Hippocampal volumes of subjects with a history of major depressive episodes but currently in remission and with no known medical comorbidity were compared to matched normal controls by using volumetric magnetic resonance images. Subjects with a history of major depression had significantly smaller left and right hippocampal volumes with no differences in total cerebral volumes. The degree of hippocampal volume reduction correlated with total duration of major depression. In addition, large (diameter 2 4.5 mm)-hippocampal low signal foci (LSF) were found within the hippocampus, and their number also correlated with the total number of days depressed. These results suggest that depression is associated with hippocampal atrophy, perhaps due to a progressive process mediated by glucocorticoid neurotoxicity. (14,15), decreased the possibility of hypertension and occult cardiovascular disease, and increased the ability to obtain subjects, although at the cost of generalizability. Each depressed subject was matched using a case-control design for age and educational level, and the groups were matched overall for height, since this variable is a predictor of overall brain size (16). Potential subjects were screened by questionnaire, medical history, review of medical records, and physical exam to exclude those with medical problems potentially affecting the central nervous system, such as a current or past neurological disorder, head trauma, hypertension, myocardial infarction or ischemia, diabetes, Cushings disease, steroid use, or drug/ alcohol abuse. These exclusionary criteria were consistent with routine Alzheimer's Disease Research Center screening criteria (17). In addition, subjects who had received more than three courses of electroconvulsive therapy (ECT) were excluded. Three subjects included in the study had received ECT previously during the course of their treatment, and the time elapsed since last ECT treatment was 34, 30, and 14 years. All subjects gave informed consent.All subjects were assessed clinically by a psychiatrist (Y.I.S.) experienced in the use of the diagnostic interview for genetic studies (DIGS), a structured interview with high reliability (18). The DIGS was used to make the diagnosis of recurrent major depression by American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria and to exclude other psychiatric diagnoses. Only depressive episodes that met full criteria for major depression were included. Time elapsed (months) since last depressed was determined. One subject with a single episode of major depression was included. In addition, the DIGS was used to score each depressive episode for duration (in days) and number of symptoms, which were identical to those used to make the diagnosis of major depression by DSM-IV criteria. The average number of depressive symptoms over the course of the total depressive episodes was determined. This was determined by averaging the number of symptoms occurring in each depressive ep...

This study takes advantage of continuing advances in the precision of magnetic resonance imaging (MRI) to quantify hippocampal volumes in a series of human subjects with a history of depression compared with controls. We sought to test the hypothesis that both age and duration of past depression would be inversely and independently correlated with hippocampal volume. A sample of 24 women ranging in age from 23 to 86 years with a history of recurrent major depression, but no medical comorbidity, and 24 case-matched controls underwent MRI scanning. Subjects with a history of depression (post-depressed) had smaller hippocampal volumes bilaterally than controls. Post-depressives also had smaller amygdala core nuclei volumes, and these volumes correlated with hippocampal volumes. In addition, post-depressives scored lower in verbal memory, a neuropsychological measure of hippocampal function, suggesting that the volume loss was related to an aspect of cognitive functioning. In contrast, there was no difference in overall brain size or general intellectual performance. Contrary to our initial hypothesis, there was no significant correlation between hippocampal volume and age in either post-depressive or control subjects, whereas there was a significant correlation with total lifetime duration of depression. This suggests that repeated stress during recurrent depressive episodes may result in cumulative hippocampal injury as reflected in volume loss.

Antidepressants may have a neuroprotective effect during depression.

Theories of the pathophysiology of schizophrenia have implicated the hippocampus, but controversy remains regarding hippocampal abnormalities in patients with schizophrenia. In vivo studies of hippocampal anatomy using high resolution magnetic resonance scanning and manual methods for volumetric measurement have yielded inconclusive results, perhaps because of the normal variability in hippocampal volume and the error involved in manual measurement techniques. To resolve this controversy, high dimensional transformations of a computerized brain template were used to compare hippocampal volumes and shape characteristics in 15 matched pairs of schizophrenia and control subjects. The transformations were derived from principles of general pattern matching and were constrained according to the physical properties of f luids. The analysis and comparison of hippocampal shapes based on these transformations were far superior to the comparison of hippocampal volumes or other global indices of hippocampal anatomy in showing a statistically significant difference between the two groups. In the schizophrenia subjects, hippocampal shape deformations were found to be localized to subregions of the structure that send projections to prefrontal cortex. The results of this study demonstrate that abnormalities of hippocampal anatomy occur in schizophrenia and support current hypotheses that schizophrenia involves a disturbance of hippocampalprefrontal connections. These results also show that comparisons of neuroanatomical shapes can be more informative than volume comparisons for identifying individuals with neuropsychiatric diseases, such as schizophrenia.