Benjamin Fischler

Determinants of symptoms in functional dyspepsia: gastric sensorimotor function, psychosocial factors or somatisation?

Background: Gastric sensorimotor dysfunction, psychosocial factors and somatisation are all implicated in symptom generation in functional dyspepsia (FD). Aim: To determine the relative contribution of each of these factors to overall dyspeptic symptom severity and weight loss in FD. Methods: In 201 consecutive tertiary care patients with FD (mean age 40.1 (SD 12.6) years), gastric sensorimotor function was studied using barostat (sensitivity, compliance and accommodation). Psychosocial factors (depression and anxiety disorders, positive and negative affect, perceived stress, alexithymia and history of abuse), somatisation and co-morbid irritable bowel syndrome (IBS) and chronic fatigue symptoms were assessed using self-report questionnaires. Variables were correlated with dyspepsia symptom severity (DSS) and weight loss. Hierarchical multiple linear regression was used to identify determinants of DSS and weight loss. Results: Multiple linear regression identified the following determinants of DSS: gastric sensitivity (β = 0.77, p = 0.25), depression (β = 0.12, p = 0.06) and somatisation (β = 0.48, p<0.0001) (controlling for age and occupation, R2 = 0.29, p<0.0001). The effect of depression on DSS is partially mediated by somatisation. Gastric sensitivity (β = 2.87, p = 0.08), history of childhood sexual abuse (β = 9.37, p = 0.0006), depression (β = 0.19, p = 0.24) and somatisation (β = 0.67, p = 0.01) are independent determinants of weight loss (controlling for gender and occupation, R2 = 0.42, p<0.0001). The effect of depression on weight loss is fully mediated by somatisation. Conclusion: Symptom severity and weight loss in FD are determined by psychosocial factors (depression, abuse history) and somatisation, and only to a lesser extent by gastric sensorimotor function. The importance of psychosocial factors and somatisation compared to gastric sensorimotor function is most pronounced in hypersensitive patients.

Relationship between anxiety and gastric sensorimotor function in functional dyspepsia.

Objective: To investigate the relationship between anxiety and gastric sensorimotor function in patients with (hypersensitive) functional dyspepsia (FD). Comorbidity between FD and anxiety disorders is high. In FD, epigastric pain is associated with gastric hypersensitivity and neuroticism, a personality trait related to anxiety. Experimentally induced anxiety in healthy volunteers is associated with changes in sensorimotor function of the proximal stomach. Methods: A total of 139 patients with FD (n = 102 women) underwent a barostat investigation to determine gastric compliance, meal accommodation, and thresholds for discomfort and pain. Anxiety was measured by the State-Trait Anxiety Inventory (STAI) scale (anxiety as a stable personality trait) and the STAI-State scale (momentary anxiety). The anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A) was filled out to detect comorbid anxiety disorders. Results: Hyper- and normosensitive patients had similar anxiety scores, but gastric compliance was significantly lower in hypersensitive patients (11.4 versus 32.8 ml/mm Hg; p < .001). In the whole patient group, no significant correlations between STAI scores and gastric sensorimotor function were found. In hypersensitive patients (n = 53, 43 women), state anxiety was negatively correlated with discomfort threshold (&rgr; = −.49; p = .001), pain threshold (&rgr; = −.48; p = .02), and gastric compliance (&rgr; = −.46; p = .002). These results were confirmed by multiple linear and logistic regression analyses. Conclusion: In hypersensitive patients with FD, state anxiety is significantly and negatively correlated with discomfort threshold, pain threshold, and compliance. These results strengthen the hypothesis that anxiety is important in FD, especially in hypersensitive patients. FD = functional dyspepsia; STAI = State-Trait Anxiety Inventory; HADS-A = Hospital Anxiety and Depression Scale-Anxiety subscale; FGID = functional gastrointestinal disorders; IBS = irritable bowel syndrome; CNS = central nervous system; MDP = minimal distending pressure; WMW test = Wilcoxon Mann-Whitney test; OR = odds ratio; ANS = autonomic nervous system; EMS = emotional motor system; PAG = periaqueductal grey; LC = locus coeruleus; HPA-axis = hypothalamo-pituitary-adrenal axis; ASI = anxiety sensitivity index; VSI = visceral sensitivity index.

Comparison of 99mTc HMPAO SPECT Scan between Chronic Fatigue Syndrome, Major Depression and Healthy Controls: An Exploratory Study of Clinical Correlates of Regional Cerebral Blood Flow

An explorative analysis of the relationship between symptomatology and cerebral blood flow in the chronic fatigue syndrome (CFS) as assessed with 99mTc HMPAO SPECT scan reveals statistically significant positive correlations between frontal blood flow on the one hand and objectively and subjectively assessed cognitive impairment, self-rating of physical activity limitations and total score on Hamilton Depression Rating Scale on the other. A pathophysiological role of frontal blood flow in the cognitive impairment and physical activity limitations in CFS is hypothesized. A comparison of cerebral blood flow between CFS, major depression (MD) and healthy controls (HC) has been performed. A lower superofrontal perfusion index is demonstrated in MD as compared with both CFS and HC. There is neither a global nor a marked regional hypoperfusion in CFS compared with HC. Asymmetry (R > L) of tracer uptake at parietotemporal level is demonstrated in CFS as compared with MD.

Generalized anxiety disorder in chronic fatigue syndrome

A structured psychiatric interview, forming part of a global psychopathological approach, revealed higher prevalence rates of current and lifetime psychiatric disorders and a higher degree of psychiatric comorbidity in patients with chronic fatigue syndrome (CFS) than in a medical control group. In contrast to previous studies, a very high prevalence of generalized anxiety disorder (GAD) was found in CFS, characterized by an early onset and a high rate of psychiatric comorbidity. It is postulated that GAD represents a susceptibility factor for the development of CFS. A significantly higher prevalence was also observed for the somatization disorder (SD) in the CFS group. Apart from a higher female‐to‐male ratio in fibromyalgia, no marked differences were observed in sociodemographic or illness‐related features, or in psychiatric morbidity, between CFS patients with and without fibromyalgia. CFS patients with SD have a longer illness duration and a higher rate of psychiatric comorbidity. These findings are consistent with the suggestion of Hickie et al. (1) that chronic fatigued subjects with SD should be distinguished from subjects with CFS.

Physical fatigability and exercise capacity in chronic fatigue syndrome: Association with disability, somatization and psychopathology

Physical fatigability and avoidance of physically demanding tasks in chronic fatigue syndrome (CFS) were assessed by the achievement or nonachievement of 85% of age-predicted maximal heart rate (target heart rate, THR) during incremental exercise. The association with functional status impairment, somatization, and psychopathology was examined. A statistically significant association was demonstrated between this physical fatigability variable and impairment, and a trend was found for an association with somatization. No association was demonstrated with psychopathology. These results are in accordance with the cognitive-behavioral model of CFS, suggesting a major contribution of avoidance behavior to functional status impairment; however, neither anxiety nor depression seem to be involved in the avoidance behavior. Aerobic work capacity was compared between CFS and healthy controls achieving THR. Physical deconditioning with early involvement of anaerobic metabolism was demonstrated in this CFS subgroup. Half of the CFS patients who did not achieve THR did not reach the anaerobic threshold. This finding argues against an association in CFS between avoidance of physically demanding tasks and early anaerobic metabolism during effort.

Sleep anomalies in the chronic fatigue syndrome. A comorbidity study.

Polysomnographic findings were compared between a group of patients with the chronic fatigue syndrome (CFS; n = 49) and a matched healthy control (HC) group (n = 20). Sleep initiation and sleep maintenance disturbances were observed in the CFS group. The percentage of stage 4 was significantly lower in the CFS group. A discriminant analysis allowed a high level of correct classification of CFS subjects and HC. Sleep-onset latency and the number of stage shifts/hour contributed significantly to the discriminant function. The presence of these anomalies as well as the decrease in stage 4 sleep were not limited to the patients also diagnosed with fibromyalgia or with a psychiatric disorder. No association was found between sleep disorders and the degree of functional status impairment. The mean REM latency and the percentage of subjects with a shortened REM latency were similar in CFS and HC.

Immune dysfunction associated with chronic professional stress in nurses

The relationship between chronic professional stress in nurses and immunity as well as the possible impact of psychopathology upon this relationship have been examined. Sixty subjects were selected on the basis of high/low scores on professional stress and psychopathology. Chronic professional stress appeared to be associated with immune dysfunction including signs of immune activation (increased numbers of cells expressing the interleukin-2 receptor, especially CD4+CD25+ cells) and possibly immune suppression (decrease in percentage of natural killer cells). The increase in activation markers, CD3+CD16CD56+ cells and serum neopterin was most pronounced in the group with high stress/low psychopathology whereas the decrease in CD8+CD11b+ cells was most pronounced in the group with high stress/high psychopathology. It is hypothesized that in the presence of chronic stress distinct psychological mechanisms are associated with specific immune dysfunctions.

Cognitive Functioning in Patients with Chronic Fatigue Syndrome

A comprehensive battery of neuropsychological tests was administered to 35 outpatients suffering from Chronic Fatigue Syndrome (CFS). They were compared to 33 normal controls matched for age, gender, intelligence, and education. The patients displayed psychomotor slowing and impaired attention. The learning rate of verbal and visual material for patients with CFS was slower, and delayed recall of verbal and visual information was impaired. Because there was a high variability in cognitive impairment within the CFS group, it would be inappropriate to generalize results to the entire CFS population. Two neuropsychological variables indicating aspects of psychomotor performance and verbal memory were found to discriminate best between patients and controls.

Attention and verbal learning in patients with Chronic Fatigue Syndrome

Former neuropsychological studies with Chronic Fatigue Syndrome (CFS) patients evaluated a broad range of cognitive functions. Several, but not all, reported subtle attentional and memory impairments suggesting possible mild cerebral involvement. In this study, a battery of attentional tests and a verbal memory task were administered to 20 CFS patients and 22 healthy controls (HC) in order to clarify the specific nature of attention and memory impairment in these patients. The results provide evidence for attentional dysfunction in patients with CFS as compared to HC. CFS patients performed more poorly on a span test measuring attentional capacity and working memory. Speeded attentional tasks with a more complex element of memory scanning and divided attention seem to be a sensitive measure of reduced attentional capacity in these patients. Focused attention, defined as the ability to attend to a single stimulus while ignoring irrelevant stimuli, appears not to be impaired. CFS patients were poorer on recall of verbal information across learning trials, and poor performance on delayed recall may be due to poor initial learning and not only to a retrieval failure.

Abuse History, Depression, and Somatization Are Associated With Gastric Sensitivity and Gastric Emptying in Functional Dyspepsia

Objective: Gastric sensitivity testing relies on subjective reporting and may therefore be influenced by psychosocial factors and somatization. Furthermore, psychological processes may affect gastric motor function (accommodation to a meal emptying) through efferent brain-gut pathways. This study sought to determine the association of abuse history, psychiatric comorbidity, and somatization with gastric sensorimotor function. Methods: In 201 patients with functional dyspepsia, gastric sensitivity and accommodation were studied with a barostat. Gastric emptying of solids was studied using a breath test. Sexual and physical abuse history, psychiatric comorbidity (depression and panic disorder), and somatization were assessed using validated questionnaires. Multiple linear regression models were used to identify patient characteristics independently associated with gastric sensitivity and emptying. Results: Age (p = .02), sexual abuse history (p < .001), physical abuse history (p = .004), and somatization (p < .001) were independently associated with gastric discomfort threshold (R2 = 0.30); a significant depression-by-sexual abuse interaction effect was also found (p = .003). None of the factors studied were associated with gastric accommodation to a meal. Physical abuse history (p = .003) and somatization (p = .048) were independently associated with gastric emptying (R2 = 0.19). Conclusions: These results demonstrate the complex relationship among abuse history, psychiatric comorbidity, somatization, and gastric sensorimotor (dys)function. Although the psychobiological mechanisms underlying these relationships remain to be determined, the autonomic nervous, stress hormone, and immune systems may be involved.FD = functional dyspepsia; FGID = functional gastrointestinal disorder; t1/2 = gastric half-emptying time; PHQ = Patient Health Questionnaire; GI = gastrointestinal; GLM = general linear model; IBS = irritable bowel syndrome; ANS = autonomic nervous system; CRF = corticotropin-releasing factor