Medical students represent a highly educated population under significant pressures. During the transition to clinical settings in the third year, they may experience a loss of external control and may counter this with an increase in obsessionality and/or other anxiety symptoms. Our study examines the phenomenology of obsessive-compulsive and other anxiety symptoms in medical students at two U.S. medical schools and relates these symptoms to self-perception of performance. Subjects anonymously completed a battery of questionnaires regarding obsessive-compulsive symptoms, attentional problems, anxiety symptoms, depressive symptoms, and perceived performance in medical school. A factor analysis of obsessional symptoms showed four primary factors: checking/doubts, contamination, long time/detail, and unpleasant thoughts/worries. These four factors were similar to those found among college students and other nonclinical populations. Anxiety, attentional, and depressive symptoms were highest in the third-year medical students. In contrast, obsessional symptoms were highest in the first-year students and lower for subsequent years. Perceived performance was not significantly correlated with obsessionality, although lower perceived performance was associated with higher levels of anxiety and depressive symptoms. Students with lower perceived performance in medical school were significantly more likely to be female, depressed, or older. The progressive decrease in number of obsessional symptoms across years and the lack of correlation with perceived performance suggest that these symptoms may be developmentally appropriate, and perhaps adaptive. In contrast, other anxiety symptoms appear to be maladaptive responses to external stressors.
BackgroundThe identification of sensitive biomarkers for the detection of ovarian cancer is of high clinical relevance for early detection and/or monitoring of disease recurrence. We developed a systematic multi-step biomarker discovery and verification strategy to identify candidate DNA methylation markers for the blood-based detection of ovarian cancer.Methodology/Principal FindingsWe used the Illumina Infinium platform to analyze the DNA methylation status of 27,578 CpG sites in 41 ovarian tumors. We employed a marker selection strategy that emphasized sensitivity by requiring consistency of methylation across tumors, while achieving specificity by excluding markers with methylation in control leukocyte or serum DNA. Our verification strategy involved testing the ability of identified markers to monitor disease burden in serially collected serum samples from ovarian cancer patients who had undergone surgical tumor resection compared to CA-125 levels.We identified one marker, IFFO1 promoter methylation (IFFO1-M), that is frequently methylated in ovarian tumors and that is rarely detected in the blood of normal controls. When tested in 127 serially collected sera from ovarian cancer patients, IFFO1-M showed post-resection kinetics significantly correlated with serum CA-125 measurements in six out of 16 patients.Conclusions/SignificanceWe implemented an effective marker screening and verification strategy, leading to the identification of IFFO1-M as a blood-based candidate marker for sensitive detection of ovarian cancer. Serum levels of IFFO1-M displayed post-resection kinetics consistent with a reflection of disease burden. We anticipate that IFFO1-M and other candidate markers emerging from this marker development pipeline may provide disease detection capabilities that complement existing biomarkers.
The division of obsessive-compulsive symptoms (OCS) into specific factors is now widely accepted. However, the utility of these categories for genetic studies remains unclear, as studies examining their heritability have been inconsistent. Less attention has been paid to the possibility that clinically significant obsessionality is primarily determined by a "core" group of OCS that crosses the boundaries between symptom subgroups. The aim of this study is to determine whether such a core group exists, and to compare its heritability to that of the more traditionally derived symptom factors. We examined the properties and heritability of obsessive-compulsive symptoms in college students, medical students, and obsessive-compulsive disorder (OCD) families using the Leyton Obsessional Inventory. In each of the three samples, we identified a core group of symptoms that comprised a single unique construct and accounted for over 90% of the variation of the four more traditional symptom factors. This core construct was highly correlated with OCD in our families and had a heritability estimate of 0.19 when OCD was not included as a covariate and 0.49 when OCD was included as a covariate. In contrast, the four symptom factors were not heritable. There appears to be an underlying unidimensional component to obsessionality, both in non-clinical and clinical samples. This component, which is heritable, accounts for the majority of the variation of the more traditionally derived symptom factors in our sample, and is composed of OCS that are not specific to any of the symptom subgroups.
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