Testing genetic models for multiple symptoms: An application to the genetic analysis of liability to depression

A model is presented which allows for the contribution of genes and environment to categorical data on multiple symptoms. The model distinguishes between parameters needed to express the relationship between a latent trait and observed responses and the parameters required to represent the causes of variation in the latent trait. The regression of the latent trait on covariates may also be specified. The model is applied to symptoms of depression in 1983 pairs of adult female monozygotic and dizygotic twins. A model which allows only for polygenic variation in the latent trait is supported as well as the mixed model, which also allows for the effects of a major gene. The likelihood is significantly lower when all genetic effects are ascribed to a single gene. Practical limitations of the method are discussed.This research is supported by Grants AG04954, AA06781, GM32782, GM30250, and MH40828 from the National Institutes of Health. We are indebted to Dr. Greg Carey for his incisive discussion.     

Behavioral treatment parameters with primary dysmenorrhea

Fourteen women with primary dysmenorrhea were administered four sessions of systematic desensitization (SD) by either a male or a female therapist. The following measures were taken during the flow periods before and after treatment and at a 6-month follow-up: menstrual symptom checklist, medication usage, invalid hours, and menstrual attitudes. At pretreatment, menstrually distressed women had significantly higher scores on all measures compared to a normative group and an explicitly nondistressed group. At posttreatment, treated women's scores on the dependent variables were significantly reduced. All indices were reduced to a nondistressed level at posttreatment and at 6-month follow-up. Type of dysmenorrhea (congestive vs. spasmodic), trait anxiety level, and therapist sex did not predict differential responsiveness to SD. SD did not affect frontalis EMG, peripheral blood flow, or pain threshold. A Retrospective Symptom Scale of menstrual distress was found to be highly reliable, valid, and sensitive.     

Neurobehavioral phenotype in carriers of the fragile X premutation

There have been contradictory findings in the fragile X (fraX) literature about possible neurocognitive and psychological symptoms due to the fraX premutation (pM). The purpose of the present study was to investigate the relationship between CGG repeat length and neurobehavioral functioning in carriers of the fraX pM. Eighty‐five female carriers of the pM with allele sizes ranging from 59–166 were administered a comprehensive IQ test (WAIS‐III) and completed a questionnaire designed to measure psychopathology (Symptom Checklist (SCL)‐90‐R). No relationship between allele size and cognition was identified. A significant negative relationship between allele size and age was found, as well as a positive relationship between allele size and depression. Follow‐up analyses separating small and large allele sizes (below and above 100 CGG repeats) indicated that individuals with larger allele sizes scored significantly higher on the Interpersonal Sensitivity and Depression subscales of the SCL‐90‐R. Despite the limitation of few individuals with high CGG repeat lengths, our findings suggest that females with larger premutated alleles (≥ 100 repeats) display some clinical manifestations of fraX syndrome. © 2001 Wiley‐Liss, Inc.     

Posttraumatic stress disorder (PTSD) and posttraumatic stress symptoms (PTSS) in families of adolescent childhood cancer survivors

OBJECTIVE: To describe rates and concordance of posttraumatic stress disorder (PTSD) and posttraumatic stress symptoms (PTSS) in adolescent childhood cancer survivors and their mothers and fathers. METHOD: Participants were 150 adolescent survivors of childhood cancer, 146 mothers, and 103 fathers who completed the Impact of Events Scale-Revised, the Posttraumatic Stress Disorder Reaction Index, and the PTSD module of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. RESULTS: PTSS are common in families of childhood cancer survivors. Parents reported more symptomatology than former patients. Mothers and fathers had relatively equal rates of current PTSD and levels of PTSS. Nearly 30% of mothers met diagnostic criteria since their child's diagnosis, with 13.7% currently experiencing PTSD. Nearly 20% of families had at least one parent with current PTSD. Ninety-nine percent of the sample had at least one family member reexperiencing symptoms. CONCLUSIONS: Both PTSD and PTSS help in understanding the experience of adolescent cancer survivors and their families. Within families of childhood cancer survivors, it is likely that some member may be experiencing treatable bothersome memories, arousal, or avoidance specific to the cancer experience.     

Histomorphometry of bone marrow biopsies in primary osteomyelofibrosis/-sclerosis (agnogenic myeloid metaplasia) - correlations between clinical and morphological features

Summary Histomorphometry was performed on representative trephine biopsies of the bone marrow on admission of 50 patients (21 male, 29 female-age 67 years) with so-called primary osteomyelofibrosis/-sclerosis (OMF) not preceded by any other subtype of chronic myeloproliferative disorders. This study was firstly aimed at testing correlations between histological features (amount of haematopoiesis, cytological aspects of mega-karyocytes, density of reticulin and collagen fibres and degree of osteosclerosis) and laboratory data, as well as spleen size and duration of relevant prediagnostic symptoms. Secondly, we concentrated on a discrimination of OMF patients into two sub-groups according to bone marrow morphology and clinical variables. Statistical evaluation of histomorphometric variables and haematological findings disclosed that there was a progressive fibro-osteosclerotic process in the evolution of disease features. Increase in medullary fibrosis was significantly paralleled by an abnormal or pleomorphic megakaryopoiesis in the bone marrow: there was an increase in irregularity of perimeters for megakaryocytes and naked nuclei combined with smaller sizes of these elements including the nuclei. Additionally, there was a greater number of pycnotic bare nuclei. A number of morphometric features (density of fibres, degree of osteosclerosis, amount of haematopoiesis) were associated with corresponding clinical data (spleen size, length of preclinical history). By consideration of a set of basic histomorphometric variables our co-hort of 50 patients could be divided into an early hyperplastic subtype with no or minimal medullary reticulin and another group with conspicuous fibrotic and osteosclerotic alterations of the bone marrow. It was noticeable that we found no significant correlation between amount of haematopoiesis or marrow cellularity with splenomegaly. This result suggests that splenic haematopoiesis (myeloid metaplasia) may represent an autonomous or neoplastic process and not only compensation for a failing fibro-osteosclerotic bone marrow.Supported by a grant from the Deutsche Forschungsgemeinschaft (DFG-Th 390/1-1)     

Adjunct effect of loratadine in the treatment of acute sinusitis in patients with allergic rhinitis

H₁-blockers are often added to the standard treatment of acute sinusitis, but this is not supported by a controlled study. A multicentric, randomized, double-blind, placebo-controlled, parallel-group study was done in 139 allergic patients (15–65 years) to assess the adjunct efficacy of loratadine in acute exacerbation of rhinosinusitis. Sinusitis was diagnosed by symptoms and confirmed by rhinoscopy and sinus radiograph. Allergy was characterized by skin tests, RAST, and history. Patients were treated with antibiotics (14 days), oral corticosteroids (10 days), and loratadine (10 mg OD) or placebo (28 days). Treatment efficacy was assessed over 28 days by symptom scores quoted daily by patients. Physicians also rated total symptom scores at entry and at day 28. At entry, both groups had similar symptoms. Placebo-treated patients improved significantly, but patients who received loratadine had a significantly greater improvement in sneezing ( P =0.003) after 14 days, and in nasal obstruction ( P =0.002) after 28 days. Physicians found that patients receiving loratadine were significantly improved compared to placebo patients ( P =0. 0125). Loratadine in addition to standard therapy was found to improve the control of some symptoms of sinusitis.     

Association between nasal and bronchial symptoms in subjects with persistent allergic rhinitis

BACKGROUND: The association between nasal and bronchial symptoms, and the course of bronchial responsiveness and airway inflammation in house dust mite sensitive persistent rhinitis over a prolonged time period has not been thoroughly explored. OBJECTIVE: To determine if nasal symptoms were associated with bronchial symptoms in persistent rhinitic subjects, and to assess their bronchial responsiveness and airway inflammation in comparison to nonrhinitic, nonatopic controls. The additional impact of pollen sensitivity on the lower airways in rhinitic subjects was also addressed. METHODS: Rhinitics and controls answered telephone symptom questionnaires once every 2 weeks for 1 year. Every 3 months, exhaled nitric oxide (eNO) and bronchial responsiveness to histamine were measured. RESULTS: Thirty-seven rhinitics and 19 controls completed the study. High nasal symptom scores in rhinitic subjects were associated with bronchial symptoms (OR = 1.7, 95% CI 1.2-2.5). Bronchial hyper-responsiveness was present in 32.4% of rhinitic subjects on at least one clinical visit during the year. Pollen allergy caused seasonal variation in eNO (P = 0.03). CONCLUSION: In persistent rhinitic subjects, high nasal symptom scores were associated with bronchial symptoms, and many subjects experienced bronchial hyper-responsiveness during the year. Persistent rhinitic subjects were more at risk than healthy adults of bronchial symptoms and airway inflammation, which are likely risk factors for asthma.     

新兵训练后功能性闭经女兵的心身症状与激素水平

目的:探讨新人伍女兵功能性下丘脑性闭经(FHA)者与月经正常者激素水平及心理健康状况的差异。方法:在某部队新人伍女兵98人接受了为期近4个月的体能训练之后,有54人出现闭经.其中闭经3个月以上者有35人(研究组)。训练后月经正常、在采血时月经周期处于第5～11天者有26人(对照组)。分别测定她们血清中的促卵泡生成素(FSH)、黄体生成素(LH)、雌二醇(E_2)、孕酮(P)、泌乳素(PRL)、睾酮(T)、ACTH、T_3、T_4的水平,并用SCL-90分别评定她们的心理健康状况。结果:FHA 者血清FSH 值为4.96±1.73 mIU/ml,LH 值为2.63±1.78 mIU/ml,E_2的值为7.23±5.37 pg/ml,对照组血清相应值为10.73±2.30mIU/ml、12.31±2.15mIU/ml、41.67±6.13pg/ml,差异有统计学意义(P<0.01),闭经组低于对照组。FHA 组SCL-90的躯体化、人际敏感、抑郁、焦虑及其他因子分大于2的比率分别为:51.4%、42.9%、48.6%、51.4%及37.1%;而对照组这5项分值大于2的比率分别为15.4%、15.4%、19.2%、21.3%及11.5%,两组间这5个因子大于2的人数差异有统计学显著意义(P<0.05),闭经组高于对照组。结论:诊断为FHA 的女兵与月经正常女兵的激素水平有差异,闭经组心身症状的发生率也高于对照组。     

Current status of intranasal glucocorticosteroids in the management of allergic rhinitis

Glucocorticosteroids are the most effective drugs for controlling inflammation of allergic rhinitis (AR). Because of their strong pharmacological action, which can be a so-called 'double-edged sword', glucocorticosteroids are usually taken intranasally so as to reduce their potential for eliciting adverse effects. Accumulating evidence suggests that intranasal glucocorticosteroids control not only nasal symptoms but also ocular symptoms. In contrast to sedating H₁-receptor antagonists, intranasal glucocorticosteroids can improve impaired performance such as daytime sleepiness associated with AR. In Japanese cedar pollinosis, treatment begun immediately after initiation of pollen release or onset of initial symptoms, known as prophylactic (initial) treatment, is recommended. The current version of the practical guideline for management of allergic rhinitis in Japan recommends the use of chemical mediator release inhibitors, second-generation H₁-receptor antagonists, or leukotriene receptor antagonists for prophylactic treatment. However, recent evidence suggests that intranasal glucocorticosteroids might also be useful as first-line drugs for prophylactic treatment. The molecular mechanism of anti-inflammatory action of glucocorticosteroids supports this contention. Moreover, a meta-analysis of studies of intranasal glucocorticosteroids given as monotherapy has revealed that these agents are superior to oral H₁-receptor antagonists and leukotriene antagonists for controlling major symptoms of AR. These findings suggest that glucocorticosteroids, especially intranasal glucocorticosteroids, might be positioned as first-line drugs for the treatment of both perennial and seasonal AR.     

阿尔茨海默病、阿尔茨海默病混合型及血管性痴呆患者心理及行为症状的比较

目的 比较阿尔茨海默病(Alzheimer Disease，AD)、AD混合型痴呆(Mixed dementia，MD)、血管性痴呆(Vascular dementia，VD)心理和行为症状(Psychological and behavioral symptoms of dementia，PBSD)的特征。方法 AD、MD及VD患者各30名参加本研究。采用Alzheimer病行为症状评定量表(The Begavioral Pathlolgy in Alzheiner Disease Rating Scale，BEHAVE—AD)、Cohen—Masfield激惹性问卷(The Cohen Mansfield Agitation Inventory，CMAI)评定痴呆患者BPSD。结果 AD患者激惹、焦虑与恐惧发生率较高，VD患者无目的游荡发生率、严重程度较低，MD患者BPSD症状无特异性。结论 AD、VD患者BPSD症状有特异性，MD患者BPSD表现无特异性。