The results of the various studies described now need to be discussed within a general framework. The first thing to highlight is that the associations were obtained from relatively small groups of highly selected patients in naturalistic settings. Consequently, supplementary controlled studies that also include less extreme cases will be necessary before generalizations become possible. Further, even in the case of the apparently more straightforward associations, it is evident that we are dealing with partial associations since there is a considerable degree of overlap between definitely anxious and definitely nonanxious major de-pressives. Because our work was specifically addressed to definite anxiety in major depression and not to the general occurrence of anxiety symptoms, extreme caution should guide comparisons with the findings from studies based on dif­ferent theoretical and experimental approaches. Despite these limitations, the accumulating biochemical, pharmacological, and clinical data in this area already appear to support the hypothesis that definite morbid anxious patterns phenotypically aggregate a particular subtype of de-pressives who are quite likely to have specific identifiable biological dysfunctions. Major depressives who also have morbid anxious symptoms were found to have a relatively high urinary MHPG excretion, poor response to lithium therapy, a late disease onset, and a history of delusions and suicidal behavior. As compared to this type of patient, the prototypical major depressive, relatively protected from anxiety, has a rather low MHPG excretion, no affective relapses during long-term lithium treatment, an early disease onset, and no history of suicide attempts or delusional symptoms. The clinical picture of anxious depressives is not really surprising. Its similarity to the classical Kraepelinian descriptions of involutional melancholia (29) im­mediately comes to mind. Further, it is worth noting that a similar symptom-grouping resulted from an earlier attempt (39) to differentiate discrete subgroups of depressed patients by factor analysis: one of these subgroups was characterized by high psychic and somatic anxiety scores, suicidal ideation, psychotic features, and a late disease onset. On the other hand, the fact that our definite morbid anxiety patients generally were the most impaired can also be viewed as a specific case of prior clinical evidence indicating that the more severe the depression, the more marked is the patient’s anxiety level (3,23,24,33). Consequently, our findings also can broadly represent further evidence supporting the hypothesis that anxiety and depression are two correlated dimensions (24). This is true, however, only if we limit our­selves to a purely descriptive clinical context. Our current knowledge of the biological correlates of the clinical aspects we found to be associated to anxiety symptoms, together with the findings on MHPG excretion and lithium therapy among anxious depressives, points to a substantial pathogenetic discontinuity among subgroups of depressed patients who appear to have a varying vulnerability to concomitant anxiety. Obviously, the research that has been undertaken to date is not sufficient for allowing a definitive answer to the question of whether the biological differences found really reflect distinct subtypes of major depression or if they are only indicative of a few main typologies. We shall have definite answers when we conduct studies that test, through stepwise, cluster, or multivariate techniques, whether we are observing first- or second-order associations or we are looking at additive or interactional effects. Yet, there is some indirect evidence that we can address at this juncture. A relatively high MHPG excretion was associated with a poor response to lithium therapy (45,46) and with a late disease onset (5,13,42,53). In turn, a poor lithium prognosis was associated with a late disease onset (45,46) and with delusional depression (46) and suicidal behavior (45,46). Further, delusional depression was associated with an increased probability of suicide attempts (40). Conse­quently, it seems reasonable to assume that many of the variables found to be associated with a definitely anxious major depression are indices (at different phenotypical levels) of a few main typologies. If further study definitively confirms this hypothesis, then the clinical category anxious depression might take on novel and stimulating meaning for the bio­logically oriented researcher as well, now often thinking of it as a label that the clinician sometimes abuses. ACKNOWLEDGMENTS 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.

This entry was posted on Thursday, August 27th, 2009 at 3:34 am and is filed under Major Affective Disorder. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.