Clinical Neuropsychiatry (2005) 2, 3, 149-165
COGNITIVE ASSESSMENT OF DEPRESSION: A NEW TEST FOR MOOD DISORDERS Francesco Benedetti, Barbara Barbini, Mara Cigala Fulgosi, Adriana Pontiggia, Cristina Colombo, Enrico Smeraldi
Summary Object: Current methods of assessment of major depression are biased by consistent discordancies between self- and observer-ratings of depression. Cognitive distortions are a regular core symptom of major depression, and are associated with the development of hopelessness and suicidality. Method: Based on previous studies showing that patients who were diagnosed with major depressive disorders denied positive statements and endorsed more negative statements about themselves than normal subjects, we developed a computerized test with two tasks: a self-description task during which subjects were asked to self-attribute or refuse positive and negative adjectives, and a recognition memory task during which subjects were asked to recognize the same adjectives randomly mixed with semantically similar others. We tested 294 normal subjects and 247 patients affected by a major depressive episode. Results: In normal subjects frequencies and latencies of both self-attribution and recognition of positive stimuli were enhanced in respect to negative stimuli, while in depressed patients negative self-scheme elements predominated in selfdescription, and information processing was slower for positive and negative elements. Single output measures were combined in a single score (named depressive differential) based on canonical coefficients derived from discriminant function analysis, which could correctly classify 92% of patients and 98% of controls. ROC analysis of depressive differential scores showed AUC=0.987, and two-graphs ROC analysis estimated sensitivity and specificity at 0.955 for the optimal cutoff value. Internal and external validity testing showed high correlations both with commonly used psychiatric rating scales and with instruments specifically developed to assess depressive cognitive style. Test-retest reliability was high. Conclusions: Further studies will define the diagnostic power in respect to depressive syndromes pertaining to diagnoses other than mood disorders, and will precise if, and when, the observed distortions normalize during antidepressant treatment. Key Words: Major depression Diagnosis Neuropsychological assessment Declaration of interest: The authors of this paper do not have any commercial association that might pose a conflict of interest in connection with this manuscript Francesco Benedetti, Barbara Barbini, Mara Cigala Fulgosi, Adriana Pontiggia, Cristina Colombo, Enrico Smeraldi Istituto Scientifico Ospedale San Raffaele Turro, Department of Neuropsychiatric Sciences, Università Vita - Salute, Milano Corresponding Author Dr. F. Benedetti, Istituto Scientifico Ospedale San Raffaele Turro, Department of Neuropsychiatric Sciences, Via Stamira dAncona 20, 20127 Milano, Italy. Tel +39/2/26433229 - Fax +39/2/26433265 - E-mail
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Introduction Dysfunctional cognitions are a regular core symptom of major depression, and include self-deprecatory and self-accusatory thoughts (e.g., Goodwin & Jamison 1990). Following the Becks cognitive model of depression, latent negative self schemas play a major role in predisposing individuals toward depression (e.g., Beck 1967). Independently from the possible pathophysiological value of cognitive distortions in depression, several clinical studies showed that marked depressive dysfunctional cognitions predict a longer duration of depressive episodes (e.g., Williams et al. 1990), depressive chronicity (e.g. Bothwell & Scott 1997) and the development of hopelessness (e.g. Cannon et al. 1999), which has been shown to be associated with suicidal behavior (e.g., Beck et al. 1983, Whisman et al. 1995).
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The assessment of negative depressive cognitions raises several methodological issues. Symptoms of mood and cognition often overlap in item content of observer rating scales, and specific self-rating scales have been developed to measure depressive attitudes and beliefs (e.g., Rosenberg 1965, Weissman 1979, Fennell & Campbell 1984). However, it is a common clinical observation that some patients report high symptomatological severity and marked negative cognitions (with low self esteem, pessimism, and suicidal thoughts) but appear to have modest levels of depressive symptoms, while others tend to minimize the intensity of depressive symptomatology and the degree of their cognitive distortion. This leads to consistent discordancies between self- and observer-ratings of depression, which are influenced by clinical features (with anxious and atypical depressives which tend to overestimate symptomatological intensity), personal-
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ity traits (with neuroticism leading to higher perceived severity), demographic variables (with lower education and older age correlating with lower self-ratings of depression) (e.g., Sayer et al. 1993, Enns et al. 2000). These variables showed a greater ability to explain discrepancies between self- and observer-ratings of psychological compared to somatic symptoms of depression. Self-report instruments dealing with cognitive depressive symptoms may then be subject to biases with regard to clinical and demographic characteristics of patients. As a matter of fact, clinical psychiatric trials usually disregard these instruments and rely on selfand observer-ratings with common rating scales: the most widely used of which were developed in the early 1960s and do not specifically focus on cognitive depressive distortions (e.g., Hamilton Depression Rating Scale, Hamilton 1960; Beck Depression Inventory, Beck et al. 1961; Zung Self-Rating Depression Scale, Zung 1965). A number of cognitive therapy researches studied negative self-concept attributions in depressed patients (see review in Clark et al. 1999). A recent study (Baving et al. 1997) on a small sample of depressed patients raised the possibility to develop a rapid and objective method of evaluation of negative cognitions toward the self associated with a major depressive episode. When rating the self-descriptiveness of positive and negative adjectives, patients affected by a major depressive episode rated as self descriptive significantly more negative and less positive words than matched controls; moreover, the speed of information processing was lower for positive than for negative elements in depressed patients, while the opposite was true in controls. A similar pattern was found in a subsequent word recognition task. These results were in agreement with previous studies showing the presence of selective biases in information processing of depressed patients, both in respect to recognition memory for verbal stimuli (e.g., Dunbar & Lishman 1984) and in respect to non verbal stimuli (e.g., Geerts & Bouhuys 1998), and with empirical studies of mood-congruent biases in information processing of patients affected by major depression, which reported biases in evaluative processes, social judgements, decision-making, attention and memory (see review in Murphy and Sahakian 2001). A more recent study suggested a neural basis of mood-congruent processing biases in depression, using a go-no go task where depressed patients showed a facilitation of performance when responding to stimuli with a negative emotional tone (Murphy et al. 1999). Functional magnetic resonance imaging during performance to the emotional go-no go task showed that depressed patients, in respect to control subjects, showed elevated neural responses specific to sad targets in rostral anterior cingulate extending to anterior medial prefrontal cortex, and, unlike controls, showed attenuated responses to emotional relative to neutral stimuli in ventral cingulate and posterior orbitofrontal cortices (Elliott et al. 2002). Based on all these data, we hypothesized that selective changes in patterns of attribution and in information processing of positive and negative stimuli could be measured as an index of the cognitive distortion linked to major depression. In particular, reaction times (and the ratio bewteen reaction times for positive and
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negative stimuli) could provide an objective index of depressive distortions which should not be subject to patients and cliniciansminimization or overestimation biases. The purpose of the present study was to develop a new and reliable method of assessment of cognitive distortion in depression based on this experimental paradigm, with the aim to develop a psychopathological instrument based on neuropsychological performance, and not on self- or clinician-ratings. The study is divided in two parts. The first part deals with test development and evaluation of possible diagnostic value: assessment of the differences in response between normal and depressed patients, definition and correction of the influences of demographic variables on response, definition of a cutoff for normal response, evaluation of test structure, evaluation of test sensitivity and specificity. The second part deals with test validation: test-retest reliability and external and internal validity.
1. Test development 1.1 Method 1.1.1 Subjects The studied sample included 294 normal subjects and 183 patients affected by a major depressive episode. Normal subjects were recruited by advertisement among workers of four factories in northern and central Italy, and among retired people participating to third-age community programs in Milan. Study design was fully explained both to each participant and to working organizations representatives. 366 subjects answered the advertisement and were screened before study inclusion. Each subject was interviewed by a trained psychiatrist, and 72 subjects were excluded because of history of mental illness or because of current use of psychotropics or drug or alcohol abuse. 294 subjects were included in the study. One-hundred eighty-three consecutively admitted inpatients affected by a major depressive episode (DSM IV criteria) were recruited. Patients were studied short after hospital admission, and before starting antidepressant therapies; the only allowed psychotropic medications were flurazepam 15 mg or lormetazepam 2 mg as hypnotics, and mood stabilizers if already prescribed as long-term treatments. Axis I diagnosis was Bipolar Disorder, depressed (n=73), or Major Depressive Disorder, recurrent (n=97) or single episode (n=13). The agreement of two independent raters (chosen among the authors of the study) was required to define the diagnosis. Inclusion criteria were: absence of other diagnoses on Axis I; absence of mental retardation on Axis II; absence of history of epilepsy, major medical and neurological disorders; no treatment with long-acting neuroleptic drugs in the last month before admission; absence of a history of drug or alcohol dependency or abuse within the last six months. Intensity of depression was rated on Hamilton Depression Rating Scale (HDRS).
Clinical Neuropsychiatry (2005), 2, 3
A New Test for Mood Disorders
The investigation was carried out in accordance with the Declaration of Helsinki; an informed consent was obtained by each participant after the procedures had been fully explained. 1.1.2 Test description In the study by Baving et al. (1997) four parallel word lists were assembled, each consisting of 100 adjectives descriptive of personality characteristics, 50 positive and 50 negative. In the present study the same adjective lists were translated from german into italian. To ensure easy comprehension for the italian population, the lists were submitted to a sample of 30 normal subjects with low education (5 years at school) who rated familiarity with the words on a 5 points scale. Unfamiliar words were replaced with semantically similar adjectives. In a self descriptiveness task, each subject was presented a word list with adjectives in random order and had to answer the question Do these words apply to you? by pressing the P (yes) or Q (no) keys on a common computer keyboard. Recorded variables were frequencies of self-attributed positive or negative adjectives and reaction times. In a subsequent word recognition task, each subject was presented with the previously seen adjectives randomly mixed with one hundred never seen others, and had to answer the question Do you recognize these words as being part of the first list? by pressing the same keys. Recorded variables were frequencies of recognition of positive and negative adjectives and reaction times. 1.1.3 Test administration Test administration was computerized using a commercially available software (SuperLab Pro v1.05, 1998). Stimuli were presented as words centered in a 15 inches color computer monitor, white (character style arial, size 90) on a blue background. Testing sessions took place in the morning. Administration of the test was preceded by a short training session, with ten words which were not part of the lists. Between the two tasks there was an interval of some 30 minutes, during which distractor tasks (mazes) were performed. 1.1.4 Data analysis Positive adjectives rated as self-descriptive and negative adjectives rated as non self-descriptive were defined positive self-scheme elements; on the contrary, negative self-attributed and positive refused adjectives were defined as negative self-scheme elements (Baving et al. 1997). Unless otherwise indicated, statistical analyses were performed with a commercially available software (Statistica 5.5, 2000). Frequencies of attribution and relative latencies were compared with Students t test among and within diagnostic groups. The effect of gender was evaluated with Students t test. Correlation coefficients were used to examine the association between age and education and test results; linear regression analyses were then used to determine and correct
Clinical Neuropsychiatry (2005), 2, 3
the effect of these variables on test responses. Construct validity was evaluated with principal component analysis. To evaluate the usefulness of the test as a diagnostic tool for depression, a forwardstepwise discriminant function analysis with diagnosis as independent variable and test output as dependent variable was performed. Distribution of test scores was evaluated with Komolgorov-Smirnov test of normality, and distribution fitting was performed with a modified version of ALMINI/GEMINI (a general purpose routine used to maximize the likelihood of each model subject to nonlinear constraints, using a Newton-Rapheson/FletcherPowell approach) (Lalouel 1979). Given the nonbinary nature of test outputs, the discriminatory power was estimated with Receiver Operating Characteristics (ROC) and two-graphs ROC analyses, which were performed using Computational Methods for Diagnostic Tests (CMDT; Greiner and Briesofsky 1999).
1.2 Results Clinical and demographic characteristics of the sample are resumed in Table 1. 1.2.1 Self-description task Mean frequencies and latencies of attribution of positive and negative self scheme elements, and analysis of differences among diagnostic groups, are shown in Table 2. Controls and patients showed significant differences in all output values. Within group comparisons showed that normal subjects showed higher frequencies (t=60.35, p
