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found a bimodal MHPG excretion distribution among 153 drug-free patients with major affective disorders (Conte et al., unpublished report).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.

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