Magnetic resonance imaging signal hypointensity and iron content of putamen nuclei in elderly depressed patients

Abstract

We previously introduced a semiquantitative scale for assessment of iron content of putamen nuclei as determined by magnetic resonance imaging (MRI) — the Signal Hypointensity in the Putamen (SHIP) scale. Such hypointensity may be related to putamen nuclei iron content, although this suggestion remains controversial, especially in the elderly. In the present study, we apply the SHIP scale to a sample of 68 elderly depressed patients (diagnosed with DSM-IV major depression using the Diagnostic Interview Schedule and clinical interview) and a group of 28 age-matched non-depressed control subjects. MRI scans were conducted on a single 1.5-T General Electric Signa system with axial acquisitions obtained parallel to the canthomeatal line. Technical parameters were as follows: (1) repetition time (TR)=500 ms and echo time (TE)=15 ms for T1-weighted images; (2) TR=2500 ms and TE=30 ms for proton-density-weighted images; and (3) TR=2500 ms and TE=80 ms for T2-weighted images. Among depressed patients, older age of depression onset and greater severity of depression were associated with increased putamen nuclei iron deposition. When depressed patients were compared with control subjects, the patient group demonstrated greater putamen nuclei iron, but the finding was significant only for the left hemisphere. Our findings support previous neuroimaging studies linking both changes in the basal ganglia and greater left-sided brain pathology to late-life depression.

Introduction

In a previous report, we introduced a new semiquantitative scale for assessment of magnetic resonance imaging (MRI) putamen nuclei iron content, the Signal Hypointensity in the Putamen (SHIP) scale (Steffens et al., 1996). The iron content in normal control subjects was examined using T2-weighted MRI hypointensity. In addition to observing increased iron deposition with aging, we noted that the increase followed a specific posterolateral-anteromedial gradient. In the present report, we use the SHIP scale to examine putamen nuclei iron content in a clinical sample of elderly depressives.

Whereas early-onset depression has been related more closely to family and genetic factors (Baron et al., 1981), late-onset depression has been associated with structural brain changes (Post, 1962, Krishnan et al., 1997). Alterations in the basal ganglia with late-life depression have been a particular area of focus. Smaller volumes of the putamen (Husain et al., 1991) and caudate (Krishnan et al., 1993) have been associated with late-onset depression. Figiel et al. (1991b)studied late- and early-onset depressed elderly and found that basal ganglia hyperintensities were more common in the late-onset group. Additionally, Figiel et al. (1991a)observed caudate hyperintensities in seven elderly depressed patients who developed neuroleptic-induced parkinsonism. It has been proposed that the basal ganglia circuit is of primary importance in the pathophysiology of affective disorder via connections with structures in both the limbic system and prefrontal cortex (McDonald and Krishnan, 1992).

Most investigators agree that iron deposition in the basal ganglia is associated with a decrease in signal intensity on MRI T2-weighted images (Thomas et al., 1993, Bartzokis et al., 1994, Vymazal et al., 1996). Several radiographic/pathological studies have correlated signal hypointensities with tissue specimens (Drayer et al., 1986, Drayer et al., 1987, Dietrich and Bradley, 1988, Drayer, 1988b, Drayer, 1989). Many investigators have concluded that the available evidence suggests that iron plays a substantial role in shortening relaxation time, and therefore they use T2 relaxation times or signal hypointensities to examine iron deposition, despite some concerns about the use of T2 as a measure of iron content (Chen et al., 1989Chen et al., 1993Jernigan et al., 1991Kucharczyk et al., 1994). In particular, Jernigan et al. (1991)reported age-related increases in magnetic resonance (MR) detectable cerebrospinal fluid (CSF), which may increase T2 and therefore affect the interpretation of hypointensities seen on T2-weighted images.

Because the globus pallidus nuclei have been shown to be rich in iron (Drayer et al., 1986, Drayer et al., 1987) and the extent of globus pallidus nuclei iron content correlates with a low signal intensity throughout the globus pallidus on T2-weighted MR images, researchers have used the hypointense signal of the globus pallidus as a standard for measuring iron in other basal ganglia structures (Drayer et al., 1987, Drayer, 1988a). We used this standard in our previous study of putamen nuclei iron content and aging (Steffens et al., 1996).

Iron content of basal ganglia structures has been examined in several neuropathologic conditions. Ye et al. (1996)demonstrated increased putamenal iron content in Parkinson's disease, and Ryvlin et al. (1995)found that putamenal T2 relaxation time correlated positively with disease duration, with decreased putamenal iron concentration in patients with a duration of illness over 10 years. Another MRI study showed increased iron deposition with nigrostriatal degeneration (Lang et al., 1994). Finally, Bartzokis et al. (1994), using MRI, found increased iron stores in the caudate and globus pallidus of patients with Alzheimer's disease. To our knowledge, no study has examined basal ganglia iron content in a psychiatric illness such as major depression.

To examine the relationship between putamen nuclei iron content and late-life depression, we undertook a study of a clinical sample of elderly depressed patients and a group of age-matched non-depressed control subjects, using the SHIP scale (see Table 1). We hypothesized that the increased iron deposition with aging that we previously reported would be seen to a greater extent in elderly depressives, particularly those with late-onset depression. Additionally, we hypothesized that the pattern of increased iron deposition seen in geriatric depression would follow a posterolateral–anteromedial gradient, as noted in our prior study of normal aging.