Hippocampal volume, memory, and cortisol status in major depressive disorder: effects of treatment.
BACKGROUND
Depression has been linked to stress, memory deficits, and hypercortisolemia. However, the relationships between depression, hippocampal structure and function, and cortisol levels are unclear and the effects of antidepressant treatment on the measures are not well studied.


METHODS
Whole hippocampal volume, performance on verbal and visual declarative memory function and cortisol status was evaluated in 38 subjects with major depressive disorder (MDD) and 33 healthy subjects. All measures were repeated in a subgroup (n = 22) of depressed patients after successful selective serotonin reuptake inhibitor (SSRI) treatment.


RESULTS
Hippocampal volume was not significantly different between patients with untreated MMD and healthy subjects, after controlling for whole brain volume, age and gender. However, depressed subjects had significantly greater deficits in delayed memory and percent retention on the verbal portion of the Wechsler Memory Scale-Revised (WMS-R) compared with healthy subjects, without significant differences in visual memory, attention, vigilance, or distractibility. Baseline plasma or urinary free cortisol (UFC) was not related to either hippocampal volume or memory deficits. Successful treatment with antidepressants did not change hippocampal volume but did result in a significant improvement in memory function and a reduction in UFC excretion.


CONCLUSIONS
Medication-free nonelderly depressed outpatients without alcohol dependence or adverse experiences in childhood had normal hippocampal volume. Focal declarative memory deficits in depression supported localized hippocampal dysfunction in depressed patients. Treatment with antidepressants significantly improved memory and depression but did not alter hippocampal volume, suggesting that antidepressants may improve hippocampal function in the absence of detectable structural changes.
Vythilingam
Meena
M
Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, Maryland 20892-2670, USA.
Vermetten
Eric
E
Anderson
George M
GM
Luckenbaugh
David
D
Anderson
Eric R
ER
Snow
Joseph
J
Staib
Lawrence H
LH
Charney
Dennis S
DS
Bremner
J Douglas
JD
D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D016555:Matched-Pair Analysis; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies; D012016:Reference Values; D016896:Treatment Outcome; D014706:Verbal Learning / Q000187:drug effects / Q000502:physiology
D000928:Antidepressive Agents; D006854:Hydrocortisone