Do sex hormones confound or mediate the effect of chronotype on breast and prostate cancer? A Mendelian randomization study.

Morning-preference chronotype has been found to be protective against breast and prostate cancer. Sex hormones have been implicated in relation to chronotype and the development of both cancers. This study aimed to assess whether sex hormones confound or mediate the effect of chronotype on breast and prostate cancer using a Mendelian Randomization (MR) framework. Genetic variants associated with chronotype and sex hormones (total testosterone, bioavailable testosterone, sex hormone binding globulin, and oestradiol) (p<5×10-8) were obtained from published genome-wide association studies (n≤244,207 females and n≤205,527 males). These variants were used to investigate causal relationships with breast (nCases/nControls = 133,384/113,789) and prostate (nCases/nControls = 79,148/61,106) cancer using univariable, bidirectional and multivariable MR. In females, we found evidence for: I) Reduced risk of breast cancer per category increase in morning-preference (OR = 0.93, 95% CI:0. 88, 1.00); II) Increased risk of breast cancer per SD increase in bioavailable testosterone (OR = 1.10, 95% CI: 1.01, 1.19) and total testosterone (OR = 1.15, 95% CI:1.07, 1.23); III) Bidirectional effects between morning-preference and both bioavailable and total testosterone (e.g. mean SD difference in bioavailable testosterone = -0.08, 95% CI:-0.12, -0.05 per category increase in morning-preference vs difference in morning-preference category = -0.04, 95% CI: -0.08, 0.00 per SD increase in bioavailable testosterone). In males, we found evidence for: I) Reduced risk of prostate cancer per category increase in morning-preference (OR = 0.90, 95% CI: 0.83, 0.97) and II) Increased risk of prostate cancer per SD increase in bioavailable testosterone (OR = 1.22, 95% CI: 1.08, 1.37). No bidirectional effects were found between morning-preference and testosterone in males. While testosterone levels were causally implicated with both chronotype and cancer, there was inconsistent evidence for testosterone as a mediator of the relationship. The protective effect of morning-preference on both breast and prostate cancer is clinically interesting, although it may be difficult to effectively modify chronotype. Further studies are needed to investigate other potentially modifiable intermediates.

Chronobiological activity of cysteinyl leukotriene receptor 1 during basal and induced autophagy in the ARPE-19 retinal pigment epithelial cell line.

Autophagy is an important cellular mechanism for maintaining cellular homeostasis, and its impairment correlates highly with age and age-related diseases. Retinal pigment epithelial (RPE) cells of the eye represent a crucial model for studying autophagy, as RPE functions and integrity are highly dependent on an efficient autophagic process. Cysteinyl leukotriene receptor 1 (CysLTR1) acts in immunoregulation and cellular stress responses and is a potential regulator of basal and adaptive autophagy. As basal autophagy is a dynamic process, the aim of this study was to define the role of CysLTR1 in autophagy regulation in a chronobiologic context using the ARPE-19 human RPE cell line. Effects of CysLTR1 inhibition on basal autophagic activity were analyzed at inactive/low and high lysosomal degradation activity with the antagonists zafirlukast (ZTK) and montelukast (MTK) at a dosage of 100 nM for 3 hours. Abundances of the autophagy markers LC3-II and SQSTM1 and LC3B particles were analyzed in the absence and presence of lysosomal inhibitors using western blot analysis and immunofluorescence microscopy. CysLTR1 antagonization revealed a biphasic effect of CysLTR1 on autophagosome formation and lysosomal degradation that depended on the autophagic activity of cells at treatment initiation. ZTK and MTK affected lysosomal degradation, but only ZTK regulated autophagosome formation. In addition, dexamethasone treatment and serum shock induced autophagy, which was repressed by CysLTR1 antagonization. As a newly identified autophagy modulator, CysLTR1 appears to be a key player in the chronobiological regulation of basal autophagy and adaptive autophagy in RPE cells.

Circadian clock, carcinogenesis, chronochemotherapy connections.

The circadian clock controls the expression of nearly 50% of protein coding genes in mice and most likely in humans as well. Therefore, disruption of the circadian clock is presumed to have serious pathological effects including cancer. However, epidemiological studies on individuals with circadian disruption because of night shift or rotating shift work have produced contradictory data not conducive to scientific consensus as to whether circadian disruption increases the incidence of breast, ovarian, prostate, or colorectal cancers. Similarly, genetically engineered mice with clock disruption do not exhibit spontaneous or radiation-induced cancers at higher incidence than wild-type controls. Because many cellular functions including the cell cycle and cell division are, at least in part, controlled by the molecular clock components (CLOCK, BMAL1, CRYs, PERs), it has also been expected that appropriate timing of chemotherapy may increase the efficacy of chemotherapeutic drugs and ameliorate their side effect. However, empirical attempts at chronochemotherapy have not produced beneficial outcomes. Using mice without and with human tumor xenografts, sites of DNA damage and repair following treatment with the anticancer drug cisplatin have been mapped genome-wide at single nucleotide resolution and as a function of circadian time. The data indicate that mechanism-based studies such as these may provide information necessary for devising rational chronochemotherapy regimens.

Dietary Polyphenol Intake Is Associated with Biological Aging, a Novel Predictor of Cardiovascular Disease: Cross-Sectional Findings from the Moli-Sani Study.

Biological aging, or the discrepancy between biological and chronological age of a subject (Δage), has been associated with a polyphenol-rich Mediterranean diet and represents a new, robust indicator of cardiovascular disease risk. We aimed to disentangle the relationship of dietary polyphenols and total antioxidant capacity with Δage in a cohort of Italians. A cross-sectional analysis was performed on a sub-cohort of 4592 subjects (aged ≥ 35 y; 51.8% women) from the Moli-sani Study (2005-2010). Food intake was recorded by a 188-item food-frequency questionnaire. The polyphenol antioxidant content (PAC)-score was constructed to assess the total dietary content of polyphenols. Total antioxidant capacity was measured in foods by these assays: trolox equivalent antioxidant capacity (TEAC), total radical-trapping antioxidant parameter (TRAP) and ferric reducing-antioxidant power (FRAP). A deep neural network, based on 36 circulating biomarkers, was used to compute biological age and the resulting Δage, which was tested as outcome in multivariable-adjusted linear regressions. Δage was inversely associated with the PAC-score (ß = -0.31; 95%CI -0.39, -0.24) but not with total antioxidant capacity of the diet. A diet rich in polyphenols, by positively contributing to deceleration of the biological aging process, may exert beneficial effects on the long-term risk of cardiovascular disease and possibly of bone health.

In vitro gastrointestinal digestion and simulated colonic fermentation of pistachio nuts determine the bioaccessibility and biosynthesis of chronobiotics.

Chronodisruption leads to obesity and other metabolic disorders that can be alleviated by food-derived potential chronobiotics, such as phytomelatonin (PMT), phenolic compounds (PCs) and dietary fiber rich pistachios. Pistachios with (PN + SC) or without (PN) the seed coat were investigated for their in vitro chronobiotic potential since they are one of the main reported PMT sources. Consequently we evaluated the bioaccessibility, permeability, and biosynthesis of pistachio chronobiotics, particularly PMT, during gastrointestinal and colonic fermentation. The maximum in vitro bioaccessibility and apparent permeability (efflux-prone) of PCs, flavonoids and PMT were sample-specific [∼1.3% (both), 27 and 3.4% (PN + SC)], but additional amounts (flavonoids > PCs > PMT) were released under simulated colonic conditions. Short-chain fatty acids (SCFAs; 38 mM; >50% butyrate, PN + SC > PN) and some metabolites (e.g., indole, benzaldehyde, phenolic acids, and aliphatic/aromatic hydrocarbons) were detected depending on the sample. The predominant pistachio butyrate production during in vitro colonic fermentation can improve chronodisruption and benefit obese individuals. Pistachio's digestion increases the bioaccessibility and intestinal permeability of potential chronobiotics (PMT and PCs) and the biosynthesis of colonic metabolites (SCFAs, among others) also with chronobiotic potential.

Women amateur street runners have a higher level of chronotype self- perception than men

Abstract Aim: The aims of the present study were to verify the self-perception level of the chronotype of amateur street runners and to test the association between the chronotype, gender, age, and preferred training time. Methods: A total of 166 amateur street runners were included (♀ = 89, age 38.9 ± 11.2 years; ♂ = 77, age 38.0 ± 9.7 years). The Brazilian version of the Horne & östberg questionnaire was used to assess chronotypes and the preferred training time was determined through a multiple choice question. Based on chronotype definitions that suggest that when free to choose, morning-types (MT) would prefer training in the morning, evening-types (ET) in the evening and neither-types (NT) would not have a predilection for any specific time. The corroboration of this hypothesis was assumed as self-perception level of the chronotypes. Results: Women showed higher self-perception levels of their chronotype compared to men (58.4% vs. 41.6%; χ2 = 4.699; p = 0.030). By chronotypes, MT, NT, and ET self-perception levels were 73.9%, 15.9%, 88.9%, respectively (χ2 = 57.489; p < 0.001). The most observed women circadian typology was MT, while in men it was NT (χ2 = 8.951; p = 0.011). However, there was no significant association between gender and preferred training time (χ2 = 2.654; p = 0.265). Age, female gender and preference to exercise during the day are associated with MT. Conclusion: Women runners showed a greater perception of their circadian traits than men, despite there was no association between gender and preferred training time.

Do malignant cells sleep at night?

Biological rhythms regulate the biology of most, if not all living creatures, from whole organisms to their constitutive cells, their microbiota, and also parasites. Here, we present the hypothesis that internal and external ecological variations induced by biological cycles also influence or are exploited by cancer cells, especially by circulating tumor cells, the key players in the metastatic cascade. We then discuss the possible clinical implications of the effect of biological cycles on cancer progression, and how they could be exploited to improve and standardize methods used in the liquid biopsy field.

Genetics of physiological dysregulation: findings from the long life family study using joint models.

Recently, Mahalanobis distance (DM) was suggested as a statistical measure of physiological dysregulation in aging individuals. We constructed DM variants using sets of biomarkers collected at the two visits of the Long Life Family Study (LLFS) and performed joint analyses of longitudinal observations of DM and follow-up mortality in LLFS using joint models. We found that DM is significantly associated with mortality (hazard ratio per standard deviation: 1.31 [1.16, 1.48] to 2.22 [1.84, 2.67]) after controlling for age and other covariates. GWAS of random intercepts and slopes of DM estimated from joint models found a genome-wide significant SNP (rs12652543, p=7.2×10-9) in the TRIO gene associated with the slope of DM constructed from biomarkers declining in late life. Review of biological effects of genes corresponding to top SNPs from GWAS of DM slopes revealed that these genes are broadly involved in cancer prognosis and axon guidance/synapse function. Although axon growth is mainly observed during early development, the axon guidance genes can function in adults and contribute to maintenance of neural circuits and synaptic plasticity. Our results indicate that decline in axons' ability to maintain complex regulatory networks may potentially play an important role in the increase in physiological dysregulation during aging.

Morning chronotype is a protective factor against chemotherapy-induced hot flashes in premenopausal women with breast cancer.

PURPOSE: Adjuvant chemotherapy in patients with breast cancer often causes hot flashes, impairing quality of life. However, the chronobiological or psychiatric factors associated with the development of chemotherapy-induced hot flashes (CIHFs) remain undetermined. The purpose of this study was to investigate whether chronotype was associated with the incidence of CIHFs. METHODS: A total of 119 premenopausal women with non-metastatic breast cancer awaiting adjuvant chemotherapy after surgery without hot flashes were included. The presence of CIHF was defined as having moderate to severe hot flashes, as measured by the subscale of hot flashes in the Menopause Rating Scale, at 4 weeks after the completion of chemotherapy. Chronotype (Morning/Intermediate/Evening) was assessed with the Composite Scale of Morningness before adjuvant chemotherapy. To examine the association between chronotype and CIHF, we built logistic regression models, adjusting for age, body mass index, sleep quality, and radiation therapy. RESULTS: CIHF occurred in 50.4% of participants. Morning type was inversely associated with CIHF (reference: Intermediate type, odds ratio [OR], 0.37; 95% confidence interval [CI], 0.16-0.94; p = 0.040) in the univariate model, and the association remained significant (OR, 0.37; CI, 0.13-0.96; p = 0.045) after adjusting for age, body mass index, sleep quality, and radiation therapy. CONCLUSIONS: Morning chronotype is a protective factor against the development of CIHF in patients with breast cancer. Chronotypes should be assessed and considered in the prediction and management of CIHF.

Meta-analysis of day-of-week variation of acute aortic rupture or dissection.

INTRODUCTION: We performed a meta-analysis to assess the presence of a day-of-week rhythmic variability of acute aortic rupture or dissection (AARD) onset. EVIDENCE ACQUISITION: Eligible studies were observational studies enrolling patients with AARD and reporting day-of-week variation of AARD. Study-specific estimates, i.e. day-of-week incidence of AARD, were combined using the random-effects model. Chronobiological analysis was performed by applying a partial Fourier series to pooled day-of-week incidence by using the inverse-variance weighted least-squares method. EVIDENCE SYNTHESIS: We identified 9 eligible studies enrolling a total of 28,036 patients with AARD. Pooled incidence of AARD was 12.8% on Sunday, 15.9% on Monday, 14.8% on Tuesday, 15.1% on Wednesday, 14.7% on Thursday, 14.1% on Friday, and 12.1% on Saturday. Chronobiological analysis identified a significant (P=0.0098) day-of-week pattern in the occurrence of AARD with a peak on Monday and a nadir on Saturday. Pooled analysis demonstrated significantly more incidence on Monday than on Saturday (relative risk: 1.247; 95% CI: 1.131 to 1.374; P=0.012). CONCLUSIONS: Incidence of AARD was 12.8%, 15.9%, 14.8%, 15.1%, 14.7%, 14.1%, and 12.1%, on Sunday, Monday, Tuesday, Wednesday, Thursday, Friday, and Saturday, respectively. A significant day-of-week pattern in the occurrence of AARD with a peak on Monday and a nadir on Saturday was identified with significantly more incidence on Monday than on Saturday.

Clinical correlates of depression chronicity among people living with HIV: What is the role of suicidal ideation?

BACKGROUND: Chronicity of depression among people living with HIV (PLWH) is associated with poorer viral suppression and mortality risk. The extent to which suicidal ideation (SI) and other baseline characteristics predict a prolonged duration of depressive illness among PLWH is not known but could help identify PLWH most at risk. METHODS: Data were drawn from a sample of 1002 depressed PLWH engaged in primary care at a metropolitan HIV clinic from 2007-2018, representing 2,569 person-years. Depression characteristics were derived from the Patient Health Questionnaire 9 (PHQ-9), administered during routine screening. Other characteristics were derived from clinic data. Unadjusted and covariate-adjusted survival analyses compared the time to depression remission between depressed participants with and without SI at their initial screening. RESULTS: At baseline, 38.4% of depressed PLWH endorsed SI. Depressed PLWH with SI took significantly longer to achieve remission from depression than those without SI. The association appeared to be mediated by depression symptom severity. When adjusted for age, depression diagnosis, any recent drug use, and depression symptom severity, baseline SI no longer predicted remission hazard. LIMITATIONS: Participants were assessed for depression with variable frequency. The analysis assumed all patients received comparable treatment for their depression. Some variables were based on clinic measurements that may be subject to misclassification bias. CONCLUSIONS: These data suggest that depressed PLWH with SI are at risk for greater chronicity of depression because their depression is more severe. Accordingly, PLWH should be urgently engaged in psychiatric care in the event of SI or severe depressive symptoms.

Limitations of the Avp-IRES2-Cre (JAX #023530) and Vip-IRES-Cre (JAX #010908) Models for Chronobiological Investigations.

The principal circadian pacemaker in mammals, the suprachiasmatic nucleus (SCN), expresses a number of neuropeptides that facilitate intercellular synchrony, helping to generate coherent outputs to peripheral clocks throughout the body. In particular, arginine vasopressin (AVP)- and vasoactive intestinal peptide (VIP)-expressing neurons have been recognized as crucial subpopulations within the SCN and have thus been the focus of many chronobiological studies. Here, we analyze the neuropeptide expression of 2 popular transgenic mouse strains commonly used to direct or restrict Cre-mediated recombination to AVP- and VIP-ergic neurons. The Avp-IRES2-Cre (JAX #023530) and Vip-IRES-Cre (JAX #010908) "driver" mouse strains express the Cre recombinase under the control of the endogenous Avp or Vip gene, respectively, allowing scientists either to ablate their gene of interest or to overexpress a transgene in a cell type-specific manner. Although these are potentially very powerful tools for chronobiologists and other scientists studying AVP- and VIP-ergic neurons, we found that neuropeptide expression in these mice is significantly decreased when an IRES(2)-Cre cassette is inserted downstream of the neuropeptide-encoding gene locus. The impact of IRES(2)-Cre cassette insertion on neuropeptide expression may be a confounding factor in many experimental designs. Our findings suggest that extreme caution must be exercised when using these mouse models to avoid misinterpretation of empirical results.

[Aspirin and preeclampsia]. / Aspirine et prééclampsie.

Indications for aspirin during pregnancy are a matter of debate and there is a recent trend to an extended prescription and an overuse of aspirin in pregnancy. Aspirin is efficient in secondary prevention of preeclampsia essentially in patients with a personal history of preeclampsia. The effect of aspirin on platelet aggregation and on the TXA2/PGI2 balance is dose-dependent. The optimum dosage, from 75mg/day to 150mg/day, needs to be determined. Fetal safety data at 150mg/day are still limited. The efficacy of aspirin seems to be subject to a chronobiological effect. It is recommended to prescribe an evening or bedtime intake. Aspirin, in primary prevention of preeclampsia, given to high-risk patients identified in the first trimester by screening tests, seems to reduce the occurrence of early-onset preeclampsia. Nevertheless, there are insufficient data for the implementation of such screening procedures in practice.

Time to think: Subjective sleep quality, trait anxiety and university start time.

Poor quality sleep is related to mental health and there is increasing interest in student wellbeing and mental health. The aim of the current study was to evaluate sleep quality, daytime dozing, anxiety proneness, chronotype and preferred start time in a sample of university students. A total of 546 university students (age range, 18-55) from two university located in South East England were included and completed an online survey. Participants' self-reported age, gender, year and field of study. Sleep quality, anxiety, daytime dozing, coffee/caffeine/tobacco use (coded as binary variables), preferred start time and chronotype were also recorded. Data were analysed using independent samples t-tests, chi-square, simple mediation-analyses and Analysis of Variance. Across the entire sample 46% percent of participants rated their sleep as fairly bad or very bad. Poor quality sleep was associated with significantly higher levels of anxiety which was not mediated by chronotype. Poor quality sleep is more prevalent in the first year of university and our sample endorsed a start time for university activities approximately 2 h later than currently timetabled. The current findings demonstrate that a large proportion of students are chronically sleep deprived, obtaining, on average, less than 7 h sleep per night on week days and this was more marked in first year students. In addition, we show that poor sleep is associated with increased anxiety. Based on the current evidence the authors suggest a review of current university timetabling and examination scheduling merits immediate consideration by policy makers and educators.

Arterial pH and blood gas values in rats under three types of general anesthesia: a chronobiological study.

The aim of study was to review the status of arterial pH, pO(2) and pCO(2) under general anesthesias in dependence on the light-dark (LD) cycle in spontaneously breathing rats. The experiments were performed using three- to four-month-old pentobarbital(P)-, ketamine/xylazine(K/X)- and zoletil(Z)-anesthetized female Wistar rats after a four-week adaptation to an LD cycle (12 h light:12 h dark). The animals were divided into three experimental groups according to the anesthetic agent used: P (light n=11; dark n=8); K/X (light n=13; dark n=11); and Z (light n=18; dark n=26). pH and blood gases from arterial blood were analyzed. In P anesthesia, LD differences in pH, pO(2), and pCO(2) were eliminated. In K/X anesthesia, parameters showed significant LD differences. In Z anesthesia, LD differences were detected for pH and pO(2) only. Acidosis, hypoxia, and hypercapnia have been reported for all types of anesthesia during the light period. In the dark period, except for P anesthesia, the environment was more stable and values fluctuated within normal ranges. From a chronobiological perspective, P anesthesia was not the most appropriate type of anesthesia in these rat experiments. It eliminated LD differences, and also produced a more acidic environment and more pronounced hypercapnia than K/X and Z anesthesias.

Is Speed a Desirable Difficulty for Learning Procedures? An Initial Exploration of the Effects of Chronometric Pressure.

PURPOSE: To determine whether "chronometric pressure" (i.e., a verbal prompt to increase speed) could predictably alter medical learners' speed-accuracy trade-off during a simulated surgical task, thus modifying the challenge. METHOD: The authors performed a single-task, interrupted time-series study, enrolling surgery residents and medical students from two institutions in September and October 2015. Participants completed 10 repetitions of a simulated blood vessel ligation (placement of two ligatures 1 cm apart). Between repetitions 5 and 6, participants were verbally encouraged to complete the next repetition 20% faster than the previous one. Outcomes included time and accuracy (ligature tightness, placement distance). Data were analyzed using random-coefficients spline models. RESULTS: The authors analyzed data from 78 participants (25 medical students, 16 first-year residents, 37 senior [second-year or higher] residents). Overall, time decreased from the 1st (mean [standard deviation] 39.8 seconds [18.4]) to the 10th (29.6 [12.5]) repetition. The spline model showed a decrease in time between repetitions 5 and 6 of 8.6 seconds (95% confidence interval: -11.1, -6.1). The faster time corresponded with declines in ligature tightness (unadjusted difference -19%; decrease in odds 0.86 [0.76, 0.98]) and placement accuracy (unadjusted difference -5%; decrease in odds 0.86 [0.75, 0.99]). Significant differences in the speed-accuracy trade-off were seen by training level, with senior residents demonstrating the greatest decline in accuracy as speed increased. CONCLUSIONS: Chronometric pressure influenced the speed-accuracy trade-off and modified the challenge level in a simulated surgical task. It may help unmask correctable deficiencies or false plateaus in learners' skill development.

Dietary fish oil differentially ameliorates high-fructose diet-induced hepatic steatosis and hyperlipidemia in mice depending on time of feeding.

Chrononutrition is the science of nutrition based on chronobiology. Numerous epidemiological studies have shown that fish oil (FO) reduces the risk of cardiovascular events through various actions such as lowering triglycerides. The present study aimed to determine the time of day when the hypertriglyceridemia-decreasing ability of FO is optimal in mice. A high-fructose diet (HFrD) that induces hyperlipidemia in mice was replaced with the same diet containing 4% FO (HFrD-4% FO) at different times of the day for 2 weeks as described below. Mice were fed with HFrD alone (CTRL) or with HFrD containing 4% FO for 12 h around the time of activity onset [breakfast (BF)-FO] or offset [dinner (DN)-FO]. Plasma and liver concentrations of triglycerides and total cholesterol were reduced in BF-FO but not in DN-FO mice compared with CTRL mice. The temporal expression of genes associated with fatty acid synthesis such as Fasn, Acaca, Scd1 and Acly in the liver was significantly suppressed in both BF-FO and DN-FO mice. Expression levels of Scd1 in epididymal adipose tissue were significantly suppressed only in the BF-FO mice. Plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid were far more increased in BF-FO than in DN-FO mice. Significantly more of these n-3 polyunsaturated fatty acids (PUFAs) were excreted in the feces of DN-FO than of BF-FO mice. These findings suggest that dietary FO exerts more hypolipidemic activity at the time of breakfast than dinner because the intestinal absorption of n-3 PUFAs is more effective at that time.

Multidirectional analyses of hepatic chronotoxicity induced by cadmium in mice.

The expression levels or activities of biological defense factors can fluctuate daily following biological rhythms. We have focused on the relationship between injection timing and the degree of toxicity of cadmium (Cd) to promote the concept of "chronotoxicology," which introduces chronobiology to the field of toxicology. Our previous studies have clearly indicated that Cd may be subject to chronotoxicity. In this report, to confirm the character of the Cd-induced chronotoxicity, we performed multidirectional examinations. Male C57BL/6J mice that received a single intraperitoneal injection of CdCl2 at ZT6 showed drastic hepatic injury estimated by histopathological analyses, i.e., nuclear condensations, fatty degenerations, and hemorrhages, but showed no injury when injected at ZT18. This difference was supported by several biochemical analyses that were indicators of hepatic injury (levels of alanine aminotransferase, aspartate aminotransferase, and malondialdehyde). The chronotoxicity of Cd was also observed in multiple strains (ICR and Balb/c), in a different injection route (subcutaneous), and in multiple injections (5 injections). Based on these results, we propose that chronotoxicology may provide important information not only for toxicology but also for occupational health, i.e., the importance of injection timing for toxicity evaluation tests, the reproducibility of animal experiments, and the improvement in the quality of risk assessments for night shift workers who may be exposed to toxic substances at various times of the day.

[Peculiarities of the psychic state and quality of life in patients with duodenal ulcer in the context of chronomedicine].

Most clinicians consider duodenum ulcer as a psychosomatic disease. Objective: To show the interdependence of this condition and mental disorders and their relation to disturbances of melatonin production . Materials and Methods: 15 patients with seasonal DU and 15 healthy subjects of the control group were examined during 3 years using laboratory, endoscopic, and standard psychodiagnostic methods. Results. It was found that all patients with exacerbation of DU experienced enhanced anxiety, reduced background mood, and impaired quality of life based on general health and mental health scoring scales. The circadian rhythm of melatonin production was markedly distorted throughout the observation period but especially during exacerbations of the disease. Conclusions. The results indicate a high degree of correlation between DU and mental disorders caused by impaired production of melatonin. It suggests common etiological mechanisms of DU and psychosomatic symptom complex.