The Good, the Bad, and the Ugly-Chances, Challenges, and Clinical Implications of Avoidance Research in Psychosomatic Medicine.

Avoidance behaviors are shaped by associative learning processes in response to fear of impending threats, particularly physical harm. As part of a defensive repertoire, avoidance is highly adaptive in case of acute danger, serving a potent protective function. However, persistent or excessive fear and maladaptive avoidance are considered key factors in the etiology and pathophysiology of anxiety- and stress-related psychosomatic disorders. In these overlapping conditions, avoidance can increase the risk of mental comorbidities and interfere with the efficacy of cognitive behavioral treatment approaches built on fear extinction. Despite resurging interest in avoidance research also in the context of psychosomatic medicine, especially in conditions associated with pain, disturbed interoception, and disorders of the gut-brain axis, current study designs and their translation into the clinical context face significant challenges limiting both, the investigation of mechanisms involved in avoidance and the development of novel targeted treatment options. We herein selectively review the conceptual framework of learning and memory processes, emphasizing how classical and operant conditioning, fear extinction, and return of fear shape avoidance behaviors. We further discuss pathological avoidance and safety behaviors as hallmark features in psychosomatic diseases, with a focus on anxiety- and stress-related disorders. Aiming to emphasize chances of improved translational knowledge across clinical conditions, we further point out limitations in current experimental avoidance research. Based on these considerations, we propose means to improve existing avoidance paradigms to broaden our understanding of underlying mechanisms, moderators and mediators of avoidance, and to inspire tailored treatments for patients suffering from psychosomatic disorders.

A Rome Working Team Report on Brain-Gut Behavior Therapies for Disorders of Gut-Brain Interaction.

BACKGROUND AND AIMS: This Rome Foundation Working Team Report reflects the consensus of an international interdisciplinary team of experts regarding the use of behavioral interventions, specifically brain-gut behavior therapies (BGBTs), in patients with disorders of gut-brain interaction (DGBIs). METHODS: The committee members reviewed the extant scientific literature and, when possible, addressed gaps in this literature through the lens of their clinical and scientific expertise. The Delphi method was used to create consensus on the goals, structure, and framework before writing the report. The report is broken into 5 parts: 1) definition and evidence for BGBT, 2) the gut-brain axis as the mechanistic basis for BGBT, 3) targets of BGBTs, 4) common and unique therapeutic techniques seen in BGBT, and 5) who and how to refer for BGBT. RESULTS: We chose to not only review for the reader the 5 existing classes of BGBT and their evidence, but to connect DGBI-specific behavioral targets and techniques as they relate directly, or in some cases indirectly, to the gut-brain axis. In doing so, we expect to increase gastrointestinal providers' confidence in identifying and referring appropriate candidates for BGBT and to support clinical decision making for mental health professionals providing BGBT. CONCLUSIONS: Both gastrointestinal medical providers and behavioral health providers have an opportunity to optimize care for DGBIs through a collaborative integrated approach that begins with an effective patient-provider relationship, thoughtful communication about the brain-gut axis and, when appropriate, a well communicated referral to BGBT.

Comprehensive Lifestyle-Modification in Patients with Ulcerative Colitis-A Randomized Controlled Trial.

Patients with ulcerative colitis suffer from impaired health-related quality of life (HrQoL). Comprehensive lifestyle-modification might increase HrQoL and decrease disease activity. Ninety-seven patients in clinical remission with impaired HrQoL were randomly assigned to a 10 week comprehensive lifestyle-modification program (LSM; n = 47; 50.28 ± 11.90 years) or control (n = 50; 45.54 ± 12.49 years) that received a single workshop of intense training in naturopathic self-help strategies. Primary outcome was HrQoL (Inflammatory Bowel Disease Questionnaire; IBDQ) at week 12. Secondary outcomes included IBDQ subscales; generic HrQoL; disease activity and microbiome. Both groups showed improvement in HrQoL from baseline to post-treatment at week 12. The IBDQ sum score showed no significant group difference (p = 0.251). If patients attended more than 50% of the training sessions, a significant group effect (p = 0.034) was evident in favor of LSM. In addition, the SF-36 mental component summary (p = 0.002) was significantly different between the groups in favor of LSM. Disease activity microbiome and adverse events did not differ. Both a single workshop and a 10-week comprehensive lifestyle-modification program can improve HrQoL in patients with ulcerative colitis in remission with no apparent effects on clinical disease activity. A treatment difference was observed when examining a subsample of patients who attended ≥ 50% of sessions.

Stress and the brain-gut axis in functional and chronic-inflammatory gastrointestinal diseases: A transdisciplinary challenge.

The broad role of stress in the brain-gut axis is widely acknowledged, with implications for multiple prevalent health conditions that are characterized by chronic gastrointestinal symptoms. These include the functional gastrointestinal disorders (FGID), such as irritable bowel syndrome and functional dyspepsia, as well as inflammatory bowel diseases (IBD) like ulcerative colitis and Crohn's disease. Although the afferent and efferent pathways linking the gut and the brain are modulated by stress, the fields of neurogastroenterology and psychoneuroendocrinology (PNE)/ psychoneuroimmunology (PNI) remain only loosely connected. We aim to contribute to bringing these fields closer together by drawing attention to a fascinating, evolving research area, targeting an audience with a strong interest in the role of stress in health and disease. To this end, this review introduces the concept of the brain-gut axis and its major pathways, and provides a brief introduction to epidemiological and clinical aspects of FGIDs and IBD. From an interdisciplinary PNE/PNI perspective, we then detail current knowledge regarding the role of chronic and acute stress in the pathophysiology of FGID and IBD. We provide an overview of evidence regarding non-pharmacological treatment approaches that target central or peripheral stress mechanisms, and conclude with future directions, particularly those arising from recent advances in the neurosciences and discoveries surrounding the gut microbiota.

Can a brief psychological expectancy intervention improve postoperative pain? A randomized, controlled trial in patients with breast cancer.

Pain after surgery remains a major health problem, calling for optimized treatment regimens to maximize the efficacy of pharmacological interventions. In this randomized controlled trial, we tested in a routine surgical treatment setting whether postoperative pain can be reduced by a brief preoperative intervention, ie, positive verbal suggestions in combination with sham acupuncture, designed to optimize treatment expectations. We hypothesized that the expectancy intervention as add-on to patient-controlled intravenous analgesia with morphine reduces patient-reported postoperative pain and improves satisfaction with analgesia. Ninety-six women undergoing breast cancer surgery were randomized at 2 stages: Before surgery, anesthesiologists delivered either positive or neutral verbal suggestions regarding the benefits of acupuncture needling on postoperative pain ("information condition"). Patients were then randomized to receive sham acupuncture or no sham acupuncture during postoperative care ("sham acupuncture condition"). Average pain during the 24-hour observation period after surgery as primary and satisfaction with analgesia as secondary outcome was assessed with standardized measures and analyzed with analysis of covariance accounting for morphine dose, surgery-related, and psychological parameters. Postoperative pain ratings were significantly reduced in patients who received positive treatment-related suggestions (F = 4.45, P = 0.038, main effect of information). Moreover, patients who received an intervention aimed at optimized treatment expectations reported significantly greater satisfaction with analgesia (F = 4.89, P = 0.030, interaction effect). Together, our proof-of-concept data support that optimizing treatment expectations through verbal suggestions may offer a promising approach to improve patient-reported outcomes. Future translational and clinical studies are needed to test such psychological strategies in different surgical interventions, patient groups, and pharmacological treatment regimens.

Functional dyspepsia.

Functional dyspepsia is one of the most prevalent functional gastrointestinal disorders. Functional dyspepsia comprises three subtypes with presumed different pathophysiology and aetiology: postprandial distress syndrome (PDS), epigastric pain syndrome (EPS) and a subtype with overlapping PDS and EPS features. Functional dyspepsia symptoms can be caused by disturbed gastric motility (for example, inadequate fundic accommodation or delayed gastric emptying), gastric sensation (for example, sensations associated with hypersensitivity to gas and bloating) or gastric and duodenal inflammation. A genetic predisposition is probable but less evident than in other functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). Psychiatric comorbidity and psychopathological state and trait characteristics could also play a part, although they are not specific to functional dyspepsia and are less pronounced than in IBS. Possible differential diagnoses include Helicobacter pylori infection and peptic ulceration. Pharmacological therapy is mostly based on the subtype of functional dyspepsia, such as prokinetic and fundus-relaxing drugs for PDS and acid-suppressive drugs for EPS, whereas centrally active neuromodulators and herbal drugs play a minor part. Psychotherapy is effective only in a small subset of patients, whereas quality of life can be severely affected in nearly all patients. Future therapies might include novel compounds that attempt to treat the underlying gastric and duodenal inflammation.

Neural underpinnings of nocebo hyperalgesia in visceral pain: A fMRI study in healthy volunteers.

Despite the clinical relevance of nocebo effects, few studies have addressed their underlying neural mechanisms in clinically-relevant pain models. We aimed to address the contribution of nocebo effects and their underlying neural circuitry to central pain amplification in visceral pain, as it may develop over repeated painful experiences due to negative pain-related expectations. Healthy volunteers received verbal suggestions of pain sensitization (nocebo group, N=28) or neutral instructions (control group, N=16). fMRI was used to investigate changes in neural responses during cued pain anticipation and painful rectal distensions delivered in successive fMRI sessions. Pain intensity was rated trial-by-trial, and expected pain intensity, state anxiety and tension were assessed prior to each session. Behavioral analyses demonstrated significantly greater increases in both expected and perceived pain in the nocebo group. The fMRI analysis performed on nocebo-responders only (N=14) revealed that these behavioral changes were associated with increased activation within the secondary somatosensory cortex and amygdala during pain anticipation and within the thalamus, insula and amygdala during painful stimulation when compared to controls. A subsequent psycho-physiological interaction analysis of the pain phase showed increased functional connectivity between the anterior insula, which was set-up as seed region based on group results, and midcingulate cortex as a function of negative expectations. These findings support that negative pain-related expectations can play a crucial role in pain amplification of visceral pain, which is mediated, at least in part, by a neural up-regulation of pain-associated areas and their connectivity. These findings may have implications for the pathophysiology and treatment of chronic abdominal pain.

Effects of a comprehensive lifestyle modification program on quality-of-life in patients with ulcerative colitis: a twelve-month follow-up.

OBJECTIVE: To analyze the effects of a comprehensive lifestyle modification program on health-related quality-of-life, psychological distress, and clinical parameters in patients with ulcerative colitis (UC) 3- and 12 months after completion of the program. MATERIAL AND METHODS: Sixty patients with UC in clinical remission or with low disease activity were randomly assigned to an intervention group or a usual-care control group. Comprehensive lifestyle modification consisted of a structured 60-h training program over a period of 10 weeks which included stress management training, psychoeducational elements, and self-care strategies. Quality-of-life, psychological distress, and clinical disease activity were assessed with standardized questionnaires (Inflammatory Bowel Disease Questionnaire (IBDQ); the MOS Short-Form 36 (SF-36); the Brief Symptom Inventory (BSI), and the Colitis Activity Index (CAI)) at baseline, and 3 months and 12 months after comprehensive lifestyle modification. RESULTS: Three months after comprehensive lifestyle modification, patients in the intervention group showed significantly greater improvement in the SF-36 scale physical function (p=0.0175), and a significantly greater reduction in anxiety scores, measured with the BSI (p=0.0294). Use of relaxation techniques was a significant predictor of improvement in the psychological sum score after 3 months of therapy (p=0.034). Though 80% of patients with an initial IBDQ score <170 in the intervention group showed an improvement of >16 points after 3 months, no significant effects of the intervention were found on the IBDQ scales, or on clinical disease parameters, including CAI scores, self-assessed disease activity, hospitalizations, or medical consultations. CONCLUSIONS: These results are consistent with possible short-term benefits of a comprehensive lifestyle modification program on some aspects of quality-of-life and emotional well-being, but no effects were discernable 12 months after completion of therapy. Comprehensive lifestyle modification had no effect on clinical disease variables. The generalizability of these data is limited because of the inclusion of patients with a relatively low disease activity who were interested in integrative medicine.

Effects of mind-body therapy on quality of life and neuroendocrine and cellular immune functions in patients with ulcerative colitis.

BACKGROUND: The aim of this study was to investigate the effects of mind-body therapy on neuroendocrine and cellular immune measures, health-related quality of life and disease activity in patients with ulcerative colitis (UC) in remission. METHODS: Thirty UC patients in remission or with low disease activity were randomly assigned to an intervention group (n = 15) or a usual-care waiting control group (n = 15). Intervention consisted of a structured 60-hour training program over 10 weeks which included stress management training, moderate exercise, Mediterranean diet, behavioral techniques and self-care strategies. Quality of life, perceived stress and disease activity were assessed with standardized questionnaires (IBDQ, SF-36, PSS, CAI). In addition, the distribution of circulating lymphocytes and lymphocyte subsets as well as the beta-adrenergic modulation of TNF-alpha production in vitro were analyzed. Urine catecholamines and plasma cortisol, prolactin and growth hormone were measured pre- and postinterventionally, and were compared with a healthy control group (n = 10). RESULTS: In response to therapy, patients in the intervention group showed significantly greater improvement in the SF-36 scale Mental Health and the Psychological Health Sum score compared with changes observed in the usual-care waiting control group. Patients in the intervention group showed significantly greater improvement on the IBDQ scale Bowel Symptoms compared with the control group. However, no significant group differences in circulating lymphocyte subsets or endocrine parameters were observed in response to therapy. In addition, no significant effects of intervention on either the basal levels of TNF-alpha or the suppressive action of the beta-adrenergic agonist isoproterenol on TNF-alpha production were observed. CONCLUSION: Mind-body therapy may improve quality of life in patients with UC in remission, while no effects of therapy on clinical or physiological parameters were found, which may at least in part be related to selective patient recruitment.