Don’t Worry, Be Happy: Psychological Interventions in Inﬂammatory Bowel Disease See “Acceptance and commitment therapy reduces psychological stress in patients with inﬂammatory bowel diseases,” by Wynne B, McHugh L, Gao W, et al, on page 935. O ver the past several decades, research into factors that inﬂuence patient outcomes in inﬂammatory bowel disease (IBD) have been steadily expanding beyond immunology to include genetics, microbiome and the envi- ronment, and, more recently, psychological elements. Psy- chosocial aspects, seen not long ago as largely irrelevant, are increasingly recognized as important in shaping the disease course. Along with the physical symptoms of their ulcerative colitis (UC) or Crohn’s disease, anxiety, depression, and stress are integral to the morbidity with which many pa- tients contend. Interventions directed at these modiﬁable factors might yield profound beneﬁt. The study by Wynne et al 1 in this issue of Gastroenterology offers one approach. Depression and anxiety should perhaps be considered extraintestinal manifestations of IBD. Both diagnoses are signiﬁcantly increased in patients with UC and Crohn’s disease, compared with the general population, even when individuals are in remission and they occur even more frequently during ﬂares of the bowel disease. 2,3 Compared with the general population, patients with IBD seem to be twice as likely to experience depressive disorders. 3 The rate of depression and/or anxiety in IBD is estimated at 15%–35% during remission and 80% for anxiety and 60% for depression during IBD relapse. 2 IBD and psychiatric comorbidity are intertwined through complex and poorly understood interactions, each inﬂuencing the other. Active IBD and its complications seem to affect psychiatric comorbidity, which subsequently impacts the disease course. Anxiety, depression, and other psychiatric comorbidities have been identiﬁed as factors which worsen outcomes—being associated with more severe disease, 4 a greater chance of repeated hospitalization, 5 an increased likelihood of being prescribed steroids or biologics, 6 and an increased likelihood of undergoing surgery. 7 IBD ﬂares and IBD-related surgery are in turn risk factors for subsequent anxiety and depression. 6 Furthermore, depression well before the onset of gastrointestinal symptoms has been suggested to be a risk factor for the later development of Crohn’s disease, although not UC, implying that depression may have an etiologic connection with CD. 8 With this background, Wynne et al 1 present the results of a study testing an intervention directed to improve the psychological outcomes of individuals with IBD, particularly targeting a decrease in stress. In a randomized trial, a behavioral/cognitive therapy was evaluated, called Acceptance and Commitment Therapy (ACT) whose “primary aim is to encourage subjects to adopt positive life values and to accept adverse experiences, including thoughts, feelings and sensations that are an inevitable consequence of life.” 1 Patients with IBD and a set level of psychological dysfunction based on a perceived stress score or poor quality of life score were randomized to ACT, in 8 weekly 90-minute group ses- sions in addition to standard care, while the control group received standard care alone. Patients receiving psychiatric services or receiving antidepressants were excluded so that the intervention is applicable to the broader segment of IBD patients without psychiatric diagnoses. Among patients randomized to the ACT program, stress levels were reduced by 39% at 8 weeks (P ¼ .01 vs control) and 45% at 20 weeks (P ¼ .004), the primary end point, compared with the standard care group—with an 8% and 11% decrease, respectively. Decrease in depression scores (in an intention-to-treat analysis) and improvement in overall well-being signiﬁcantly differed between groups (in a per- protocol analysis), although anxiety was not decreased. The study was ﬂawed because a sizeable number of patients who enrolled did not complete the study. After enrolling 122 patients, only 65% were included in the ﬁnal analysis, owing to patient drop out and missing data. The study is consequently not large enough to identify sub- groups or factors associated with a positive response. Sub- sequent studies will need to anticipate this with a larger sample size to determine which individuals beneﬁt most from these interventions. Although the primary end point was positive, a number of secondary end points failed to demonstrate a beneﬁt. In addition, hair cortisol, which was assayed as a measure of decreased stress, also did not change signiﬁcantly with the intervention. Even in stress reduction, the beneﬁt was relatively modest. Still, this study underscores that psychological dysfunction, even outside of a clear psychiatric diagnosis, remains a sig- niﬁcant aspect of the morbidity that accompanies UC and Crohn’s disease. In addition, this trial provides further evidence that a short-term intervention can signiﬁcantly improve psy- chological impairments associated with IBD. Other therapeutic trials of approaches to psychological dysfunction in IBD have demonstrated some beneﬁts including cognitive-behavioral therapy, 9 yoga, 10 a mind–body relaxation response trial, 11 and other mindfulness based techniques. 12 The ACT program is a simple intervention, relatively inexpensive to conduct, and scalable to other centers. This study contributes to this body of literature with added sophistication regarding methodology, even if the ﬁeld still is in its infancy and needs further development. Subsequent studies will need to anticipate a large dropout in these time consuming programs to identify which in- dividuals beneﬁt most from these interventions. EDITORIALS Gastroenterology 2019;156:856–873