Altered brain structural connectivity in patients with longstanding gut inflammation is correlated with psychological symptoms and disease duration

Turkiewicz, Joanna; Bhatt, Ravi; Wang, Hao; Vora, Priten; Krause, Ben; Sauk, Jenny; Jacobs, Jonathan P.; Bernstein, Çharles N.; Kornelsen, Jennifer; Labus, Jennifer S.; Gupta, Abha R.; Mayer, Emeran A.

doi:10.1016/j.nicl.2021.102613

Cited by 22 publications

(22 citation statements)

References 93 publications

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“…However, this negative result is difficult to interpret given the absence of group differences in chronic stress levels in our UC cohort, indicating essentially normal perceived chronic stress in this sample despite elevated clinical symptoms of anxiety as quantified with the HADS. While sample characteristics of UC were in this respect similar to an earlier study in a different sample of UC that used a comparable recruitment strategy ( 75 ), other studies from our own group ( 76 ) and other groups [e.g., ( 63 )] reported more psychological impairment in patients, including elevated chronic stress levels. The lack of elevated chronic stress in this UC sample obviously limits the interpretation of these results, although owing to our approach to test the interaction this does not per se exclude an impact but rather a disease-specific differential association compared to controls.…”

Section: Discussionsupporting

confidence: 70%

Altered Brain Structure in Chronic Visceral Pain: Specific Differences in Gray Matter Volume and Associations With Visceral Symptoms and Chronic Stress

et al. 2021

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Structural brain alterations in chronic pain conditions remain incompletely understood, especially in chronic visceral pain. Patients with chronic-inflammatory or functional bowel disorders experience recurring abdominal pain in concert with other gastrointestinal symptoms, such as altered bowel habits, which are often exacerbated by stress. Despite growing interest in the gut-brain axis and its underlying neural mechanisms in health and disease, abnormal brain morphology and possible associations with visceral symptom severity and chronic stress remain unclear. We accomplished parallelized whole-brain voxel-based morphometry analyses in two patient cohorts with chronic visceral pain, i.e., ulcerative colitis in remission and irritable bowel syndrome, and healthy individuals. In addition to analyzing changes in gray matter volume (GMV) in each patient cohort vs. age-matched healthy controls using analysis of covariance (ANCOVA), multiple regression analyses were conducted to assess correlations between GMV and symptom severity and chronic stress, respectively. ANCOVA revealed reduced GMV in frontal cortex and anterior insula in ulcerative colitis compared to healthy controls, suggesting alterations in the central autonomic and salience networks, which could however not be confirmed in supplemental analyses which rigorously accounted for group differences in the distribution of sex. In irritable bowel syndrome, more widespread differences from healthy controls were observed, comprising both decreased and increased GMV within the sensorimotor, central executive and default mode networks. Associations between visceral symptoms and GMV within frontal regions were altered in both patient groups, supporting a role of the central executive network across visceral pain conditions. Correlations with chronic stress, on the other hand, were only found for irritable bowel syndrome, encompassing numerous brain regions and networks. Together, these findings complement and expand existing brain imaging evidence in chronic visceral pain, supporting partly distinct alterations in brain morphology in patients with chronic-inflammatory and functional bowel disorders despite considerable overlap in symptoms and comorbidities. First evidence pointing to correlations with chronic stress in irritable bowel syndrome inspires future translational studies to elucidate the mechanisms underlying the interconnections of stress, visceral pain and neural mechanisms of the gut-brain axis.

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Section: Discussionsupporting

confidence: 70%

Altered Brain Structure in Chronic Visceral Pain: Specific Differences in Gray Matter Volume and Associations With Visceral Symptoms and Chronic Stress

et al. 2021

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“…This in turn might result in difficulties in interpersonal relationships and the development of psychological comorbidities, as well as problems in patient–physician interactions and decreased medication adherence ( Agostini et al, 2019 ; Colonnello and Agostini, 2020 ). This hypothesis is further supported by neuroimaging studies of patients with IBD, which found alterations in brain areas (e.g., the midcingulate cortex), that are involved in emotion processing ( Agostini et al, 2011 , 2013a , b , 2017 ; Vogt, 2013 ; Zikou et al, 2014 ; Kragel et al, 2018 ; Hou et al, 2019 ; Colonnello and Agostini, 2020 ; Fan et al, 2020 ; Skrobisz et al, 2020 ; Thomann et al, 2020 ; Turkiewicz et al, 2021 ; Yeung, 2021 ). This is in line with previous studies that reported that IBD patients are characterized by mentalizing deficits compared to healthy controls (HCs).…”

Section: Introductionmentioning

confidence: 72%

“…With regard to the psychological burden of anxiety and depression, the direction of (neuro-)inflammatory processes and disease activity in CD/UC seems to be bidirectional – with patients with anxiety symptoms developing more often disease flares, and patients with disease activity developing more anxiety ( Gracie et al, 2018 ). Additionally, recent neuroimaging studies have shown that patients with (active) IBD have an altered brain structure, which is associated with symptoms of depression and anxiety ( Agostini et al, 2011 , 2013a , b , 2017 ; Vogt, 2013 ; Zikou et al, 2014 ; Kragel et al, 2018 ; Hou et al, 2019 ; Colonnello and Agostini, 2020 ; Fan et al, 2020 ; Skrobisz et al, 2020 ; Thomann et al, 2020 ; Turkiewicz et al, 2021 ; Yeung, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Higher Levels of Psychological Burden and Alterations in Personality Functioning in Crohn’s Disease and Ulcerative Colitis

et al. 2021

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Aims: Is there evidence for increased psychological distress and alterations in personality functioning in patients with Crohn’s disease (CD) and ulcerative colitis (UC) compared to healthy controls (HCs)?Background: In patients with CD and UC, perceived stress is closely associated with changes in disease activity. The stress response is influenced by psychological burden and personality functioning, but only little is known about these factors in inflammatory bowel diseases (IBD).Study: A total of 62 patients with an endoscopic ensured CD/UC without remission (n = 31 per group) and 31 HC were included. Patients with an active CD/UC and HC were individually matched (n = 93, 31 per group) for age, sex, education, and disease activity. Depression and anxiety were assessed to evaluate the effect of psychological burden (Patient Health Questionnaire-9/PHQ-9, Generalized Anxiety Disorder-7/GAD-7). Personality functioning was measured by validated questionnaires for psychodynamic structural characteristics, mentalization, and attachment (Operationalized Psychodynamic Diagnosis-Structure Questionnaire/OPD-SQ, Mentalization Questionnaire/MZQ, and Experiences in Close Relationships scale/ECR-RD 12).Results: Levels of depression and anxiety were higher in CD/UC patients than in HC with large effect sizes. Comparing personality functioning in CD/UC with HC, psychodynamic structural characteristics differed between CD/UC and HC with medium effect sizes, with structural differences occurring primarily in the domain of self-perception and regulation. Only minor differences were found regarding mentalization and attachment. CD and UC differed only with small effect sizes.Conclusion: Our data show that compared to HC, patients with CD/UC are characterized by a higher level of psychological burden and structural alterations in the domain of self.

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“…Among the disorders of gutbrain interaction, altered structural covariance of the striatum has been found in functional dyspepsia patients compared to HCs [25]. Only two studies to date have been published using graph analysis on structural brain MRI data in IBS [17,26]: one using binary graphs of regional gray matter volume comparing IBS to HCs [17], and one using weighted graphs of diffusion weighted imaging to study connectivity comparing patients with ulcerative colitis, IBS and HCs [26].…”

Section: Introductionmentioning

confidence: 99%

Altered Structural Covariance of Insula, Cerebellum and Prefrontal Cortex Is Associated with Somatic Symptom Levels in Irritable Bowel Syndrome (IBS)

et al. 2021

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Somatization, defined as the presence of multiple somatic symptoms, frequently occurs in irritable bowel syndrome (IBS) and may constitute the clinical manifestation of a neurobiological sensitization process. Brain imaging data was acquired with T1 weighted 3 tesla MRI, and gray matter morphometry were analyzed using FreeSurfer. We investigated differences in networks of structural covariance, based on graph analysis, between regional gray matter volumes in IBS-related brain regions between IBS patients with high and low somatization levels, and compared them to healthy controls (HCs). When comparing IBS low somatization (N = 31), IBS high somatization (N = 35), and HCs (N = 31), we found: (1) higher centrality and neighbourhood connectivity of prefrontal cortex subregions in IBS high somatization compared to healthy controls; (2) higher centrality of left cerebellum in IBS low somatization compared to both IBS high somatization and healthy controls; (3) higher centrality of the anterior insula in healthy controls compared to both IBS groups, and in IBS low compared to IBS high somatization. The altered structural covariance of prefrontal cortex and anterior insula in IBS high somatization implicates that prefrontal processes may be more important than insular in the neurobiological sensitization process associated with IBS high somatization.

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Altered brain structural connectivity in patients with longstanding gut inflammation is correlated with psychological symptoms and disease duration

Cited by 22 publications

References 93 publications

Altered Brain Structure in Chronic Visceral Pain: Specific Differences in Gray Matter Volume and Associations With Visceral Symptoms and Chronic Stress

Altered Brain Structure in Chronic Visceral Pain: Specific Differences in Gray Matter Volume and Associations With Visceral Symptoms and Chronic Stress

Higher Levels of Psychological Burden and Alterations in Personality Functioning in Crohn’s Disease and Ulcerative Colitis

Altered Structural Covariance of Insula, Cerebellum and Prefrontal Cortex Is Associated with Somatic Symptom Levels in Irritable Bowel Syndrome (IBS)

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