Original articlePrincipal components of the beck depression inventory and regional cerebral metabolism in unipolar and bipolar depression
Introduction
Phenomenological and neurobiological heterogeneity in depression have important implications for understanding and treating affective disorders. Differences in symptomology and neurobiology have been reported between unipolar (UP) and bipolar (BP) depression and for melancholic, endogenomorphic (Klein 1974; Young et al 1986), and atypical depressive subtypes (Nierenberg et al 1998). Identifying depressive subtype differences has become increasingly important as their treatments diverge (Klein 1974; Fawcett et al 1983a; Liebowitz et al 1984a; Liebowitz et al 1984b; Clark et al 1984), especially for UP versus BP depression (Post et al 1987; Post 1995; Sachs et al 2000).
In this study, we determined clustering of depressive symptoms in a combined group of medication-free UP and BP patients using Principle Components Analysis (PCA) of the Beck Depression Inventory (BDI). We then compared these symptom clusters and their interrelationships between UPs and BPs, and examined the relationships of the clusters to regional cerebral metabolism for glucose (rCMRglu) measured by positron emission tomography (PET).
Principal components and other factor analyses of the BDI have been reported for many different psychiatric and nonpsychiatric populations (Beck and Beamesderfer 1974; Beck et al 1988; Steer et al 1986; Startup et al 1992). The vast majority of studies have been in populations with mixed psychiatric diagnoses (Pichot and Lemperiere 1964; Cropley and Weckowicz 1966; Weckowicz et al 1967; Beck and Lester 1973; Lester and Beck 1977; Welch and Ellis 1991; Tanaka and Huba 1984) and in substance abuse patients (Steer et al 1977; Steer et al 1982; Shaw et al 1979; Reynolds and Gould 1981; Clark et al 1985; Louks et al 1989; Haviland et al 1991). There have been only five reports of BDI factor analysis in populations solely composed of primary affective disorder patients, with three reports in UP depression (Brown et al 1995; Startup et al 1992; Steer et al 1987), and two reports in mixed affective populations (Faravelli et al 1986; Steer et al 1989). Patients were antidepressant-free in only one study (Brown et al 1995). All five reports used PCA with orthogonal rotation, a technique we will also use here. No reports specifically examined BPs or compared BPs to UPs.
Abnormal regional CMRglu and cerebral blood flow (CBF) in frontal cortex and paralimbic regions have been found in affective disorder patients compared with healthy controls Dougherty and Rauch 1997, Drevets 1998. Additionally, severity of overall depressive symptoms has been correlated with rCMRglu/CBF in certain brain regions, most consistently in frontal or dorsolateral frontal cortex Buchsbaum et al 1986, Schlegel et al 1989, Baxter et al 1989, Upadhyaya et al 1990, Austin et al 1992, Drevets et al 1992, Yazici et al 1992, Bonne et al 1996, Iidaka et al 1997, Ketter et al 1996.
Specific symptoms or symptom clusters have also been correlated with rCMRglu/CBF in depressed patients, reflecting anergic and anxious depression (Ebmeier et al 1997), psychomotor slowing Mayberg et al 1994, Austin et al 1992, poverty of speech (Dolan et al 1993), anxiety and somatic symptoms (Philpot et al 1993), cognitive impairment Austin et al 1992, Philpot et al 1993, Bench et al 1992, Bench et al 1993, Dolan et al 1992, Dolan et al 1994, and psychotic symptoms Buchsbaum et al 1986, Philpot et al 1993. These studies included all or almost all unipolar patients only. The only study that correlated depressive symptoms with absolute (vs. normalized) regional CBF or CMRglu was a two-dimensional scintigram study (Schlegel et al 1989). One study correlated PCA clustered symptoms with normalized regional CBF determined by SPECT (Bench et al 1993); however, they derived components by PCA of 11 “variables” that had been constructed by a priori grouping of items from the Schedule for Schizophrenia and Affective Disorders and Mini-Mental Status Examination.
In the current study, we derived BDI principal components in a combined group of medication-free UP and BP patients, each with primary affective disorder. We separately compared relationships between BDI components and between individual BDI items for UPs and BPs. We then obtained correlative topographies for BDI components and cerebral metabolism, to uncover neural substrates of these depressive symptom clusters. No a priori grouping of BDI items was used, so that depressive phenomenology determined the depressive symptom clusters. We obtained correlative topographies for absolute, as well as normalized, rCMRglu.
Global normalization lowers variance and may improve detection of processes or associations in more discrete brain regions; however, normalization can compromise detection of processes or associations in regions of brain large enough to affect global metabolism. Absolute metabolism may permit better detection of involvement of large regions of brain. Discrepancies between absolute versus normalized data remain an unresolved problem in the field. We will highlight both the areas of convergent and divergent data, so that readers and future studies can address this issue.
Based on our prior report (Dunn et al, unpublished data, 1997) and the literature Sieden and Dykstra 1977, Bermanzohn and Siris 1992, Graybiel et al 1994, Heinz et al 1994, Salamone et al 1997, Koob and Nestler 1997, Volkow et al 2001, Wexler et al 2001, we hypothesized anhedonia symptoms would correlate with rCMRglu in dopamine-enriched brain regions associated with reward, that is in basal ganglia, medial prefrontal cortex and anterior cingulate. We also hypothesized psychomotor symptoms and their neural substrates would play a more prominent role in BP than UP depression phenomenology and neurobiology APA 1994, Benazzi 1997, Sobin and Sackeim 1997.
Section snippets
Subjects
Sixty primary affective disorder patients enrolled in treatment studies at the National Institute of Mental Health (NIMH) provided BDI results for the PCA, and valid PET scans were obtained from 58 of these patients. Most patients had been referred to NIMH by their psychiatrist because of treatment-resistant illness; the remainder was self-referred. Patients were medication-free ≥ 2 weeks for BDI administration and PET scanning. All studies were NIMH IRB approved, and each patient provided oral
BDI PCA
A four-component model was derived that explained 63.8% of the total variance of all BDI items (Table 1). When only BDI items loading ≥ .6 were included (i.e., above the horizontal line in Table 1), each component had unique items, yet 15 of 21 BDI items were included. These highly loaded BDI components were conceptualized as: negative cognitions, psychomotor-anhedonia, vegetative symptoms, and somatic symptoms, and explained 21.4, 21.2, 12.9 and 8.3% of the variance, respectively. The fourth
BDI principal components analyses
Four depressive symptom clusters were derived from the BDI and conceptualized as negative cognitions, psychomotor-anhedonia, vegetative, and somatic symptoms. Despite the compromised status of the somatic symptom component, the statistical validity of this PCA is strongly supported by the high proportion of total variance (64%) explained by these components when compared with other studies in primary affective disorders, where total variance explained ranged from 44% to 57% (Brown et al 1995;
Acknowledgements
This work was supported in part by Theodore and Vada Stanley. Previously presented in abstract form at the 151st Annual Meeting of the American Psychiatric Association (1988), Toronto, Canada.
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