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PubMed2007

Clonality and prognostic implications of p53 and epidermal growth factor receptor somatic aberrations in multiple primary lung cancers.

PURPOSE: For treatment decision and prognostic applications, we evaluated p53/epidermal growth factor receptor (EGFR) somatic aberrations in multiple primary lung cancers to differentiate multifocal tumors from intrapulmonary metastasis. EXPERIMENTAL DESIGN: Fifty-eight multiple primary lung cancers of 1,037 patients in a 10-year period were identified to investigate somatic mutations and altered expression of p53 and EGFR for clonality assessment. Genomic DNA was extracted from microdissected cells of paraffin-embedded multiple primary lung cancer tissues. Overexpression and somatic mutations in exons of p53 (exons 5-8) and tyrosine kinase domain of EGFR (exons 18-22) were examined by immunohistochemical staining and DNA sequencing, respectively. RESULTS: High frequency of somatic mutations in p53 (33 of 58, 56.9%) and/or EGFR (44 of 58, 75.9%) resulted in high discrimination rate of tumor clonality (50 of 58, 86.2%) of multiple primary lung cancers. Twenty-two cases (37.9%) were assessed as having the same clonality and 28 cases (48.3%) were determined as having different clonality, which further supported the carcinogenic theory of field cancerization. Notably, the occurrence of lymph node metastasis was more commonly observed in tumors with the same clonality (P = 0.045) and was associated with poor patient 5-year survival rate (P = 0.001). However, no correlation was found between tumor clonality and patient survival (P = 0.630). The EGFR somatic aberrations in 58 multiple primary lung cancers, including vascular invasion associated with EGFR overexpression (P = 0.012) and mutation (P = 0.025), further suggested the potential benefits of target therapy of inoperable multiple primary lung cancers. CONCLUSIONS: Our results suggest that analysis of somatic alterations in p53 and EGFR can significantly improve the clonality assessment and impact management of multiple primary lung cancer patients.

DNA Mutational Analysis↗
PubMed2002

Chromatin reprogramming of male somatic cell-derived XIST and TSIX in ES hybrid cells.

In mammalian somatic cells, the X chromosome is active in XY males, whereas one X chromosome is inactivated in XX females. On the active male X chromosome, the XIST and TSIX genes are transcribed in undifferentiated cells of pre-implantation embryos (undifferentiated state) and then down-regulated upon cell differentiation (differentiated state). To explore the epigenetic mechanism involved in the on-off switching of XIST and TSIX transcription in the active X chromosome, male somatic cells were hybridized with male embryonic stem (ES) cells. Fluorescence in situ hybridization analysis revealed that the XIST gene derived from somatic cells was derepressed, as shown by the advent of two pinpoint signals. This was confirmed by strand-specific RT-PCR of XIST and TSIX genes. To analyze changes in chromatin structure in the promoter regions of XIST and TSIX derived from somatic cells, histone tail modifications were studied by chromatin immunoprecipitation analysis. Histones H3 and H4, which were hypoacetylated in the somatic cells, were hyperacetylated in the hybrid cells, and histone H3 lysine 4, which was hypomethylated in the somatic cells, was hypermethylated in the hybrid cells, indicating that the reactivation of XIST and TSIX was linked with chromatin modifications. In the telomeric region of DXPAS34, acetylation of histones H3 and H4 was dependent on reactivation of XIST and TSIX, whereas histone H3 lysine 4 was constitutively methylated independent of the transcriptional activity of those genes. We propose that the chromatin reprogramming is linked with the resetting of the memory found in the process of choosing an active X chromosome.

Animals↗
PubMedDate not supplied

Do somatic complaints predict subsequent symptoms of depression?

BACKGROUND: Evidence suggests substantial comorbidity between symptoms of somatization and depression in clinical as well as nonclinical populations. However, as most existing research has been retrospective or cross-sectional in design, very little is known about the specific nature of this relationship. In particular, it is unclear whether somatic complaints may heighten the risk for the subsequent development of depressive symptoms. METHODS: We report findings on the link between symptoms of somatization (assessed using the SCL-90-R) and depression 5 years later (assessed using the CES-D) in an initially healthy cohort of community adults, based on prospective data from the RENO Diet-Heart Study. RESULTS: Gender-stratified multiple regression analyses revealed that baseline CES-D scores were the best predictors of subsequent depressive symptoms for men and women. Baseline scores on the SCL-90-R somatization subscale significantly predicted subsequent self-reported symptoms of depressed mood 5 years later, but only in women. However, somatic complaints were a somewhat less powerful predictor than income and age. CONCLUSIONS: Our findings suggest that somatic complaints may represent one, but not necessarily the most important, risk factor for the subsequent development of depressive symptoms in women in nonclinical populations. The results also highlight the importance of including social variables in studies on women's depression as well as conducting additional research to further examine predictors of depressive symptoms in men.

Adult↗
PubMed1986

In situ localization of human fibronectin (FN) genes to chromosome regions 2p14----p16, 2q34----q36, and 11q12.1----q13.5 in germ line cells, but to chromosome 2 sites only in somatic cells.

The locations of the genes for fibronectin (FN) on chromosomes of human germ line and somatic cells were determined by in situ molecular hybridization with two 3H-labeled DNA probes, one for the region encoding the cell attachment domain of human FN, the other for the 3' noncoding and part of the coding region. Pachytene chromosomes of two males and lymphocyte chromosomes of one of these males and a female were used. Two regions of hybridization on pachytene and somatic chromosome 2 (p14----p16 and q34----q36) were found, but not in all individuals. A third region of hybridization was found at 11q12.1----q13.5 in meiotic, but not with significant frequency in somatic chromosomes. It is not clear if these differences between meiotic and somatic chromosomes, and the large differences between individuals at some of the other hybridization sites, resulted solely from technical factors. The differences between the findings in meiotic and somatic preparations might be due to the presence of four strands in pachytene chromosomes versus only one per somatic chromatid. Individual differences in DNA sequences in the chromosome segment containing the gene, differences in gene locations among individuals, or between meiotic and mitotic chromosomes might account for the other findings. The results confirm some of the earlier studies with cell hybrids that mapped FN genes to chromosomes 2 or 11. The combined findings suggest that some of these loci may be coding for the plasma form of FN and others for the cellular form. The expression of the different FN types by differentiated cells might then depend on the loci that are activated.

Chromosome Banding↗
PubMed1979

Psychogenesis of somatic disorders. An overview.

Psychogenesis, considered as a linear sequential process by which psychological influences lead to somatic disturbances, is only a link in a larger bio-psycho-social interactional field. Therefore, in practice, a multilateral approach of the whole person, in his psychological, social and somatic aspects, in health and disease, in his habitual and his therapeutical contacts, should be stressed. it seems unlikely that the somatic symptoms we are confronted with can be considered as pure psychogenetically determined phenomena. This does not exclude that in the complex psychosomatic interaction, there exists at one or more stages a transition from the sphere of psychological functioning to the somatic area, ending up in somatic symptoms. This process, which we call psychogenesis, is not a single event but should be considered as an abstraction, grouping a number of component processes possibly occurring at different moments in the total system. We have distinguished four components: a psychopathological component, a psychophysiological component, a phychophysiological component, a physiopathological component and a 'somatic illness experience' component. For each of these components, a number of conceptions are proposed according to the different theoretical models of psychosomatic connections. Most of these formulations are largely hypothetical or based only on fragmentary observations. Still, they offer guidelines for further research.

Humans↗
PubMed1982

Alexithymia and somatization.

Although alexithymia was originally described in patients with classical psychosomatic illnesses, attempts to specifically correlate these illnesses with alexithymia have not been successful. Despite the prominent role of somatization in the clinical description of alexithymia, a specific correlation between alexithymia and somatization has not been established. Data are presented which suggest that alexithymia is significantly more prevalent in somatizers than in healthy subjects, or subjects with classical psychosomatic illness in the absence of somatization. Other findings suggest that alexithymia may be a widespread phenomenon not necessarily associated with somatization or other illness. In the absence of debilitating somatization alexithymia may be useful in facilitating task-oriented behavior over prolonged periods of time without distraction.

Awareness↗
PubMed1995

Correlates of somatic causal attributions in primary care patients with fatigue.

Researchers in the field of chronic fatigue in tertiary care found that patients' somatic (e.g. viral) explanations for their condition may lead to chronicity of symptoms. We studied the influence of a somatic attributional bias on outcome and reported symptoms in primary care patients with fatigue. We compared fatigue scores on a specific scale, and number of presented symptoms, in two groups of primary care patients with 'functional' fatigue: 75 with a high score on the somatic subscale of the Fatigue Attribution Scale (S-FAS), and 95 with a low score on the S-FAS. At the index visit, patients with low and high scores on the S-FAS were not different for age, sex, fatigue scores, and levels of depressive symptoms. Patients with high scores on the S-FAS presented significantly more somatic and psychological symptoms-a total of 36 symptoms for 24 patients (25.3%) in the low-score group, and a total of 52 symptoms for 31 patients (41.3%) in the high-score group. Forty-two days later, at the follow-up visit, the fatigue scores were similar in both groups. In primary care patients with fatigue not due to somatic illness or major depression, the tendency to attribute fatigue to somatic causes is not associated with a worse outcome, but with a higher number of reported symptoms.

Adult↗
PubMed1997

Somatic complaints associated with depressive symptoms in HIV-positive patients.

BACKGROUND: Although several studies have indicated the association of mood states including depression with somatic complaints in HIV patients, there has been no report on Japanese HIV patients. The purpose was to examine the relationship between somatic complaints and mood states in HIV patients without AIDS. METHODS: Subjects were 50 HIV patients without AIDS. As controls, we used 47 healthy persons without HIV, matched for age and gender of the subjects. After the Structured Clinical Interview for the DSM-III-R, several inventories including the Profile of Mood States (POMS) were administered. The presence or absence of somatic complaints were examined. RESULTS: No patients fulfilled the criteria for the DSM-III-R Mood Disorders Including Major Depression. However, scores on depression as measured by the POMS were significantly higher for the HIV group than for the healthy group. Although depressive symptoms in the HIV group may not be strong enough to warrant a psychiatric diagnosis of mood disorders, these HIV patients may be prone to a depressive state. The HIV patients indicated somatic complaints more frequently. Among these, the presence or absence of five complaints (i.e., abdominal distress, sleep disturbance, smothering sensations, chest pain or discomfort, and numbness or chills) was significantly discriminated based on scores on depression. DISCUSSION: The results suggest that depressive symptoms accompany several somatic complaints in HIV patients without AIDS. Although a longitudinal follow-up study is required, the assessments of somatic symptoms may bring clinical benefits such as earlier diagnosis and/or intervention for a depressive state.

Adaptation, Psychological↗
PubMed1997

Somatization in cross-cultural perspective: a World Health Organization study in primary care.

OBJECTIVE: The purpose of this study was to examine the phenomenon of somatization in different cultures by determining its frequency and correlates in primary care settings in 14 countries. METHOD: Consecutive primary care patients (N = 25,916) were screened with the 12-item General Health questionnaire, and a stratified sample (N = 5,438) was interviewed with the Composite International Diagnostic Interview. Interviewed patients were also assessed for physical disease burden, self-rated overall health, physician-rated physical health status, number of disability days, and interviewer-rated occupational role functioning. The authors determined center-specific associations with the use of logistic regression analyses in which confounding variables were controlled. RESULTS: ICD-10 defined somatization disorder was relatively uncommon in most primary care settings. A less restrictively defined form was more common. Symptom rates were much higher in South American sites. There was a modest association with low education. Otherwise, frequency of unexplained somatic symptoms did not clearly vary according to geography or level of economic development. Somatizing patients were at elevated risk for self-reported disease burden, negative perception of their health, and comorbid depression and generalized anxiety disorder. Somatization was also commonly associated with disability. Cultures did not differ markedly in the pattern of these associated features. CONCLUSION: Somatization is a common problem in primary care across cultures and is associated with significant problems and disability.

Absenteeism↗
PubMed1999

Gender difference in the prevalence of clinical depression: the role played by depression associated with somatic symptoms.

OBJECTIVE: This study tested the hypothesis that female subjects may exhibit a higher prevalence than male subjects of depression associated with somatic symptoms but not a higher prevalence of depression not associated with these other symptoms. METHOD: The author reanalyzed research interview data on major depression from the National Comorbidity Survey, dividing respondents into those who met overall criteria for major depression and exhibited fatigue and appetite and sleep disturbance ("somatic depression") and those who met overall criteria but did not exhibit these somatic criteria ("pure depression"). RESULTS: Female subjects exhibited a higher prevalence than male subjects of somatic depression but not a higher prevalence of pure depression. Somatic depression was associated with a high prevalence of anxiety disorder and, among female subjects, with body aches and onset of depression during early adolescence. CONCLUSIONS: The gender difference in depression may result from a difference in a specific subtype of anxious somatic depression.

Adolescent↗
PubMed2002

Gender differences in the prevalence of somatic versus pure depression: a replication.

OBJECTIVE: Using data from the Epidemiologic Catchment Area (ECA) study, the author attempted to replicate the finding of the National Comorbidity Survey that the prevalence of depression associated with somatic symptoms was much higher among women than men. METHOD: The author reanalyzed data from the ECA study. He divided respondents into those who met criteria for major depression and exhibited appetite and sleep disturbances and fatigue (somatic depression) and those who met depression criteria but did not exhibit all of these somatic criteria (pure depression). RESULTS: The reanalysis revealed that the prevalence of somatic depression but not pure depression was much higher among women than men. Somatic depression was associated with high rates of pain; among women, it was associated with high rates of anxiety disorders and chronic dysphoria. CONCLUSIONS: The gender difference in depression may result from a difference in a specific type of depression-anxious somatic depression.

Adult↗
PubMed2003

A 20-year longitudinal observational study of somatic antidepressant treatment effectiveness.

OBJECTIVE: This observational study examined the effectiveness of somatic antidepressant treatments as administered in the community. METHOD: The study group consisted of 285 subjects with an intake diagnosis of major depressive disorder who had entered the National Institute of Mental Health Collaborative Depression Study as early as 1978, had at least one additional affective episode, and had been followed for up to 20 years, as recently as 1999. The characteristics that distinguished subjects receiving various levels of somatic antidepressant treatment were accounted for in what was called a propensity for treatment intensity model. The effectiveness of somatic antidepressant treatment during major affective episodes was then examined. RESULTS: Those who received higher levels of antidepressant treatment tended to have more prior episodes, more severe depressive symptoms, and more intensive somatic therapy during prior episodes and prior well intervals than those who received lower levels. Treatment effectiveness analyses that were stratified by propensity for treatment intensity demonstrated that those who received higher levels of antidepressant treatment were significantly more likely to recover from affective episodes. In contrast, those treated with lower levels were no more likely to recover than those who did not receive somatic treatment. CONCLUSIONS: Despite the indications of more severe depressive illness, those who received higher levels of somatic antidepressant treatment were more likely to recover from recurrent affective episodes. Results from this observational study extend the generalizability of reports from randomized clinical trials of antidepressants to a wider, more representative group of individuals who suffer from major depression.

Adult↗
PubMed2006

Symptom dimensions of depression following myocardial infarction and their relationship with somatic health status and cardiovascular prognosis.

OBJECTIVE: The reporting of depressive symptoms following myocardial infarction may be confounded by complaints originating from the myocardial infarction. Therefore, it is difficult to estimate the effects of post-myocardial infarction depression and its treatment on cardiovascular prognosis. The authors' goal was to study the relationship between depressive symptom dimensions following myocardial infarction and both somatic health status and prospective cardiovascular prognosis. METHOD: In two studies of myocardial infarction patients (N=494 and 1,972), the Beck Depression Inventory was used to determine the dimensional structure of depressive symptoms following myocardial infarction. Three symptom dimensions-somatic/affective, cognitive/affective, and appetitive-were compared with baseline left ventricular ejection fraction, Charlson comorbidity index, Killip class, and previous myocardial infarction. The relationship between depressive symptom dimensions and prospective cardiovascular mortality and cardiac-related readmissions was also examined (mean follow-up duration=2.5 years). RESULTS: Somatic/affective symptoms were associated with poor health status (left ventricular ejection fraction, Charlson comorbidity index, Killip class, and previous myocardial infarction) and predicted cardiovascular mortality and cardiac events. Cognitive/affective symptoms were only marginally associated with somatic health status and not with cardiovascular death and cardiac events. Appetitive symptoms were related to somatic health status but did not predict cardiovascular death or cardiac events. CONCLUSIONS: Somatic/affective depressive symptoms following myocardial infarction were confounded by somatic health status yet were prospectively associated with cardiac prognosis even after somatic health status was controlled. Cognitive/affective depressive symptoms were only marginally related to health status and not to cardiac prognosis. These findings suggest that treatment of depression following myocardial infarction might improve cardiovascular prognosis when it reduces somatic/affective symptoms.

Cause of Death↗
PubMedDate not supplied

Correlation between somatic sensation inventory scores and hyperarousal scale scores.

Somatization mechanisms are poorly understood. The authors tested whether somatization might involve altered central nervous system information processing. They measured somatization using the Somatization Sensation Inventory (SSI) and information processing style using the Hyperarousal Scale, scores of which correlate with electroencephalogram(EEG) measures of cortical electrical responsiveness. SSI scores correlated highly with Hyperarousal scores. On logistic regression, two SSI items and two Hyperarousal items accounted for most of this correlation. These specific hyperarousal items had previously been found to covary with EEG activity and cortical evoked potential amplitudes. The authors concluded that somatization may involve altered CNS processing of somatic stimuli.

Adult↗
PubMedDate not supplied

Identifying somatization disorder in a population-based health examination survey: psychosocial burden and gender differences.

Despite its enormous medical burden, little is known about the epidemiology of somatization in the community. The present study screened a representative population-based survey of 7,466 subjects in the age range of 25 to 69 years for the occurrence of somatization. A total of 137 (1.84%) individuals experienced six or more symptoms from at least two different body sites without an identifiable organic cause. These patients exhibited a lower quality of life (P < or = 0.0001) and suffered from higher levels of emotional stress (P < or = 0.0001) than their counterparts in the healthy subsample (n=906). Somatization was not associated with a medical diagnosis, but disability days, the use of medical services, and the level of medication was higher in the somatization disorder group (P < or = 0.004). The somatization risk was only 1.6-fold higher for women in comparison to men but escalated for women rapidly to an approximately 4-fold risk when being female was combined with low social class and high emotional distress. Against expectation, the somatization risk for men also mounted 3-fold under the identical risk constellation.

Adult↗
PubMed1989

Somatic symptoms among older Soviet immigrants: an exploratory study.

This exploratory study investigates the overlap of somatization and depressive symptoms among older Jewish-Soviet immigrants to the United States. It has been suggested that this group has depression often masked by somatic complaints. In order to test this hypothesis fifty-five respondents completed the Symptom Checklist 90, PERI Demoralization Scale and the Social Support Network Inventory. The somatization subscale was found to be significantly higher among older Soviet immigrants than in a depressed group, yet the depression subscale was significantly lower. Compared to a group of normal controls both the depression and somatization subscales were significantly elevated. Somatization, depression, and demoralization were elevated in Soviet immigrants. The results of this study are discussed in the context of the available literature on cross-cultural psychiatry and somatization. The clinical relevance of these findings is highlighted.

Acculturation↗
PubMed1992

[Use of the Adinfer diagnostic system in a study of somatic disorders in general practice].

Somatic complaints are very common in general medical practice. They are not identified as psychic disorders and are treated symptomatically. We explore two kind of problems: 1. methodological problems such as the instruments to use to examine somatic complaints (it is evident that a checklist does not give the best results with suggestible patients); and 2. the relationships between somatic complaints and psychic disorders such as anxiety, depression and somatoform disorders. Psychiatric nosology is by no means clear and includes many diagnoses from "hysteria" to "hypochondria" or "psychosomatic", "somatization". In this study, we compare the symptoms collected by general practitioners, and their clinical diagnoses to those obtained by an automatic DSM-III diagnostic program. Adinfer was modified so that three DSM decision trees were systematically scanned: depressive, anxiety and somatoform disorders. This allows for an epidemiological study of somatic complaints and their relationship to depression and anxiety. The subjects' score on rating scales for anxiety and depression are compared with the diagnoses made by the expert system. We discuss the significance of somatic symptoms, the DSM classes and the value of expert systems in epidemiological studies.

Adult↗
PubMed1994

[Prediction of somatization disorders in pre-pubertal girls].

Several studies of female adult populations suggest that somatization problems appear during adolescence and that they are related to behavioural problems during childhood. This study uses Cloninger's personality model to verify the link between personality traits and the beginning of somatization problems in elementary school girls. This model is based on the interaction of three dimensions: novelty seeking, harm avoidance and social reward dependence. Subjects were part of a longitudinal study of the social adjustment of children from Montreal and Val d'Or families. Evaluations of the girls' behaviour in kindergarten were used to establish personality types according to Cloninger's model. The somatization problems were assessed at age ten following interviews with mothers and girls, and ratings by mothers and teachers. The results showed that somatization problems at age ten were more likely when novelty seeking and harm avoidance were high in kindergarten. The kindergarten girls with 'passive-aggressive' or 'explosive-schizoid' personality profiles were more at risk of higher levels of somatization problems at age ten. However, Cloninger's hypothesized link between high levels of somatization problems and the 'histrionic' personality profile was not confirmed.

Adolescent↗