The importance of contextual aspects in the care for patients with functional somatic symptoms.

Functional somatic symptoms refer to physical symptoms that cannot be (bio) medically explained. The pattern or clustering of such symptoms may lead to functional syndromes like chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, among many others. Since the underlying pathophysiology remains unknown, several explanatory models have been proposed, nearly all including social and psychological parameters. These models have stimulated effectiveness studies of several psychological and psychopharmacological therapies. While the evidence for their effectiveness is steadily growing, effect-sizes are at most moderate and many patients do not benefit. We hypothesize that the context in which interventions for functional somatic symptoms are delivered substantially influences their effectiveness. Although this hypothesis is in line with explanatory models of functional somatic symptoms, to our knowledge, studies primarily focusing on the influence of contextual aspects on treatment outcome are scarce. Contextual research in the field of somatic symptoms has (irrespective whether these symptoms can be medically explained or not), however, just begun and already yielded some valuable results. These findings can be organized according to Duranti's and Goodwin's theoretical approach to context in order to substantiate our hypothesis. Based on this approach, we categorized empirical findings in three contextual aspects, i.e. 1) the setting, 2) the behavioural environment, and 3) the language environment. Collectively, some support is found for the fact that early identification of patients with functional somatic symptoms, starting treatment as soon as possible, having a neat appearance and an organized office interior, a warm and friendly nonverbal approach and a language use without defensiveness are contextual parameters which enhance the assessment by the patient of the physician's competence to help. Nonetheless, in vivo studies addressing the most aspects, i.e. nonverbal behaviour and language, are needed for better understanding of these contextual aspect. Moreover, future research should address to what extent optimizing contextual aspects improve care for functional somatic symptoms.

Identification of inflammatory markers suitable for non-invasive, repeated measurement studies in biobehavioral research: A feasibility study.

INTRODUCTION: Studying the role of the immune system in the interaction between mental and physical health is challenging. To study individuals with an intensive, longitudinal study design that requires repetitive sampling in their daily life, non-invasive sampling techniques are a necessity. Urine can be collected in a non-invasive way, but this may be demanding for participants and little is known about fluctuation of inflammatory markers in urine over time. The aim of this study was to investigate the feasibility of non-invasive sampling, and to explore intra-individual differences in inflammatory markers in urine. MATERIALS & METHODS: Ten healthy individuals collected 24-hour urine for 63 consecutive days. In a pilot analysis, 39 inflammatory markers were examined for detectability in urine, stability over time and under storage conditions, and daily fluctuations. Multiplex analyses were used to quantify levels of eight selected markers: C-reactive protein (CRP), Fractalkine, Interleukin-1 receptor-antagonist (IL-1RA), interferon-α (IFNα), interferon-γ (IFNγ), Interferon gamma-induced protein 10 (IP10), Macrophage inflammatory protein-1ß (MIP-1ß), and Vascular Endothelial Growth Factor (VEGF). Cross-correlations were calculated between the overnight and 24-hour samples were calculated, to examine whether 24-hour urine could be replaced by the overnight portion for better feasibility. We examined intra- and interindividual differences in the levels of inflammatory markers in urine and the fluctuations thereof. RESULTS: This study showed that levels of selected inflammatory markers can be detected in urine. Cross-correlation analyses showed that correlations between levels of inflammatory markers in the night portion and the 24-hour urine sample varied widely between individuals. In addition, analyses of time series revealed striking inter- and intra-individual variation in levels of inflammatory markers and their fluctuations. CONCLUSION: We show that the assessment of urinary inflammatory markers is feasible in an intensive day-to-day study in healthy individuals. However, 24-hour urine cannot be replaced by an overnight portion to alleviate the protocol burden. Levels of inflammatory markers show substantial variation between and within persons.

Individual variation in temporal relationships between exposure to radiofrequency electromagnetic fields and non-specific physical symptoms: A new approach in studying 'electrosensitivity'.

BACKGROUND: Everyday exposure to radiofrequency electromagnetic fields (RF-EMF) emitted from wireless devices such as mobile phones and base stations, radio and television transmitters is ubiquitous. Some people attribute non-specific physical symptoms (NSPS) such as headache and fatigue to exposure to RF-EMF. Most previous laboratory studies or studies that analyzed populations at a group level did not find evidence of an association between RF-EMF exposure and NSPS. OBJECTIVES: We explored the association between exposure to RF-EMF in daily life and the occurrence of NSPS in individual self-declared electrohypersensitive persons using body worn exposimeters and electronic diaries. METHODS: We selected seven individuals who attributed their NSPS to RF-EMF exposure. The level of and variability in personal RF-EMF exposure and NSPS were determined during a three-week period. Data were analyzed using time series analysis in which exposure as measured and recorded in the diary was correlated with NSPS. RESULTS: We found statistically significant correlations between perceived and actual exposure to wireless internet (WiFi - rate of change and number of peaks above threshold) and base stations for mobile telecommunications (GSM + UMTS downlink, rate of change) and NSPS scores in four of the seven participants. In two persons a higher EMF exposure was associated with higher symptom scores, and in two other persons it was associated with lower scores. Remarkably, we found no significant correlations between NSPS and time-weighted average power density, the most commonly used exposure metric. CONCLUSIONS: RF-EMF exposure was associated either positively or negatively with NSPS in some but not all of the selected self-declared electrohypersensitive persons.

Functional outcomes of child and adolescent mental disorders. Current disorder most important but psychiatric history matters as well.

BACKGROUND: Various sources indicate that mental disorders are the leading contributor to the burden of disease among youth. An important determinant of functioning is current mental health status. This study investigated whether psychiatric history has additional predictive power when predicting individual differences in functional outcomes. METHOD: We used data from the Dutch TRAILS study in which 1778 youths were followed from pre-adolescence into young adulthood (retention 80%). Of those, 1584 youths were successfully interviewed, at age 19, using the World Health Organization Composite International Diagnostic Interview (CIDI 3.0) to assess current and past CIDI-DSM-IV mental disorders. Four outcome domains were assessed at the same time: economic (e.g. academic achievement, social benefits, financial difficulties), social (early motherhood, interpersonal conflicts, antisocial behavior), psychological (e.g. suicidality, subjective well-being, loneliness), and health behavior (e.g. smoking, problematic alcohol, cannabis use). RESULTS: Out of the 19 outcomes, 14 were predicted by both current and past disorders, three only by past disorders (receiving social benefits, psychiatric hospitalization, adolescent motherhood), and two only by current disorder (absenteeism, obesity). Which type of disorders was most important depended on the outcome. Adjusted for current disorder, past internalizing disorders predicted in particular psychological outcomes while externalizing disorders predicted in particular health behavior outcomes. Economic and social outcomes were predicted by a history of co-morbidity of internalizing and externalizing disorder. The risk of problematic cannabis use and alcohol consumption dropped with a history of internalizing disorder. CONCLUSION: To understand current functioning, it is necessary to examine both current and past psychiatric status.

Stressful life events and leukocyte telomere attrition in adulthood: a prospective population-based cohort study.

BACKGROUND: Telomere attrition might be one of the mechanisms through which psychosocial stress leads to somatic disease. To date it is unknown if exposure to adverse life events in adulthood is associated with telomere shortening prospectively. In the current study we investigated whether life events are associated with shortening of telomere length (TL). METHOD: Participants were 1094 adults (mean age 53.1, range 33-79 years) from the PREVEND cohort. Data were collected at baseline (T1) and at two follow-up visits after 4 years (T2) and 6 years (T3). Life events were assessed with an adjusted version of the List of Threatening Events (LTE). TL was measured by monochrome multiplex quantitative PCR at T1, T2, and T3. A linear mixed model was used to assess the effect of recent life events on TL prospectively. Multivariable regression analyses were performed to assess whether the lifetime life events score or the score of life events experienced before the age of 12 predicted TL cross-sectionally. All final models were adjusted for age, sex, body mass index, presence of chronic diseases, frequency of sports, smoking status, and level of education. RESULTS: Recent life events significantly predicted telomere attrition prospectively (B = -0.031, p = 0.007). We were not able to demonstrate a significant cross-sectional relationship between the lifetime LTE score and TL. Nor did we find exposure to adverse life events before the age of 12 to be associated with TL in adulthood. CONCLUSIONS: Exposure to recent adverse life events in adulthood is associated with telomere attrition prospectively.

Does neuroticism make you old? Prospective associations between neuroticism and leukocyte telomere length.

BACKGROUND: Telomere attrition, causing accelerated aging, might be one of the mechanisms through which neuroticism leads to somatic disease and increased all-cause mortality. In the current study we investigated whether neuroticism is prospectively associated with shorter telomere length (TL), a biological marker of aging. METHOD: Participants were 3432 adults (mean age 52.9 years, range 32-79). Data were collected at baseline (T1) and at two follow-up visits after 4 years (T2) and 6 years (T3). Neuroticism was assessed using the 12-item neuroticism scale of the Revised Eysenck Personality Questionnaire (EPQ-R) at T2 and T3. TL was measured by a monochrome multiplex quantitative polymerase chain reaction (PCR) assay at T1, T2 and T3. A linear mixed model was used to assess whether neuroticism could predict TL prospectively after adjusting for age, sex, body mass index (BMI), frequency of sports, smoking status, presence of chronic diseases and level of education. RESULTS: Neuroticism was a significant negative predictor of TL at follow-up (B = -0.004, p = 0.044) after adjusting for sex, age, baseline TL and various biological and lifestyle factors. CONCLUSIONS: High neuroticism is significantly and prospectively associated with telomere attrition independent of lifestyle and other risk factors.

Association between anxiety but not depressive disorders and leukocyte telomere length after 2 years of follow-up in a population-based sample.

BACKGROUND: Telomere length is considered an emerging marker of biological aging. Depression and anxiety are associated with excess mortality risk but the mechanisms remain obscure. Telomere length might be involved because it is associated with psychological distress and mortality. The aim of this study was to test whether anxiety and depressive disorders predict telomere length over time in a large population-based sample. Method All analyses were performed in a longitudinal study in a general population cohort of 974 participants. The Composite International Diagnostic Interview (CIDI) was used to measure the presence of anxiety and depressive disorders. Telomere length was measured using monochrome multiplex polymerase chain reaction (PCR) at approximately 2 years of follow-up. We used linear multivariable regression models to evaluate the association between anxiety and depressive disorders and telomere length, adjusting for adverse life events, lifestyle factors, educational level and antidepressant use. RESULTS: The presence of anxiety disorders predicted shorter telomeres at follow-up (ß = -0.073, t = -2.302, p = 0.022). This association was similar after controlling for adverse life events, lifestyle factors, educational level and antidepressant use (ß = -0.077, t = -2.144, p = 0.032). No association was found between depressive disorders and shorter telomeres at follow-up (ß = 0.010, t = 0.315, p = 0.753). CONCLUSIONS: This study found that anxiety disorders predicted shorter telomere length at follow-up in a general population cohort. The association was not explained by adverse life events, lifestyle factors, educational level and antidepressant use. How anxiety disorders might lead to accelerated telomere shortening and whether this might be a mediator explaining the excess mortality risk associated with anxiety deserve further investigation.

Empirical foundations for the diagnosis of somatization: implications for DSM-5.

BACKGROUND: The aim of this study was to develop empirically validated criteria for the diagnoses of clinically relevant somatization. METHOD: This study was performed in a population-representative cohort consisting of 461 males (47.8%) and 503 females (52.2%), with an average age of 55.8 years (s.d.=11.1). Somatization, anxiety and depression were derived from the Composite International Diagnostic Interview. Mplus was used to perform confirmative factor analyses on the current DSM-IV symptom groups; on alternative symptom clusters previously suggested; and to perform latent class analysis in order to define an empirically derived cut-off for somatization. RESULTS: The existence of symptom groups as described in DSM-IV was not supported by our data, whereas a differentiation between cardiopulmonary, musculoskeletal, gastrointestinal and general somatic symptoms did fit our data. Latent class analysis revealed two classes characterized by few (n=859) and many (n=105) symptoms. The class of subjects could be approached by a simple cut-off of four functional symptoms (sensitivity 79%, specificity 98%, positive predictive value 82%, negative predictive value 97%) regardless of the number of organ systems involved. CONCLUSIONS: This study in a large population-representative cohort suggests that a simple symptom count can be used as a dimensional diagnosis of somatization. In those instances in which a categorical diagnosis is preferred, a simple cut-off of four out of 43 functional symptoms best fitted our data. We did not find any added value for incorporating the number of symptom clusters into the diagnostic criteria.

Abnormalities in dendritic cell and macrophage accumulation in the pancreas of nonobese diabetic (NOD) mice during the early neonatal period.

Dendritic cell (DC), macrophage (Mphi) and lymphocyte infiltrations have been observed in normal human perinatal pancreata, but have never been investigated so early in control mice. In type 1 diabetes-prone NOD mice, these cells are thought to infiltrate first the periphery of the islets of Langerhans around weaning before further islet infiltration and beta-cell destruction. We quantified, during the first month of life, the numbers of DC (characterized by CD11c positivity and dendritic morphology), histiocyte-like Mphi (characterized by ER-MP23 positivity) and Mphi with scavenging potential (characterized by BM8 positivity) in C57BL/6, DBA/2 and BALB/c control, and NOD and lymphocyte-deficient NODscid mouse pancreata. First, CD11c+ DC were present at low densities from birth onwards in control pancreata, while densities were higher in NOD and NODscid. Second, high numbers of BM8+ and ER-MP23+ Mphi were observed at birth in all strains investigated. After birth, particularly BM8+ cells disappeared progressively in control strains, but not in NOD and NODscid. Third, NOD mice also had more ER-MP23+ Mphi at birth compared to controls. Finally, DC and Mphi localizations were similar in all strains, i.e., mostly as dispersed cells in perivascular, periductular, peri-islet areas and interlobular septa. The most remarkable finding was that particularly BM8+ Mphi, were seen at sites of islet neogenesis and predominantly at the duct-islet interface. Our data showed that different types of APC were present in the pancreas during postnatal development in various control mouse strains and some differences were observed in NOD and NODscid mice from birth onwards.