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.

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.

Magnetic-resonance morphometry in patients with major depression.

Magnetic-resonance morphometry performed on 72 patients with major depression compared with 38 control subjects replicated previously reported, statistically significant reductions in the volumes of the caudate (P < 0.03) and putamen (P < 0.05) in depressed patients. Borderline statistical significance was observed for whole-brain (P < 0.07) and frontal volume (P < 0.10) in a subsample of 32 patients matched on age and sex with 32 control subjects, whereas statistical significance was observed for the full sample (P < 0.007 and P < 0.03, respectively). Chronological age was related to volume of the frontal lobes (P < 0.0002), caudate (P < 0.0001), putamen (P < 0.008), thalamus (P < 0.002), cerebellum (P < 0.007), lateral ventricles (P < 0.0001), and ratios of [whole brain]/[whole brain + cerebrospinal fluid (CSF)] (P < 0.0001) and [frontal]/[frontal + CSF] (P < 0.0001). Age of first depressive episode was related to putamen volume after accounting for chronological age (R2= 0.16, P < 0.005), and a correlation of 0.26 (P < 0.04) was observed between caudate volume and global mental status. Results are in accord with previous reports of basal-ganglia abnormalities in depressed patients and support the role of subcortical structures in mediating affective disorder.

Relative accuracy and reproducibility of regional MRI brain volumes for point-counting methods.

Volumetric magnetic resonance imaging (MRI) methods for the measurement of various neuroanatomical regions are of great interest in studies of neuropsychiatric disorders. Both manual and semiautomated methods have been developed. Manual methods include tracing and point counting. Point counting methods are widely used in post-mortem and microscopy studies. Point counting has been well validated for these purposes. In this article, we report in a series of separate studies the accuracy and reproducibility of point-counting methods. Absolute accuracy was evaluated with a spherical phantom. Accuracy and time efficiency were subsequently assessed with an anatomically realistic phantom and various size grids. The point-counting method was also compared to a tracing method. Finally, the reproducibility of the point-counting method for the caudate and putamen was evaluated on four subjects in a test-retest experiment. These studies provide an estimate of the accuracy and time efficiency of point-counting methods. The test-retest reliability was also high for both caudate and putamen. Findings suggest that point counting is a reliable and efficient method for estimating volumes.

An open-label, multicenter observational study for patients with Alzheimer's disease treated with memantine in the clinical practice.

BACKGROUND/AIMS: In this post-marketing observational study, the safety and effectiveness of memantine were evaluated in patients with Alzheimer's disease (AD). METHODS: In a 6-month, observational, open-label study at 202 specialist sites in Greece, the effectiveness of memantine was evaluated using the Mini-Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale at baseline, and after 3 and 6 months. Discontinuation rates and adverse drug reactions (ADRs) were also recorded to evaluate the safety profile of memantine. RESULTS: 2,570 patients participated in the study. Three and 6 months after baseline, MMSE and IADL scores were significantly improved compared to baseline. At the end of the study, 67% of the patients had improved their MMSE score; 7.1% of the patients reported ≥1 ADRs, and treatment was discontinued due to ADR in 0.7%. CONCLUSION: Memantine was well tolerated and had a positive effect on the patient's cognitive and functional ability in real-life clinical practice, in agreement with randomized, controlled trials.

Escitalopram in clinical practice in Greece: treatment response and tolerability in depressed patients.

OBJECTIVE: To evaluate the effectiveness and tolerability of escitalopram (10-20 mg/day) in adult outpatients suffering from major depressive disorder in naturalistic settings. METHODS: An open-label, 3-month, surveillance study was conducted in 434 investigative sites in Greece enrolling 5175 patients. Clinical Global Impression-Severity (CGI-S) scale and patient-rated Sheehan Disability Scale (SDS) were used as efficacy measurements and treatment discontinuation rates due to adverse events was used to assess tolerability. RESULTS: Clinically significant improvement in CGI-S scores was recorded after 3 months. At baseline, patients reported marked or extreme disability for work (38%), social life (41%) and family life (37%), whereas after 3 months of treatment, 80.6%, 79.5% and 83.5% of patients indicated either no or mild disability, respectively. Escitalopram had good tolerability, demonstrated by a very low rate of discontinuations due to adverse events. CONCLUSION: In this large naturalistic study, escitalopram was well tolerated and improved both depressive symptoms and function.

Drug pharmacokinetics and the carbon dioxide breath test.

The interrelationship of the pharmacokinetics of a drug and the expiration of carbon dioxide formed as a metabolite have been studied. The pharmacokinetic characteristics of the drug that affect the usefulness of the carbon dioxide excretion as a measure of liver function were examined by means of computer simulations. The parent drug extraction ratio, fraction demethylated, volume of distribution, and absorption rate of an oral dosage form all contribute to the carbon dioxide breath test result. A drug that would be a useful substrate when the carbon dioxide breath test is used as a probe for changes in liver function should be at least 50% metabolized by demethylation, have a hepatic extraction ratio of 0.2-0.5, and be administered in a form that is rapidly absorbed.

Magnetic resonance imaging of the corpus callosum: predictors of size in normal adults.

Eighty normal adults were studied with MRI to investigate the relationship between regional morphology of the corpus callosum and characteristics such as age, gender, education, and cranial size. The variability coefficient was 20% in total callosal area and from 19% to 40% in regional callosal area. Increasing age and smaller cranial area were both associated with smaller total and regional callosal areas; there were no effects of gender and education. The relative effects of age and cranial size varied across regions and were most prominent for anterior subdivisions. However, age and cranial size together explained less than half the variance in regional callosal size. Further study is needed to identify additional correlates of regional callosal anatomy.

In vivo quantitation of basal ganglia and thalamic degenerative changes in two temporal lobectomy patients with affective disorder.

The authors examined the brain magnetic resonance imaging scans of two epilepsy patients who had temporal lobectomies, one on the right and one on the left, with postoperative symptoms of affective disorders. Degenerative changes of ipsilateral thalamus and putamen after surgery, with coincident affective disorder, were noted. The authors discuss a possible relationship between postlobectomy degeneration and depression.