Biomedical subjects

Ania Korszun

Publications and source records attributed to Ania Korszun.

13 recordsLinked to original sources

PubMed2007

Interrelationship of childhood trauma, neuroticism, and depressive phenotype.

Both childhood trauma (CT) and genetic factors contribute to the pathophysiology of depression. We studied the relationship of CT to age of onset (AO) of depression, personality traits, and expression of symptom dimensions in 324 adults with recurrent unipolar depression. Subjects received structured psychiatric interviews and completed CT, depressive symptom, and personality rating questionnaires. Experience of at least one type of trauma was reported by 79.9% of subjects, and the most common forms of trauma were physical neglect, emotional abuse, and emotional neglect. There was an earlier AO of depression in the groups that reported CT compared to those that reported none, with earliest AO occurring in those who had experienced the highest levels of CT. There were no significant correlations between overall CT scores and neuroticism or extraversion. Total CT was a significant (P=.008) predictor of the Mood symptom dimension, mostly accounted for by emotional abuse (P=.019), and physical neglect predicted the Anxiety symptom dimension (P=.002). All types of CT are commonly reported in individuals with depression, and emotional abuse and physical neglect, though previously less well identified, appear to have an important role in the pathogenesis of depressive disorders. The effect of CT on individuals with an underlying genetic vulnerability to depression may result in differences in depressive phenotype characterized by earlier AO of depression and the expression of specific depressive symptom dimensions.

Adolescent↗

PubMed2006

Metyrapone improves endothelial dysfunction in patients with treated depression.

OBJECTIVES: This study sought to examine the effect of metyrapone on endothelial dysfunction in patients with treated recurrent major depression. BACKGROUND: Depression is an independent risk factor for the development of coronary heart disease, and patients with depression have endothelial dysfunction, an atherogenic abnormality. This abnormality may be attributable to abnormal hypothalamic-pituitary-adrenal (HPA) axis function, a feature of depression, resulting in increased exposure to cortisol. Cortisol administration produces endothelial dysfunction in healthy subjects. METHODS: We measured endothelial function using flow-mediated dilation (FMD) of the brachial artery in 30 patients with depression and in 36 matched control subjects. Patients were randomized (double blind) to metyrapone (an inhibitor of cortisol synthesis) or placebo, and FMD was remeasured 6 h later. RESULTS: At baseline, FMD was impaired in patients versus control subjects (mean [standard error]), -1.27% [0.91%] vs. 4.37% [0.59%] (p < 0.001). The FMD was similar in the placebo and the metyrapone patient groups at baseline (0.17% [1.04%] vs. -2.72% [1.30%], p = 0.11). Metyrapone significantly reduced plasma cortisol levels. There was a significant improvement in FMD in the metyrapone group from -2.72% [1.30%] to 3.82% [0.99%] (p < 0.001), whereas the change in the placebo group, from 0.17% [1.04%] to 1.15% [1.14%], was not significant. Analysis of covariation showed that the effect of metyrapone was significant (p = 0.034). CONCLUSIONS: Inhibition of cortisol production by metyrapone ameliorates the endothelial dysfunction seen in depression, suggesting that the mechanism of the endothelial dysfunction may involve cortisol.

Adult↗

PubMed2006

Dental implant treatment for patients with psychiatric disorders.

The literature with respect to whether or not psychiatric disorders represent a contraindication to dental implant treatment is sparse and contradictory. This paper describes three cases in which patients with psychiatric disorders were provided with dental implant retained prostheses. It is concluded that mental health disorders are not necessarily a contraindication to dental implant treatment and dental implant treatment can provide valuable psychological support. If any doubt exists about the effect of a psychiatric disorder on the prognosis of implant treatment the opinion of a psychiatrist should be obtained. The development of liaison psychiatry for dental hospitals should be seen as an ideal.

Aged↗

PubMed2005

Whole genome linkage scan of recurrent depressive disorder from the depression network study.

Genome-wide linkage analysis was carried out in a sample of 497 sib pairs concordant for recurrent major depressive disorder (MDD). There was suggestive evidence for linkage on chromosome 1p36 where the LOD score for female-female pairs exceeded 3 (but reduced to 2.73 when corrected for multiple testing). The region includes a gene, MTHFR, that in previous studies has been associated with depressive symptoms. Two other regions, on chromosomes 12q23.3-q24.11 and 13q31.1-q31.3, showed evidence for linkage with a nominal P < 0.01. The 12q peak overlaps with a region previously implicated by linkage studies of unipolar and bipolar disorders and contains a gene, DAO, that has been associated with both bipolar disorder and schizophrenia. The 13q peak lies within a region previously linked strongly to panic disorder. A fourth modest peak with an LOD of greater than 1 on chromosome 15q lies within a region that showed genome-wide significant evidence of a recurrent depression locus in a previous sib-pair study. Both the 12q and the 15q findings remained significant at genome-wide level when the data from the present study and the previous reports were combined.

Adolescent↗

PubMed2005

Inhibition of cortisol production with metyrapone prevents mental stress-induced endothelial dysfunction and baroreflex impairment.

OBJECTIVES: This study was designed to investigate the role of cortisol in stress-induced endothelial dysfunction and impaired baroreflex sensitivity (BRS) by blocking cortisol production with metyrapone before subjecting healthy volunteers to mental stress. BACKGROUND: Mental stress raises cortisol levels and is associated with increased coronary heart disease (CHD) morbidity and mortality, especially from sudden cardiac death. It also causes endothelial dysfunction and impaired BRS. METHODS: We measured brachial artery flow-mediated dilation (FMD), a measure of endothelial function, and BRS in 36 subjects without CHD risk factors who were then randomized in a double-blind fashion to oral metyrapone 750 mg x 2 or placebo. Five hours later we subjected subjects to mental stress and then remeasured endothelial function and BRS. RESULTS: Prestress cortisol levels were significantly higher in the placebo group at 270.5 (30.9) nmol/l versus 89.1 (11.8) nmol/l (p = 0.01), and the increase with stress was higher at 57.9 (17.9) nmol/l versus 11.2 (2.2) nmol/l (p < 0.001). In the placebo group, compared to baseline, FMD and BRS fell significantly from 4.5% (0.7%) to 1.4% (1.1%) (p = 0.02) and 21.4 (2.3) ms/mmHg to 16.3 (1.5) ms/mmHg (p = 0.04), respectively. In the metyrapone group, FMD and BRS were unchanged from baseline: 4.3% (0.9%) versus 5.1% (0.8%) (p = 0.48) and 26.4 (2.9) ms/mmHg versus 24.9 (2.6) ms/mmHg (p = 0.62), respectively. Analysis of covariation showed a significant effect of metyrapone on change in both FMD (p = 0.009) and BRS (p = 0.024). CONCLUSIONS: Stress-related endothelial dysfunction and BRS impairment can be prevented by blocking cortisol production with metyrapone, demonstrating a direct or facilitative role for cortisol in these phenomena and suggesting mechanisms by which stress contributes to CHD and sudden cardiac death.

Adult↗

PubMed2005

Assessment of professional attitude and conduct in medical undergraduates.

One year after implementation of a new schedule of summative assessment of professional attitude and conduct (AC) for medical undergraduates at the University of Wales College of Medicine (UWCM), we evaluated its effectiveness and obtained feedback of the perceptions of participating teachers and students. An anonymous questionnaire was administered to all 4th year students and their clinical teachers. Four out of 180 students actually failed to complete the 4th year as a result of unsatisfactory AC. Of these, three students were identified as having a problem which benefited from supportive remediation. One hundred and twenty out of 244 (49%) teachers and 166 out of 195 (85%) students completed the feedback questionnaires. The majority of students and teachers agreed that AC should be an integral part of their assessment. However, several problems were highlighted, in particular, students' perception that marks were sometimes based on assessment of knowledge rather than attitude and conduct and teachers' reluctance to identify unprofessional behaviour in students. The use of longitudinal assessment of professional AC was found to be effective at identifying students with persistent AC problems and also provided an opportunity for formative experience. The reluctance of teachers to identify negative behaviours, compared to deficiencies in skill and knowledge, is an important aspect of developing a reliable method of evaluating professional attitudes.

Attitude↗

PubMed2004

The Depression Network (DeNT) Study: methodology and sociodemographic characteristics of the first 470 affected sibling pairs from a large multi-site linkage genetic study.

BACKGROUND: The Depression Network Study (DeNt) is a multicentre study designed to identify genes and/or loci linked to and/or associated with susceptibility to unipolar depression in Caucasian families. This study presents the method and socio-demographic details of the first 470 affected sibling pairs recruited from 8 different sites in Europe and the United States of America. METHODS: Probands fulfilling either the Diagnostic and Statistical Manual 4th edition (DSM-IV) or the International Classification of Diseases 10th edition (ICD-10) criteria for recurrent unipolar depression of moderate or severe degree and who had at least one similarly affected sibling were eligible for the study. Detailed clinical and psychological assessments were undertaken on all subjects including an interview using the Schedules for Clinical Assessment in Neuropsychiatry. Blood samples were collected from all participants to extract DNA for linkage analysis. RESULTS: The different sites used different recruitment strategies depending on local health care organisation but despite this there was remarkable similarity across sites for the subjects recruited. Although the Bonn site had significantly older subjects both for age of onset and age at interview, for the sample as a whole, subjects were interviewed in their mid-40s and had experienced the onset of their recurrent depression in their 20s. Preliminary genome screening was able to include 929 out of the 944 subjects (98.4%) typed at 932 autosomal and 544 X chromosome markers. CONCLUSIONS: This paper describes the methodology and the characteristics of the subjects from the 414 families included in the first wave of genotyping from the multi-site DeNT study. Ultimately the study aims to collect affected sibling pairs from approximately 1200 families.

Age of Onset↗

PubMed2004

Familiality of symptom dimensions in depression.

BACKGROUND: Depression is a clinically heterogeneous disorder thought to result from multiple genes interacting with environmental and developmental components. A dimensional rather than a categorical approach to depressive phenotype definition may be more useful for identification of susceptibility genes. OBJECTIVES: To perform an exploratory factor analysis on a range of depressive and anxiety symptoms in a large, well-defined sample of depressed siblings, as well as a confirmatory factor analysis in a separate large group of unrelated depressed subjects, and to analyze correlations of identified symptom dimensions between depressed siblings. DESIGN: Subjects (N = 1034), including 475 sibling pairs, with a history of at least 2 depressive episodes were recruited from the Depression Network Study, a large-scale multicenter collection of families affected by recurrent unipolar depression. Subjects were interviewed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and diagnosed according to the DSM-IV and the International Classification of Diseases, 10th Revision, using a computerized scoring program (CATEGO5). Factor analysis was carried out on 26 depression symptom items, including 4 anxiety screening items. Confirmatory factor analysis was performed on an independent sample of 485 depressed individuals. RESULTS: Four interpretable factors were identified: (1) mood symptoms and psychomotor retardation; (2) anxiety; (3) psychomotor agitation, guilt, and suicidality; and (4) appetite gain and hypersomnia. For each symptom group, a quantitative scale was constructed, and correlations between siblings were calculated. There was a moderate degree of sibling homotypia for some depressive symptoms, and factors 1, 2, and 3 showed significant positive familial correlation (0.145 [P =.001], 0.335 [P<.001], and 0.362 [P<.001], respectively). CONCLUSIONS: This is the first study of large, well-defined samples of depressed subjects in whom symptom dimensions have been derived and then confirmed using independent material. The significant correlations between siblings for 3 of the dimensions suggest substantial familial, perhaps genetic, etiologies.

Adult↗

PubMed2004

Basal circadian and pulsatile ACTH and cortisol secretion in patients with fibromyalgia and/or chronic fatigue syndrome.

The objective of this study was to evaluate and compare the basal circadian and pulsatile architecture of the HPA axis in groups of patients with FMS, CFS, or both syndromes with individually matched control groups. Forty patients with either FMS (n = 13), FMS and CFS (n = 12), or CFS (n = 15) were matched by age (18-65), sex, and menstrual status to healthy controls. Subjects were excluded if they met criteria for major Axis I psychiatric disorders by structured clinical interview (SCID). Subjects were admitted to the General Clinical Research Center where meals and activities were standardized. Blood was collected from an intravenous line every 10 min over 24 h for analysis of ACTH and cortisol. Samples were evaluable for ACTH in 36 subject pairs and for cortisol in 37 subject pairs. There was a significant delay in the rate of decline from acrophase to nadir for cortisol levels in patients with FMS (P <.01). Elevation of cortisol in the late evening quiescent period was evident in half of the FMS patients compared with their control group, while cortisol levels were numerically, but not significantly, lower in the overnight period in patients with CFS compared with their control group. Pulsatility analyses did not reveal statistically significant differences between patient and control groups. We conclude that the pattern of differences for basal circadian architecture of HPA axis hormones differs between patients with FMS and CFS compared to their matched control groups. The abnormalities in FMS patients are consistent with loss of HPA axis resiliency.

Adrenocorticotropic Hormone↗

PubMed2002

Use of actigraphy for monitoring sleep and activity levels in patients with fibromyalgia and depression.

OBJECTIVE: The hallmark symptom of fibromyalgia (FM) is widespread chronic pain, but most patients are also impaired due to fatigue and sleep disturbance, and there is a strong association with depression. We compared levels of activity and sleep patterns in FM patients, with and without comorbid depression, to those of normal healthy controls and depressed patients. METHODS: Actigraphy was carried out on 16 patients with uncomplicated FM, 6 FM patients with comorbid depression, 9 patients with recurrent major depression, and 28 healthy controls over a period of 5-7 days. The means of daytime activity levels, nighttime activity levels, and percentage time spent asleep during the daytime and nighttime were calculated and compared. RESULTS: Controls showed high levels of activity during the day and uninterrupted periods of sleep at night. Patients with FM alone showed similar levels of daytime activity, but disturbed sleep with significantly increased levels of activity at night compared to normal controls. Patients with depression alone also showed disturbed sleep compared to normal controls. However, patients with FM and comorbid depression showed the most impairment, with significantly reduced daytime activity and significantly increased daytime sleeping compared to controls, as well as more sleep interruption and movement during the night. CONCLUSION: Actigraphy is a useful means of studying activity levels and sleep patterns and demonstrated significant differences between FM patients with and without comorbid depression.

Depressive Disorder↗

PubMed2002

The hypothalamic-pituitary-gonadal axis in mood disorders.

This article has demonstrated that stress and HPA axis activation affect the reproductive axis. Despite similarities in the HPA axis picture between women with major depression and those with hypothalamic amenorrhea and exercise or nutritional amenorrhea, no abnormalities in LH secretion have been documented in major depression. Lower estradiol in the follicular phase in depressed women and lower testosterone in depressed men however, have been observed [81, 92]. Although PMS would appear to be the best candidate for a mood disorder associated with abnormalities in reproductive hormones, no abnormalities in LH, estradiol or progesterone have been documented in PMS either [62]. Similarly, blockade of progesterone appears to be ineffective as a treatment for PMS [79]. Complete elimination of monthly cycling with leuprolide improves mood, however. No published studies have examined women with major depression to determine whether leuprolide will exacerbate or improve depressive symptoms. Some studies suggest beneficial effects of estrogen on mood in postmenopausal women, but no placebo controlled studies have explored estrogen augmentation in the treatment of major depression in either post- or premenopausal women, although estrogen is beneficial in women with perimenopause-related mood disorders [78].

Amenorrhea↗

PubMed2002

Facial pain, depression and stress - connections and directions.

Chronic facial pain is associated with depression, stress and other chronic pain disorders such as fibromyalgia. There is growing evidence that all these conditions share underlying pathophysiological processes. This review explores this relationship and examines the role of the main stress hormone axis, the hypothalamic-pituitary-adrenal axis, in the pathogenesis of facial pain including possible future therapeutic approaches.

Chronic Disease↗

PubMedDate not supplied

Baroreflex sensitivity is reduced in depression.

OBJECTIVES: Depression is independently associated with increased cardiovascular morbidity and mortality, including sudden cardiac death, and this risk is observed even in patients who have been successfully treated for depression. Recent studies have emphasized the importance of impaired baroreceptor sensitivity (BRS) as a predisposing factor for sudden death in patients with manifest cardiac disease. Our objective was to test the hypothesis that BRS is impaired in subjects with depression in remission and with no other cardiac risk factors. METHODS: We measured BRS by the sequence method in 36 patients with treated recurrent depression, who were euthymic at the time of study and with no manifest cardiac disease or "conventional" cardiac risk factors, compared with 39 healthy controls. Exclusion criteria included manifest heart disease or any risk factor for IHD (smoking, hypertension, diabetes, hypercholesterolemia, or body mass index >30). Nine subjects were not on any medication, and 22 were taking antidepressants. None of the controls was taking any medication. RESULTS: BRS was significantly lower in patients than in controls (19.5 [1.78] versus 25.4 [1.69] ms/mm Hg, p = .017). Analysis of covariance, in which age, sex, cholesterol, and body mass index were included, also showed that depression was a significant (p = .027) predictor of BRS. There was no significant difference in BRS adjusted by age and sex between the subjects taking antidepressants compared with those on no medications (p = .40). CONCLUSIONS: These data indicate that BRS is impaired in otherwise healthy patients with depression and may contribute to their increased cardiac risk.

Adult↗