Seasonal patterns of sickness absence due to diagnosed mental disorders: a nationwide 12-year register linkage study.

AIMS: Although seasonality has been documented for mental disorders, it is unknown whether similar patterns can be observed in employee sickness absence from work due to a wide range of mental disorders with different severity level, and to what extent the rate of change in light exposure plays a role. To address these limitations, we used daily based sickness absence records to examine seasonal patterns in employee sickness absence due to mental disorders. METHODS: We used nationwide diagnosis-specific psychiatric sickness absence claims data from 2006 to 2017 for adult individuals aged 16-67 (n = 636,543 sickness absence episodes) in Finland, a high-latitude country with a profound variation in daylength. The smoothed time-series of the ratio of observed and expected (O/E) daily counts of episodes were estimated, adjusted for variation in all-cause sickness absence rates during the year. RESULTS: Unipolar depressive disorders peaked in October-November and dipped in July, with similar associations in all forms of depression. Also, anxiety and non-organic sleep disorders peaked in October-November. Anxiety disorders dipped in January-February and in July-August, while non-organic sleep disorders dipped in April-August. Manic episodes reached a peak from March to July and dipped in September-November and in January-February. Seasonality was not dependent on the severity of the depressive disorder. CONCLUSIONS: These results suggest a seasonal variation in sickness absence due to common mental disorders and bipolar disorder, with high peaks in depressive, anxiety and sleep disorders towards the end of the year and a peak in manic episodes starting in spring. Rapid changes in light exposure may contribute to sickness absence due to bipolar disorder. The findings can help clinicians and workplaces prepare for seasonal variations in healthcare needs.

Differences in clinical and cognitive variables in seasonal affective disorder compared to depressive-related disorders: Evidence from a population-based study in Finland.

BACKGROUND: Seasonal affective disorder (SAD) is a type of depression with seasonal pattern. Although it involves some idiosyncratic symptoms, it can overlap with other depressive disorders such as major depressive disorder (MDD) or dysthymia. We aimed to characterize the differences in specific cognitive and clinical symptoms between SAD and depressive-related disorders. METHODS: In total, 4554 Finnish subjects from the population-based Health 2011 Survey were interviewed with the Munich version of Composite International Diagnostic Interview (M-CIDI) and filled in the Seasonal Pattern Assessment Questionnaire (SPAQ). From this sample for our analysis, we included those participants who fulfilled the criteria for SAD (n=171), MDD (n=153) or dysthymia (n=84) and their 816 psychologically healthy controls matched by age and gender. In addition to M-CIDI and SPAQ, the Beck Depression Inventory, the General Health Questionnaire, an abbreviated version of the Mini-Mental State Examination, the category verbal fluency test, and the CERAD 10-word list were used. RESULTS: Subjects with dysthymia showed major deficits in both clinical and cognitive domains compared to MDD, SAD and healthy controls. Although clinical comorbidity was mild in SAD, these participants showed similar cognitive deficits to dysthymic subjects and greater impairments than MDD. CONCLUSIONS: SAD subjects show a differential clinical and cognitive profile compared to other depressive-related disorders. Although less severe clinical symptoms are found in these individuals, some cognitive impairment already appears in subjects with SAD recruited from a population-based study.

The association of air pollution and depressed mood in 70,928 individuals from four European cohorts.

BACKGROUND: Exposure to ambient air pollution may be associated with impaired mental health, including depression. However, evidence originates mainly from animal studies and epidemiological studies in specific subgroups. We investigated the association between air pollution and depressed mood in four European general population cohorts. METHODS: Data were obtained from LifeLines (the Netherlands), KORA (Germany), HUNT (Norway), and FINRISK (Finland). Residential exposure to particles (PM2.5, PM2.5absorbance, PM10) and nitrogen dioxide (NO2) was estimated using land use regression (LUR) models developed for the European Study of Cohorts for Air Pollution Effects (ESCAPE) and using European wide LUR models. Depressed mood was assessed with interviews and questionnaires. Logistic regression analyses were used to investigate the cohort specific associations between air pollution and depressed mood. RESULTS: A total of 70,928 participants were included in our analyses. Depressed mood ranged from 1.6% (KORA) to 11.3% (FINRISK). Cohort specific associations of the air pollutants and depressed mood showed heterogeneous results. For example, positive associations were found for NO2 in LifeLines (odds ratio [OR]=1.34; 95% CI: 1.17, 1.53 per 10 µg/m(3) increase in NO2), whereas negative associations were found in HUNT (OR=0.79; 95% CI: 0.66, 0.94 per 10 µg/m(3) increase in NO2). CONCLUSIONS: Our analyses of four European general population cohorts found no consistent evidence for an association between ambient air pollution and depressed mood.

Work-family conflicts and subsequent sleep medication among women and men: a longitudinal registry linkage study.

Work and family are two key domains of life among working populations. Conflicts between paid work and family life can be detrimental to sleep and other health-related outcomes. This study examined longitudinally the influence of work-family conflicts on subsequent sleep medication. Questionnaire data were derived from the Helsinki Health Study mail surveys in 2001-2002 (2929 women, 793 men) of employees aged 40-60 years. Data concerning sleep medication were derived from the Finnish Social Insurance Institution's registers covering all prescribed medication from 1995 to 2007. Four items measured whether job responsibilities interfered with family life (work to family conflicts), and four items measured whether family responsibilities interfered with work (family to work conflicts). Cox proportional hazard models were fitted, adjusting for age, sleep medication five years before baseline, as well as various family- and work-related covariates. During a five-year follow-up, 17% of women and 10% of men had at least one purchase of prescribed sleep medication. Among women, family to work conflicts were associated with sleep medication over the following 5 years after adjustment for age and prior medication. The association remained largely unaffected after adjusting for family-related and work-related covariates. Work to family conflicts were also associated with subsequent sleep medication after adjustment for age and prior medication. The association attenuated after adjustment for work-related factors. No associations could be confirmed among men. Thus reasons for men's sleep medication likely emerge outside their work and family lives. Concerning individual items, strain-based ones showed stronger associations with sleep medication than more concrete time-based items. In conclusion, in particular family to work conflicts, but also work to family conflicts, are clear determinants of women's sleep medication.

TRIB1 constitutes a molecular link between regulation of sleep and lipid metabolism in humans.

Epidemiological studies show association between sleep duration and lipid metabolism. In addition, inactivation of circadian genes induces insulin resistance and hyperlipidemia. We hypothesized that sleep length and lipid metabolism are partially controlled by the same genes. We studied the association of total sleep time (TST) with 60 genetic variants that had previously been associated with lipids. The analyses were performed in a Finnish population-based sample (N = 6334) and replicated in 2189 twins. Finally, RNA expression from mononuclear leucocytes was measured in 10 healthy volunteers before and after sleep restriction. The genetic analysis identified two variants near TRIB1 gene that independently contributed to both blood lipid levels and to TST (rs17321515, P = 8.92(*)10(-5), Bonferroni corrected P = 0.0053, ß = 0.081 h per allele; rs2954029, P = 0.00025, corrected P = 0.015, ß = 0.076; P<0.001 for both variants after adjusting for blood lipid levels or body mass index). The finding was replicated in the twin sample (rs17321515, P = 0.022, ß = 0.063; meta-analysis of both samples P = 8.1(*)10(-6), ß = 0.073). After the experimentally induced sleep restriction period TRIB1 expression increased 1.6-fold and decreased in recovery phase (P = 0.006). In addition, a negative correlation between TRIB1 expression and slow wave sleep was observed in recovery from sleep restriction. These results show that allelic variants of TRIB1 are independently involved in regulation of lipid metabolism and sleep. The findings give evidence for the pleiotropic nature of TRIB1 and may reflect the shared roots of sleep and metabolism. The shared genetic background may at least partially explain the mechanism behind the well-established connection between diseases with disrupted metabolism and sleep.

Hormonal contraception and mental health: results of a population-based study.

BACKGROUND: The effects of oral contraceptives (OCs) on mental health are not clear, and no study has been focused on the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on mental health. The aim of this study was to analyse the association between the use of OCs and the LNG-IUS and psychological well-being and psychopathology. METHODS: The associations between the current use of OCs and the LNG-IUS, and their duration versus mood symptoms [Beck Depression Inventory (BDI)], psychological well-being [(General Health Questionnaire-12 (GHQ-12)] and recent psychiatric diagnoses [(Composite International Diagnostic Interview (CIDI)] were examined among women who participated in the Finnish-population-based Health 2000 study. Analyses were performed on the 30- to 54-year-old sample (n = 2310); some of the analyses were extended to include the younger age group (18- to 54-year-old sample; n = 3223). RESULTS: Overall, hormonal contraception was well tolerated with few significant effects on psychological well-being. The length of OC use was inversely associated with some BDI items ('dissatisfaction, irritability, lost interest in people, earlier waking and lost interest in sex'), and directly associated with 'worries about one's health' (BDI) and with a current diagnosis of 'alcohol dependence' (CIDI). The current use of the LNG-IUS was inversely associated with 'earlier waking' (BDI) and with 'impaired concentration' (GHQ), while the length of LNG-IUS use was inversely associated with 'strain' (GHQ). CONCLUSIONS: The influence of hormonal birth control on mental health is modest and mainly favourable. The length of current OC use seems to have some beneficial effects on mood although the longer the duration of use, the greater the association with a diagnosis of alcohol dependence. Knowledge of the use of hormonal contraception might be of value when assessing psychopathology in women. The cross-sectional design, with partly retrospective data collection, precludes any causal conclusions.

Work-related accidents and daylight saving time in Finland.

BACKGROUND: Recent research has indicated that transitions into and out of daylight saving time (DST) unbalance the physiological circadian rhythm and may lead to sleep disturbance. Sleep deprivation may have negative effects on motivation, attention and alertness and thus it is possible that transitions into and out of DST may increase accident rates. AIMS: To explore the impact of DST transitions on the number of occupational accidents in Finland. METHODS: For the study, we analysed all occupational accidents that happened in Finland 1 week before and 1 week after DST transitions during the years 2002-06. RESULTS: Transitions into and out of DST did not significantly increase the number of occupational accidents. CONCLUSIONS: It seems that sleep deprivation after DST transition is not harmful enough to impact on occupational accident rates.

DISC1 association, heterogeneity and interplay in schizophrenia and bipolar disorder.

Disrupted in schizophrenia 1 (DISC1) has been associated with risk of schizophrenia, schizoaffective disorder, bipolar disorder, major depression, autism and Asperger syndrome, but apart from in the original translocation family, true causal variants have yet to be confirmed. Here we report a harmonized association study for DISC1 in European cohorts of schizophrenia and bipolar disorder. We identify regions of significant association, demonstrate allele frequency heterogeneity and provide preliminary evidence for modifying interplay between variants. Whereas no associations survived permutation analysis in the combined data set, significant corrected associations were observed for bipolar disorder at rs1538979 in the Finnish cohorts (uncorrected P=0.00020; corrected P=0.016; odds ratio=2.73+/-95% confidence interval (CI) 1.42-5.27) and at rs821577 in the London cohort (uncorrected P=0.00070; corrected P=0.040; odds ratio=1.64+/-95% CI 1.23-2.19). The rs821577 single nucleotide polymorphism (SNP) showed evidence for increased risk within the combined European cohorts (odds ratio=1.27+/-95% CI 1.07-1.51), even though significant corrected association was not detected (uncorrected P=0.0058; corrected P=0.28). After conditioning the European data set on the two risk alleles, reanalysis revealed a third significant SNP association (uncorrected P=0.00050; corrected P=0.025). This SNP showed evidence for interplay, either increasing or decreasing risk, dependent upon the presence or absence of rs1538979 or rs821577. These findings provide further support for the role of DISC1 in psychiatric illness and demonstrate the presence of locus heterogeneity, with the effect that clinically relevant genetic variants may go undetected by standard analysis of combined cohorts.

Replication of linkage on chromosome 7q22 and association of the regional Reelin gene with working memory in schizophrenia families.

Schizophrenia is a common and complex mental disorder. Hereditary factors are important for its etiology, but despite linkage signals reported to several chromosomal regions in different populations, final identification of predisposing genes has remained a challenge. Utilizing a large family-based schizophrenia study sample from Finland, we have identified several linked loci: 1q32.2-q42, 2q, 4q31, 5q and 7q22. In this study, an independent sample of 352 nuclear schizophrenia families (n=1626) allowed replication of linkage on 7q21-32. In a sample of 245 nuclear families (n=1074) originating from the same geographical region as the families revealing the linkage, SNP and microsatellite association analyses of the four regional candidate genes, GRM3, RELN, SEMA3A and VGF, revealed no significant association to the clinical diagnosis of schizophrenia. Instead, quantifiable trait component analyses with neuropsychological endophenotypes available from 186 nuclear families (n=861) of the sample showed significant association to RELN variants for traits related to verbal (P=0.000003) and visual working memory (P=0.002), memory (P=0.002) and executive functioning (P=0.002). Trait-associated allele-positive subjects scored lower in the tests measuring working memory (P=0.0004-0.0000000004), memory (P=0.02-0.0001) and executive functioning (P=0.001). Our findings suggest that allelic variants of RELN contribute to the endophenotypes of schizophrenia.

Sleep-related disturbances and physical inactivity are independently associated with obesity in adults.

OBJECTIVE: To study relationships between obesity, physical inactivity and sleep-related disturbances (obstructive sleep apnea (OSA), sleep duration, sleep disturbances concomitant with daytime tiredness) in adults (> or =30 years). DESIGN: Cross-sectional study with a random population sample. PARTICIPANTS: A total of 3377 men (mean age 52.3, s.d. 14.8, years) and 4264 women (56.4, s.d. 17.2, years). MAIN OUTCOME MEASURES: Dependent variables, measured: Waist circumference (WC) and body mass index (BMI). Independent variables, from a detailed interview/questionnaire: probable OSA, other sleep-related disturbances, sleep duration, type and frequency of leisure physical activity. Age, mental health, smoking and education were included in analyses as potential confounders. RESULTS: In men, OSA and physical inactivity increased likelihood for abdominal obesity (WC > or =102 cm). Physical inactivity also increased, but long (> or =9 h/day) sleep decreased likelihood for abdominal overweight (WC: 94-101 cm) in men. In women, abdominal obesity (WC > or =88 cm) was associated positively with OSA, moderate sleep-related disturbances, and physical inactivity. Education modulated the influence of age on abdominal obesity in both genders. Using BMI as the dependent variable did not change the general information obtained by the model. In addition, abdominal obesity was found to be an independent risk factor also in multivariable models predicting categories of a combined sleep duration and sleep disturbances. CONCLUSIONS: Sleep duration and sleep-related disturbances are associated with obesity, even after controlling for OSA and physical inactivity. The results support the hypothesis of vicious circle between sleep and obesity.

A haplotype within the DISC1 gene is associated with visual memory functions in families with a high density of schizophrenia.

We have previously reported evidence of linkage and association between markers on 1q42 and schizophrenia in a study sample of 498 multiply affected Finnish nuclear families, leading to the recent identification of four significantly associated haplotypes that specifically implicate the Translin-Associated Factor X (TRAX) and Disrupted in Schizophrenia 1 and 2 (DISC1 and DISC2) genes in the genetic etiology of schizophrenia. Previously, the DISC genes were found to be disrupted by a balanced translocation (1;11)(q42.1;q14.3) that cosegregated with schizophrenia and related disorders in a large Scottish pedigree. Interestingly, we also reported earlier suggestive linkage between endophenotypic quantitative traits of visual and verbal memory and microsatellite markers in close proximity to TRAX/DISC, on 1q41. Here, we tested if the identified allelic haplotypes of TRAX/DISC would be associated with visual and/or verbal memory function impairments that are known to aggregate with schizophrenia in families. One haplotype of DISC1, HEP3, displayed association with poorer performance on tests assessing short-term visual memory and attention. Analysis of affected and unaffected offspring separately revealed that both samples contribute to the observed association to visual working memory. These results provide genetic support to the view that the DISC1 gene contributes to sensitivity to schizophrenia and associated disturbances and affects short-term visual memory functions. This finding should stimulate studies aiming at the molecular characterization of how the specific alleles of DISC1 affect the visual memory functions and eventually participates in the development of schizophrenia.

Time patterns and seasonal mismatch in suicide.

OBJECTIVE: Physical time-givers may have a modifying effect on the time patterns of death from suicide. METHOD: Data on a total of 1397 suicides in Finland over a year were collected using the method of psychological autopsy. We linked versatile information on each individual to meteorological data adjusted for local weather conditions, and to the universal astronomic data. RESULTS: The number of suicides with seasonal mismatch was greater than the expected in the northernmost region of the country (P = 0.03). The northern location was the most significant predictor of such suicides (P = 0.001). They were associated with the changes in ambient temperature during the preceding day (P < 0.00001), the changes to colder preceding suicides in the spring. CONCLUSION: Our findings show that mismatch between the changes in ambient temperature and those in the length of day may precede death from suicide in some individuals.

The serotonin transporter promoter repeat length polymorphism, seasonal affective disorder and seasonality.

BACKGROUND: Conflicting results have been reported in previous association studies of the serotonin transporter promoter repeat length polymorphism (5-HTTLPR), seasonal affective disorder (SAD) and seasonality (seasonal variations in mood and behaviour). The aim of this study was to test for association in new case-control and population-based materials, and to perform a combined analysis of all published studies of 5-HTTLPR and SAD. METHOD: One hundred and forty-seven new SAD cases and 115 controls were genotyped for 5-HTTLPR and in total 464 patients and 414 controls were included in the pooled analysis. In addition, 226 individuals selected for unusually high or low seasonality scores from a population based material and 46 patients with non-seasonal depression were analysed. Different genetic models were tested and seasonality was analysed both as a qualitative (high v. low) and as a quantitative trait in the different sample sets. RESULTS: No association between 5-HTTLPR and SAD was found in the new case-control material, in the combined analysis of all samples, or when only including 316 patients with controls (N = 298) selected for low seasonality. A difference was detected between the population based high and low seasonality groups, when assuming a recessive effect of the short allele (20% and 10% short allele homozygotes, respectively, OR (95% CI): 2.24 (1.03-4.91)). Quantitative analysis of seasonality revealed no association with 5-HTTLPR in any sample set. CONCLUSIONS: These results do not suggest a major role of the short variant of 5-HTTLPR in susceptibility to SAD, but provide modest evidence for an effect on seasonality.

Bright-light exposure combined with physical exercise elevates mood.

BACKGROUND: Physical exercise alleviates depressive symptoms, as does exposure to bright light, especially in those with seasonal variation. Our objective was to compare the effect of exercise alone or combined with morning bright light on mood and the health-related quality of life in healthy subjects. METHODS: Study subjects were working-age adults, randomized in two groups (n=80): exercise in bright light (group A), or exercise in normal indoor illumination (group B). Intervention lasted for 8 weeks and questionnaire data on mood and the health-related quality of life were collected at study entry, and at weeks 4 and 8. RESULTS: Physical exercise both in normal indoor illumination and in bright light was effective at alleviating depressive symptoms. The exercise was significantly more effective at alleviating so-called atypical depressive symptoms when combined with bright-light exposure. LIMITATIONS: There was no active placebo condition, but a comparative, randomized trial was executed. CONCLUSIONS: Physical exercise in bright light had a positive effect on mood and health-related quality of life in a sample of healthy, working-age people. Further research is needed to explore the mechanisms of the apparent additive effect of exercise and light.

Bipolar disorder susceptibility region on Xq24-q27.1 in Finnish families.

Bipolar disorder (BPD) is a common disorder characterized by episodes of mania, hypomania and depression. The genetic background of BPD remains undefined, although several putative loci predisposing to BPD have been identified. We have earlier reported significant evidence of linkage for BPD to chromosome Xq24-q27.1 in an extended pedigree from the late settlement region of the genetically isolated population of Finland. Further, we established a distinct chromosomal haplotype covering a 19 cM region on Xq24-q27.1 co-segregating with the disorder. Here, we have further analyzed this X-chromosomal region using a denser marker map and monitored X-chromosomal haplotypes in a study sample of 41 Finnish bipolar families. Only a fraction of the families provided any evidence of linkage to this region, suggesting that a relatively rare gene predisposing to BPD is enriched in this linked pedigree. The genome-wide scan for BPD predisposing loci in this large pedigree indicated that this particular X-chromosomal region provides the best evidence of linkage genome-wide, suggesting an X-chromosomal gene with a major role for the genetic predisposition of BPD in this family.

Genome-wide scan in a nationwide study sample of schizophrenia families in Finland reveals susceptibility loci on chromosomes 2q and 5q.

We have previously carried out two genome-wide scans in samples of Finns ascertained for schizophrenia from national epidemiological registers. Here, we report data from a third genome scan in a nationwide Finnish schizophrenia study sample of 238 pedigrees with 591 affected individuals. Of the 238 pedigrees, 53 originated from a small internal isolate (IS) on the eastern border of Finland with a well established genealogical history and a small number of founders, who settled in the community 300 years ago. The total study sample of over 1200 individuals were genotyped, using 315 markers. In addition to the previously identified chromosome 1 locus, two new loci were identified on chromosomes 2q and 5q. The highest LOD scores were found in the IS families with marker D2S427 (Z(max) = 4.43) and in the families originating from the late settlement region with marker D5S414 (Z(max) = 3.56). In addition to 1q, 2q and 5q, some evidence for linkage emerged at 4q, 9q and Xp, the regions also suggested by our previous genome scans, whereas, in the nationwide study sample, the region at 7q failed to show further evidence of linkage. The chromosome 5q finding is of particular interest, since several other studies have also shown evidence for linkage in the vicinity of this locus.

Chromosome 1 loci in Finnish schizophrenia families.

We have earlier reported evidence for linkage to two regions on chromosome 1q32--q42 in schizophrenia families collected for two separate studies in Finland. Here we report the results of a fine mapping effort aimed at further definition of the chromosomal region of interest using a large, population-based study sample (221 families, 557 affected individuals). Most affecteds (78%) had a DSM-IV schizophrenia diagnosis and the remaining had schizophrenia spectrum disorders. We genotyped a total of 147 microsatellite markers on a wide 45 cM region of chromosome 1q. The results were analyzed separately for families originating from an internal isolate of Finland and for families from the rest of Finland, as well as for all families jointly. We used traditional two-point linkage analysis, SimWalk2 multipoint analysis and a novel gamete-competition association/linkage method. Evidence for linkage was obtained for one locus in the combined sample (Z(max) = 2.71, D1S2709) and in the nuclear families from outside the internal isolate (Z(max) = 3.21, D1S2709). In the families from the internal isolate the strongest evidence for linkage was obtained with markers located 22 cM centromeric from this marker (Z(max) = 2.30, D1S245). Multipoint analysis also indicated these loci. Some evidence for association with several markers was observed using the gamete-competition method. Interestingly, the strongest evidence for linkage in the combined study sample was obtained for marker D1S2709, which is an intragenic marker of the DISC1 gene, previously suggested as a susceptibility gene for schizophrenia. These results are consistent with the presence of susceptibility gene(s) in this chromosomal region, a result also implied in other recent family studies of schizophrenia.