MK4MDD

Genetic/Epigenetic Locus Search Cross Data Search

Study Report

Reference

Citation	O'Brien, 2004 PubMed
Full Info	O'Brien, J.T., Lloyd, A., McKeith, I., Gholkar, A. and Ferrier, N. (2004) A longitudinal study of hippocampal volume, cortisol levels, and cognition in older depressed subjects. Am J Psychiatry, 161, 2081-2090.

Study

Hypothesis or Background	This study determined whether cognitive impairments and structural brain changes in older depressed subjects, especially in the hippocampus, are related to hypercortisolemia.
Sample Information	Sixty-one depressed subjects over age 60 who met DSM-IV criteria for major depression and 40 healthy comparison subjects
Method Detail	Subjects underwent structural magnetic resonance imaging, neuropsychological testing, apolipoprotein E (APOE) genotyping, and salivary cortisol assessment (over 3 days) with follow-up 6 months later. Hippocampal volume was measured by manual segmentation that was blind to diagnosis. Average area under the curve for salivary cortisol over the 3 days was calculated. Cognitive function was assessed by using a combined memory z score.
Method Keywords	magnetic resonance imaging (MRI)
Result	Depressed subjects showed multiple impairments in attention, working memory, visual memory, verbal memory, new learning, and executive function in relation to comparison subjects. They had hypercortisolemia (53% increase in area under the curve) and a reduction in right hippocampal volume (6% decrease). Hippocampal volume reduction was not associated with increased cortisol levels but was significantly correlated with continuing memory deficits at 6 months. Persisting mild cognitive impairment was seen in 20 (41%) of 49 subjects at 6 months and was associated with reduced hippocampal volume but not severity of depression, cortisol levels, or APOE genotype.
Conclusions	Older depressed subjects have persisting cognitive impairments associated with hippocampal volume reduction, but the results do not support cortisol-mediated hippocampal neurotoxicity as the major etiological mechanism. Neuropathological studies are required to investigate the basis for hippocampal changes, while follow-up will determine whether hippocampal atrophy is a risk factor for cognitive decline.

Relationships reported by O'Brien, 2004

Component A Approved Name (Name in Paper)	Component A Type	Component B Approved Name (Name in Paper)	Component B Type	Statistical Result	Relationship Description	Result Category (Positive/Negative))
MDD	syndrome	Memory (memory deficits)	cognition and behavior		Hippocampal volume reduction was significantly correlated with continuing memory deficits at 6 months.	Positive
MDD	syndrome	Executive functions (executive function)	cognition and behavior		Depressed subjects showed multiple impairments in attention, working memory, visual memory, verbal memory, new learning, and executive function in relation to comparison subjects.	Positive
MDD	syndrome	Attention (attention)	cognition and behavior		Depressed subjects showed multiple impairments in attention, working memory, visual memory, verbal memory, new learning, and executive function in relation to comparison subjects.	Positive
MDD	syndrome	right hippocampus (right hippocampal volume)	brain morphology and function	53% increase; 6% decrease	Depressed subjects had hypercortisolemia (53% increase in area under the curve) and a reduction in right hippocampal volume (6% decrease).	Positive
MDD	syndrome	Hydrocortisone (cortisol)	molecule		Depressed subjects had hypercortisolemia (53% increase in area under the curve) and a reduction in right hippocampal volume (6% decrease).	Positive
MDD	syndrome	Working memory (working memory)	cognition and behavior		Depressed subjects showed multiple impairments in attention, working memory, visual memory, verbal memory, new learning, and executive function in relation to comparison subjects.	Positive
MDD	syndrome	Visual memory (visual memory)	cognition and behavior		Depressed subjects showed multiple impairments in attention, working memory, visual memory, verbal memory, new learning, and executive function in relation to comparison subjects.	Positive
MDD	syndrome	Learning (new learning)	cognition and behavior		Depressed subjects showed multiple impairments in attention, working memory, visual memory, verbal memory, new learning, and executive function in relation to comparison subjects.	Positive