Slippery slope on the mountain of speculation
The impression I receive from this paper: NPY is involved in the neurobiological stress system and associated with a range of conditions. Elevated NPY somewhat correlates with "perceived stress, anger, depression, negative thoughts and maladaptive coping" in CFS patients. There is mention of a connection between dysregulation of the immune and neurobiological stress systems, but they do not appear to speculate much about the direction of causation in regard to the psychological symptoms (others will no doubt be doing such speculating though) but they hint that elevated NPY may be due to infection, immune activation and inflammation. I have no idea if hypocortisolism would be more or less of a problem in CCC defined CFS.
However, the lack of clarification on "symptoms" is disappointing because in the Background section text there is talk of "CFS symptoms" and "clinical symptoms", but as others have already pointed out the results focus is on psychological and psychosocial measurements. It is possible that physical symptoms help to explain the reported correlation of NPY with "general health" and "fatigue disruption rating" but these measurements are probably influenced by psychological symptoms as well. They talk about hypocortisolism in CFS, but we don't know if this actually relates to psychological symptoms and the elevated NPY, and they failed to emphasize enough that hypocortisolism is far from being a universal finding in CFS.
It is unclear how useful or helpful a "stress related NPY elevated" subset would be, it seems problematic, especially without knowing the cause of elevated NPY, with significant overlap of NPY levels with healthy controls, and questionable relevance to CFS, as well as the usual issues with measuring or interpreting "stress". Suppose a CFS patient with normal NYP goes through a rough stressful year so their NPY and negative psychological symptoms are elevated, then the rough year is over and things returns to baseline. Are we supposed to believe that such a patient temporarily had a different subset of CFS? Suppose another patient has elevated NPY and is therefore told they fit into the "stress related" subset even if they don't feel stressed, are we supposed to believe they need stress reduction techniques anyway?
People with temporary influenza who are otherwise healthy often appear irritable and more "vulnerable" to psychosocial stresses, probably because they feel terrible and may also have immune-mediated changes to cognitive function etc. CFS is often described as feeling like a permanent influenza, and the prolonged duration of years or even decades as opposed to mere days or weeks would have additional downstream consequences. Using that comparison, I don't have a problem with the possibility that CFS partly involves an immune-related dysregulation of neurobiological stress system which worsens the effects of the psychosocial stresses imposed on patients by the devastating effects that CFS has on their lives.
What I am uncomfortable with is how related research and speculation typically get simplistically generalized to justify hypothetical "mind over body" mechanisms in all CFS patients by default even when the findings are far from universal and the supposed relationship with "stress" is still unclear. Hypocortisolism for example is frequently employed to help explain so-called "effort/stress intolerance" and other symptoms in CFS (eg like Van Houdenhove et al 2009 as cited by this new Fletcher/Klimas paper), but as far as I know such HPA axis abnormalities reported in the CFS literature are usually relatively mild and non-uniform, usually found in a minority of patients, don't usually exist until years into the illness, and are possibly related to reduced activity. Also note that, like elevated NPY, HPA axis disturbances are also found in infectious and auto-immune diseases, they are not restricted to so-called functional illnesses and mental disorders as some people may have you believe.
There are so many unresolved issues relating to CFS criteria, the concept of stress, and so-called psychoneuroimmunological mechanisms, it is an interesting but extremely slippery slope which must be approached with great care.