Independent information from epidemiological, clinical, biological, and phar­macological research impels formulation of the hypothesis that suicidal tendency represents a behavioral characteristic typically concentrated in specific subgroups of major depressives. Epidemiologically, the tendency for suicide attempters to repeat self-destructive acts is a rule rather than an exception. Clinically, suicide proneness has been shown to be associated with delusional depression (40). When major depressive suicide attempters were biologically compared to nonattempters, it was found that the patients in the former group had: a different genetic makeup (48); critically lowered CSF concentrations of 5-HIAA (7,52) and possibly HVA (34); increased chances for higher 17-OH-corticosteroid urinary concentration (10); lowered MAO platelet activity (9); higher melatonin plasma levels (4); ce­rebral ventricular enlargement (28,35); and augmenting average evoked responses (2). Further, in post-mortem studies of specific brain areas suicide attempters present either subnormal 5-HT concentrations (7) or supranormal densities of 5-HT 2 receptors (38,50). Pharmacologically, a history of suicidal behavior seems to have predictive value for a poor response to lithium therapy (45,46). Assuming suicide proneness as a marker of a distinct subgroup of major af­fective disorders, we analyzed the distribution of autoaggressive antecedents among definitely nonanxious major depressives. Previous suicidal behavior was indeed specific to the anxious depressives. Fourteen of the 15 patients composing our group of suicide attempters also were definitely anxious depressives whereas the relationship between anxiety-no anx­iety in the group of 60 nonattempters was exactly 1 (x 2 = 7.59, p = 0.006; odds ratio = 14). Since the information on suicidal behavior was collected after the cases were classified as anxious or nonanxious, the observed association cannot now help us to deal with the issue of whether suicidal behavior represents a consequence of collapsing anxious defenses. What we can say is that anxiety and suicidal behavior may have generally common or similar pathogenetic determinants and a partially interchangeable functional significance, for example, the patient’s attempt to alleviate his suffering from depression.

St. Francis Day Hospital, Dublin 5, Ireland (more…)

Studies undertaken during the late sixties (19,32) report a reduction in urinary MHPG excretion in depressed patients as compared to normal controls. This peripheral index undoubtedly is one of the most frequently used tools in research on the catecholaminergic correlates of affective disorders (31,43,44,53). Even if there is still some uncertainty about this measure, it seems sufficiently reliable for us to use it as a basis for subdividing major affective disorders into two fundamental subtypes, the relatively low and high groups. We ourselves found a bimodal MHPG excretion distribution among 153 drug-free patients with major affective disorders (Conte et al., unpublished report). Furthermore, and more importantly, relatively low and high excretors differ in age at onset (5,13,42,53), the number of platelet alpha-2-adrenoceptors (43), urinary Cortisol levels (41), cerebral ventricular size (53), clinical responsiveness to both antidepressant drugs (31,44,47,53) and long-term lithium treatment (45,46), and, possibly, a proclivity to develop mania (31). As for the MHPG relationship with symptoms, the emerging picture is that none of the latter in itself is sufficiently able to influence MHPG excretion so that the division of the patients into low and high excretors is appreciably affected, despite the fact that a slight effect on MHPG cannot always be excluded (31,42,44). This general conclusion also appears to be applicable to anxiety. As previously noted, studies focused on anxiety symptoms may inevitably unify mere situational phenomena with well-established traits. At the same time, it is extremely difficult to take into account the possibility that these traits sometimes can be effectively masked by positive chance circumstances and thus elude clinical detection. Con­sequently, studies of the relationship between MHPG excretion and anxiety in depression have not addressed the issue of whether the biological phenotypes of low and high excretors indicate a markedly different susceptibility to anxiety. With the latter as the investigational framework, we compared the MHPG excretion of 29 definitely anxious patients (14 males, 15 females) with major affective disorders with that of 16 definitely nonanxious ones (4 males, 12 fe­males). Since our general sample median MHPG value for males tended to shift to the right of that for the females, we used sex as a supplementary variable in the two-way ANOVA analysis of the present data. This indicates that being both male and definitely anxious positively, but independently, affects MHPG excre­tion (sex effect: F (1,41 ) = 1535, p = 0.001; anxiety effect: F (1,4 i) = 6AS,p = 0.016; interaction: F (l,41) = 0.03, p = NS). Independent nonparametric analyses after division of the patients into defi­nitely low and definitely high MHPG excretor groups (cut-off points: the median values of 1,650 Mg/24 hr for males and 1,119 /ug/24 hr for females) clearly indicate that the association between high MHPG excretion and anxiety is a strong one. The finding that 88.5% of the 26 high excretors (23 patients) were definitely anxious and that 32% of the 19 low excretors (6 patients) were definitely non-anxious means that the relative risk of anxiety is fully 16.6 times greater in the former than in the latter biochemically defined group. Thus, anxiety traits unrelated to the chance circumstances surrounding any particular episode are not randomly distributed among patients with major de- pressive disorders. On the contrary, they are strongly associated with readily distinguishable biochemical patterns.

Department of Social Psychiatry, University of Limburg, 6200 MD Maastricht, The Netherlands

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The subjects were 10 anxious ambulatory patients whose demographic char­acteristics are shown in Table 1. The patients were diagnosed according to DSM-III criteria and found to have had a generalized anxiety disorder of variable duration (2-6 months) for which they had been receiving various somatic treat­ments that were withdrawn for an adequate period before starting the new treat­ment. Patients were accurately screened for concurrent major medical and neu­rological illnesses. Severe and persistent insomnia was ruled out through specific inquiry. Anxiety and depression ratings were obtained by means of the Hamilton Anxiety and Depression Rating Scales (HARS and HDRS) that were administered by a trained rater. As controls for a baseline MSLT comparison, we selected five subjects with an Association of Sleep Disorders Centers diagnosis (2) of persistent psycho­physiological insomnia (PPI) who had been kept off drugs for at least 3 weeks before sleep EEG and MSLT recordings. After the baseline clinical examinations, the patients were randomly assigned to receive either CDDZ 2 mg at 8:30 a.m., or APZ 0.5 mg at 8:30 a.m. and at 3:30 P.M. Subjects and raters were not unaware of the medication. Baseline MSLT recordings, however, were performed under placebo conditions and took place at 10 a.m., 12 a.m., 2 p.m., 4 p.m., and 6 p.m., according to standard rules (6). At the same times, patients subjectively rated their vigilance levels on the Stanford Sleepiness Scale (SSS) (11), and a venous blood sample was drawn for later parent drugs plasma levels determination. Blood pressure and heart rate were also monitored manually. MSLT sessions took place for every patient at day 0 (baseline), at the first day of drug administration (acute condition), and after 30 days of therapy (chronic condition). HARS, HDRS, and a side-effects list were filled out by the same rater at baseline and at days 14 and 30 of treatment. A venous blood drawing was repeated on day 30 of treatment, at the first (10 a.m.) and last (6 p.m.) naps. Plasma levels of parent compounds were assayed by electron-capture gas-liquid chromatography, as already described (3,4). Several dose adjustments became necessary after the first week of treatment in order to alleviate excessive residual anxiety or excessive daytime sedation. Among CDDZ patients, 3 of 5 required a reduction to 1 mg of the daily dose because of excessive subjective daytime drowsiness, whereas 2 subjects in the APZ group required a daily dosage increase to 2 mg and to 3 mg, respectively, because of excessive residual anxiety. All patients, however, continued to assume their drags according to the original time schedule. Nonparametric statistics (Friedman 2-way ANOVA and Kraskall-Wallis Г -test) were used to compare treatments and correlate vari­ables (Spearman Ranked Correlation).