DISCUSSION

All the 50 patients studied fulfilled the diagnostic criteria of the DSM-IV for Major Depression in moderate to severe degree, namely they presented with one of the two first items of the diagnosis criteria consisted of drop of mood or loss of interest or pleasure in all or most activities, fulfilling at least five of the items of this diagnostic criteria of DSM-IV. In all cases, there was a recurrence history every one or two years at least during the last 2 years.

The presence of depressive mood was stated also by the Rorschach Test that was applied for purposes of diagnosis and research.

We gathered a high reproducibility index in localization of areas of hypoperfusion in NeuroSPECT by means of statistical expression of the significance of results of cerebral perfusion by means of comparison voxel by voxel with a normative database. For this purpose, we had to normalize the brain volume and this was performed by means of the stereotactic Talairach technique. Another contribution of this paper, is the report of the technique of projection of the Brodmann areas involved in behavioral activities that is an automatic method and therefore has a maximal reproducibility. The definition of these behavioral Brodmann areas demonstrates the exact localization of areas of hypoperfusion in the brain and allows the quantification of extension of the functional impairment. This methodology defines the functional substratum involved in Major Depression and allows the definition of important working hypothesis.

The most important basal results in terms of absolute hypoperfusion are defined in Brodmann areas 38 and 11 in the left hemisphere, followed by right 38 area, right 12, right 11 and left 22. All of these areas have been reported earlier to have significant functional meaning (29, 33, 40) and in depressive pathology (6, 11, 21). Areas 11 and 12 are segments of the frontal subcortical orbito-frontal circuit related to mood and personality.

In regards to area 38 of Brodmann, the polar temporal area, there has been reports (29) of low concentration of serotoninergic neurotransmission (P < 0.01) in post-mortem studies in suicides. This has important correlation with cognitive emotional performance that is shared with the entorhinal cortex and the perirhinal cortex in the medial segment of the temporal lobe.

We did not observe involvement in areas 8 and 9 in basal conditions and these areas are part of the dorsolateral prefrontal circuit as it has been reported previously (36, 37). (Table 1).

In comparison with normal subjects, the most important difference upon performance of the Wisconsin Test is the absence of frontal activation (prefrontal dorsal lateral area, areas 8 and 9) that is observed in the anterior image, also in both lateral images of the NeuroSPECT. This observation is shared with patients with schizophrenia (23), denoting a diminution of executive function and also a diminution of higher order logic functions in depressive patients, mimicking what appears in clinical observations.

Another area of importance that is concordant with literature ( 22, 35, 38) is area 25 that in our work presents in the left hemisphere a statistical difference (P < 0.026) between basal and activation NeuroSPECT. This in conjunction with area 10 and 32, the dorsolateral columns of PAG and V.M. nucleus of the hypothalamus are participating in the modulation of emotion based in the anticipation of future consequences of behavior. Area 25 of Brodmann is also known as Subgenual and appears in PET studies with diminution of blood flow and glucose metabolism and MRI patients showing a reduction of volume of gray matter in patients with Major Depression.(22).

The results of hypoperfusion in the orbito-frontal cortex (areas 11 and 12 of Brodmann) and anterior temporal (area 38 of Brodmann) in basal conditions were expected. The most important observation of this investigation refers to the changes induced in patients with Major Depression by the Wisconsin Test, that we stated above, recreates situation of environmental stress. This test in depressive patients expresses a significant functional inhibition of the anterior Cyngulate gyrus and the Subgenual region (bilateral areas 24 and left area 25).

This observation is seminal indeed, because the anterior Cyngulate gyrus is responsible of the dynamic response of the depressive patients in front of stress and this is characterized by lack of motivation, lack of interest or pleasure, absence of reward oriented behavior and indifference to pain. The left hemisphere (41) in the dorsolateral prefrontal area (area 8, 9 and 46) that paradoxically appears to be insensible to the activation of the Wisconsin Test erroneously interpret this situation. This error leads to autodepreciation, sentiments of guilt and eventually to suicide,(42) demonstrating the importance for clinical work of this diagnostic precision.

The findings that we are reporting by means of this technique correlating semiology and NeuroSPECT offer a new tool for the clinical evaluation of depressive patients and is of great usefulness for the clinician that has to define more exactly the severity of the clinical involvement and has to orient the therapeutic elements in function of the responsive capacity of the brain of the patient.

The understanding of this important technological contribution by the clinician is an invitation to a subject more pleasant than the one we expected, namely, it permits to rekindle the words of Sigmund Freud when he abandoned neurology: "Let the biologists go there way as far as they can and we should go also as far we can, because one day our roads will cross".