Sixty-two patients (29 men and 33 women; mean age 52.9 ± 9.4 years) par­ticipated in the study. The inclusion criteria were: (a) a diagnosis of Major Af­fective Disorder (Major Depression, Recurrent, n = 32; Bipolar Disorder, n = 30) established on the basis of DSM-III criteria (1); (b) a past history of at least three major depressive episodes; (c) no history of CNS disease, head trauma with loss of consciousness, or alcohol or drug abuse; (d) no evidence of concurrent organic or neurological illnesses; (e) no steroid medication intake for at least 3 months prior to the study. The patients were classified as having a definitely anxious or nonanxious depression whether they had scored respectively more than 9 points or less than 6 points on the Covi anxiety scale (6) during at least three different depressive episodes (Sacchetti et al., this volume). According to this criterion, 29 patients (17 men, 12 women; mean age 55.6 ± 6.7 years) were classified as anxious and 33 (12 men, 21 women; mean age 50.5 ± 10.6 years) as nonanxious. The CT control group was composed of 49 healthy age- and sex-matched subjects who had undergone CT scans for minor accidental head trauma without loss of consciousness (most had been involved in automobile accidents). Inclusion criteria for the controls were the same as items (c), (d), and (e) described above plus no past history or present evidence of psychiatric disorder. Ten to 12 CT slices were obtained for each patient and control. Cerebral ventricular size was measured by manual planimetry on the CT slice that showed the lateral ventricles at their largest and was expressed as Ventricular Brain Ratio (VBR) (24). All the measurements were performed by two raters who were un­aware of the nature of the study and the subjects’ diagnoses. Interrater reliability was determined and found to be high (r = 0.91).

1. American Psychiatric Association. (1980): Diagnostic and Statistical Manual of Mental Disorders, 3rd. ed. American Psychiatric Association, Washington, D.C. 2. Barron, S. A., Jacobs, L., and Kinkel, W. R. (1976): Neurology, 14:1011-1013. 3. Breier, A., Charney, D. S., and Heninger, G. R. (1985): Am. J. Psychiatry, 142:787-797. 4. Cassano, G. B. (1983): In: The Benzodiazepines: From Molecular Biology to Clinical Practice, edited by E. Costa, pp. 287-293. Raven Press, New York. 5. Cazzullo, C. L., Sacchetti, E., Vita, A., Ciussani, S., Conte, G., Pennati, A., and Invernizzi, G. (1984): IRCSMed. Sci., 12:917-918. 6. Covi, L., and Lipman, R. S. (1984): Clin. Neuropharmacol, 7Sl:924-925. 7. de Leon, M. J., and Ajax, E. G. (1983): In: The Dementias, edited by R. Mayeux and W. G. Rosen, pp. 103-121. Raven Press, New York. 8. Goldberg, D., and Hillier, V. (1979): Psychol. Med, 9:139-146. 9. Goldberg, D., and Simpson, N. (1985): In: Drug Treatment of Neurotic Disorders: Focus on Alprazolam, edited by M. H. Lader and H. С Davies, pp. 76-83. Churchill Livingstone, New York. 10. Hamilton, M. (1983): Br. J. Clin. Pharmacol., 15:165S-169S. 11. Invernizzi, G., and Sacchetti, E. (1985): In: Proceedings of the IVth National Congress of the Italian Society of Biological Psychiatry (Pavia, Italy, 19-20 October 1985), edited by G. Nappi, P. Pinelli, and D. Kemali, pp. 75-80. Emi Ras, Pavia, Italy. 12. Jacoby, R. J., and Levy, R. (1980): Br. J. Psychiatry, 136:270-275. 13. Jacoby, R. J., Levy, R., and Bird, J. M. (1981): Br. J. Psychiatry, 139:288-292. 14. Kraepelin, E. (1921): Manic Depressive Insanity and Paranoia. E. & S. Livingstone, Edinburgh. 15. Nasrallah, H. A., McCalley-Whitters, M., and Chapman, S. (1984): Am. J. Psychiatry, 141:919. 16. Overall, J. E., Hollister, L. E., Johnson, M., and Pennington, V. (1966): JAMA, 195:946-948. 17. Paykel, E. S. (1971): Br. J. Psychiatry, 118:275-288. 18. Pearlson, G. D., Garbacz, D. J., Morberg, P. J., Ahn, H. A., and DePaulo, J. R. (1985): J. Nerv. Mem. Dis., 173:42-50. 19. Pearlson, G. D., Garbacz, D. J., Tompkins, M. A., Ahn, H. S., Gutterman, D. F., Veroff, A. E., and DePaulo, J. R. (1984): Am. J. Psychiatry, 141:253-257. 20. Prusoff, B. A., and Paykel, E. S. (1977): Int. Pharmacopsychiatry, 12:153-159. 21. Reveley, M. A. (1985): Br. J. Psychiatry, 146:367-371. 22. Sacchetti, E., Vita, A., Conte, G., Pennati, A., Alciati, A., Calzeroni, A., Invernizzi, G., and Cazzullo, С L. (1985): Presented at the IVth World Congress of Biological Psychiatry (Philadelphia, 8-13 September 1985). Abstract Book, p. 181. 23. Scott, M. L., Golden, C. J., Ruedrich, S. L., and Bishop, R. J. (1983): Psychiatry Res., 8:91-93. 24. Synek, V., and Reuben, J. R. (1976): Br. J. Radiol, 49:233-237. 25. Targum, S. D., Rosen, L. N., DeLisi, L. E., Weinberger, D. R., and Citnn, С . М . (1983): Biol. Psychiatry, 18:329-336. 26. Vita, A., Sacchetti, E., Calzeroni, A., Invernizzi, G, and Cazzullo, С L. (1986): In: Advances in Neuroimaging, edited by T. Reisner, H. Binder, and E. Deisenhammer, pp. 243-247. Verlag Wiener Medizinischen Akademie, Vienna.
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Institute of Psychiatry, University of Milan, School of Medicine, 20122 Milan, Italy
Marked anxiety symptoms often accompany episodes of major depression (3,10,16,17,20), but the way in which such symptoms can be employed for sub-classifying affective disorders is still an unresolved issue. It has been suggested that anxiety symptoms may mark the more severe forms of depressive disorders (9). In fact, clinical ratings of anxiety and depression have been positively cor­related in patients with major affective disorders (4,8). Furthermore, a parallel increase in the number of DSM-III (1) defined symptoms of anxiety and depres­sion has been found in patients seen in primary care settings (9). If it is actually true that the more severe the major depression, the greater the probability of the presence of concomitant anxiety, depression with anxiety symptoms could be expected to be associated with the presence of other severity indices. One of the most promising of these recently has been shown to be cerebral ventricular dilation as assessed by Computed Tomography (CT). Ventricular enlargement has been found among the most severely and socially impaired depressives, those presenting characteristics such as delusional symp­toms (11,23,25,26), suicidal tendencies (11,15), frequent hospitalizations (18,19), persisting unemployment (18), and, at least in the elderly, high mortality rates (13). As part of a comprehensive effort to improve our knowledge of major depres­sion with anxious symptomatology (Sacchetti et al., this volume), we undertook a study to determine whether anxious and nonanxious major depressives have different brain morphological characteristics.

This research was supported in part by the C.N.R. grant no. 86.01935.56. The authors thank Dr. June Shmelzer La Rosa for her precious assistance in revising the manuscript.

The mean VBR for our patients was 6.3 ± 3.9, significantly higher than that of the age- and sex-matched controls (4.5 ± 2.6) (student Mest = 2.8; p < 0.01). Since VBR was positively correlated with the controls’ ages (r = 0.53; p < 0.01), any patient’s age-corrected VBR exceeding the age-corrected mean VBR of con­trol subjects by more than 2 standard deviations was considered abnormal. Ac­cording to this criterion, 16 patients (26%) had abnormally large cerebral ven­tricles. The incidence of ventricular enlargement in major depressives with and with­out anxiety proved to be significantly different. Eleven of the 29 anxious de­pressives (38%) but only 5 of the 33 nonanxious depressives (15%) had dilated cerebral ventricles (x 2 - 4.03; p = 0.04). Thus, in our sample, the likelihood of a patient with cerebral ventricular enlargement having concurrent marked symptoms of anxiety during depressive episodes was more than three times as high as that of one with normal ventricles (odds ratio = 3.42). To the best of our knowledge, this is the first time a relationship between anxiety and CT scan evidence of brain atrophy in major depression has been reported. However, in the only available previous report on this subject, Jacoby and Levy (12) found that depressed patients with enlarged ventricles were less anxious than those with normal ones. Their sample was entirely composed of aged individuals (mean age 73.2 years; age range 63-86 years) who were clinically depressed, but whose depressions were not operationally defined. Furthermore, the definition of ventricular dilation was a subjective one and did not take any normative data into account. Finally, the clinical rating of anxiety was made on the basis of the episode at the time of the study, so that situational, episodic anxiety was not distinguished from a consistent symptomatological pattern of the patients’ depressive episodes. All these factors make it difficult to interpret the results of the Jacoby and Levy study and impossible to compare them to our own. Although additional studies are needed to draw any definite conclusions from the present results, they warrant comment. The higher incidence of ventricular enlargement in the major depressions that usually are associated with anxiety symptoms suggests that the clinical distinction between anxious and nonanxious depressives may actually reflect major differ­ences in the underlying biological characteristics of these patients. Moreover, the finding of a morphological brain abnormality in patients with anxious depression would support the working hypothesis that the presence of anxiety symptoms may mark the more severe forms of major depressive illness. It is important to stress that affective patients with cerebral ventricular en­largement and those with definite anxious symptomatology have many common clinical and biological characteristics. Clinical features previously found to be associated with ventricular enlargement in major affective disorders, such as late age at onset (5,11,26), past history of delusional symptoms (11,25,26), suicidal tendencies (11,15), and poor response to long-term lithium treatment (11,22,26), also seem to be overrepresented in patients whose depressive episodes consistently show concurrent marked anxiety (Sacchetti et al., this volume). This pattern seems to strengthen the observed direct relationship between anxiety and ven­tricular dilation and, more importantly, strongly suggests that anxiety symptoms constitute part of the clinical-biological picture of a specific subtype of affective disorder, closely resembling that of the early clinical descriptions of the so-called involutional melancholia (14). This was defined as a depression of the later years, with prominent anxiety, frequent delusional symptoms, and high suicide proneness, a disorder for which an organic basis always had been suspected. Apart from the question of whether this affective subtype merits nosological autonomy (it is not given in recent references such as DSM-III), involutional melancholia could be conceived as the most extreme form (as far as age at onset, clinical picture, and severity are concerned) of a specific subtype of affective disorder accompanied by cerebro-morphological abnormalities. At present, the etiological role of organic brain disease in affective disorders and the issue of whether cerebral ventricular enlargement actually reflects such a disease still await clarification. We know that ventricular dilation is a nonspecific abnormality present in such diverse conditions as schizophrenia (21), affective disorders (11-13,18,19,23, 25,26), dementias (7), personality disorders (26), and even in normal aging (2). This abnormality, however, may well be the "final common pathway" of different organic brain processes (still unknown) that may be specific to each clinical condition in which enlargement is demonstrable. Should the CT finding of ventricular enlargement in major depression definitely be proven to demonstrate a neuropathological process, we will have identified a possible causal factor for a specific subtype of depression, with concurrent marked anxiety and a severe clinical and prognostic picture. In this case, the Kraepelinian hypothesis of brain organicity relative to involutional melancholia would be given new experimental support after a century, thanks to the advent of novel brain imaging techniques and their application to psychiatric research.