ABSTRACT
BACKGROUND: Self-reported consanguinity is associated with risk for schizophrenia (SZ) in several inbred populations, but estimates using DNA-based coefficients of inbreeding are unavailable. Further, it is not known whether recessively inherited risk mutations can be identified through homozygosity by descent (HBD) mapping. METHODS: We studied self-reported and DNA-based estimates of inbreeding among Egyptian patients with SZ (nâ¯=â¯421, DSM IV criteria) and adult controls without psychosis (nâ¯=â¯301), who were evaluated using semi-structured diagnostic interview schedules and genotyped using the Illumina Infinium PsychArray. Following quality control checks, coefficients of inbreeding (F) and regions of homozygosity (ROH) were estimated using PLINK software for HBD analysis. Exome sequencing was conducted in selected cases. RESULTS: Inbreeding was associated with schizophrenia based on self-reported consanguinity (χ2â¯=â¯4.506, 1 df, pâ¯=â¯0.034) and DNA-based estimates for inbreeding (F); the latter with a significant Fâ¯×â¯age interaction (ßâ¯=â¯32.34, pâ¯=â¯0.0047). The association was most notable among patients older than age 40 years. Eleven ROH were over-represented in cases on chromosomes 1, 3, 6, 11, and 14; all but one region is novel for schizophrenia risk. Exome sequencing identified six recessively-acting genes in ROH with loss-of-function variants; one of which causes primary hereditary microcephaly. CONCLUSIONS: We propose consanguinity as an age-dependent risk factor for SZ in Egypt. HBD mapping is feasible for SZ in adequately powered samples.
Subject(s)
Inbreeding , Schizophrenia , Adult , Consanguinity , Egypt/epidemiology , Homozygote , Humans , Polymorphism, Single Nucleotide , Schizophrenia/epidemiology , Schizophrenia/geneticsABSTRACT
BACKGROUND: Schizophrenia (SZ) is associated with cognitive impairment that contributes to disability, but the cognitive dysfunction is relatively refractory to pharmacologic intervention. Though Valproate augmentation is reported to improve psychopathology among patients with SZ, its effects on cognitive functions have not been investigated systematically. METHODS: Using a randomized double blind placebo controlled design, the effects of Valproate or placebo as adjuncts to risperidone (RISP) treatment were evaluated among patients with early course SZ (Nâ¯=â¯109). Domains of cognitive function, estimated using the Arabic version of the Penn Computerized Neurocognitive Battery, were the prime outcomes. Clinical severity and social function were secondary outcomes. We also explored the effects of valproate treatment on serological responses to Toxoplama Gondii (TOXO), a putative risk factor for cognitive dysfunction in SZ. RESULTS: There were no significant differences between Valproate and placebo (PLA) treated groups with respect to changes in cognitive functions, positive or negative symptom scores or daily function scores at the beginning and end of the study. No significant Valproate/PLA differences were noted on TOXO serostatus or TOXO-related cognitive dysfunction. CONCLUSION: Valproate treatment may not be beneficial for cognitive dysfunction in SZ or for TOXO infection.
Subject(s)
Antimanic Agents/pharmacology , Antipsychotic Agents/pharmacology , Cognitive Dysfunction/drug therapy , Risperidone/pharmacology , Schizophrenia/drug therapy , Toxoplasmosis/drug therapy , Valproic Acid/pharmacology , Adolescent , Adult , Antimanic Agents/administration & dosage , Antipsychotic Agents/administration & dosage , Cognitive Dysfunction/etiology , Double-Blind Method , Drug Synergism , Drug Therapy, Combination , Humans , Middle Aged , Risperidone/administration & dosage , Schizophrenia/complications , Treatment Outcome , Valproic Acid/administration & dosage , Young AdultABSTRACT
BACKGROUND: Hepatitis C virus (HCV) infection is associated with cognitive dysfunction in clinic-based studies. The risk could be attributed to factors such as antiviral medications, substance abuse, or coincidental infection. AIM: The aim was to evaluate cognitive function in relation to HCV antibody titers in a community-based sample of asymptomatic individuals at low risk for substance abuse. METHOD: Adults were ascertained from a community in Mansoura, Egypt, where HCV is endemic (n = 258). Cognitive performance was evaluated using the Arabic version of the Penn Computerized Neurocognitive Battery. Substance abuse and psychopathology were also assessed. Antibodies to HCV and Toxoplasma gondii (TOX), a common protozoan that can affect cognition, were estimated using serological IgG assays. RESULTS: The prevalence of HCV and TOX infection was 17.6% and 52.9%, respectively. HCV antibody titers were significantly associated with worse function in four cognitive tests for accuracy and three tests for speed, after adjusting for covariates (p < .05, beta coefficients, 2.1-3.2). TOX antibody titers were associated with impaired accuracy in one test. CONCLUSIONS: The association between HCV antibody titers and cognitive impairment is not mediated by antiviral treatment or substance abuse in this sample. Whether HCV has a causal role in the cognitive dysfunction should be investigated.
Subject(s)
Antibodies, Viral/isolation & purification , Cognition/physiology , Cognitive Dysfunction/complications , Hepacivirus/immunology , Hepatitis C/complications , Adult , Cognitive Dysfunction/psychology , Cognitive Dysfunction/virology , Cross-Sectional Studies , Female , Hepatitis C/psychology , Hepatitis C/virology , Humans , Male , Middle Aged , Young AdultABSTRACT
INTRODUCTION: With the globalization of biomedical research and the advent of "precision medicine," there is increased need for translation of neuropsychological tests, such as computerized batteries that can be incorporated in large-scale genomic studies. Estimates of translational validity are obtained by administering the test in the original and the translated versions to bilingual individuals. We investigated the translation of a neuropsychological battery from English to Arabic and how practice effects influence translational validity estimates. METHODS: The Penn computerized neurocognitive battery (Penn CNB) includes tests that were validated with functional neuroimaging and provides measures of accuracy and speed of performance in several cognitive domains. To develop an Arabic version of the CNB, the English version was translated into Arabic, then back translated and revised. The Arabic and the original English versions were administered in a randomized crossover design to bilingual participants (N = 22). RESULTS: Performance varied by cognitive domain, but generally improved at the second session regardless of the language of the initial test. When performance on the English and Arabic version was compared, significant positive correlations were detected for accuracy in 8/13 cognitive domains and for speed in 4/13 domains (r = .02 to .97). When the practice estimates using linear models were incorporated, the translational validity estimates improved substantially (accuracy, r = .50-.96, speed, r = .63-.92, all correlations, p = .05 or better). CONCLUSION: While crossover designs control for order effects on average performance, practice effects, regardless of language, still need to be removed to obtain estimates of translational validity. When practice effect is controlled for, the Arabic and English versions of the Penn-CNB are well correlated, and the Arabic version is suitable for use in research.
Subject(s)
Cognition/physiology , Neuropsychological Tests , Practice, Psychological , Translations , Adolescent , Adult , Female , Humans , Male , Middle Aged , Reproducibility of Results , Statistics as Topic , Surveys and Questionnaires , Young AdultABSTRACT
OBJECTIVES: To develop Arabic versions of English language questionnaires to estimate morningness/eveningness and sleep variables. METHODS: We translated the Composite scale of morningness (CSM) and the sleep timing questionnaire (STQ) [with added siesta questions] into Arabic; the Arabic versions were then back translated. The revised Arabic and the original English versions were next administered to bi-lingual Egyptians using a crossover design (n=25). The Arabic versions of both scales were subsequently administered to an independent Egyptian sample (n=79) and the siesta variables examined in relation to the CSM. RESULTS: Satisfactory correlations were present between the English and Arabic versions for total CSM scores (Spearman's ρ=0.90, p<0.001). All but one of the STQ variables were significantly correlated (Spearman's ρ=0.45-0.88, p≤0.05). In the Arabic version, the frequency of siesta naps per week was significantly correlated with the total CSM score, with evening types taking more naps (Spearman's ρ=-0.23, p≤0.05). CONCLUSIONS: Arabic versions of the STQ and CSM have been developed in Egypt, and are freely available. They can be used for behavioral research related to sleep and circadian function and can be adapted for use in other Arab speaking populations.
Subject(s)
Circadian Rhythm/physiology , Sleep/physiology , Surveys and Questionnaires , Translations , Adolescent , Adult , Cross-Over Studies , Egypt , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
OBJECTIVE: To evaluate reproduction among patients with bipolar I disorder (BP1) or schizophrenia (SZ) in Egypt. METHODS: BP1 patients (n=113) were compared with community based, demographically balanced controls (n=124) and SZ patients (n=79, DSM-IV). All participants were evaluated using structured interviews and corroborative data were obtained from relatives. Standard indices of procreation were included in multivariate analyses that incorporated key demographic variables. RESULTS: Control individuals were significantly more likely to have children than BP1 or SZ patients (controls 46.8%, BP1 15.9%, SZ 17.7%), but the BP1-SZ differences were non-significant. The average number of children for BP1 patients (0.37±0.9) and SZ patients (0.38±0.9) was significantly lower than for controls (1.04±1.48) (BP1 vs controls, p<0.001; SZ vs controls, p<0.001). The frequency of marriages among BP1 patients was nominally higher than the SZ group, but was significantly lower than controls (BP1: 31.9% SZ: 27.8% control: 57.3%). Even among married individuals, BP1 (but not SZ) patients were childless more often than controls (p=0.001). The marital fertility, i.e., the average number of children among patients with conjugal relationships for controls (1.8±1.57) was significantly higher than BP1 patients (1.14±1.31, p=0.02), but not significantly different from SZ patients (1.36±1.32, p=0.2). CONCLUSION: Selected reproductive measures are significantly and substantially reduced among Egyptian BP1 patients. The reproductive indices are similar among BP1 and SZ patients, suggesting a role for general illness related variables. Regardless of the cause/s, the impairment constitutes important, under-investigated disability.
ABSTRACT
We have recently found that consanguinity is a risk factor for bipolar I disorder (BP1) and schizophrenia (SZ) in Egypt. Inbreeding has been associated with increased cellular stress and impaired physiological function in plants and animals. Previous studies have reported that telomere length (TL), an index of oxidative stress and cellular senescence is significantly reduced among patients with SZ or mood disorders compared with control individuals. Hence we evaluated TL as a possible mediator of the observed association between consanguinity and BP1/SZ risk. Patients with BP1 (n=108), or SZ (n=60) were compared with screened adult controls in separate experiments. TL was estimated using a quantitative PCR (qPCR) based assay. The inbreeding coefficient/consanguinity rate was estimated in two ways: using 64 DNA polymorphisms ('DNA-based' rate); and from family history data ('self report'). Significant correlation between TL and DNA based inbreeding was not observed overall, though suggestive trends were present among the SZ cases. No significant case-control differences in TL were found after controlling for demographic variables. In conclusion, reduced TL may not explain a significant proportion of observed associations between consanguinity and risk for BP1/SZ.
Subject(s)
Bipolar Disorder/genetics , Inbreeding , Schizophrenia/genetics , Telomere/genetics , Adult , Analysis of Variance , Bipolar Disorder/epidemiology , Case-Control Studies , Egypt/epidemiology , Female , Genetic Predisposition to Disease , Humans , Linear Models , Male , Risk Factors , Schizophrenia/epidemiology , Young AdultABSTRACT
BACKGROUND: Consanguinity has been suggested as a risk factor for psychoses in some Middle Eastern countries, but adequate control data are unavailable. Our recent studies in Egypt have shown elevated parental consanguinity rates among patients with bipolar I disorder (BP1), compared with controls. We have now extended our analyses to schizophrenia (SZ) in the same population. METHODS: A case-control study was conducted at Mansoura University Hospital, Mansoura, Egypt (SZ, n=75; controls, n=126, and their available parents). The prevalence of consanguinity was estimated from family history data ('self report'), followed by DNA analysis using short tandem repeat polymorphisms (STRPs, n=63) ('DNA-based' rates). RESULTS: Self-reported consanguinity was significantly elevated among the patients (SZ: 46.6%, controls: 19.8%, OR 3.53, 95% CI 1.88, 6.64; p=0.000058, 1 d.f.). These differences were confirmed using DNA-based estimates for coefficients of inbreeding (inbreeding coefficients as means+/-standard error, cases: 0.058+/-0.007, controls: 0.022+/-0.003). CONCLUSIONS: Consanguinity rates are significantly elevated among Egyptian SZ patients in the Nile delta region. The associations are similar to those observed with BP1 in our earlier study. If replicated, the substantial risk associated with consanguinity raises public health concerns. They may also pave the way for gene mapping studies.
Subject(s)
Consanguinity , Microsatellite Repeats/genetics , Polymorphism, Genetic/genetics , Schizophrenia/epidemiology , Schizophrenia/genetics , Adult , Case-Control Studies , DNA Mutational Analysis/methods , Egypt/epidemiology , Female , Humans , Male , Odds Ratio , Self Disclosure , Young AdultABSTRACT
BACKGROUND: In most developing countries, as in Egypt; postmenopausal breast cancer cases are offered a radical form of surgery relying on their unawareness of the subsequent body image disturbance. This study aimed at evaluating the effect of breast cancer surgical choice; Breast Conservative Therapy (BCT) versus Modified Radical Mastectomy (MRM); on body image perception among Egyptian postmenopausal cases. METHODS: One hundred postmenopausal women with breast cancer were divided into 2 groups, one group underwent BCT and the other underwent MRM. Pre- and post-operative assessments of body image distress were done using four scales; Breast Impact of Treatment Scale (BITS), Impact of Event Scale (IES), Situational Discomfort Scale (SDS), and Body Satisfaction Scale (BSS). RESULTS: Preoperative assessment showed no statistical significant difference regarding cognitive, affective, behavioral and evaluative components of body image between both studied groups. While in postoperative assessment, women in MRM group showed higher levels of body image distress among cognitive, affective and behavioral aspects. CONCLUSION: Body image is an important factor for postmenopausal women with breast cancer in developing countries where that concept is widely ignored. We should not deprive those cases from their right of less mutilating option of treatment as BCT.
Subject(s)
Body Image , Breast Neoplasms/surgery , Decision Making , Mastectomy, Modified Radical/psychology , Mastectomy, Segmental/psychology , Adult , Aged , Aged, 80 and over , Breast Neoplasms/psychology , Cultural Characteristics , Developing Countries , Egypt , Female , Humans , Middle Aged , Neoplasm Staging , Postmenopause , Postoperative Period , Prognosis , Prospective Studies , Quality of Life , Plastic Surgery Procedures , Treatment OutcomeABSTRACT
We aimed to contrast rates of consanguinity among patients with bipolar I disorder (BP1) and controls in a population with customary consanguineous marriages (i.e., marriage between related individuals). Consanguinity increases risk for numerous monogenic and polygenic diseases. Whether the risk for BP1 increases with consanguinity has not been investigated systematically. Two independent studies were conducted in Egypt: (1) Case-control study 93 patients with BP1, 90 screened adult control individuals, and available parents. The inbreeding coefficient/consanguinity rate was estimated in two ways: using 64 DNA polymorphisms ("DNA-based" rate); and from family history data ("self report"); (2) Epidemiological survey: total of 1,584 individuals were screened, from whom self-reported consanguinity data were obtained for identified BP1 cases (n = 35) and 150 randomly selected, unaffected control individuals. DNA-based consanguinity rates showed significant case-control differences (P = 0.0039). Self-reported consanguinity rates were also elevated among BP1 patients in both samples (Study #1 OR = 2.66, 95% confidence intervals, CI: 1.34, 5.29; Study #2: OR = 4.64, 95% CI: 2.01, 10.34). In conclusion, two independent, systematic studies indicate increased consanguinity among Egyptian BP1 patients in the Nile delta region. Self-reported estimates of consanguinity are bolstered by DNA-based estimates, and both show significant case-control differences for BP1.