The Interplay of Biopsychosocial Factors and Quality of Life in Inflammatory Bowel Diseases: A Network Analysis.

GOAL: The aim of this study was to investigate the network of biopsychosocial factors and quality of life (QoL) in persons with inflammatory bowel diseases (IBDs) and explore the influence of psychological factors on the course of the disease. BACKGROUND: QoL of persons with IBD depends on disease activity but also on numerous interacting psychosocial factors. The influence of psychosocial factors on the disease course in controversially discussed. MATERIALS AND METHODS: In 2 independent IBD samples (sample 1: n=209, anonymous internet survey; sample 2: n=84, outpatients with active disease), we measured QoL, anxiety, depression, illness identity, self-esteem, loneliness, childhood trauma, and visceral sensitivity with questionnaires. In addition, fatigue, hemoglobin levels, and response to therapy were assessed in sample 2. We estimated multiple regularized partial correlation networks and conducted accuracy and stability tests of the networks. RESULTS: In both samples, QoL had the strongest relationships with visceral sensitivity and the illness identity engulfment. Depression was the most central factor in the networks. Baseline depression scores, visceral sensitivity, and engulfment were associated with response to therapy in sample 2. CONCLUSIONS: This first network study to assess the interplay between biopsychosocial factors and QoL in IBD reveals a comparable network structure in 2 samples. Results partly replicate findings from previous studies with regard to the importance of depression and yield information on the central role of the newly introduced concepts of illness identity and visceral sensitivity. Preliminary findings point to an influence of these parameters on the disease course, which indicates their role as a possible target in individualized therapy.

Chronic isoprenaline/phenylephrine vs. exclusive isoprenaline stimulation in mice: critical contribution of alpha1-adrenoceptors to early cardiac stress responses.

Hyperactivity of the sympathetic nervous system is a major driver of cardiac remodeling, exerting its effects through both α-, and ß-adrenoceptors (α-, ß-ARs). As the relative contribution of subtype α1-AR to cardiac stress responses remains poorly investigated, we subjected mice to either subcutaneous perfusion with the ß-AR agonist isoprenaline (ISO, 30 mg/kg × day) or to a combination of ISO and the stable α1-AR agonist phenylephrine (ISO/PE, 30 mg/kg × day each). Telemetry analysis revealed similar hemodynamic responses under both ISO and ISO/PE treatment i.e., permanently increased heart rates and only transient decreases in mean blood pressure during the first 24 h. Echocardiography and single cell analysis after 1 week of exposure showed that ISO/PE-, but not ISO-treated animals established α1-AR-mediated inotropic responsiveness to acute adrenergic stimulation. Morphologically, additional PE perfusion limited concentric cardiomyocyte growth and enhanced cardiac collagen deposition during 7 days of treatment. Time-course analysis demonstrated a diverging development in transcriptional patterns at day 4 of treatment i.e., increased expression of selected marker genes Xirp2, Nppa, Tgfb1, Col1a1, Postn under chronic ISO/PE treatment which was either less pronounced or absent in the ISO group. Transcriptome analyses at day 4 via RNA sequencing demonstrated that additional PE treatment caused a marked upregulation of genes allocated to extracellular matrix and fiber organization along with a more pronounced downregulation of genes involved in metabolic processes, muscle adaptation and cardiac electrophysiology. Consistently, transcriptome changes under ISO/PE challenge more effectively recapitulated early transcriptional alterations in pressure overload-induced experimental heart failure and in human hypertrophic cardiomyopathy.