918
BIOL PSYCHIATRY 199 ! ;29:918-922
MRI Deep Wh' te Matter Hyperintensity in a Psychiatric Populatior Raymond F. Deicken, Victor I. Reus, Luisa Manfredi, and Owen M. Wolkowitz
The authors evaluated magnetic resonance imaging (MRI) of deep white matter hyperintensity (DWMH) in 90 adult psychiatric inpatients in whom MRls were clinically indicated and 25 age-m:ztched, medically healthy controls. Forty-two percent of the psychiatric patients and 12% of the controls had evidence of DWMH on MRI. Both incidence and severity of DWMH were sign~cantly correlated with age in both group~. Even after controlling for age in the psychiatric population, DWMH was significantly associated with hypertension, history of myocardial infarction or angina, abnormal electrocardiogram, and abnormal neurological examinations.
Introduction Most studies e f deep white matter hyperintensities (DWMH) identified by magnetic resonance imaging :, .~. .".". : have ~ecused on the grading of white matter lesions, cerebrovascular risk factors, neurological abnormalities, or neuropathological correlates in nonpsychiatric populations. However, relatively few studies have examined the incidence of DWMH and cerebrovascular risk factors in psychiatric populations. Because of the subcortical locztion of white matter hyperintensities, it is conceivable that such lesions might have an effect on behavior and cognition and thus might be associated with different psychiatric presentations. Four recent studies suggest that a significant percentage of patients with Bipolar Affective Disorder (oupont et al 1990) and patients with Major Depression (Coffey et al 1988, 1990; Krishnan et al 1988) exhibit DWMH on MRI. Because DWMH appears to be present in patients with primary psychiatric disorders, we decided to systematically examine the occurrence of DWMH and its relationship to cerebrovascular risk factors in a mixed population of adult psychiatric patients. Patients and M e t h o d s We evaluated 90 consecutive MRI studies of psychiatric inpatients admitted to the Behavioral Neuroscience Service at UCSF Langley Porter Psychiatric Institute (a tertiary ca~e referral center) between 1986 and 1988. The psychiatric population consisted of
From the University of CaliforniaSchool of Medicine, Department of Psychiatry, San Francisco, C A 94143. .~,ddressreprint requests to Raymond F. Deicken, M.D., M.S., Veterans Administration Medical Center, Department of Psychiatry, 116-N, 4150 Clement Street,San Francisco,C A 94121. Received November 14, 1989; revised September 7, 1990. Presented at the 142rid Annual Meeting of the American PsychiatricAssociation,San Fr~:isco, California,May 6-I I, 1989.
© 1991 Society of Biological Psychiatry
0006-3223/91/$03.50
MR! Deep White Matter Hyperintensity
BIOLPSYCHIATRY
919
1991 ;29:9| 8-922
30 men and 60 women whose mean _+ SD age was 43.9 _+ 21.5 years. The most common psychiatric diagnoses in this population were major depression (n - 31), bipolar disorder (n = 26), schizophrenia (n = 15), dementia (n = 9), organic affective disorder (n = 3), and somatoform disorder (n = 3). The MRI studies were obtained during the first week of admission for the following indications: (1) abnormal neurological examination or movement disorder (n = 27), (2) iustory of head trauma seizure disorder with no prior brain imaging (n = 3), (3) late onset Fb~chosis, i.e., greater than 40 years old (n = 10), (4) refractory psychosis or mood disorder (n -51), and (5) dementia (n = 9). To determine the basal incidence of DWMH in normal individuals, we also examined MRI studies of 25 control subjects who were free of any medical or psychiatric illness or history of substance abuse, and who had a normal neurological examination and no identified cerebrovascular symptoms or risk factors. The control group comprised 14 men and 11 women whose mean _ SD age was 46.7 _+ 21.9 years. All scans were performed at the UCSF Magnetic Resonance Umt on a 0.5-T Diasonics MT/S system using spinecho technique f i r 2000 msec, TE 28/56 msec). Section thickness was 5 mm, with a 2.6-mm gap between sections. Lqplane p~el resolution was 1.7 mm and 20 consecutive axial sections through the brain were obtained. All scans were independently reviewed and DWMH identified by two semor board-certified UCSF neuroradiologists blind to the purposes of the study. D W ~ was defined as focal parenchymal areas of increased signal intensity in the white matter. Careful notation was made of the presence and location of DWMH. The extent or severity of DWMH was assessed by using a modification of the 4-point grading scale described by Brant-Zawadzki et al (1985): grade 0 = no lesions; grade 1 = s ~ lesions confined to the subependymal region of the ventricles or small subcortical or white matter lesions; grade 2 = subependymal and discrete separate lesions; and grade 3 = loci that are large and coalescing. The psychiatric patients were divided into two groups according to the presence or absence of DWMH. The medical records of each psychiatric patient were reviewed by a research psychiatrist blind to the MRI results, and the following clinical characteristics were obtained from the medical history, physical, and neurological examinatior:s: (1) hypertension (HTN), which was defined as a systolic blood pressure (BP) greater than 160 mmHg or a diastolic BP greater than 90, a previous history of HTN, or previous or current treatment for HTN; (2) diabetes mellitus (by history); (3) history of myocardial infarction (MI) or angina; (4) history of transient ischemic attack (TIA) or stroke; (5) history of smoking; (6) history of alcohol use; (7) history of head trauma; (8) history of birth trauma; (9) history of electroconvulsive therapy; (10) family history of major psychiatric disorder (defined as a history of schizophrenia, major mood disorder, dementia, or alcoholism in first- or second-degree relative); (11) family history of cardiovascular disease (defined as a history of MI, angina, TIA, or stroke in firstor second-degree relative); (12) abnormal EEG as interpreted by a UCSF board certified neurologist/clinical electroencephalographer blind to the purposes of the study; (13) abnormal ECG as interpreted by a UCSF board certified cardiologist blind to the purposes of the study; (14) dex~methasone suppression test (DST) nor, suppression (defined as a 4:00 PM postdexamethasone cortisol of greater than 5 tLg/dl); and (15) the presence of abnormalities on the admitting neurological examination as performed by psychiatric residents (defined as visual field defects, cranial nerve dysfunction, abnormal motor or sensory examination, pathological reflexes, and cerebellar or extrapyramidal system signs that could not be attributed to nevroleptic medication). These clin-
920
BIOL PSYCHIATRY 1991;29:918-922
R.F. Deicken et al
ical characteristics as well as age were compared between psychiatric patients with and without DWMH.
Results Of the 90 psychiatric patient MRI studies that were evaluated, 38 (42%) had evidence of DWMH. As for the normal controls, 3 of the 25 (16%) had evidence of DWMH, and all three cases were in subjects greater than 70 years old. N¢ significant sex differences were noted in the incidence of DWMH for either psychiatric patients or the control group. A regression a~olvsis.., of the incidence of DWMH versus age in the combined population of psychiatric patients and controls revealed a significant co~°relation of r - 0.63 (p 0.0001). In addition, a s-;g~ificant correlation, r = 0.66 (p = 0.0001), emerged between the grading of DWMH and age in the combined population of psychiatric patients and controls. Regression analyses of age versus grading of DWMH in psychiatric patients and controls separately revealed correlations of r = 0.75 (p - 0.0001) and r - 0.52 (p = 0.0075), respectively. These results suggest that both the incidence and severity of DWMH increase with age. With regard to the location and grading of DWMH, 27 of the 38 psychiatric patients (71%) and all 3 of the controls with DWMH had hyperintensities in both hemispheres. The DWMH were distributed in the centmm semiovale (30 patients, 79%; and all 3 controls), corona radiata (28 patients, 74%), and adjacent to occipital (15 patients, 39%) and frontal (17 patients, 45%) horns of the lateral ventricles. As for the grading of DWMH, all three control subj~ts with DWMH had grade i severity. In the psychiatric patients with DWMH, 20 patients (52.6%) had grade ! severity, 12 patient~" (31.5%) had grade 2 severity, and 6 patients (15.7%) had grade 3 severity. A comparison of selected clinical characteristics in psychiatric patients with and without DWMH is shown in Table 1. The mean _ SD age for patients with DWMH was 62 17.8 years and for patients without DWMH, it was 32 4- 13.5 years. Because of this significant difference in mean age between patients with and without DWMH, we performed an analysis of covariance (ANCOVA) with DWMH as the dependent variable and age as the covariate for each of the clinical characteristics on Table 1. This analysis of covariance revealed that hypertension (F" = 9.98, df = 1, p = 0.002), history of Ml/angina i F = 6.18, df - !, p = 0.015), al'aormal neurological examination (F = 4.19, df = 1; p = 0._04), and ahncJrmzl ~ C ~ (F = 4. !6, df = l, p = 0.04) were significantly more prevalent in psychiatric patients with DWMH than in those patients without DWMH.
Discussion The overall incidence of DWMH in this study w ~ 42% for psychiatric patients and 12% for the control subjects. Both the incidence and severity of DWMH were positively correlated with advancing age in both psychiatric patients and controls, supporting aging itself as a strong factor for DWMH. However, the selection bias in our inclusion criteria for ordering MRI scans and the teffiary care nature of our referral center limit the significance of our study results, and argue for caution in extrapolating our findings to a general population of psychiatric patients. In this study, hypertension, history of Ml/angina, and abnormal neurological exami-
MRI Deep White Matter Hyperintensity
niOLPSYORATRY I991~29~.91g..922
921
Table !. Comparison of Selected Clinical Characteristics in Psychiatric Patients With and Without DWMH Present (n = 38) Hypertension Diabetes History Ml/angina ~ s * q ~ TIA/stroke Abnormal neurological examination History o~ smoking History of alcohol use History of head trauma History of birth trauma History of ECT Family history of psychiatric disorder Family history of cardiovascular disease Abnormal EEG Abnormal ECG DST nonsuppression
17 ! 7 3 !9 18 13 4 3 3 19 13 8/26 21 10/32
(44.7%) (18.4%) (7.9%) (50.0%) {47.4~ ) (34.2%) (10.5%) (7.9%) (7.9%) {50.0%) (34.2%) (307%) (55.3%~ (31.3%)
Absent (n = 52) 0a 0 0 t' 0 8 25 25 10 0 I 31 14 6/42 $ 11/37
(15.4%)" (48%) (48.1%) (19.2%) (1.9%) (59.6%) (26.9%) (14.3%) (i5.4%)" (29.7%)
~p -- 0.002 by ANCOVA, adjusted for age. bp = 0.015 by ANCOVA, adjusted for age. "p = 0.04 by ANCOVA, adjusted for age.
nation were significantly more prevalent in patients with DWMH than in those without DWMH, even after controlling for age differences between the two groups. In addition, abnormal ECGs were also more prevalent in the psychiatric DWMH group, a finding that, to the best of our knowledge, has not been previously reported in the literature. Although etiology of DWMH in our psychiatric population remains speculative, several findings from this study and others would support a vascular-ischemic etiology for a significant percentage of the DWMH in this study. First, the DWMH seen in our patients has been shown by neuropathology studies of other patients to be associated with arteriosclerotic changes in the long, penetrating medullary arteries that supply the deep hemispheric white matter (Kinkel et al 1985; Awad et al 1986; Kirkpatrick and Hayman 1987). Second, hypertension, history of MI or angina, and abnormal ECG appear to be significant factors_ ~sociated with DWMH in t_his s.nady. Th.ird, other investigators_ have reported DWMH to be associated with. risk factors for arteriosclerosis such as cerebrovascular disease, coronary artery disease, and diabetes (Kinkel et al 1985; Gerard and Weisberg 1986; Inzitari et al 1987; Coffey et al 1988; Kertesz et al 1988). Thus, although we have no neuropathological verificatien, the clinical and MRI findings in our patients and those of comparable studies are not inconsistent with subcorticai arte~osclerotic encephalopathy. From a neuropsychiatric perspective, it is worthwhile noting that psychiatric disturbances are commonly seen in many syndromes that arise from diseases of the subcortical gray and white matter (Cummings 1986). Our relatively high incidence of DWMH in patients with major psychiatric disorders, taken together with recent reports by other investigators (Dupont et al 19.o0; Coffey et al 1988, 1990; Kirshnan et al I988), suggest that DWMH and cerebrovascular risk factors may be more closely associated with psychiatric disorders, especially in the aged, than has been previously described.
922
BIOLPSYCHIATRY
R.F. Deicken et al
1991:29:918-922
The authors would like to gratefully acknowledge that Harman V. Peeke, Ph.D. assisted with the statistical analysis in this study.
References Awad IA, Johnson PC, Spetzler RF, et al (1986): Incidental subcortical lesion,~ identified on magnetic resonance imaging in the elderly: ll. Postmortem pathological correlations. Stroke 17:1090-1097. Brant-Zawadzki M, Fein G, Van Dyke C, et al (1985): MR imaging of the aging brain. Am J Neuroradiol 6:675-682. Coffey CE, Figiel GS, Djang WT, et al (1988): Leukoencel~alopathy in elderly depressed patients referred for EL'~f. 8iol Psychiatry 24:!43-161. Coffey CE, Figicl GS, Djang WT, et al (1990): Subcortical hyperintensity on magnetic resonance imaging: A comparison of normal and depressed elderly subjects. Am J Psychiatry 147:187189. Cummings JL (1986): Subcortical dementia. "Br J Psychiatry 149:682-697. Dupont RM, Jemigan TL, Butters N, et al (1990): Subcortical abnormalities detected in bipolar affective diso~er using magnetic resonance imaging: Clinical and neuropsychological significance. Arch Gen Psychiatry 47:55-59. Gerard G, Weisherg LA (1986): MR! periventricular lesions in adults. Neurology 36:998-1001. Inzitari D, Diaz F, Fox A, et al (1987): Vascular risk factors and leukoaraiosis. Arch Neuro144:4247. Kertesz A, Black SE, Tokar G, et al (1988): Periventricular and subcortical hyperintensities on magnetic resonance imaging: "Rims, caps, and unidentified bright objects." Arch Neuro145:404408. Kinkel WR, Jacobs L, Polachini I, et al (1985): Subcortical arteriosclerotic encephalopathy (Binswanger's disease). Arch Neurol 42:95 !-959. Kirkpatrick JB, Hayman LA (1987): White-matter lesions in MR imaging of clinically healthy brains of elderly subjects: Possible pathologic basis. Radiology 162:509-51 i. Krishnan KR, Goli V, Ellinwood EH, et al (1988): Leukoencephalopathy in patients diagnosed as major depressive. Biol Psychiatry 23:519-522.
BIOL PSYCHIATRY 199 ! ;29:918-922
MRI Deep Wh' te Matter Hyperintensity in a Psychiatric Populatior Raymond F. Deicken, Victor I. Reus, Luisa Manfredi, and Owen M. Wolkowitz
The authors evaluated magnetic resonance imaging (MRI) of deep white matter hyperintensity (DWMH) in 90 adult psychiatric inpatients in whom MRls were clinically indicated and 25 age-m:ztched, medically healthy controls. Forty-two percent of the psychiatric patients and 12% of the controls had evidence of DWMH on MRI. Both incidence and severity of DWMH were sign~cantly correlated with age in both group~. Even after controlling for age in the psychiatric population, DWMH was significantly associated with hypertension, history of myocardial infarction or angina, abnormal electrocardiogram, and abnormal neurological examinations.
Introduction Most studies e f deep white matter hyperintensities (DWMH) identified by magnetic resonance imaging :, .~. .".". : have ~ecused on the grading of white matter lesions, cerebrovascular risk factors, neurological abnormalities, or neuropathological correlates in nonpsychiatric populations. However, relatively few studies have examined the incidence of DWMH and cerebrovascular risk factors in psychiatric populations. Because of the subcortical locztion of white matter hyperintensities, it is conceivable that such lesions might have an effect on behavior and cognition and thus might be associated with different psychiatric presentations. Four recent studies suggest that a significant percentage of patients with Bipolar Affective Disorder (oupont et al 1990) and patients with Major Depression (Coffey et al 1988, 1990; Krishnan et al 1988) exhibit DWMH on MRI. Because DWMH appears to be present in patients with primary psychiatric disorders, we decided to systematically examine the occurrence of DWMH and its relationship to cerebrovascular risk factors in a mixed population of adult psychiatric patients. Patients and M e t h o d s We evaluated 90 consecutive MRI studies of psychiatric inpatients admitted to the Behavioral Neuroscience Service at UCSF Langley Porter Psychiatric Institute (a tertiary ca~e referral center) between 1986 and 1988. The psychiatric population consisted of
From the University of CaliforniaSchool of Medicine, Department of Psychiatry, San Francisco, C A 94143. .~,ddressreprint requests to Raymond F. Deicken, M.D., M.S., Veterans Administration Medical Center, Department of Psychiatry, 116-N, 4150 Clement Street,San Francisco,C A 94121. Received November 14, 1989; revised September 7, 1990. Presented at the 142rid Annual Meeting of the American PsychiatricAssociation,San Fr~:isco, California,May 6-I I, 1989.
© 1991 Society of Biological Psychiatry
0006-3223/91/$03.50
MR! Deep White Matter Hyperintensity
BIOLPSYCHIATRY
919
1991 ;29:9| 8-922
30 men and 60 women whose mean _+ SD age was 43.9 _+ 21.5 years. The most common psychiatric diagnoses in this population were major depression (n - 31), bipolar disorder (n = 26), schizophrenia (n = 15), dementia (n = 9), organic affective disorder (n = 3), and somatoform disorder (n = 3). The MRI studies were obtained during the first week of admission for the following indications: (1) abnormal neurological examination or movement disorder (n = 27), (2) iustory of head trauma seizure disorder with no prior brain imaging (n = 3), (3) late onset Fb~chosis, i.e., greater than 40 years old (n = 10), (4) refractory psychosis or mood disorder (n -51), and (5) dementia (n = 9). To determine the basal incidence of DWMH in normal individuals, we also examined MRI studies of 25 control subjects who were free of any medical or psychiatric illness or history of substance abuse, and who had a normal neurological examination and no identified cerebrovascular symptoms or risk factors. The control group comprised 14 men and 11 women whose mean _ SD age was 46.7 _+ 21.9 years. All scans were performed at the UCSF Magnetic Resonance Umt on a 0.5-T Diasonics MT/S system using spinecho technique f i r 2000 msec, TE 28/56 msec). Section thickness was 5 mm, with a 2.6-mm gap between sections. Lqplane p~el resolution was 1.7 mm and 20 consecutive axial sections through the brain were obtained. All scans were independently reviewed and DWMH identified by two semor board-certified UCSF neuroradiologists blind to the purposes of the study. D W ~ was defined as focal parenchymal areas of increased signal intensity in the white matter. Careful notation was made of the presence and location of DWMH. The extent or severity of DWMH was assessed by using a modification of the 4-point grading scale described by Brant-Zawadzki et al (1985): grade 0 = no lesions; grade 1 = s ~ lesions confined to the subependymal region of the ventricles or small subcortical or white matter lesions; grade 2 = subependymal and discrete separate lesions; and grade 3 = loci that are large and coalescing. The psychiatric patients were divided into two groups according to the presence or absence of DWMH. The medical records of each psychiatric patient were reviewed by a research psychiatrist blind to the MRI results, and the following clinical characteristics were obtained from the medical history, physical, and neurological examinatior:s: (1) hypertension (HTN), which was defined as a systolic blood pressure (BP) greater than 160 mmHg or a diastolic BP greater than 90, a previous history of HTN, or previous or current treatment for HTN; (2) diabetes mellitus (by history); (3) history of myocardial infarction (MI) or angina; (4) history of transient ischemic attack (TIA) or stroke; (5) history of smoking; (6) history of alcohol use; (7) history of head trauma; (8) history of birth trauma; (9) history of electroconvulsive therapy; (10) family history of major psychiatric disorder (defined as a history of schizophrenia, major mood disorder, dementia, or alcoholism in first- or second-degree relative); (11) family history of cardiovascular disease (defined as a history of MI, angina, TIA, or stroke in firstor second-degree relative); (12) abnormal EEG as interpreted by a UCSF board certified neurologist/clinical electroencephalographer blind to the purposes of the study; (13) abnormal ECG as interpreted by a UCSF board certified cardiologist blind to the purposes of the study; (14) dex~methasone suppression test (DST) nor, suppression (defined as a 4:00 PM postdexamethasone cortisol of greater than 5 tLg/dl); and (15) the presence of abnormalities on the admitting neurological examination as performed by psychiatric residents (defined as visual field defects, cranial nerve dysfunction, abnormal motor or sensory examination, pathological reflexes, and cerebellar or extrapyramidal system signs that could not be attributed to nevroleptic medication). These clin-
920
BIOL PSYCHIATRY 1991;29:918-922
R.F. Deicken et al
ical characteristics as well as age were compared between psychiatric patients with and without DWMH.
Results Of the 90 psychiatric patient MRI studies that were evaluated, 38 (42%) had evidence of DWMH. As for the normal controls, 3 of the 25 (16%) had evidence of DWMH, and all three cases were in subjects greater than 70 years old. N¢ significant sex differences were noted in the incidence of DWMH for either psychiatric patients or the control group. A regression a~olvsis.., of the incidence of DWMH versus age in the combined population of psychiatric patients and controls revealed a significant co~°relation of r - 0.63 (p 0.0001). In addition, a s-;g~ificant correlation, r = 0.66 (p = 0.0001), emerged between the grading of DWMH and age in the combined population of psychiatric patients and controls. Regression analyses of age versus grading of DWMH in psychiatric patients and controls separately revealed correlations of r = 0.75 (p - 0.0001) and r - 0.52 (p = 0.0075), respectively. These results suggest that both the incidence and severity of DWMH increase with age. With regard to the location and grading of DWMH, 27 of the 38 psychiatric patients (71%) and all 3 of the controls with DWMH had hyperintensities in both hemispheres. The DWMH were distributed in the centmm semiovale (30 patients, 79%; and all 3 controls), corona radiata (28 patients, 74%), and adjacent to occipital (15 patients, 39%) and frontal (17 patients, 45%) horns of the lateral ventricles. As for the grading of DWMH, all three control subj~ts with DWMH had grade i severity. In the psychiatric patients with DWMH, 20 patients (52.6%) had grade ! severity, 12 patient~" (31.5%) had grade 2 severity, and 6 patients (15.7%) had grade 3 severity. A comparison of selected clinical characteristics in psychiatric patients with and without DWMH is shown in Table 1. The mean _ SD age for patients with DWMH was 62 17.8 years and for patients without DWMH, it was 32 4- 13.5 years. Because of this significant difference in mean age between patients with and without DWMH, we performed an analysis of covariance (ANCOVA) with DWMH as the dependent variable and age as the covariate for each of the clinical characteristics on Table 1. This analysis of covariance revealed that hypertension (F" = 9.98, df = 1, p = 0.002), history of Ml/angina i F = 6.18, df - !, p = 0.015), al'aormal neurological examination (F = 4.19, df = 1; p = 0._04), and ahncJrmzl ~ C ~ (F = 4. !6, df = l, p = 0.04) were significantly more prevalent in psychiatric patients with DWMH than in those patients without DWMH.
Discussion The overall incidence of DWMH in this study w ~ 42% for psychiatric patients and 12% for the control subjects. Both the incidence and severity of DWMH were positively correlated with advancing age in both psychiatric patients and controls, supporting aging itself as a strong factor for DWMH. However, the selection bias in our inclusion criteria for ordering MRI scans and the teffiary care nature of our referral center limit the significance of our study results, and argue for caution in extrapolating our findings to a general population of psychiatric patients. In this study, hypertension, history of Ml/angina, and abnormal neurological exami-
MRI Deep White Matter Hyperintensity
niOLPSYORATRY I991~29~.91g..922
921
Table !. Comparison of Selected Clinical Characteristics in Psychiatric Patients With and Without DWMH Present (n = 38) Hypertension Diabetes History Ml/angina ~ s * q ~ TIA/stroke Abnormal neurological examination History o~ smoking History of alcohol use History of head trauma History of birth trauma History of ECT Family history of psychiatric disorder Family history of cardiovascular disease Abnormal EEG Abnormal ECG DST nonsuppression
17 ! 7 3 !9 18 13 4 3 3 19 13 8/26 21 10/32
(44.7%) (18.4%) (7.9%) (50.0%) {47.4~ ) (34.2%) (10.5%) (7.9%) (7.9%) {50.0%) (34.2%) (307%) (55.3%~ (31.3%)
Absent (n = 52) 0a 0 0 t' 0 8 25 25 10 0 I 31 14 6/42 $ 11/37
(15.4%)" (48%) (48.1%) (19.2%) (1.9%) (59.6%) (26.9%) (14.3%) (i5.4%)" (29.7%)
~p -- 0.002 by ANCOVA, adjusted for age. bp = 0.015 by ANCOVA, adjusted for age. "p = 0.04 by ANCOVA, adjusted for age.
nation were significantly more prevalent in patients with DWMH than in those without DWMH, even after controlling for age differences between the two groups. In addition, abnormal ECGs were also more prevalent in the psychiatric DWMH group, a finding that, to the best of our knowledge, has not been previously reported in the literature. Although etiology of DWMH in our psychiatric population remains speculative, several findings from this study and others would support a vascular-ischemic etiology for a significant percentage of the DWMH in this study. First, the DWMH seen in our patients has been shown by neuropathology studies of other patients to be associated with arteriosclerotic changes in the long, penetrating medullary arteries that supply the deep hemispheric white matter (Kinkel et al 1985; Awad et al 1986; Kirkpatrick and Hayman 1987). Second, hypertension, history of MI or angina, and abnormal ECG appear to be significant factors_ ~sociated with DWMH in t_his s.nady. Th.ird, other investigators_ have reported DWMH to be associated with. risk factors for arteriosclerosis such as cerebrovascular disease, coronary artery disease, and diabetes (Kinkel et al 1985; Gerard and Weisberg 1986; Inzitari et al 1987; Coffey et al 1988; Kertesz et al 1988). Thus, although we have no neuropathological verificatien, the clinical and MRI findings in our patients and those of comparable studies are not inconsistent with subcorticai arte~osclerotic encephalopathy. From a neuropsychiatric perspective, it is worthwhile noting that psychiatric disturbances are commonly seen in many syndromes that arise from diseases of the subcortical gray and white matter (Cummings 1986). Our relatively high incidence of DWMH in patients with major psychiatric disorders, taken together with recent reports by other investigators (Dupont et al 19.o0; Coffey et al 1988, 1990; Kirshnan et al I988), suggest that DWMH and cerebrovascular risk factors may be more closely associated with psychiatric disorders, especially in the aged, than has been previously described.
922
BIOLPSYCHIATRY
R.F. Deicken et al
1991:29:918-922
The authors would like to gratefully acknowledge that Harman V. Peeke, Ph.D. assisted with the statistical analysis in this study.
References Awad IA, Johnson PC, Spetzler RF, et al (1986): Incidental subcortical lesion,~ identified on magnetic resonance imaging in the elderly: ll. Postmortem pathological correlations. Stroke 17:1090-1097. Brant-Zawadzki M, Fein G, Van Dyke C, et al (1985): MR imaging of the aging brain. Am J Neuroradiol 6:675-682. Coffey CE, Figiel GS, Djang WT, et al (1988): Leukoencel~alopathy in elderly depressed patients referred for EL'~f. 8iol Psychiatry 24:!43-161. Coffey CE, Figicl GS, Djang WT, et al (1990): Subcortical hyperintensity on magnetic resonance imaging: A comparison of normal and depressed elderly subjects. Am J Psychiatry 147:187189. Cummings JL (1986): Subcortical dementia. "Br J Psychiatry 149:682-697. Dupont RM, Jemigan TL, Butters N, et al (1990): Subcortical abnormalities detected in bipolar affective diso~er using magnetic resonance imaging: Clinical and neuropsychological significance. Arch Gen Psychiatry 47:55-59. Gerard G, Weisherg LA (1986): MR! periventricular lesions in adults. Neurology 36:998-1001. Inzitari D, Diaz F, Fox A, et al (1987): Vascular risk factors and leukoaraiosis. Arch Neuro144:4247. Kertesz A, Black SE, Tokar G, et al (1988): Periventricular and subcortical hyperintensities on magnetic resonance imaging: "Rims, caps, and unidentified bright objects." Arch Neuro145:404408. Kinkel WR, Jacobs L, Polachini I, et al (1985): Subcortical arteriosclerotic encephalopathy (Binswanger's disease). Arch Neurol 42:95 !-959. Kirkpatrick JB, Hayman LA (1987): White-matter lesions in MR imaging of clinically healthy brains of elderly subjects: Possible pathologic basis. Radiology 162:509-51 i. Krishnan KR, Goli V, Ellinwood EH, et al (1988): Leukoencephalopathy in patients diagnosed as major depressive. Biol Psychiatry 23:519-522.
