Artificial intelligence based discovery of the association between depression and chronic fatigue syndrome

Abstract:

BACKGROUND: Both of the modern medicine and the traditional Chinese medicine classify depressive disorder (DD) and chronic fatigue syndrome (CFS) to one type of disease. Unveiling the association between depressive and the fatigue diseases provides a great opportunity to bridge the modern medicine with the traditional Chinese medicine.

METHODS: In this work, 295 general participants were recruited to complete Zung Self-Rating Depression Scales and Chalder Fatigue Scales, and meanwhile, to donate plasma and urine samples for 1H NMR-metabolic profiling. Artificial intelligence methods was used to analysis the underlying association between DD and CFS. Principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to analyze the metabolic profiles with respect to gender and age. Variable importance in projection and t-test were employed in conjunction with the PLS-DA models to identify the metabolite biomarkers. Considering the asymmetry and complexity of the data, convolutional neural networks (CNN) model, an artificial intelligence method, was built to analyze the data characteristics between each groups.

RESULTS: The results showed the gender- and age-related differences for the candidate biomarkers of the DD and the CFS diseases, and indicated the same and different biomarkers of the two diseases. PCA analysis for the data characteristics reflected that DD and CFS was separated completely in plasma metabolite. However, DD and CFS was merged into one group.

LIMITATION: Lack of transcriptomic analysis limits the understanding of the association of the DD and the CFS diseases on gene level.

CONCLUSION: The unmasked candidate biomarkers provide reliable evidence to explore the commonality and differences of the depressive and the fatigue diseases, and thereby, bridge over the traditional Chinese medicine with the modern medicine.

Copyright © 2019 Elsevier B.V. All rights reserved.

Source: Zhang F, Wu C, Jia C, Gao K, Wang J, Zhao H, Wang W, Chen J. Artificial intelligence based discovery of the association between depression and chronic fatigue syndrome. J Affect Disord. 2019 Mar 8;250:380-390. doi: 10.1016/j.jad.2019.03.011. [Epub ahead of print]

Silicone breast implants and depression, fibromyalgia and chronic fatigue syndrome in a rheumatology clinic population

Abstract:

INTRODUCTION: Silicone breast implants (SBI) may induce systemic autoimmune disease as part of autoimmune syndrome induced by adjuvants (ASIA). This syndrome bears similarities to fibromyalgia and chronic fatigue syndrome (CFS). We sought to determine whether there are any associations between SBI and depression, fibromyalgia and CFS in a rheumatology clinic population.

METHODS: The electronic files of rheumatology clinic patients at the Royal Adelaide Hospital between 2000 and 2017 were searched for patients who had received SBI prior to rheumatological diagnosis. Demographics, diagnosis, implant history and whether the patient had depression, fibromyalgia or CFS were recorded. Controls were rheumatology clinic patients, half of whom had systemic sclerosis (SSc) and the other half had systemic lupus erythematosus (SLE). They were matched to cases 3:1 for age (within 2 years) and gender.

RESULTS: Thirty patients had received SBI (mean age 47.9, 100% female). Twelve had a diagnosis of depression, 6 of fibromyalgia and 3 of CFS. Implant rupture was not associated with any of these (p = 1). There was no difference in the incidence of depression (p = 1), fibromyalgia (p = 0.76) or CFS (p = 0.3) between cases and SLE controls. When compared with SSc controls, there were significantly more patients with fibromyalgia and/or CFS in the case group (20.0% of cases vs 2.2% of SSc controls, p = 0.01) but no difference in depression (p = 0.12).

CONCLUSION: Fibromyalgia and CFS are more common in patients with silicone implants than SSc controls but not SLE controls. Prospective study of development of depression, fibromyalgia and CFS in recipients of SBI is required.

Source: Khoo T, Proudman S, Limaye V. Silicone breast implants and depression, fibromyalgia and chronic fatigue syndrome in a rheumatology clinic population. Clin Rheumatol. 2019 Jan 31. doi: 10.1007/s10067-019-04447-y. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30706290

Effects of unsupportive social interactions, stigma, and symptoms on patients with myalgic encephalomyelitis and chronic fatigue syndrome.

Abstract:

Prior research has found a heightened risk of suicide in patients with myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). It is possible that a number of factors including stigma, unsupportive social interactions, and severe symptoms could lead to the development of depression, suicidal ideation, and heightened risk of suicide in this patient population. Prior studies have indicated that patients often report the legitimacy of their illness being questioned by family, friends, and even their physicians.

This study aimed to determine whether stigma experienced, social support, symptomology, and functioning may be associated with depression and endorsement of suicidal ideation (SI) in patients with a self-reported diagnosis of ME or CFS. Findings indicated that participants that endorsed both SI and depression, in contrast to those that did not, experienced more frequent unsupportive social interactions in the form of blame for their illness, minimization of its severity, and social distancing from others.

In addition, 7.1% of patients with ME and CFS endorsed SI but do not meet the criteria for clinical depression These findings highlight the importance of stigma and unsupportive social interactions as risk factors for suicidal thoughts or actions among patients with ME and CFS. Community psychologists have an important role to play in helping educate health care professionals and the public to these types of risk factors for patients marginalized by ME and CFS.

Source: McManimen SL, McClellan D, Stoothoff J, Jason LA. Effects of unsupportive social interactions, stigma, and symptoms on patients with myalgic encephalomyelitis and chronic fatigue syndrome. J Community Psychol. 2018 Nov;46(8):959-971. doi: 10.1002/jcop.21984. Epub 2018 May 4. https://www.ncbi.nlm.nih.gov/pubmed/30311972

SEID diagnostic criteria applied on an adolescent cohort: evaluation of subgroup differences and prognostic utility

Systemic exertion intolerance disease diagnostic criteria applied on an adolescent chronic fatigue syndrome cohort: evaluation of subgroup differences and prognostic utility

Abstract:

OBJECTIVE: Existing case definitions for chronic fatigue syndrome (CFS) all have disputed validity. The present study investigates differences between adolescent patients with CFS who satisfy the systemic exertion intolerance disease (SEID) diagnostic criteria (SEID-positive) and those who do not satisfy the criteria (SEID-negative).

METHODS: 120 adolescent patients with CFS with a mean age of 15.4 years (range 12-18 years) included in the NorCAPITAL project (ClinicalTrials ID: NCT01040429) were post-hoc subgrouped according to the SEID criteria based on a comprehensive questionnaire. The two subgroups were compared across baseline characteristics, as well as a wide range of cardiovascular, inflammatory, infectious, neuroendocrine and cognitive variables. Data from 30-week follow-up were used to investigate prognostic differences between SEID-positive and SEID-negative patients.

RESULTS: A total of 45 patients with CFS were SEID-positive, 69 were SEID-negative and 6 could not be classified. Despite the fact that clinically depressed patients were excluded in the NorCAPITAL project, the SEID-positive group had significantly higher score on symptoms suggesting a mood disorder (Mood and Feelings Questionnaire): 23.2 vs 13.4, difference 9.19 (95% CI 5.78 to 12.6). No other baseline characteristics showed any group differences. When accounting for multiple comparisons, there were no statistically significant differences between the groups regarding cardiovascular, inflammatory, infectious, neuroendocrine and cognitive variables. Steps per day and Chalder Fatigue Questionnaire at week 30 showed no differences between the groups.

CONCLUSION: The findings question the discriminant and prognostic validity of the SEID diagnostic criteria in adolescent CFS, and suggest that the criteria tend to select patients with depressive symptoms.

Source: Asprusten TT, Sulheim D, Fagermoen E, Winger A, Skovlund E, Wyller VB. Systemic exertion intolerance disease diagnostic criteria applied on an adolescent chronic fatigue syndrome cohort: evaluation of subgroup differences and prognostic utility. BMJ Paediatr Open. 2018 Mar 16;2(1):e000233. doi: 10.1136/bmjpo-2017-000233. eCollection 2018.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887832/ (Full article)

Negative Affectivity, Depression, and Resting Heart Rate Variability (HRV) as Possible Moderators of Endogenous Pain Modulation in Functional Somatic Syndromes

Abstract:

Background: Several studies have shown that patients with functional somatic syndromes (FSS) have, on average, deficient endogenous pain modulation (EPM), as well as elevated levels of negative affectivity (NA) and high comorbidity with depression and reduced resting heart rate variability (HRV) compared to healthy controls (HC). The goals of this study were (1) to replicate these findings and (2) to investigate the moderating role of NA, depression, and resting HRV in EPM efficiency within a patient group with fibromyalgia and/or chronic fatigue syndrome (CFS). Resting HRV was quantified as the root mean square of successive differences between inter-beat intervals (RMSSD) in rest, a vagally mediated time domain measure of HRV.

Methods: Seventy-eight patients with fibromyalgia and/or CFS and 33 HC completed a counter-irritation paradigm as a measure of EPM efficiency. Participants rated the painfulness of electrocutaneous stimuli (of individually calibrated intensity) on the ankle before (baseline phase), during (counter-irritation phase) and after (recovery phase) the application of a cold pain stimulus on the forearm. A larger reduction in pain in the counter-irritation phase compared to the baseline phase reflects a more efficient EPM.

Results: In contrast to our expectations, there was no difference between pain ratings in the baseline compared to counter-irritation phase for both patients and HC. Therefore, reliable conclusions on the moderating effect of NA, depression, and RMSSD could not be made. Surprisingly, patients reported more pain in the recovery compared to the counter-irritation and baseline phase, while HC did not. This latter effect was more pronounced in patients with comorbid depression, patients who rated the painfulness of the counter-irritation stimulus as high and patients who rated the painfulness of the electrocutaneous stimuli as low. We did not manage to successfully replicate the counter-irritation effect in HC or FSS patients. Therefore, no valid conclusions on the association between RMSSD, depression, NA and EPM efficiency can be drawn from this study. Possible reasons for the lack of the counter-irritation effect are discussed.

Source: Van Den Houte M, Van Oudenhove L, Van Diest I, Bogaerts K, Persoons P, De Bie J, Van den Bergh O. Negative Affectivity, Depression, and Resting Heart Rate Variability (HRV) as Possible Moderators of Endogenous Pain Modulation in Functional Somatic Syndromes. Front Psychol. 2018 Mar 6;9:275. doi: 10.3389/fpsyg.2018.00275. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845717/ (Full article)

Rethinking childhood adversity in chronic fatigue syndrome

Abstract:

Background: Previous studies have consistently shown increased rates of childhood adversity in chronic fatigue syndrome (CFS). However, such aetiopathogenic studies of CFS are potentially confounded by co-morbidity and misdiagnosis particularly with depression.

Purpose: We examined the relationship between rates of childhood adversity using two complimentary approaches (1) a sample of CFS patients who had no lifetime history of depression and (2) a modelling approach.

Methods: Childhood trauma questionnaire (CTQ) administered to a sample of 52 participants with chronic fatigue syndrome and 19 controls who did not meet criteria for a psychiatric disorder (confirmed using the Structured Clinical Interview for DSM-IV). Subsequently, Mediation Analysis (Baye’s Rules) was used to establish the risk childhood adversity poses for CFS with and without depression.

Results: In a cohort of CFS patients with depression comprehensively excluded, CTQ scores were markedly lower than in all previous studies and, in contrast to these previous studies, not increased compared with healthy controls. Post-hoc analysis showed that CTQ scores correlated with the number of depressive symptoms during the lifetime worst period of low mood. The probability of developing CFS given a history of childhood trauma is 4%, a two-fold increased risk compared to the general population. However, much of this risk is mediated by the concomitant development of major depression.

Conclusions: The data suggests that previous studies showing a relationship between childhood adversity and CFS may be attributable to the confounding effects of co-morbid or misdiagnosed depressive disorder.

Abbreviations: CFS: Chronic fatigue syndrome; CTQ: Childhood trauma questionnaire; MDD: Major depressive disorder; CA: Childhood adversity; P: Probability.

Source: Clark JE, Davidson SL, Maclachlan L, Newton JL, Watson S. Rethinking childhood adversity in chronic fatigue syndrome. Fatigue. 2017 Oct 10;6(1):20-29. doi: 10.1080/21641846.2018.1384095. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774185/ (Full article)

Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model

Abstract:

INTRODUCTION: Chronic Fatigue Syndrome (CFS) is a poorly understood illness that is characterized by diverse somatic symptoms, hypothalamic pituitary adrenal (HPA) axis dysfunction and heightened inflammatory indicators. These symptoms are often exacerbated and accompanied by psychological distress states and depression. Since depression is known to be associated with HPA axis dysfunction and greater inflammation, a psychoneuroendocrinological (PNE) model of inflammation was examined in persons diagnosed with CFS in order to uncover underlying biopsychosocial mechanisms in this poorly understood chronic illness.

METHODS: Baseline data were drawn from two randomized controlled trials testing the efficacy of different forms of psychosocial intervention, and included psychological questionnaires, di-urnal salivary cortisol, and blood samples. Data were analyzed with structural equation modeling (SEM).

RESULTS: The sample (N=242) was mostly middle-aged (Mage=49.36±10.9, range=20-73years), Caucasian (70.1%), female (84.6%), highly educated (88.6% completed some college, college, or graduate program), and depressed (CES-D M=23.87±12.02, range 2-57). The SEM supporting a psychoneuroendocrinological model of immune dysregulation in CFS fit the data χ2 (12)=17.725, p=0.1243, RMSEA=0.043, CFI=0.935, SRMR=0.036. Depression was directly related to evening salivary cortisol and inflammation, such that higher evening cortisol predicted greater depressive symptoms (β=0.215, p<0.01) and higher pro-inflammatory cytokines (interleukin-2 [IL-2], IL-6, and tumor necrosis factor-alpha [TNF-α] levels (β=0.185, p<0.05), when controlling for covariates.

DISCUSSION: Results highlight the role of depression, cortisol and inflammation in possible biological mechanisms involved in the pathophysiology of CFS. Time-lagged, longitudinal analyses are needed to fully explore these relationships.

Copyright © 2017. Published by Elsevier B.V.

Source: Milrad SF, Hall DL, Jutagir DR, Lattie EG, Czaja SJ, Perdomo DM, Fletcher MA, Klimas N, Antoni MH. Depression, evening salivary cortisol and inflammation in chronic fatigue syndrome: A psychoneuroendocrinological structural regression model. Int J Psychophysiol. 2017 Sep 13. pii: S0167-8760(17)30162-9. doi: 10.1016/j.ijpsycho.2017.09.009. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28918107

Cognitive and behavioral coping in people with Chronic fatigue syndrome: An exploratory study searching for intervention targets for depressive symptoms

Abstract:

The aim of the study was to find relevant coping factors for the development of psychological interventions for people with chronic fatigue syndrome who suffer from depressive symptoms. A total of 30 adults with chronic fatigue syndrome filled in the Cognitive Emotion Regulation Questionnaire, the COPE and the Hospital Anxiety and Depression Scale. The findings suggested that cognitive coping strategies have a stronger influence than behavioral coping strategies on depressive symptoms. Especially, the cognitive coping strategies refocusing positive, positive reappraisal and catastrophizing were of importance. These findings suggest that these coping strategies should be part of psychological programs for people with chronic fatigue syndrome.

Source: Kraaij V, Bik J, Garnefski N. Cognitive and behavioral coping in people with Chronic fatigue syndrome: An exploratory study searching for intervention targets for depressive symptoms. J Health Psychol. 2017 May 1:1359105317707259. doi: 10.1177/1359105317707259. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28810458

‘It’s personal to me’: A qualitative study of depression in young people with CFS/ME

Abstract:

BACKGROUND: Paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has a prevalence of 0.4-2.4% and is defined as ‘generalised disabling fatigue persisting after routine tests and investigations have failed to identify an obvious underlying cause’. One-third of young people with CFS/ME have probable depression. Little is known about why depression develops, the relationship between depression and CFS/ME, or what treatment might be helpful.

METHODS: We conducted nine semi-structured interviews with young people with CFS/ME (aged 13-17 years, 8/9 female) and probable depression, covering perceived causes of depression, the relationship between CFS/ME and depression, and treatment strategies.

RESULTS: Most thought CFS/ME caused depression. Many discussed a cyclical relationship: low mood made CFS/ME worse. A sense of loss was common. CFS/ME restricted activities participants valued and changed systemic structures, causing depression. There was no single helpful treatment approach. Individualised approaches using combinations of cognitive behavioural therapy (CBT), medication, activity management and other strategies were described.

CONCLUSION: This study suggests that depression may be secondary to CFS/ME in young people because of the impact of CFS/ME on quality of life. Clinicians treating young people with CFS/ME need to consider strategies to prevent development of depression, and research is needed into approaches that are effective in treating CFS/ME with co-morbid depression.

© The Author(s) 2016.

 

Source: Taylor AK, Loades M, Brigden AL, Collin SM, Crawley E. ‘It’s personal to me’: A qualitative study of depression in young people with CFS/ME. Clin Child Psychol Psychiatry. 2016 Oct 14. pii: 1359104516672507. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/27742756

 

The Cognitive Behavioral Treatment of Depression and Low Self-Esteem in the Context of Pediatric Chronic Fatigue Syndrome (CFS/ME): A Case Study

Abstract:

PROBLEM: Up to one in three young people with chronic fatigue syndrome (CFS/ME) also has depressive symptoms. It is not known how best to treat young people with this comorbidity.

METHOD: This case report seeks to describe and discuss the use of a cognitive behavioral approach for depression and low self-esteem in a 16-year-old girl with CFS/ME.

FINDINGS/CONCLUSION: Therapy was effective in remediating the young person’s mood difficulties, but appeared to exacerbate their CFS/ME symptoms. Therefore, it is crucial that CFS/ME and mood treatments are designed and trialed to ensure a complementary approach. Good communication and joint working between involved professionals is also important, and ideally, treatments for mood and for CFS/ME would be provided by the same team to facilitate this.

© 2015 Wiley Periodicals, Inc.

 

Source: Loades M. The Cognitive Behavioral Treatment of Depression and Low Self-Esteem in the Context of Pediatric Chronic Fatigue Syndrome (CFS/ME): A Case Study. J Child Adolesc Psychiatr Nurs. 2015 Nov;28(4):165-74. doi: 10.1111/jcap.12125. Epub 2015 Oct 16. https://www.ncbi.nlm.nih.gov/pubmed/26470755