations were confirmed by the analyses that tested thespecific association (expressed as odds ratio [OR]) of GADsymptoms with GAD diagnosis (Figure); only muscletension was associated with GAD. Furthermore, it is ofnote that muscle tension was the only symptom that wasassessed, specifically in GAD.

Finally, a stepwise logistic regression confirmed theprevious observation, even when considering the reciprocaleffects of all symptoms (Table 2). According to thebackward method, all the GAD symptoms were includedin the initial model as potential predictors of GAD

diagnosis. At each of the 6 performed steps, the predictorsthat contributed the least were removed from the modeluntil only muscle tension showed a significant effect in themodel. Given the high rates of comorbidity, the same casecould have been considered under different labels (typical-

1

Fos

Table 2How the GAD symptoms predict the GAD diagnosis: stepwise logistic regression

Wald Significance OR 95.0% CI for OR

Lower Upper

Step 1 Feeling wound up, tense, or restless b.01 .95 1.01 0.57 1.81Easily becoming fatigued or worn-out .33 .56 1.18 0.66 2.11Concentration problems .46 .49 1.23 0.67 2.24Irritability .08 .76 1.12 0.51 2.48Significant tension in muscles 70.08 b.01 10.84 6.20 18.95Restless and unsatisfying sleep .90 .34 1.36 0.72 2.56

Step 2 Easily becoming fatigued or worn-out .33 .56 1.18 0.66 2.10Concentration problems .49 .48 1.23 0.68 2.23Irritability .09 .75 1.13 0.52 2.46Significanttension in muscles 72.08 b.01 10.87 6.27 18.87Restless and unsatisfying sleep .92 .33 1.36 0.72 2.55

Step 3 Easily becoming fatigued or worn-out .32 .57 1.18 0.66 2.10Concentration problems .48 .48 1.23 0.68 2.23Significant tension in muscles 72.35 b.01 10.92 6.29 18.94Restless and unsatisfying sleep 1.03 .30 1.38 0.74 2.57

Step 4 Concentration problems 1.05 .30 1.32 0.77 2.27Significant tension in muscles 72.51 b.01 10.73 6.21 18.54Restless and unsatisfying sleep 1.00 .31 1.37 0.73 2.55

Step 5 Concentration problems 1.675 .19 1.41 0.83 2.38Significant tension in muscles 72.472 b.01 10.67 6.18 18.40

Step 6 Significant tension in muscles 71.869 b.01 10.18 5.95 17.42

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ly, GAD and MDD), thus obscuring the differences.Although the logistic regression analysis takes into accountthis kind of bias, we repeated the above analysis,comparing the cases with GAD with the subjects who didnot meet such a diagnosis. Therefore, stepwise logisticregression was repeated, also considering GAD withoutcomorbidity as dependent variable, thus excluding GADcomorbid with other diagnosis from the analysis. Accord-ing to this analysis, none of the considered symptoms wasfound to be significantly associated with GAD withoutcomorbid diagnoses condition.

4. Discussion

The present study attempted to estimate the occurrence ofGAD and its DSM-IV symptoms in the general population.The originality of the approach described in this study was toinvestigate symptoms of GAD regardless of the diagnosis ofGAD. According to the hypothesis that GAD represents adiscrete syndrome, our expectations were as follows:

- all the symptoms (diagnostic criteria) of GAD shouldbe significantly more frequent in those patients whomeet the diagnosis of GAD compared with thoseaffected by all the other psychiatric conditions;

- the occurrence of GAD comorbid with some othercondition should not be the most common presentationof the disorder;

- there should be distinctive features associated with thedisorder, except for the diagnostic criteria, comparedwith other psychiatric conditions.

However, three main findings were obtained from thisstudy. First, GAD is usually associated with other diagnoses(especially with mood disorders), its occurrence alone beingrelatively rare. Second, the symptoms of GAD are frequentin all the disorders included in the mood/anxiety spectrum.Finally, none of DSM-IV symptoms required for GAD, withthe exception of muscle tension, is specifically associatedwith this disorder.

Eighty-three percent of the patients with a current GADdiagnosis during the last 2 years reported at least 1 or moreother concurrent disorders. Generalized anxiety disorderwith comorbid condition was present only in 17% of thecases. These findings are consistent with previous epidemi-ologic investigations reporting similar rates of comorbidity[3,4,37-39], and they can be contextualized in the ongoingwider debate regarding the high comorbidity rate of anxietyand mood disorders [40-43]. It has been suggested that thephenomenon of comorbidity is partially related to the use ofa standardized diagnostic interview, which identifies severalclinical aspects that, in the past, remained unnoticed after theprincipal diagnosis was made [44]. Alternatively, it ispossible that comorbidity is a by-product of DSM, ThirdEdition, and DSM-IV classification system [30,44]; distortedrates of diagnostic comorbidity can be due to overlappingcriteria sets and diagnostic decision rules, and the frequentco-occurrence of mental disorders (eg, MDD and GAD) maybe considered an evidence against the idea that thesedisorders represent discrete disease entities. A third inter-pretation of the phenomenon of “psychiatric comorbidity” isthat psychopathology consists of discrete entities notappropriately reflected by current diagnostic categories[44]. All these hypotheses are in line with the concept that

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the nature of psychopathology is intrinsically composite andchangeable, and what is currently conceptualized as the co-occurrence of multiple disorders could be better reformulatedas the complexity of many psychiatric conditions, whichcannot be explained by a categorical model [44,45].Although the problem of the high rates of GAD comorbidityhas been widely investigated, most parts of the availableliterature approach this issue from a categorical point ofview. In this study, we considered the occurrence of thesymptoms of GAD irrespective of the diagnoses, accordingto a transnosographic perspective [14,30,46]. There areadvantages in exploring symptoms independently of thediagnosis. Because there is no prepostulated paradigm, itallows the analysis of different diagnostic systems and thecomparison of qualitative vs quantitative aspects of adisorder. On the other hand, a potential limitation of thebottom-up procedure of the FPI, exploring symptomsregardless of any predefined diagnostic system, is that itcould increase the diagnostic overlap because the symptomsare not considered within a specific context. Nevertheless,the use of clinical interviewers and the semistructured natureof the FPI can reduce the impact of this limitation.

If GAD is a discrete entity, the expectation is that itsdiagnostic descriptors are more common in those patientswho have the disorder, thus representing useful elements indistinguishing GAD from other affective disorders. However,our results show that GAD symptoms are frequent in almostall the diagnoses taken into account, whereas sleep distur-bances were totally unspecific, as reported previously [14],and manifestations such as fatigue and difficulty in concen-trating prevailed in MDD. Muscle tension was the onlysymptom actually associated with a higher risk of havingGAD. This finding reproduces what was already reported byJoorman and Stöber a few years ago [47]. Some symptomsconsidered are very broad and general and can be experiencedin a range of physical and mental conditions, and somesymptoms may be qualitatively different if they areexperienced in association with feelings of worry and muscletension. For this reason, stepwise logistic regression analyseswere adopted to consider the reciprocal effects of allsymptoms. Given the high rate of GAD in comorbidcondition, we performed logistic regression analyses, com-paring all patients with GAD (including those with GADalone and with GAD with comorbid conditions) with subjectswho did not presented GAD diagnosis. We did not find anyassociation of GAD symptoms with the diagnosis.

Overall, these results suggest that the DSM-IV pattern ofsymptoms proposed for GAD is not specific for thiscondition. These findings challenge the real validity of theDSM-IV definition of GAD because DSM-IV criteria forGAD seem to be inappropriate for identifying clearpathognomonic features for this disorder and in guidingclinicians through the differential diagnosis between GADand other psychiatric conditions.

The high rate of GAD comorbidity could be due to theuncertain boundaries between this condition and other

affective disorders, as previously suggested [30,41,42,48].Based on our results, GAD appears as a nonspecificcondition that is rarely present alone and is frequentlyassociated with mood disorders. It has been suggested thatGAD should be reclassified as a mood disorder because of itshigh comorbidity with MDD. Researches in line with ourobservations [49-51,42] concluded that both GAD and MDDshare a single general “distress” factor [40,49,52,53], whichis also related to dysthymia and social phobia [42]. A singlecommon factor between anxiety and mood disorders wasalso included in the concept of the general neuroticsyndrome by Krueger et al [54], whereas it has beensuggested that anxiety and depressive disorders are variantsof a single condition [55-58]. Alternatively, this overlap hasbeen interpreted as an artifact of the current diagnosticsystem [5,44,59,60].

Based on these observations, ambitious proposals havebeen suggested to overcome the shortcomings of the DSM-IV classification system, placing emphasis on dimensionscorresponding to broader biologically and environmentallybased constructs of temperament and personality (eg,neuroticism/negative affectivity [61]). These hypothesesfollow from the theories and evidence that the observedoverlap in families of disorders (eg, comorbidity andsymptom overlap in anxiety and mood disorders) is becausethese conditions emerge from shared biologic/genetic andpsychosocial diatheses (eg, Mineka et al [14], Clark [62], andKendler et al [63]). Under this framework, the DSMdisorders represent different manifestations of core vulner-abilities, and such variability stems from the influence ofother more specific etiologic agents (eg, environmentallybased psychological vulnerabilities or other genetic orbiological influences; cf. [62,64]). According to theseimplications, it appears as a common mistake to treat DSMdisorders as they were natural entities, according to thepremature nosologization concept of van Praag [65].Clinicians should rethink their approach to mental disorders,considering them as clusters. Therefore, they should betreated using broad treatment protocols that target a range ofdisorders and different associations of symptoms.

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