Narrow-band UVB radiation triggers diverse changes in the gene expression and induces the accumulation of M1 macrophages in human skin.

BACKGROUND: The underlying molecular mechanisms that determine the biological effects of UVB radiation exposure on human skin are still only partially comprehended. OBJECTIVES: Our goal is to examine the human skin transcriptome and related molecular mechanisms following a single exposure to UVB in the morning versus evening. METHODS: We exposed 20 volunteer females to four-fold standard erythema doses (SED4) of narrow-band UVB (309-313 nm) in the morning or evening and studied skin transcriptome 24 h after the exposure. We performed enrichment analyses of gene pathways, predicted changes in skin cell composition using cellular deconvolution, and correlated cell proportions with gene expression. RESULTS: In the skin transcriptome, UVB exposure yielded 1384 differentially expressed genes (DEGs) in the morning and 1295 DEGs in the evening, of which the most statistically significant DEGs enhanced proteasome and spliceosome pathways. Unexposed control samples showed difference by 321 DEGs in the morning vs evening, which was related to differences in genes associated with the circadian rhythm. After the UVB exposure, the fraction of proinflammatory M1 macrophages was significantly increased at both timepoints, and this increase was positively correlated with pathways on Myc targets and mTORC1 signaling. In the evening, the skin clinical erythema was more severe and had stronger positive correlation with the number of M1 macrophages than in the morning after UVB exposure. The fractions of myeloid and plasmacytoid dendritic cells and CD8 T cells were significantly decreased in the morning but not in the evening. CONCLUSIONS: NB-UVB-exposure causes changes in skin transcriptome, inhibiting cell division, and promoting proteasome activity and repair responses, both in the morning and in the evening. Inflammatory M1 macrophages may drive the UV-induced skin responses by exacerbating inflammation and erythema. These findings highlight how the same UVB exposure influences skin responses differently in morning versus evening and presents a possible explanation to the differences in gene expression in the skin after UVB irradiation at these two timepoints.

Does the duration of diabetes increase the risk of cancer? A nationwide population-based cohort of patients with new-onset diabetes and a matched reference cohort.

Diabetes mellitus and cancer are both common health issues, but the correlation between these two diseases remains unclear. We investigated the association of cumulative exposure of diabetes mellitus as an indication of hyperglycemia in terms of disease duration on multiple cancer types. We hypothesized that the risk of cancer would increase over time after the onset of diabetes. The study population consisted of a population-based cohort of 398,708 people and it was constructed from the Finnish CARING project. The Diabetes group consisted of 185,258 individuals, and the non-diabetic reference group comprised 187,921 individuals. Over 4.1 million person-years were accumulated, and the median follow-up time was 10.55 years. In the diabetes group, 25,899 cancer cases were observed compared with 23,900 cancers in the non-diabetic group. We did not find a clear relationship between the duration of diabetes mellitus and most cancer types examined. However, for cancers of the pancreas, prostate gland, bronchus, and lungs, a temporal relationship was found. Furthermore, even within the cancer types where the relationship was detected, it did not change over time. These findings indicate that diabetes does not independently increase the risk of cancer. Instead, the development of diabetes may be attributed to shared risk factors with cancer, such as obesity and/or insulin resistance accompanied by hyperinsulinemia. Thus, it is likely that the clock for increased cancer risk starts ticking already before onset of diabetes and hyperglycemia.

Impacts of temperature and solar radiation changes in northern Europe on key population health behaviors: a scoping review of reviews.

AIM: Climate change threatens health directly as well as indirectly through impacts on health-related behaviors. Physical activity, nutrition and sleep are key health-related behaviors for population health. We aimed at elucidating the impacts of climate change which emerge gradually on these three key health-related behaviors, particularly focusing on scenarios and projections relevant to people living in the northern Europe. METHODS: We conducted a systematic literature search in three different databases in January 2023 to identify English language review articles summarizing the effects of climate change on either physical activity, nutrition, sleep, or their combination. RESULTS: We identified 15 review articles on the topic. Data on climate change impacts on nutrition and sleep were sparse, and those on physical activity were heterogeneous. The climate in northern Europe will become warmer and sunnier in summer as well as warmer and darker in winter, which will probably increase the level of physical activity, but decrease the consumption of fruits and vegetables, as well as increase the occurrence of sleep disturbances in a population. CONCLUSIONS: The anticipated changes in physical activity, nutrition and sleep driven by climate change influence population health and call for grass-roots action plans for adaptation.

Systemic hormonal contraception and risk of venous thromboembolism.

INTRODUCTION: The increased risk of venous thromboembolism associated with the use of hormonal contraception is well recognized, but evidence regarding hormonal contraception containing natural estradiol is limited. This study aimed to assess the associations between the patterns of use of different systemic hormonal contraceptives and the risk of venous thromboembolism during 2017-2019. MATERIAL AND METHODS: All fertile-aged women (15-49 years) living in Finland in 2017 and using hormonal contraception in 2017 and their 1:1 age- and residence-matched controls not using hormonal contraception in 2017 (altogether 587 559 women) were selected from the Prescription Centre. All incident venous thromboembolism cases during 2018-2019 and their 4:1 age-matched controls were further analyzed in a prospective nested case-control design to assess the associations between the use (starting, stopping, continuous vs no use) of different hormonal contraception types and venous thromboembolism. RESULTS: Altogether, 1334 venous thromboembolism cases occurred during the follow-up period (incidence rate 1.14 per 1000 person-years, 95% confidence interval [CI] 1.08-1.20), with an incidence rate ratio of hormonal contraception vs no hormonal contraception use of 1.42 (95% CI 1.27-1.58). Compared with non-use, starting the use of gestodene and ethinylestradiol (adjusted odds ratio [aOR] 2.85; 95% CI 1.62-5.03), drospirenone and ethinylestradiol (aOR 1.55; 95% CI 0.98-2.44), desogestrel and ethinylestradiol (aOR 1.97; 95% CI 0.99-3.92), and transdermal patch releasing norelgestromin and ethinylestradiol (aOR 5.10; 95% CI 1.12-23.16), as well as continuing the use of gestodene and ethinylestradiol (aOR 2.60; 95% CI 1.61-4.21), drospirenone and ethinylestradiol (aOR 1.55; 95% CI 1.02-2.37), cyproterone-acetate and estrogen/ethinylestradiol (aOR 1.66; 95% CI 1.06-2.61), and vaginal ring releasing etonogestrel and ethinylestradiol (aOR 3.27; 95% CI 1.95-5.48) were associated with venous thromboembolism risk. Regarding the type of estrogen, the highest risk was associated with current use (vs non use in the previous 180 days) of ethinylestradiol-containing preparations (aOR 2.20; 95% CI 1.82-2.65), followed by estradiol-containing preparations (aOR 1.39; 95% CI 1.04-1.87) with no risk for progestin-only hormonal contraception. Current use of estradiol-containing preparations was not associated with venous thromboembolism risk after exclusion of cyproterone-acetate and estrogen/ethinylestradiol (aOR 1.05; 95% CI 0.66-1.66). CONCLUSIONS: An increased risk of venous thromboembolism is associated with ethinylestradiol-containing combined preparations. The use of estradiol-containing combined preparations confers only a slightly increased risk, possibly driven by cyproterone-containing combined oral contraceptives, whereas the use of progestin-only contraception is not associated with venous thromboembolism.

Trends and predictors in all-cause and cause-specific mortality in diabetic and reference populations during 21 years of follow-up.

BACKGROUND: Patients with diabetes mellitus (DM) have a markedly higher overall mortality from coronary heart disease (CHD), as well as many other causes of death like cancer. Since diabetes is a multisystem disease, this fact together with the increased lifespan among individuals with diabetes may also lead to the emergence of other diabetes-related complications and ultimately to diversification of the causes of death. METHODS: The study population of this observational historic cohort study consisted of subjects with DM, who had purchased for at least one insulin prescription and/or one oral antidiabetic between January 1, 1997 and December 31, 2010 (N=199 354), and a reference population matched by age, sex and hospital district (N=199 354). Follow-up was continued until December 31, 2017. All-cause and cause-specific mortality (cancer, CHD and stroke) was analysed with Poisson and Cox's regression. Associations between baseline medications and mortality were analysed using LASSO (Least Absolute Shrinkage and Selection Operator) models. RESULTS: The mortality rates were significantly elevated among the patients with DM. However, the relative risk of all-cause mortality between the DM and reference populations tended to converge during the follow-up. The lowering trend was most apparent in CHD mortality. The difference between DM and reference populations in stroke mortality vanished with a later entrance to the follow-up period. There were a few differences between DM and no-DM groups with respect to how baseline medications were associated with mortality. CONCLUSIONS: The gap between the mortality of patients with diabetes compared to subjects who are non-diabetic diminished markedly during the 21-year period. This was driven primarily by the reduced CHD mortality.

Suicidality and psychological distress in adults aged 18 to 29 years in a population-based study in Finland.

BACKGROUND: Suicidality is a major concern for young adults. We analyzed which specific items of psychological distress best predicted suicidality in a nationwide population-based sample of young adults. METHODS: A random sample (n=1995) of adults aged 18 to 29 years living in Finland, was recruited to a health examination survey (Health 2011). We analyzed the total scores on the General Health Questionnaire (GHQ-12) and the Beck Depression Inventory (BDI-13) among the participants (n=837). We assigned the participants having suicidality on the basis of two direct self-harm items on a survey questionnaire, and analyzed which of the items of the GHQ-12 were significant predictors of suicidality. RESULTS: The associations of the GHQ-12 items with suicidality were significant with the odds ratios ranging from 1.95 to 7.35. The strongest association of suicidality was with the item 11. In factor analysis, suicidality was loaded most strongly on the same factor together with the item 10. LIMITATIONS: The definition of suicidality was based on two self-reported items. CONCLUSIONS: Feeling oneself worthless was robustly associated with suicidality. It seems to be a strong predictor and could be used as a screening question for suicidality in clinical appointments.

Sunlight and health: shifting the focus from vitamin D3 to photobiomodulation by red and near-infrared light.

Both sun exposure and serum vitamin D levels have been associated with lower risks of all-cause mortality and chronic age-related diseases, e.g., cancer, diabetes and cardiovascular disease, in epidemiological studies. These associations have mainly been ascribed to beneficial effects of vitamin D. However, a vast body of randomized controlled trials (RCTs) and Mendelian randomization studies have failed to confirm any major health benefits from vitamin D supplementation. In this review, we present tentative evidence showing that red and near-infrared light, both being present in sunlight, could explain the associations between sunlight exposure and better health status. Body irradiation with red and near-infrared light, usually termed as photobiomodulation (PBM), has demonstrated beneficial effects in animal models of chronic diseases. Beyond this, preliminary evidence from RCTs suggest potential clinical benefit from PBM for chronic diseases. PBM is currently being investigated in many pre-registered clinical trials, results of which will eventually clarify the role of red and near-infrared light in the prevention and treatment of common age-related chronic diseases.

Suicidality in relation to depressive symptoms and psychological distress in adults aged 30 to 101 years in a population-based study in Finland.

BACKGROUND: Screening for suicidality has importance in terms of public health. We investigated which specific items of psychological distress best predicted suicidality in a population-based sample. METHODS: A random sample of adults aged 30-101 years, being representative of the general population living in Finland, attended a health examination survey (Health 2011). We analyzed (n = 4373) the total scores on the General Health Questionnaire (GHQ-12) and the Beck Depression Inventory (BDI-13), as well as alcohol use, depressive and anxiety disorders as assessed with the Munich-Composite International Diagnostic Interview (M-CIDI) among the participants. We assigned the participants having suicidality on the basis of the self-harm item on the BDI-13, and analyzed which of the items of the GHQ-12 were significant predictors of suicidality. RESULTS: After adjusting for background variables, five items of the GHQ-12 remained as significant predictors for suicidality: items 11, 9, 4, 6, and 5 in this descending order. LIMITATIONS: The definition of suicidality was based on only a single item of the BDI-13. CONCLUSIONS: Certain items of the GHQ-12 demonstrated strong associations with suicidality, and the GHQ-12 or a brief version of it might be used as a screening instrument for suicidality.

Narrow-band ultraviolet B (NB UV-B) exposures improve mood in healthy individuals differently depending on chronotype.

The evening chronotype is associated with psychological symptoms such as depressed mood, while skin exposure to ultraviolet radiation (UVR) may affect mood and behavior through neural and humoral routes. This pilot study aimed to investigate the impact of whole-body narrow-band (NB) UV-B exposure on current mood state and circulating 25-hydroxyvitamin D3 (25(OH)D3), interleukin-6 (IL-6), cortisol and ß-endorphin (ß-END) levels in healthy participants. Here, eleven healthy women received full-body NB UV-B exposures on four afternoons, and the chronotype was assessed with a shortened version of Horne and Östberg's Morningness-Eveningness Questionnaire (MEQ). Perceived mood was evaluated using the Visual Analogue Scale (VAS), and serum 25(OH)D3, IL-6, cortisol and ß-END concentrations were monitored daily. Decreasing VAS values showed mood to improve significantly over the five days after the four suberythematous NB UV-B exposures (p = .038), and the more the circadian preference was inclined toward eveningness, the greater the improvement in the mood dimension of wellbeing (p = .021). Baseline mood state was correlated with baseline 25(OH)D3 (r = -0.54, 95% CI: -0.86 to -0.09) and with baseline cortisol (r = -0.57, 95% CI: -0.87 to -0.04). During the NB UV-B exposures, 25(OH)D3 increased significantly, as expected, and IL-6 declined significantly by -0.35 (95% CI: -0.69 to -0.07) pg/mL from the initial values of 1.12 ± 0.66 pg/mL (p = .025). In conclusion, in our pilot study, NB UV-B exposure improved mood, especially among those with evening preference for their daily activities, as well as circulating 25(OH)D3 levels, whereas circulating IL-6 levels decreased. Abbreviations: UVR: Ultraviolet radiation; NB UV-B: narrow-band UV-B; VAS: Visual Analogue Scales; ß-END: ß-endorphin; IL-6: Interleukin-6.

Tanning dependence and seasonal affective disorder are frequent among sunbathers but are not associated.

Ultraviolet radiation (UVR) is a known risk factor for skin cancers. Those who are tanning dependent seek out UVR exposure. Many tanners have expressed symptoms of seasonal affective disorder (SAD), but conclusive evidence of a connection with tanning dependence is lacking. We evaluated the frequency of tanning dependence or abuse and symptoms of SAD among Finnish sunbathers and analysed whether phenomena are associated which could indicate a common biological mechanism. Sunbathing related tanning dependence/abuse among Finnish sunbathers were assessed using the Structured Interview for Tanning Abuse and Dependence measure (SITAD), and symptoms of SAD were assessed with the Seasonal Pattern Assessment Questionnaire (SPAQ). Of 229 sunbathers, 8% (n = 18) were classified as tanning-dependent, and 26% (n = 59) were classified as tanning abusers. Additionally, 16% (n = 37) met the criteria for SAD, and 26% (n = 60) met the criteria for subsyndromal seasonal affective disorder (S-SAD), but there was no significant association between tanning dependence or abuse and SAD or S-SAD. Sunbathing dependence or abuse and SAD/S-SAD were frequent among sunbathers, and they may promote sun-seeking risk behaviour. However, within this sample, tanning dependence and SAD/S-SAD were not associated.

Ultraviolet B radiation modifies circadian time in epidermal skin and in subcutaneous adipose tissue.

BACKGROUND: Recent findings suggest that circadian time regulates cellular functions in the skin and may affect protection against ultraviolet radiation (UVR). It is not known, however, whether UVR through skin directly affects the expression of circadian genes. We investigated the effect of ultraviolet B (UVB) exposure on cryptochrome circadian clock 1 (CRY1), cryptochrome circadian clock 2 (CRY2), and circadian associated repressor of transcription (CIART) genes. METHODS: Healthy volunteers (n = 12) were exposed to narrow-band UVB radiation of four standard erythemal dose (SED). Epidermal/dermal and subcutaneous adipose tissue samples were obtained by punch biopsies from irradiated and non-irradiated skin 10 cm away from the irradiated site 24 hours after UVB exposure. Gene expression of CRY1, CRY2, and CIART was measured using RT-PCR (TaqMan). RESULTS: Ultraviolet B radiation affected mRNA expression in the epidermal/dermal skin and in the subcutaneous adipose tissue. It down-regulated expression of CRY2 gene in the epidermal/dermal skin, whereas it up-regulated expression of CRY1 and CIART genes in the subcutaneous adipose tissue. CONCLUSION: We showed for the first time that UVB radiation affects expression of circadian genes in the subcutaneous adipose tissue. Further studies are warranted to understand the mechanisms in detail.

Alcohol use and smoking in burn patients at the Helsinki Burn Center.

OBJECTIVE: We investigated alcohol use and smoking at time of burn and their relationships with severity of burn and presence of mental disorders. METHODS: Consecutive acute burn patients (N=107) admitted to the Helsinki Burn Center were assessed with the structured clinical interview for mental disorders (SCID) at baseline and after 6 months. Information regarding being under the influence of alcohol and having smoking-related activity at burn as well as about hazardous drinking (Alcohol Use Disorders Identification Test) and heavy smoking before the burn was recorded. RESULTS: Around half (52%) of the acute burn patients were under the influence of alcohol and 19% had been both drinking and smoking at the time of the burn. Patients under the influence at the time of burn had significantly higher prevalence of lifetime mental disorders compared to those patients who were not under the influence of alcohol (73.2% vs. 45.1%, p=0.003), especially alcohol dependence (55.4% vs. 13.7%, p<0.001) and anxiety disorders (28.6% vs. 9.8%, p=0.015). Patients who had both alcohol use and smoking at burn had even more often at least one mental disorder (95.0% vs. 51.7%, p<0.001), in specific alcohol dependence (90.0% vs. 23.0%, p<0.001), or psychotic disorder (25.0% vs. 6.9%, p=0.016). The main characteristics of the burns themselves did not differ significantly between these groups. CONCLUSION: Half of the burn patients were under the influence of alcohol at the time of the burn in this study. In almost all patients where alcohol and smoking contributed to the burn a diagnosable alcohol use disorder was present. Interventions for those with alcohol use disorders and the associated risk behaviors are important for the prevention of burns.

Eveningness associates with smoking and sleep problems among pregnant women.

Sleep problems during pregnancy impair maternal health and increase the risk for adverse pregnancy outcome. The circadian preference toward eveningness has been associated with sleep problems in previous studies. Here, we studied whether evening-type women had more sleep problems during their pregnancy, as compared with other chronotypes, in a sample consisting of 1653 pregnant women from the Finnish CHILD-SLEEP Birth Cohort. Chronotype was assessed with a shortened version of the morningness-eveningness questionnaire. Pregnant evening-type women reported more sleep problems, including troubles of falling asleep (OR = 3.4, p < 0.0001), poor sleep quality (OR = 2.9, p < 0.01) and daily tiredness (OR = 3.2, p < 0.0001) than the morning-type women, even after controlling for sleep duration and sleep deprivation. They had higher scores on Epworth Sleepiness Scale (p < 0.05), Basic Nordic Sleep Questionnaire (p < 0.0001) and Global Seasonality Score (p < 0.01) and were also more often smokers, also during pregnancy (p < 0.001) and reported poorer general health (p < 0.001) than the morning-type women. They also reported having had more sleep problems during their childhood (OR = 1.5, p < 0.05) and adolescence (OR = 2.0, p < 0.001) than the morning-type women. Our results indicate that eveningness is associated with more sleep problems and unhealthy life habits during pregnancy.

Anxiety and quality of life after first-trimester termination of pregnancy: a prospective study.

INTRODUCTION: Possible effects of termination of pregnancy (TOP) on mental health are a matter of debate. MATERIAL AND METHODS: We assessed anxiety and quality of life during a one-year follow up after first-trimester TOP using the State-Trait Anxiety Inventory (STAI) Scale and EuroQoL Quality of Life Questionnaire (EQ-5D, EQ-VAS) in 742 women participating in a randomized controlled trial on early provision of intrauterine contraception. The measurements were performed before TOP, at 3 months and 1 year after TOP. Inclusion criteria were age ≥18 years, residence in Helsinki, duration of gestation <12 weeks, non-medical indication for TOP, and approval of intrauterine contraception. The trial was registered with Clinical Trials [NCT01223521]. RESULTS: When compared with baseline, the overall anxiety level was significantly lower and quality of life higher at 3 months and at 1 year. Reduction of anxiety and improvement of quality of life was especially evident (p < 0.001) in the 58% of women reporting clinically relevant anxiety at baseline. High levels of anxiety at baseline, history of psychiatric morbidity and smoking predicted significantly greater risk of poorer quality of life and elevated level of anxiety during the follow up. CONCLUSIONS: TOP is associated with a significant overall reduction of anxiety and an improvement of quality of life among women undergoing it for non-medical indications. High baseline anxiety, history of psychiatric morbidity and smoking are risk factors of persistently high levels of anxiety and poor quality of life after an induced abortion. These data are important when designing and providing post-abortion care.

[Update on Current Care Guideline: Insomnia]. / KÄYPÄ HOITO-SUOSITUS (Päivitystiivistelmä). Unettomuus.

Insomnia symptoms must be differentiated from insomnia disorder. The correct aiagnosis or insomnia aisoraer is important, as insomnia may also be a symptom of many other diseases. Cognitive behavioral methods are recommended as first-line treatment options. Treatment of acute insomnia with hypnotics should not exceed two weeks. In elderly persons adverse effects of hypnotics may exceed their beneficial effects in long-term use. Antidepressive medications acting on the histamine-1 system may be used in very small doses. The new guideline includes e.g. insomnia in pregnant and menopausal women and in cancer patients, and driving issues.

Narrow-band ultraviolet B radiation induces the expression of ß-endorphin in human skin in vivo.

BACKGROUND: Ultraviolet radiation (UVR) from the sun and solaria has addictive properties that may develop into dependence. In mice, UVR addiction was connected to ß-endorphin (ß-END) formed in the skin after UVR exposure. In humans, the formation of ß-END in skin keratinocytes has not been confirmed in vivo. OBJECTIVE: To determine with immunohistochemistry if sub-erythematous narrow-band UV-B (NB-UV-B) exposures stimulate p53 mediated expression of pro-opiomelanocortin (POMC), ß-END and α-melanocyte stimulating hormone (α-MSH) in human skin keratinocytes in vivo. METHODS: Within 12 healthy volunteers, 7 received a single 1 standard erythema dose (SED) of NB-UV-B on their whole body, and 5 volunteers received a cumulative dose of 3 SED delivered on two subsequent days i.e., 1+2 SED. Skin biopsies were taken immediately before the first exposure and at 24h from the last UV-B exposure to assess p53, ß-END, POMC, and α-MSH expression. RESULTS: Nuclear p53 expression increased in all samples taken at 24h after NB-UV-B exposure. UV-B irradiation also increased epidermal ß-END expression in 11 out of 12 samples taken at 24h after UV-B exposure. The brownish staining was localized in the cytoplasm of keratinocytes and around the nuclei, being more pronounced in the basal cell layers. POMC and α-MSH staining showed no obvious meaningful increase since only one section of each showed any change compared with basal levels. CONCLUSIONS: Our study is the first to show that UV-B exposures increase ß-END expression in epidermal keratinocytes of human skin in vivo, which could be the link to proposed UVR addiction.

Hormone therapy and mood in perimenopausal and postmenopausal women: a narrative review.

OBJECTIVE: Between 15% and 50% of women experience depressive symptoms during the menopausal transition; in 15% to 30% of perimenopausal women, they are severe enough to be regarded as a depressive disorder. Fluctuations in gonadal hormone levels are thought to contribute to these depressive conditions. Hormone therapy is commonly used to alleviate climacteric symptoms, but its effects on mood are less clear. We narratively reviewed the literature on the effects of different types of hormone therapy on mood. METHODS: Using PubMed/Medline, we searched for studies of hormone therapy in relation to depressive symptoms and disorders in perimenopause and postmenopause. RESULTS: A number of studies consistently reported estrogen therapy to be effective in improving mood in perimenopausal women. However, its efficacy for overt depression or during postmenopause was more questionable. The progestogenic component in combined hormone therapy was found to potentially counteract the beneficial influence of estrogens on mood and to even induce negative mood symptoms. In specifically focused studies, a combination of hormone therapy and antidepressants was effective in depressed perimenopausal and postmenopausal women. CONCLUSIONS: Hormone therapy may contribute to alleviating menopause-related depressive symptoms. Its administration should be followed across time and should be specifically individualized. In cases of more severe depressive conditions, a combination of antidepressant and hormone therapy should be considered.

Behavioral trait of morningness-eveningness in association with articular and spinal diseases in a population.

Earlier studies have revealed that the more the preference to schedule daily activities towards the evening hours is, the higher the odds for a range of health hazards are. Therefore, we wanted to analyze, whether the behavioral trait of morningness-eveningness is associated with articular and spinal diseases or those with musculoskeletal disorders. Participants (n = 6089), as part of the National FINRISK 2007 Study, were derived from the general population, aged 25 to 74 years, living in Finland. Chronotype was assessed based on six items from the original Horne-Östberg Morningness-Eveningness Questionnaire. Information about risk factors and the diagnoses of articular and spinal diseases were based on the self-reported information. Our results suggest that Evening-types have higher odds for articular and spinal diseases as compared with Morning-types, and this risk is heightened especially regarding spinal disease and backache (odds ratios of 1.8 to 2.1, and 1.6 to 1.8, respectively) and remains significant after controlling for the sex, age, education, civil status, physical activity, alcohol use, and smoking, and additionally for the body-mass index, insufficient sleep, or depressive symptoms.

Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium.

OBJECTIVES: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach. DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress. PARTICIPANTS: Current, former and never smokers of European ancestry aged ≥16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). PRIMARY OUTCOME MEASURES: Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis. RESULTS: The analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR=1.02, 95% CI 0.97 to 1.07) or psychological distress (OR=1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers. CONCLUSIONS: Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the development of depression and anxiety.