journal of Affective !Isevier
Disorders,
153
19 (1990) 153-162
AD 00713
Comparison of regional brain metabolism in bulimia nervosa and affective disorder assessed with positron emission tomography J.O. Hagman, Department
M.S. Buchsbaum, of Psychiatry,
J.C. Wu, S.J. Rao, C.A. Reynolds
University of California-Irvine,
and B.J. Blinder
Medical Sciences I, D-404, Irvine, CA 92717, U.S.A.
(Received 16 June 1989) (Accepted 13 December 1989)
Summary Women with bulimia often present with symptoms of depression in addition to bingeing and purging Jehavior. Brain metabolism in eight women with bulimia nervosa was compared to that in eight women vith major affective disorder and eight normal women, using positron emission tomography and l%fluoro!-deoxyglucose. Normal women have higher right than left cortical metabolic rates and active basal ganglia. Bulimics lost the normal right activation in some areas, but maintained basal ganglia activity. Depressives retained right hemisphere activation, but had decreased metabolism in basal ganglia. This uggests that although women with bulimia frequently present with symptoms of depression, the patho)hysiologic changes associated with bulimia differ from major affective disorder.
Uey words:
Depression;
Eating
disorders;
l&Fluoro-deoxyglucose;
Introduction The significance and relative importance of dejressive symptoms in bulimia have been the focus )f many biological and clinical studies. Women vith bulimia nervosa often present with symptoms )f depression in addition to bingeing and purging )ehavior. DSM-III (1980) included ‘depressed nood and self-deprecating thoughts following eatng binges’ in the diagnostic criteria for bulimia. deflecting the controversy over depressive symp-
Address for correspondence: Jennifer 0. Hagman M.D., 3epartment of Psychiatry, University of California-Irvine, Yledical Sciences 1, D-404, Irvine, CA 92717, U.S.A. 1165-0327/90/$03.50
0 1990 Elsevier Science Publishers
Cerebral
metabolic
rate; Serotonin
toms in bulimia, the current DSM-IIIR (1987) criteria for bulimia nervosa deleted the presence of depressed mood in the symptoms necessary for the diagnosis. A study by Hudson et al. (1983) found that 88% of a sample of bulimics displayed a lifetime diagnosis of a major affective disorder. Pope et al. (1989) found no difference in the character of depressive symptoms, using the Hamilton Rating Scale for Depression, between bulimic and depressed subjects. Family history studies have yielded a high prevalence of major affective disorder in the relatives of patients with bulimia (Pyle et al., 1981; Hudson et al., 1982). However, a recent review of the published studies (Levy et al., 1989) including studies of clinical data, family history, pharmacotherapy and neurobiology, con-
B.V. (Biomedical
Division)
154
eluded that. while many bulimic patients are depressed. a preponderance of evidence suggests that bulimia is not a variant of depression. A positron emission tomography (PET) study of patients with anorexia nervosa, some of whom also reported bulimic symptoms of bingeing and purging. reported increased metabolism in basal ganglia (Herholz et al.. 1987). A study of normal weight patients with bulimia (Wu et al.. 1990) found normal metabolic rates in the basal ganglia. This is in contrast to patients with affective disorder where two studies have found reduced metabolism in the basal ganglia (Buchsbaum et al., 1987: Baxter et al., 1985). However, neither of these studies directly compared bulimics and affectives statistically. Another PET study of depression (Baxter et al.. 1989) compared metabolic activity in subjects with unipolar, bipolar, and obsessive compulsive disorder with and without depression. and found that presence of depressive symptoms in all three disorders was correlated with decreased metabolism in the left dorsal anterolateral prefrontal cortex (middle frontal gyrus). Previous studies had suggested that these were biologically distinct psychiatric illnesses (Baxter et al., 1985, 1987; Schwartz et al.. 1987). Since depressive symptoms are often present in patients with bulimia it is possible that a similar abnormality may be found upon PET scanning. The current report is the first study to compare brain metabolism in women with bulimia nervosa, major affective disorder and normal women under the same experimental conditions.
a count of the number of episodes per week of bingeing and vomiting, and received a global clinical rating of depressive symptoms by a psychiatrist (scale 1 to 7 most severe). None of the bulimic subjects had a prior history of anorexia nervosa. Although depressive symptoms were evaluated in the initial interview, axis I DSM-IIIR diagnoses of depression were not made initially in the bulimic group. For the current analysis, the senior author located six of the eight bulimic subjects and administered the major affective disorder section of the Present State Exam-lifetime version (PSE. Wing et al., 1974) to five to assess depressive illness. One bulimic subject was hospitalized receiving electroconvulsive therapy (ECT) for major depression in another state, and two subjects had moved without leaving new addresses or phone numbers. In the six bulimic women contacted, four met criteria for dysthymic disorder. and two met criteria for major depressive disorder during the period in which the PET scan was performed. The two bulimic subjects who were not reached for interview had scores of 12 and 17 on the Hamilton. and clinical global ratings of depression severity of 3 and 4, respectively. None of the depressed group had a prior history of bulimia nervosa or anorexia nervosa. Subjects were off all psychoactive medications for a minimum of 30 days, were in good physical health and none had significant abnormalities on physical examination or laboratory screening tests, including ketone bodies in urine. Subjects with a history of seizure disorders, major head trauma or current substance abuse were excluded.
Methods Subjects Eight female patients with bulimia (two left handed), eight age matched women with major affective disorder (unipolar type, one left handed) and eight age and sex matched normal controls served as subjects (Table 1). All subjects met DSM-IIIR criteria for bulimia nervosa, or major depression in the patient groups, as assessed by non-structured psychiatric interview. None of the normal controls had any history of psychiatric illness. Each of the bulimic patients completed the Eating Attitudes Test (EAT, Garner and Garfinkel, 1979), the Hamilton Depression Rating Scale,
Scanning procedure und quantification Subjects performed the visual continuous performance task (CPT, Nuechterlein et al., 1983) during 18-fluoro-2-deoxyglucose uptake and were scanned as described elsewhere (Buchsbaum et al., 1987). For each PET slice, the outer brain contour was outlined with a boundary-finding technique developed for skull on CT scans as described elsewhere (Buchsbaum et al., 1984, 1989). This corrects for minor rotation of the head. Four lobes (and four regions within each lobe) are specified from the cortical peel: frontal (superior, middle, inferior, precentral), parietal (postcentral, supramarginal, angular, superior), temporal (superior,
155 TABLE
1
CLINICAL
CHARACTERISTICS
OF SUBJECTS
Height (inches) Age (years) Weight (pounds) Hamilton depression score Clinical rating Binge frequency (weekly) Vomit frequency (weekly) EAT score
Bulimia
Depression
Control
65.1* 2.4 28.6f 6.5 127 f13.6 20.8+_ 6.9 4.25 1.2 14.1 f 10.0 14.3* 9.2 37.8 + 10.3
64.3* 3.1 29.4* 5.7 133 f16.9 31x* 5.1 * 4.1 f 1.5
64.9* 3.6 28.9* 7.7 139 +33.1
* P < 0.005, f-test.
middle, inferior, posterior) and occipital (area 19, area 17, area 2-17, area 18), for right and left hemisphere. Subcortical regions were identified stereotaxically. The proportional locations of boxes identified on the Matsui and Hirano (1978) atlas were then transferred automatically to the PET slices (Buchsbaum et al., 1987), and mean glucose metabolic rates were calculated for the left and right sided boxes. Four brain regions (and three structures within each region) chosen for subcortical analysis were: medial frontal structures (paracentral, medial frontal, superior frontal), thalamus (anterior, medial, lateral), basal ganglia (caudate, putamen, and limbic (hippocampus, globus pallidus), amygdala, uncus). Glucose computation Values of glucose use were calculated according to the Sokoloff (Sokoloff et al., 1977) model using our adaptation of a program developed by Sokoloff (Buchsbaum et al., 1987) and constants from Phelps et al. (1979). Each pixel of each slice was converted from raw counts to glucose use in pmol/lOO g tissue/mm. All subjects had plasma glucose values within normal limits during uptake and scanning. For each area of interest, the value was expressed as average glucose use (sum of pixel values/number of pixels contained in the area). Data were analyzed expressed in units of pmol glucose/100 g brain/mm and also as ratios to whole slice glucose metabolic rate (relative analysis). Statistical analysis Glucose data were
analyzed
using
repeated
measures of analysis of variance (ANOVA) (BMDP AV, Dixon, 1982) with the Huynh-Feldt corrected degree of freedom. First, bulimics, depressives and controls were contrasted in a three group design. The ANOVA was then repeated for three combinations of two groups: bulimia vs. depression, bulimia vs. control, and depression vs. control. Analyses were also repeated with left handed subjects excluded. The results of the two group ANOVA analyses with all significant interactions are reported in the tables unless otherwise specified in the results. To further analyze differences between the groups, t-tests were used to test significance of left minus right hemisphere differences, and differences between specific structures in each subject group. To explore the question of whether PET differentiates bulimia from depression, or controls from both patient groups, we used hierarchical cluster analysis (BMDP 2M, Dixon, 1982) for subcortical data to match tables 5 and 6. Results Cortical surface As we found in an earlier analysis of only bulimic patients (Wu et al., 1990) using data from only three PET slices, patients with bulimia had significant loss of the normal right hemisphere metabolic rate exceeding the left (Fig. 1). The three groups had significantly different patterns of cortical brain metabolism in the lobe by hemisphere by group analysis (Table 2). Bulimics were significantly less asymmetrical than controls and depressed subjects in the temporal lobe, while both bulimic and depressed subjects had increased
156
Fig. 1. Typical PET scans in patients with bulimia nervosa, major affective disorder, and a normal control. Note that the control has greater right than left hemisphere metabolic rates, unlike the bulimic who is symmetrical. The patient diagnosed with major depression shows reduction of metabolism in the basal ganglia.
right hemisphere lateralization in the occipital lobe. No differences in whole brain cortical metabolic rate, and no lobe by group interactions were found. When the analysis was repeated with left handers excluded the significance of the lobe by hemisphere by group interaction remained (F = 6.54, df = 6, 54, P < 0.00001). As a follow up ANOVA, we contrasted each pair of groups. The bulimia vs. control contrast was significant for lobe by structure by hemisphere by group (F = 2.52, df = 8.65, 121.16, P=O.Ol).There was a significant interaction between hemisphere and
group for bulimia vs. depression, with bulimics showing less right lateralization (Table 2). The same independent groups and repeated measures were used in the relative cortical peel analysis. There was a significant lobe by hemisphere by group interaction (Table 3) demonstrating a loss of normal right hemisphere lateralization in metabolic activity primarily in the temporal lobe for bulimics but not for depressives and increased right occipital lobe activity in the bulimic and depressed groups. There was also a significant interaction between lobe, region, hemisphere and
157 TABLE
2
ABSOLUTE
CORTICAL
METABOLISM Control
Bulimia
Lobe
Frontal Parietal Temporal Occipital Mean
Right
Left
Right
Left mean
SD
mean
SD
mean
SD
19.3 18.9 16.1 18.2 18.1
2.6 3.1 2.5 2.9 3.0
19.5 19.6 16.1 19.4 18.7
2.1 3.1 2.5 * * * 3.5 ** 3.3
19.4 19.0 15.1 17.3 17.7
3.8 3.5 3.2 3.9 3.9
Right
Left
mean
SD
mean
SD
mean
SD
19.6 19.8 16.0 19.2 18.6
3.9 3.7 3.8 4.5 * 4.2
21.5 20.6 16.7 20.5 19.8
5.0 4.9 4.0 4.9 5.0
22.0 21.1 17.6 20.9 20.4
5.3 5.2 4.3 5.1 5.2
ANOVA (F = 6.44, df = 6.44, P c 0.00001). Lobe by hemisphere by group interaction. ANOVA bulimia vs. depression: hemisphere by group interaction (F = 4.48, df = 1, 14, P = 0.0527). ANOVA bulimia vs. control: (F = 7.64, df = 3, 42, P = 0.003) lobe by hemisphere by group interaction. ANOVA depression vs. control: (F = 10.11, df = 2.61, 36.61, P = 0.0041)lobe by hemisphere by group T-tests on left minus right differences: * Depression vs. control P < 0.05. ** Bulimia vs. control P i 0.05. *** Bulimia vs. depression P c 0.05.
group (Table 4). Post-hoc t-tests revealed greatest effects between bulimics and controls in the left minus right difference in the middle and inferior temporal gyri. Bulimics showed greater left than right hemisphere rates, but normals and depressives were greater on the right. Both the bulimic
TABLE
Frontal Parietal Temporal Occipital Mean
and depressed group had increased right hemisphere lateralization in the occipital lobe as a result of decreases in left occipital activity. Posthoc t-tests found that depressed subjects had significantly lower left hemisphere activity and than both bulimics and controls, and significantly
3
RELATIVE Lobe
interaction.
CORTICAL
METABOLIC
RATES
Bulimia
Depression
Control
Left
Right
Left
Right
Left
Right
1.13 1.10 0.94 1.06 + 1.06
1.14 1.15 0.94 * 1.13 * * 1.09
1.15 1.12 0.89 1.02 ++ 1.04
1.16 1.17 0.94 1.13 * * * 1.10
1.14 1.09 0.89 1.09 1.06
1.16 1.12 0.94 1.11 1.08
ANOVA (F = 6.77, df = 6, 63, P < 0.00001). Lobe by hemisphere by group interaction. ANOVA bulimia vs. depression: (F= 2.82, df = 3, 42, P = 0.05) lobe by hemisphere by group interaction. hemisphere by group: (F= 5.45, df = 1, 14, P = 0.349) ANOVA bulimia vs. control: (F= 7.96, df = 3, 42, P = 0.0003) lobe by hemisphere by group interaction. ANOVA depression vs. control: (F = 10.70, df = 2.94, 41.16, P = 0.00001) lobe by hemisphere by group interaction. T-tests on left minus right scores: * Bulimics vs. depressives P = 0.02. ** Bulimics vs. control P = 0.02. Bulimic vs. depressives P = 0.02. *** Depressives vs. control P = 0.001. T-tests: + Bulimic vs. depression P c 0.05. ++ Depression vs. control P c 0.05.
158 TABLE
4
RELATIVE
CORTICAL
METABOLISM Bulimia
Depression
Control
Left
Right
Left
Right
Left
Right
superior middle inferior precentral
1.10 1.10 1.16 1.16
1.08 1.13 1.15 * * 1.20
1.12 1.10 1.15 1.21
1.07 * 1.18 1.18 1.20
1.10 1.12 1.17 1.19
1.09 1.16 1.21 1.21
Parietal postcentral supramarginal angular superior
1.13 1.09 1.10 1.08
1.14 1.16 1.15 1.13
1.15 1.13 1.10 1.12
1.13 1.19 1.16 1.18 *
1.10 1.10 1.10 1.09
1.11 1.17 1.13 1.09
Temporal superior middle inferior posterior
0.97 1.03 0.91 0.85
1.03 0.98 * * * 0.91 * * * 0.84
0.95 0.93 0.X5 0.83
1.06 0.95 0.92 0.84
0.97 0.97 0.89 0.75
1.06 1.01 0.92 0.77
Occipital area 19 area 17 area 2-17 area 18
1.06 1.15 1.07 0.97
1.04 1.25 1.23 * * 1.01
1 .Ol 1.13 1 .Ol 0.93
1.03 1.26 * 1.23 * 1.00
1.06 1.21 1.10 1 .oo
1.05 1.24 1.12 1.03
Frontal
ANOVA (F= 1.67, df = 17.63, 185.13, P = 0.049) lobe by region by hemisphere by group interaction. ANOVA bulimia vs. control: (F= 2.57, d/ = 8.11, 113.47, P = 0.01) lobe by region by hemisphere by group T-tests on Table 3 left-right differences: * Depression vs. control P i 0.05. ** Bulimia vs. control P < 0.05. *** Bulimia vs. depression P -e0.05.
greater sphere (Table
TABLE
difference between right and left hemimetabolism than bulimics and controls 3). When the relative data analysis was
interaction.
repeated with left handers excluded, a significant hemisphere by group effect emerged (F = 3.72, df= 2, 18, P = 0.04) and the lobe by hemisphere
5
ABSOLUTE Region
MEDIAL
FRONTAL
SUBCORTICAL
Bulimia
22.1 19.8 21.0 14.3
RATES
Depression
Left mean Media1 frontal Thalamus Basal ganglia Limbic
AND
Right SD
mean
4.2 4.0 5.2 3.9
21.2 20.5 21.0 14.6
Control
Left
Right
Left
Right
SD
mean
SD
mean
SD
mean
SD
mean
SD
4.4 4.4 5.3 4.6
23.2 16.3 18.4 14.2
4.5 3.8 5.5 4.2
22.1 18.3 19.1 14.8
5.2 * 4.5 6.7 4.5
24.7 21.8 23.1 16.0
5.5 6.0 6.2 4.5
26.3 24.1 23.0 15.4
6.6 6.4 6.6 4.6
ANOVA (F = 2.59. df = 6, 63, P = 0.03) region by hemisphere by group interaction. ANOVA bulimia vs. control: ( F = 2.98, df= 3, 42, P = 0.01) region by hemisphere by group interaction. ANOVA depression vs. control: ( F = 4.08, d/ = 3. 42, P = 0.01) region by hemisphere by group interaction. T-test left-right difference: * Depressive vs. control P = 0.02.
159
by group interaction 54, P < 0.00001).
remained (F = 6.86, df = 6, .
Subcortical and medial frontal analysis Bulimic and depressed women had lower metabolic rates than normals in medial frontal structures, especially in the right hemisphere, associated with reversal of the normal right greater than left hemisphere metabolism pattern. Depressed women had lower metabolic rates than normals and bulimics in the basal ganglia and thalamus, especially in the left hemisphere. Limbic structures were most similar across the three groups. This pattern was statistically confirmed with a four way ANOVA (Table 5). A marginally significant interaction was found in clinical group by region (F = 2.19, df = 6,63, P = 0.056) with the pattern of diminished medial frontal metabolism in both bulimic and depressed subjects, and diminished metabolism in the thalamus and basal ganglia in the depressed group. There was a significant interaction for region by group in the two group ANOVA with bulimia and depression (F = 3.24, df = 2.76, 38.70, P = 0.357). When the analysis was repeated with left handers excluded, the significant interaction between group, region and hemisphere remained (F = 2.30, df = 6, 54, P = 0.048). The region by structure by hemisphere by group interaction was significant for depression vs. control (F = 2.30, df = 5.31, 74.32, P = 0.05). Since we (Buchsbaum et al., 1986) and others (Baxter et al., 1985) found reduced relative metabolic rates in the basal ganglia, we examined the ratios of caudate and putamen to whole slice
TABLE
metabolic rate. Depressives (1.27 + 0.13) had lower ratios than bulimics (1.42 + 0.14) for right putamen (P < 0.024, one tailed t-test); caudate was similar but not significant. Analysis of relative subcortical structures using the same four way ANOVA, independent groups and repeated measures yielded similar results, with a significant region by group interaction (F = 2.32, df = 6,63, P = 0.043) and a marginal group by region by hemisphere interaction (Table 6). Unlike the absolute analysis, left medial frontal structures were diminished only in the bulimic group. The finding of increased left lateralization remained, but appeared to be due to relatively diminished right hemisphere activity. When this analysis was repeated without left handers, there were no significant differences. There was a significant interaction between region, structure, hemisphere and group for bulimia vs. control (F = 2.31, df = 6, 84, P = 0.04), and a significant region by group interaction for bulimia vs. depression (F = 5.24, df = 3, 42, P = 0.0037). Cluster analysis To explore the degree of similarity in metabolic rates between bulimic, depressed and normal subjects, we examined the dendrograms for the 24 individuals for subcortical areas to match tables 5 and 6. The left minus right and left plus right scores for both relative and absolute data were entered into a hierarchical cluster analysis. The dendrogram revealed three clusters including 20 of 24 subjects (Fig. 2). This clustering revealed heterogeneity among bulimic subjects across clusters,
6
RELATIVE Region
Medial frontal Thalamus Basal ganglia Limbic
MEDIAL
FRONTAL
AND SUBCORTICAL
Bulimia
RATES Depression
Control
Left
Right
Left
Right
Left
Right
1.15 1.11 1.25 0.94
1.11 * 1.15 * 1.25 0.96
1.25 0.95 1.12 0.97
1.19 1.06 * * 1.16 1.02
1.18 1.11 1.12 1.05
1.24 1.23 1.20 1.00
ANOVA (F= 2.20, df = 6, 63, P = 0.054) region by hemisphere by group interaction. ANOVA depression vs. control: (F= 3.48, df = 3, 42, P = 0.02) region by hemisphere T-tests: * Bulimic vs. depression P < 0.05. ** Depression vs. control P < 0.05.
by group
interaction.
Fig. 2. Hierarchical cluster analysis and number of patients in each of three clusters. Note that cluster 1 ia largely normals and that cluster 2 contains predominately depressed subjects. Bulimic subjects are scattered across clusters 2 and 3. with three bulirmc subjects not clustered.
with depressed and control subjects clustered more uniformly. Similar clustering was seen in the cortical data. Clinical correlations Binge and purge frequency and EAT scores for the bulimic group were correlated with brain metabolism rates in an exploratory analysis. EAT score was negatively correlated with left parietal left mid-thalamus and left posterior cortex, thalamus. Binge frequency was negatively correlated with left frontal cortex and right posterior thalamus. Vomiting episodes were positively correlated with right caudate and right posterior thalamus. All correlations reported were significant for P < 0.05. These results are presented as exploratory hypotheses. Some may have occurred by chance given the large number of correlations. Discussion Normal women have higher right than left cortical metabolic rates and active basal ganglia. Bulimics lose the normal right activation in some areas but maintain basal ganglia metabolic activity. Depressives retain right hemisphere activation, but show decreases in basal ganglia metabolism. This suggests that although women with bulimia frequently present with symptoms of depression, often are co-diagnosed with affective disorder, and
typically respond to pharmacologic treatment with antidepressant, medications, the pathophysiologic basis of bulimia differs from that of major affective disorder. There were several brain areas where bulimic and depressed women showed brain metabolic patterns similar to each other and different from controls; cluster analysis supported this grouping. Both groups showed reversal of right hemisphere lateralization in medial frontal structures with higher left hemisphere metabolism, and increased right lateralization in the occipital lobe. The occipital lobe contains primarily visual cortex, and has not been implicated in affect regulation. Our previous analysis of bulimia with PET found decreased hemispheric lateralization, specifically with loss of the normal right greater than left hemisphere difference. In our current analysis of the same sample but with improved analytic methods, this result was again confirmed, and was most pronounced in the temporal lobe, basal ganglia and in medial frontal structures. The depressed group in contrast showed either normal or enhanced right lateralization in most areas, with the exception of medial frontal structures. We did not find decreased relative metabolism in the left frontal lobe in either the bulimic or depressed group, as would have been expected based on Baxter et al.‘s (1989) findings of decreased left ALPFC metabolism in psychiatric disorders accompanied by depressive symptoms. However, one of the areas of similarity between bulimia and depressed subjects did involve shifts in lateralization in medial frontal structures. Both bulimic and depressed subjects had abnormalities in basal ganglia metabolism. Basal ganglia metabolism was lower in our depressed group, but was not diminished in the bulimic women, although the bulimics showed a loss of right hemisphere lateralization in the basal gangha. The basal ganglia provide significant input into the thalamic relay to the cortex, and are thus involved in processing sensory, and perhaps emotional tone inputs. It is possible that there are different sequences of events (biological or environmental) which can lead to the development of depressive symptoms, with subsequently different underlying brain alterations. Some authors (Johnson-Sabine et al., 1984)
161
have suggested that the dysphoric mood in bulimic persons is not due to major affective disorder, rather is related to the presence of abnormal eating behavior and its subsequent impact on brain chemistry. Bulimics often fast between binges, inducing a state of semi-starvation. Keyes et al. (1950) found that normal subjects who are deprived of food developed depressive symptoms when they lost weight. However, this does not explain the presence of depression prior to the onset of an eating disorder (Piran et al., 1985; Walsh et al., 1985). Hemispheric lateralization has been recognized as an important factor in affect regulation (FlorHenry, 1984). Bulimic subjects differed most from controls and depressed subjects in loss of right hemisphere lateralization, and the few similarities between bulimic and depressed subjects involved shifts in right hemisphere lateralization. Although the bulimic and depressed subjects were rated as equally depressed on global clinical assessment by a psychiatrist, the significant difference in structured rating of depression on the Hamilton may suggest a difference in the subjective experience of depression for the patient. To better elucidate the significance of mood disturbance in the syndrome of bulimia future studies should include bulimic women with and without depressive symptoms. It is possible that the variations in severity of affective disorder in patients with bulimia are associated with changes in brain metabolism and neurochemistry. Other factors which were not controlled for in our study and could theoretically have contributed to brain metabolism differences include nutritional status, length of illness, and stage of menstrual cycle at the time of scan. Due to the small subject sample, our study must be considered preliminary, however, our results suggest that although there are a few regions of metabolic similarity, the syndrome of bulimia nervosa and the accompanying symptoms of depression are associated with a pattern of overall brain metabolism that differs from the pattern found in women with major affective disorder (unipolar type) and normal women.
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Johnson-Sabine, E.C., Wood, K.H. and Wakeling, A. (1984) Mood changes in bulimia nervosa. Br. J. Psychiatry 145, 512-516. Keyes, A., Brozek, J., Henshel, A. et al. (1950) The Biology of Human Starvation, Vol 1. University of Minnesota Press, Minneapolis, MN. Levy, A.B., Dixon, K.N. and Stem, S.L. (1989) How are depression and bulimia related? Am. J. Psychiatry 146, 162-169. Matsui, T. and Hirano, A. (1978) An Atlas of the Human Brain for Computerized Tomography. I&u-Shoin, Tokyo. Nuechterlein, K.H., Parasuraman, R. and Jiang, Q. (1983) Visual sustained attention: image degradation produced rapid decrement over time. Science 220, 327-329. Phelps, M.E., Huang, S.C., Hoffman, E.J. et al. (1979) Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-D-glucose: validation of method. Ann. Neurol. 6, 371-388. Piran, N., Kennedy, S., Garfinkel, P.E. et al. (1985) Affective disturbance in eating disorders. J. New. Ment. Dis. 173, 395-400. Pope, H.G., Hudson, J.I. and Yurgelun-Todd, J. (1989) De-
pressive symptoms in bulimic, depressed and non-psychiatric control subjects. J. Affect. Disord. 16, 93-99. Pyle, R.L., Mitchell, J.E. and Eckert, E.D. (1981) Bulimia: a report of 34 cases. J. Clin. Psychiatry 42, 60. Sokoloff, L., Reivich, M., Kennedy, C. et al. (1977) The (14)Cdeoxyghtcose method for the measurement of local cerebral glucose utilization: theory, procedure and normal values in the conscious and anesthetized albino rat. J. Neurochem. 28, 897-916. Schwartz, J.M., Baxter, L.R., Mazziotta, J.C. et al. (1987) The differential diagnosis of depression: relevance of positron emission tomography (PET) studies of cerebral glucose metabolism to the bipolar-unipolar dichotomy. J. Am. Med. Ass. 258, 136881374. Walsh, B.T., Roose, S.P., Glassman, A.H. et al. (1985) Bulimia and depression. Psychosom. Med. 47, 123-131. Wing, J.K., Cooper, J.E. and Sartorius, N. (1974) The Measurement and Classification of Psychiatric Symptoms. Cambridge University Press, London. Wu, J.C., Hagman, J., Buchsbaum, M.S. et al. (1990) Greater left cerebral hemispheric metabolism in bulimia assessed by positron emission tomography. Am. J. Psychiatry (in press).
Disorders,
153
19 (1990) 153-162
AD 00713
Comparison of regional brain metabolism in bulimia nervosa and affective disorder assessed with positron emission tomography J.O. Hagman, Department
M.S. Buchsbaum, of Psychiatry,
J.C. Wu, S.J. Rao, C.A. Reynolds
University of California-Irvine,
and B.J. Blinder
Medical Sciences I, D-404, Irvine, CA 92717, U.S.A.
(Received 16 June 1989) (Accepted 13 December 1989)
Summary Women with bulimia often present with symptoms of depression in addition to bingeing and purging Jehavior. Brain metabolism in eight women with bulimia nervosa was compared to that in eight women vith major affective disorder and eight normal women, using positron emission tomography and l%fluoro!-deoxyglucose. Normal women have higher right than left cortical metabolic rates and active basal ganglia. Bulimics lost the normal right activation in some areas, but maintained basal ganglia activity. Depressives retained right hemisphere activation, but had decreased metabolism in basal ganglia. This uggests that although women with bulimia frequently present with symptoms of depression, the patho)hysiologic changes associated with bulimia differ from major affective disorder.
Uey words:
Depression;
Eating
disorders;
l&Fluoro-deoxyglucose;
Introduction The significance and relative importance of dejressive symptoms in bulimia have been the focus )f many biological and clinical studies. Women vith bulimia nervosa often present with symptoms )f depression in addition to bingeing and purging )ehavior. DSM-III (1980) included ‘depressed nood and self-deprecating thoughts following eatng binges’ in the diagnostic criteria for bulimia. deflecting the controversy over depressive symp-
Address for correspondence: Jennifer 0. Hagman M.D., 3epartment of Psychiatry, University of California-Irvine, Yledical Sciences 1, D-404, Irvine, CA 92717, U.S.A. 1165-0327/90/$03.50
0 1990 Elsevier Science Publishers
Cerebral
metabolic
rate; Serotonin
toms in bulimia, the current DSM-IIIR (1987) criteria for bulimia nervosa deleted the presence of depressed mood in the symptoms necessary for the diagnosis. A study by Hudson et al. (1983) found that 88% of a sample of bulimics displayed a lifetime diagnosis of a major affective disorder. Pope et al. (1989) found no difference in the character of depressive symptoms, using the Hamilton Rating Scale for Depression, between bulimic and depressed subjects. Family history studies have yielded a high prevalence of major affective disorder in the relatives of patients with bulimia (Pyle et al., 1981; Hudson et al., 1982). However, a recent review of the published studies (Levy et al., 1989) including studies of clinical data, family history, pharmacotherapy and neurobiology, con-
B.V. (Biomedical
Division)
154
eluded that. while many bulimic patients are depressed. a preponderance of evidence suggests that bulimia is not a variant of depression. A positron emission tomography (PET) study of patients with anorexia nervosa, some of whom also reported bulimic symptoms of bingeing and purging. reported increased metabolism in basal ganglia (Herholz et al.. 1987). A study of normal weight patients with bulimia (Wu et al.. 1990) found normal metabolic rates in the basal ganglia. This is in contrast to patients with affective disorder where two studies have found reduced metabolism in the basal ganglia (Buchsbaum et al., 1987: Baxter et al., 1985). However, neither of these studies directly compared bulimics and affectives statistically. Another PET study of depression (Baxter et al.. 1989) compared metabolic activity in subjects with unipolar, bipolar, and obsessive compulsive disorder with and without depression. and found that presence of depressive symptoms in all three disorders was correlated with decreased metabolism in the left dorsal anterolateral prefrontal cortex (middle frontal gyrus). Previous studies had suggested that these were biologically distinct psychiatric illnesses (Baxter et al., 1985, 1987; Schwartz et al.. 1987). Since depressive symptoms are often present in patients with bulimia it is possible that a similar abnormality may be found upon PET scanning. The current report is the first study to compare brain metabolism in women with bulimia nervosa, major affective disorder and normal women under the same experimental conditions.
a count of the number of episodes per week of bingeing and vomiting, and received a global clinical rating of depressive symptoms by a psychiatrist (scale 1 to 7 most severe). None of the bulimic subjects had a prior history of anorexia nervosa. Although depressive symptoms were evaluated in the initial interview, axis I DSM-IIIR diagnoses of depression were not made initially in the bulimic group. For the current analysis, the senior author located six of the eight bulimic subjects and administered the major affective disorder section of the Present State Exam-lifetime version (PSE. Wing et al., 1974) to five to assess depressive illness. One bulimic subject was hospitalized receiving electroconvulsive therapy (ECT) for major depression in another state, and two subjects had moved without leaving new addresses or phone numbers. In the six bulimic women contacted, four met criteria for dysthymic disorder. and two met criteria for major depressive disorder during the period in which the PET scan was performed. The two bulimic subjects who were not reached for interview had scores of 12 and 17 on the Hamilton. and clinical global ratings of depression severity of 3 and 4, respectively. None of the depressed group had a prior history of bulimia nervosa or anorexia nervosa. Subjects were off all psychoactive medications for a minimum of 30 days, were in good physical health and none had significant abnormalities on physical examination or laboratory screening tests, including ketone bodies in urine. Subjects with a history of seizure disorders, major head trauma or current substance abuse were excluded.
Methods Subjects Eight female patients with bulimia (two left handed), eight age matched women with major affective disorder (unipolar type, one left handed) and eight age and sex matched normal controls served as subjects (Table 1). All subjects met DSM-IIIR criteria for bulimia nervosa, or major depression in the patient groups, as assessed by non-structured psychiatric interview. None of the normal controls had any history of psychiatric illness. Each of the bulimic patients completed the Eating Attitudes Test (EAT, Garner and Garfinkel, 1979), the Hamilton Depression Rating Scale,
Scanning procedure und quantification Subjects performed the visual continuous performance task (CPT, Nuechterlein et al., 1983) during 18-fluoro-2-deoxyglucose uptake and were scanned as described elsewhere (Buchsbaum et al., 1987). For each PET slice, the outer brain contour was outlined with a boundary-finding technique developed for skull on CT scans as described elsewhere (Buchsbaum et al., 1984, 1989). This corrects for minor rotation of the head. Four lobes (and four regions within each lobe) are specified from the cortical peel: frontal (superior, middle, inferior, precentral), parietal (postcentral, supramarginal, angular, superior), temporal (superior,
155 TABLE
1
CLINICAL
CHARACTERISTICS
OF SUBJECTS
Height (inches) Age (years) Weight (pounds) Hamilton depression score Clinical rating Binge frequency (weekly) Vomit frequency (weekly) EAT score
Bulimia
Depression
Control
65.1* 2.4 28.6f 6.5 127 f13.6 20.8+_ 6.9 4.25 1.2 14.1 f 10.0 14.3* 9.2 37.8 + 10.3
64.3* 3.1 29.4* 5.7 133 f16.9 31x* 5.1 * 4.1 f 1.5
64.9* 3.6 28.9* 7.7 139 +33.1
* P < 0.005, f-test.
middle, inferior, posterior) and occipital (area 19, area 17, area 2-17, area 18), for right and left hemisphere. Subcortical regions were identified stereotaxically. The proportional locations of boxes identified on the Matsui and Hirano (1978) atlas were then transferred automatically to the PET slices (Buchsbaum et al., 1987), and mean glucose metabolic rates were calculated for the left and right sided boxes. Four brain regions (and three structures within each region) chosen for subcortical analysis were: medial frontal structures (paracentral, medial frontal, superior frontal), thalamus (anterior, medial, lateral), basal ganglia (caudate, putamen, and limbic (hippocampus, globus pallidus), amygdala, uncus). Glucose computation Values of glucose use were calculated according to the Sokoloff (Sokoloff et al., 1977) model using our adaptation of a program developed by Sokoloff (Buchsbaum et al., 1987) and constants from Phelps et al. (1979). Each pixel of each slice was converted from raw counts to glucose use in pmol/lOO g tissue/mm. All subjects had plasma glucose values within normal limits during uptake and scanning. For each area of interest, the value was expressed as average glucose use (sum of pixel values/number of pixels contained in the area). Data were analyzed expressed in units of pmol glucose/100 g brain/mm and also as ratios to whole slice glucose metabolic rate (relative analysis). Statistical analysis Glucose data were
analyzed
using
repeated
measures of analysis of variance (ANOVA) (BMDP AV, Dixon, 1982) with the Huynh-Feldt corrected degree of freedom. First, bulimics, depressives and controls were contrasted in a three group design. The ANOVA was then repeated for three combinations of two groups: bulimia vs. depression, bulimia vs. control, and depression vs. control. Analyses were also repeated with left handed subjects excluded. The results of the two group ANOVA analyses with all significant interactions are reported in the tables unless otherwise specified in the results. To further analyze differences between the groups, t-tests were used to test significance of left minus right hemisphere differences, and differences between specific structures in each subject group. To explore the question of whether PET differentiates bulimia from depression, or controls from both patient groups, we used hierarchical cluster analysis (BMDP 2M, Dixon, 1982) for subcortical data to match tables 5 and 6. Results Cortical surface As we found in an earlier analysis of only bulimic patients (Wu et al., 1990) using data from only three PET slices, patients with bulimia had significant loss of the normal right hemisphere metabolic rate exceeding the left (Fig. 1). The three groups had significantly different patterns of cortical brain metabolism in the lobe by hemisphere by group analysis (Table 2). Bulimics were significantly less asymmetrical than controls and depressed subjects in the temporal lobe, while both bulimic and depressed subjects had increased
156
Fig. 1. Typical PET scans in patients with bulimia nervosa, major affective disorder, and a normal control. Note that the control has greater right than left hemisphere metabolic rates, unlike the bulimic who is symmetrical. The patient diagnosed with major depression shows reduction of metabolism in the basal ganglia.
right hemisphere lateralization in the occipital lobe. No differences in whole brain cortical metabolic rate, and no lobe by group interactions were found. When the analysis was repeated with left handers excluded the significance of the lobe by hemisphere by group interaction remained (F = 6.54, df = 6, 54, P < 0.00001). As a follow up ANOVA, we contrasted each pair of groups. The bulimia vs. control contrast was significant for lobe by structure by hemisphere by group (F = 2.52, df = 8.65, 121.16, P=O.Ol).There was a significant interaction between hemisphere and
group for bulimia vs. depression, with bulimics showing less right lateralization (Table 2). The same independent groups and repeated measures were used in the relative cortical peel analysis. There was a significant lobe by hemisphere by group interaction (Table 3) demonstrating a loss of normal right hemisphere lateralization in metabolic activity primarily in the temporal lobe for bulimics but not for depressives and increased right occipital lobe activity in the bulimic and depressed groups. There was also a significant interaction between lobe, region, hemisphere and
157 TABLE
2
ABSOLUTE
CORTICAL
METABOLISM Control
Bulimia
Lobe
Frontal Parietal Temporal Occipital Mean
Right
Left
Right
Left mean
SD
mean
SD
mean
SD
19.3 18.9 16.1 18.2 18.1
2.6 3.1 2.5 2.9 3.0
19.5 19.6 16.1 19.4 18.7
2.1 3.1 2.5 * * * 3.5 ** 3.3
19.4 19.0 15.1 17.3 17.7
3.8 3.5 3.2 3.9 3.9
Right
Left
mean
SD
mean
SD
mean
SD
19.6 19.8 16.0 19.2 18.6
3.9 3.7 3.8 4.5 * 4.2
21.5 20.6 16.7 20.5 19.8
5.0 4.9 4.0 4.9 5.0
22.0 21.1 17.6 20.9 20.4
5.3 5.2 4.3 5.1 5.2
ANOVA (F = 6.44, df = 6.44, P c 0.00001). Lobe by hemisphere by group interaction. ANOVA bulimia vs. depression: hemisphere by group interaction (F = 4.48, df = 1, 14, P = 0.0527). ANOVA bulimia vs. control: (F = 7.64, df = 3, 42, P = 0.003) lobe by hemisphere by group interaction. ANOVA depression vs. control: (F = 10.11, df = 2.61, 36.61, P = 0.0041)lobe by hemisphere by group T-tests on left minus right differences: * Depression vs. control P < 0.05. ** Bulimia vs. control P i 0.05. *** Bulimia vs. depression P c 0.05.
group (Table 4). Post-hoc t-tests revealed greatest effects between bulimics and controls in the left minus right difference in the middle and inferior temporal gyri. Bulimics showed greater left than right hemisphere rates, but normals and depressives were greater on the right. Both the bulimic
TABLE
Frontal Parietal Temporal Occipital Mean
and depressed group had increased right hemisphere lateralization in the occipital lobe as a result of decreases in left occipital activity. Posthoc t-tests found that depressed subjects had significantly lower left hemisphere activity and than both bulimics and controls, and significantly
3
RELATIVE Lobe
interaction.
CORTICAL
METABOLIC
RATES
Bulimia
Depression
Control
Left
Right
Left
Right
Left
Right
1.13 1.10 0.94 1.06 + 1.06
1.14 1.15 0.94 * 1.13 * * 1.09
1.15 1.12 0.89 1.02 ++ 1.04
1.16 1.17 0.94 1.13 * * * 1.10
1.14 1.09 0.89 1.09 1.06
1.16 1.12 0.94 1.11 1.08
ANOVA (F = 6.77, df = 6, 63, P < 0.00001). Lobe by hemisphere by group interaction. ANOVA bulimia vs. depression: (F= 2.82, df = 3, 42, P = 0.05) lobe by hemisphere by group interaction. hemisphere by group: (F= 5.45, df = 1, 14, P = 0.349) ANOVA bulimia vs. control: (F= 7.96, df = 3, 42, P = 0.0003) lobe by hemisphere by group interaction. ANOVA depression vs. control: (F = 10.70, df = 2.94, 41.16, P = 0.00001) lobe by hemisphere by group interaction. T-tests on left minus right scores: * Bulimics vs. depressives P = 0.02. ** Bulimics vs. control P = 0.02. Bulimic vs. depressives P = 0.02. *** Depressives vs. control P = 0.001. T-tests: + Bulimic vs. depression P c 0.05. ++ Depression vs. control P c 0.05.
158 TABLE
4
RELATIVE
CORTICAL
METABOLISM Bulimia
Depression
Control
Left
Right
Left
Right
Left
Right
superior middle inferior precentral
1.10 1.10 1.16 1.16
1.08 1.13 1.15 * * 1.20
1.12 1.10 1.15 1.21
1.07 * 1.18 1.18 1.20
1.10 1.12 1.17 1.19
1.09 1.16 1.21 1.21
Parietal postcentral supramarginal angular superior
1.13 1.09 1.10 1.08
1.14 1.16 1.15 1.13
1.15 1.13 1.10 1.12
1.13 1.19 1.16 1.18 *
1.10 1.10 1.10 1.09
1.11 1.17 1.13 1.09
Temporal superior middle inferior posterior
0.97 1.03 0.91 0.85
1.03 0.98 * * * 0.91 * * * 0.84
0.95 0.93 0.X5 0.83
1.06 0.95 0.92 0.84
0.97 0.97 0.89 0.75
1.06 1.01 0.92 0.77
Occipital area 19 area 17 area 2-17 area 18
1.06 1.15 1.07 0.97
1.04 1.25 1.23 * * 1.01
1 .Ol 1.13 1 .Ol 0.93
1.03 1.26 * 1.23 * 1.00
1.06 1.21 1.10 1 .oo
1.05 1.24 1.12 1.03
Frontal
ANOVA (F= 1.67, df = 17.63, 185.13, P = 0.049) lobe by region by hemisphere by group interaction. ANOVA bulimia vs. control: (F= 2.57, d/ = 8.11, 113.47, P = 0.01) lobe by region by hemisphere by group T-tests on Table 3 left-right differences: * Depression vs. control P i 0.05. ** Bulimia vs. control P < 0.05. *** Bulimia vs. depression P -e0.05.
greater sphere (Table
TABLE
difference between right and left hemimetabolism than bulimics and controls 3). When the relative data analysis was
interaction.
repeated with left handers excluded, a significant hemisphere by group effect emerged (F = 3.72, df= 2, 18, P = 0.04) and the lobe by hemisphere
5
ABSOLUTE Region
MEDIAL
FRONTAL
SUBCORTICAL
Bulimia
22.1 19.8 21.0 14.3
RATES
Depression
Left mean Media1 frontal Thalamus Basal ganglia Limbic
AND
Right SD
mean
4.2 4.0 5.2 3.9
21.2 20.5 21.0 14.6
Control
Left
Right
Left
Right
SD
mean
SD
mean
SD
mean
SD
mean
SD
4.4 4.4 5.3 4.6
23.2 16.3 18.4 14.2
4.5 3.8 5.5 4.2
22.1 18.3 19.1 14.8
5.2 * 4.5 6.7 4.5
24.7 21.8 23.1 16.0
5.5 6.0 6.2 4.5
26.3 24.1 23.0 15.4
6.6 6.4 6.6 4.6
ANOVA (F = 2.59. df = 6, 63, P = 0.03) region by hemisphere by group interaction. ANOVA bulimia vs. control: ( F = 2.98, df= 3, 42, P = 0.01) region by hemisphere by group interaction. ANOVA depression vs. control: ( F = 4.08, d/ = 3. 42, P = 0.01) region by hemisphere by group interaction. T-test left-right difference: * Depressive vs. control P = 0.02.
159
by group interaction 54, P < 0.00001).
remained (F = 6.86, df = 6, .
Subcortical and medial frontal analysis Bulimic and depressed women had lower metabolic rates than normals in medial frontal structures, especially in the right hemisphere, associated with reversal of the normal right greater than left hemisphere metabolism pattern. Depressed women had lower metabolic rates than normals and bulimics in the basal ganglia and thalamus, especially in the left hemisphere. Limbic structures were most similar across the three groups. This pattern was statistically confirmed with a four way ANOVA (Table 5). A marginally significant interaction was found in clinical group by region (F = 2.19, df = 6,63, P = 0.056) with the pattern of diminished medial frontal metabolism in both bulimic and depressed subjects, and diminished metabolism in the thalamus and basal ganglia in the depressed group. There was a significant interaction for region by group in the two group ANOVA with bulimia and depression (F = 3.24, df = 2.76, 38.70, P = 0.357). When the analysis was repeated with left handers excluded, the significant interaction between group, region and hemisphere remained (F = 2.30, df = 6, 54, P = 0.048). The region by structure by hemisphere by group interaction was significant for depression vs. control (F = 2.30, df = 5.31, 74.32, P = 0.05). Since we (Buchsbaum et al., 1986) and others (Baxter et al., 1985) found reduced relative metabolic rates in the basal ganglia, we examined the ratios of caudate and putamen to whole slice
TABLE
metabolic rate. Depressives (1.27 + 0.13) had lower ratios than bulimics (1.42 + 0.14) for right putamen (P < 0.024, one tailed t-test); caudate was similar but not significant. Analysis of relative subcortical structures using the same four way ANOVA, independent groups and repeated measures yielded similar results, with a significant region by group interaction (F = 2.32, df = 6,63, P = 0.043) and a marginal group by region by hemisphere interaction (Table 6). Unlike the absolute analysis, left medial frontal structures were diminished only in the bulimic group. The finding of increased left lateralization remained, but appeared to be due to relatively diminished right hemisphere activity. When this analysis was repeated without left handers, there were no significant differences. There was a significant interaction between region, structure, hemisphere and group for bulimia vs. control (F = 2.31, df = 6, 84, P = 0.04), and a significant region by group interaction for bulimia vs. depression (F = 5.24, df = 3, 42, P = 0.0037). Cluster analysis To explore the degree of similarity in metabolic rates between bulimic, depressed and normal subjects, we examined the dendrograms for the 24 individuals for subcortical areas to match tables 5 and 6. The left minus right and left plus right scores for both relative and absolute data were entered into a hierarchical cluster analysis. The dendrogram revealed three clusters including 20 of 24 subjects (Fig. 2). This clustering revealed heterogeneity among bulimic subjects across clusters,
6
RELATIVE Region
Medial frontal Thalamus Basal ganglia Limbic
MEDIAL
FRONTAL
AND SUBCORTICAL
Bulimia
RATES Depression
Control
Left
Right
Left
Right
Left
Right
1.15 1.11 1.25 0.94
1.11 * 1.15 * 1.25 0.96
1.25 0.95 1.12 0.97
1.19 1.06 * * 1.16 1.02
1.18 1.11 1.12 1.05
1.24 1.23 1.20 1.00
ANOVA (F= 2.20, df = 6, 63, P = 0.054) region by hemisphere by group interaction. ANOVA depression vs. control: (F= 3.48, df = 3, 42, P = 0.02) region by hemisphere T-tests: * Bulimic vs. depression P < 0.05. ** Depression vs. control P < 0.05.
by group
interaction.
Fig. 2. Hierarchical cluster analysis and number of patients in each of three clusters. Note that cluster 1 ia largely normals and that cluster 2 contains predominately depressed subjects. Bulimic subjects are scattered across clusters 2 and 3. with three bulirmc subjects not clustered.
with depressed and control subjects clustered more uniformly. Similar clustering was seen in the cortical data. Clinical correlations Binge and purge frequency and EAT scores for the bulimic group were correlated with brain metabolism rates in an exploratory analysis. EAT score was negatively correlated with left parietal left mid-thalamus and left posterior cortex, thalamus. Binge frequency was negatively correlated with left frontal cortex and right posterior thalamus. Vomiting episodes were positively correlated with right caudate and right posterior thalamus. All correlations reported were significant for P < 0.05. These results are presented as exploratory hypotheses. Some may have occurred by chance given the large number of correlations. Discussion Normal women have higher right than left cortical metabolic rates and active basal ganglia. Bulimics lose the normal right activation in some areas but maintain basal ganglia metabolic activity. Depressives retain right hemisphere activation, but show decreases in basal ganglia metabolism. This suggests that although women with bulimia frequently present with symptoms of depression, often are co-diagnosed with affective disorder, and
typically respond to pharmacologic treatment with antidepressant, medications, the pathophysiologic basis of bulimia differs from that of major affective disorder. There were several brain areas where bulimic and depressed women showed brain metabolic patterns similar to each other and different from controls; cluster analysis supported this grouping. Both groups showed reversal of right hemisphere lateralization in medial frontal structures with higher left hemisphere metabolism, and increased right lateralization in the occipital lobe. The occipital lobe contains primarily visual cortex, and has not been implicated in affect regulation. Our previous analysis of bulimia with PET found decreased hemispheric lateralization, specifically with loss of the normal right greater than left hemisphere difference. In our current analysis of the same sample but with improved analytic methods, this result was again confirmed, and was most pronounced in the temporal lobe, basal ganglia and in medial frontal structures. The depressed group in contrast showed either normal or enhanced right lateralization in most areas, with the exception of medial frontal structures. We did not find decreased relative metabolism in the left frontal lobe in either the bulimic or depressed group, as would have been expected based on Baxter et al.‘s (1989) findings of decreased left ALPFC metabolism in psychiatric disorders accompanied by depressive symptoms. However, one of the areas of similarity between bulimia and depressed subjects did involve shifts in lateralization in medial frontal structures. Both bulimic and depressed subjects had abnormalities in basal ganglia metabolism. Basal ganglia metabolism was lower in our depressed group, but was not diminished in the bulimic women, although the bulimics showed a loss of right hemisphere lateralization in the basal gangha. The basal ganglia provide significant input into the thalamic relay to the cortex, and are thus involved in processing sensory, and perhaps emotional tone inputs. It is possible that there are different sequences of events (biological or environmental) which can lead to the development of depressive symptoms, with subsequently different underlying brain alterations. Some authors (Johnson-Sabine et al., 1984)
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have suggested that the dysphoric mood in bulimic persons is not due to major affective disorder, rather is related to the presence of abnormal eating behavior and its subsequent impact on brain chemistry. Bulimics often fast between binges, inducing a state of semi-starvation. Keyes et al. (1950) found that normal subjects who are deprived of food developed depressive symptoms when they lost weight. However, this does not explain the presence of depression prior to the onset of an eating disorder (Piran et al., 1985; Walsh et al., 1985). Hemispheric lateralization has been recognized as an important factor in affect regulation (FlorHenry, 1984). Bulimic subjects differed most from controls and depressed subjects in loss of right hemisphere lateralization, and the few similarities between bulimic and depressed subjects involved shifts in right hemisphere lateralization. Although the bulimic and depressed subjects were rated as equally depressed on global clinical assessment by a psychiatrist, the significant difference in structured rating of depression on the Hamilton may suggest a difference in the subjective experience of depression for the patient. To better elucidate the significance of mood disturbance in the syndrome of bulimia future studies should include bulimic women with and without depressive symptoms. It is possible that the variations in severity of affective disorder in patients with bulimia are associated with changes in brain metabolism and neurochemistry. Other factors which were not controlled for in our study and could theoretically have contributed to brain metabolism differences include nutritional status, length of illness, and stage of menstrual cycle at the time of scan. Due to the small subject sample, our study must be considered preliminary, however, our results suggest that although there are a few regions of metabolic similarity, the syndrome of bulimia nervosa and the accompanying symptoms of depression are associated with a pattern of overall brain metabolism that differs from the pattern found in women with major affective disorder (unipolar type) and normal women.
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