Introduction
Chronic fatigue syndrome (CFS) is a debilitating and complex disorder, relatively common in adults and associated with a myriad of symptoms (Kawatani et al. Reference Kawatani, Mizuno, Shiraishi, Takao, Joudoi, Fukuda, Watanabe and Tomoda2011). This condition, also known as myalgic encephalomyelitis (ME), is characterized by persistent severe fatigue, unrelated to exertion and not relieved by rest, that lasts at least 6 months and is associated with muscle/joint pain, significant impairment of short-term memory, poor concentration and disturbed sleep (Reeves et al. Reference Reeves, Lloyd, Vernon, Klimas, Jason, Bleijenberg, Evengard, White, Nisenbaum and Unger2003; Sanders & Korf, Reference Sanders and Korf2008; CDC, 2012a ). Overall, evidence suggests a population prevalence of at least 0.2–0.4% (NICE, 2007). Individuals with a diagnosis of CFS generally experience physical impairments and difficulties in cognitive and psychological functioning (Brooks et al. Reference Brooks, Rimes and Chalder2011), which contribute to considerable personal suffering and a decreased quality of life (Solomon et al. Reference Solomon, Nisenbaum, Reyes, Papanicolaou and Reeves2003). Fibromyalgia (FM) is also a common condition that, like CFS, is concomitant with a myriad of symptoms, including chronic widespread pain, muscular stiffness, debilitating fatigue, cognitive and mood dysfunction, and sleep disturbance (CDC, 2012b ; Low & Schweinhardt, Reference Low and Schweinhardt2012; Sommer et al. Reference Sommer, Häuser, Burgmer, Engelhardt, Gerhold, Petzke, Schmidt-Wilcke, Spath, Tolle, Uceyler, Wang, Winkelmann and Thieme2012). Despite the high incidence of these conditions, a vast proportion of patients presenting with chronic fatigue, pain and cognitive dysfunctions do not show specific organic abnormalities (Kroenke & Mangelsdorff, Reference Kroenke and Mangelsdorff1989; Cho et al. Reference Cho, Skowera, Cleare and Wessely2006; Henningsen et al. Reference Henningsen, Zipfel and Herzog2007). Studies have assessed the involvement of psychological, social and biological factors (Wessely, Reference Wessely1998; Lyall et al. Reference Lyall, Peakman and Wessely2003; Caseras et al. Reference Caseras, Mataix-Cols, Giampietro, Rimes, Brammer, Zelaya, Chalder and Godfrey2006, Reference Caseras, Mataix-Cols, Rimes, Giampietro, Brammer, Zelaya, Chalder and Godfrey2008).
Both CFS and FM are known to be associated with other co-morbid psychiatric disorders (Wolfe, Reference Wolfe1997; Van Houdenhove et al. Reference Van Houdenhove, Egle and Luyten2005). Indeed, the prevalence of both depression and anxiety is high in CFS and FM patients (Wessely & Powell, Reference Wessely and Powell1989; McBeth & Silman, Reference McBeth and Silman2001; Chou, Reference Chou2013), and a recent study in a sample of 640 CFS patients found that 14% of patients had an anxiety disorder, 14% had a depressive disorder and 18% had both depression and anxiety disorders (Cella et al. Reference Cella, White, Sharpe and Chalder2013). A previous study in FM found that 57% of patients reported concurrent depression (Okifuji et al. Reference Okifuji, Turk and Sherman2000) and another study reported that a quarter had a current depressive episode and two-thirds a prior depressive episode (Epstein et al. Reference Epstein, Kay, Clauw, Heaton, Klein, Krupp, Kuck, Leslie, Masur, Wagner, Waid and Zisook1999).
One risk factor suggested as being relevant to the onset of these disorders is the occurrence of childhood stressors. Childhood stressors, especially maltreatment and abuse, are highly prevalent in the general population: for example, a 2009 meta-analysis, examining 65 studies from 22 countries, reported the global prevalence of childhood sexual abuse (CSA) as 19.7% for females and 7.9% for males (Pereda et al. Reference Pereda, Guilera, Forns and Gomez-Benito2009). In addition, a UK survey of 2869 young adults found that maltreatment (both intra- and extra-familial) was experienced by 16% of the sample, with 11% of respondents reporting experiences of more severe forms of sexual abuse (May-Chahal & Cawson, Reference May-Chahal and Cawson2005). Several review studies have shown that individuals who suffer childhood abuse are more likely to be depressed, to experience other types of psychiatric disorders, and to have more physical symptoms (Arnow, Reference Arnow2004; Maniglio, Reference Maniglio2009). In fact there is now a wealth of evidence confirming childhood abuse as a vulnerability factor for adulthood depression (Chen et al. Reference Chen, Murad, Paras, Colbenson, Sattler, Goranson, Elamin, Seime, Shinozaki, Prokop and Zirakzadeh2010; Danese & McEwen, Reference Danese and McEwen2012) and anxiety (Sareen et al. Reference Sareen, Henriksen, Bolton, Afifi, Stein and Asmundson2013), and also for somatoform disorders (Lampe et al. Reference Lampe, Doering, Rumpold, Solder, Krismer, Kantner-Rumplmair, Schubert and Sollner2003). With specific relevance to patients with fatigue syndromes, CFS patients have a high prevalence of stressful life events (Johnson et al. Reference Johnson, DeLuca and Natelson1999), and a history of childhood abuse in FM patients has been associated with more severe physical symptoms and greater functional disability (Walen et al. Reference Walen, Oliver, Groessl, Cronan and Rodriguez2001). Indeed, there is some evidence to suggest that a history of childhood abuse may play an important role in the development and severity of both CFS (Johnson et al. Reference Johnson, Schmaling, Dmochowski and Bernstein2010) and FM (Van Houdenhove et al. Reference Van Houdenhove, Egle and Luyten2005). A review by Häuser et al. (Reference Häuser, Kosseva, Uceyler, Klose and Sommer2011), assessing emotional, physical and sexual abuse during childhood in FM patients, found a significant correlation between all three types of abuse and FM. This association is particularly relevant from a mechanistic point of view because childhood abuse has been shown to induce changes in the function of biological systems, such as the inflammatory system and the hypothalamic–pituitary–adrenal (HPA) axis (Danese & McEwen, Reference Danese and McEwen2012), which have been found to be abnormal in patients with CFS (Fuite et al. Reference Fuite, Vernon and Broderick2008).
The aim of this review was to summarize the existing literature about the association between multiple forms of childhood abuse and CFS or FM. As mentioned, there is one existing review on the association between emotional, physical and sexual abuse during childhood in FM patients (Häuser et al. Reference Häuser, Kosseva, Uceyler, Klose and Sommer2011). However, in this review we have also included two other types of childhood abuse (emotional and physical neglect), and have reviewed studies in both CFS and FM patients. Moreover, we looked at the clinical symptoms associated with the occurrence of childhood abuse in these patients, including depression, anxiety and pain.
Method
We performed a search of the literature using PubMed and considering cohort studies and case-control studies without any exclusion in terms of age and gender. Keywords included: ‘childhood abuse’ or ‘childhood trauma’; ‘chronic fatigue syndrome’ or ‘fibromyalgia’ or ‘myalgic encephalomyelitis’ or ‘chronic pain’. No study characteristics or publication date restrictions were imposed. Papers concerning animal models were excluded. The search was limited to English-language studies. We identified a total of 31 papers, three of which were identified from references.
Results
We identified seven papers regarding CFS, 21 papers regarding FM, and three papers that considered both CFS and FM.
Childhood stressors and CFS
Childhood sexual and physical abuse
Ten studies examined the association between childhood sexual and/or physical abuse, and CFS (Table 1). Among these, four were case-control studies. The first two studies, conducted by Taylor & Jason (Reference Taylor and Jason2001) and Heim et al. (Reference Heim, Wagner, Maloney, Papanicolaou, Solomon, Jones, Unger and Reeves2006), reported a higher incidence of childhood sexual (range 16–28% v. 2–10%) and physical abuse (range 28–29% v. 5–9%) in CFS patients than in controls. More recently, these results were replicated in studies by Heim et al. (Reference Heim, Nater, Maloney, Boneva, Jones and Reeves2009) and Heins et al. (Reference Heins, Knoop, Lobbestael and Bleijenberg2011), where CFS patients were again found to be more likely to report a previous history of childhood sexual (range 10–33% v. 4–11%) and physical abuse (range 6–33% v. 1–10%) when compared with control subjects.
Table 1. Studies examining the association between childhood stressors and chronic fatigue syndrome
CFS, Chronic fatigue syndrome; GHQ-12, 12-item General Health Questionnaire; SF-36, Medical Outcomes Study Short Form 36-item Health Survey; MFI, Multidimensional Fatigue Inventory; CDC, Centers for Disease Control and Prevention; CTQ, Childhood Trauma Questionnaire; CTQ-SF, Childhood Trauma Questionnaire Short Form; CIS, Checklist Individual Strength; SIP, Sickness Impact Profile; tCAS, total childhood adversity score; SPAQ, Sexual and Physical Abuse Questionnaire; ACR, American College of Rheumatology; FM, fibromyalgia; RA, rheumatoid arthritis; MS, multiple sclerosis; ↑, high prevalence of childhood abuse; ↓, low prevalence of childhood abuse.
Some studies investigated CFS-only populations or used non-healthy comparison samples with medical conditions, and reported similarly high rates of childhood sexual and physical abuse. Tietjen et al. (Reference Tietjen, Brandes, Peterlin, Eloff, Dafer, Stein, Drexler, Martin, Hutchinson, Aurora, Recober, Herial, Utley, White and Khuder2010) showed that a large percentage of patients with CSF reported a history of childhood sexual or physical abuse (35% and 26.5% respectively). These results are supported by a study investigating the prevalence of childhood sexual and physical abuse in CFS patients compared with patients with CFS-like illness; Clark et al. (Reference Clark, Goodwin, Stansfeld, Hotopf and White2011) demonstrated that childhood sexual and physical abuse were both associated with the development of CFS. Other studies have also found a high prevalence of a previous history of childhood sexual (17.8%) (Kempke et al. Reference Kempke, Luyten, Claes, Van Wambeke, Bekaert, Goossens and Van Houdenhove2013) and physical abuse (range 15–25%) in CFS patients (Johnson et al. Reference Johnson, Schmaling, Dmochowski and Bernstein2010; Kempke et al. Reference Kempke, Luyten, Claes, Van Wambeke, Bekaert, Goossens and Van Houdenhove2013). Finally, a study investigating a sample of 58 CFS patients found a significant association between a previous history of childhood physical abuse and diagnosis of CFS (Post et al. Reference Post, Altshuler, Leverich, Frye, Suppes, McElroy, Keck, Nolen, Kupka, Grunze and Rowe2013).
To our knowledge only one study has reported conflicting evidence. In a sample of 95 patients suffering from CFS or FM, 52 with reumathoid arthritis (RA) or multiple sclerosis (MS), and 95 healthy controls, Van Houdenhove et al. (Reference Van Houdenhove, Neerinckx, Lysens, Vertommen, Van Houdenhove, Onghena, Westhovens and D'Hooghe2001) demonstrated that CFS or FM patients had a lower prevalence of childhood victimization, including childhood sexual, physical and emotional abuse, and physical and emotional neglect, when compared with RA/MS patients and healthy controls; however, the results were not significant (14% v. 17% v. 20%).
Childhood emotional abuse
Among the above-mentioned papers, six assessed the association between childhood emotional abuse and CFS (Table 1). Two case-control studies reported that subjects with CFS had a higher prevalence of childhood emotional abuse when compared with healthy controls (range 13–42% v. 4–20%) (Heim et al. Reference Heim, Wagner, Maloney, Papanicolaou, Solomon, Jones, Unger and Reeves2006, Reference Heim, Nater, Maloney, Boneva, Jones and Reeves2009; Heins et al. Reference Heins, Knoop, Lobbestael and Bleijenberg2011).
Some studies have investigated CFS-only populations, without including a control group. Tietjen et al. (Reference Tietjen, Brandes, Peterlin, Eloff, Dafer, Stein, Drexler, Martin, Hutchinson, Aurora, Recober, Herial, Utley, White and Khuder2010) showed that 53% of CFS patients experienced childhood emotional abuse. Similarly, two descriptive studies demonstrated a high prevalence of previous episodes of childhood emotional abuse in patients with a diagnosis of CFS (range 24–38%) (Johnson et al. Reference Johnson, Schmaling, Dmochowski and Bernstein2010; Kempke et al. Reference Kempke, Luyten, Claes, Van Wambeke, Bekaert, Goossens and Van Houdenhove2013).
Childhood emotional and physical neglect
Six of the above-mentioned papers assessed the association between childhood emotional and/or physical neglect, and CFS (Table 1). Three case-control studies showed that subjects with CFS have significantly higher rates of both childhood emotional (range 24–60% v. 8–28%) and physical neglect (range 13–25% v. 3–7%) when compared with healthy controls (Heim et al. Reference Heim, Wagner, Maloney, Papanicolaou, Solomon, Jones, Unger and Reeves2006, Reference Heim, Nater, Maloney, Boneva, Jones and Reeves2009; Heins et al. Reference Heins, Knoop, Lobbestael and Bleijenberg2011).
Other studies have also investigated this association. Tietjen et al. (Reference Tietjen, Brandes, Peterlin, Eloff, Dafer, Stein, Drexler, Martin, Hutchinson, Aurora, Recober, Herial, Utley, White and Khuder2010) demonstrated that a large proportion of patients with CSF reported a history of childhood emotional (45.6%) and physical neglect (32%). Two more studies reported a high prevalence of childhood emotional (range 31–37%) (Johnson et al. Reference Johnson, Schmaling, Dmochowski and Bernstein2010; Kempke et al. Reference Kempke, Luyten, Claes, Van Wambeke, Bekaert, Goossens and Van Houdenhove2013) and physical neglect (14%) in patients with a diagnosis of CFS (Johnson et al. Reference Johnson, Schmaling, Dmochowski and Bernstein2010).
Childhood stressors and FM
Childhood sexual and physical abuse
Twenty-four studies have examined the association between childhood sexual and/or physical abuse, and FM (Table 2). Among these, six were case-control studies. Three studies reported a higher incidence of childhood sexual (range 7–37% v. 6–22%) and physical abuse (range 8–34% v. 4–12%) in FM patients than in controls (Boisset-Pioro et al. Reference Boisset-Pioro, Esdaile and Fitzcharles1995; Ruiz-Perez et al. Reference Ruiz-Perez, Plazaola-Castano, Caliz-Caliz, Rodriguez-Calvo, Garcia-Sanchez, Ferrer-Gonzalez, Guzman-Ubeda, del Rio-Lozano and Lopez-Chicheri2009; Smith et al. Reference Smith, Papp, Tooley, Montague, Robinson and Cosper2010). Anderberg et al. (Reference Anderberg, Marteinsdottir, Theorell and von Knorring2000) also demonstrated that FM patients had a higher prevalence of childhood sexual (7.5% v. 5%) and physical or psychological abuse (27.5% v. 13%) than patients without a history of abuse. In two other case-control studies, FM patients were more likely to report a previous history of childhood sexual (10.5% v. 0) (Imbierowicz & Egle, Reference Imbierowicz and Egle2003) and physical abuse (42% v. 34%) (Ciccone et al. Reference Ciccone, Elliott, Chandler, Nayak and Raphael2005) when compared with controls.
Table 2. Studies examining the association between childhood stressors and fibromyalgia
FM, Fibromyalgia; ACR, American College of Rheumatology; CECA.Q, Childhood Experience of Care and Abuse Questionnaire; NPSC, National Population Survey of Canada; RA, rheumatoid arthritis; MPI, McGill Pain Questionnaire; CHQ, Childhood History Questionnaire; PDI, Pain Disability Index; CTQ, Childhood Trauma Questionnaire; SBI-P, Structural Biographical Interview for Pain Disorders; ACE, Adverse Childhood Experiences Questionnaire; VAS, Visual Analogue Scale; JPFS, juvenile primary fibromyalgia syndrome; CSI, Children's Somatization Inventory; FIQ-C, Fibromyalgia Impact Questionnaire for Children; YSR, Achenbach Youth Self Report; PSQ, Pain Symptom Questionnaire; CIDI, Composite International Diagnostic Interview; OA, osteoarthritis; CTQ-SF, Childhood Trauma Questionnaire Short Form; FIQ, Fibromyalgia Impact Questionnaire; tCAS, total childhood adversity score; WHO, World Health Organization; CSA, childhood sexual abuse; CDC, Centers for Disease Control and Prevention; CMI, Child Maltreatment Interview; ↑, high prevalence of childhood abuse; ↓, low prevalence of childhood abuse;=, no difference in prevalence of childhood abuse.
Ten studies have investigated FM-only populations, without including a control group, and reported similarly high rates of childhood sexual and physical abuse. Malleson et al. (Reference Malleson, al-Matar and Petty1992) showed that, in a sample of 81 children with diffuse idiopathic pain, 35 patients fulfilled criteria for FM diagnosis and 7% of patients also had a previous history of CSA. However, the authors did not specify whether patients reporting CSA were also diagnosed with FM. In addition, Goldberg et al. (Reference Goldberg, Pachas and Keith1999) reported that 65% of FM patients had a previous history of CSA and 47% experienced childhood physical abuse. Four more studies reported a high prevalence of childhood sexual (range 11–33%) and physical abuse (range 11–55%) in FM patients (Bell et al. Reference Bell, Lewis, Brooks, Schwartz, Lewis, Caspi, Cunningham and Baldwin2004; Weissbecker et al. Reference Weissbecker, Floyd, Dedert, Salmon and Sephton2006; Pae et al. Reference Pae, Masand, Marks, Krulewicz, Han, Peindl, Mannelli and Patkar2009; Kosseva et al. Reference Kosseva, Schild, Wilhelm-Schwenk, Biewer and Häuser2010). Similarly, in a sample of 88 FM patients, 8% were reported to have a previous history of sexual abuse and 16% experienced severe physical abuse, in childhood or adulthood (Häuser, Reference Häuser2005). Accordingly, in a sample of 26 FM patients, five patients experienced episodes of childhood sexual or physical abuse (McLean et al. Reference McLean, Williams, Stein, Harris, Lyden, Whalen, Park, Liberzon, Sen, Gracely, Baraniuk and Clauw2006). However, the authors did not report the specific percentage for each type of abuse separately. Tietjen et al. (Reference Tietjen, Brandes, Peterlin, Eloff, Dafer, Stein, Drexler, Martin, Hutchinson, Aurora, Recober, Herial, Utley, White and Khuder2010) demonstrated that a large percentage of patients with FM had a history of childhood sexual (39%) and physical abuse (27%). More recently, Loevinger et al. (2012) found that 19 out of 107 FM patients had a high total mean score (of 77.2) on the childhood trauma questionnaire (CTQ; Bernstein & Fink, Reference Bernstein and Fink1998), but the specific results for the childhood sexual and physical abuse subscale were not reported.
These results are supported by three studies investigating the prevalence of CSA in FM patients compared with patients with RA or osteoarthritis (OA). In the first study, Walker et al. (Reference Walker, Keegan, Gardner, Sullivan, Bernstein and Katon1997) found a higher mean score on the childhood sexual (15.0 v. 10.4) and physical abuse (15.3 v. 10.9) subscale of the CTQ in FM patients when compared with RA patients (Walker et al. Reference Walker, Keegan, Gardner, Sullivan, Bernstein and Katon1997). Moreover, FM patients were more likely to report a history of sexual (51% v. 32%) and physical abuse (39% v. 16%) during childhood or adulthood, and also increased duration of sexual abuse when compared to RA patients (Carpenter et al. Reference Carpenter, Hugler, Enzenauer, Des Rosier, Kirk and Brehm1998). More recently, Nicolson et al. (Reference Nicolson, Davis, Kruszewski and Zautra2010) demonstrated that FM patients had a higher mean score on the CSA subscale of the CTQ when compared with OA patients (8.9 v. 6.7). However, when considering any experience of childhood physical abuse, Nicolson et al. (Reference Nicolson, Davis, Kruszewski and Zautra2010) found was no difference between the two groups (3.9 v. 3.9).
Several studies have investigated female-only populations and found similar results. Finestone et al. (Reference Finestone, Stenn, Davies, Stalker, Fry and Koumanis2000) showed that women who had experienced CSA had a greater risk of FM diagnoses than non-abused control patients (23% v. 8%). In a sample of 62 adolescent female in-patients from a psychiatric unit, CSA was assessed in patients who also met criteria for juvenile primary fibromyalgia syndrome (JPFS; Lommel et al. Reference Lommel, Kapoor, Bamford, Melguizo, Martin and Crofford2009). The authors found a higher prevalence of CSA in JPFS patients than in patients without JPFS (416% v. 286%). Sigurdardottir & Halldorsdottir (Reference Sigurdardottir and Halldorsdottir2013) investigated a sample of seven women who had experienced CSA and reported that five out of seven women also had FM. Finally, a study investigating a sample of 29 FM patients did not find any association between a previous history of childhood physical or sexual abuse and diagnosis of FM (Post et al. Reference Post, Altshuler, Leverich, Frye, Suppes, McElroy, Keck, Nolen, Kupka, Grunze and Rowe2013). However, the study did report a significant relationship between the total childhood adversity score (tCAS), including childhood sexual and physical abuse, and the overall number of co-morbidities, including irritable bowel syndrome and diabetes.
To our knowledge only one study has reported conflicting evidence. The case-control study of Ciccone et al. (2005) provided no evidence for a significant increase in CSA in the FM group when compared with controls (26.9% v. 30.2%).
Childhood emotional abuse
Among the papers discussed, eight assessed the relationship between childhood emotional abuse and FM (Table 2). Three studies assessed a previous history of emotional abuse using the CTQ. Specifically, Walker et al. (Reference Walker, Keegan, Gardner, Sullivan, Bernstein and Katon1997) report a higher mean CTQ score on the childhood emotional abuse subscale in FM patients when compared with RA patients (15.3 v. 11) (Walker et al. Reference Walker, Keegan, Gardner, Sullivan, Bernstein and Katon1997). A later study by Nicolson et al. (Reference Nicolson, Davis, Kruszewski and Zautra2010) demonstrated that FM patients had a higher mean score when compared with OA patients (11.4 v. 9.0). More recently, the descriptive study by Loevinger et al. (2012) found that 19 out of 107 FM patients had a considerably high total mean score on the CTQ (77.2); however, the authors did not report the specific result for the childhood emotional abuse subscale.
In line with previous reports, other studies have investigated this association and found similar outcomes. Smith et al. (Reference Smith, Papp, Tooley, Montague, Robinson and Cosper2010) showed that FM patients had a higher prevalence of childhood emotional abuse (58.5% v. 18%) when compared with controls, and Kosseva et al. (Reference Kosseva, Schild, Wilhelm-Schwenk, Biewer and Häuser2010) found that 16% of FM patients reported experiencing severe childhood emotional abuse. Lastly, Tietjen et al. (Reference Tietjen, Brandes, Peterlin, Eloff, Dafer, Stein, Drexler, Martin, Hutchinson, Aurora, Recober, Herial, Utley, White and Khuder2010) demonstrated that a large percentage of patients with FM had a history of childhood emotional abuse (54%).
By contrast, the descriptive study by Weissbecker et al. (Reference Weissbecker, Floyd, Dedert, Salmon and Sephton2006) found a low mean CTQ score for FM patients (10.6) when considering childhood emotional abuse. However, their results were still higher than scores reported for a female normative Health Maintenance Organization (HMO) sample (Bernstein & Fink, Reference Bernstein and Fink1998). Lastly, Ruiz-Perez et al. (Reference Ruiz-Perez, Plazaola-Castano, Caliz-Caliz, Rodriguez-Calvo, Garcia-Sanchez, Ferrer-Gonzalez, Guzman-Ubeda, del Rio-Lozano and Lopez-Chicheri2009) report a similar prevalence of childhood emotional abuse in FM patients when compared with controls without a diagnosis of FM (15.5% v. 17%).
Childhood emotional and physical neglect
Eight papers also assessed the association between childhood emotional and/or physical neglect, and FM (Table 2). Three papers used the CTQ to assess these specific forms of abuse. Walker et al. (Reference Walker, Keegan, Gardner, Sullivan, Bernstein and Katon1997) found a higher mean score on the childhood emotional (49.2 v. 34.3) and physical (5.0 v. 3.7) neglect subscales in FM patients than in RA patients. In addition, Nicolson et al. (Reference Nicolson, Davis, Kruszewski and Zautra2010) found that FM patients had a higher mean CTQ score on the childhood emotional neglect subscale when compared with OA patients (10.7 v. 9.5). However, when looking at the childhood physical neglect subscale, the authors did not find any difference between the two groups (7.1 v. 7.1) (Nicolson et al. Reference Nicolson, Davis, Kruszewski and Zautra2010). Lastly, as mentioned, Loevinger et al. (2012) found that 19 out of 107 FM patients had a considerably high total mean CTQ score but they did not report the specific score on the childhood emotional and physical neglect subscales.
Four other studies were able to replicate these results. Anderberg et al. (Reference Anderberg, Marteinsdottir, Theorell and von Knorring2000) demonstrated that FM patients had a higher prevalence of childhood neglect when compared with controls (17.5% v. 8%), but the authors did not specifically assessed physical and emotional neglect. Tietjen et al. (Reference Tietjen, Brandes, Peterlin, Eloff, Dafer, Stein, Drexler, Martin, Hutchinson, Aurora, Recober, Herial, Utley, White and Khuder2010) found that a large percentage of patients with FM had a history of childhood emotional (47%) and physical neglect (32%). Similarly, Bell et al. (Reference Bell, Lewis, Brooks, Schwartz, Lewis, Caspi, Cunningham and Baldwin2004) and Kosseva et al. (Reference Kosseva, Schild, Wilhelm-Schwenk, Biewer and Häuser2010) found a high prevalence of childhood emotional (range 25–46%) and physical neglect (range 8–13%) among FM patients.
By contrast, the descriptive study conducted by Weissbecker et al. (Reference Weissbecker, Floyd, Dedert, Salmon and Sephton2006) found unclear evidence, as mentioned earlier, reporting a low mean CTQ score for FM patients when considering childhood emotional (12.6) and physical neglect (10) subscales. However, as for the emotional abuse, those results were still higher than scores reported for a female normative HMO sample (Bernstein & Fink, Reference Bernstein and Fink1998).
Effects of childhood stressors on symptom profiles
Depressive symptoms
To our knowledge, only one study has examined the association between childhood abuse and depression in CFS patients (Table 3). Heins et al. (Reference Heins, Knoop, Lobbestael and Bleijenberg2011) demonstrated that CFS patients with a history of childhood stressors, including sexual, physical and emotional abuse, and physical and emotional neglect, were more likely to report a lifetime history of depression when compared to patients without a history of abuse (44% v. 25%). Sigurdardottir & Halldorsdottir (Reference Sigurdardottir and Halldorsdottir2013) examined this association in FM patients, and reported that, in a sample of seven women with CSA, five had FM and all had depression.
Table 3. Studies examining the association between childhood stressors and symptom profiles
CFS, Chronic fatigue syndrome; BDI-PC, Beck Depression Inventory for Primary Care; FM, fibromyalgia; CSA, childhood sexual abuse; SCL, Symptom Checklist Questionnaire; RA, rheumatoid arthritis; SF-36, Medical Outcomes Study Short Form 36-item Health Survey.
Anxiety symptoms
The study mentioned above in patients with CFS also examined the interaction between childhood abuse and anxiety (Table 3). Heins et al. (Reference Heins, Knoop, Lobbestael and Bleijenberg2011) reported that CFS patients who had experienced childhood abuse, including sexual, physical and emotional abuse, and physical and emotional neglect were more likely to develop anxiety disorder when compared to controls (21% v. 15%).
Pain symptoms
To our knowledge, no studies have investigated the association between childhood abuse and pain in CFS patients. However, two studies have examined the interaction between childhood abuse and pain in patients with FM (Table 3). In the study by Walker et al. (Reference Walker, Keegan, Gardner, Sullivan, Bernstein and Katon1997), a significant association was found between childhood abuse, including sexual, physical and emotional abuse, and physical and emotional neglect, and pain symptoms, in FM patients when compared to RA patients. In a sample of seven women with a history of CSA, five were diagnosed with FM and all seven suffered chronic and widespread pain (Sigurdardottir & Halldorsdottir, Reference Sigurdardottir and Halldorsdottir2013).
Discussion
This review presents the current literature on the relationship between multiple forms of childhood stressors and the fatigue syndromes, CFS and FM. Our results highlight a strong relationship between experiences of childhood abuse and the occurrence of CFS and FM. However, when looking at a specific type of abuse, such as CSA, and the presence of CFS/FM, only two studies have reported conflicting evidence. The first study by Van Houdenhove et al. (Reference Van Houdenhove, Neerinckx, Lysens, Vertommen, Van Houdenhove, Onghena, Westhovens and D'Hooghe2001) demonstrated that CFS or FM patients had a lower prevalence of childhood victimization, including CSA, when compared with RA/MS patients and healthy controls. This inconsistent result may be attributed mainly to the administration of a specific questionnaire when assessing experiences of CSA, the Questionnaire on Burdening Experiences, which has not been validated according to international standards. Similarly, the second study, by Ciccone et al. (2005), provided no evidence for a significant increase in CSA in the FM group when compared with controls. In this case, one of the major causes of this contrasting finding may be due to the inclusion in both groups (FM patients and controls) of subjects with co-morbid depression, which might partly explain the increased rate of childhood trauma in the controls. Aside from those two studies, overall our findings confirm and extend evidence linking early life experience and CFS/FM, also providing evidence for an association between childhood abuse and other co-morbid symptoms, such as depression, anxiety and pain, in individuals with CFS and FM.
There may be several underlying mechanisms driving the association between childhood abuse and a higher prevalence of CFS and FM. We focus on two, not mutually exclusive, possible biological mechanisms linking a history of childhood stressors and the increased risk of CFS/FM: increased inflammation and abnormal HPA axis activity (Fig. 1); however, it is important to stress that the biological substrates of CFS and FM are still unclear. Moreover, we cannot exclude the possibility that psychological changes associated with a history of childhood stressors play a role in this increased risk of CFS/FM, including low self-esteem, greater social introversion, lower general activity levels and unhelpful perceptions and coping skills (Masuda et al. Reference Masuda, Nozoe, Matsuyama and Tanaka1994; Chartier et al. Reference Chartier, Walker and Naimark2009).
Fig. 1. Biological mechanisms involved in the interaction between childhood stressors and the development of fatigue syndromes. HPA, hypothalamic–pituitary–adrenal.
The first such mechanism is inflammation, whereby childhood stressors lead to increased inflammation and the subsequent development of CFS (Maes & Twisk, Reference Maes and Twisk2010). There is an increasing body of evidence supporting the activation of the immune system and of abnormal inflammatory processes in individuals with a history of childhood stressors. Specifically, we have demonstrated that adults with a history of childhood abuse and social isolation have elevated inflammation levels in adulthood, as shown by the levels of the inflammatory marker, C-reactive protein (CRP) (Danese et al. Reference Danese, Pariante, Caspi, Taylor and Poulton2007, Reference Danese, Moffitt, Harrington, Milne, Polanczyk, Pariante, Poulton and Caspi2009; Hepgul et al. Reference Hepgul, Pariante, Dipasquale, DiForti, Taylor, Marques, Morgan, Dazzan, Murray and Mondelli2012). Carpenter et al. (Reference Carpenter, Gawuga, Tyrka, Lee, Anderson and Price2010) examined plasma interleukin (IL)-6 concentrations in healthy subjects without depression or post-traumatic stress disorder (PTSD), during a standard stress challenge, the Trier Social Stress Test (TSST). Their results still showed a significant relationship between a previous history of childhood maltreatment and an increased level of plasma IL-6 concentration, when compared with individuals without such history. More recently, a study by Heath et al. (Reference Heath, Chesney, Gerhart, Goldsmith, Luborsky, Stevens and Hobfoll2013) reported that individuals exposed to a history of sexual or physical abuse are more likely to be diagnosed with PTSD and exhibit high CRP levels than patients without PTSD, suggesting a possible role of PTSD in explaining the association between childhood stressors and immune system activation. The inflammatory response in patients with a previous history of childhood stressors has also been shown to be exaggerated in the presence of stressful conditions during adulthood (Pace et al. Reference Pace, Mletzko, Alagbe, Musselman, Nemeroff, Miller and Heim2006). This evidence is consistent with the notion that inflammatory markers may also play a role in the pathophysiology of CFS and FM (Pariante, Reference Pariante2009). Levels of pro-inflammatory cytokines, such as IL-1, tumour necrosis factor (TNF)-α (Maes et al. Reference Maes, Twisk and Ringel2012) and nuclear factor (NF)-κB (Morris & Maes, Reference Morris and Maes2012), have been shown to be higher in CFS patients than in healthy controls. In addition, Raison et al. (Reference Raison, Lin and Reeves2009) demonstrated that CRP levels are significantly higher in subjects with CFS and insufficient fatigue (ISF, a milder form of chronic fatigue) when compared with healthy control subjects. Furthermore, a dysregulation of cytokines, including IL-1, IL-6 and IL-8, has been shown to be present in FM patients and to be associated with more pain and fatigue symptoms (Wallace, Reference Wallace2006). Therefore, it is plausible that increased inflammation in individuals with a history of CSA may in turn cause fatigue and somatic symptoms such as those seen in CFS patients (Maes & Twisk, Reference Maes and Twisk2010). Indeed, this increase in inflammatory markers as a result of childhood maltreatment has also been associated with the later development of other adult psychiatric conditions, such as depression (Danese et al. Reference Danese, Moffitt, Pariante, Ambler, Poulton and Caspi2008). For example, individuals with a history of adversities during childhood are at greater risk of both inflammatory abnormalities and mood disorders later in life, especially in the context of additional adult stressors (Heim et al. Reference Heim, Newport, Bonsall, Miller and Nemeroff2001). Clearly, the association between childhood abuse, inflammation and adult fatigue may not need to be ‘causal’: fatigue and inflammation may both be only associated with the third, common factor, childhood trauma (Pariante, Reference Pariante2009). To the best of our knowledge, no studies have investigated inflammatory markers in individuals with childhood abuse and a diagnosis of CFS or FM. Hence, future research would need to clarify whether indeed inflammation may, at least in part, mediate the relationship between childhood stressors and the development of these chronic conditions.
The HPA axis may also be involved in the association between childhood abuse and CFS/FM. Of note, most studies have found a reduced basal cortisol output in CFS, whereas FM and depression tend to be associated with an increased cortisol output. For example, patients with CFS have lower activity of the HPA axis (Strickland et al. Reference Strickland, Morriss, Wearden and Deakin1998; Di Giorgio et al. Reference Di Giorgio, Hudson, Jerjes and Cleare2005), including a blunted salivary cortisol response to awakening (Roberts et al. Reference Roberts, Wessely, Chalder, Papadopoulos and Cleare2004), that is associated with poorer response to cognitive behavioural therapy (CBT) (Roberts et al. Reference Roberts, Papadopoulos, Wessely, Chalder and Cleare2009). There are many other factors that may affect HPA axis hypoactivity in CFS patients, such as inactivity, sleep disturbance and medication (Cleare, Reference Cleare2004), but there is no evidence for a unique or uniform dysfunction of the HPA axis in these conditions. By contrast, studies in FM patients have shown higher cortisol levels (Catley et al. Reference Catley, Kaell, Kirschbaum and Stone2000; Crofford et al. Reference Crofford, Young, Engleberg, Korszun, Brucksch, McClure, Brown and Demitrack2004) and exaggerated HPA axis response to stimulation (Griep et al. Reference Griep, Boersma and de Kloet1993; Crofford et al. Reference Crofford, Pillemer, Kalogeras, Cash, Michelson, Kling, Sternberg, Gold, Chrousos and Wilder1994). Of interest, HPA axis hyperactivity is one of the most consistent findings in depression; indeed, it is conceptualized not only as a consequence of depression but also as a biological marker of vulnerability, often brought about by childhood stressors, and predisposing to the development of depression (Pariante & Lightman, Reference Pariante and Lightman2008). Moreover, childhood abuse per se is associated with abnormal HPA axis activity, although both hyper- and hypoactivity have been described. For example, some clinical studies have shown that individuals who have been sexually or physically abused during childhood exhibit hyperactivation of the HPA axis when exposed to a standardized psychosocial stress, the TSST (Heim & Nemeroff, Reference Heim and Nemeroff2002; Heim et al. Reference Heim, Mletzko, Purselle, Musselman and Nemeroff2008a ). By contrast, other studies have shown that adults reporting a previous experience of childhood abuse have a hypoactivation of the HPA axis and a consequent lower production of cortisol (Bremner et al. Reference Bremner, Vythilingam, Anderson, Vermetten, McGlashan, Heninger, Rasmusson, Southwick and Charney2003, Reference Bremner, Vermetten and Kelley2007; Carpenter et al. Reference Carpenter, Carvalho, Tyrka, Wier, Mello, Mello, Anderson, Wilkinson and Price2007). It is possible that early and severe stress may lead to an initial heightened stress response, which reduces over time (Gunnar & Vazquez, Reference Gunnar and Vazquez2001; Susman, Reference Susman2006; Heim et al. Reference Heim, Newport, Mletzko, Miller and Nemeroff2008b ). Of note, the relationship between childhood abuse and HPA axis activity was assessed in two of the papers we reviewed and they showed contrasting evidence, with one study reporting an increased (Weissbecker et al. Reference Weissbecker, Floyd, Dedert, Salmon and Sephton2006) and one a blunted cortisol awakening response (Heim et al. Reference Heim, Nater, Maloney, Boneva, Jones and Reeves2009). Of note, Heim et al. (Reference Heim, Nater, Maloney, Boneva, Jones and Reeves2009) reported that only those individuals with CFS and exposure to childhood trauma exhibit decreased mean cortisol levels after awakening whereas individuals with CFS without childhood trauma experience do not differ from controls. Therefore, further studies are needed to obtain a clearer understanding of the involvement of the HPA axis.
One of the main limitations of our review is that the quality of the findings varied across the studies reviewed. Indeed, many of the studies, being case-control, were empirically weakened by the inability to examine cause and effect in the relationship between childhood abuse and CFS or FM. There was also no uniformity in the diagnostic criteria used for the assessment of childhood abuse and other clinical symptoms. Furthermore, sample sizes were often small and several studies did not include a control or a comparison group.
In conclusion, to our knowledge this is the first review to summarize the existing literature on the relationship between different forms of childhood abuse, and CFS and FM. Despite the limitations of the available literature, we show evidence for the involvement of childhood abuse in the aetiology of both these conditions. In addition, we highlight the link between childhood abuse and the development of other symptoms such as depression, anxiety and pain, in both CFS and FM patients. Demonstrating a causal relationship between childhood abuse and an increased risk for the development of CFS and FM could have significant implications in terms of raising awareness, targeting more vulnerable individuals and identifying biological mechanisms underlying this putative causal relationship. Finally, it is important to note that these biological mechanisms, such as low cortisol, are potentially reversible as has been shown in a previous study of CBT (Roberts et al. Reference Roberts, Papadopoulos, Wessely, Chalder and Cleare2009).
Acknowledgements
This work was supported by a grant (Ref. MR/J002739/1) from the Medical Research Council (UK) to study ‘Persistent Fatigue Induced by Interferon-alpha: A New Immunological Model for Chronic Fatigue Syndrome’. Additional support has been offered by the Commission of European Communities Seventh Framework Programme (Collaborative Project Grant Agreement no. 22963, Mood Inflame), the National Institute for Health Research Mental Health Biomedical Research Centre in Mental Health at South London and Maudsley National Health Service (NHS) Foundation Trust and King's College London, the Psychiatry Research Trust, UK (McGregor 97), and the Institute of Psychiatry at King's College London.
Declaration of Interest
None.
