An adequate case definition presents particular difficulty when anxious depression is being studied in a biological context. For one thing, the inclusion procedures usually employed in clinical-phenomenological studies did not seem very satisfactory for our experimental purposes. First, the term depression gen­erally is applied in favor of the minor neurotic depressions, that is, the types for which current knowledge of the biological correlates of major depression has as yet to be applied. Similarly, the application of a diagnosis of anxiety often applies to simple anxious moods or to emotional lability, to situations with a paucity of presenting symptoms. This may involve the risk of overestimation of the diagnosis of anxious depression, if it is true that signs of anxiety are present in at least 90% of cases of depression (27). Further, the sporadic presentation of anxiety symptoms as a reaction to fleeting situations is a universal that adds to the difficulties of distinguishing between anxious and nonanxious depression. The application of more stringent inclusion criteria, however, involves the risk that the conclusions from the most recent experimental work will not be completely comparable to those dating farther back. Acknowledging that this Gordian knot could not be undone to complete sat­isfaction, we thought it preferable to use criteria usually employed in biologically oriented research to distinguish between anxious and nonanxious depression. This not only involved a benchmark relative to intensity, but also one of symp-tomatological consistency in the course of a few independent depressive episodes in the same individuals. Consequently, our series of analyses included only those patients who fully met the criteria for both a primary (20) and major affective disorder (1) and for whom a subclassification as definitely anxious or definitely nonanxious was pos­sible. Operationally, the definitely anxious patients were those who scored at least 9 points on the Covi anxiety scale (18) during the course of at least three independent depressive episodes. Definitely nonanxious patients were those with less than 6 Covi scale points when tested during each of three independent de­pressive episodes. None of the patients had a detectable concomitant medical or neurological illness. It was thus possible to evaluate 88 patients (39 males, 49 females; mean age 51.2 ± 10.9 years; 51 with recurrent depression, 37 with bipolar disorder); 50 were definitely anxious, 38 definitely nonanxious. A patient’s inclusion in the different analyses was exclusively based on the possibility of determining whether his or her anxiety proneness was high or low. The following criteria and procedures were also used for different analyses. a. Urinary 3-methoxy-s-hydroxy-phenyl-ethylenglycol (MHPG) was measured (43) during the depressive episodes of hospitalized patients who scored higher than 21 (26) on the Hamilton Rating Scale for Depression, had been drug free for at least 3 weeks previously, and had been on bed rest and fed with a vanillil-mandelic acid (VMA)-free diet for 5 days. MHPG was quantified by gas chro­matography, using 24 hr urine of the last 3 days of the baseline period and calculating the mean. b. Responsiveness to lithium prophylaxis was assessed in those patients who, after at least two depressive episodes in the course of 2 years, were on lithium follow-up therapy (least duration: 24 months; mean: 52 ± 8 months). The dosages were individually adjusted to maintain lithium plasma levels at between 0.5 and 0.9 mEq/1 12 hr after the last lithium administration. Patients were classified (46) as responders if they had had no major affective episode requiring supple­mentary medication in the period between 8 months after starting lithium and the end of the follow-up therapy. Nonresponders were patients who had had two major affective episodes during the same period. Patients who had had minor affective breakdowns or one major episode were excluded, since classification of their responsiveness would have been potentially unreliable. с Age at onset was defined as the patient’s age at the time of his first major affective episode. Previous possible minor episodes or mood swings were not taken into consideration. d. Data on the presence or absence of suicidal behavior and/or delusions du ring depressive episodes were recorded on patients’ charts, having been col­lected on the spot or retrospectively. Patients with overt suicidal thinking but not suicide attempts were excluded. Similarly, our reference regarding delusions was DSM-III (1), with mood congruent delusions as the only one taken into account. Patients were considered delusional if they had experienced delusions in at least two individual episodes and nondelusional if delusions had never been documented in past episodes.

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