Fatigue in Multiple Sclerosis Is Associated With Childhood Adversities

Fatigue is a common and disabling symptom in patients with Multiple Sclerosis (PwMS). Its pathogenesis, however, is still not fully understood. Potential psychological roots, in particular, have received little attention to date. The present study examined the association of childhood adversities, specific trait characteristics, and MS disease characteristics with fatigue symptoms utilizing path analysis. Five hundred and seventy-one PwMS participated in an online survey. Standardized psychometric tools were applied. The Childhood Trauma Questionnaire (CTQ) served to assess childhood adversities. Trait variables were alexithymia (Toronto Alexithymia Scale; TAS-26) and early maladaptive schemas (Young Schema Questionnaire; YSQ). Current pathology comprised depression (Beck’s Depression Inventory FastScreen; BDI-FS) and anxiety symptoms (State-Trait Anxiety Inventory; STAI-state), as well as physical disability (Patient determined Disease Steps; PDDS). The Fatigue Scale for Motor and Cognitive Functions (FSMC) was the primary outcome variable measuring fatigue. PwMS displayed high levels of fatigue and depression (mean FSMC score: 72; mean BDI-II score: 18). The final path model revealed that CTQ emotional neglect and emotional abuse remained as the only significant childhood adversity variables associated with fatigue. There were differential associations for the trait variables and current pathology: TAS-26, the YSQ domain impaired autonomy and performance, as well as all current pathology measures had direct effects on fatigue symptoms, accounting for 28.2% of the FSMC variance. Bayesian estimation also revealed indirect effects from the two CTQ subscales on FSMC. The final model fitted the data well, also after a cross-validation check and after replacing the FSMC with the Chalder Fatigue Questionnaire (CFQ). This study suggests an association psychological factors on fatigue in Multiple Sclerosis. Childhood adversities, as well as specific trait characteristics, seem to be associated with current pathology and fatigue symptoms. The article discusses potential implications and limitations.


Supplement 3
Calculation of scale scores

Fatigue Scale for Motor and Cognitive Functions (FSMC)
The FSMC is a 20-item fatigue measure. Ten items measure symptoms of motor and cognitive fatigue, respectively [16]. PwMS had to score their responses on a five-point Likert scale (from "1" = absolutely agree" to "5" = "absolutely disagree"). The global FSMC score is the sum of the 20 item scores [range: 20-100]. The present study did not consider the two sub-scores for motor and cognitive fatigue.

Chalder Fatigue Questionnaire (CFQ)
The CFQ [17] is awell-established measure to assess patients' fatigue severity. It includes 11 items referring to symptom severity in the past month. PwMS had to score their responses on a four-point Likert scale ("0" = "less than usual", to "3" "much more than usual") [18]. The analyses in the present study made use of the CFQ global severity score (CFQ; sum of all items; range: 0-33).

Beck Depression Inventory (BDI-II) and Beck Depression Inventory FastScreen (BDI-II-FS)
The BDI comprises 21 items. For each item, respondents have to select a response option. The symptoms severity varies between the response options and can reach a value from "0" to "3".
Higher values indicate a higher symptom severity. The total score for depression severity is the sum of severity ratings of each depression item (range 0-63). For the inclusion into the path model, we computed the seven-item Beck Depression Inventory FastScreen (BDI-II-FS) and which is the sum of the respective seven items that omit vegetative and somatic symptoms of depression (range: 0-21).

Toronto-Alexithymia-Scale-26 (TAS-26)
The Toronto-Alexithymia-Scale-26 (TAS-26) is a reliable and valid tool for the assessment of alexithymia. The original version of the TAS-26 is a self-report scale and comprises 26 items. Respondents rate each item on a five-point Likert scale ("1" = "not at all true" to "5" = "absolutely true"). The total alexithymia score is the sum of responses to 18 of the 26 items (range: 18-90).

Childhood Trauma Questionnaire (CTQ)
The present study utilized the short-version of the German CTQ [27]. This version contains 28 items. It served to assess the exposure to different types of childhood adversities. Respondents have to score each item on a five-point Likert scale ("1" = "never true"; "5" = "very often true"). Each subscale contains five items. The sum score of the items for each scale ranges from 5 to 25. Additional three items form the denial subscale of the questionnaire (designed to detect socially desirable responses or false-negative trauma reports). The present study did not consider the latter scale.

State-Trait Anxiety Inventory (STAI)
The State-Trait Anxiety Inventory is a widely used measure of anxiety. It contains two subscales with ten items per scale: 1. the State Anxiety Scale evaluates the current state of anxiety, asking how respondents feel currently; 2. the Trait Anxiety Scale evaluates relatively stable aspects of anxiety proneness. PwMS had to score their responses on an 8-point scale ("1" = "almost never" to "8" = "almost always"). The present study aimed to focus on the current symptoms of anxiety rather than on anxiety as a personality trait. Therefore, it utilized the State Anxiety Scale (STAI-State, range: 10 -80). The German version of Grimm [29] asks not for the symptoms of anxiety at the very moment but the current symptoms. Therefore, it matched the current psychopathology in relation to the aforementioned depression and fatigue measures best.