Depression Duration But Not Age Predicts Hippocampal Volume Loss in Medically Healthy Women with Recurrent Major Depression

Abstract

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.

Gray Matter Changes in Late Life Depression—a Structural MRI Analysis

“…These results can be interpreted according to the two most prevalent hypotheses, the toxic stress, and the dementia prodrome. According to the toxic-stress hypothesis of depression, high levels of glucocorticoids (McEwen, 1997;Sapolsky, 1993) induce shrinking of the highly sensitive hippocampal gray matter (Sapolsky et al, 1985;Sheline et al, 1999;Steffens et al, 2000;Videbech and Ravnkilde, 2004). According to the prodromal dementia hypothesis of LLD, a subgroup of subjects develops LLD as a very early clinical presentation of dementia (Alexopoulos et al, 1993;O'Brien et al, 2004;Steffens et al, 2000).…”

BDNF in schizophrenia, depression and corresponding animal models

“…Brain imaging studies have reported a small but significant reduction in the volume of hippocampus in patients with depression or post-traumatic stress disorder. [81][82][83] Atrophy and decreased functions of the hippocampus could explain the reduction, observed in depressed patients, in negative feedback control that this brain region exerts on the hypothalamic-pituitary-adrenal axis. 84 Other studies have shown decreased plasma levels of BDNF in patients with major depression 15 and increased BDNF level in hippocampus in postmortem tissue from patients treated with antidepressant drugs.…”

The phenotypes of bipolar disorder: relevance for genetic investigations

“…Two groups found significant reductions in grey matter volume in the subgenual prefrontal cortex in family history-positive subjects, suggesting that studying more homogenous patient groups may result in more consistent findings as further studies emerge. 203,204 Some of the changes may constitute primary biological traits associated with the risk of developing mood disorder, while others may represent sequelae of the illness and its burden 205 or treatment effects. 195 Primary changes that could be used as endophenotypes should be detectable in a proportion of unaffected relatives, but such studies are less common.…”