Elsevier

Biological Psychiatry

Volume 53, Issue 2, 15 January 2003, Pages 150-156
Biological Psychiatry

Original article
Regional cerebral blood flow in depressed patients with white matter magnetic resonance hyperintensity

https://doi.org/10.1016/S0006-3223(02)01548-2Get rights and content

Abstract

Background

Functional neuroimaging studies have consistently demonstrated decreased regional cerebral blood flow (rCBF) or metabolism in the frontal lobe, temporal lobe, or anterior cingulate gyrus of depressed patients. On the other hand, white matter hyperintensity as defined by magnetic resonance imaging (MRI) has been the most consistently replicated finding in structural neuroimaging studies on depression; however, these functional and structural neuroimaging findings of depression have not been well integrated. We aimed to clarify the possible associations of MRI-defined subcortical hyperintensities with rCBF changes in depressed patients.

Methods

Twelve depressed patients with subcortical hyperintensities defined by MRI, 11 depressed patients without MRI hyperintensities, and 25 healthy volunteers underwent 99mTc ECD SPECT. Group comparisons of their rCBF and correlation analysis between MRI hyperintensity and rCBF in patients were performed with a voxel-based analysis using statistical parametric mapping (SPM) software.

Results

Depressed patients showed decreased rCBF compared with control subjects in the frontal lobe, temporal lobe, and anterior cingulate gyrus whether subcortical hyperintensity existed or not; however, the patients with MRI hyperintensity showed decreased rCBF in the thalamus, basal ganglia, and brainstem in addition to cortical areas. Further, the score for white matter hyperintensity correlated negatively with rCBF in subcortical brain structures, including the thalamus and right basal ganglia.

Conclusions

Our study indicates that depressed patients with MRI hyperintensities may have dysfunction in subcortical brain structures in addition to dysfunction in the fronto-temporal cortical structures.

Introduction

The continuing development of new neuroimaging technologies has led to the in vivo elucidation of the functional and anatomical pathology in depressed patients Drevets 2000, Soares and Mann 1997a, Soares and Mann 1997b. Functional neuroimaging studies using 133Xe blood flow, single photon emission computed tomography (SPECT), and positron emission tomography (PET) have consistently demonstrated decreased regional cerebral blood flow (rCBF) in the frontal lobes of depressed patients Austin et al 1992, Bench et al 1992, Bench et al 1993, Curran et al 1993, Ebert et al 1993, Ito et al 1996, Lesser et al 1994, Mayberg et al 1994, Murata et al 2000, Rubin et al 1995, Sackeim et al 1990, Schlegel et al 1989, Vasile et al 1996, Yazici et al 1992. Some studies have reported an inverse correlation between prefrontal rCBF and severity of depression Drevets et al 1992, Soares and Mann 1997a, and some have suggested an association between decreased prefrontal blood flow and frontal lobe syndrome that includes retardation, lack of insight, and impaired executive functions in depressed patients (George et al 1994). Furthermore, several studies have demonstrated reduced CBF in the temporal lobes Austin et al 1992, Curran et al 1993, Ito et al 1996, Lesser et al 1994, Mayberg et al 1994, Philpot et al 1993, Rubin et al 1995, Sackeim et al 1990, Vasile et al 1996 or anterior cingulate gyrus Curran et al 1993, Ito et al 1996 of depressed patients.

On the other hand, there have also been a number of magnetic resonance imaging (MRI) studies investigating structural brain abnormalities in patients with depression (Soares and Mann 1997b). The most consistent structural finding from these MRI studies on depressed patients was a high incidence of white matter hyperintensities Awad et al 1986, Coffey et al 1989, Schmidt et al 1991. In elderly depressed patients, white matter hyperintensities are assumed to occur as a consequence of ischemic cerebrovascular disease involving small vessels. Because of the high incidence of white matter hyperintensities, it is suggested that there is a subgroup of depression with vascular lesions (Krishnan et al 1997). Krishnan and colleagues used the term “MRI-defined vascular depression” to describe the pathology in the depressed patients with white matter hyperintensities. It is known that the symptoms of depressed patients with white matter hyperintensities resemble the frontal lobe syndrome George et al 1994, Krishnan 1993, Krishnan and McDonald 1995. Cerebrovascular lesions usually occur over brain structures receiving blood from perforating arteries supplying the subcortical structures, including the basal ganglia and thalamus, or at the borders of vascular territories (Fujikawa et al 1993). Thus, patients with white matter hyperintensities may have lesions mainly at the subcortical structures. This suggests that lesions over white matter and subcortical structures may interrupt brain networks and cause deficits in frontal lobe function Coffey et al 1990, Greenwald et al 1996. In demented patients, a correlation between white matter lesions and decreased blood flow has been reported (Waldemar et al 1994); however, in most functional neuroimaging studies of depressed patients, MRI findings were not taken into account, and the possible effects of hyperintensity lesions on T2-weighted images, such as white matter hyperinensities, on rCBF or metabolism have not been well investigated Drevets 2000, Soares and Mann 1997b. In other words, emerging findings from functional and structural neuroimaging of depression have been investigated separately and have not been integrated. Thus, in the present study we aimed to examine the association of MRI hyperintensities with rCBF changes in depressed patients and to elucidate the pathophysiology of depression.

Section snippets

Subjects

We studied two groups of patients who met DSM-IV criteria for major depression. At first, we consecutively collected 12 patients with subcortical hyperintensities, 10 female and 2 male, aged 37–68 years (58.3 ± 9.2, mean ± SD) from Tokyo Medical and Dental University–affiliated psychiatric hospitals. Magnetic resonance imaging subcortical hyperintensities were judged as positive if the patient had a score of 2 or more in a modified Fazekas classification system (Krishnan et al 1993) (see MRI

Results

A comparison between the depressed patients without MRI hyperintensities and control subjects revealed significantly decreased rCBF in the frontal lobe, temporal lobe, and anterior cingulate gyrus in the bilateral hemispheres of the depressed patients, as shown in Figure 1 (one significant cluster with peak Talairach coordinates [x, y, z (mm)] at [−40, 30, 10] [Z score = 3.35] and [34, −2, 52] [Z score = 3.10]). On the other hand, the depressed patients with MRI hyperintensities showed

Discussion

Decreased frontal blood flow and increased incidence of white matter hyperintensity have been the most consistently replicated findings in neuroimaging studies of depression Drevets 2000, Soares and Mann 1997a, Soares and Mann 1997b; however, few studies have investigated the association between these functional and anatomical findings. Although functional studies examining rCBF usually employed criteria to exclude findings from neurologic or organic brain studies Bench et al 1992, Maes et al

Acknowledgements

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology and a research grant for nervous and mental disorders from the Ministry of Health, Labor and Welfare of Japan (11B-3).

Dr. Junko Mukai and the staffs of the Section of Psychiatry and Behavioral Science, Tokyo Medical and Dental University, and of the Brain Imaging Projects, National Institute of Radiologic Sciences, are gratefully acknowledged.

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