METHOD

Patients

We have two groups of patients with a total of 50 patients studied randomly and that fulfilled exclusion criteria corresponding to DSM-IV abuse or dependence of psychoactive substances, bipolar disease, TOC, schizophrenia, surgical or neurodegenerative diseases and brain trauma.

The sample corresponds to a group "A" of 23 patients that had brain SPECT with HMPAO Tc-99m performed under basal conditions and group "B" of 27 patients, that had the injection of HMPAO delivered at the time of completion of the first set of 10 consecutive correct answers during the Wisconsin Test.

Group "A" had a mean age of 35,3 years and a sex distribution of 60,9% of men and 39,1% of women. Group "B" with a mean age of 36,8 years and 66,7% of men and 33,3% of women. There did not exist statistical significant differences for age or sex among these groups (P > 0.67 for age and P > 0.67 for sex).

The diagnosis of depression in this group of patients was made when the patient presented 5 or more of the symptoms defined in scheme I, for a period of time at least of two weeks and demanding always the presence of depressive mood or lack of interest or pleasure in activities that are usually pleasurable.

All the sample corresponded to patients with Major to Moderately Severe depression. Background analysis of the symptomatology of the patient restropectively demonstrated that this disorder was episodic in the majority of the cases and there were at least in three opportunities periods of depression during the last two years in all cases.

WISCONSIN TEST

We applied the Wisconsin card sorting test (22), consisted of a maximum of 128 questions in series of 10 correct consecutive answers and after each set there is a change of strategy that has to be noticed and defined by the patient.

Selection of cards is performed by computer in order to correct human bias. Also the velocity of response is calculated and the results are compared with normative databases for age matched groups, sex matched groups, dexterity and academic level defined by the computer.

EXCLUSION AND INCLUSION CRITERIA

The clinical diagnosis was performed by a psychiatrist defining the patients with the semiologic category of Major Depression using the DSM-IV and a functional psychological study performed by a psychologist, the Rorschach test (23, 24, 25, 26, 27) that orients the diagnosis and allows to exclude other pathologies and define qualitative elements that can orient treatment.

Once the diagnosis of major depression was established in some cases with the help of the family of the patient, the brain SPECT was performed.

Method. NeuroSPECT

Preparation of the Patient

Patient discontinued antidepressive medication at least 5 days before the performance of the NeuroSPECT test and 24 hours before, discontinued also consumption of tea, coffee, chocolate and cola beverages (29). Besides these limitations, the NeuroSPECT examination is performed under normal dietary conditions.

Contraindication of NeuroSPECT. Test can not be performed in pregnant women or in women suspected of the possibility of pregnancy.

TECHNIQUE

Injection of the radiopharmaceutical

a) 30mCi of HMPAO Tc-99m (Ceretec Amersham) (1110 mBq) in basal conditions are injected intravenously with the patient in dorsal decubitus in a room with ambient noise and light under control, the patient has the eyes opened and the injection is performed into antecubital vein that is cannulated 10 minutes before. The intravenous injection is given in an approximate volume of 2 ml. followed by a bolus of normal saline of 10 ml. 60 to 90 minutes after the injection, the NeuroSPECT images are gathered.

b) Wisconsin Test: the same amount of HMPAO is injected after the patient has completed the first set of 10 consecutive correct answers without control of environmental light or sound.

Acquisition Technique

The patient lies on whole body table with the head fixed in a head holder of special design with pillows under his knees, arms at the side of his trunk and the head is supported with a Velcro band on the forehead and chin.

For the SPECT acquisition we use a NeuroSPECT Sophy DSX (SMV, Ohio, USA) system with rectangular head and Ultra High Resolution collimator; we use an energy window 140 Kev with a window width of 20%. The matrix is 64 x 64 with a circular orbit and Step&Shoot motion with 64 steps and 360 degrees rotation. The time of acquisition per projection is 30 seconds with a zoom factor of 1.66 and at the end of acquisition we verify the possibility of a motion artifact in a Cine mode and the Sinogram will demonstrate the existence of patient motion. If there is patient motion, the acquisition is repeated without the necessity of reinjecting the patient.

NeuroSPECT Image Processing

The acquisition is tridimensionally reconstructed by back projection by means of a Butterworth filter 4.25, delimiting non-useful information by means of an elliptic ROI. We perform oblique reorientation for transaxial, coronal, and sagittal planes with a volume zoom of 35%.

The reconstructed tridimensional raw images are transferred in a M03 format to a PC computer in order to reprocess, quantify and normalize their volume.

a) Normalization of HMPAO brain uptake.

The computer performs an analysis of voxel by voxel brain uptake of HMPAO, the results are normalized and expressed as percentage of maximal uptake observed in the brain and the results displayed by means of a color scale that defines as normal values the ones observed between a range of 72% + 5 in red color, values above the normal mean, in silver color values above 82%, values below 60% (larger than 2 standard deviations below normal mean) expressed in color yellow, 50% of maximum in color green and below 40% in color blue.

Volume Normalization

We use the technique of Talairach (Arcila et al Alasbimn, Lima 1997). We reorient the tridimensional volume of the brain defining a line that fits the inferior pole of the occipital lobe and the inferior edge of the frontal lobe; this line is automatically rendered horizontal. We correct for lateral deviations defining a line above the interhemisphere fissure and automatically orienting this line in the vertical plane. In this reoriented image we define the intermediate level of the pons and anterior plane of the temporal lobes. We limit the volume of analysis in the lateral planes, superior and inferior planes of the brain. With this information, the Talairach technique renders the brain volume into a normalized volume and allows therefore, a voxel by voxel comparison of the HMPAO uptake in the brain cortex with a normal data base, corrected also volumetrically, for normal individuals at the age of 18 to 45 or normals of age 45 to 80 years. In this tridimensional image, we define a new color scale that represents in color red values above the normal mean and two standard deviations above the normal mean and color Silver, all values below the normal mean, in color green and all values below two standard deviations below the normal mean, in color BLUE. We define, therefore, areas of abnormal hypoperfusion that have 95% of probability of being hypoperfused and demonstrated in color BLUE and areas of hyperperfusion in color SILVERS that have 95% probability of being effectively hyperperfused in comparison with the normal database (Segami Corp., Maryland, USA).

The intraobserver reproducibility of these measurements was reported at the Alasbimn Meeting in Lima, Peru, 1997 and has a mean of reproducibility of 3.6 mm. that is considered acceptable for this type of technology.

In order to define with high reproducibility the exact localization of areas of hypoperfusion observed in Major Depression, we produced a template of 14 areas of Brodmann in each hemisphere that are involved with behavioral activities by means of the program CORELDRAW 8. We used the Brodmann areas as reference for clinical and experimental functional cerebral and pathological reported information. All these behavioral Brodmann areas are projected automatically by the computer on the anterior, left and right lateral and both para-sagittal images of the three dimensional images of the brain. The projection of this template is automatic and therefore the reproducibility of the results is 100%.

Quantification of extension of hypoperfusion in each Brodmann area. By consensus of both investigators, we estimated the percentage of each Brodmann area that appeared hypoperfused and demonstrated by the color blue in the image. These results were expressed, as percentage of the Brodmann area that we estimated was significantly hypoperfused.

Statistical analysis

The analysis of distribution of age and sex in both groups studied, basal studies and frontal stimulation by means of Wisconsin Test was performed by means of the Fisher Test. The comparison of basal results and brain SPECT results during the Wisconsin Test were performed by means of the Kruskal-Wallis Test with the correction of Pocock for multiple comparisons in dependent samples. We consider as abnormal results, all areas that demonstrated to be in hypoperfusion in an area larger than 40% and/or a significant difference between and the basal and Wisconsin Test with a P value < 0.05.