The effect of vitamin D supplementation on depressive symptoms in adults: A systematic review and meta-analysis of randomized controlled trials.

Neurosteroid and immunological actions of vitamin D may regulate depression-linked physiology. Meta-analyses investigating the effect of vitamin D on depression have been inconsistent. This meta-analysis investigated the efficacy of vitamin D in reducing depressive symptoms among adults in randomized placebo-controlled trials (RCT). General and clinical populations, and studies of ill individuals with systemic diseases were included. Light therapy, co-supplementation (except calcium) and bipolar disorder were exclusionary. Databases Medline, PsycINFO, CINAHL and The Cochrane Library were searched to identify relevant articles in English published before April 2022. Cochrane risk-of-bias tool (RoB 2) and GRADE were used to appraise studies. Forty-one RCTs (n = 53,235) were included. Analyses based on random-effects models were performed with the Comprehensive Meta-analysis Software. Results for main outcome (n = 53,235) revealed a positive effect of vitamin D on depressive symptoms (Hedges' g = -0.317, 95% CI [-0.405, -0.230], p < 0.001, I2 = 88.16%; GRADE: very low certainty). RoB assessment was concerning in most studies. Notwithstanding high heterogeneity, vitamin D supplementation ≥ 2,000 IU/day appears to reduce depressive symptoms. Future research should investigate possible benefits of augmenting standard treatments with vitamin D in clinical depression. PROSPERO registration number: CRD42020149760. Funding: Finnish Medical Foundation, grant 4120 and Juho Vainio Foundation, grant 202100353.

Association between alexithymia and substance use: A systematic review and meta-analysis.

Alexithymia has been associated with substance use, but the magnitude of the association has not been evaluated and sub-group differences, if any, are unknown. The aim of this meta-analysis is to systematically review the association between alexithymia and substance use (alcohol or illicit drugs). We identified studies through a systematic review of PubMed and Web of Science and obtained a total of 52 publications using the Toronto Alexithymia Scale-20 scale. Random effects meta-analysis was used to evaluate the overall and sub-group associations. Of the studies, 50 were cross-sectional and two longitudinal. Alexithymia was associated with any substance use (Cohen's d = 0.62, 95% confidence interval [CI] 0.49-0.76), with little difference between estimates for use of alcohol or illicit drugs. A stronger association was observed for the alexithymia dimension "Difficulty in Identifying Feelings" (d = 0.64, 95% CI = 0.47-0.81) and "Difficulty in Describing Feelings" (d = 0.44, 95% CI = 0.32-0.55) than for "Externally Oriented Thinking" (d = 0.19, 95% CI = 0.09-0.28). The association was stronger in studies with clinical patient populations (d = 0.83, 95% CI = 0.62-1.05) than in those investigating general or student populations, and in studies with a majority of male rather than female participants. These findings suggest a strong overall association between alexithymia and substance use and a very strong association among clinical patient populations. The association may be stronger with the emotion-related dimensions than with the cognition-related dimension of alexithymia. As nearly all the studies were cross-sectional, more longitudinal studies are needed.

Cerebrospinal fluid dynamics in idiopathic intracranial hypertension: a literature review and validation of contemporary findings.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a rare disease of unknown aetiology related possibly to disturbed cerebrospinal fluid (CSF) dynamics and characterised by elevated intracranial pressure (ICP) causing optic nerve atrophy if not timely treated. We studied CSF dynamics of the IIH patients based on the available literature and our well-defined cohort. METHOD: A literature review was performed from PubMed between 1980 and 2020 in compliance with the PRISMA guideline. Our study includes 59 patients with clinical, demographical, neuro-ophthalmological, radiological, outcome data, and lumbar CSF pressure measurements for suspicion of IIH; 39 patients had verified IIH while 20 patients did not according to Friedman's criteria, hence referred to as symptomatic controls. RESULTS: The literature review yielded 19 suitable studies; 452 IIH patients and 264 controls had undergone intraventricular or lumbar CSF pressure measurements. In our study, the mean CSF pressure, pulse amplitudes, power of respiratory waves (RESP), and the pressure constant (P0) were higher in IIH than symptomatic controls (p < 0.01). The mean CSF pressure was higher in IIH patients with psychiatric comorbidity than without (p < 0.05). In IIH patients without acetazolamide treatment, the RAP index and power of slow waves were also higher (p < 0.05). IIH patients with excess CSF around the optic nerves had lower relative pulse pressure coefficient (RPPC) and RESP than those without (p < 0.05). CONCLUSIONS: Our literature review revealed increased CSF pressure, resistance to CSF outflow and sagittal sinus pressure (SSP) as key findings in IIH. Our study confirmed significantly higher lumbar CSF pressure and increased CSF pressure waves and RAP index in IIH when excluding patients with acetazolamide treatment. In overall, the findings reflect decreased craniospinal compliance and potentially depleted cerebral autoregulation resulting from the increased CSF pressure in IIH. The increased slow waves in patients without acetazolamide may indicate issues in autoregulation, while increased P0 could reflect the increased SSP.

The effects of loneliness and social isolation on all-cause, injury, cancer, and CVD mortality in a cohort of middle-aged Finnish men. A prospective study.

OBJECTIVES: Loneliness and social isolation both increase mortality and are likely to affect health via several pathways. However, information on the potential pathways remains scarce. We investigated the associations between loneliness, social isolation, and mortality, and possible mechanisms underlying these connections. METHODS: The analyzed data comprised a prospective population-based cohort of Finnish men (42-61 years at baseline, n = 2588) who were followed up for an average of 23.2 years. Mortality data were obtained from the national population register in 2012. Cox proportional hazards analysis with adjustments for possible confounding factors was used to examine the associations between loneliness and social isolation at baseline and all-cause, injury, cancer, and cardiovascular disease (CVD) mortality. Mediation analysis was conducted to investigate the mechanisms underlying the associations of loneliness and social isolation with mortality. RESULTS: Loneliness predicted all-cause mortality, even after adjustments for all covariates. Loneliness predicted cancer mortality, except after adjustments for lifestyle variables or Human Population Laboratory (HPL) depression scores, and also predicted CVD mortality, except after adjustments for HPL depression scores. Social isolation predicted all-cause mortality and injury mortality. The effect of social isolation on all-cause mortality was mediated by loneliness and HPL depression scores. CONCLUSIONS: Our findings suggest that both loneliness and social isolation increase the risk of all-cause mortality, while they have differing effects on different causes of death. Loneliness and depressive symptoms may mediate the effect of social isolation on increased mortality.

Depression and loneliness may have a direct connection without mediating factors.

PURPOSE OF THE ARTICLE: There is growing interest in loneliness and its various adverse effects on mental and physical health. While depression is one of the adverse health effects associated with loneliness, there have been some limitations in previous studies: 1) Research has mostly been carried out either in depressed patient samples or in general population samples with depressive symptoms as an outcome, 2) the follow-up times have been rather short, and 3) the mechanisms through which loneliness associates with depression are still unclear. MATERIALS AND METHODS: We examined the association between loneliness and incident depression and possible mechanisms underlying this association in a population-based sample of middle-aged men (N = 2339; mean age 53; mean follow-up time 23.5 years). The association between loneliness and depression was explored with Cox proportional hazard analysis, and mediation analyses were performed with the PROCESS macro for SPSS. We used 13 health and lifestyle-related variables as covariates for adjustments in multivariate models and as mediators in simple mediation models. RESULTS: Those with depression as an outcome (n = 99) had significantly higher loneliness scale scores at baseline, and baseline loneliness was associated with depression, despite adjustments for potential confounding factors. No mediating factors were observed. CONCLUSIONS: There was a strong direct association between loneliness and the incidence of depression. Based on our results, we encourage future researchers to look for possible mediators in wider range of variables.

Parental Alcohol Problems, Parental Divorce, and Type 2 Diabetes in Adulthood: A Longitudinal Prospective Cohort Study in Middle-Aged Men.

OBJECTIVE: Type 2 diabetes is a chronic disease and a serious global public health concern increasing both mortality and morbidity. Previous studies have found evidence for an association between early psychological stress and diabetes later in life. METHODS: This study examined the association between parental alcohol problems and parental divorce and the incidence of type 2 diabetes in Finnish men aged 42 to 61 years (n = 754) in a prospective setting. Information on parental alcohol problems and parental divorce was derived from school records and subjective experiences of the same events from self-rated questionnaires. The average follow-up time for the participants until the first type 2 diabetes diagnosis was 23.3 years (25th-75th percentile, 21.2-27.9 years). RESULTS: Cox regression analyses revealed that parental alcohol problems (hazard ratio = 3.09, 95% confidence interval = 1.38-6.88) were associated with an increased risk of type 2 diabetes during the follow-up, even after adjustment for age, marital status, education, Human Population Laboratory Depression Scale scores, smoking, alcohol consumption, body mass index, and serum high-sensitivity C-reactive protein. In a similar model, parental divorce (hazard ratio = 1.69, 95% confidence interval = 0.40-7.05) was not associated with an increased risk of type 2 diabetes during the follow-up. CONCLUSIONS: Our findings suggest that not all adverse childhood experiences contribute equally to the risk of type 2 diabetes. Parental alcohol problems, but not parental divorce, were associated with an increased risk of type 2 diabetes in men. These findings highlight the need for early interventions targeting parents with excessive alcohol consumption to reduce their offspring's risk of life-style-related disorders.

Maternal depression and inflammation during pregnancy.

BACKGROUND: Maternal depression during pregnancy increases the risk for adverse developmental outcomes in children. However, the underpinning biological mechanisms remain unknown. We tested whether depression was associated with levels of and change in the inflammatory state during pregnancy, if early pregnancy overweight/obesity or diabetes/hypertensive pregnancy disorders accounted for/mediated these effects, and if depression added to the inflammation that typically accompanies these conditions. METHODS: We analyzed plasma high-sensitivity C-reactive protein (hsCRP) and glycoprotein acetyls at three consecutive stages during pregnancy, derived history of depression diagnoses before pregnancy from Care Register for Healthcare (HILMO) (N = 375) and self-reports (N = 347) and depressive symptoms during pregnancy using the Center for Epidemiological Studies Depression Scale completed concurrently to blood samplings (N = 295). Data on early pregnancy body mass index (BMI) and diabetes/hypertensive pregnancy disorders came from medical records. RESULTS: Higher overall hsCRP levels, but not change, during pregnancy were predicted by history of depression diagnosis before pregnancy [HILMO: mean difference (MD) = 0.69 standard deviation (s.d.) units; 95% confidence interval (CI) 0.26-1.11, self-report: MD = 0.56 s.d.; 95% CI 0.17-0.94] and higher depressive symptoms during pregnancy (0.06 s.d. per s.d. increase; 95% CI 0.00-0.13). History of depression diagnosis before pregnancy also predicted higher overall glycoprotein acetyls (HILMO: MD = 0.52 s.d.; 95% CI 0.12-0.93). These associations were not explained by diabetes/hypertensive disorders, but were accounted for and mediated by early pregnancy BMI. Furthermore, in obese women, overall hsCRP levels increased as depressive symptoms during pregnancy increased (p = 0.006 for interaction). CONCLUSIONS: Depression is associated with a proinflammatory state during pregnancy. These associations are mediated by early pregnancy BMI, and depressive symptoms during pregnancy aggravate the inflammation related to obesity.

Adverse childhood experiences and alexithymia in patients with major depressive disorder.

The purpose of the article: Adverse childhood experiences (ACEs) have been postulated to negatively affect the development of emotional regulation. However, little is known about specific associations between ACEs, depressive symptoms, and alexithymia or its components [i.e. difficulty in identifying feelings (DIF), difficulty in describing feelings to others (DDF) and externally-oriented thinking (EOT)] in patients with major depressive disorder (MDD). The aims of the present cross-sectional study were to (1) compare ACEs (emotional neglect, emotional abuse, physical neglect, physical abuse, sexual abuse) between alexithymic and non-alexithymic patients with MDD; (2) explore whether specific ACEs, depressive symptoms or the interaction between sex and depressive symptoms predicted TAS-20 or its components.Materials and Methods: The study sample consisted of 186 psychiatric outpatients with MDD (aged 21-61 years, mean 33.87 years, SD 10.88) recruited from the Department of Psychiatry, Kuopio University Hospital between 2016-2019. Alexithymia and its components were assessed using the 20-item Toronto Alexithymia Scale (TAS-20). ACEs were assessed with the Trauma and Distress Scale (TADS).Results: Almost all patients with alexithymia and 80% of non-alexithymic patients reported that they had experienced emotional abuse or neglect, at least sometimes. Approximately 60% of MDD patients reported having experienced physical neglect and 30% described physical abuse. Emotional and physical abuse and neglect predicted DDF score.Conclusions: These findings suggest that among MDD patients, early experiences of emotional and physical abuse and neglect is associated with difficulties in describing feelings in adulthood.

Kuopio birth cohort - design of a Finnish joint research effort for identification of environmental and lifestyle risk factors for the wellbeing of the mother and the newborn child.

BACKGROUND: A Finnish joint research effort Kuopio Birth Cohort (KuBiCo) seeks to evaluate the effects of genetics, epigenetics and different risk factors (medication, nutrition, lifestyle factors and environmental aspects) during pregnancy on the somatic and psychological health status of the mother and the child. METHODS: KuBiCo will ultimately include information on 10,000 mother-child pairs who have given their informed consent to participate in this cohort. Identification of foetal health risk factors that can potentially later manifest as disease requires a repository of relevant biological samples and a flexible open up-to-date data handling system to register, store and analyse biological, clinical and questionnaire-based data. KuBiCo includes coded questionnaire-based maternal background data gathered before, during and after the pregnancy and bio-banking of maternal and foetal samples that will be stored in deep freezers. Data from the questionnaires and biological samples will be collected into one electronic database. KuBiCo consists of several work packages which are complementary to each other: Maternal, foetal and placental metabolism and omics; Paediatrics; Mental wellbeing; Prenatal period and delivery; Analgesics and anaesthetics during peripartum period; Environmental effects; Nutrition; and Research ethics. DISCUSSION: This report describes the set-up of the KuBiCo and descriptive analysis from 3532 parturients on response frequencies and feedback to KuBiCo questionnaires gathered from June 2012 to April 2016. Additionally, we describe basic demographic data of the participants (n = 1172). Based on the comparison of demographic data between official national statistics and our descriptive analysis, KuBiCo represents a cross-section of Finnish pregnant women.

Bifrontal active and sham rTMS in treatment-resistant unipolar major depression.

BACKGROUND AND AIM: Prevention of the recurrence of major depression and its residual symptoms requires effective treatment. Our aim was to study the effects of bifrontal active rTMS controlled by sham rTMS in treatment-resistant unipolar major depressive disorder (MDD). METHODS: Thirty-seven patients with treatment-resistant MDD were randomized into two groups. One group received a total of 30 sessions of active bifrontal rTMS (10 Hz rTMS on left dorsolateral prefrontal cortex (DLPFC) and 1 Hz rTMS on right DLPFC) and the other group received bilateral sham rTMS on five days a week for six weeks. RESULTS: Depressive symptoms significantly improved in both the groups, but without a significant group difference. Furthermore, patients with psychotic depression improved similarly to those with moderate or severe depression. CONCLUSIONS: The results of present study indicate a large sham effect of stimulation treatment. The intensive structured treatment protocol may explain the positive outcome in both the groups. It is important to recognize, appreciate, and utilize placebo effects as a significant means of rehabilitation in psychiatric care.

Comparison of early maladaptive schemas between borderline personality disorder and chronic depression.

Borderline personality disorder (BPD) and chronic depression (CD) are common and challenging mental disorders. Maladaptive cognitive schemas have been proposed to increase vulnerability to both disorders. In order to elucidate the role of maladaptive cognitive schemas in BPD and CD, this study compared psychiatric outpatients with BPD (N = 30) and CD (N = 30) in terms of early maladaptive schemas (EMSs). The groups were compared using the Young Schema Questionnaire short form-extended (YSQ-S2-extended) and the 15D health status questionnaire. BPD patients showed higher endorsement on the majority of EMSs, poorer social functioning, and greater concurrent distress than CD patients. However, after controlling for concurrent effects of psychological distress, the groups did not differ in 14 out of the 18 EMSs. These findings point to significant similarities in maladaptive beliefs between the 2 disorders and do not support broad, specific patterns of EMSs associated with either disorder. The results highlight the need for further study of the role of maladaptive schemas in the development and treatment of chronic mental disorders.

The Association Between Musculoskeletal Pain and Circulating Ornithine: A Population-Based Study.

Objective: Based on several previous clinical studies, we hypothesized that ornithine levels are different among subjects with persistent musculoskeletal pain compared with other subjects in the population. Design: The study sample consisted of 221 adults with nonpersistent pain, 76 with persistent pain, and 61 with no pain. Concentrations of glutamic acid, ornithine, citrulline, arginine, proline, and spermidine were analyzed using a mass spectrometer. Setting: Lapinlahti municipality in Finland. Results: For the subjects with no pain, nonpersistent pain, and persistent pain, the ornithine concentrations for men were 85.3 µmol/L (SD = 28.9 µmol/L), 98.9 µmol/L (SD = 37.8 µmol/L), and 102.1 µmol/L (SD = 37.1 µmol/L; P = 0.033), respectively. The corresponding concentrations for women were 82.8 µmol/L (SD = 25.2 µmol/L), 83.7 µmol/L (SD = 27.8 µmol/L), and 103.2 µmol/L (SD = 34.9 µmol/L; P = 0.0031). There were no significant differences between the pain groups for any of the other investigated amino acids. Relative sex-specific ornithine concentration adjusted for age, glomerular filtration rate, smoking, body mass index, physical activity, and depressive symptoms was associated with pain ( P = 0.025), the ornithine level being higher in the persistent pain group than in the no pain ( P = 0.006) and nonpersistent pain ( P = 0.032) groups. Conclusion: Ornithine levels are elevated in general population subjects with persistent pain.

Cytokine profile and maternal depression and anxiety symptoms in mid-pregnancy-the FinnBrain Birth Cohort Study.

Maternal prenatal psychological symptoms are associated with child health outcomes, e.g., atopic diseases. Altered prenatal functioning of the immune system is a potential mechanism linking maternal symptoms with child health. Research on prenatal distress and cytokines is warranted. The study population comprised consecutive N = 139 women from a general population-based FinnBrain Birth Cohort Study. Standardized questionnaires for depressive, overall anxiety, and pregnancy-related anxiety symptoms were used. Serum concentrations of selected cytokines were analyzed using Multiplex bead arrays from samples drawn at the gestational week 24. The concentrations of T helper (Th)2-related interleukins (IL)-9 and IL-13 and Th1-related IL-12 correlated positively with prenatal depressive and overall anxiety symptom scores (p values, range 0.011-0.029). Higher interferon (IFN)-γ/IL-4 ratio (p = 0.039) and Th2-related IL-5 (p = 0.007) concentration correlated positively with depressive symptoms. Pregnancy-related anxiety score correlated positively with IL-12 (p = 0.041), IL-13 (p = 0.025), and anti-inflammatory IL-10 (p = 0.048) concentrations. IL-6 and TNF-α concentrations were unrelated to prenatal symptoms. As a novel finding, we observed positive correlations between concentrations of potentially proallergenic cytokines and maternal prenatal psychological symptoms. Different symptom measures may yield distinct cytokine responses. This provides hypotheses for studies on mechanisms bridging prenatal stress and child health.

Dietary patterns are associated with the prevalence of alexithymia.

Recent evidence supports the association between healthy dietary patterns and a reduced risk of depression. The objective was: (1) to examine the associations between dietary patterns and alexithymic features; and (2) investigate whether these possible associations are explained by depressive symptoms in a cross-sectional study among the Finnish general population aged 25-65 years. The study population was a part of the population-based Kuopio Depression Study (KUDEP) conducted in central-eastern Finland (n = 1747). Dietary data were collected using a food frequency questionnaire and dietary patterns from 22 predefined food groups, which were extracted by factor analysis. Alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20) and depression using the 21-item Beck Depression Inventory (BDI-21). Altogether, 173 of the study subjects (9.9%) were alexithymic. Three dietary patterns were identified: "prudent," "Western" and "traditional." Lower scores for a healthy prudent dietary pattern and higher scores for an unhealthy Western dietary pattern were associated with an increased likelihood of belonging to the alexithymic group among subjects with elevated depressive symptoms. Among subjects without depressive symptoms, alexithymia was associated with lower scores in the prudent dietary pattern, but also with higher scores in the traditional dietary pattern. General population subjects with alexithymic features may have unhealthier dietary patterns than non-alexithymic subjects.

[Methods of brain stimulation based on weak electric current--future tool for the clinician?]. / Heikkoon sähkövirtaan perustuvat aivojen stimulaatiomenetelmät--tulevaisuuden kliinikon työkalu?

Methods of brain stimulation based on a weak electric current are non-invasive neuromodulation techniques. They include transcranial direct current, alternating current and random noise stimulation. These methods modify the membrane potential of neurons without triggering the action potential, and have been successfully utilized to influence cognition and regulation of emotions in healthy experimental subjects. In clinical studies, indications of the efficacy of these techniques have been obtained in the treatment of depression, schizophrenia, memory disorders and pain as well as in stroke rehabilitation. It is hoped that these techniques will become established as part of the care and rehabilitation of psychiatric and neurologic patients in the future.

Psychosocial problems in adolescents associated with frequent health care use.

BACKGROUND: The prevalence of somatic, mental and behavioural problems increases in puberty. Nevertheless, compared to adults, health service utilization by adolescents, and associated factors such as risky health behaviours, have been poorly explored. In order to improve health care services, there is a need for further research on adolescents frequently using primary health care. OBJECTIVES: We aimed to investigate adolescents who seek help for health issues, and examine whether particular socio-economic or psychological factors predict frequent primary health care use. METHODS: Finnish adolescents aged 13-18 years (N = 793) attending comprehensive, upper secondary and vocational schools participated in the study in 2005. Data were collected using a questionnaire that included the Youth Self Report (YSR), as well as questions on the psychosocial background of the adolescents and substance use. Data regarding the frequency of use of health services were gathered from medical records of the local public health care services. RESULTS: Altogether, 288 in the sample had used primary health care services making a combined total of 1411 health care visits. Female gender associated with frequent primary health care use. Furthermore, a high level of alcohol consumption and mental health symptoms in girls, and increased self-reported somatic complaints in the YSR in boys were associated with frequent primary health care use. Attending upper secondary school was related to less frequent primary health care use. CONCLUSION: Few adolescents frequently use primary health care, but they account for a considerable proportion of all adolescent health care visits. There are higher levels of alcohol consumption, as well as socio-economic, educational and gender differences among adolescent frequent primary health care users.

Reduced serum adiponectin levels in alexithymia.

OBJECTIVES: Clinical studies have demonstrated that circulating cytokine profiles may differ between alexithymic and non-alexithymic subjects. We examined whether the levels of adiponectin (µg/ml) and resistin (ng/ml) are independently related to alexithymic features in a population-based sample. METHODS: In 2005, clinical data including laboratory assessments were obtained from a sub-sample (n = 308) of the Kuopio Depression Study general population study including subjects aged 25-64 years. Based on the Toronto Alexithymia Scale score in 1998, 1999, 2001 and 2005, a group of subjects with high alexithymic features (n = 85) was formed and compared with non-alexithymic controls (n = 206). RESULTS: Serum adiponectin levels were significantly lower in subjects with alexithymic features than in non-alexithymic control subjects. No difference was found in resistin levels. Similarly, in a logistic regression model adjusted for age, gender and body mass index (BMI), lowered levels of adiponectin, but not resistin, were associated with an increased likelihood of belonging to the group with alexithymic features. Further adjustments for cardiovascular risk factors (i.e. smoking, BMI, metabolic syndrome, alcohol use, and coronary heart disease), depressive symptoms (Hamilton Depression Rating Scale with 17 items) and the use of antidepressants in addition to age and gender did not change these patterns. CONCLUSIONS: Our findings suggest that a disturbed anti-inflammatory balance may characterize alexithymia. In addition, our results widen the concept of alexithymia and highlight the role of immune system alterations and stress in alexithymic individuals.

Sleep duration and incidence of lung cancer in ageing men.

BACKGROUND: Previous studies have suggested an association between sleep duration and cancer. However, the information on sleep duration regard to risk of lung cancer is scanty. METHODS: Analysed data comprised prospective population-based cohort of 2586 men (aged 42-60 years) from Eastern Finland. Baseline survey and clinical examinations took place 1984-1989, and diagnosed lung cancers were obtained until the end of 2011 through linkage with the Finnish Cancer Registry. Self-reported sleep was categorized as ≤6.5 h, 7-7.5 h, and ≥8 h. Subjects with prior history of cancer or psychotropic medication (hypnotics or sedatives) were excluded from the analyses. Cox proportional hazards models with adjustments for possible confounders were used to examine the association. RESULTS: Significant association between sleep duration and increased lung cancer risk was observed after adjustments for age, examination years, cumulative smoking history, family cancer history and Human Population Laboratory Depression scale scores (HR 2.12, 95% CI 1.17-3.85 for ≤6.5 h sleep, and HR 1.88, 95% CI 1.09-3.22 for ≥8 h sleep). Associations were even stronger among current smokers (HR 2.23, 95% CI 1.14-4.34 for ≤6.5 h sleep, and HR 2.09, 95% CI 1.14-3.81 for ≥8 h sleep). After further adjustments for alcohol consumption, physical activity, body mass index, marital status, education years, night work, employment status, asthma and chronic bronchitis, the association remained significant both in the whole study population and among smokers. When cumulative smoking history was replaced by current smoking in the adjustments, the increased risk was limited to those who slept<6.5 h. CONCLUSIONS: Sleep duration of less than 7-7.5 hours or more than 7-7.5 hours associates with increased lung cancer risk. The physiological factors underlying the association are complex, and they may relate to melatonin excretion patterns, low-grade inflammation in cancer development process or disruptions in circadian rhythmicity.