Chronic functional somatic symptoms: a single syndrome?

BACKGROUND: Reliable longitudinal data of patients with functional somatic symptoms in general practice are lacking. AIMS: To identify distinctive features in patients with chronic functional somatic symptoms, and to determine whether these symptoms support the hypothesis of the existence of specific somatic syndromes. DESIGN OF STUDY: Observational study, with a comparison control group. SETTING: Four primary care practices affiliated with the University of Nijmegen in the Netherlands. METHOD: One hundred and eighty-two patients diagnosed between 1998 and 2002 as having chronic functional somatic symptoms and 182 controls matched by age, sex, socioeconomic status, and practice were included. Data on comorbidity, referrals, diagnostic tests, and hospital admissions over a period of 10 years prior to the diagnosis were collected. Medication use and number of visits to the general practitioner (GP) were extracted from the moment computerised registration was started. RESULTS: In the 10 years before the diagnosis of chronic functional somatic symptoms, significantly more patients than controls presented functional somatic symptoms in at least two body systems, and used more somatic and psychotropic drugs. They visited the GP twice as much, statistically had significantly more psychiatric morbidity, and were referred more often to mental health workers and somatic specialists. The number of patients undergoing diagnostic tests was higher for patients with chronic functional somatic symptoms than for controls, but hospital admissions rates were equal. CONCLUSION: Patients with chronic functional somatic symptoms have a great diversity of functional somatic symptoms. They use more somatic and psychotropic drugs than controls in the years before diagnosis. Moreover, they show high rates of referrals and psychiatric morbidity. The diversity of symptoms of patients with chronic functional somatic symptoms supports the concept that symptoms do not cluster in well defined distinct syndromes. Therefore, patients with chronic functional somatic symptoms should preferably not be classified into medical subspecialty syndromes.     

Psychosomatic nursing assessment of psychiatric patients

This article presents the results of a research study on 547 mental patients testing a form of nursing assessment of mental patients in psychiatric and in general hospitals, as a means to assess their nursing needs and as a basis for planning, implementation and evaluation of their personalized holistic nursing care. The study showed that more depressive than schizophrenic patients went to the general hospital for help. The reverse was observed in the psychiatric hospital. The psychological nursing needs of the patients were significantly correlated with their somatic nursing needs. The psychological as well as the somatic nursing needs of the patients were significantly correlated with sex, age, somatic health state and mental health state in general, and not with their concrete psychiatric diagnosis. It is concluded that the psychiatric nursing assessment should be oriented towards the investigation of the patient's psychosomatic nursing needs rather than be based on his medical diagnosis.     

Progression of somatic CTG repeat length heterogeneity in the blood cells of myotonic dystrophy patients

The genetic basis of myotonic dystrophy (DM) is the expansion of an unstable CTG repeat in the 34 UTR of the DM protein kinase gene on chromosome 19. One of the principal features of the DM mutation is an extraordinarily high level of somatic mosaicism, due to an extremely high degree of somatic instability both within and between different tissues. This instability appears to be biased towards further expansion and continuous throughout the life of an individual, features that could be associated with the progressive nature of the disease. Although increasing measured allele size between patients clearly correlates with an increased severity of symptoms and an earlier age of onset, this correlation is not precise and measured allele length cannot be used as an accurate predictor of age of onset. In order to further characterize the dynamics of DM CTG repeat somatic instability, we have studied repeat length changes over time in 111 myotonic dystrophy patients with varying clinical severity and CTG repeat size over time intervals of 1-7 years. We have found a direct progression of the size heterogeneity over time related to initial CTG repeat size and the time interval and always biased towards further expansion. Attempts to mathematically model the dynamics have proved only partially successful suggesting that individual specific genetic and/or environmental factors also play a role in somatic mosaicism.      

Predictors of a Functional Somatic Syndrome Diagnosis in Patients with Persistent Functional Somatic Symptoms

Background

Functional somatic syndromes (FSS) are characterized by the existence of multiple persistent functional somatic symptoms. Not many patients fulfilling the criteria for an FSS, receive a formal diagnosis, and it is unknown which factors explain this discrepancy. Patients that tend to worry and patients that gather more health information may have an increased chance of an FSS diagnosis. We hypothesized that high intelligence and high neuroticism increase the probability of an FSS diagnosis in patients with persistent functional somatic symptoms.

Purpose

This study aims to investigate patient factors that might be important in the process of syndrome labeling.

Methods

Our study was performed in a large, representative population cohort (n?=?976) in Groningen, The Netherlands, and included two assessment waves. Intelligence was measured using the General Aptitude Test Battery version B 1002-B. Neuroticism was measured using the 12-item neuroticism scale of the Eysenck Personality Questionnaire-Revised. Functional somatic symptoms were measured with the somatization section of the Composite International Diagnostic Interview. Current FSS diagnosis was assessed with a questionnaire. We performed multivariable logistic regression analyses including sum scores of neuroticism, intelligence scores, sex, number of functional somatic symptoms, and age as potential predictors of having an FSS diagnosis.

Results

From the 976 participants that completed measurements at follow-up, 289 (26.4 %) participants reported at least one persistent functional somatic symptom, and these subjects were included in the main analyses (38.4 % males, mean age of 55.2 years (SD?=?10.7), 36–82 years). High numbers of functional somatic symptoms ((OR)?=?1.320; 95 % (CI)?=?1.097–1.588), female sex (OR?=?9.068; 95 % CI?=?4.061–20.251), and high intelligence (OR?=?1.402; 95 % CI?=?1.001–1.963) were associated with an FSS diagnosis, while age (OR?=?0.989; 95 % CI?=?960–1.019) and neuroticism (OR?=?0.956; 95 % CI?=?0.872–1.048) were not.

Conclusion

This study suggests that high intelligence, but not high neuroticism, increases the chance of syndrome labeling in patients with persistent functional somatic symptoms.     

Increased risk of developing dementia in patients with major affective disorders compared to patients with other medical illnesses

BACKGROUND: The association between affective disorder and subsequent dementia is unclear. Our aim was to investigate whether patients with unipolar or bipolar affective disorder have an increased risk of developing dementia compared to patients with other chronic illnesses. METHOD: By linkage of the psychiatric and somatic nation-wide registers of all hospitalised patients in Denmark, 2007 patients with mania, 11741 patients with depression, 81380 patients with osteoarthritis and 69149 patients with diabetes were identified according to diagnosis at first-ever discharge from a psychiatric or somatic hospital between 1 January 1977 and 31 December 1993. The risk of receiving a diagnosis of dementia on subsequent re-admission was estimated with the use of survival analyses. RESULTS: Patients with unipolar or bipolar affective disorder had a greater risk of receiving a diagnosis of dementia than patients with osteoarthritis or diabetes. Differences in age and gender and the effect of alcohol- or drug-abuse did not explain these associations. CONCLUSION: Patients with unipolar or bipolar affective disorder seem to have an increased risk of developing dementia compared to patients with other illnesses. LIMITATION: The study includes only patients who have been hospitalised at least once. CLINICAL RELEVANCE: Patients with unipolar or bipolar affective disorder may be at increased risk of developing dementia.     

A practical approach to fibromyalgia

Fibromyalgia is the name given to a collection of symptoms with no clear physiologic cause, The constellation of symptoms are clearly recognizable as a distinct pathologic entity. The diagnosis is made through clinical observations made by the examiner. Differential diagnosis must include other somatic syndromes as well as disease entities like hepatitis, hypothyroidism, diabetes mellitus, electrolyte imbalance, multiple sclerosis, and cancer. Diagnostic criteria are given as guidelines for the diagnosis, not as absolute requirements. Treatment of this condition remains individualized and relies heavily on having a therapeutic relationship with a provider. Treatment of this syndrome needs to be looked at as an ongoing process. Goal oriented treatment aimed at maintaining specific functions can be directed at helping a patient get restorative sleep, alleviating the somatic pains that ail the patient, keeping a person productive, regulating schedules or through goal oriented agreements made with the patient. Since this syndrome is chronic and may effect all areas of a persons functioning the family and social support system of the person being treated need to be evaluated. Patients often seek alternative medical treatments for this problem including diet therapy, acupuncture, and herbal therapy. Treatment must involve more than just the symptoms presented and the patient can only be treated successfully if they are willing to work at changing their own perceptions, and ways of relating to stressors in their world.     

Somatic mitochondrial DNA mutations in Chinese patients with osteosarcoma

Somatic mutations in mitochondrial DNA (mtDNA) have been long proposed to drive the pathogenesis and progression of human malignancies. Previous investigations have revealed a high frequency of somatic mutations in the D‐loop control region of mtDNA in osteosarcoma. However, little is known with regard to whether or not somatic mutations also occur in the coding regions of mtDNA in osteosarcoma. To test this possibility, in the present study we screened somatic mutations over the full‐length mitochondrial genome of 31 osteosarcoma tumour tissue samples, and corresponding peripheral blood samples from the same cohort of patients. We detected a sum of 11 somatic mutations in the mtDNA coding regions in our series. Nine of them were missense or frameshift mutations that have the potential to hamper mitochondrial respiratory function. In combination with our earlier observations on the D‐loop fragment, 71.0% (22/31) of patients with osteosarcoma carried at least one somatic mtDNA mutation, and a total of 40 somatic mutations were identified. Amongst them, 29 (72.5%) were located in the D‐loop region, two (5%) were in the sequences of the tRNA genes, two (5%) were in the mitochondrial ATP synthase subunit 6 gene and seven (17.5%) occurred in genes encoding components of the mitochondrial respiratory complexes. In addition, somatic mtDNA mutation was not closely associated with the clinicopathological characteristics of osteosarcoma. Together, these findings suggest that somatic mutations are highly prevalent events in both coding and non‐coding regions of mtDNA in osteosarcoma. Some missense and frameshift mutations are putatively harmful to proper mitochondrial activity and might play vital roles in osteosarcoma carcinogenesis.     

Experimental evidence for interpretive but not attention biases towards somatic information in patients with chronic fatigue syndrome

Objective: This study tested whether CFS patients have an attentional information processing bias for illness‐related information and a tendency to interpret ambiguous information in a somatic fashion. Design:25 patients meeting research criteria for a diagnosis of CFS were compared to 24 healthy matched controls on a modified Stroop task and an ambiguous cues task. Method: In the modified Stroop task, participants colour named a series of somatic, depressed and neutral words in order to ascertain whether the somatic words were more distracting to the CFS patients than the depressed and neutral words when compared to controls. In the ambiguous cues task, participants were presented with a tape‐recorded list of 30 words including 15 ambiguous illness words (e.g., vein/vain) and 15 unambiguous words. For each word, they were asked to write down the first word that came into their head. A somatic bias score was obtained for each subject by summing the number of somatic responses to the ambiguous word cues. Results: Although CFS patients were significantly slower in colour naming all of the Stroop word categories than controls, there was no evidence for illness or depressed words creating greater interference than neutral words. However, on the ambiguous cues task, CFS patients made significantly more somatic interpretations than controls and this bias was significantly associated with the extent to which they currently reported symptoms. Conclusion: CFS patients have an interpretive bias for somatic information which may play a part in the maintenance of the disorder by heightening patients' experience of physical symptoms and helping to maintain their negative illness schemas. Although patients did not show an attentional bias in this study, this may be related to the methodology employed.     

Accuracy of diagnosing depression in primary care: the impact of chronic somatic and psychiatric co-morbidity

BACKGROUND: Depression is highly co-morbid with both psychiatric and chronic somatic disease. These types of co-morbidity have been shown to exert opposite effects on underdiagnosis of depression by general practitioners (GPs). However, past research has not addressed their combined effect on underdiagnosis of depression. METHOD: Co-morbidity data on 191 depressed primary-care patients selected by a two-stage sampling procedure were analysed. Diagnoses of major depression and/or dysthymia in the last 12 months were assessed using a standardized psychiatric interview (CIDI) and compared with depression diagnoses registered by GPs in patient contacts during the same period. Presence of psychiatric and chronic somatic co-morbidity was determined using the CIDI and contact registration, respectively. RESULTS: Regression analysis showed a significant interaction effect between psychiatric and chronic somatic co-morbidity on GPs' diagnosis of depression, while taking into account the effects of sociodemographic variables, depression severity and number of GP contacts. Subsequent stratified analysis revealed that in patients without chronic somatic co-morbidity, a lower educational level, a less severe depression, and fewer GP contacts all significantly increased the likelihood of not being diagnosed as depressed. In contrast, in patients with chronic somatic co-morbidity, only having no psychiatric co-morbidity significantly decreased the likelihood of receiving a depression diagnosis. CONCLUSIONS: Our results indicate that the effects of psychiatric co-morbidity and other factors on underdiagnosis of depression by GPs differ between depressed patients with and without chronic somatic co-morbidity. Efforts to improve depression diagnosis by GPs seem to require different strategies for depressed patients with and without chronic somatic co-morbidity.     

A Rapid Ex Vivo Clinical Diagnostic Assay for Fas Receptor-Induced T Lymphocyte Apoptosis

Deleterious mutations in genes involved in the Fas apoptosis pathway lead to Autoimmune Lymphoproliferative Syndrome (ALPS). Demonstration of an apoptosis defect is critical for the diagnosis and study of ALPS. The traditional in vitro apoptosis assay, however, requires a week of experimental procedures. Here, we show that defects in Fas-induced apoptosis in PBMCs can be evaluated directly ex vivo using multicolor flow cytometry to analyze the apoptosis of effector memory T cells, a Fas-sensitive subset of PBMCs. This method allowed us to sensitively quantify defective apoptosis in ALPS patients within a few hours. Some ALPS patients (ALPS-sFAS) without germline mutations have somatic mutations in Fas specifically in double-negative αβ T cells (DNTs), an unusual lymphocyte population that is characteristically expanded in ALPS. Since DNTs have been notoriously difficult to culture, defective apoptosis has not been previously demonstrated for ALPS-sFAS patients. Using our novel ex vivo apoptosis assay, we measured Fas-induced apoptosis of DNTs for the first time and found that ALPS-sFAS patients had significant apoptosis defects in these cells compared to healthy controls. Hence, this rapid apoptosis assay can expedite the diagnosis of new ALPS patients, including those with somatic mutations, and facilitate clinical and molecular investigation of these diseases.     

Factors leading to the reporting of ''functional'' somatic symptoms by general practice attenders.

The aim of this study was to examine the prevalence of 'functional' somatic symptoms in general practice and the factors associated with reporting these symptoms. During a one month period, all attenders aged 16 years and over at a general practice near Leeds were screened for functional somatic symptoms using the Bradford somatic inventory. The general practitioner recorded the patients' personal data and diagnostic assessment. Data were analysed from 670 Europid patients who completed the Bradford somatic inventory at their first attendance during the month. Higher mean numbers of functional somatic symptoms were found in patients with psychiatric and functional syndromes than in patients with organic illness or in well patients. The symptom score on the Bradford somatic inventory was significantly related to five factors: current anxious mood, current depressed mood, sex, chronic physical illness in a parent and a history of depressive illness. Using multiple linear regression analysis, all five factors were found to be independent predictors of symptom scores on the Bradford somatic inventory. This study highlights the multifactorial aetiology of functional somatic symptoms reported by general practice attenders.     

Similarity of depression in diabetic and psychiatric patients.

Diabetic and psychiatric out-patients were studied to determine whether the symptom profile of depression was similar in medically ill and medically well subjects. The diagnosis of major depression was determined using psychiatric interviews and DSM-IIIR criteria. The 21-item Beck Depression Inventory (BDI) was used to characterize the prevalence and severity of depression symptoms, and the measure was divided into cognitive (13 symptoms) and somatic (eight symptoms) subsets. Seventeen (81%) of 21 symptoms (including 12/13 cognitive and 5/8 somatic symptoms) were not statistically different in prevalence or severity between the depressed diabetic patients (N = 41) and the depressed psychiatric patients (N = 68). Both of these depressed groups were significantly different from a nondepressed diabetic comparison group (N = 58) in the prevalence and severity of every BDI symptom except weight loss. These data show that the symptom profile of depression in diabetic patients (in particular the cognitive symptoms) is similar to that in depressed psychiatric patients and is readily differentiated from the symptom profile in nondepressed diabetic patients. Our observations support the diagnostic validity of the DSM-IIIR criteria for major depression in this medically-ill outpatient sample.     

Atypical symptoms in hospitalised patients with major depressive episode: frequency, clinical characteristics, and internal validity

OBJECTIVE: The objective was (1) to assess the frequency of atypical depression (AD) in depressed inpatients; (2) to compare clinical features of patients with atypical and nonatypical depression (Non-AD) (3) to evaluate the meaning of single psychopathological symptoms with special respect to mood reactivity. METHOD: Diagnoses of 1073 inpatients were assessed according to DSM-IV using SCID (Structured Clinical Interview for the DSM-IV) and AMDP (Association for Methodology and Documentation). Diagnosis of atypical depression was defined according to criteria of the DSM-IV specifier for AD. All patients were rated using HAMD-21 (Hamilton Depression Scale). RESULTS: A high percentage of patients met criteria for AD (15.3%, 95% CI 13.0-17.9%). Women were more likely to suffer from AD (OR=1.54, p=0.037). There were no significant differences between AD and Non-AD patients regarding age, HAMD total baseline score, and diagnosis of any bipolar illness. In terms of psychopathology patients with AD were significantly more likely to suffer from somatic anxiety, somatic symptoms, guilt, genital symptoms, depersonalisation and suspiciousness as defined by HAMD-21 items. Interestingly, mood reactivity was not found to be significantly associated with the presence of two or more additional symptoms of AD. LIMITATIONS: Results were assessed by a post-hoc analysis, based on prospectively collected data. Compared to other inpatient samples with MDE, prevalence of bipolar disorder was rather low. CONCLUSION: (1) Frequency of AD may be underestimated, especially in inpatient samples. Further studies of inpatient samples are recommended. (2) Quality of distinct anxiety symptoms may be different in both groups, with AD patients being more likely to suffer from somatic symptoms and somatic anxiety. The presence of suspiciousness and even paranoid phenomena may not exclude a diagnosis of AD, but may be related to rejection sensitivity. (3) The mandatory presence of mood reactivity for the diagnosis of AD needs further consideration, regarding its validity for the concept.     

Somatic mutations activating Wiskott–Aldrich syndrome protein concomitant with RAS pathway mutations in juvenile myelomonocytic leukemia patients

The WAS gene product is expressed exclusively in the cytoplasm of hematopoietic cells and constitutional genetic abrogation of WASP leads to Wiskott–Aldrich syndrome (WAS). Moreover, mutational activation of WASP has been associated with X‐linked neutropenia. Although studies reported that patients with constitutional WAS mutations affecting functional WASP expression may present juvenile myelomonocytic leukemia (JMML)‐like features, confounding differential diagnosis above all in the copresence of mutated RAS, an activating somatic mutation of WASP has not been previously described in JMML patients. In our ongoing studies on JMML genomics, we at first detected a somatic WAS mutation in a major clone found at two consecutive relapses in one of two twins with JMML. Both twins were treated with hematopoietic stem cell transplantation after diagnosis of JMML. The somatic WAS mutation detected here displayed an activating WASP phenotype. Screening of 46 sporadic JMML patients at disease onset for mutations in the same PBD domain of WAS revealed two additional singleton patients carrying minor mutated clones. This is the first study to associate somatically acquired WASP mutations with a hematopoietic malignancy and increases insight in the complexity of the genomic landscape of JMML that shows low recurrent mutations concomitant with general hyperactivation of RAS pathway signaling.     

Anxiety in family practice

The time course of patient initiated visits, somatic, functional, and other medical complaints was studied in a group of 58 patients from a family practice who had been diagnosed and treated for anxiety. The findings were contrasted with two other groups of patients from the same practice: 101 depressives and 101 controls. Results indicate that the anxiety patients differed markedly from the depressives in having a very short-lived episode of anxiety or somatic complaints in contrast to depressives' much longer history of somatic and functional complaints which appeared to precede by months the diagnosis of depression. The findings suggest that the anxiety patients in this practice either had a qualitatively different condition from the depressives, or possibly suffered from a short-lived and unrecognized depression.     

Anxiety, depression, and somatization in DSM-III hypochondriasis

To assess the severity of distress and of somatization in hypochondriasis, the authors administered several validated self-rating scales of depression, anxiety, somatic symptoms, and anger/hostility to 21 psychiatric outpatients with the DSM-III diagnosis of hypochondriasis and to matched groups of other nonpsychotic psychiatric patients, family practice patients, and employees. Anxiety and somatic symptoms were highest in hypochondriacal patients; depression and anger/hostility did not differ from those of other psychiatric patients but were higher than in the other groups. The findings do not support the theory that hypochondriasis is a defense against anxiety or that it is a masked depression or depressive equivalent. The findings are consistent with the view that the interaction of severe anxiety and severe somatic symptoms is a common feature of the psychopathology of hypochondriasis.     

Biochemical abnormalities in psychiatric outpatients

This research project was an outgrowth of the observations of the senior author over a period exceeding four decades of practice, teaching, and research as internist and psychiatrist, with primary emphasis on relationships between psyche and soma. Patients at the Outpatient Psychiatric Clinic of the Howard University Hospital, Washington, DC, were given thorough annual physical examinations and laboratory evaluations of blood and urine. The authors found a significantly high incidence of medical illnesses and abnormal laboratory findings not previously suspected. There was a significant and direct correlation between psychopathology as projected in the Lipman Personality Image Projection (LPIP) test and abnormal laboratory and physical findings. The results in this study concur with previous reports that so-called purely psychogenic stress symptoms may be related to unrecognized medical illnesses. These somatic illnesses may remain unrecognized for indefinite periods of time in the traditional psychiatric outpatient setting from which patients are often referred elsewhere for treatment of nonpsychiatric illness. Initial and periodic physical and laboratory examinations should be performed by psychiatrists trained to recognize nonpsychiatric diseases that often present with psychiatric symptoms. A thorough knowledge of the mind-body relationship is essential to the practice of modern psychiatry.     

Age related shift in the mutation spectra of germline and somatic NF2 mutations: hypothetical role of DNA repair mechanisms

It has been suggested that somatic mutations that accumulate due to an age related decline in the efficiency of DNA repair mechanisms might contribute to the increased incidence of cancer in older people. However, there is little direct evidence for this phenomenon. The spectra of germline and somatic mutations can be compared in cancer genes that cause inherited tumour syndromes and sporadic tumours, respectively. In addition, mosaic patients reflect the nature of mutations that occur in early development. Hence, we hypothesised that the "temporal mutation record" of a human cancer gene might provide insight into mechanisms of mutagenesis in the germline, in early development, and in adulthood. We compared the ratio of frameshift to nonsense mutations in three diseases that are related to the NF2 tumour suppressor gene: classic neurofibromatosis 2 (NF2), caused by germline NF2 mutations; mosaic NF2; and unilateral sporadic vestibular schwannoma (USVS), caused by somatic NF2 inactivation. Nonsense mutations predominated in both classic and mosaic NF2, but the ratio of nonsense to frameshift mutations was reversed in USVS. Moreover, in USVS patients, the ratio of somatic frameshift to nonsense mutations increased significantly with increasing age at diagnosis. This pattern is consistent with an age related decline in the efficiency of DNA repair mechanisms. Similar studies for other familial cancer genes may provide further evidence for this hypothesis.     

抑郁症的躯体症状

目的对伴躯体症状的抑郁症进行概要的介绍与评述。方法利用文献综述法,整合国内外相关研究,对伴躯体症状的抑郁症相关内容进行总结归纳。结果概述了伴躯体症状的抑郁症的发病率,病理机制、抑郁症和躯体症状的关系及伴躯体症状的抑郁症诊断、治疗、预后。结论全面掌握伴躯体症状的抑郁症将有助于疾病的早期治疗,降低误诊率,避免医疗资源浪费,减轻患者的心理及经济压力,尽快恢复社会功能。