Hippocampal volume, spectroscopy, cognition, and mood in patients receiving corticosteroid therapy

Brown, E. Sherwood; Woolston, Dixie J.; Frol, Alan B.; Bobadilla, Leonardo; Khan, David A.; Hanczyc, Margaret; Rush, A. John; Fleckenstein, James L.; Babcock, Evelyn E.; Cullum, C. Munro

doi:10.1016/j.biopsych.2003.09.010

Cited by 240 publications

(172 citation statements)

References 56 publications

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“…Consistent with our results, reduced hippocampal NAA ratios have been described in prescription corticosteroid-treated patients. 79 Importantly, the negative correlation between average diurnal cortisol and glutamate was stronger in bipolar patients as compared to healthy controls despite the fact that average diurnal cortisol was actually dampened in patients on chronic lithium prophylaxis (Table 3). It is an intriguing speculation that patients suffering from bipolar disorder are biologically more sensitive to the adverse effects of stress and glucocorticoids.…”

Section: Discussionmentioning

confidence: 96%

Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol

et al. 2008

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While an excess of glucocorticoids is associated with hippocampal pathology in mood disorders, lithium exerts robust neuroprotective and neurotrophic effects. Here, 21 stably remitted bipolar I patients who had been on chronic lithium maintenance therapy, on average, for more than a decade, and 19 carefully matched healthy controls were studied using 3 T 1 Hmagnetic resonance spectroscopy of left and right hippocampus. Salivary cortisol samples were obtained to assess activity of the hypothalamus-pituitary-adrenal system. Absolute concentrations of N-acetylaspartate (NAA), choline-containing compounds and total creatine were similar in euthymic bipolar patients and healthy controls. Hippocampal glutamate concentrations were significantly increased as an effect of patient status (patients > controls) and laterality (left hippocampus > right hippocampus). Hippocampal glutamate content (Glu) was strongly correlated with NAA. Across groups and within the patient group, diurnal saliva cortisol levels showed a significant inverse relationship with both Glu and NAA. Taken together, these results add to the concept of bipolar disorder as an illness involving disturbed hippocampal structural plasticity under the opposing influences of lithium and glucocorticoids.

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Section: Discussionmentioning

confidence: 96%

Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol

et al. 2008

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“…It is generally accepted that abnormalities of the HPA axis can result in mood disorders, such as those seen in Cushing's syndrome and Addison's disease. [9][10][11] Choice of therapy depends on the responsible clinicians. 12 Clear guidelines on whether to start preventative treatments before administration of corticosteroids do not exist.…”

Section: Louisa Ward Mbchb Joji George Mbbs Mrcpsychmentioning

confidence: 99%

Corticosteroid-induced psychosis in rheumatoid arthritis

Ward¹,

George²

2016

Prog. Neurol. Psychiatry

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“…16,17 Exposure to higher levels of cortisol results in hippocampal damage by inhibiting synaptic transmission, decreasing dendritic branching and causing neuronal injury and death. [18][19][20] These negative effects are proposed as potential physiological mechanisms underlying the documented association of higher cortisol levels with age-related cognitive decline and onset of dementia. [21][22][23][24][25] Stressful life events have long been hypothesized to impair neuroendocrine function, with elevated cortisol levels associated with acute stress, and impaired diurnal rhythms of cortisol associated with chronic stress.…”

Section: Introductionmentioning

confidence: 99%

Serotonin transporter polymorphism, memory and hippocampal volume in the elderly: association and interaction with cortisol

et al. 2007

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The s allele variant of the serotonin transporter gene (5-HTT) has recently been observed to moderate the relationship of stress to depression and anxiety. To date no study has considered interactive effects of 5-HTT genotype, stress and hypothalamic-pituitary-adrenal (HPA) function on cognition in healthy, older adults, which may reflect developmental, functional or neurodegenerative effects of the serotonin transporter polymorphism. We investigated whether 5-HTT genotype interacts with cumulative life stress and HPA-axis measures of waking and diurnal cortisol slope to impact cognition in 154 non-depressed, older adults. Structural images of hippocampal volume were acquired on a subsample of 56 participants. The 5-HTT s allele was associated with both significantly lower delayed recall and higher waking cortisol levels. Presence of the s allele interacted with higher waking cortisol to negatively impact memory. We also observed a significant interaction of higher waking cortisol and the s allele on lower hippocampal volume. Smaller hippocampi and higher cortisol were associated with lower delayed recall only in s allele carriers. No impact or interactions of cumulative life stress with 5-HTT or cortisol were observed. This is the first investigation to identify an association of the 5-HTT s allele with poorer memory function in older adults. The interactive effects of the s allele and waking cortisol levels on reduced hippocampal volume and lower memory suggest that the negative effect of the serotonin polymorphism on memory is mediated by the HPA axis. Further, given the significant association of the s allele with higher waking cortisol in our investigation, future studies may be needed to evaluate the impact of the serotonin transporter polymorphism on any neuropsychiatric or behavioral outcome which is influenced by HPA axis function in older adults.

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Hippocampal volume, spectroscopy, cognition, and mood in patients receiving corticosteroid therapy

Cited by 240 publications

References 56 publications

Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol

Glutamate as a spectroscopic marker of hippocampal structural plasticity is elevated in long-term euthymic bipolar patients on chronic lithium therapy and correlates inversely with diurnal cortisol

Corticosteroid-induced psychosis in rheumatoid arthritis

Serotonin transporter polymorphism, memory and hippocampal volume in the elderly: association and interaction with cortisol

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