HPA axis and aging in depression: Systematic review and meta-analysis

Martino Belvederi Murri; Carmine Pariante; Valeria Mondelli; Mattia Masotti; Anna Rita Atti; Zefiro Mellacqua; Marco Antonioli; Lucio Ghio; Marco Menchetti; Stamatula Zanetidou; Marco Innamorati; Mario Amore

doi:10.1016/j.psyneuen.2013.12.004

HPA axis and aging in depression: Systematic review and meta-analysis

Martino Belvederi Murri^*, Carmine Pariante, Valeria Mondelli, Mattia Masotti, Anna Rita Atti, Zefiro Mellacqua, Marco Antonioli, Lucio Ghio, Marco Menchetti, Stamatula Zanetidou, Marco Innamorati, Mario Amore

^*Corresponding author for this work

Research output: Contribution to journal › Literature review › peer-review

283 Citations (Scopus)

Abstract

One of the most consistent findings in the biology of depression is an altered activity of the hypothalamic pituitary adrenal (HPA) axis. However, data concerning this issue have never been examined with a focus on the older population. Here we present a systematic review and meta-analysis, based on studies investigating levels of cortisol, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) in depressed participants older than 60 and compared with healthy controls. We found 20 studies, for a total of 43 comparisons on different indices of HPA axis functioning. Depression had a significant effect (Hedges' g) on basal cortisol levels measured in the morning (0.89), afternoon (0.83) and night (1.39), but a smaller effect on cortisol measured continuously (0.51). The effect of depression was even higher on postdexamethasone cortisol levels (3.22), whereas it was non-significant on morning ACTH and CRH levels. Subgroup analyses indicated that various methodological and clinical factors can influence the study results. Overall, older participants suffering from depression show a high degree of dysregulation of HPA axis activity, with differences compared with younger adults. This might depend on several mechanisms, including physical illnesses, alterations in the CNS and immune-endocrinological alterations. Further studies are needed to clarify the implications of altered HPA axis activity in older patients suffering from depression. Novel pharmacological approaches might be effective in targeting this pathophysiological feature, thus improving the clinical outcomes.

Original language	English
Article number	N/A
Pages (from-to)	46-62
Number of pages	17
Journal	Psychoneuroendocrinology
Volume	41
Issue number	N/A
DOIs	https://doi.org/10.1016/j.psyneuen.2013.12.004
Publication status	Published - Mar 2014

Keywords

Cortisol
ACTH
CRH
Depression
Depressive symptoms
Elderly
Older adults
HPA axis
Dexamethasone
Antidepressant
DEXAMETHASONE-SUPPRESSION TEST
PITUITARY-ADRENAL AXIS
LATE-LIFE DEPRESSION
SALIVARY CORTISOL
MAJOR DEPRESSION
HYPERCORTISOLEMIC DEPRESSION
PSYCHOGERIATRIC POPULATION
GERIATRIC DEPRESSION
ALZHEIMERS-DISEASE
METABOLIC SYNDROME

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10.1016/j.psyneuen.2013.12.004

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title = "HPA axis and aging in depression: Systematic review and meta-analysis",

abstract = "One of the most consistent findings in the biology of depression is an altered activity of the hypothalamic pituitary adrenal (HPA) axis. However, data concerning this issue have never been examined with a focus on the older population. Here we present a systematic review and meta-analysis, based on studies investigating levels of cortisol, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) in depressed participants older than 60 and compared with healthy controls. We found 20 studies, for a total of 43 comparisons on different indices of HPA axis functioning. Depression had a significant effect (Hedges' g) on basal cortisol levels measured in the morning (0.89), afternoon (0.83) and night (1.39), but a smaller effect on cortisol measured continuously (0.51). The effect of depression was even higher on postdexamethasone cortisol levels (3.22), whereas it was non-significant on morning ACTH and CRH levels. Subgroup analyses indicated that various methodological and clinical factors can influence the study results. Overall, older participants suffering from depression show a high degree of dysregulation of HPA axis activity, with differences compared with younger adults. This might depend on several mechanisms, including physical illnesses, alterations in the CNS and immune-endocrinological alterations. Further studies are needed to clarify the implications of altered HPA axis activity in older patients suffering from depression. Novel pharmacological approaches might be effective in targeting this pathophysiological feature, thus improving the clinical outcomes.",

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author = "Murri, {Martino Belvederi} and Carmine Pariante and Valeria Mondelli and Mattia Masotti and Atti, {Anna Rita} and Zefiro Mellacqua and Marco Antonioli and Lucio Ghio and Marco Menchetti and Stamatula Zanetidou and Marco Innamorati and Mario Amore",

year = "2014",

month = mar,

doi = "10.1016/j.psyneuen.2013.12.004",

language = "English",

volume = "41",

pages = "46--62",

journal = "Psychoneuroendocrinology",

issn = "0306-4530",

publisher = "Elsevier",

number = "N/A",

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TY - JOUR

T1 - HPA axis and aging in depression

T2 - Systematic review and meta-analysis

AU - Murri, Martino Belvederi

AU - Pariante, Carmine

AU - Mondelli, Valeria

AU - Masotti, Mattia

AU - Atti, Anna Rita

AU - Mellacqua, Zefiro

AU - Antonioli, Marco

AU - Ghio, Lucio

AU - Menchetti, Marco

AU - Zanetidou, Stamatula

AU - Innamorati, Marco

AU - Amore, Mario

PY - 2014/3

Y1 - 2014/3

N2 - One of the most consistent findings in the biology of depression is an altered activity of the hypothalamic pituitary adrenal (HPA) axis. However, data concerning this issue have never been examined with a focus on the older population. Here we present a systematic review and meta-analysis, based on studies investigating levels of cortisol, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) in depressed participants older than 60 and compared with healthy controls. We found 20 studies, for a total of 43 comparisons on different indices of HPA axis functioning. Depression had a significant effect (Hedges' g) on basal cortisol levels measured in the morning (0.89), afternoon (0.83) and night (1.39), but a smaller effect on cortisol measured continuously (0.51). The effect of depression was even higher on postdexamethasone cortisol levels (3.22), whereas it was non-significant on morning ACTH and CRH levels. Subgroup analyses indicated that various methodological and clinical factors can influence the study results. Overall, older participants suffering from depression show a high degree of dysregulation of HPA axis activity, with differences compared with younger adults. This might depend on several mechanisms, including physical illnesses, alterations in the CNS and immune-endocrinological alterations. Further studies are needed to clarify the implications of altered HPA axis activity in older patients suffering from depression. Novel pharmacological approaches might be effective in targeting this pathophysiological feature, thus improving the clinical outcomes.

AB - One of the most consistent findings in the biology of depression is an altered activity of the hypothalamic pituitary adrenal (HPA) axis. However, data concerning this issue have never been examined with a focus on the older population. Here we present a systematic review and meta-analysis, based on studies investigating levels of cortisol, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) in depressed participants older than 60 and compared with healthy controls. We found 20 studies, for a total of 43 comparisons on different indices of HPA axis functioning. Depression had a significant effect (Hedges' g) on basal cortisol levels measured in the morning (0.89), afternoon (0.83) and night (1.39), but a smaller effect on cortisol measured continuously (0.51). The effect of depression was even higher on postdexamethasone cortisol levels (3.22), whereas it was non-significant on morning ACTH and CRH levels. Subgroup analyses indicated that various methodological and clinical factors can influence the study results. Overall, older participants suffering from depression show a high degree of dysregulation of HPA axis activity, with differences compared with younger adults. This might depend on several mechanisms, including physical illnesses, alterations in the CNS and immune-endocrinological alterations. Further studies are needed to clarify the implications of altered HPA axis activity in older patients suffering from depression. Novel pharmacological approaches might be effective in targeting this pathophysiological feature, thus improving the clinical outcomes.

KW - Cortisol

KW - ACTH

KW - CRH

KW - Depression

KW - Depressive symptoms

KW - Elderly

KW - Older adults

KW - HPA axis

KW - Dexamethasone

KW - Antidepressant

KW - DEXAMETHASONE-SUPPRESSION TEST

KW - PITUITARY-ADRENAL AXIS

KW - LATE-LIFE DEPRESSION

KW - SALIVARY CORTISOL

KW - MAJOR DEPRESSION

KW - HYPERCORTISOLEMIC DEPRESSION

KW - PSYCHOGERIATRIC POPULATION

KW - GERIATRIC DEPRESSION

KW - ALZHEIMERS-DISEASE

KW - METABOLIC SYNDROME

U2 - 10.1016/j.psyneuen.2013.12.004

DO - 10.1016/j.psyneuen.2013.12.004

M3 - Literature review

SN - 0306-4530

VL - 41

SP - 46

EP - 62

JO - Psychoneuroendocrinology

JF - Psychoneuroendocrinology

IS - N/A

M1 - N/A

ER -

HPA axis and aging in depression: Systematic review and meta-analysis

Abstract

Keywords

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