- Email: [email protected]
Brain T1 measured by magnetic resonance imaging in Bulimia
116
BIOL PSYCHIATRY 1990;27:116-119
Brain T1 Measured by Magnetic Resonance Imaging in Bulirnia Graham W. Hoffman, Everett H. Ellinwood, Jr., W.J. Kenneth Rockwell, Robert J. Herfkens, J. Ken Nishita, and Linda F. Guthrie
Introduction Proton longitudinal rel,-vtationtime (TI), as measured by magnetic resonance imaging (MRI), has been shown to be altered in the brains of certain groups of psychiatric patients. RangelGuerra et al. (1983) found that average Tl in frontal and temporal lobes of patients with bipolar affectivedisorderwas increased over controis,but returned to normal following I week of lithium treatment. Multiple studies have found that brain TI is altered .iaring the course of alcohol withdrawal (Eisenhofer et al. 1982; Smith et al. !985; Smith et al. 1988), or following electroconvulsive therapy (Mander et al. 1987). Using a 1.5 Tesla magnetic imager, we measured TI in various brain regions for a group of unmedicated bulimics compared with controls.
Methods Eight consecutive unmedicated bulimic women undergoing treatment at the Duke Medical Center Eating Disorders Unit were included in the From the ~ t s of Psychia~ (G.W.H., E.H.E., Jr., W.J.K.R., LK.N., L.F.G.), Pharmacology (E.H.E., Jr.), and Radiology (R.J.H.), Duke University Medical Center, Durham, NC. This work was supported by NIH research grants MH42210 and T32 MH15177, and by the Tom and Sarah Kern Anorexia Nervosa Fund. Address reprint requests to Everett H. Ellinwood, Jr., Box 3~t70, Duke University Medical Center, Durham, NC 27710. Received March 10, 1989; revised May 16, 1989.
© 1990 Society of Biological Psychiatry
study, All patients met DSM-IlI criteria for bulimia (American Psychmtric Association 1980), as determined from independent semistructured interviews by two psyc~atrists (W.J.K.R. & G.W.H.). Duration of illness ranged from 15 months to 12 yr (mean +_ st)6.5 _ 3.1 yr). Frequency of binging ranged from 5 to 42 times/week (mean 15 +- 13.4). Vomiting occttrred more frequently (range 5 to 84 times/week, mean 36.5 + 27.7), often following a binge episode, but sometimes occurring after a light snack or without prior food intake at all. Laxative use occurred in two patients, at a frequency of 3-5 times/week for each. No one currently used diuretics. A lifetime diagnosis of anorexia nervosa, or current diagnosis of major affecfive disorder or alcohol abuse was ruled out by personal interview plus review of previous hospital records. The time period between last previous purging and MRI scanning ranged from 2 to lO days. The seven controls were chosen from eight, age-matched women volunteers from the community who were without a history of medical or psychiatric illness. The eighth voh,nteer in this group was excluded because of a history of alcohol dependence. All patients and the Jeven volunteer controls gave written consent to participate ~n the research after receiving a full explanation of the nature of the procedure; pregnancy was ruled out prior to scanning by
0006-3223190/$03.50
Brief Reports
qualitative serum beta-HCG (human-chorionic gonadotrapin) test. The bulimic patients were between 18 and 27 yr of age (mean 24.2 __. 3.2 yr); controls were between 18 and 31 (mean 24.2 ___ 3.4 yr). The patient group averaged 106% of ideal body weight according to the 1983 Metropolitan Life Insurance tables (light frame); controls averaged 107%.
Image Acquisition MRI was performed on a 1.5 T whole-body system from Genera!! Electric (Milwaukee, WI). ~eans were ,~bt-~ined for broth groups concurrently over the course of 7 m~:ths. The subject's head was pos~tior~ed with the canthomeatal line at 0 ° from the ~c~-tical ~xis, and the imager's laser grid ceatered at the nasion. Consecutive axial slices extending from the lower temporal lobes to the internal cranial vault were obtained using a spin-echo pulse sequence, with slice thickness 5 mm, repetition time f i R ) 500 msec, time to echo (TE) 20 msec, and two excitations. TI was quantified using a multiple saturationrecovery (MSR) sequence (Breger et al. 1986), ~vith interpulse times (TI) of 3200, 1600, 800, 400, and 200 msec, and TE of 20 msec, on a single 3-mm thick coronal slice through the amygdala and third ventricle. Position of this coronal slice was chosen each time by one of the investigators (G.W.H.) in order to minimize intersubject positional variability; slice location was determined by axial series landmarks, viewed on the GE Signa system's on-line computer console at the time of image acquisit;.on.
Image Analysis The single-slice coronal series was utilized for rzgional TI quantification, calculated from five images (TI/TE 3200/20, 1600/20, 800/20, 400/20, and 200/20). The region of interest on the system monitor screen was a 4 x 4 mm square cursor which the rater placed bilaterally within the cortical gray matter of the cingulate, superior, middle, and inferior gy~ of the frontal
toOL ~¥CHt~'mY
I17
1990;27:116-I 19
lobe; the caudate; or within white matter, at level of the corona radiata bilaterally. ~ e r regions, such as temporal gray and whit~ matter, or putamen, were either too poorly defined or too narrow to allow cursor placement for many subjects and were not included ha the measurements. An iterative chi-square minimization program for a three parameter fit was utilized for determination of TI at each region of interest. The long-term reproducibility of MSR T1 measurements in brain on our imaging system is within 14% (Breger et al. 1986). Gray matter TI was averaged bilaterally over each of the six regions mentioned above. Results Table 1 shows mean T I values of bulimics and controls by region. Of interest is the fact that mean TI was less in the bulirnic group for every region mea3ured, although this difference is significant only for the inferior frontal gray matter. Figure 1 is a scattergram of TI values for the inferior frontal gray matter. It is apparent that TI values for the bulimic group are more tightly clustered than for controls (as occurs for every region measured, given the smaller standard deviation values for bulimics in Table I). Also, for the inferior frontal gyms gray matter, there are no overlapping values between bulimics and controls.
This study is limited by the relatively small number of subjects, due to the expense of the procedure. Despite this limitation, there appears to be a robust decrease ha T1 for inferior frontal gray matter Jr: the bulimic group compared with the controls. The implications of this decrease are uaclear at present, although lesions in this region have lr,een associated with behavioral dyscontrol and voracious appetite (Fuster 1989). It is interesting that several authors (Heinz et al. 1977; Artmann et al. 1985) have speculated that a decrease in brain tissue water content may underlie the reversible atrophy (or "pseu-
118
BIOL PSYCHIATRY
Brief Reports
1990;27:116--119
Table 1. TI Values for Various Brain Regions in Bulimics and Controls
Region White matter Frontal Gray matter Cingulate Superior frontal Middle frontal Inferior frontal Caudate
Bulimies (N = 8) Mean _+ SD (msec)
Controls (n = 7) Mean -4- SD (msec)
% difference
683 ± 31
700 ± 58
+2.0%
0.45
+6.3% +2.7% +7.5% + 12.2%
0.27 0.77 0.09
1218 1138 1132 ! 134 1055
-+ +± -+
90 58 63 42 35
1299 1170 1225 1291 1108
-~ 134 _+ 113 ~ 109 ± 62 ± 69
+4.8%
P value
0.002 0.i8
1400 o 1379
e1339 o 1322
1500
1291 01284 o 1 2 "~
01248
"S" O')
E
1200
1185 Q ollT7 o 11"/2
Q 1190
1151
o
~
11.34 01116
1100
1000
10"/9 o 109'7
'
Bulimics
'
Controls
Figure 1. Scattergram of cortical gray inferior gyrus TI values for bulimics (1134 +_ 42 msec) (x +_ S.D.) and controls (1291 -+ 62 msec) (Z = 3.18, p = 0.0015, Wilson Rank Sum Test).
Brief Reports
BIOLPS¥CH~TRY 1990;2"/:116-119
119
Artmann H, Ccau H, Adelman M, Sc~eiffer R (198~: Reversible and ~on-reversible ,~argement of nervosa patients. In addition, TI has been found cerebrospinal fluid spaces in anorexia nervosa. to correlate well with the water content of tissue Neuroradiology 27:304-312. from a variety of plant and animal sources (for Bottomley PA, Hardy CI, Argersinger RE, AHenreview see Foster 1984). Ideally, then, we should Moore G (1987): A review of proton nuclear magbe able to measure both cortical atrophy and netic resonance relaxation in pathology: Are TI and T2 diagnostic.'?Med P,.~ys 14(!): 1-37. brain TI in a group of subjects in order to investigate the relationship between relative water Breger RK, Wehrfi ~ , Charles HC, Mac~all JR, Hanghton VM (1986): Reproducibility of relaxcontent and cerebral "atrophy." Along these lines, ation and spin density parameters in phantoms the sagittal cerebral-cranial ratio, a measure of the human brain measured by MR imaging ~ 1.5 cortical atrophy, has been calculated previously Tesla. Magn Reson Med 3:649-662. for this group of bulimic patients (see Hoffman Eisenhofer G, Whiteside E, Lambie D, Johnson R et al. 1989); however, the correlation (Pearson (1982): Brain water during alcohol withdrawal. r) between TI values for the inferior frontal gray Lancet 1:50. region T I and the sagittat cerebral-cranial ratio Foster MA (1984): Proton relaxation in small biological samples. In Foster MA (ed), Magnettc was only 0.28. Furthermore.,, TI for this region Resonance in Medicine and Biology. New York: correlated poorly with the number of days since Pergamon Press, pp 148-168. last purging behavior (r = 0.29), suggesting that recent vomiting behavior does not contrib- Fuster JM (1989): The Prefrontal Cortex: Anatomy, Physiology and Neurophysiology of the Frontal ute greatly to brain hydration status. Lobe. New York, NY: Raven Press, p 70. In vitro studies and in vivo work with cell Heinz ER, Martinez J, Haenggeli A (1977): Reverscuitures have demonstmteo other possible causes ibility of cerebral atrophy in anorexia nervosa. J Comput Assist Tomogr 1:415-418. of decreased T1 besides dehydration: reduced levels of potassium, sodium, glycogen, or pro- Hoffman GW, Ellinwood EH, Rockwell WJK Heftkens RJ, Nishita JK, Guthrie LF (1989): Cerebral tein content, as well as decreased tissue growth atrophy in bulimia. Biol Psychiatry 25:894-902. rate (for review see Bottomley et al. 1987). If Mander AJ, Whittield A, Kean DM, Smith MA, the T I findings are confirmed in future studies, Douglas RHB, Kendell RE (1987): Cerebral and the mechanisms and time course for reversal of brainstem ch~ges after ECT revealed by nuclear the altered T I found m those brain regions magnetic resonance imaging. Br J Psychiatry showing the most robust alterations deserve fur151:69-71. ther study. Rangel-Guerra RA, Perez-Payan H, Minkoff L, Todd L (1983): Nuclear magnetic resonance in bipolar affe~tlve d~sorders. ?JNR 4:229-23i. Smith MA, Chick J, Kean DM, et al (1985): Brain References water in chronic alcoholic patients measured by magnetic resonance imaging. Lancet 1:1273--1274~ American Psychiatric Association Committee on NoSmith MA, Chick J, Engleman HM, et al (1988): menclature and Statistics (1980): Diagnostic and Brain hydration during alcohol withdrawal in alStatistical Manual of Mental Disorders (ed 3), coholics measured by magnet resonance imaging. Washington, DC: American Psychiatric AssociDrug Alcohol Dependence 21:25-28. ation.
doatrophy") which has been found in anorexia
BIOL PSYCHIATRY 1990;27:116-119
Brain T1 Measured by Magnetic Resonance Imaging in Bulirnia Graham W. Hoffman, Everett H. Ellinwood, Jr., W.J. Kenneth Rockwell, Robert J. Herfkens, J. Ken Nishita, and Linda F. Guthrie
Introduction Proton longitudinal rel,-vtationtime (TI), as measured by magnetic resonance imaging (MRI), has been shown to be altered in the brains of certain groups of psychiatric patients. RangelGuerra et al. (1983) found that average Tl in frontal and temporal lobes of patients with bipolar affectivedisorderwas increased over controis,but returned to normal following I week of lithium treatment. Multiple studies have found that brain TI is altered .iaring the course of alcohol withdrawal (Eisenhofer et al. 1982; Smith et al. !985; Smith et al. 1988), or following electroconvulsive therapy (Mander et al. 1987). Using a 1.5 Tesla magnetic imager, we measured TI in various brain regions for a group of unmedicated bulimics compared with controls.
Methods Eight consecutive unmedicated bulimic women undergoing treatment at the Duke Medical Center Eating Disorders Unit were included in the From the ~ t s of Psychia~ (G.W.H., E.H.E., Jr., W.J.K.R., LK.N., L.F.G.), Pharmacology (E.H.E., Jr.), and Radiology (R.J.H.), Duke University Medical Center, Durham, NC. This work was supported by NIH research grants MH42210 and T32 MH15177, and by the Tom and Sarah Kern Anorexia Nervosa Fund. Address reprint requests to Everett H. Ellinwood, Jr., Box 3~t70, Duke University Medical Center, Durham, NC 27710. Received March 10, 1989; revised May 16, 1989.
© 1990 Society of Biological Psychiatry
study, All patients met DSM-IlI criteria for bulimia (American Psychmtric Association 1980), as determined from independent semistructured interviews by two psyc~atrists (W.J.K.R. & G.W.H.). Duration of illness ranged from 15 months to 12 yr (mean +_ st)6.5 _ 3.1 yr). Frequency of binging ranged from 5 to 42 times/week (mean 15 +- 13.4). Vomiting occttrred more frequently (range 5 to 84 times/week, mean 36.5 + 27.7), often following a binge episode, but sometimes occurring after a light snack or without prior food intake at all. Laxative use occurred in two patients, at a frequency of 3-5 times/week for each. No one currently used diuretics. A lifetime diagnosis of anorexia nervosa, or current diagnosis of major affecfive disorder or alcohol abuse was ruled out by personal interview plus review of previous hospital records. The time period between last previous purging and MRI scanning ranged from 2 to lO days. The seven controls were chosen from eight, age-matched women volunteers from the community who were without a history of medical or psychiatric illness. The eighth voh,nteer in this group was excluded because of a history of alcohol dependence. All patients and the Jeven volunteer controls gave written consent to participate ~n the research after receiving a full explanation of the nature of the procedure; pregnancy was ruled out prior to scanning by
0006-3223190/$03.50
Brief Reports
qualitative serum beta-HCG (human-chorionic gonadotrapin) test. The bulimic patients were between 18 and 27 yr of age (mean 24.2 __. 3.2 yr); controls were between 18 and 31 (mean 24.2 ___ 3.4 yr). The patient group averaged 106% of ideal body weight according to the 1983 Metropolitan Life Insurance tables (light frame); controls averaged 107%.
Image Acquisition MRI was performed on a 1.5 T whole-body system from Genera!! Electric (Milwaukee, WI). ~eans were ,~bt-~ined for broth groups concurrently over the course of 7 m~:ths. The subject's head was pos~tior~ed with the canthomeatal line at 0 ° from the ~c~-tical ~xis, and the imager's laser grid ceatered at the nasion. Consecutive axial slices extending from the lower temporal lobes to the internal cranial vault were obtained using a spin-echo pulse sequence, with slice thickness 5 mm, repetition time f i R ) 500 msec, time to echo (TE) 20 msec, and two excitations. TI was quantified using a multiple saturationrecovery (MSR) sequence (Breger et al. 1986), ~vith interpulse times (TI) of 3200, 1600, 800, 400, and 200 msec, and TE of 20 msec, on a single 3-mm thick coronal slice through the amygdala and third ventricle. Position of this coronal slice was chosen each time by one of the investigators (G.W.H.) in order to minimize intersubject positional variability; slice location was determined by axial series landmarks, viewed on the GE Signa system's on-line computer console at the time of image acquisit;.on.
Image Analysis The single-slice coronal series was utilized for rzgional TI quantification, calculated from five images (TI/TE 3200/20, 1600/20, 800/20, 400/20, and 200/20). The region of interest on the system monitor screen was a 4 x 4 mm square cursor which the rater placed bilaterally within the cortical gray matter of the cingulate, superior, middle, and inferior gy~ of the frontal
toOL ~¥CHt~'mY
I17
1990;27:116-I 19
lobe; the caudate; or within white matter, at level of the corona radiata bilaterally. ~ e r regions, such as temporal gray and whit~ matter, or putamen, were either too poorly defined or too narrow to allow cursor placement for many subjects and were not included ha the measurements. An iterative chi-square minimization program for a three parameter fit was utilized for determination of TI at each region of interest. The long-term reproducibility of MSR T1 measurements in brain on our imaging system is within 14% (Breger et al. 1986). Gray matter TI was averaged bilaterally over each of the six regions mentioned above. Results Table 1 shows mean T I values of bulimics and controls by region. Of interest is the fact that mean TI was less in the bulirnic group for every region mea3ured, although this difference is significant only for the inferior frontal gray matter. Figure 1 is a scattergram of TI values for the inferior frontal gray matter. It is apparent that TI values for the bulimic group are more tightly clustered than for controls (as occurs for every region measured, given the smaller standard deviation values for bulimics in Table I). Also, for the inferior frontal gyms gray matter, there are no overlapping values between bulimics and controls.
This study is limited by the relatively small number of subjects, due to the expense of the procedure. Despite this limitation, there appears to be a robust decrease ha T1 for inferior frontal gray matter Jr: the bulimic group compared with the controls. The implications of this decrease are uaclear at present, although lesions in this region have lr,een associated with behavioral dyscontrol and voracious appetite (Fuster 1989). It is interesting that several authors (Heinz et al. 1977; Artmann et al. 1985) have speculated that a decrease in brain tissue water content may underlie the reversible atrophy (or "pseu-
118
BIOL PSYCHIATRY
Brief Reports
1990;27:116--119
Table 1. TI Values for Various Brain Regions in Bulimics and Controls
Region White matter Frontal Gray matter Cingulate Superior frontal Middle frontal Inferior frontal Caudate
Bulimies (N = 8) Mean _+ SD (msec)
Controls (n = 7) Mean -4- SD (msec)
% difference
683 ± 31
700 ± 58
+2.0%
0.45
+6.3% +2.7% +7.5% + 12.2%
0.27 0.77 0.09
1218 1138 1132 ! 134 1055
-+ +± -+
90 58 63 42 35
1299 1170 1225 1291 1108
-~ 134 _+ 113 ~ 109 ± 62 ± 69
+4.8%
P value
0.002 0.i8
1400 o 1379
e1339 o 1322
1500
1291 01284 o 1 2 "~
01248
"S" O')
E
1200
1185 Q ollT7 o 11"/2
Q 1190
1151
o
~
11.34 01116
1100
1000
10"/9 o 109'7
'
Bulimics
'
Controls
Figure 1. Scattergram of cortical gray inferior gyrus TI values for bulimics (1134 +_ 42 msec) (x +_ S.D.) and controls (1291 -+ 62 msec) (Z = 3.18, p = 0.0015, Wilson Rank Sum Test).
Brief Reports
BIOLPS¥CH~TRY 1990;2"/:116-119
119
Artmann H, Ccau H, Adelman M, Sc~eiffer R (198~: Reversible and ~on-reversible ,~argement of nervosa patients. In addition, TI has been found cerebrospinal fluid spaces in anorexia nervosa. to correlate well with the water content of tissue Neuroradiology 27:304-312. from a variety of plant and animal sources (for Bottomley PA, Hardy CI, Argersinger RE, AHenreview see Foster 1984). Ideally, then, we should Moore G (1987): A review of proton nuclear magbe able to measure both cortical atrophy and netic resonance relaxation in pathology: Are TI and T2 diagnostic.'?Med P,.~ys 14(!): 1-37. brain TI in a group of subjects in order to investigate the relationship between relative water Breger RK, Wehrfi ~ , Charles HC, Mac~all JR, Hanghton VM (1986): Reproducibility of relaxcontent and cerebral "atrophy." Along these lines, ation and spin density parameters in phantoms the sagittal cerebral-cranial ratio, a measure of the human brain measured by MR imaging ~ 1.5 cortical atrophy, has been calculated previously Tesla. Magn Reson Med 3:649-662. for this group of bulimic patients (see Hoffman Eisenhofer G, Whiteside E, Lambie D, Johnson R et al. 1989); however, the correlation (Pearson (1982): Brain water during alcohol withdrawal. r) between TI values for the inferior frontal gray Lancet 1:50. region T I and the sagittat cerebral-cranial ratio Foster MA (1984): Proton relaxation in small biological samples. In Foster MA (ed), Magnettc was only 0.28. Furthermore.,, TI for this region Resonance in Medicine and Biology. New York: correlated poorly with the number of days since Pergamon Press, pp 148-168. last purging behavior (r = 0.29), suggesting that recent vomiting behavior does not contrib- Fuster JM (1989): The Prefrontal Cortex: Anatomy, Physiology and Neurophysiology of the Frontal ute greatly to brain hydration status. Lobe. New York, NY: Raven Press, p 70. In vitro studies and in vivo work with cell Heinz ER, Martinez J, Haenggeli A (1977): Reverscuitures have demonstmteo other possible causes ibility of cerebral atrophy in anorexia nervosa. J Comput Assist Tomogr 1:415-418. of decreased T1 besides dehydration: reduced levels of potassium, sodium, glycogen, or pro- Hoffman GW, Ellinwood EH, Rockwell WJK Heftkens RJ, Nishita JK, Guthrie LF (1989): Cerebral tein content, as well as decreased tissue growth atrophy in bulimia. Biol Psychiatry 25:894-902. rate (for review see Bottomley et al. 1987). If Mander AJ, Whittield A, Kean DM, Smith MA, the T I findings are confirmed in future studies, Douglas RHB, Kendell RE (1987): Cerebral and the mechanisms and time course for reversal of brainstem ch~ges after ECT revealed by nuclear the altered T I found m those brain regions magnetic resonance imaging. Br J Psychiatry showing the most robust alterations deserve fur151:69-71. ther study. Rangel-Guerra RA, Perez-Payan H, Minkoff L, Todd L (1983): Nuclear magnetic resonance in bipolar affe~tlve d~sorders. ?JNR 4:229-23i. Smith MA, Chick J, Kean DM, et al (1985): Brain References water in chronic alcoholic patients measured by magnetic resonance imaging. Lancet 1:1273--1274~ American Psychiatric Association Committee on NoSmith MA, Chick J, Engleman HM, et al (1988): menclature and Statistics (1980): Diagnostic and Brain hydration during alcohol withdrawal in alStatistical Manual of Mental Disorders (ed 3), coholics measured by magnet resonance imaging. Washington, DC: American Psychiatric AssociDrug Alcohol Dependence 21:25-28. ation.
doatrophy") which has been found in anorexia