INTRODUCTION

Depression is a disorder in increasing incidence in our midst with 8% of the Chilean general population [ Minoletti, A.,Vicente,B., personal communication] afflicted. This hinders the development of adults and therefore of our community, becoming a major health problem in our country.

The distinguished psychoanalyst Otto Kernberg has expressed the opinion that a major frequency of depression exists in developing societies that suffer a high level of stress, like our society (1). From a biological point of view, stress is envisioned producing changes in the genetic expression and subsequent anatomic adaptative phenomena in neurochemical changes, responsible for chronic synaptic changes that determine susceptibility to repeated bouts of depression (2). Concordantly with this biological vision is the fact that there are individuals that are susceptible to develop the changes outlined (3).

With this background in mind, we have correlated findings of patients of major depressive disorder (DSM-IV) (4) and NeuroSPECT findings (5, 6, 7) in basal conditions and during cortical activation by means of the Wisconsin Test (8).

Justification for the use of frontal stimulation for these studies (9) is the fact that frontal functions are better observed under a stress environment representative of daily life. Therefore, by means of the Wisconsin Test we stress the patient in a standardized manner, while the functional NeuroSPECT images are gathered during the performance of the test.

BRAIN CIRCUITRY INVOLVED

Extensive studies of language and memory have provided important information on internal representation of frontal functions that can be localized in the brain (10). The main question is no longer if the study of brain cortical localization is useful in order to understand cognitive functions, but the definition of the neuronal mechanism involved in the performance of these functions.

Nevertheless, it is important that we keep in mind the fact that the areas of the brain identified in relation with a specific function do not perform independently in a similar manner than when they are interacting with other areas of the brain.

If we review the diagnostic criteria of DSM-IV for major depression (scheme I) defined as items, we can state that a large number of symptomatologic presentations are associated with brain areas involved with human behaviour (11, 12, 13, 14) corresponding to three circuits, circuits that begin in the prefrontal dorsolateral cortex, orbito-frontal cortex and anterior cyngulate gyrus. All these areas have afferences and efferences that are specific and we have to consider also in this group of areas, area 38 of Brodmann that is the anterior temporal pole (scheme I).(Please see Spanish Version).

The dorsolateral prefrontal cortex defined by Cummings (15) like the executive cortex and by us as the superior intelligence area, is limited to areas 8 and 9 of Brodmann with afferences from areas 9, 10, 46 and 7 of Brodmann, also from the dorsal thalamus, the parafascicular area of the thalamus, substancia nigra, medial pars-compacta, dorsal raphe and the periacueductal gray substance (PAG) (16). PAG is related with active emotions of "fight and flight" confrontational situations also with the influence of environment and sympathic excitation.

Dysfunction of subcortical frontal circuit is related with the appearance of poor organizational strategies, impairment of strategies for memory searches, environmental dependence and difficulty for keeping or changing behaviors, failures in working spatial memory that are detailed in scheme II.(Please see Spanish Version).

The second circuit is the orbito-frontal subcortical circuit related in different publications (17, 18, 19, 20) with characteristics of personality and animic state, (please see scheme III). This circuit originates in area 10 and 11 of Brodmann with afferences from area 22 located in the superior gyrus of the temporal lobe and area 12 of Brodmann.(Please see Spanish Version).

Minor inputs to these areas originate in the entorhinal cortex (16), rostro medial parafascicular thalamus, amygdala, medial pars-compacta of substancia nigra, dorsal raphe and central tegument of mesencephalon. It is important to state that the size of the actual areas described does not define a proportional relationship with the importance of the influence and we believe that therefore they have to be considered indistinctively.

It is also of importance to state that the minor afferent inputs of the orbito-frontal circuit are similar to the minor inputs of the dorsolateral pre-frontal cortex, except for the consideration of the amygdala and entorhinal cortex of the limbic system plus relations with areas 9 with the ventrolateral zone of PAG, this area is related to strategies of quietness, immobility, hyporeactivity, environmental detachment and sympathic inhibition (16).

The efferent targets of the orbito-frontal circuit are the 12, 25 and 32 of Brodmann. Other minor efferences correspond to area 9, 33 and 38, the latter has been observed in patients that have commited suicide, to show a diminution of serotoninergic content (28).

The last circuit of interest corresponds to the anterior cyngulate gyrus represented by the anterior segment of area 24 of Brodmann with afferences from area 28, 35, hyppocampus and minor afferences from area 12, amygdala, subparafascicular thalamus, dorsal raphe and mesenchepalic central tegument. This circuit is related with motivation and with the capacity of adapting to rapid changes of alternating stimuli. Both characteristics can be seen with detail in scheme IV.(Please see Spanish Version)

The principal efferences correspond to the pars-compacta of the substancia nigra, the medial subthalamic nucleus and lateral hypothalamus. Minor efferences correspond to the medial line thalamic nuclei, globus pallidus dorsal interior and exterior, lateral habenula, central gray substance and tegument of the pontine peduncular nucleus.

We want to point out the importance that functional abnormalities of the subgenual area, located in the subcallosum area of the anterior cyngulate described by Damasio, hypothesizing that this area is related to the evaluation of the results of a certain behavior in terms of reward or punishment (21).

We want to enphasize therefore, that the functional changes observed by NeuroSPECT represent changes in stages of a circuit with neurochemical characteristic and specific neuroanatomic locations, that can be seen in scheme V. Therefore, abnormalities observed in any of the stages of the circuits can elicit the same symptomatology. (Please see Spanish Version)

In this paper, we report the results of a comparative evaluation of basal NeuroSPECT and NeuroSPECT during the activation of the frontal lobe by means of the Wisconsin Test in patients with Major Depressive disorder.