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B R I T I S H J O U R N A L O F P S YC H I AT RY ( 2 0 0 2 ) , 1 8 1 , 3 4 8 ^ 3 5 3

Correspondence between depression and a reliable index of


hypothalamic–pituitary–adrenal (HPA) axis
activation, late-night salivary cortisol
EDITED BY KHALIDA ISMAIL
(reviewed by Kirschbaum & Hellhammer,
Contents & Cortisol, stress and depression & Non-right-handedness and 1994). In both humans and animals various
schizophrenia & Genetic variation in European suicide rates & Chronic fatigue models of acute and chronic stress (e.g.
physical trauma, public speaking, caregiver
syndrome or neurasthenia? & Explanatory models in psychiatry & Sexual dysfunction
stress in carers of people with Alzheimer’s
and antipsychotics disease) are reliably associated with hyper-
cortisolaemia (Kirschbaum & Hellhammer,
1994). If depression is considered to be an
extreme form of chronic stress, why is there
Cortisol, stress and depression suggesting that cortisol is a trait marker so little consistency between studies
for depression. One inference of these com- examining cortisol in populations with
Strickland et al (2002) are to be con- bined findings is that life events preceding depression (Haskett, 1993)?
gratulated for their Herculean task of depression lead to raised cortisol and low- Strickland et al may have seren-
testing the elegant hypothesis that cortisol ered serotonin, whereas life events not lead- dipitously discovered a crucial, if seemingly
is the biological link between stressful life ing to depression are associated with raised trivial, psycho-biological ‘co-factor’ in
events and the onset of depression. In a cortisol and normal or even enhanced sero- depression that dramatically distinguishes
large community sample they found that tonin function (in what might be described between cases with or without HPA axis
cortisol was not elevated in currently as the ‘depression-resistant’ subgroup). In activation: perceived stress (as measured
depressed or vulnerable subjects, but was order to disentangle these apparently dis- by the Life Events and Difficulties Schedule
increased after recent life events, and hence parate findings it seems that a longitudinal (LEDS), see Strickland et al; al; p. 170,
concluded that ‘the hypothalamic–pituitary– study including a subgroup analysis of Fig. 1c). Equally depressed patients may
adrenal [HPA] axis is sensitive to social people with major depression is inevitable, not be equally ‘stressed’ and this may have
stress but does not mediate vulnerability and I am sure that Strickland’s group will biological as well as clinical consequences.
to depression’
depression’ (italics added). However, it not disappoint us. The increased cardiac (Carney et al, al, 1997)
is possibly premature to bury the ‘HPA- and oncological (Persky et al, al, 1987)
hypothesis’ under this evidence alone. Bhagwagar, Z., Whale, R. & Cowen, P. J. (2002) State
Z.,Whale, morbidity and mortality associated with
The rationale for a community study is that and trait abnormalities in serotonin function in major
depression may particularly apply to the
depression. British Journal of Psychiatry,
Psychiatry, 180,
180, 24^28.
it captures the effects of life events, but this depressed–stressed–hypercortisolaemic sub-
Harris, T. O., Borsanyi, S., Messari, S., et al (2000)
exclusive approach misses the other natura- group. Clearly more research is needed to
Morning cortisol as a risk factor for subsequent major
listic event in depression, namely admission depressive disorder in adult women. British Journal of explore this possibility.
to hospital. Thus, the proportion of pa- Psychiatry,
Psychiatry, 177,
177, 505^510.
tients in the ‘depressed’ group showing se- McAllister-Williams, R. H., Anderson, R. J. & Young, Carney, R. M., Freedland, K. E., Sheline,Y. I., et al
vere illness was less than 10% (9 out of A. H. (2001) Corticosterone selectivity attenuates (1997) Depression and coronary heart disease: a review
94), leaving more than 90% with mild 8-OH-DPAT mediated hypothermia in mice. for cardiologists. Clinical Cardiology,
Cardiology, 20,
20, 196^200.
International Journal of Neuropsychopharmacology,
Neuropsychopharmacology, 4, 1^8.
(51%, n¼48)48) to moderate (41%, n¼37) 37) ill-
ness. Given the well-replicated finding of Strickland, P. L., Deakin, J. F. W., Percival, C., et al Haskett, R. F. (1993) The HPA axis and depressive
(2002) Bio-social origins of depression in the disorders. In Biology of Depressive Disorders, Part A:
elevated cortisol in major depression community. Interactions between social adversity, A Systems Perspective (eds J. J. Mann & D. J. Kupfer),
(Harris et al,
al, 2000) it would be helpful to cortisol and serotonin neurotransmission. British Journal pp. 171^189. New Y York:
ork: Plenum.
provide a subgroup analysis for the severely of Psychiatry,
Psychiatry, 180,
180, 168^173.
depressed sample. Nevertheless, it is parti- Kirschbaum, C. & Hellhammer, D. H. (1994) Salivary
B. Moore Mersey Care NHS Trust, Moss House, cortisol in psychoneuroendocrine research: recent
cularly interesting that there was signifi- developments and applications.
cantly elevated cortisol in a subgroup of Moss Street,Garston, Liverpool L19 2NA,UK.
Psychoneuroendocrinology,
Psychoneuroendocrinology, 19,
19, 313^333.
bruce.moore@merseycare.nhs.uk
E-mail: bruce.moore@
women who had experienced recent life
events, whether or not they were currently Persky,V. W., Kempthorne-Rawson, J. & Shekelle,
B.(1987) Personality and risk of cancer: 20 -year
R. B.(1987)
depressed. It is possible that exposure to life follow-up of the Western Electric Study. Psychosomatic
events is a watershed in the evolution of The study of Strickland et al (2002) Medicine,
Medicine, 49,
49, 435^449.
depression, some people showing enhanced underpins the considerable inconsistency
serotonin activity and avoiding depression, in the literature that addresses the area of Strickland, P. L., Deakin, J. F., Percival, C., et al
(2002) Bio-social origins of depression in the
and others showing reduced serotonin func- peripheral markers in depression. community
community.. Interactions between social adversity,
tion and becoming depressed, as suggested It has been argued that neuroendocrine cortisol and serotonin neurotransmission. British Journal
by animal studies (McAllister-Williams et challenge tests (such as the prolactin of Psychiatry,
Psychiatry, 180,
180, 168^173.
al,
al, 2001). response to dexfenfluramine used by the
Weiss, D. & Coccaro, E. F. (1997) Neuroendocrine
Moreover, the investigation of state authors) is not a valid probe of central
challenge studies of suicidal behavior. Psychiatric Clinics of
and trait abnormalities in major depres- neuronal function (for discussion see Weiss North America,
America, 20,
20, 563^579.
sion by Bhagwagar et al (2002) shows that & Coccaro, 1997) and this may account for
recovery from depression is accompanied the negative findings of the study. More M. R. Garland Beaumont Hospital, Dublin 9,
by a restoration of HPA-axis function, perplexing is the lack of association mgarland@ireland.com
Ireland. E-mail: mgarland@

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