Mai Elassy

Does telomere length mediate associations between inbreeding and increased risk for bipolar I disorder and schizophrenia

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.

Consanguinity and increased risk for schizophrenia in Egypt

BACKGROUNDnConsanguinity 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.nnnMETHODSnA 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).nnnRESULTSnSelf-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).nnnCONCLUSIONSnConsanguinity 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.

Treatment adherence towards prescribed medications in bipolar-II acute depressed patients: relationship with cyclothymic temperament and "therapeutic sensation seeking" in response towards subjective intolerance to pain.

BACKGROUNDnTreatment adherence (TA) is crucial during almost any phase of bipolar disorder (BD), including type-II (BD-II) acute depression. While a number of issues have been traditionally accounted on the matter, additional factors should be likewise involved, including affective temperaments and some clinically suggestive psychopathological traits whose systematic assessment represents the aim of this study.nnnMETHODSnTwo hundred and twenty BD-II acute depressed outpatients were consecutively evaluated using the Structured Clinical Interviews for Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition Axis-I and II Disorders, Hamilton scales for Depression and Anxiety, Temperament Evaluation of the Memphis Pisa Paris San Diego-Auto-questionnaire-110-item, Visual Analogue Scale (VAS), Zuckermans Sensation-Seeking Scale-Form-V (SSS-V), Barratts Impulsivity Scale-11-item, State-Trait Anxiety Inventory modules, Severity module of the Clinical Global Impression Scale for BD, Morisky 8-Item Medication Adherence Scale (MMAS-8) and the Clinician Rating Scale (CRS). Patients were divided into non-adherent vs. treatment-adherent cases depending on MMAS-8+CRS scores.nnnRESULTSnIn the TA(-) group, higher VAS and cyclothymic temperament scores were highly correlated (r=.699; p≤.001). Those latter scores, along with SSS-V scores and the occurrence of lifetime addiction to painkiller and/or homeopathic medications available over the counter defined a therapeutic sensation seeking pattern allowing to correctly classify as much as 93.9% [Exp(B)=3.490; p≤.001] of TA(-) cases (49/220).nnnLIMITSnLack of objective TA measures and systematic pharmacological record; recall bias on some diagnoses; and relatively small sample size.nnnCONCLUSIONSnStating the burden of TA in BD, additional studies on this regard are aimed, ideally contributing to enhance the management of BD itself.

Consanguinity associated with increased risk for bipolar I disorder in Egypt

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 (nu2009=u200935) and 150 randomly selected, unaffected control individuals. DNA‐based consanguinity rates showed significant case–control differences (Pu2009=u20090.0039). Self‐reported consanguinity rates were also elevated among BP1 patients in both samples (Study #1 ORu2009=u20092.66, 95% confidence intervals, CI: 1.34, 5.29; Study #2: ORu2009=u20094.64, 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.

Sensation seeking in major depressive patients: Relationship to sub-threshold bipolarity and cyclothymic temperament

BACKGROUNDnHigh levels of sensation seeking (SS) have been traditionally reported for lifetime bipolar disorder (BD) and/or substance use disorder (SUD) rather than major depressive disorder (MDD). Nonetheless, a renewed clinical attention toward the burden of sub-threshold bipolarity in MDD, solicits for a better assessment of unipolar major depressive episodes (MDEs) via characterization of putative differential psychopathological patterns, including SS and predominant affective temperament.nnnMETHODSnTwo hundred and eighty currently depressed cases of MDD and 87 healthy controls were screened using the Zuckermans sensation seeking scale-Form-V, the Hypomania Check List-32-item (HCL-32), the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Auto-questionnaire-110-item, the Barratt Impulsivity Scale-11-item, the State-Trait Anxiety Inventory modules and the Structured Clinical Interview for DSM-IV axis-I disorders. Cases were divided into HCL-32(+)(sub-threshold bipolar)/HCL-32(-)(true unipolar depressed) depending on the HCL-32 total score.nnnRESULTSnUpon correlation and multivariate regression analyses, the HCL-32(+) patients showed the highest levels of SS, higher prevalence of cyclothymic temperament, and higher rates of multiple lifetime axis-I co-morbidities, including SUD.nnnLIMITSnRecall bias on some diagnoses, including BD, grossly matched healthy control group, lack of ad-hoc validated measures for ADHD, SUD, or axis-II disorders.nnnCONCLUSIONSnIn our sample, the occurrence of higher levels of SS in sub-threshold bipolar cases outlined a differential psychopathological profile compared to DSM-defined true unipolar cases of MDE. If confirmed by replication studies, these findings may aid clinicians in delivering a more accurate diagnosis and a safer use of antidepressants in some MDD cases.

Factor structure and reliability of the Italian adaptation of the Hypomania Check List-32, second revision (HCL-32-R2)

OBJECTIVEnTo assess the psychometric properties of the Italian adaptation of the Hypomania-Check-List 32-item, second revision (HCL-32-R2) for the detection of bipolarity in major depressive disorder (MDD) treatment-seeking outpatients.nnnMETHODSnA back-to-back Italian adaption of the Bipolar Disorders: Improving Diagnosis, Guidance, and Education English module of the HCL-32-R2 was administered between March 2013 and October 2014 across twelve collaborating sites in Italy. Diagnostic and Statistical Manual Fourth edition (DSM-IV) diagnoses were made adopting the mini-international neuropsychiatric interview, using bipolar disorder (BD) patients as controls.nnnRESULTSnIn our sample (n=441, of whom, BD-I=68; BD-II=117; MDD=256), using a cut-off of 14 allowed the HCL-32-R2 to discriminate DSM-IV-defined MDD patients between true unipolar (HCL-32-R2(-)) and sub-threshold bipolar depression (HCL-32-R2(+)) with sensitivity=89% and specificity=79%. Area under the curve was .888; positive and negative predictive values were 75.34% and 90.99% respectively. Owing to clinical interpretability considerations and consistency with previous adaptations of the HCL-32, a two-factor solution (F1=hyperactive/elated vs. F2=irritable/distractible/impulsive) was preferred using exploratory and confirmatory factor analyses, whereas items n.33 (I gamble more) and n.34 (I eat more) introduced in the R2 version of the scale slightly loaded onto F2 and F1 respectively. Cronbach׳s α=.88 for F1 and .71 for F2.nnnLIMITATIONSnNo cross-validation with any additional validated screening tool; treatment-seeking outpatient sample; recall bias; no systematic evaluation of eventual medical/psychiatric comorbidities, current/lifetime pharmacological history, neither record of severity of current MDE.nnnCONCLUSIONSnOur results seem to indicate fair accuracy of HCL-32 as a screening instrument for BD, though replication studies are warranted.

Factor structure and reliability of the Arabic adaptation of the Hypomania Check List-32, second revision (HCL-32-R2).

OBJECTIVEnTo assess the psychometric properties of the Arabic adaptation of the Hypomania-Check-List 32-item, second revision (HCL-32-R2) for the detection of bipolarity in major depressive disorder (MDD) inpatients suffering a current major depressive episode (MDE).nnnMETHODnThe Bipolar Disorders: Improving Diagnosis, Guidance, and Education Arabic module of the HCL-32-R2 was administered to mother-tongue Arabic MDE inpatients between March 2013 and October 2014. Diagnostic and Statistical Manual Fourth edition (DSM-IV) diagnoses were made adopting the mini-international neuropsychiatric interview, using bipolar disorder (BD) patients as controls.nnnRESULTSnIn our sample (n=500, of whom, BD-I=329; BD-II=70; MDD=101), using a cut-off of 17 allowed the HCL-32-R2 to discriminate DSM-IV-defined MDD patients between true unipolar (HCL-32-R2(-)) and sub-threshold bipolar depression (HCL-32-R2(+)) with sensitivity=82% and specificity=77%. Area under the curve was .883; positive and negative predictive values were 93.44% and 73.23% respectively. Owing to clinical interpretability considerations and consistency with previous adaptations of the HCL-32, a two-factor solution (F1=hyperactive/elated vs. F2=irritable/distractible/impulsive) was preferred using exploratory and confirmatory factors analyses. Item n.33 (I gamble more) and n.34 (I eat more) introduced in the R2 version of the HCL-32 loaded onto F1, though very slightly. Cronbachs alphas were F1=.86 and F2=.60.nnnLIMITATIONSnNo cross-validation with any additional validated screening tool. Inpatients only sample; recall bias; no systematic evaluation of eventual medical/psychiatric comorbidities, current/lifetime pharmacological history, or record of severity of current MDE.nnnCONCLUSIONSnIn our sample, the HCL-32 fairly discriminated between MDD and BD-I but not BD-II, therefore soliciting for replication studies for use in Arabic-speaking depressed inpatients.

Reduced Fertility and Fecundity among Patients with Bipolar I Disorder and Schizophrenia in Egypt.

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.

Practice effects distort translational validity estimates for a Neurocognitive Battery

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.

Arabic versions of the sleep timing questionnaire and the composite scale of morningness.

OBJECTIVESnTo develop Arabic versions of English language questionnaires to estimate morningness/eveningness and sleep variables.nnnMETHODSnWe 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.nnnRESULTSnSatisfactory correlations were present between the English and Arabic versions for total CSM scores (Spearmans ρ=0.90, p<0.001). All but one of the STQ variables were significantly correlated (Spearmans 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 (Spearmans ρ=-0.23, p≤0.05).nnnCONCLUSIONSnArabic 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.