Journal of Affectiue Disorders, 21 (1991) 67-14 0 1991 Elsevier Science Publishers B.V. (Biomedical ADONIS 016503279100059N
67 Division)
0165-0327/91/$03.50
JAD 00771
Computed tomography of the brain in unipolar depression B. Van den Bossche I, M. Maes ‘, C. Brussaard 2, C. Schotte and A. De Schepper 2
‘, P. Cosyns ‘, J. De Moor
’
’ Department of Psychiatry and ’ Department of Radiology, University Hospital Antwerp, Edegem, Belgium (Received 12 April 1990) (Revision received 26 September 1990) (Accepted 3 October 1990)
Summary Several authors have reported enlarged lateral brain ventricles in major depressive patients as compared to healthy controls. Also, the enlargement of brain lateral ventricles has been related to delusions, psychomotor retardation and some biochemical data such as cortisol secretion and L-tryptophan serum levels. The present study was undertaken to investigate if melancholic depressives are characterised by a higher degree of brain atrophy than normal controls and minor depressives, the origin of any brain atrophy, and whether measures of brain atrophy are related to cortisol secretion and L-tryptophan serum levels. We investigated 10 healthy controls and 35 depressive patients categorised according to DSM-III. In contrast to previous studies, we determined a combination of indices which makes it possible to differentiate between central and cortical diffuse atrophy. We found no evidence for the existence of abnormal atrophy of the brain in melancholies; nor did we find any correlation between CT scan measurements and cortisol or tryptophan.
Key words:
Depression;
Computed
tomography;
Brain atrophy;
Introduction Previous research has shown that some schizophrenics have enlarged lateral ventricles (Johnstone et al., 1976; Weinberger et al., 1979; Golden et al., 1980; Donnelly et al., 1980; Crow, 1980; Andreasen et al., 1982). Morphologic brain alter-
Address for correspondence: Dr. B. Van den Bossche, Department of Psychiatry, University Hospital Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium.
Cortisol;
Tryptophan
ations have also been investigated in depressive patients. Some investigators have reported the presence of enlarged lateral ventricles (as assessed by means of VBR, a planimetric index) in depressed (Scott et al., 1983; Targum et al., 1983; Pearlson et al., 1985; Dolan et al., 1985) and bipolar patients (Pearlson and Veroff, 1981; Pearlson et al., 1981, 1984a,b; Nasrallah et al., 1982, 1985; Luchins and Meltzer, 1983; Luchins et al., 1984) as compared with healthy controls. Associations were demonstrated between enlarged lateral ventricles and the presence of delusions (Targum
68
et al., 1983; Luchins et al., 1984) unemployment (Pearlson et al., 1984a, 1985) total number of admissions to hospital (Pearlson et al., 1985) and psychomotor retardation (Schlegel et al., 1989). On the other hand, Rossi et al. (1987) and Schlegel and Kretzschmar (1987) found no significant differences in VBR measurements between depressive patients and healthy controls. Depressive patients have a significantly greater width of the third ventricle, a significantly different Huckmann number and frontal horn index (all linear indices) than controls (Schlegel and Kretzschmar, 1987). Brain atrophy is defined as a loss of substance within the brain, which may involve the white matter, the grey matter or both. A significant increase in the size of the ventricular system is apparent after the sixth decade, together with a progressive increase in the width of the cerebral sulci, as part of the normal aging process (Zatz et al., 1982). The existence of enlarged lateral ventricles, too prominent for age, is indicative of either hydrocephalus or atrophy. Brain atrophy is associated with various conditions and can be focal or diffuse. Diffuse brain atrophy has been classified as due to central atrophy, in which the ventricular enlargement is more prominent than the widening of the sulci, cortical atrophy, in which the sulci are wide relative to the ventricles, or the combination of central and cortical atrophy. Diffuse atrophy is most often due to the combination of central and cortical atrophy (i.e., white and grey matter). CT scan findings have been described that distinguish ventricular enlargement in non-communicating hydrocephalus from that in atrophy (TerBrugge et al., 1987). Once one has decided that diffuse atrophy is present, one has to differentiate between central and cortical atrophy. The ventricular size index (VSI) yields information about ventricular enlargement, as does the ventricular brain ratio (VBR). Several authors have described different versions of the VBR method (Synek and Reuben, 1976; Pearlson et al., 1981; Weinberger et al., 1982; Reveley, 1985). In addition, some authors have examined the relationship between CT scan measurements and biological markers of depression, i.e., hypothalamic-pituitary-adrenal axis hyperactivity (Carroll et al., 1976; Rubinow et al., 1984; Stokes et
al., 1984) and decreased availability of L-tryptophan (L-TRP) (Shaw et al., 1987; Joseph et al., 1984: Moller et al., 1986; Maes et al., 1987). Kellner et al. (1983) established a positive relationship between the VBR and urinary free cortisol. Standish-Barry et al. (1986) found a negative correlation between free plasma tryptophan and the Evans ratio (Evans, 1942). The aims of the present study were to (1) investigate whether severely depressed patients are characterised by CT abnormalities, (2) determine whether diffuse atrophy (central, cortical or mixed) of the brain is present and (3) determine the putative correlations between the dexamethasone suppression test (DST), L-TRP and CT scan measurements of the brain. Subjects and methods Subjects Forty-five subjects participated in this study: 35 unipolar depressed inpatients and 10 controls. From December 1987 until September 1988, patients consecutively admitted to the psychiatric ward were screened to see whether they met the DSM-III criteria for minor depression, including dysthymic disorder (300.40) and adjustment disorder with depressed mood (309.00) major depression without melancholia (296.X2) or major depression with melancholia (296.X3). After checking for exclusion criteria such as a history of birth trauma, head injury. epilepsy, addiction to alcohol or tranquillisers, neurological diseases, long-term hospitalisation and electroconvulsive therapy, 35 patients remained. All 35 gave their informed consent to participate in the study. Diagnoses were made by means of the Structured Clinical Interview for DSM-IIIR axis 1, patient version (Spitzer et al., 1985). The severity of illness was measured by means of the Hamilton Depression Rating Scale (HDRS) (Hamilton, 1960). Results of routine examinations by an internist and routine urine and blood plasma tests were within normal limits. Ambulatory patients undergoing a CT scan in the same period to examine the cervical vertebrae because of cervicalgia, or the maxillary and frontal sinuses because of sinusitis, were included in the
69 study as controls, after informed consent and checking for the exclusion criteria. To exclude depression, controls were also rated on the HDRS. All subjects were free of any medication. Some patients received a low-dosage schedule of benzodiazepines during the study period (i.e., di-Kchlorazepam < 25 mg and/or flurazepam < 27.5 mg) in the case of severe anxiety or sleep disorders. Methods Six days after admission a blood sample was taken at 8 a.m. for the determination of E-tryptophan, valine, leucine, phenylalanine, isoleucine and tyrosine. Amino acid determinations were done by the method proposed by Tumell and Cooper (1982) with slight modifications. Determinations were done by liquid chromatography, pre-column derivatisation with ortho-phthaldialdehyde and fluorimetric detection at an excitation wavelength of 330 nm and an emission wavelength of 418 nm (Schoeffel FS970 Fluorimeter). The interassay coefficient of variation for L-TRP was 8.6% (mean = 76 x 10m6, n = 5) for valine 8.6% (mean = 209 x 10e4, n = 5), for leucine 7.9% n = 5), for tyrosine 8.4% (mean = 159 X 10e6, (mean = 65 x 10e6, n = 5) for phenylalanine 9.5% (mean = 81 x 10m9, n = 5) and for isoleucine 10.2% (mean = 73 X 10m4, n = 5) (all in pmol/l). The ratio between L-TRP and the five competing amino acids was calculated (L-TRP/CAA). The same day at 11 p.m. dexamethasone (1 mg orally) was administered to the patient. The following day at 8 a.m. fasting blood samples were taken for the assay of post-dexamethasone cortisol. Cortisol levels were determined with a commercial enzyme immunoassay. The interassay coefficient of variation in the low range (mean = 8.8 pg/dl, n = 10) was 9% and in the medium range (mean = 20.0 pg/dl, n = 20) 10%. Twelve days after admission, the CT scans were performed (all without injection of contrast material) using a 512 X 512 matrix scanner (CT GE 9800); lo-12 slices with a thickness of 10 mm were taken, parallel with the orbitomeatal line. The ventricular size index (VSI) was calculated by taking the ratio of the frontal horn diameter to the bifrontal diameter at the level of the sella media (Terbrugge et al., 1987) (see Tables 3 and 4,
x1/x2). The fluid brain ratio was also determined. At the level of the sella media the surfaces were measured of the area occupied by fluid in the ventricles and in the subarachnoidal spaces (1) and the area occupied by the brain parenchyma (2). For this purpose a density mask was used (Haug, 1977; Pederson et al., 1976). The mask measured area 1 with a density of O-15 Hounsfield units (HU), and area 2 with a density of 25-60 HU. The fluid brain ratio was computed as the ratio l/2 (see Tables 3 and 4, x3/x4). Statistics The independence of the classification systems was ascertained by the x2-test. Relationships between variables were computed by means of Pearson’s product moment and the point-biserial correlation coefficients. Transformations were used to reach normality of distribution (tested by means of the Kolmogorov-Smimov test). Intergroup differences were checked by means of analysis of variance (ANOVA) and analysis of covariance (ANCOVA). The significance level was set at (Y= 0.05 (two-tailed). Results Table 1 shows the demographic data of the healthy controls and depressed patients in this
TABLE 1 DEMOGRAPHIC DATA OF THE 45 SUBJECTS IN THIS STUDY Category
Index
Number men/ women
Age (years) mean(f1 SD)
HC
4/6
49.1 ( f 15.7)
Minor depression (300.40,309.00)
md
3/10
46.8 (+ 15.6)
Major depression without melancholia (296.X2)
MD-M
4/9
50.3 ( f 12.6)
Major depression with melancholia (296.X3)
MD+M
2/7
52.8 (zk 16.3)
Major depression (296.X2, 296.X3)
MD+M
6/16
51.2 (f 13.9)
Healthy
controls
70 TABLE HDRS
2 SCORES
TABLE OF THE SUBJECTS Index
Category
RESULTS HEALTHY HDRS * mean(f1
SD)
controls
HC
5.4 (i4.9)
Minor depression (300.40,309.00)
md
16.8 (+- 2.9)
Major depression without melancholia (296.X2)
MD-M
21.8 (i 2.9)
Major depression with melancholia (296.X3)
MD+M
Major depression
MD+M
Healthy
3
28.1 (k5.1)
OF BRAIN CONTROLS
CT SCAN MEASUREMENTS IN AND DEPRESSIVE INPATIENTS
Index
xl
x2
x4
HC md MD-M MD+M MDiM
3.42 (k0.52) 3.22(*0.62) 3.33 (k0.39) 3.40(+0.51) 3.36(*0.43)
7.5 (+ 3.8) 12.28 (i 1.34) 11.74(+0.96) 8.2(_t5.9) 11.71 (k1.14) 8.6 (k3.7) 11.15(~0.58) 11.1 (k7.0) 11.48(i0.97) 9.7(*5.3)
F value P value
0.30 0.74
x3
0.45 0.65
3.00 0.06
162 (+ 17) 144(?21) 145 (k19) 149(+14) 147(+17) 2.95 0.06
* The HDRS scores are statistically significantly different between the distinct groups: F= 58.3, df = 3,41, P 3.5 Fg/dl) or between patients with higher and lower (< 0.08) L-TRP/CA.A ratios. Discussion The results of the present study show that there are no differences in the measured CT scan parameters and computed indices between severely depressed patients and minor depressives or healthy controls. The VSI values of our patients and controls are within the normal limits (Terbrugge et al., 1987). For the FBR no reference values are known. If our healthy controls are accepted as a reference, we have no reason to conclude that our depressed patients show abnormal FBR values. Consequently, there is no evidence for diffuse atrophy of the brain in our severely depressed patients. Our results and conclusions are in contrast with the results of Scott et al. (1983) Targum et al. (1983), Pearlson et al. (1985) and Dolan et al. (1985) who found an increased VBR in unipolar depressed patients. Pearlson and Veroff (1981), Pearlson et al. (1981, 1984a,b), Nasrallah et al. (1982, 1985), Luchins and Meltzer (1983) and Luchins et al. (1984) also found enlarged VBR values in severely depressed patients, but some of their subjects were bipolar depressives. However, our findings agree with the negative results of Rossi et al. (1987) and Schlegel and Kretzschmar
(1987) who found no difference in VBR between depressive patients and healthy controls. As stated in the Introduction, one of the aims of this study was to determine the nature of diffuse atrophy if our results had shown its presence. Therefore we preferred to determine both FBR and VSI instead of VBR and VSI or VBR alone. Most previous studies only determined VBR. The finding of an increased VBR is indicative of either hydrocephalus or diffuse atrophy. Characteristics of the VSI have been described to distinguish between these two possibilities (TerBrugge et al., 1987). To evaluate the role of the cortex in diffuse atrophy, one can consider whether the sulci are wide relative to the possible enlargement of the lateral ventricles (cortical atrophy). In this case the index of total atrophy (FBR) would be high relative to the index of central atrophy (VSI). FBR is a new index in the field of psychiatric brain research. It is clear that both the widening of the sulci, an indication of cortical atrophy, and the enlargement of the lateral ventricles, an indication of central atrophy, determine the value of this ratio. For this reason the FBR is an index of total atrophy. As a method for measuring surfaces, just as the VBR is a method to assess surfaces, it was validated by Degryse et al. (1987). In comparison to VBR it is much more accurate. We would like to emphasise the obvious inaccuracy of VBR measurements. The accuracy of this method depends on the ability of the assessor manipulating the joystick to delineate the ventricles and the brain. Even with the density method as an aid to delineate the ventricles, the delineation of the brain remains crude. The usefulness of the method of computerised counting of pixels between given Hounsfield ranges as a method of surface measuring was proven, in analogy, by Van Gaal (1990). Our line of research investigates diffuse brain atrophy. Schlegel and Kretzschmar (1987) formulated a hypothesis about focal brain atrophy. They determined both planimetric (VBR) and linear indices but found significant differences between severely depressed subjects and controls only for some of the linear indices. Consequently, those authors stressed the topographical importance of their linear indices. Their hypothesis was that a mild atrophy in the caudate nucleus region, due to transient metabolic disorders, is the cause
72
of the mild enlargement of the ventricles. This hypothesis is supported by positron emission tomography findings in depressed subjects (Baxter et al., 1985) and by neuropathological examinations in affective disorders (Brown et al., 1986). We did not find a correlation between any of the measured CT scan parameters or computed indices (MI, FBR) and the post-dexamethasone cortisol values. This is in agreement with the results of Targum et al. (1983), who did not find a correlation between DST and VBR. However, Kellner et al. (1983) found a positive correlation between urinary free cortisol in a 24-h sample and VBR in severely depressive patients. Also, Schlegel and Kretzschmar (1987) found greater linear parameters (measuring the lateral ventricles of the brain) in DST non-suppressors than in DST suppressors. In contrast to the findings of Standish-Barry et al. (1986), who found a significant negative correlation between free plasma tryptophan and the Evans ratio, we did not find any correlation between the ratio of plasma tryptophan and its competing amino acids and any of the linear or planimetric measurements. References American Psychiatric Association (1980) Diagnostic and Statistical Manual of Mental Disorders, 3rd edn. American Psychiatric Association, Washington, DC. Andreasen, N.C., Olsen, S.A., Dennert, J.W. and Smith, M.R. (1982) Ventricular enlargement in schizophrenia: relationship to positive and negative symptoms. Am. J. Psychiatry 139, 297-301. Baxter, L.R., Phelps, M.E., Mazziotta, J.C., Schwartz, J.M., Gemer, R.H., Selin, C.E. and Sumida, R.M. (1985) Cerebral metabolic rates for glucose in mood disorders. Arch. Gen. Psychiatry 42,441-447. Bentson, J.R., Reza, M., Winter, J. and Wilson, G. (1978) Steroids and apparent cerebral atrophy on computed tomography scans. J. Comp. Ass. Tomogr. 2, 16. Brown, R., Colter, N., Corselis, J.A.N., Crow, T.J., Frith, C.D., Jagoe, R., Johnstone, E.C. and Marsh, L. (1986) Postmortem evidence of structural brain changes in schizophrema. Arch. Gen. Psychiatry 43, 36-42. Carroll, B.J., Curtis, G.C. and Mendels, J. (1976) Neuroendocrine regulation in depression. II. Discrimination of depressed from non-depressed patients. Arch. Gen. Psychiatry 33, 1051-1058. Carroll, B.J., Feinberg, M., Greden, J., Tarika, J., Albala, A.H., Haskett, R.F., James, N.Mcl., Kronfol, Z., Lohr, N., Steiner,
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67 Division)
0165-0327/91/$03.50
JAD 00771
Computed tomography of the brain in unipolar depression B. Van den Bossche I, M. Maes ‘, C. Brussaard 2, C. Schotte and A. De Schepper 2
‘, P. Cosyns ‘, J. De Moor
’
’ Department of Psychiatry and ’ Department of Radiology, University Hospital Antwerp, Edegem, Belgium (Received 12 April 1990) (Revision received 26 September 1990) (Accepted 3 October 1990)
Summary Several authors have reported enlarged lateral brain ventricles in major depressive patients as compared to healthy controls. Also, the enlargement of brain lateral ventricles has been related to delusions, psychomotor retardation and some biochemical data such as cortisol secretion and L-tryptophan serum levels. The present study was undertaken to investigate if melancholic depressives are characterised by a higher degree of brain atrophy than normal controls and minor depressives, the origin of any brain atrophy, and whether measures of brain atrophy are related to cortisol secretion and L-tryptophan serum levels. We investigated 10 healthy controls and 35 depressive patients categorised according to DSM-III. In contrast to previous studies, we determined a combination of indices which makes it possible to differentiate between central and cortical diffuse atrophy. We found no evidence for the existence of abnormal atrophy of the brain in melancholies; nor did we find any correlation between CT scan measurements and cortisol or tryptophan.
Key words:
Depression;
Computed
tomography;
Brain atrophy;
Introduction Previous research has shown that some schizophrenics have enlarged lateral ventricles (Johnstone et al., 1976; Weinberger et al., 1979; Golden et al., 1980; Donnelly et al., 1980; Crow, 1980; Andreasen et al., 1982). Morphologic brain alter-
Address for correspondence: Dr. B. Van den Bossche, Department of Psychiatry, University Hospital Antwerp, Wilrijkstraat 10, 2650 Edegem, Belgium.
Cortisol;
Tryptophan
ations have also been investigated in depressive patients. Some investigators have reported the presence of enlarged lateral ventricles (as assessed by means of VBR, a planimetric index) in depressed (Scott et al., 1983; Targum et al., 1983; Pearlson et al., 1985; Dolan et al., 1985) and bipolar patients (Pearlson and Veroff, 1981; Pearlson et al., 1981, 1984a,b; Nasrallah et al., 1982, 1985; Luchins and Meltzer, 1983; Luchins et al., 1984) as compared with healthy controls. Associations were demonstrated between enlarged lateral ventricles and the presence of delusions (Targum
68
et al., 1983; Luchins et al., 1984) unemployment (Pearlson et al., 1984a, 1985) total number of admissions to hospital (Pearlson et al., 1985) and psychomotor retardation (Schlegel et al., 1989). On the other hand, Rossi et al. (1987) and Schlegel and Kretzschmar (1987) found no significant differences in VBR measurements between depressive patients and healthy controls. Depressive patients have a significantly greater width of the third ventricle, a significantly different Huckmann number and frontal horn index (all linear indices) than controls (Schlegel and Kretzschmar, 1987). Brain atrophy is defined as a loss of substance within the brain, which may involve the white matter, the grey matter or both. A significant increase in the size of the ventricular system is apparent after the sixth decade, together with a progressive increase in the width of the cerebral sulci, as part of the normal aging process (Zatz et al., 1982). The existence of enlarged lateral ventricles, too prominent for age, is indicative of either hydrocephalus or atrophy. Brain atrophy is associated with various conditions and can be focal or diffuse. Diffuse brain atrophy has been classified as due to central atrophy, in which the ventricular enlargement is more prominent than the widening of the sulci, cortical atrophy, in which the sulci are wide relative to the ventricles, or the combination of central and cortical atrophy. Diffuse atrophy is most often due to the combination of central and cortical atrophy (i.e., white and grey matter). CT scan findings have been described that distinguish ventricular enlargement in non-communicating hydrocephalus from that in atrophy (TerBrugge et al., 1987). Once one has decided that diffuse atrophy is present, one has to differentiate between central and cortical atrophy. The ventricular size index (VSI) yields information about ventricular enlargement, as does the ventricular brain ratio (VBR). Several authors have described different versions of the VBR method (Synek and Reuben, 1976; Pearlson et al., 1981; Weinberger et al., 1982; Reveley, 1985). In addition, some authors have examined the relationship between CT scan measurements and biological markers of depression, i.e., hypothalamic-pituitary-adrenal axis hyperactivity (Carroll et al., 1976; Rubinow et al., 1984; Stokes et
al., 1984) and decreased availability of L-tryptophan (L-TRP) (Shaw et al., 1987; Joseph et al., 1984: Moller et al., 1986; Maes et al., 1987). Kellner et al. (1983) established a positive relationship between the VBR and urinary free cortisol. Standish-Barry et al. (1986) found a negative correlation between free plasma tryptophan and the Evans ratio (Evans, 1942). The aims of the present study were to (1) investigate whether severely depressed patients are characterised by CT abnormalities, (2) determine whether diffuse atrophy (central, cortical or mixed) of the brain is present and (3) determine the putative correlations between the dexamethasone suppression test (DST), L-TRP and CT scan measurements of the brain. Subjects and methods Subjects Forty-five subjects participated in this study: 35 unipolar depressed inpatients and 10 controls. From December 1987 until September 1988, patients consecutively admitted to the psychiatric ward were screened to see whether they met the DSM-III criteria for minor depression, including dysthymic disorder (300.40) and adjustment disorder with depressed mood (309.00) major depression without melancholia (296.X2) or major depression with melancholia (296.X3). After checking for exclusion criteria such as a history of birth trauma, head injury. epilepsy, addiction to alcohol or tranquillisers, neurological diseases, long-term hospitalisation and electroconvulsive therapy, 35 patients remained. All 35 gave their informed consent to participate in the study. Diagnoses were made by means of the Structured Clinical Interview for DSM-IIIR axis 1, patient version (Spitzer et al., 1985). The severity of illness was measured by means of the Hamilton Depression Rating Scale (HDRS) (Hamilton, 1960). Results of routine examinations by an internist and routine urine and blood plasma tests were within normal limits. Ambulatory patients undergoing a CT scan in the same period to examine the cervical vertebrae because of cervicalgia, or the maxillary and frontal sinuses because of sinusitis, were included in the
69 study as controls, after informed consent and checking for the exclusion criteria. To exclude depression, controls were also rated on the HDRS. All subjects were free of any medication. Some patients received a low-dosage schedule of benzodiazepines during the study period (i.e., di-Kchlorazepam < 25 mg and/or flurazepam < 27.5 mg) in the case of severe anxiety or sleep disorders. Methods Six days after admission a blood sample was taken at 8 a.m. for the determination of E-tryptophan, valine, leucine, phenylalanine, isoleucine and tyrosine. Amino acid determinations were done by the method proposed by Tumell and Cooper (1982) with slight modifications. Determinations were done by liquid chromatography, pre-column derivatisation with ortho-phthaldialdehyde and fluorimetric detection at an excitation wavelength of 330 nm and an emission wavelength of 418 nm (Schoeffel FS970 Fluorimeter). The interassay coefficient of variation for L-TRP was 8.6% (mean = 76 x 10m6, n = 5) for valine 8.6% (mean = 209 x 10e4, n = 5), for leucine 7.9% n = 5), for tyrosine 8.4% (mean = 159 X 10e6, (mean = 65 x 10e6, n = 5) for phenylalanine 9.5% (mean = 81 x 10m9, n = 5) and for isoleucine 10.2% (mean = 73 X 10m4, n = 5) (all in pmol/l). The ratio between L-TRP and the five competing amino acids was calculated (L-TRP/CAA). The same day at 11 p.m. dexamethasone (1 mg orally) was administered to the patient. The following day at 8 a.m. fasting blood samples were taken for the assay of post-dexamethasone cortisol. Cortisol levels were determined with a commercial enzyme immunoassay. The interassay coefficient of variation in the low range (mean = 8.8 pg/dl, n = 10) was 9% and in the medium range (mean = 20.0 pg/dl, n = 20) 10%. Twelve days after admission, the CT scans were performed (all without injection of contrast material) using a 512 X 512 matrix scanner (CT GE 9800); lo-12 slices with a thickness of 10 mm were taken, parallel with the orbitomeatal line. The ventricular size index (VSI) was calculated by taking the ratio of the frontal horn diameter to the bifrontal diameter at the level of the sella media (Terbrugge et al., 1987) (see Tables 3 and 4,
x1/x2). The fluid brain ratio was also determined. At the level of the sella media the surfaces were measured of the area occupied by fluid in the ventricles and in the subarachnoidal spaces (1) and the area occupied by the brain parenchyma (2). For this purpose a density mask was used (Haug, 1977; Pederson et al., 1976). The mask measured area 1 with a density of O-15 Hounsfield units (HU), and area 2 with a density of 25-60 HU. The fluid brain ratio was computed as the ratio l/2 (see Tables 3 and 4, x3/x4). Statistics The independence of the classification systems was ascertained by the x2-test. Relationships between variables were computed by means of Pearson’s product moment and the point-biserial correlation coefficients. Transformations were used to reach normality of distribution (tested by means of the Kolmogorov-Smimov test). Intergroup differences were checked by means of analysis of variance (ANOVA) and analysis of covariance (ANCOVA). The significance level was set at (Y= 0.05 (two-tailed). Results Table 1 shows the demographic data of the healthy controls and depressed patients in this
TABLE 1 DEMOGRAPHIC DATA OF THE 45 SUBJECTS IN THIS STUDY Category
Index
Number men/ women
Age (years) mean(f1 SD)
HC
4/6
49.1 ( f 15.7)
Minor depression (300.40,309.00)
md
3/10
46.8 (+ 15.6)
Major depression without melancholia (296.X2)
MD-M
4/9
50.3 ( f 12.6)
Major depression with melancholia (296.X3)
MD+M
2/7
52.8 (zk 16.3)
Major depression (296.X2, 296.X3)
MD+M
6/16
51.2 (f 13.9)
Healthy
controls
70 TABLE HDRS
2 SCORES
TABLE OF THE SUBJECTS Index
Category
RESULTS HEALTHY HDRS * mean(f1
SD)
controls
HC
5.4 (i4.9)
Minor depression (300.40,309.00)
md
16.8 (+- 2.9)
Major depression without melancholia (296.X2)
MD-M
21.8 (i 2.9)
Major depression with melancholia (296.X3)
MD+M
Major depression
MD+M
Healthy
3
28.1 (k5.1)
OF BRAIN CONTROLS
CT SCAN MEASUREMENTS IN AND DEPRESSIVE INPATIENTS
Index
xl
x2
x4
HC md MD-M MD+M MDiM
3.42 (k0.52) 3.22(*0.62) 3.33 (k0.39) 3.40(+0.51) 3.36(*0.43)
7.5 (+ 3.8) 12.28 (i 1.34) 11.74(+0.96) 8.2(_t5.9) 11.71 (k1.14) 8.6 (k3.7) 11.15(~0.58) 11.1 (k7.0) 11.48(i0.97) 9.7(*5.3)
F value P value
0.30 0.74
x3
0.45 0.65
3.00 0.06
162 (+ 17) 144(?21) 145 (k19) 149(+14) 147(+17) 2.95 0.06
* The HDRS scores are statistically significantly different between the distinct groups: F= 58.3, df = 3,41, P 3.5 Fg/dl) or between patients with higher and lower (< 0.08) L-TRP/CA.A ratios. Discussion The results of the present study show that there are no differences in the measured CT scan parameters and computed indices between severely depressed patients and minor depressives or healthy controls. The VSI values of our patients and controls are within the normal limits (Terbrugge et al., 1987). For the FBR no reference values are known. If our healthy controls are accepted as a reference, we have no reason to conclude that our depressed patients show abnormal FBR values. Consequently, there is no evidence for diffuse atrophy of the brain in our severely depressed patients. Our results and conclusions are in contrast with the results of Scott et al. (1983) Targum et al. (1983), Pearlson et al. (1985) and Dolan et al. (1985) who found an increased VBR in unipolar depressed patients. Pearlson and Veroff (1981), Pearlson et al. (1981, 1984a,b), Nasrallah et al. (1982, 1985), Luchins and Meltzer (1983) and Luchins et al. (1984) also found enlarged VBR values in severely depressed patients, but some of their subjects were bipolar depressives. However, our findings agree with the negative results of Rossi et al. (1987) and Schlegel and Kretzschmar
(1987) who found no difference in VBR between depressive patients and healthy controls. As stated in the Introduction, one of the aims of this study was to determine the nature of diffuse atrophy if our results had shown its presence. Therefore we preferred to determine both FBR and VSI instead of VBR and VSI or VBR alone. Most previous studies only determined VBR. The finding of an increased VBR is indicative of either hydrocephalus or diffuse atrophy. Characteristics of the VSI have been described to distinguish between these two possibilities (TerBrugge et al., 1987). To evaluate the role of the cortex in diffuse atrophy, one can consider whether the sulci are wide relative to the possible enlargement of the lateral ventricles (cortical atrophy). In this case the index of total atrophy (FBR) would be high relative to the index of central atrophy (VSI). FBR is a new index in the field of psychiatric brain research. It is clear that both the widening of the sulci, an indication of cortical atrophy, and the enlargement of the lateral ventricles, an indication of central atrophy, determine the value of this ratio. For this reason the FBR is an index of total atrophy. As a method for measuring surfaces, just as the VBR is a method to assess surfaces, it was validated by Degryse et al. (1987). In comparison to VBR it is much more accurate. We would like to emphasise the obvious inaccuracy of VBR measurements. The accuracy of this method depends on the ability of the assessor manipulating the joystick to delineate the ventricles and the brain. Even with the density method as an aid to delineate the ventricles, the delineation of the brain remains crude. The usefulness of the method of computerised counting of pixels between given Hounsfield ranges as a method of surface measuring was proven, in analogy, by Van Gaal (1990). Our line of research investigates diffuse brain atrophy. Schlegel and Kretzschmar (1987) formulated a hypothesis about focal brain atrophy. They determined both planimetric (VBR) and linear indices but found significant differences between severely depressed subjects and controls only for some of the linear indices. Consequently, those authors stressed the topographical importance of their linear indices. Their hypothesis was that a mild atrophy in the caudate nucleus region, due to transient metabolic disorders, is the cause
72
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