The purpose of this study is to identify daily activity patterns, negative life events and autonomic abnormalities that may be related to non-improvement in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). For both naturalistic studies and behavioral intervention trials, roughly 50% of patients report worsening or unchanged illness. The proposed four year study would be the first to look at the relation between illness non-improvement, patient activities at home and autonomic function. Our long-range goal is to identify physiological signals and activity patterns that predict non-improvement and relapse and develop a self-management program that prescribes improvement-linked behaviors and discourages non-improvement activities.

Given the enduring debilitation and poor quality of life in ME/CFS, this study proposes to identify important activity patterns (e.g., push-crash), negative life events and autonomic dysfunction that may be associated with non-improvement. This will be accomplished with weekly online diaries, objective measures (actigraphy, heart rate monitors) and semi-structured phone interviews. Non-improvement is a rarely studied, but commonly reported outcome in this illness. For both naturalistic studies and behavioral intervention trials, roughly 50% of ME/CFS patients report worsening or unchanged illness. Also, the patient's self-management efforts may (paradoxically) produce symptom worsening and contribute to illness non-improvement. Non-improvement may also have biological relevance because activity limitations and sleep disruption in ME/CFS have both been associated with autonomic dysregulation (reduced heart rate variability). This (R01) prospective observational six month study of both daily and weekly in vivo assessments would be the first to look at non-improvement in relation to ongoing patient activities and autonomic function.

Specific Aim 1: To assess the relation between non-improvement and prospectively assessed activity patterns and life events. Hypothesis 1: Non-improvement will be significantly associated with these dimensional variables: (a) illness-exacerbating activity patterns (e.g., "push-crash") reported on home web diaries; (b) daily hassles assessed in web diaries; and (c) negative life events reported in phone interviews.

Specific Aim 2: To assess the relation between improvement and prospectively assessed activity patterns and life events. Hypothesis 2: Improvement will be significantly associated with: (a) illness-moderating activity patterns (e.g., healthy pacing) reported on home web diaries; (b) daily uplifts assessed in web diaries; and (c) positive life events assessed in phone interviews.

Specific Aim 3: To assess the relation between activity patterns and symptoms. Hypothesis 3: (a) the "push-crash" pattern will predict greater actigraphy variability and symptom variability; (b) the "limiting activity" pattern will be associated with very low actigraphy counts and high symptom severity; and (c) a healthier "pacing" pattern will be associated with moderate variability of actigraphy and symptoms.

Our secondary aim hypothesizes that autonomic dysregulation (reduced heart rate variability [HRV]) will be characteristic of both non-improvers and patients with a limiting activity pattern as compared to improvers and those with a healthy pacing pattern. The long-range goal is to develop a new self-management protocol that more clearly identifies non-improvement activities and how they can be changed. An important aspect of this new self-management protocol would be to identify early signals of impending relapse, particularly HRV status, via home-use portable devices that could be utilized by patients and their doctors as a warning to modify non-improvement activities, e.g., excessive activity or exercise, to prevent behavioral collapse into inactivity.

Inclusion Criteria:

Fukuda-based ME/CFS symptoms including:

• six months of unexplained, debilitating fatigue
• 4/8 secondary symptoms impaired memory or concentration unrefreshing sleep sore throats headache muscle pain joint pain tender lymph nodes post-exertional malaise

Exclusion Criteria:

Medical: fatigue clearly attributable to self-report medical conditions.

Psychiatric any psychosis alcohol/ substance abuse within two years prior or after illness onset. depression with melancholic/psychotic features within 5 years of onset .

Two other exclusionary criteria:

• patients not dose-stabilized for at least 3 months on antidepressants ;
• patients at risk of suicide or need of urgent psychiatric treatment.

Patients with a diagnosed chronic fatigue syndrome