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Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction

Tom Kindlon

Senior Member
(I'm mainly posting this now for the comment in the second message)

Full text at: http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archgenpsychiatry.2008.508

Arch Gen Psychiatry.2009 Jan;66(1):72-80. doi: 10.1001/archgenpsychiatry.2008.508.
Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction.
Heim C1,Nater UM,Maloney E,Boneva R,Jones JF,Reeves WC.



Childhood trauma appears to be a potent risk factor for chronic fatigue syndrome (CFS).

Evidence from developmental neuroscience suggests that early experience programs the development of regulatory systems that are implicated in the pathophysiology of CFS, including the hypothalamic-pituitary-adrenal axis.

However, the contribution of childhood trauma to neuroendocrine dysfunction in CFS remains obscure.


To replicate findings on the relationship between childhood trauma and risk for CFS and to evaluate the association between childhood trauma and neuroendocrine dysfunction in CFS.

Design, Setting, and


A case-control study of 113 persons with CFS and 124 well control subjects identified from a general population sample of 19 381 adult residents of Georgia.


Self-reported childhood trauma (sexual, physical, and emotional abuse; emotional and physical neglect), psychopathology (depression, anxiety, and posttraumatic stress disorder), and salivary cortisol response to awakening.


Individuals with CFS reported significantly higher levels of childhood trauma and psychopathological symptoms than control subjects.

Exposure to childhood trauma was associated with a 6-fold increased risk of CFS. Sexual abuse, emotional abuse, and emotional neglect were most effective in discriminating CFS cases from controls.

There was a graded relationship between exposure level and CFS risk.

The risk of CFS conveyed by childhood trauma further increased with the presence of posttraumatic stress disorder symptoms.

Only individuals with CFS and with childhood trauma exposure, but not individuals with CFS without exposure, exhibited decreased salivary cortisol concentrations after awakening compared with control subjects.


Our results confirm childhood trauma as an important risk factor of CFS.

In addition, neuroendocrine dysfunction, a hallmark feature of CFS, appears to be associated with childhood trauma.

This possibly reflects a biological correlate of vulnerability due to early developmental insults.

Our findings are critical to inform pathophysiological research and to devise targets for the prevention of CFS.

PMID: 19124690 [PubMed - indexed for MEDLINE]

Tom Kindlon

Senior Member
This is a comment of mine I posted on Co-Cure back in 2009 which I thought I'd post somewhere now:

To me, on the basic design of the study, it looks fine except for one major flaw: the definition of Chronic Fatigue Syndrome used (however I'm happy to be corrected that there are other flaws).

A problem is that for most readers of the study, they won't even be aware that the authors aren't using the Fukuda definition as normally defined but are using the "empirical" defintion (Reeves, 2005) version of the Fukuda definition.

I'm appending the text below (see Appendix 1).

There are no direct references to the Reeves (2005) empiric definition paper so as I say, most people won't know how unusually CFS is defined. All one basically has is the reference to paper 3

3. Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva RS, Morrissey M, Devlin R. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Popul Health Metr. 2007;5:5.

where one would see that the emperic definition was used.

But how many people are going to notice that?


The other point of note is that despite the paper appearing quite a comprehensive review of the area, there is actually no mention of:

Sexual abuse, physical abuse, chronic fatigue, and chronic fatigue syndrome: a community-based study. Taylor RR, Jason LA. J Nerv Ment Dis. 2001 Oct;189(10):709-15. (Appendix 2 of my post contains the abstract)

The authors would be aware of the study as four of them were involved in:

Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study. Heim C, Wagner D, Maloney E, Papanicolaou DA, Solomon L, Jones JF, Unger ER, Reeves WC. Arch Gen Psychiatry. 2006 Nov;63(11):1258-66. PMID: 17088506

which had the following quote:

"The only published community-based study on the relationship between childhood adversity and CFS assessed sexual and physical abuse in one question each and did not find significant associations with CFS.30 However, chronic fatigue cases diagnosed as having a primary psychiatric disorder were treated as a separate group in this study, and rates of abuse were markedly elevated in this group. Unfortunately, these psychiatric disorders were not specified, and it remained unclear whether these disorders corresponded to those defined as exclusionary for CFS in the 1994 research case definition. In a subsequent report based on the same sample,31 childhood abuse was found to predict fatigue and anxiety disorders, including PTSD, which are not exclusionary of CFS. In sum, the association between childhood adversity and the risk for CFS warrants further investigation. The failure to use psychometrically validated dimensional instruments to measure multiple types of childhood trauma has been a particular difficulty in previous studies of CFS.27-30"

To not make readers aware of this study seems strange in the current study which includes 49 references. There aren't exactly many random community studies in the area.

The current paper also gives an idea of the background of Christine Heim before her involvement with the CDC CFS program (she is involved in a lot of their studies now) which the team were probably aware of before the start of the involvement:
"Based on these considerations, we suggest that hypocortisolism as a consequence of childhood trauma might be a preexisting risk factor that is associated with failure of the organism to adapt and compensate in response to challenge and thereby promotes the development of CFS and associated emotional and somatic disorders.11"

11. Heim C, Ehlert U, Hellhammer DH. The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology. 2000;25(1):1-35.

"Dysfunction of the HPA axis characterized by lower-than-normal cortisol secretion is one of the hallmark biological features of CFS.11,12 Of note, similar hypocortisolism has also been observed in animal models of early-life stress16,17 and in adults with childhood adverse experience.18,19"

18. Heim C, Newport DJ, Bonsall R, Miller AH, Nemeroff CB. Altered pituitaryadrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. Am J Psychiatry. 2001;158(4):575-581.

"The salivary cortisol response to awakening has received considerable scientific attention34,35 and has been shown to be sensitive to detect HPA axis dysregulation related to stress and disease, including CFS36-38 and early adverse experience.39,40"

39. Meinlschmidt G, Heim C. Decreased cortisol awakening response after early loss experience. Psychoneuroendocrinology. 2005;30(6):568-576.

I hope all the media coverage this study is getting will encourage others to do something to challenge the use of the Reeves 2005 "empiric" definition for 2005. The literature is going to be even more of a mess if it continues to be used.

Tom Kindlon

Appendix 1.

"Subjects were diagnosed with CFS if they met criteria of the 1994 case definition21 as applied following recommendations of the International Chronic Fatigue Syndrome Study Group regarding measurement of the major illness domains.22 Subjects completed a series of rating scales to assess symptoms of CFS and functioning, including the 36-Item Short Form Health Survey,24 the Multidimensional Fatigue Inventory,25 and theCDC Symptom Inventory.26 Classification as a current CFS case was based on cutoff scores in these rating scales with respect to the 3 dimensions of CFS specified in the case definition, ie, impairment, fatigue, and accompanying symptoms.3 Subjects meeting these criteria at the time of the study were classified as having CFS (n=113). Subjects who met no criteria were classified as well (n=124). By definition, case and control groups differed on all scales (all P<.001) (details in the article by Reeves et al3)."


Appendix 2

This study wasn't referred to:

Sexual abuse, physical abuse, chronic fatigue, and chronic fatigue syndrome: a community-based study.

Taylor RR, Jason LA.

J Nerv Ment Dis. 2001 Oct;189(10):709-15.

Department of Occupational Therapy, University of Illinois at Chicago, 60612, USA.

Using a randomly selected community-based sample, this investigation examined whether histories of childhood sexual, physical, and death threat abuse predicted adulthood outcomes of specific medical and psychiatric conditions involving chronic fatigue. This study also tested prior suggestions that most individuals with chronic fatigue syndrome report a past history of interpersonal abuse. Multinomial logistic regression was used to examine the relationship between abuse history and chronic fatigue group outcomes while controlling for the effects of sociodemographics. Compared with healthy controls, childhood sexual abuse was significantly more likely to be associated with outcomes of idiopathic chronic fatigue, chronic fatigue explained by a psychiatric condition, and chronic fatigue explained by a medical condition. None of the abuse history types were significant predictors of chronic fatigue syndrome. A closer examination of individuals in the chronic fatigue syndrome group revealed that significantly fewer individuals with CFS reported abuse as compared with those who did not. The implications of these findings are discussed.

PMID: 11708672