Quantitative cerebral anatomy in depression. A controlled magnetic resonance imaging study.

Magnetic resonance imaging was used to examine cerebral anatomy in 48 inpatients with severe depression who were referred for electroconvulsive therapy and in 76 normal control subjects. The magnetic resonance imaging measures included determinations of regional cerebral volumes and ratings of the frequency and severity of cortical atrophy, lateral ventricular enlargement, and subcortical hyperintensity. The mean total frontal lobe volume was found to be 7% smaller in the inpatients with severe depression (235.88 mL) than in the normal control subjects (254.32 mL)--a difference that was statistically significant even after adjusting for the effects of age, sex, education, and intracranial size. No group differences were observed in the volumes of the cerebral hemispheres, the temporal lobes, or the amygdala-hippocampal complex, nor in the frequency of cortical atrophy. Neither did the groups differ with respect to the total volumes of the lateral and third ventricles, nor in the frequency of lateral ventricular enlargement. Patients with depression had a significantly higher frequency of subcortical hyperintensity in the periventricular white matter, with an odds ratio of 5.32.

Magnetic resonance imaging of the caudate nuclei in depression. Preliminary observations.

A role of the caudate nucleus in depression has been suggested from relevant clinical conditions, such as patients with Huntington's disease or caudate infarcts, as well as animal studies. Correlations of caudate nucleus disease with depressive symptoms have been limited to autopsy studies and cases of gross pathological disorder, such as large infarcts. We used serial axial high-field magnetic resonance images and an unbiased stereological technique to estimate the volumes of the caudate nuclei in 50 patients who met DSM-III criteria for major depression (23 men, 48.3 +/- 17 years old) in comparison with 50 age- and gender-matched normal controls free of major neurological and psychiatric disorders. Depressed patients had smaller caudate nucleus volumes (5.2 +/- 1.6 cm3) compared with controls (6.2 +/- 1.7 cm3). Right and left caudate nucleus volumes were smaller in depressed patients compared with controls. Age was negatively correlated with caudate nucleus volumes in depressed patients as well as in controls. Caudate nucleus volumes in depressed patients were inversely correlated with the bicaudate and bifrontal indices. These results may be the first demonstration of diminished caudate nucleus volumes in depression and suggest a role for the caudate nucleus in the pathogenesis of major depression.

Brain anatomic effects of electroconvulsive therapy. A prospective magnetic resonance imaging study.

To determine prospectively whether electroconvulsive therapy (ECT) produces structural brain changes, 35 inpatients with depression underwent magnetic resonance imaging before and twice after (at 2 to 3 days and at 6 months) completion of a course of brief-pulse, bilateral ECT. The magnetic resonance images were analyzed blindly for evidence of changes in brain structure using two approaches: measurement of regional brain volumes and a pairwise global comparison. Structural brain abnormalities were present in many patients before ECT. The course of ECT produced no acute or delayed (6-month) change in brain structure as measured by alterations of the total volumes of the lateral ventricles, the third ventricle, the frontal lobes, the temporal lobes, or the amygdala-hippocampal complex. In five subjects, the pairwise global comparisons revealed an apparent increase in subcortical hyperintensity, most likely secondary to progression of ongoing cerebrovascular disease during follow-up. Our results confirm and extend previous imaging studies that also found no relationship between ECT and brain damage.

In vivo assessment of pituitary gland volume with magnetic resonance imaging: the effect of age.

We used sagittal and coronal T1 weighted magnetic resonance images, at 1.5 Tesla, to measure the height, width, length, and cross-sectional area and to generate two estimates of pituitary gland volume in 35 normal volunteers aged 26-79 yr (19 females and 16 males). Subjects over 50 yr of age had significantly smaller pituitary gland height (P = 0.03), area (P = 0.04), and volume (P = 0.04) than those under 50 yr (by two-tailed t test). Overall, age was negatively correlated with pituitary volume (V1: r = -0.51; P = 0.003; V2: r = -0.47; P = 0.008), area (r = -0.43; P = 0.009), and height (r = -0.46; P = 0.005), but not with pituitary length or width. There were no statistically significant differences in pituitary size between men and women (by two-tailed t test). These findings suggest that pituitary gland height provides a good single measure for the assessment of pituitary gland size and that age must be controlled for in studies of pituitary gland size.

Pituitary size in depression.

Magnetic resonance images centered at the pituitary stalk were used to measure pituitary gland size in 19 patients with major depression compared with that in age- and sex-matched controls. Depressed patients had significantly greater pituitary cross-sectional area (P = 0.0009) and volume (P = 0.007) than the controls. This difference was particularly prominent in elderly depressed patients compared to elderly controls. These results provide the first demonstration of structural alterations in the pituitary gland in major depression.

Cerebral white matter disease in late-onset paranoid psychosis.

We examined magnetic resonance (MR) scans of the heads of 8 patients with late onset psychosis and 8 aged controls. Although some patients had mild cognitive impairment, none had depression or a history or examination suggesting focal brain disease. Thus, all patients met DSM-III-R criteria for late-onset schizophrenia. All 8 patients showed significant leukoencephalopathy or vascular pathology on MR imaging, and temporoparietal and occipital lesions were especially prominent. Little such pathology was evident on control scans. We suggest that focal brain disease of vascular origin may be associated with late-onset psychosis, and that MR scanning of such cases may provide important clues to pathogenesis.

Hyperintense lesions on magnetic resonance images in bipolar disorder.

BACKGROUND: To examine the magnetic resonance (MR) images of bipolar patients across a wide age range for the presence of hyperintense lesions compared to age- and gender-matched control subjects. METHODS: Consecutive admissions to a mood disorders unit over a 2-year period were evaluated retrospectively for the presence of bipolar disorder by DSM-III-R criteria and whether they received an MR scan. Bipolar patients (n = 70, mean age = 49.9 +/- 19.7 years) were age- and gender-matched to control subjects (n = 70, mean age = 53.2 +/- 18.1 years) and the MR scans were rated to assess for the presence of hyperintensites. RESULTS: Compared to control subjects, the bipolar patients demonstrated hyperintense lesions in the subependymal region, subcortical gray nuclei, and the deep white matter. CONCLUSIONS: Hyperintense lesions in bipolar patients are found in both the subcortical white matter and gray nuclei and may play an important role in the etiology of bipolar illness.

Magnetic resonance findings in patients with early-onset Alzheimer's disease.

The magnetic resonance scans of 22 patients with early-onset Alzheimer's disease (AD) were compared to 16 age-matched neurologically normal controls for the presence of white matter subcortical hyperintensities (SCH) and periventricular hyperintensities (PVH). Patients with AD were significantly more likely to have evidence of PVH (p less than 0.01) than age-matched controls. There was no significant difference between the two groups in either the frequency of SCH or the size of the largest lesion. Within the AD group, there was no difference demonstrated in the location of the SCH, either in the anterior-posterior plane or between the two hemispheres. Patients with AD more frequently demonstrated ventriculomegaly (p less than 0.001) and sulcal widening (p less than 0.05) compared with controls. This study suggests that the SCH seen in early-onset AD patients on MRI are related more to the aging process than to the AD process and that the increased frequency of PVH may have a relationship to the disease process.

Leukoencephalopathy in elderly depressed patients referred for ECT.

Using brain magnetic resonance imaging (MRI) and high-resolution computed tomography (CT), we identified changes in the subcortical white matter in 44 of 67 elderly depressed inpatients (66%) referred for electroconvulsive therapy (ECT). This "leukoencephalopathy" was frequently associated with other structural brain changes, including cortical atrophy, lateral ventricular enlargement, and lacunar infarctions of the basal ganglia and thalamus. Many (58%) of the patients had developed late-onset depressive disorders, and the majority (86%) had been refractory to and/or intolerant of antidepressant drug therapy. Nevertheless, all but 1 of the 44 patients subsequently responded to a course of ECT, which in general was well tolerated. Although the precise etiology of the leukoencephalopathy remains unclear, clinical data suggest that it may result from arteriosclerotic disease of the medullary arteries that supply the subcortical brain regions. Several lines of evidence suggest that leukoencephalopathy may have implications for the pathophysiology of depressive illness, at least in some elderly patients.

Platelet [3H]-imipramine binding and leukoencephalopathy in geriatric depression.

We examined the relationship between platelet [3H]-imipramine binding and leukoencephalopathy as assessed by 1.5 Tesla Magnetic Resonance Imaging (MRI) in 21 elderly depressed patients who satisfied DSM-III criteria for major depression. Both drug-free platelet [3H]-imipramine binding and brain MRI studies were obtained during the same episode of depression. Our findings show a significant inverse relationship between frequency of subcortical hyperintensity (SCH) and the number (Bmax) of platelet [3H]-imipramine binding sites. Patients with Bmax less than 850 fmol/mg protein had significantly larger SCH compared with patients with a higher Bmax. These data provide further support to the potential use of platelet [3H]-imipramine binding studies and brain MR imaging as diagnostic adjuncts in geriatric depression and suggest, moreover, that these two biological markers may be linked in geriatric patients with depression.

A brain magnetic resonance imaging study of pituitary gland morphology in anorexia nervosa and bulimia.

Magnetic resonance imaging (MRI) of the brain was used to examine the morphology and dimensions of the pituitary gland in 18 patients with eating disorders (8 anorectics and 10 bulimics), in comparison with 13 healthy volunteers. None of the 18 patients with anorexia or bulimia had any radiological evidence suggestive of pituitary macroadenoma, cyst, or empty sella. Measurements revealed that the anorectics and bulimics had smaller pituitary gland cross-sectional areas (p less than 0.05) and smaller pituitary gland heights, compared with healthy controls. These preliminary findings in anorectics and bulimics are suggestive of pituitary atrophy secondary to nutritional or endocrine alterations, rather than a primary pituitary pathology.

Assessment of posterior fossa structures with midsagittal MRI: the effects of age.

Midsagittal magnetic resonance (MR) images of 36 normal volunteers, ranging in age from 26 to 79 years, were used to evaluate the effects of age on the size of posterior fossa structures (cerebellar vermis, midbrain, pons, medulla and fourth ventricle). Our results demonstrate a highly statistically significant age-related decline in the cross-sectional area of the midbrain (r = -.44, p less than 0.007), a less prominent decline in the area of the anterior cerebellar vermis (r = -.33, p less than 0.05) and striking intercorrelations between the dimensions of the pons, medulla and cerebellar vermis. To the best of our knowledge, this is the first MRI demonstration of midbrain atrophy during aging in normal adults.

Subcortical hyperintensities on brain magnetic resonance imaging: a comparison between late age onset and early onset elderly depressed subjects.

Subcortical structural changes have been reported to occur in some elderly subjects with late age onset depression. Given the association between diseases affecting subcortical structures and affective disorders, this suggests that these structural changes may be involved in the etiology of late age onset depression in some patients. With the advent of Brain Magnetic Resonance Imaging (MRI), "in vivo" analysis of these subcortical structures is now possible. The authors report a higher occurrence of caudate (60% vs. 11%) and large deep white matter hyperintensities (60% vs. 11%) in late age onset elderly depressed subjects compared with early onset elderly depressed subjects. These results suggest that late age onset depression may be mediated by caudate and white matter structural changes in some patients.

Caffeine augmentation of ECT.

In a randomized, double-blind, placebo-controlled pilot study of 40 depressed inpatients, the authors compared two techniques for maintaining seizure duration during pulse unilateral ECT: pretreatment with intravenous caffeine versus electrical stimulus intensity dosing. Both techniques effectively maintained seizure duration, but with caffeine this was accomplished without any increase in mean stimulus intensity over the course of ECT. There were no differences between the two techniques in therapeutic outcome or cognitive side effects from ECT, and caffeine pretreatment was well tolerated. The authors discuss the clinical and research implications of these findings with respect to strategies for maintaining seizure duration during ECT.

Subcortical hyperintensity on magnetic resonance imaging: a comparison of normal and depressed elderly subjects.

Subcortical hyperintensity on T2-weighted brain magnetic resonance imaging was significantly more common and more severe in elderly depressed patients referred for ECT than in a matched control group of normal elderly subjects. The potential clinical and research implications of these findings are discussed.

Effects of ECT on brain structure: a pilot prospective magnetic resonance imaging study.

The authors describe a pilot prospective investigation of the effects of ECT on brain structure using magnetic resonance imaging (MRI). In nine patients with major depression, a course of ECT produced no acute changes in brain structure according to blind raters' assessments of cortical atrophy and global comparison of pre- and post-ECT studies. There were also no significant changes in the ventricle-brain ratios. Pre-ECT brain abnormalities were common in these patients yet were also unaffected by ECT. Future MRI studies of ECT should include more subjects and should address long-term changes and subtle brain abnormalities.

Quantitative cerebral anatomy of the aging human brain: a cross-sectional study using magnetic resonance imaging.

Seventy-six healthy adults underwent magnetic resonance imaging (1.5 T) to investigate the effects of age on regional cerebral volumes and on the frequency and severity of cortical atrophy, lateral ventricular enlargement, and subcortical hyperintensity. Increasing age was associated with (1) decreasing volumes of the cerebral hemispheres (0.23% per year), the frontal lobes (0.55% per year), the temporal lobes (0.28% per year), and the amygdala-hippocampal complex (0.30% per year); (2) increasing volumes of the third ventricle (2.8% per year) and the lateral ventricles (3.2% per year); and (3) increasing odds of cortical atrophy (8.9% per year), lateral ventricular enlargement (7.7% per year), and subcortical hyperintensity in the deep white matter (6.3% per year) and the pons (8.1% per year). Many elderly subjects did not exhibit cortical atrophy or lateral ventricular enlargement, however, indicating that such changes are not inevitable consequences of advancing age. These data should provide a useful clinical context within which to interpret changes in regional brain size associated with "abnormal" aging.

Simultaneous major depression and panic disorder: treatment with electroconvulsive therapy.

BACKGROUND: Major depression and panic disorder commonly occur together. Patients with simultaneous depression and panic disorder may have a higher lifetime rate of suicide attempts and an overall worse prognosis than patients with either depression or panic disorder alone. In addition, preliminary work suggests that some of these patients may not respond satisfactorily to antidepressants. In this report, we describe the clinical courses of eight consecutive patients with simultaneous major depression and panic disorder who were referred for ECT at our institution. METHOD: Eight consecutive patients who met DSM-III-R criteria for simultaneous major depression and panic disorder received ECT. All eight patients were evaluated by a structured clinical interview and the patients' major depression and panic disorder were evaluated with a 7-point Clinical Global Impressions severity rating scale. RESULTS: Before ECT was begun, each subject's panic disorder and depression were rated as at least markedly ill. After receiving ECT, all eight showed improvement in their depression. In addition, none of the eight patients reported having a panic attack from the time of their fourth ECT treatment until discharge. CONCLUSION: In this report, eight consecutive patients with simultaneous major depression and panic disorder improved with ECT. Further work is required which examines the potential utility of ECT in treating these patients.

MRI abnormalities in adolescent bipolar affective disorder.

There is increasing evidence for structural differences in the brains of patients with affective disorders. Recent magnetic resonance imaging (MRI) studies have reported focal signal hyperintensities in the deep white matter of bipolar patients. These previous reports had focused on adult patients with prior episodes of illness. In this case report, the authors discuss a young adolescent patient during her first episode of mania and the finding of subcortical focal signal hyperintensities on brain MRI. The etiology, pathophysiology, and clinical correlates of these lesions will be reviewed.

Pituitary abnormalities in eating disorders: further evidence from MRI studies.

1. The frequent occurrence of hypothalamo-pituitary dysfunction in patients with eating disorders as well as prior reports that nutritional and endocrine status influence pituitary morphology, led us to hypothesize that pituitary size and shape may be altered in patients with eating disorders. 2. Magnetic resonance imaging (MRI) does not use ionizing radiation and is currently one of the most feasible modalities available to study the pituitary gland in vivo. Using MRI, we have previously reported in a preliminary study that female patients with eating disorders had significantly smaller pituitary glands than controls. In addition MRI excluded any pituitary mass lesions. 3. In this report, we confirm our previous MRI findings and provide further evidence of pituitary abnormalities in an expanded sample of eating disorder patients. Preliminary data on pituitary volume estimates from MRI scans are provided for a subset of patients and controls.