Study Of First-degree Relatives Research Articles

Mismatch negativity amplitude in first-degree relatives of individuals with psychotic disorders: Links with cognition and schizotypy

Mismatch negativity (MMN) amplitude is reliably reduced in psychotic disorders. While several studies have examined this effect in first-degree relatives of individuals with schizophrenia, few have sought to quantify deficits in relatives of individuals with other psychotic disorders. While some conclude that, compared to healthy subjects, first-degree relatives of schizophrenia show reduced MMN, others contradict this finding. Furthermore, though MMN is often shown to be associated with cognitive impairments and clinical symptoms in psychotic disorders, to our knowledge no studies have sought to fully examine these relationships in studies of first-degree relatives. The present study sought to clarify the extent of MMN amplitude reductions in a large sample of siblings of individuals with diverse psychotic disorders (n = 67), compared to probands with psychosis (n = 221) and never psychotic comparison subjects (n = 251). We further examined associations of MMN amplitude with cognition and schizotypal symptoms across these groups. We found that MMN amplitude was intact in siblings compared to probands. MMN amplitude was associated with cognition and schizotypal symptoms dimensionally across levels of familial risk. The present results imply that MMN reductions do not reflect genetic risk for psychotic disorders per se, and instead emerge as a result of, or in conjunction with, clinical features associated with psychosis. Such findings carry important implications for the utility of MMN amplitude as an indicator of inherited risk, and suggest that this component may be best conceptualized as an endophenotype for clinical symptoms and cognitive impairments, rather than risk for psychosis per se.

Brain areas associated with resilience to depression in high-risk young women.

Previous structural brain-imaging studies in first-degree relatives of depressed patients showed alterations that are generally accepted as vulnerability markers for depression. However, only half of the relatives had depression at follow-up, while the other half did not. The aim of this study was to identify the brain areas associated with resilience to depression in high-risk subjects with familial depression. We recruited 59 young women with a history of depressed mothers. Twenty-nine of them (high-risk group [HRG]) had no depression history, while 30 (depressive group) had at least 1 depressive episode in adolescence. The brain structures of the groups were compared through voxel-based morphometry and analysis of cortical thickness. Individual amygdala nuclei and hippocampal subfield volumes were measured. The analysis showed larger amygdala volume, thicker subcallosal cortex and bilateral insula in the women in the HRG compared with those in the depressive group. In addition, we detected more gray matter in the left temporal pole in the HRG. The larger gray matter volume and increased cortical thickness in the key hub regions of the salience network (amygdala and insula) and structurally connected regions in the limbic network (subcallosal area and temporal pole) might prevent women in the HRG from converting to depression.

Prevalence of glaucoma in first-degree relatives of patients with primary open-angle glaucoma and normal-tension glaucoma

Objective: To determine the prevalence of glaucoma in first-degree relatives of patients with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG).
 Methods: Observational study of first-degree relatives of patients with POAG and NTG who were screened for glaucoma.
 Results: A total of 66 first-degree relatives of patients with glaucoma (POAG/NTG) were included in the study. We found a prevalence rate of 16.6%: 13.6% were diagnosed to have the disease and 3% were newly detected to have glaucoma during the study. We found that although 66.7% of the subjects were aware of the family history of glaucoma, only 36.4% were aware that they were at increased risk of developing glaucoma.
 Conclusion: In our study, we found high prevalence of glaucoma in first-degree relatives of patients with glaucoma. This highlights the importance of selective screening of high-risk groups such as first-degree relatives of patients with POAG/NTG.

Prevalence of hypertension amongst spouses in urban area of Nagpur city, Maharashtra, India

Background: Students of human biology share an interest in studies of family clusters of heart disease and its antecedents. The recent inclusion of husband and wife pairs (spouse pairs) has added a new dimension to earlier studies of first degree relatives. Blood pressure is influenced by environmental factors operating within genetic limits. Since married couples share a similar environment, the study can identify environmental factors. This study was done to find out prevalence and control of hypertension among spouses in urban area of Nagpur.Methods: This was a community based cross sectional study conducted in urban area of Nagpur city. 260 couples in whom both husband and wife were of age 30 or more were included. Blood pressure was measured and classified as per WHO guidelines.Results: Prevalence of hypertension was found to be 51.9% among husbands and 40.8% among wives. 57.8% husbands and 50.9% wives were unaware of their hypertensive status. Among those who were aware, 35.1% husbands and 15.4% wives had their blood pressure.Conclusions: The observation suggests need for targeting married couples as a unit of intervention for hypertension awareness and control. This study also emphasizes the need to increase the knowledge of current guidelines for detection and treatment of hypertension among physicians.

Opportunistic Screening for Glaucoma Amongst Glaucoma Patients’ First Degree Relatives who Accompanied them to Glaucoma Clinic

Aim: To identify people with glaucoma and glaucoma suspect amongst first degree relatives accompanying their glaucoma patient relatives to the Glaucoma Clinic, University of Port Harcourt Teaching Hospital, Port Harcourt. Materials and Methods: It was a prospective population-based study of first-degree relatives of Primary open-angle glaucoma patients who accompanied them to the glaucoma clinic. All participating individuals underwent comprehensive eye examination including vision screening, refraction, slit lamp biomicroscopy, applanation tonometry, gonioscopy and dilated fundus examination. Persons with definite and suspected glaucoma were subjected to threshold standard automated perimetry. Results: A total of 95 individuals who were first-degree relatives of 41 patients with Primary open angle glaucoma were examined. Fifty-seven of them (60%) were males, and 38 (40%) were females, with a mean age of 37.71± 8.15 years. Eighty-three (87.37%) were offspring and 12 (12.63%) siblings. Eighteen (18.9%) were observed to have definite Primary open angle glaucoma; 7 (7.4%) of them had been previously diagnosed. Another 16 (16.8%) of the relatives were found to be Glaucoma suspect. Twelve (66.7%) of those with glaucoma were males while 6 (33.3%) were females;13 (72.2%) were offspring while 5 (27.8%) were siblings. Prevalence of primary open angle glaucoma was 13.7% for offspring and 5.3% for siblings. Conclusion: Prevalence of primary open angle glaucoma amongst first degree relatives of glaucoma patients is higher than the general population. Targeted screening of at-risk group will help in early detection and treatment.

4 Value of contrast-enhanced cardiovascular magnetic resonance (CMR) in detection of additional abnormalities in family memebers of sudden cardiac death due to cardiomyopathy

Introduction/background The prevalence of Sudden Cardiac Death (SCD) in the Irish people aged 15–35 years is estimated at 2.68 per 100,000/yr. Over 1/3 of SCD deaths are attributed to cardiomyopathies which are frequently inherited in an autosomal dominant pattern, meaning 1st degree relatives have a 50% chance of being affected. Population screening for these conditions is challenging due to low prevalence, genetic heterogeneity and variable penetrance, along with insensitive diagnostic tools. Conventional echocardiography is an accepted tool in screening, however sensitivity varies considerably. Gadolinium contrast cardiac MRI (gCMR) in this population has not previously been evaluated. Hypotheses The addition of gCMR as standard evaluation of 1st degree relatives of SCD victims will aid in identification of affected relatives at an earlier stage and improve our ability to prevent further deaths. Methods This is a single center observational study of first degree relatives of SCD victims due to Cardiomyopathy. Assessment compromised a history, family pedigree, electrocardiogram (ECG), ambulatory ECG monitoring (Holter), exercise testing (EST), 2-Dimensional Echocardiogram (ECHO), signal average ECG (SAECG), and gCMR. All results interpreted by experienced physicians, and where necessary expert opinion from relevant specialities was sought. Patients were excluded from the study if they were aged below 16 years, pregnant or breastfeeding, or had renal impairment GFR Results 102 individuals were included. 41 had abnormal gCMR (A-gCMR). Of these 54% had only structural abnormalities and almost 1/3 had structural abnormality with fibrosis as demonstrated by late gadolinium enhancement (LGE). 6 individuals had fibrosis only – ie no other structural findings. CMR and ECHO agreed on 68% of results. gCMR changed the diagnosis completely in 30 individuals. gCMR identified a new diagnosis in 14% of individuals whose ECHO was reported as being normal. 38% of these new diagnoses were based on the identification of LGE. gCMR was normal in 17% whose ECHO was reported to be abnormal (false positive ECHO) with most common issue being over-diagnosis of diastolic dysfunction. A-gCMR positively correlated with abnormalities on the other non-imaging investigations compared with A-ECHO (an additional 14% had abnormal ECG and 7% had abnormalities on all 3 of ECG, EST and Holter). Conclusion Addition of contrast enhanced CMR improves diagnostic accuracy and sensitivity compared to ECHO used in conventional screening in the 1st degree relatives of SCD due to Cardiomyopathy. Acknowledgment The Research was funded by Meath foundation The Adelaide & Meath Hospital, Tallaght Dublin 24.

Screening First Degree Relatives of Persons with Primary Open Angle Glaucoma in India.

ABSTRACTPurpose: To report the results of screening first degree relatives of persons identified with primary open angle glaucoma in a tertiary eye hospital glaucoma services.Design: A cross-sectional study of first degree relatives of persons with primary open angle glaucoma.Materials and methods: First degree relatives of patients identified with primary open angle glaucoma were invited to participate in a screening evaluation in the base hospital to detect glaucoma. All participating individuals had comprehensive eye examination including vision screening, refraction, slit-lamp biomicroscopy, applanation tonometry, gonioscopy, frequency doubling peri-metry and dilated fundus examination. Persons with definite and suspected glaucoma were subject to full threshold automated perimetry.Results: A 514 first degree relatives of 346 persons with primary open angle glaucoma, of 4972 individuals who were invited to participate attended the screening examination (Response Rate 7%). Fifty-five percent of those who attended were males and mean age of participants was 56.8 years. Sixty-eight relatives (13.3% of those screened) were detected to have definite glaucoma. Sixty percent of those detected with definite glaucoma were siblings. Fifteen percent of siblings, 4% of off-springs and 20% of parents who attended the screening examination had definite open angle glaucoma.Conclusion: Prevalence of open angle glaucoma amongst first degree relatives of persons with glaucoma is higher than in the general population as reported in previous studies. Significant barriers, however, exist in the uptake of eye care services among relatives of persons known to have primary open angle glaucoma.How to cite this article: Rajendrababu S, Gupta N, Vijayakumar B, Kumaragurupari R, Krishnadas SR. Screening First Degree Relatives of Persons with Primary Open Angle Glaucoma in India. J Curr Glaucoma Pract 2014;8(3):107-112.

Tissue Studies in Screened First-degree Relatives Reveal a Distinct Crohnʼs Disease Phenotype

First-degree relatives of patients with Crohn's disease (CD) are at risk of developing the disease with 5% to 15% reported to be affected over time. Yet, a much greater proportion of them (>40%) shows features of "subclinical inflammation" with elevated intestinal inflammatory markers such as fecal calprotectin. The meaning of these findings is unclear in the absence of tissue data. Thirty-eight asymptomatic first-degree relatives of patients with CD underwent ileocolonoscopy and other tests including fecal calprotectin. All known causes of intestinal inflammation were carefully excluded. Age and gender-matched controls consisted of 10 individuals who underwent colonoscopy for other reasons. Histology was scored based on known methods. Compared with controls, the relatives had significantly greater median values for fecal calprotectin and histological scores. In relatives, endoscopy identified 3 different phenotypes: (1) normal, (2) with minor lesions (aphthae or small superficial erosions), and (3) with typical CD inflammation. Based on the histological scores, the clustering analysis produced 3 corresponding highly separated clusters (61%, 26%, and 13% of the total, respectively) with divisive coefficient D = 0.94. When followed up (on the average for 53 mo), individuals in the second cluster had histological scores similar to baseline values (P = 0.12). Tissue studies in first-degree relatives of patients with CD reveal 3 distinct groups: normal, with minimal inflammation, and with frank disease. The second cluster represents a novel phenotype, which does not seem to develop the disease over time. These findings explain previous observations of "subclinical inflammation" in such population.

Advances in the understanding and challenges facing the management of first-episode schizophrenia

Symptoms of schizophrenia typically first appear in adolescence, a time of transition involving biological, social and emotional changes. Schizophrenia and related psychotic illnesses can significantly impair educational and social development; consequently, early identification and treatment is paramount and can affect long-term outcome. Singh (2010) states that early intervention is cost effective and does ameliorate the course of early psychosis, referring specifically to specialist early intervention teams, and their impact on longterm disease outcome and prognosis. Much research is now available in this area, and the papers selected for this supplement focus on intervention at this critical stage, related side effects as well as mortality risk factors associated with schizophrenia. The stress–vulnerability model for schizophrenia suggests that the onset and course of schizophrenia may be determined by an underlying vulnerability, with clinical manifestation being modulated by environmental stressors. It has long been recognized, since the days of Kraepelin (1913), that people with schizophrenia are more likely to be obese and to suffer from metabolic problems such as diabetes mellitus. Leonard et al. review evidence concerning a disordered immune system in schizophrenia and postulate that the relationship between the therapeutic benefits of antipsychotics, the pathology of schizophrenia and these metabolic syndromes are linked to chronic, low-grade inflammation. As maternal infections have been implicated as a causative factor, the resulting inflammatory changes could contribute to neurodevelopmental difficulties, and a sensitized immune system that activates in adolescence. Leonard et al. also discuss the important role played by pro-inflammatory cytokines which modulate neuronal action, differentiation and survival during neurodevelopment, and more specifically influence activity and survival of neurons that utilize neurotransmitters such as serotonin, glutamate and dopamine. Interleukin-6 is particularly important in schizophrenia as it could augment dopaminergic function which, in turn, would affect psychotic symptoms. In addition to the dopaminergic system, some pro-inflammatory cytokines enhance the activity of the glutamatergic system, via the tryptophan–kynurenine pathway, and this might contribute to the cognitive decline sometimes seen in schizophrenia. The inflammation hypothesis of schizophrenia raises the possibility of using anti-inflammatory drugs, such as COX-2 inhibitors, as adjuncts to traditional antipsychotic medication. Van Haren et al. find further evidence to suggest that schizophrenia is a progressive brain disease, and that the most significant decline in grey matter volume occurs in the critical first year of illness. Indeed, there appears to be a linear correlation of grey matter loss with age in schizophrenia, as opposed to the exponential decline seen in healthy individuals. Van Haren et al. also suggest there is a link between the extent of volume loss and severity of symptoms and social functioning, but do acknowledge other studies refute this theory. Although antipsychotic medication remains a confounding factor for grey matter loss, studies in first-degree relatives and at-risk individuals show that cumulative antipsychotic intake can only explain some of these brain volume changes. This review highlights the need for further large studies that follow patients over a long period of time, to further clarify the relationship between brain volume change, antipsychotic intake and outcome. Indeed, the potential to attenuate brain volume changes could potentially improve long-term outcome, which again highlights the need for early intervention and effective treatment in this morbid disease. The advent of ‘atypical’, or second generation antipsychotics, engendered a therapeutic optimism in the treatment of first-episode patients (NICE, 2002). Taylor et al. reviewed the effectiveness of antipsychotic medications in first episode schizophrenia and found traditional randomized controlled trials (RCTs), whilst being necessary, lacked generalizability to real-world clinical scenarios. A need for long-term observational studies to complement the RCTs was recognized, and several high-profile studies have now been published, often using discontinuation rate of antipsychotic medication as the primary outcome. The rationale behind this is that a

Familial risk of oral clefts by morphological type and severity: population based cohort study of first degree relatives

Familial risk of oral clefts by morphological type and severity: population based cohort study of first degree relatives

Familial risk of oral clefts by morphological type and severity: population based cohort study of first degree relatives

Objective To estimate the relative risk of recurrence of oral cleft in first degree relatives in relation to cleft morphology.Design Population based cohort study.Setting Data from the medical birth registry...

Prevalencia de factor V Leiden, protrombina 20210 A y homozigosis de la MTHFR: a propósito de un estudio en el Departamento de Salud n.° 19 de la Comunidad Valenciana

The prevalence of genetic markers in ETV disease patients in the 19th Health Department of Valencian Community were: FVL: 9.2%; PT20210 A: 10.5% and Ho-MTHFR: 23.7%. The FVL and PT20210 A prevalence results are lower respect to the literature, while Ho-MTHFR patients, have a higher prevalence with statistical significance difference respect the control group. We considered FVL, PT20210 A and Ho-MTHFR as ETV risk markers. The prevalence of genetic markers in healthy population of the same Health Department were: FVL: 5.8%; PT20210 A: 7.1%, and Ho-MTHFR: 7.7%. We must considered the specific study of these genetic risk markers (FVL, PT20210 A, Ho-MTHFR) in ETV disease affected subjects. The study of first degree relatives of the analyzed patients, should be of great utility to planified genetic advice and practice ETV prophylaxis.

Genetics of polycystic ovary syndrome: searching for the way out of the labyrinth

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder presenting a challenge for clinical investigators. It is the most common endocrine disorder of women in reproductive age, a multifaceted reproductive, cosmetic and metabolic problem, with an enigmatic pathophysiological and molecular basis. Although the familial segregation has been noticed very early in the description of the syndrome and family studies in first-degree relatives of women diagnosed with PCOS reveal clustering of the disease, the genetic studies have not as yet determine the pattern of heredity. Part of the problem in genetic studies has been the lack of uniform criteria for diagnosis, heterogeneity of phenotypic features and the fact that the disorder is only expressed clinically in women during their reproductive years. Even within affected families and between sisters with polycystic ovaries, there is heterogeneity in presentation. However, regardless of diagnostic criteria used to identify profanes and to determine affected status in the kindred, the foundation of genetic studies suggests a strong familial component. Currently, PCOS is considered a polygenic trait that might result from the interaction of susceptible and protective genomic variants under the influence of environmental factors, whose role is under intensive investigation. Candidate genes cover a broad spectrum of an endless list of molecules which participate on every step of reproductive and metabolic pathways of this syndrome. Focused research in identification of these genes may provide valuable information and shed some light on the way out of the genomic labyrinth, elucidating the underlying pathophysiology and aiming at a more efficient therapeutic approach of this complicated endocrine disorder.

Impact of Genetic Versus Environmental Factors on the Control of Muscle Glycogen Synthase Activation in Twins

Storage of glucose as glycogen accounts for the largest proportion of muscle glucose metabolism during insulin infusion in normal and insulin-resistant subjects. Studies in first-degree relatives have indicated a genetic origin of the defective insulin activation of muscle glycogen synthase (GS) in type 2 diabetes. The aim of this study was to evaluate the relative impact of genetic versus nongenetic factors on muscle GS activation and regulation in young and elderly twins examined with a 2-h euglycemic-hyperinsulinemic (40 mU x m(-2) x min(-1)) clamp combined with indirect calorimetry and excision of muscle biopsies. The etiological components were determined using structural equation modeling. Fractional GS activity; GS phosphorylation at sites 2, 2 + 2a, and 3a + 3b corrected for total GS protein; and GS kinase 3 (GSK3) activity were similar in both age groups, whereas total GS activity and protein were lower in elderly compared with younger twins. GS fractional activity increased significantly during insulin stimulation in both young and elderly twins. Conversely, there was a significant decrease in GS phosphorylation at site 3a + 3b and GSK3 activity during insulin stimulation in both age groups, whereas GS phosphorylation at site 2 and 2 + 2a only decreased on insulin stimulation in the younger twins. The increment in whole-body glucose disposal (Rd) and nonoxidative glucose metabolism (insulin - basal) correlated significantly with the increment in GS fractional activity. Fractional GS activity had a major environmental component in both age groups. GSK3 activity exhibited a genetic component in young (basal: a2 = 0.42; insulin: a2 = 0.58) and elderly (insulin: a2 = 0.56) twins. Furthermore, GS phosphorylation at site 2 (insulin: a2 = 0.69) in the elderly and at site 3a + 3b (insulin: a2 = 0.50) in the young twins had a genetic component. In conclusion, GSK3 activity and GS phosphorylation, particularly at sites 2 and 3a + 3b, had major genetic components. Total and fractional GS activities per se were, on the other hand, predominantly controlled by environmental factors. Moreover, GS activity was intact with increasing age, despite a significant reduction in nonoxidative glucose metabolism.

A 25-year follow-up study of glucose tolerance in first-degree relatives of type 2 diabetic patients: association of impaired or diabetic glucose tolerance with other components of the metabolic syndrome.

A follow-up study of first-degree relatives of type 2 diabetic patients presented the opportunity to study the association of components of the metabolic syndrome with oral glucose tolerance in these subjects. In 1992, 25 years after the first analysis of the cohort, we performed 75-g oral glucose tolerance tests and measured anthropometric data (body mass index, waist-hip ratio), insulin and C-peptide concentrations, and parameters of lipoprotein metabolism (free fatty acids, triglycerides, cholesterol, HDL cholesterol). Of 135 participants, 71 had normal glucose tolerance (GT), 22 had impaired GT, and 42 had diabetic GT (WHO 1985 criteria). Impaired glucose tolerance and diabetes were significantly (Kruskal-Wallis test) associated with advanced age (p=0.001), higher body mass index (p=0.005) and waist-hip ratio (p=0.027), systolic hypertension (p=0.031), elevated basal insulin concentrations (p<0.001), higher free fatty acids (p<0.001) and triglycerides (p=0.017), and lower HDL cholesterol (p=0.003); no associations were found with total and LDL cholesterol levels (Friedewald's formula, p=0.25). Abnormalities (obesity, hypertriglyceridemia, low HDL cholesterol, hypertension, pathological oral glucose tolerance) were associated with significant deterioriations in all other components of the metabolic syndrome, if their number exceeded three. Disturbances of oral glucose tolerance are present in a high percentage of first-degree relatives after 25 years of follow-up (51% of those tested). Impaired or diabetic glucose tolerance in such a cohort was associated with overweight, hypertension and disturbances of lipoprotein metabolism characteristic of the metabolic syndrome. Hypercholesterolemia (LDL-cholesterol) is not a component of the metabolic syndrome in a German population with a high hereditary burden regarding type 2 diabetes. A metabolic syndrome should certainly be diagnosed if three components are present, although even in the presence of only two components, an elevated risk is evident.

Eye movement and neuropsychological studies in first-degree relatives of schizophrenic patients

The aim of the study was to compare the results of oculomotor and neuropsychological tests in first-episode schizophrenic patients, in both their parents and matched healthy controls. Eye movement tests included fixation and a smooth pursuit task and neuropsychological tests which comprised the Trail Making Test (TMT) A and B, the Stroop Test A and B, and the Wisconsin Card Sorting Test (WCST). There was a significant difference between the 21 patients and their 33 healthy parents in the results of both the eye movement tests and the TMT and WCST but not in the Stroop test. On the other hand, a significant difference between parents and their matched control subjects was found in both oculomotor tests, in the Stroop B, and in two indices of the WCST (completed categories, CC and percentage of conceptual level responses, %CONC). A correlation was obtained between patients and their fathers in the intensity of smooth pursuit disturbances and two indices of the WCST (CC and %CONC), but not between patients and their mothers. The results obtained confirm those of other studies pointing to the presence of a significant impairment on oculomotor and neuropsychological tests in first-degree nonpsychotic relatives (parents) of schizophrenic patients, which may be used as an endophenotypic markers of genetic predisposition to schizophrenia.

Recurrence of depression in those with prepubertal onset was associated with higher rates of depression in relatives

Wickramaratne PJ, Greenwald S, Weissman MM. Psychiatric disorders in the relatives of probands with prepubertal-onset or adolescent-onset major depression. J Am Acad Child Adolesc Psychiatry2000 Nov; 39 : 1396 –405....

Trait versus state aspects of the MMPI during the early course of schizophrenia

Scores on the Minnesota Multiphasic Personality Inventory (MMPI)-168 item version were examined during periods of clinical remission and of psychosis for recent-onset schizophrenia patients ( n=19) and at comparable time intervals for demographically matched normal participants ( n=19). To determine diagnostic specificity, MMPIs for participants with bipolar affective disorder in remission ( n=12) were also examined. Methods for distinguishing between stable vulnerability indicators, mediating vulnerability factors and episode indicators of psychopathology were adapted from Nuechterlein and Dawson, 1984. MMPI scales Pa, Sc and validity scale F showed a combination of trait and state qualities, characteristic of mediating vulnerability factors. These scales reflect changes that occur during psychotic episodes but also apparently tap personality characteristics that endure into periods of clinical remission. Unexpectedly, some MMPI scales that are not typically associated with psychotic disorders (i.e. Hs, D, and Hy) were significantly higher in schizophrenia patients across psychotic and clinically remitted states than in normal participants. In clinical remission, higher scores on scales Hs, D and Hy, showed some specificity to schizophrenia relative to bipolar disorder. While MMPI-168 scales Pd and Pt fit the pattern for vulnerability indicators, it was uncertain whether they belonged to the stable versus mediating subtype. MMPI scores that continue to be higher in remission than in a normal sample may reflect either enduring vulnerability factors or the impact of schizophrenia and the individuals attempts to cope with the disorder. Studies of first-degree relatives will be needed to provide converging evidence that certain personality characteristics reflect genetic predisposition to schizophrenia.

Genetic screening for colorectal cancer and intervention

There is a complex interaction between environmental/dietary factors and genetics underlying the pathogenesis of colon carcinogenesis. Little data exist concerning the impact of diet on the phenotypic expression of genetically linked colon cancer. As a result, it has been difficult to develop rationally designed dietary intervention studies in first-degree relatives of patients with established familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) and other familial colon cancer syndromes. Only 2 double-blinded, placebo-controlled trials have been published concerning the use of preventive strategies in patients with genetically inherited colorectal cancer syndromes, both in patients with FAP. One study evaluated the effects of vitamin C plus vitamin E with or without a high-dose wheat bran fiber supplement on the recurrence of rectal adenomas. Over a 48-month intervention period, only the wheat bran fiber intervention significantly reduced polyp growth. A second study reported that intervention with the NSAID sulindac for 9 months in young patients with FAP resulted in a significant reduction in both polyp number and size in the rectosigmoid colon. All of the large-scale (i.e., >500 randomized participants) phase III nutrient or chemopreventive agent intervention studies thus far have targeted participants with a history of non-familial, sporadic colorectal adenomas. Current clinical adenoma trials do not measure whether the regimen being tested can prevent genotoxic events occurring in early stages of abnormal cell development that contribute to the eventual formation of adenomas nor whether the agent(s) can inhibit events occurring during the progression of adenomas to carcinomas. Therefore, future clinical trial designs may have to consider (i) lengthening the clinical trial period before adenomas develop, (ii) testing at early patient ages and/or (iii) measuring the growth of adenomas as they progress to carcinomas.

Genetic screening for colorectal cancer and intervention

There is a complex interaction between environmental/dietary factors and genetics underlying the pathogenesis of colon carcinogenesis. Little data exist concerning the impact of diet on the phenotypic expression of genetically linked colon cancer. As a result, it has been difficult to develop rationally designed dietary intervention studies in first-degree relatives of patients with established familial adenomatous polyposis (FAP), hereditary nonpolyposis colorectal cancer (HNPCC) and other familial colon cancer syndromes. Only 2 double-blinded, placebo-controlled trials have been published concerning the use of preventive strategies in patients with genetically inherited colorectal cancer syndromes, both in patients with FAP. One study evaluated the effects of vitamin C plus vitamin E with or without a high-dose wheat bran fiber supplement on the recurrence of rectal adenomas. Over a 48-month intervention period, only the wheat bran fiber intervention significantly reduced polyp growth. A second study reported that intervention with the NSAID sulindac for 9 months in young patients with FAP resulted in a significant reduction in both polyp number and size in the rectosigmoid colon. All of the large-scale (i.e., >500 randomized participants) phase III nutrient or chemopreventive agent intervention studies thus far have targeted participants with a history of non-familial, sporadic colorectal adenomas. Current clinical adenoma trials do not measure whether the regimen being tested can prevent genotoxic events occurring in early stages of abnormal cell development that contribute to the eventual formation of adenomas nor whether the agent(s) can inhibit events occurring during the progression of adenomas to carcinomas. Therefore, future clinical trial designs may have to consider (i) lengthening the clinical trial period before adenomas develop, (ii) testing at early patient ages and/or (iii) measuring the growth of adenomas as they progress to carcinomas. © 1996 Wiley-Liss, Inc.