Journal of Affective Disorders 84 (2005) 133 139 www.elsevier.

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Research report

Dimensional psychopathology of depression: detection of an activation dimension in unipolar depressed outpatients

M. Biondi a,*, A. Picardi b, M. Pasquini a, P. Gaetano a, P. Pancheri a
a

Clinica Psichiatrica III, Dipartimento di Scienze Psichiatriche e Medicina Psicologica, University La Sapienza of Rome, ` , 30-00185 Rome, Italy Viale dellUniversita b Department of Epidemiology and Biostatistics, Italian National Institute of Health, Rome, Italy Received 3 January 2001; accepted 3 April 2002

Abstract Background: Despite the high prevalence of bipolar spectrum disorders, most instruments currently available for the assessment of depression do not explore symptoms of activation such as anger, irritability, aggressiveness, hostility, and psychomotor activation. Methods: Two samples of adults with unipolar depression were studied. They had no comorbid DSM-IV disorder, and they were free from antidepressant drugs. The first sample (n = 380) was assessed with the SVARAD, a validated scale for the rapid assessment of the main psychopathological dimensions. The second sample (n = 143) was assessed with the MMPI-2. Factor analysis was performed on SVARAD items and MMPI-2 clinical scales. Results: In both samples, we obtained a three-factor solution with factors interpreted as a depressive dimension, an anxious dimension, and an activation dimension. The latter dimension appeared to be clinically relevant in 20 27% of patients. Limitations: The presence of a comorbid disorder may have been missed in some cases. Also, some bipolar II patients might have been misdiagnosed as unipolar and included in the study. Further, our findings apply only to a selected psychiatric population, and it should be tested whether they generalize to other settings of care and other countries. Conclusions: Our results suggest that depressive mixed states are not rare even in patients diagnosed as unipolar, and that some unipolar patients might actually be pseudounipolar and belong to the bipolar spectrum. More generally, our findings suggest that some depressed patients have prominent symptoms of activation that can easily go unnoticed using instruments that do not explore such symptoms. Detecting these symptoms has important treatment implications. n 2002 Published by Elsevier B.V.
Keywords: Depression; Assessment instruments; Factor analysis; Dimensional psychopathology; Activation

1. Introduction Current nosography of depression emphasizes a few prototypes of depressive disorder. However, in

* Corresponding author. Tel.: +39-6-445-4765. E-mail address: massimo.biondi@uniroma1.it (M. Biondi). 0165-0327/$ - see front matter n 2002 Published by Elsevier B.V. doi: 10.1016/S0165-0327(02)00103-9

practice, it is common to observe that clinical manifestations vary widely around these prototypes. The diverse combination of a limited number of symptom clusters, also called psychopathological dimensions (Van Praag et al., 1990; Pancheri, 1995; Goldberg, 2000), differs from patient to patient, and gives rise to the wide variety of clinical pictures that can be observed in depressed patients.

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Currently, standardized assessment of depression is imperative, and various instruments are available to this purpose. However, a frequent problem with instruments for the assessment of depressed patients is that most of them do not cover symptoms of activation such as anger, irritability, aggressiveness, hostility, and psychomotor activation. The accurate assessment of this psychopathological dimension in depressed patients is important, because an increasing body of literature suggests that the prevalence of bipolar disorders is much higher than usually believed (Hirschfeld, 2001). Already in the 1980s, authors such as Akiskal (Akiskal, 1983; Akiskal and Mallya, 1987) and Klerman (1981) underscored the need to broaden the concept of bipolarity in order to include various bipolar conditions beyond classic mania. It has also been pointed out that many patients who do not satisfy the DSM-IV or ICD-10 criteria for bipolar II disorder belong to a broad bipolar spectrum which includes depression with brief hypomanic episodes, cyclothymic depression, hypomania induced by antidepressants or other somatic treatments, and hyperthymic depression (Akiskal and Pinto, 1999). Recent epidemiological studies have shown that the lifetime prevalence of bipolar spectrum disorders might be as high as 5% (Akiskal et al., 2000). The relevance of symptoms of activation has been repeatedly emphasized even in cases of unipolar depression (Fava et al., 1986; Fava et al., 1991). This study was designed to assess the importance of this psychopathological dimension in unipolar depressed outpatients free from antidepressant drugs.

2.2. Subjects All newly admitted patients who met the criteria specified below were included in the study: a current diagnosis of DSM-IV axis I depressive disorder, with the exception of diagnoses pertaining to the bipolar spectrum; no comorbid psychiatric diagnosis on DSM-IV axis I or II; no treatment with antidepressant drugs in the preceding 2 months; absence of severe medical illness; and at least 18 years of age. Two independent samples of patients were enrolled in the study. The first sample included 380 patients. Their mean age was 47.4 F 15.4 years, and 61.6% were female. The DSM-IV diagnosis was major depressive disorder in 154 patients (40.5%), dysthymic disorder in 125 (32.9%), depressive disorder not otherwise specified in 56 (14.7%), adjustment disorder with depressed mood in 20 (5.3%), and adjustment disorder with mixed anxiety and depressed mood in 25 (6.6%). The second sample consisted of 143 patients. Their mean age was 43.0 F 15.4 years, and 67.1% were female. The DSM-IV diagnosis was major depressive disorder in 37 patients (25.9%), dysthymic disorder in 60 (42.0%), depressive disorder not otherwise specified in 30 (21.0%), and adjustment disorder with depressed mood in 16 (11.2%). Gender distribution did not differ significantly between the two groups (v2-test), while mean age was higher in the first sample than in the second sample ( P < 0.01, t-test). Diagnostic distribution was also found to be different between the two samples ( P = 0.01, v2-test), with a greater proportion of cases of major depressive disorder in the first sample and of dysthymic disorder in the second sample. 2.3. Study instruments

2. Methods 2.1. Setting The study was performed on two different samples of depressed outpatients, recruited at the Outpatient Center of the 3rd Psychiatric Clinic of the University of Rome between 1997 and 2000. In this Center, patients undergo a careful psychiatric examination of about 90 min duration, and then are diagnosed according to DSM-IV criteria by resident physicians. All diagnoses are confirmed and the patients clinical course supervised by a faculty psychiatrist with more than 20 years of clinical experience.

The first sample was assessed with the Scala Valutazione Rapida Dimensionale (SVARAD) by their physician at the end of the visit. All resident physicians had been instructed in the proper use of this instrument as part of their training in psychiatry. The SVARAD is a 10-item instrument specifically developed for rapid assessment of the main psychopathological dimensions (Pancheri et al., 1999a). All items are rated on a five-point scale ranging from 0 to

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4, with higher scores indicating greater severity. Scores of 1 indicate a severity level at the border between normality and psychopathology, whereas scores of 2 or more attest the presence of clinically relevant symptoms. A validation study has provided evidence of inter-rater reliability, content validity, and criterion validity (Pancheri et al., 1999b). It has also been shown that, thanks to its brevity and ease of use, the SVARAD can be extensively used even in clinical settings where there is only a very limited amount of time allotted to research (Pancheri et al., 2001). The items of the instrument explore the following dimensions: (1) apprehension/fear; (2) sadness/demoralization; (3) rage/aggressiveness; (4) obsessionality; (5) apathy; (6) impulsiveness; (7) reality distortion; (8) thought disorganization; (9) somatic preoccupation/ somatization; (10) activation. Of these, three (items 3, 6, 10) assess symptoms pertaining to the activation dimension, and hence will be described in more detail. The definition of item 3 (rage/aggressiveness) is as follows: irritation, anger, resentment; irritability, litigiousness, hostility; verbal or physical violence. The content of item 6 (impulsiveness) is defined as the tendency to suddenly behave in an inadequate or potentially harmful way, without reflecting enough on the causes or the consequences of ones own actions. Finally, item 10 (activation) is defined as follows: increased motor activity, acceleration of ideas, disinhibition, increased energy and self-confidence, euphoria or irritability. The second sample was assessed with the Minnesota Multiphasic Personality Inventory 2 (MMPI2) (Butcher et al., 1989). Patients completed the inventory in the waiting room of the Outpatient Center, just before being visited. The MMPI-2 is one of the most widely used psychometric instruments. It consists of a long series of statements to which the subject must respond with true or false, and it gives scores on three validity scales and 10 clinical scales, providing information on both personality and psychopathology. Scale scores are computed in the form of standardized T-scores, with scores higher than 70 indicating a considerable departure from the norms. Symptoms of activation are mainly assessed by three clinical scales that will be described in more detail. The scale Ma (hypomania) measures elevated or unstable mood, psychomotor activation, acceleration of ideas. High

scores on the scale Pd (psychopathic deviance) indicate intolerance towards social rules, impulsiveness, sensitivity, aggressiveness. Finally, high scores on the scale Pa (paranoia) indicate vigilance, sensitivity, litigiousness, distrust, suspicion, and possibly paranoid delusions. 2.4. Data analysis Factor analysis was performed on all SVARAD items in the first sample, and on all MMPI-2 clinical scales except scale 5 Mf (masculinity femininity) in the second sample. The number of factors to be extracted was determined according to the scree-plot method (Cattell, 1966). In the first sample, factors were extracted using the principal axis method. Principal component analysis was used in the second sample. All analyses were run under SPSS, version 8.0 for Windows (Norusis, 1998).

3. Results 3.1. First sample Three factors were extracted, explaining a total variance of 33.4%. Orthogonal rotation was performed using the Varimax method. The cutoff for size of loading to be interpreted was set at 0.32. This cutoff corresponds to 10% of common variance between a variable and a factor, and it is widely used in factor analysis (Tabachnick and Fidell, 1996). Factor I was saturated by items such as rage/aggressiveness, impulsiveness, and activation. It was interpreted as an activation dimension. Factor II was clearly a pure depression dimension, with high loadings on items such as sadness/demoralization and apathy. Factor III was defined by items such as apprehension/fear and somatic preoccupation/somatization. It was interpreted as an anxiety dimension. The rotated factor matrix is reported in Table 1, where variables are ordered and grouped by size of loading to facilitate interpretation. Blank spaces indicate loadings of 0.32 or under. The activation dimension appeared to be clinically relevant in a sizable proportion of patients, because 104 patients (27.4%) scored 2 or more on at least one

136 Table 1 Rotated factor solution: SVARAD SVARAD item Impulsiveness Rage/aggressiveness Activation Sadness/demoralization Apathy Apprehension/fear Preoccupation/somatization Reality distortion Obsessionality Variance explained Interpretation

M. Biondi et al. / Journal of Affective Disorders 84 (2005) 133139

Factor I 0.87 0.71 0.33

Factor II

Factor III

0.72 0.66 0.48 0.43

16.1% Activation

11.6% Depression

5.7% Anxiety

of the items with high loadings on the activation dimension. In detail, 98 patients scored 2 or more on item 3 (rage/aggressiveness), 36 on item 6 (impulsiveness), and three on item 10 (activation). 3.2. Second sample Three factors were extracted, accounting for 73.2% of total variance. Orthogonal solution with the Quartimax method was performed. This method minimizes complexity of variables and was preferred to Varimax rotation because there were two complex variables, that is, variables with high loadings on two different factors. With a cutoff for size of loading to be interpreted of 0.32, Factor I was defined by scales Si (social introversion), Pt (psychasthenia), Sc (schizophrenia), and D (depression). It was interpreted
Table 2 Rotated factor solution: MMPI-2 MMPI-2 Scale Si (social introversion) Pt (psychasthenia) Sc (schizophrenia) D (depression) Ma (hypomania) Pa (paranoia) Pd (psychopathic deviance) Hy (hysteria) Hs (hypochondriasis) Variance explained Interpretation Factor I 0.91 0.73 0.70 0.64 0.35

as a depression dimension. Factor II included scales Ma (hypomania), Pa (paranoia), Pd (psychopathic deviance), and Sc (schizophrenia). It was interpreted as an activation dimension. Factor III was saturated by scales Hs (hypochondriasis), Hy (hysteria), and D (depression). It was interpreted as an anxiety dimension. The rotated factor matrix is reported in Table 2, where variables are ordered and grouped by size of loading to facilitate interpretation. Blank spaces indicate loadings of 0.32 or under. Also in this analysis, the activation dimension appeared to be clinically relevant in a substantial proportion of patients. A total of 29 patients (19.9%) scored above 70 on the Ma scale, or on both the Pa and Pd scales. In detail, six patients scored high on the Ma scale, 46 on the Pd scale, and 45 on the Pa scale.

Factor II 0.34 0.56 0.82 0.72 0.59

Factor III 0.33 0.56

0.92 0.75 28.6% Depression 22.4% Activation 22.2% Anxiety

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4. Discussion Overall, our findings seem to indicate that depressive disorders are characterized by three fundamental psychopathological dimensions: a pure depressive dimension, an anxious dimension, and an activation dimension characterized by anger, irritability, aggressiveness, hostility, and psychomotor activation. It is worth noting that these three dimensions emerged consistently in two distinct groups of unipolar depressed patients, using two different instruments. Interestingly, such dimensions correspond to three basic human emotions: sadness, fear, and anger (Plutchik, 1980). A strong point of our study is that, when the assessment took place, patients were free from antidepressant drugs, which may induce hypomania or mania (Wehr and Goodwin, 1987) and precipitate mixed states (Akiskal and Mallya, 1987). Hence, it is unlikely that our detection of an activation dimension in depressed patients is to be ascribed to concurrent pharmacological treatment. However, it should also be acknowledged that our study has some limitations. First, patients were not assessed using a structured diagnostic interview. However, the diagnoses were probably reliable, because they were made after an accurate psychiatric examination and were confirmed by a faculty psychiatrist with more than 20 years of clinical experience who reviewed all clinical charts. Although the presence of a comorbid disorder may have been missed in some cases, this should not have substantially affected the results. Another issue is the possible misdiagnosis of bipolar II patients in our sample. A recent study has found that a sizable proportion of bipolar patients are misdiagnosed as unipolar (Ghaemi et al., 2000). Indeed, apparent unipolar depression might turn out to be bipolar II disorder on careful questioning (Akiskal, 1996), and a study has shown that clinicians specifically trained to recognize bipolar II disorder outperform structured instruments such as the SADS or the SCID in the diagnosis of bipolar II disorder (Dunner and Tay, 1993). We cannot rule out the possibility that some bipolar patients might have been included in our study, because the residents lacked the long training required to be able to identify past hypomanic episodes with high reliability. How-

ever, they had been instructed to ask systematically about a history of mood swings, hypomania or mania in all patients presenting with depression. This should have reduced the risk of misdiagnosis. It should also be recognized that our findings apply only to a selected psychiatric population. It remains to be tested whether they generalize to other settings of care and other countries. Our results need to be replicated in different cultures, using the same instruments or other instruments that include items exploring symptoms of activation. The presence of a depressive dimension and of an anxious dimension was not unexpected. Their cardinal importance in psychiatric patients is well recognized, even in consulting samples in primary care (Goldberg et al., 1987). The most interesting finding of our study is probably the detection of an activation dimension in a sample of unipolar depressive patients. This finding might at first come as a surprise. However, the presence of symptoms of activation in depression had already been emphasized by ancient Greek physicians such as Hippocrates and Aretaeus of Cappadocia, as well as by Kraepelin and Weygandt at the end of the nineteenth century (Angst and Marneros, 2001). Also, psychoanalysts (Abraham, 1948; Freud, 1975) and cognitive psychotherapists (Guidano, 1987) have underscored the importance of aggressive impulses, anger, and rage in depressed patients. Moreover, several psychometric studies have detected an activation dimension in depressed patients who were assessed with psychometric instruments that explore symptoms of activation (Pull et al., 1979; Overall and Hollister, 1980; Fava et al., 1986; Riley et al., 1989; Fava et al., 1991; Moreno et al., 1994). The observation of cases of depression characterized by anger, irritability, aggressiveness, hostility, and psychomotor activation casts some doubts over the classical psychoanalytic aggression-turnedinward model as an universal explanation for depressive behavior (Akiskal, 2000). More likely, the observation of depressed patients with prominent symptoms of activation might be related to factors such as the patients cognitive and emotional organization (Guidano and Liotti, 1983; Arciero and Guidano, 2000), and his or her temperament (Akiskal, 1995). At least partial confirmation of the role

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of temperament has been recently provided (Perugi et al., 1997). Psychobiological disposition might also play a part, especially in cases of loss-induced depression (Biondi and Picardi, 1996). In our study, we used multivariate statistical techniques. However, the activation dimension was not a statistical artifact. Rather, it was found to be clinically relevant in a substantial proportion of patients. Some of them might specifically belong to a distinct group of angry hostile depressed patients (Fava et al., 1991), an hypothesis that has received partial support (Bagby et al., 1997). However, many of these patients with clinically relevant symptoms of activation were probably experiencing a depressive mixed state. Until recently, depressive mixed states have been underrecognized and under-researched. However, in the last decade there has been renewed interest in these psychiatric conditions (Perugi et al., 1997; Koukopoulos and Koukopoulos, 1999) which seem to be much more prevalent than commonly believed, even in patients diagnosed as unipolar (Benazzi and Akiskal, 2001). The results of our study suggest that depressive mixed states are not rare even in patients receiving a diagnosis of unipolar depression, and that a number of unipolar patients might actually be pseudounipolar (Akiskal, 1996) and belong to the bipolar spectrum. More in general, our findings suggest that in a substantial proportion of depressed patients diagnosed as unipolar there are symptoms of activation that can easily go unnoticed using instruments that do not include items dealing with such symptoms. Indeed, the majority of the rating scales for depressive symptomatology do not include items exploring these symptoms. For instance, in a similar sample of unipolar depressed patients, we were not able to detect an activation dimension with a factor analysis of the 17-item Hamilton Depression Rating Scale (Pancheri et al., 2002). The inadequate assessment of symptoms of activation by the majority of rating scales for depression raises some concern, because the proper identification of these symptoms is important and has considerable implications for the choice of treatment. First, in depressive mixed states antidepressants should be used with caution, while the use of mood stabilizers is imperative (Montgomery et al., 2000). Second, symptoms of activation may preferentially respond to treatment with serotonergic anti-

depressants, though further studies are needed to substantiate this recommendation (Fava, 1998). In conclusion, the activation dimension in depressive disorders deserves greater clinical recognition and research. Our study corroborates the opinion that the use of dimensional models of psychopathology in addition to categorical models might be profitable (Van Praag et al., 1990; Costello, 1992; Pancheri, 1995; Angst et al., 2000; Goldberg, 2000). A dimensional assessment might help clinicians to recognize symptoms of activation in their patients presenting with a depressive disorder.

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