Comparative Functional Study of Two Psychiatric Pathologies by means of BrainSPECT Tc 99 HMPAO: Major Depression and Borderline Personality Disorder.

COMPARATIVE FUNCTIONAL STUDY OF TWO PSYCHIATRIC PATHOLOGIES BY MEANS OF BRAINSPECT TC 99 HMPAO: MAJOR DEPRESSION AND BORDERLINE PERSONALITY DISORDER.

CONCLUSIONS

It is necessary to make some precisions in relation to the investigation, as they influence the conclusions.

We have experienced the difficulty in applying questionnaires more connected to clinic ambulatory practice; it is preferred a more general report in relation to dimensional aspects, in this case those referred to impulsivity and affectivity. It is also present the over simplification of the taxonomic aspects (categories) in the moment of making diagnosis (27). For example, it is necessary to have available clinics habituated to taxonomic/dimensional diagnosis.

The study confirms information emphasized by literature (28) in relation to difficulty in establishing diagnosis in a more objective way in Borderline patients moderately compensated (who do not require hospitalization). It is of great importance the relatives report (CIE 10). In this case, the same as in patients with organic damage of the frontal lobule (29), it is indispensable a verification with close relatives.

It is also important to point out that many of the behavioral manifestations in patients with organic frontal damage are shared, though in less intensity, with the patients with Borderline personality disorder, this suggests that both categories of pathologies share similar anatomo-functional substrates.

In studying brain perfusion of borderline patients in basal conditions versus stimulation conditions through the test of Wisconsin, it is evident a significant change in the blood brain flow, mostly in the areas we expected to perform abnormally. That is, in the areas mentioned by literature, linked to conduct and also in this work hypothesis. The more sensible areas discussed in this paper are part of two of the three cortical/subcortical circuits reviewed previously – www.alasbimnjournal.cl/revistas/7/prado.html April 2000. The Dorsolateral Prefrontal circuit related to executive capacity and the anterior cyngulate circuit related to motivation. No significant changes were observed in the frontal-orbital area related to affectivity, while analyzing areas 11 and 12 separately; but when analyzing them in the merged modality they show significant changes in the right hemisphere.

While using comparatively samples of patients with Mayor Depression it was found in both groups significative differences in cortical perfusion corresponding to the anterior cyngulate circuit, being much more pronounced in borderline patients. However, in Major Depression in the orbital- frontal area it is evident that there is an extension of the hypoperfusion larger than 50% (corresponding to the circuit of the same name, related to affectivity), in basal conditions as well as in conditions of stimulation bilaterally. This fact was not observed in the sample of borderline patients, where the extension of the hypoperfusion was not larger than 25% in average.

In the group of depressive patients (different from the borderline patients) there were no changes in the cortex corresponding to the dorsolateral prefrontal cortex (executive capacity).

As this is an initial study, it is important to protect the real image/area reproducibility; for this we have undertaken to merge the adjacent areas 11 and 12 (orbital- frontal) and 32 + 24 (anterior cyngulate + area 32).

By this mechanism in the borderline patients there is persistence of the significance of the merged areas 32 + 24 versus area 24 by itself (of P 0.0003 and 0.000109 respectively) in the left hemisphere and (P 0.00005 to 0.000197) in right hemisphere. In the depressive patients, the statistical significance was less (from P 0.003 to 0.008 in left hemisphere and from P 0.002 to P 0.0257 in the right hemisphere).

While merging areas 11 and 12, in the orbital- frontal area in borderline patients, is significative with P 0.021 to the right and P 0.018 to the left. The fact that the area 11 by itself is not significative suggests that the orbital-frontal change is produced at the expenses of area 12.

In depressive patients it is always expressed by more than 50% of hypoperfusion in the left hemisphere frontal orbit area (areas 11 + 12) decreasing the hypoperfusion in right hemisphere to 45% average, in basal conditions as well as in stimulation conditions with the test of Wisconsin. In the depressive patients while evaluating area 11 (right to left) the flow is evenly decreased (more than 50%) in basal conditions as well as in stimulation. If area 12 is added de decrease already mentioned is only in left frontal orbit area.

Other areas which are sensible in the right hemisphere in borderline patients to the stimulation through the test of Wisconsin, are the right afferent area of the dorsolateral prefrontal area with a P 0.005 and the area 40, 32, 44, 46 and 9 with a P 0.05.

On the other hand, in the left side the area 40 shows larger significance than to right, P 0.005 and area 44 P 0.05 same than the right. One can see also a left impairement of area 25 of Brodmann or subgenual P 0.005, defined by Damasio as the area that being dysfunctional would be responsible of anhedonia.

Also the left areas 44, 36 and 28 show a compromise with a P 0.05

On the other hand the analysis of other areas in depressive patients show significance at the area 28 of Brodmann P 0.04 and the 38 P 0.03 to the right.

Analysis of the Significance of Functional Changes in Different Cerebral Areas as a Consequence of Activation with the Wisconsin test.

Area M. Corresponds to the anterior projection of the dorsolateral prefrontal cortex which is related to superior intelligence. Normally this area is stimulated increasing brain blood flow during the activation. (www.alasbimnjournal.cl/revistas/3/villanuevaa.htm).

In these experiments we observe a paradoxical diminution of cerebral blood flow when we compare with Neurospect gathered in basal conditions namely P 0.003 in right hemisphere and P 0.042 in left hemisphere.

One of the behavioral characteristics described in patients with borderline personality disorder are significant variations in social behaviors, occupational or interrelation activities. These disruptive behaviors are associated frequently to frustration felt by the patient in front of personal events or external events sometimes of minor significance that lead however to a record full of disadaptative performances. This fact is observed even in patients with high intellectual coefficient that during the moment of crisis looses its significance, for O. Kernberg, the patient "derails".

Another difficulty of borderline patients is their incapacity of establishing priorities in their daily life. This presupposes an adequate perception of emotional details and their evaluation within a structured totality. In periods of stress during which affectivity could be more involved, their responsiveness is more unpredictable. This difficulty to assess the emotional weight for adaptative purposes, is more severe and permanent in schizophrenia. In schizophrenia the dorsolateral prefrontal area, in particular area 46, diminishes cerebral blood flow during cerebral activation (35) by means of the Wisconsin test.

In borderline patients we observe similar diminution, but we think with a lesser intensity than the reported for schizophrenia., this however is clearly significant in the borderline patients.

The difficulties of flexibility of behaviors or to keep stable patterns of behavior seen in borderline patients, is predicted by D.S.M. IV only to start improving spontaneously on or about 40 years of age. Borderline patients have a poor memory of information during periods of dysfunctional periods. These week memories of self affecting circumstances provoked by their behavior is an explanation of their incapability of avoiding repeating these situations, thus the patient has not learned from experience.

From this information we may understand that borderline patients have a poor memory for information for recent or remote information in particularly situations that are damaging repeatedly. Anna Freud (36) explains these facts like mechanisms of defense like negation or intelectualization and Gazzaniga (37) would state that human beings process 98% of perceptions automatically, the left hemisphere being always ready to explain the facts from its limited observation angle influenced by reports of inaccurate memories.

Both investigators coincide in stating the difficulty of changing opinion that this patients have or the inflexibilities of the judgement with regards to perceived stimuli. This condition is very evident in the borderline patients which show in their characteristic pattern of confrontation and polarization in their affective relationships, thus there is a tendency of overvaluing to the extreme the other subject (D.S.M. IV). This phenomenon also has a tendency to attenuate itself after the age of 45. At this age the right hemisphere becomes more dominant, there is more common sense (such will define the capability of detecting social and environmental clues and of an adaptative response) Also there is a stronger and better capacity to structure in a globality. It is necessary to emphasize that all these features correspond functionally to the dorso lateral prefrontal circuit.

We have reported in previous publications (www.alasbimnjournal.cl/revistas/3/pradoia.htm) that the conducts of utilization of the environment and the conducts of imitation are clearly stated in the features of DSM IV and refers to a loss of control in different activities that are potentially conducive to self inflicting damage such as uncontrolled gambling, reckless driving, drugs consumptions or lack of control of appetite and lack of control in spending.

In this circuit we locate the capability to perform tasks as required by complex attention and guidance of conduct with intelligent thinking. In these patients a dysfunction in this circuitry would difficult this capability intermittently.

The dorsolateral prefrontal cortex has been related to superior intelligence, this concept refers to the way the intellectual coefficient is utilized. Weschler’s report states that intelligence is the total capacity, global or aggregated (corresponds to the product of various abilities), in order to think rationally, of performing with a purpose and struggle effectively with the environment. In conditions of stress this area mysfunctions transiently in border line patients.

In normal individuals this area has an increase of cerebral blood flow during the activation with an approximate increase of 15% of blood flow, as measured with Xe133. In this case we observe a paradoxical diminution of blood flow in comparison with Spect recorded in basal conditions in the anterior projection (Area M). In the lateral projection there is a diminution in Area 46 right (P 0.046 and area 9 right (P 0.016).

The same response occurs in patients who suffer schizophrenia (39) where the principal area affected is area 46 of Brodmann.

Area 25

Border line patients show a more marked diminution of cerebral blood flow (p 0.006), during activation of the area of the area 25 of Brodmann. This area corresponds to the subgenual region which according to Damasio, is responsible in a dysfunctional state of loss of pleasure, of anhedonia and negative anticipation. The area 25 allows the evaluation of facts of life in terms of reward and punishment.

In this study area 25 appears affected only in the left hemisphere. Concerning the displeasure that would express itself in this area, it is important to remember that this is a frequent response in borderline patients facing their mistakes in the Wisconsin test as a displeasure feeling that is recorded during the two minutes of window of NeuroSPECT as a diminution of blood flow or extension of the magnitude of the area hypoperfused.

In every day life these patients would present a tendency to displeasure or a poor tolerance to frustration induced by unexpected changes in plans or an increase on the demands on themselves.

Anterior Cyngulate and Area 32

In borderline personality disorder these areas are clearly more sensitive with a marked diminution of blood flow during activation and a P 0.00005 in the right hemisphere and 0.0003 in the left hemisphere and for Area 32 0.031 in the right and 0.006 in the left hemisphere respectively (Graphic III).

GRAPH 3

Both areas, anterior cyngulate and Area 32 correspond to the area of cortex that is located in front of the corpus callosum in its anterior and dorsal areas.

The dorsal area of the anterior cyngulate gyrus is related to cognitive motivation, while the ventral area is related to general motivation in emotions (both areas are constituents of the limbic system).

The cerebral blood flow of this area shows a clear difference when we compare basal versus activation studies: the demand of the Wisconsin test of changing of strategies is accompanied by a diminution of blood flow and function in conditions of frustration.

It is very probable that the dysphoria presented by these patients at that particular time could inactivate temporarily these structure (Area 24 and 32) and indirectly the area dorsolateral prefrontal due to emotional interferences because in basal conditions this same type of patients do not show a significant compromise or this type of function in this location.

It is of interest to support the findings of this study through the correlation with typical maneuvers of the borderline patients that can be related with neuropsychological aspects.

The loss of motivation of these patients that is manifested by changes of demand of the environment (D.SM.IV) can be related to an episodic mutism and apathy as a response to the demands of a task.

Of note there are reports stating the dysfunction of the anterior cyngulate gyrus in experiences of psychic emptiness (www.alasbimnjournal.cl/revistas/3/pradoia.htm) this is an emotional state that could precede acts of hetero or auto inflicting damage .

It is possible to notice in these self inductive lesions of behaviors the need of a diminution of fear (a low serotoninergic stimulation) and a increase of the pain threshold that facilitate this type of behavior. The anterior cyngulate gyrus has a high density of opiate receptors (41) and also an extensive serotonynergic innervation.

Orbito-Frontal Area

In borderline patients there are no significant changes in area 11, however area 12 in this same region shows an extension of hypoperfusion during the activation in the right hemisphere, while in mayor depressive patients these changes of increase of extension of hypoperfusion in the órbito-frontal lobule are stable and independent of the Wisconsin stressor and occur in both hemispheres. The findings in the patients with borderline personality disorder may be related to irritability, impropriety, euphoria, impulsivity, unwarranted familiarity and abnormalities of mood. This occurs in patients with border line personality disorder intermittently and related to situations of stress, in this study during the Wisconsin test.

Areas 28 – 36 and 40 –44

Among these areas 40 and 44 are related to language and areas 28 and 36 are related to codification of episodic memory. The areas related to language and memory could correspond to areas of the cortex that facilitate some of the behaviors that we have studied and this could by a hypothesis for future research.

Area 38 of Brodmann

This area is hypoperfused in basal conditions and during activation with the Wisconsin test and therefore does not present significant changes with the activation procedures (extension of hypoperfusion 47%) and in depression (extension of hypoperfusion 58%).

Area 38 is a segment of the temporal pole and facilitates the interaction of cognition and emotional aspects. In post mortem studies of suicides there is a low concentration of serotonynergic neurotransmission of that site. Of note is the finding of a loss of function of area 38 in both pathologies, that invite a study of aspects related to control of impulses and affective instability.

Therefore, in this hemodynamic cerebral study we have reported by means of cortical activation, that NeuroSPECT demonstrates in mayor depression and borderline personality disorder regional differences that are characteristically significant during the Wisconsin test. At the same time it demonstrates the existence of cortical areas that facilitate function in a nonspecific way and that participates in both processes.