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- We studied cortical amyloid – episodic memory association in twin pairs - Cognitively discordant twin pairs were identified using telephone interview - 45 twin pairs participated in PET imaging and in-person neuropsychological testing - Within-twin pair differences in amyloid and memory were associated with each other - Higher amyloid is related to poorer memory even when controlling for genetic effects We studied the association between episodic memory and cortical fibrillar β-amyloid pathology within twin pairs. Using telephone-administered cognitive screening of 1415 twin pairs in a population-based older Finnish Twin Cohort study, we identified 45 (mean [SD] age 72.9 [4.0] years, 40% women) cognitively discordant same-sex twin pairs (24 dizygotic and 21 monozygotic) without neurological or psychiatric disorders other than AD or mild cognitive impairment. In-person neuropsychological testing was conducted. Cortical amyloid was measured with carbon 11-labelled Pittsburgh compound B ([11C]PiB) positron emission tomography imaging and quantified as the average standardized uptake value ratio in cortical regions affected in AD. Larger within-twin pair differences in verbal immediate (r = -0.42) and delayed free recall (r = -0.41), and visual delayed free recall (r = -0.46) were associated with larger within-twin pair differences in [11C]PiB uptake (p 's < 0.01). Correlations were not significantly different in dizygotic and monozygotic pairs suggesting that the episodic memory-cortical amyloid relationship is not confounded by genetic effects. However, larger samples are needed to draw more definitive conclusions. [ABSTRACT FROM AUTHOR]

Objective: Binge eating disorder (BED) is a clinical eating disorder that is strongly and bidirectionally related to overweight and obesity. Little is known about how subclinical features of BED relate to weight development in adolescence and young adulthood.Method: Women (n = 2825) and men (n = 2423) from the community-based longitudinal FinnTwin16 cohort participated. Seven eating-related cognitions and behaviors similar to the defining features of BED were extracted from the Eating Disorder Inventory-2 and were assessed at a mean age of 24. We used linear mixed models to assess the association of features of BED with BMI trajectories across four waves of data collection (mean ages 16, 17, 18, and 24).Results: The number of features of BED at wave 4 (age 24) was significantly associated with BMI from age 16 years onwards. Those reporting more features of BED had gained more weight throughout adolescence and into their twenties.Conclusions: Features of BED in young adulthood were preceded by steeper BMI trajectories in adolescence. A higher number of features were consistently associated with higher BMI and more weight gain. [ABSTRACT FROM AUTHOR]

Background: Developmental relationships between tobacco use and suicide-related behaviors (SRB) remain unclear. Our objective was to investigate the longitudinal associations of tobacco use in adolescence and SRB in adulthood.Methods: Using a prospective design, we examined whether tobacco use in adolescence is associated with SRB (intentional self-injury, suicide ideation) in young adulthood in a population-based sample of 1330 twins (626 males, 704 females). The baseline and follow-up data were collected by professionally administered semi-structured poly-diagnostic interviews at ages 14 and 22, respectively.Results: After adjusting for multiple potential confounders, those who reported early-onset of regular tobacco use had a significantly increased risk for intentional self-injury, such as cutting or burning, at age 22 (adjusted odds ratio [AOR] 4.57, 95% CI 1.93-10.8) in comparison to those who had not at all initiated tobacco use. Also, daily cigarette smoking at baseline was associated with future intentional self-injury (AOR 4.45, 95% CI 2.04-9.70). Early-onset tobacco use was associated with suicidal ideation in females (AOR 3.69, 95% CI 1.56-8.72) but not in males. Considering any SRB, baseline daily smokers (AOR 2.13, 95% CI 1.12-4.07) and females with early onset of regular tobacco use (AOR 3.97, 95% CI 1.73-9.13) had an increased likelihood. Within-family analyses among twin pairs discordant for exposure and outcome controlling for familial confounds showed similar, albeit statistically non-significant, associations.Conclusion: Early-onset tobacco use in adolescence is longitudinally associated with SRB (intentional self-injury and/or suicide ideation) in young adulthood, particularly among females. Further investigation may reveal whether this association has implications for prevention of SRB in adolescence and young adulthood. [ABSTRACT FROM AUTHOR]

Although the relationship of alcohol use with mortality has been extensively studied, these epidemiological studies are mainly based on single assessments of alcohol use and do not differentiate between causal and non-causal explanations. With four decades of follow-up in the older Finnish Twin Cohort, we examined the relationship of mortality with patterns of alcohol use in a genetically informative sample of MZ and DZ pairs. Three questionnaire surveys of the Finnish Twin Cohort of like-sex twin pairs born 1930–1957 were conducted in 1975, 1981 & 1990. Alcohol consumption was assessed in an identical fashion in all surveys as the use of beer, wine and spirits. These were converted to the number of standard drinks consumed on average. Based on responses to all three surveys from 11,382 men and women, we first analysed the average consumption, ranging from abstinence over all 15 years (29% of all) to an average of 28 or more drinks per week (2%). Next, 3,656 persons whose consumption level (abstinent, one drink per week, 2–6, 7–13 or 14 or more drinks weekly) was the same across all time points were studied. Total mortality was obtained for response date in 1990 to end of follow-up 12/31/2016 with 1,977 deaths. Individual and within pair analyses were conducted using Cox proportional hazards regression models to derive hazard ratios (HR) for death. In analyses of all individuals, the lowest age-sex adjusted mortality was found for those drinking 1 drink per week on average, while consistent abstainers (HR 1.27,95%CI 1.09 to 1.49) and those consuming more had significantly elevated risks. The HR for 14 to 20 drinks weekly was 2.95, 21 to 27 drinks/wk had an HR of 4.42 while consuming 28 or more drinks/wk on average between 1975 and 1990 had an HR of 5.42 (95%CI 4.14to 7.10). For those with stable drinking patterns (n=3,656 twins, 648 deaths) the pattern was similar: those consistently drinking just one drink weekly had the lowest mortality, HR elevated to 1.49 for consistent abstainers; those drinking 2–6 drinks weekly had an HR of 1.43, 7 to 13 drinks an HR of 3.23, and those drinking at least 14 drinks at all three surveys an HR of 4.91. Within-family analyses found a pattern of mortality similar to the individual-based analyses, with an HR of 6.38 (3.14 to 13.0) for those twins consuming, on average, 28 or more drinks weekly in the prior 15 years compared to their co-twins drinking one drink weekly on average, with estimates for intermediate amounts lying between the two extremes. Our within-pair analyses were consistent with the individual analyses, with increased risks at the high end of use, but with a significant increase in mortality already at levels considered by many to represent safe drinking (i.e. 7 to 13 drinks weekly). Interestingly the results were similar and significant in both MZ and DZ pairs. The increased mortality associated with alcohol use is not due to genetic or other influences shared by co-twins but compatible with a causal effect. [ABSTRACT FROM AUTHOR]

This paper examines the links between risky health behaviors and labor market success. We provide new evidence on the joint relationships between the most prominent forms of risky health behavior − alcohol consumption, smoking and physical inactivity − and long-term labor market outcomes. We use twin data for Finnish men and women linked to register-based individual information on earnings and labor market attachment. The twin data allow us to account for shared family and environmental factors and to measure risky health behaviors in 1975 and 1981. The long-term labor market outcomes were measured in adulthood as an average over the period 1990–2009. The sample sizes are 2156 and 2498 twins, for men and women, respectively. We find that being both a smoker and a heavy drinker in early adulthood is negatively related to long-term earnings and employment later in life, especially for men. We conclude that how and why risky health behaviors cluster and how that affects individual level outcomes call for more attention. [ABSTRACT FROM AUTHOR]

Background: We assessed whether the Eating Disorder Inventory (EDI) is suitable for screening binge eating disorder (BED) in young women.Method: Young women (N=2825) from the 1975-79 birth cohorts of Finnish twins were assessed by questionnaires, including subscales of the EDI. For a subset of women (N=548), we established DSM-5 diagnoses of BED; 16 women had lifetime BED. We compared screening properties of the EDI scales using receiver operating characteristic (ROC) analysis, determined optimal cutoff points, and calculated sensitivities and specificities.Results: The best screen for DSM-5 BED was the global score of three subscales (Bulimia, Drive for Thinness, Body Dissatisfaction) with an area under the curve (AUC) of 0.86. Its sensitivity was 87% and specificity 76% at cutoff ≥21. Three individual subscales had acceptable screening properties: Bulimia (AUC 0.83; sensitivity 80%, specificity 78% at cutoff ≥2), Drive For Thinness (AUC 0.82; sensitivity 87%, specificity 72% at cutoff ≥7), and Body Dissatisfaction (AUC 0.81; sensitivity 93%, specificity 60% at cutoff ≥8).Conclusion: The EDI performed well as a screening tool for BED in our community-based sample of young twin women. Future studies should assess its value in other populations and in clinical settings. [ABSTRACT FROM AUTHOR]

The understanding of the molecular genetic contributions to smoking is largely limited to the additive effects of individual single nucleotide polymorphisms (SNPs), but the underlying genetic risk is likely to also include dominance, epistatic, and gene-environment interactions. To begin to address this complexity, we attempted to identify genetic interactions between rs16969968, the most replicated SNP associated with smoking quantity, and all SNPs and genes across the genome. Using the UK Biobank European subsample, we found one SNP, rs1892967, and two genes, PCNA and TMEM230 , that showed a significant genome-wide interaction with rs16969968 for log10 CPD and raw CPD, respectively, in a sample of 116 442 individuals who self-reported currently or previously smoking. We extended these analyses to individuals of South Asian descent and meta-analyzed the combined sample of 117 212 individuals of European and South Asian ancestry. We replicated the gene findings in a meta-analysis of five Finnish samples (N=40 140): FinHealth, FINRISK, Finnish Twin Cohort, GeneRISK, and Health-2000–2011. To our knowledge, this represents the first reliable epistatic association between single nucleotide polymorphisms for smoking behaviors and provides a novel direction for possible future functional studies related to this interaction. Furthermore, this work demonstrates the feasibility of these analyses by pooling multiple datasets across various ancestries, which may be applied to other top SNPs for smoking and/or other phenotypes. • We explored interactions between rs16969968 and all SNPs and genes genome-wide. • One SNP, rs1892967, and two genes, PCNA and TMEM230 , significantly interacted with rs16969968 for smoking quantity. • We replicated the gene findings in a meta-analysis of five Finnish samples comprising over 40, 000 individuals. • This is the first reliable epistatic association between single nucleotide polymorphisms for smoking behaviors. [ABSTRACT FROM AUTHOR]

• Obesity matrisome include 130 signature genes in adipose tissue and 71 in adipocytes. • Adipocyte obesity matrisome show hypertrophic inflammatory phenotype. • Adipose tissue obesity matrisome shows remodeling phenotype. • Novel metabolism-linked matrisome genes are CTSA, CSTO, FAM20B and NGLY1. Adipose tissue is a central regulator of metabolic health and its failure in obesity is a major cause of weight associated comorbidities, such as type 2 diabetes. Many extracellular matrix proteins, represented by matrisome, play a critical role in balancing adipose tissue health and dysfunction. Extracellular matrix components, produced by different cell types of adipose tissue, can modulate adipocyte function, tissue remodeling during expansion, angiogenesis, and inflammation and also form fibrotic lesions in the tissue. In this study, we investigated changes in matrisome of whole adipose tissue and adipocytes in human obesity. We investigated further the networks and biological pathways of the genes related to the changes and their association to development of metabolic dysfunction linked to type 2 diabetes. We used transcriptome data and clinical metabolic parameters from a rare weight-discordant MZ twin cohort. The Heavy-Lean differential matrisome gene expression (Δmatrisome) and differential metabolic parameters reflect changes in adipose tissue upon weight gain and changes in whole body glucose, insulin metabolism, as well as lipid status. We report that obesity Δmatrisome shows high specificity with 130 and 71 of the 1068 matrisome genes showing altered expression in the adipose tissue and adipocytes of heavier co-twin, respectively. The Δmatrisome differs considerably between adipose tissue vs adipocytes which reflects inflammation of hypertrophic adipocytes and the remodeling activity of the rest of the tissue resident cells. The obesity Δmatrisome is discussed extensively in the light of existing evidence and novel significant associations to obesity are reported to matrisome genes; cathepsin A, cathepsin O, FAM20B and N-glycanase1. [ABSTRACT FROM AUTHOR]

Subclinical psychosis, including schizotypal indicators and psychotic experiences, predicts future suicidal ideation. This relationship may reflect unmeasured confounding from environmental factors, genetic factors, or both. We used a genetically-informative twin design to understand if the association between subclinical psychosis and suicidal ideation is independent of shared genetic and environmental factors. We analysed cross-sectional associations of age-22 self-reported subclinical psychosis (positive, negative, and disorganised features) with suicidal ideation in twins participating in the FinnTwin12 study (maximum n = 1213). Then, we analysed the reverse association of age-14 suicidal ideation with age-22 subclinical psychosis. Associations were studied first among individuals and then within monozygotic (MZ) and dizygotic (DZ) pairs. Individual-level analyses showed that all subclinical psychosis factors were associated with suicidal ideation. In within-pair analyses, estimates of associations were lower for MZ pairs than DZ pairs, except for the negative schizotypy-suicidal ideation association where estimates were consistent across individual-level and within-pair analyses. Findings provide evidence that the association between negative features and suicide ideation is not explained by familial factors and may be causal, though the possibility of confounding by individual-specific environmental factors and reverse causation cannot be ruled out. The relationships of positive and disorganised subclinical psychosis features with suicidal ideation cannot be explained by confounding due to environmental factors shared between siblings, but their associations may be due to shared genetic factors. [ABSTRACT FROM AUTHOR]

• The moderate-strength association between PA and cognition or reduced dementia incidence may be explained in part by familial factors. • In MZ co-twin control design, PA may increase GM volume in striatal, prefrontal and hippocampal regions independent of familial factors. • In MZ co-twin control design, LTPA may expedite preconcious visual processing and dampen strength of unattended deviant somatosensory stimuli. Regular physical activity (PA) offers positive effects on the human body. However, the effects of PA on cognition and in the brain are less clear. In this paper, we narratively review the relationship of PA with cognition and dementia, first from general perspective and then through genetically informed studies on the topic. Then we move on to imaging studies on exercise and brain anatomy first by presenting an overall picture of the topic and then discussing brain imaging studies addressing PA and brain structure in twins in more detailed way. Regarding PA and cognition or dementia, genetically informed studies are uncommon, even though the relationship between PA and cognitive ageing has been extensively studied. It is challenging to find twin pairs discordant for PA and dementia. Concerning brain imaging studies, among PA discordant young adult twin pairs, the more active co-twins showed larger gray matter volumes in striatal, prefrontal, and hippocampal regions and in electrophysiological studies automatic deviance-detection processes differed in brain regions involved with sensorimotor, visual and memory functions. [ABSTRACT FROM AUTHOR]

Background: Longitudinal studies enhance understanding of the complex reciprocal relationship between smoking and depression from adolescence to young adulthood. Examining bi-directional associations between cigarette smoking and depressive symptoms in a genetically informative twin design can help to understand whether the associations are independent of shared genetic and environmental factors.Methods: We analyzed longitudinal data on smoking and depressive symptoms in twins participating in the adolescent (mean age 17.5) and young adult (mean age 21.9) surveys of the FinnTwin12 study (maximum N = 2,954 individuals; 1,154 twin pairs). At both waves, self-reported depressive symptoms, assessed with the 10-item version of the General Behavior Inventory (GBI), and smoking status were analyzed. The bi-directional associations were first studied among individuals and then within monozygotic and dizygotic twin pairs.Results: When adjusted for multiple covariates and baseline depressive symptoms, daily smokers at age 17 had higher depressive symptom scores at age 22 than never smokers (Incidence Rate Ratio = 1.17, 95% CI: 1.03-1.33). Similarly, when adjusted for covariates and baseline smoking, higher score in GBI at age 17 was associated with an increased likelihood of being a non-daily (Relative Risk Ratio (RRR) = 1.06, 95% CI: 1.01-1.11) or daily (RRR = 1.05, 95% CI: 1.00-1.10) smoker at age 22. No associations were found in within-pair analyses, suggesting that the individual-level association is explained by shared familial liabilities.Conclusion: During the developmental period from adolescence to adulthood, cigarette smoking and depressive symptoms are reciprocally associated. However, these associations are confounded by shared genetic and other familial liabilities. [ABSTRACT FROM AUTHOR]

Highlights • Heavier women had lower serum DHEA, DHT and SHBG compared to their leaner co-twins. • Serum DHEA concentration was best predicted by percent body fat within twin pairs. • Insulin resistance did not explain serum androgen or SHBG levels within twin pairs. • STS and AKR1C genes were more expressed in adipose tissue from the heavier women. • Intra-abdominal fat and leptin were important regarding adipocyte expression of STS. Abstract Objective Obesity may alter serum steroid concentrations and metabolism. We investigated this in healthy young women with increased body fat and their leaner co-twin sisters. Design Age and genetic background both strongly influence serum steroid levels and body composition. This is a cross-sectional study of 13 female monozygotic twin pairs (age, 23–36 years), ten of which were discordant for body mass index (median difference in body weight between the co-twins, 19 kg). Methods We determined body composition by dual energy X-ray absorptiometry and magnetic resonance imaging, serum androgens by liquid chromatography-tandem mass spectrometry, and mRNA expression of genes in subcutaneous adipose tissue and adipocytes. Results The heavier women had lower serum dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), and sex hormone-binding globulin (SHBG) (P < 0.05 for all) compared to their leaner co-twins with no differences in serum testosterone or androstenedione levels. Serum DHEA correlated inversely with %body fat (r = −0.905, P = 0.002), and DHT positively with SHBG (r = 0.842, P = 0.002). In adipose tissue or adipocytes, expressions of STS (steroid sulfatase) and androgen-related genes were significantly higher in the heavier compared to the leaner co-twin, and within pairs, correlated positively with adiposity but were not related to serum androgen levels. None of the serum androgen or SHBG levels correlated with indices of insulin resistance. Conclusions Serum DHEA levels were best predicted by %body fat, and serum DHT by SHBG. These or other serum androgen concentrations did not reflect differences in androgen-related genes in adipose tissue. General or intra-abdominal adiposity were not associated with increased androgenicity in young women. [ABSTRACT FROM AUTHOR]

Background and aims Studies report that both high and low total cholesterol (TC) elevates SAH risk. There are few prospective studies on high-density lipoproteins (HDL-C) and low-density lipoproteins (LDL-C), and apparently none concerns apolipoproteins A and B. We aimed to clarify the association between lipid profile and SAH risk. Methods The National FINRISK study provided risk-factor data recorded at enrolment between 1972 and 2007. During 1.52 million person-years of follow-up until 2014, 543 individuals suffered from incident hospitalized SAH or outside-hospital-fatal SAH. Cox proportional hazards model was used to calculate the hazard ratios and multiple imputation predicted ApoA1, ApoB, and LDL-C values for cohorts from a time before apolipoprotein-measurement methods were available. Results One SD elevation (1.28 mmol/l) in TC elevated SAH risk in men (hazard ratio (HR) 1.15 (95% CIs 1.00–1.32)). Low HDL-C levels increased SAH risk, as each SD decrease (0.37 mmol/l) in HDL-C raised the risk in women (HR 1.29 (95% CIs 1.07–1.55)) and men (HR 1.20 (95% CIs 1.14–1.27)). Each SD increase (0.29 g/l) in ApoA1 decreased SAH risk in women (HR 0.85 (95% CIs 0.74–0.97)) and men (HR 0.88 (95% CIs 0.76–1.02)). LDL-C (SD 1.07 mmol/l) and ApoB (SD 0.28 g/l) elevated SAH risk in men with HR 1.15 (95% CIs 1.01–1.31) and HR 1.26 (95% CIs 1.10–1.44) per one SD increase. Age did not change these findings. Conclusions An adverse lipid profile seems to elevate SAH risk similar to its effect in other cardiovascular diseases, especially in men. Whether SAH incidence diminishes with increasing statin use remains to be studied. [ABSTRACT FROM AUTHOR]

Objectives: To assess factors associated with successful weight maintenance over ten years in a prospective general population sample of young adults.Material and Methods: Our study comprised 2452 women and 2227 men born in 1975-1979 (mean age at baseline 24 years, attrition 27.1%). Weight maintenance was defined as weight maintained within ±5% of baseline body mass index (BMI). We examined the role of various sociodemographic and lifestyle factors in successful weight maintenance.Results: Relatively few young adults were able to maintain their weight over ten years (28.6% of women vs. 23.0% of men); net weight loss was uncommon (7.5% and 3.8%). Most participants gained weight (mean annual weight gain was 0.9 kg in women and 1.0 kg in men). Among women, exercise was associated with successful weight maintenance, but having two or more children, frequent use of sweet drinks, irregular eating, history of dieting (intentional weight loss) and low life satisfaction were associated with weight gain. Among men, higher baseline BMI and higher education were associated with successful weight maintenance, whereas irregular eating, history of dieting and smoking were associated with weight gain.Conclusions: Only about a quarter of young adults were able to resist weight gain. Regular eating and having no history of dieting were associated with successful weight maintenance in young women and men. [ABSTRACT FROM AUTHOR]

Responses to sweetness are reported in two populations, one segmented by gender and age, and the other one by gender only. The strength of the association between liking for specific sweet foods and liking for an aqueous sucrose solution (20% w/v) is also tested, and health attitudes examined. British adults (n = 1855, age 17–82, mean 55 years, 90% women) and Finnish young adults (n = 1292, age 20–25, mean 22 years, 54% women) rated their liking of ten sweet foods and beverages based on product names, and completed questionnaires on Craving for Sweet Foods (CSF) and General Health Interest (GHI). One-half of Brits and a third of Finns rated liking and intensity of sucrose solution. In factor analysis, identical categories of liking for sweet products were formed in each population, one consisting of five processed sweets (“Goodies”), and the other of naturally sweet fruits and berries (“Fruits”). Sugared and sugar-free s oft drinks and fruit juice loaded on the third factor. After age 50, British men scored higher than British women in CSF and liking for several sweet products; Finnish women scored higher than Finnish men in CSF and liking for most sweet products. GHI was positively associated with liking for Fruits and negatively with liking for sugared soft drinks. Sucrose solution was better liked by British men than women, with no gender difference in Finns. Liking for sucrose solution was only weakly associated with liking for sweet products based on product names. In two demographically different European populations, attraction to sweet gathered in similar product categories, but manifested differently at different ages and each gender. [ABSTRACT FROM AUTHOR]

Obesity and ageing are associated with lower serum testosterone levels in men. How fat distribution or adipose tissue metabolism, independent of genetic factors and age, are related to sex steroid metabolism is less clear. We studied the associations between adiposity and serum sex hormone concentrations, and mRNA expression of genes regulating sex hormone metabolism in adipose tissue in young adult male monozygotic (MZ) twin pairs. The subjects [n = 18 pairs; mean age, 32 years; individual body mass indexes (BMIs) 22–36 kg/m 2 ] included 9 male MZ twin pairs discordant for BMI [intra-pair difference (Δ) in BMI ≥3 kg/m 2 ]. Sex steroid concentrations were determined by liquid chromatography–tandem mass spectrometry, body composition by dual-energy X-ray absorptiometry and magnetic resonance imaging, and mRNA expressions from subcutaneous adipose tissue by Affymetrix. In BMI-discordant pairs (mean ΔBMI = 5.9 kg/m 2 ), serum dihydrotestosterone (DHT) was lower [mean 1.9 (SD 0.7) vs . 2.4 (1.0) nmol/l, P = 0.040] and mRNA expressions of DHT-inactivating AKR1C2 ( P = 0.021) and cortisol-producing HSD11B1 ( P = 0.008) higher in the heavier compared to the leaner co-twins. Serum free 17 β -estradiol (E2) was higher [2.3 (0.5) vs . 1.9 (0.5) pmol/l, P = 0.028], and in all twin pairs, serum E2 and estrone concentrations were higher in the heavier than in the leaner co-twins [107 (28) vs . 90 (22) pmol/l, P = 0.006; and 123 (43) vs . 105 (27) pmol/l, P = 0.025]. Within all twin pairs, i.e. independent of genetic effects and age, 1) the amount of subcutaneous fat inversely correlated with serum total and free testosterone, DHT, and sex hormone-binding globulin (SHBG) concentrations ( P < 0.01 for all), 2) intra-abdominal fat with total testosterone and SHBG ( P < 0.05), and 3) liver fat with SHBG ( P = 0.006). Also, 4) general and intra-abdominal adiposity correlated positively with mRNA expressions of AKR1C2 , HSD11B1 , and aromatase in adipose tissue ( P < 0.05). In conclusion, acquired adiposity was associated with decreased serum DHT and increased estrogen concentrations, independent of genetic factors and age. The reduction of DHT could be linked to its increased degradation (by AKR1C2 and HSD11B1) and increased estrogen levels to increased adiposity-related expression of aromatase in adipose tissue. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoking and depression are major public health concerns, but longitudinal research on the association between smoking and antidepressant use is scarce. The purpose of this study was to investigate, whether smoking predicts antidepressant medication during a 10-year follow-up.Methods: A questionnaire was administered to Finnish adult twins in 1990. Antidepressant prescription data during 1995-2004 were obtained from the register of the Finnish Social Insurance Institution and linked to the survey data. Cox Proportional Hazard Models among 10,652 individuals (1075 cases, 9577 controls) assessed the risk for depression in the cohort, whereas within-pair comparisons of smoking twins with their non-smoking co-twins controlled for shared familial influences.Results: Daily smokers had a significantly elevated likelihood for having antidepressant prescriptions in the follow-up. Based on the analysis among those without baseline depression, heavy daily smokers had a significantly elevated likelihood (HR 1.56, 95% CI 1.17-2.08) for antidepressant prescription when adjusted for all confounders. Similar analysis using pairs discordant for antidepressant medication confirmed that daily smoking twins had a higher likelihood for prescriptions (HR 1.98, 95% CI 1.11-3.54) compared with their non-smoking co-twins. The estimates were for MZ pairs (HR 1.78, 95% CI 0.48-6.55) and DZ pairs (HR 1.92, 95% CI 0.99-3.72), respectively.Limitations: Changes in smoking status after baseline cannot be accounted for. Reversed association between depression and smoking cannot be ruled out.Conclusion: Daily smoking predicts antidepressant medication, even when controlling for essential confounders and familial factors. This study highlights the need of systematically assessing depressive symptoms among smokers. [ABSTRACT FROM AUTHOR]

The consequences of heavy alcohol use remain a serious public health problem. Consistent evidence has demonstrated that both genetic and social influences contribute to alcohol use. Research on gene-environment interaction (GxE) has also demonstrated that these social and genetic influences do not act independently. Instead, certain environmental contexts may limit or exacerbate an underlying genetic predisposition. However, much of the work on GxE and alcohol use has focused on adolescence and less is known about the important environmental contexts in young adulthood. Using data from the young adult wave of the Finnish Twin Study, FinnTwin12 ( N = 3402), we used biometric twin modeling to test whether education moderated genetic risk for alcohol use as assessed by drinking frequency and intoxication frequency. Education is important because it offers greater access to personal resources and helps determine one’s position in the broader stratification system. Results from the twin models show that education did not moderate genetic variance components and that genetic risk was constant across levels of education. Instead, education moderated environmental variance so that under conditions of low education, environmental influences explained more of the variation in alcohol use outcomes. The implications and limitations of these results are discussed. [ABSTRACT FROM AUTHOR]

The definition of anorexia nervosa was revised for the Fifth Edition of the Diagnostic and Statistical Manual (DSM-5). We examined the impact of these changes on the prevalence and prognosis of anorexia nervosa. In a nationwide longitudinal study of Finnish twins born 1975–1979, the women (N = 2825) underwent a 2-stage screening for eating disorders at mean age 24. Fifty-five women fulfilled DSM-IV criteria for lifetime anorexia nervosa. When we recoded the interviews using DSM-5 criteria, we detected 37 new cases. We contrasted new DSM-5 vs. DSM-IV cases to assess their clinical characteristics and prognosis. We also estimated lifetime prevalences and incidences and tested the association of minimum BMI with prognosis. We observed a 60% increase in the lifetime prevalence of anorexia nervosa using the new diagnostic boundaries, from 2.2% to 3.6%. The new cases had a later age of onset (18.8 y vs. 16.5, p = 0.002), higher minimum BMI (16.9 vs. 15.5 kg/m 2 , p = 0.0004), a shorter duration of illness (one year vs. three years, p = 0.002), and a higher 5-year probability or recovery (81% vs. 67%, p = 0.002). Minimum BMI was not associated with prognosis. It therefore appears that the substantial increase in prevalence of anorexia nervosa is offset by a more benign course of illness in new cases. Increased diagnostic heterogeneity underscores the need for reliable indicators of disease severity. Our findings indicate that BMI may not be an ideal severity marker, but should be complemented by prognostically informative criteria. Future studies should focus on identifying such factors in prospective settings. [ABSTRACT FROM AUTHOR]

Leisure-time physical activity is a key contributor to physical and mental health. Yet the role of physical activity in modulating cortical function is poorly known. We investigated whether precognitive sensory brain functions are associated with the level of physical activity. Physical activity history (3-yr-LTMET), physiological measures and somatosensory mismatch response (sMMR) in EEG were recorded in 32 young healthy twins. In all participants, 3-yr-LTMET correlated negatively with body fat%, r = −0.77 and positively with VO 2max , r = 0.82. The fat% and VO 2max differed between 15 physically active and 17 inactive participants. Trend toward larger sMMR was seen in inactive compared to active participants. This finding was significant in a pairwise comparison of 9 monozygotic twin pairs discordant for physical activity. Larger sMMR reflecting stronger synchronous neural activity may reveal diminished gating of precognitive somatosensory information in physically inactive healthy young men compared to the active ones possibly rendering them more vulnerable to somatosensory distractions from their surroundings. [ABSTRACT FROM AUTHOR]

Objective: Some studies indicate an association between napping and increased risk of type 2 diabetes. We studied this prospectively in a sample representative of general population.Methods: A questionnaire was administered to the Finnish Twin Cohort in 1990 (response rate 77%, age 33-60 years). The study population included 12,244 subjects who replied to the question "Do you sleep during the daytime (take naps)?" with five response alternatives ranging from "no need" to "every or almost every day." Information on incident cases of diabetes was obtained by linkage to nationwide registers. Logistic regression models were used to obtain odds ratios (ORs) (95% confidence intervals) for incident type 2 diabetes risk in 1991-2004 by napping category. Adjustments were made for 11 socio-demographic and lifestyle covariates. For subjects aged 33-45 years at baseline, a questionnaire in 2011 provided information on prevalent diabetes.Results: Thirty-four per cent had no need for napping, and 15% did so on ≥3 days weekly. There were 356 incident type 2 diabetes cases during the follow-up. Using the 'no need' category as the reference, the risk of type 2 diabetes was significantly increased only among those napping most frequently [OR 1.86 (1.29-2.67), age- and sex-adjusted]. After adjusting for other covariates, the results were essentially the same, but when adjusted for body mass index, the association decreased (to about 1.3) and was statistically non-significant. Analysis of 2011 self-reported type 2 diabetes was in line with the register data.Conclusions: Frequent napping is associated with future risk of type 2 diabetes. This association is largely explained by obesity. [ABSTRACT FROM AUTHOR]

Background: This study investigated how cigarette smoking and alcohol use predict disability retirement.Methods: Data from the longitudinal nationwide Finnish Twin Cohort study were analyzed, with clustered study design applied when computing 95% confidence intervals (CI). The sample included 21,719 individuals. Smoking and alcohol use were assessed with a questionnaire in 1975. Registry data on retirement events up till end of 2004 were obtained from the Social Insurance Institution and the Finnish Centre for Pensions.Results: Disability pension was granted to 4251 participants. Among men, adjusted for age and alcohol use, former (HR=1.45, 95%CI 1.28, 1.65, p<.001) and daily smokers (HR=1.93, 95%CI 1.71, 2.17, p<.001) showed elevated disability pension risk compared to never smokers. Among women, daily smokers (HR=1.25, 95%CI 1.11, 1.40, <.001) had elevated risk. The age and smoking adjusted risk estimates for alcohol were elevated among abstainers (men HR=1.41, 95%CI 1.21, 1.65, p<.001; women HR=1.36, 95%CI 1.23, 1.52, p<.001) and heavy drinkers (men HR=1.30, 95%CI 1.18, 1.43, p<.001; women HR=1.34, 95%CI 1.04, 1.72, p=.026). Those being persistent smokers and binge drinkers had over three-fold disability risk compared to those who were binge drinkers but had only a few smoking years (men: HR=3.32, 95%CI 2.43, 4.54, p<.001; women: HR=4.05, 95%CI 2.05, 8.00, p<.001). Among men and women who were not binge drinkers, longer smoking duration was needed for elevated disability risk.Conclusions: Both smoking and excess alcohol use significantly predict disability retirement. In order to extend working careers, more attention should be paid to health behaviors, in addition to working conditions. [ABSTRACT FROM AUTHOR]

Major depression is associated with alterations in the auditory P3 event-related potential (ERP). However, the persistence of these abnormalities after recovery from depressive episodes, especially in young adults, is not well known. Furthermore, the potential influence of substance use on this association is poorly understood. Young adult twin pairs (N = 177) from the longitudinal FinnTwin16 study were studied with a psychiatric interview, and P3a and P3b ERPs elicited by task-irrelevant novel sounds and targets, respectively. Dyadic linear mixed-effect models were used to distinguish the effects of lifetime major depressive disorder from familial factors and effects of alcohol problem drinking and tobacco smoking. P3a amplitude was significantly increased and P3b latency decreased, in individuals with a history of lifetime major depression, when controlling the fixed effects of alcohol abuse, tobacco, gender, twins' birth order, and zygosity. These results suggest that past lifetime major depressive disorder may be associated with enhanced attentional sensitivity. • Attention and past lifetime major depressive disorder studied in young adult twins. • Influences of alcohol drinking and tobacco smoking were controlled. • Major depression history associated with enhanced auditory P3a and accelerated P3b. • Effects of major depression could increase the sensitivity of auditory attention. [ABSTRACT FROM AUTHOR]

Background: Disturbed sleep is associated with mood disorders. Both depression and insomnia may increase the risk of disability retirement. The longitudinal links among insomnia, depression and work incapacity are poorly known.Methods: We examined association of self-reported sleep quality with incident symptoms of depression and disability retirement due to depressive disorders in a longitudinal population-based sample of twins (n=12,063 individuals). These adults were categorized by their sleep quality in 1975 and 1981, excluding individuals with depressed mood in 1975/1981. The outcomes were the Beck Depression Inventory (BDItot) and its subscale Negative Attitudes Towards Self (BDINATS) in 1990 as dichotomized measures, and the incidence of disability retirement due to depressive disorder during 1991-2004.Results: Onset of poor sleep between 1975 and 1981 predicted incident depression (BDItot OR=4.5, 95% CI: 2.7-7.4, BDINATS OR=2.0, 95% CI: 1.4-2.7), while persistent poor sleep showed somewhat weaker effects (BDItot; OR=2.5, 95% CI: 1.0-6.0, BDINATS OR=1.9, 95% CI: 1.1-3.3). Among those with few recent stressful life events, onset of poor sleep predicted strongly depression (BDINATS OR=9.5, 95% CI: 3.7-24.2). Likewise onset of poor sleep by 1981 increased the risk of disability retirement due to depression (OR=2.9, 95% CI: 1.8-4.9) with a similar risk among those with persistent poor sleep (OR=2.7, 95% CI: 1.3-5.7).Limitations: Lack of baseline diagnostic interviews; sleep quality based on self-report.Conclusions: Poor sleep is of importance in etiology of depression and disability retirement due to depression. This emphasizes the importance of early detection and treatment of sleep disturbances. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Low socio-economic status (SES) is strongly related to smoking, but studies examining the association of SES with nicotine dependence (ND) are scarce. The aim of this study was to examine the associations of SES and marital status with smoking, multiple measures of ND, and cotinine as a nicotine intake biomarker. Methods: The sample comprised 1746 ever smokers, sampled from the National FINRISK 2007 Study, who had completed a tobacco specific questionnaire in addition to the standard clinical examination. The Fagerström Test for Nicotine Dependence (FTND), the Heaviness of Smoking Index (HSI), the Nicotine Dependence Syndrome Scale (NDSS), and the Hooked On Nicotine Checklist (HONC) were assessed, while plasma cotinine was measured as a biomarker of nicotine exposure in daily smokers. Univariate and multivariate associations were assessed by linear regression and multinomial logistic regression. Results: In multivariate models, lower education was associated with higher FTND and HSI, income with HSI, and occupation with HSI (men only), FTND, HONC and NDSS scores. Lower education was related to higher cotinine levels among daily smokers, although the association diminished slightly after adjusting for daily smoking amount. Living without a spouse was associated with daily smoking and higher ND. Conclusion: In this cross-sectional study low SES was linked with higher ND among current smokers, while low SES was associated with higher cotinine levels among daily smokers. Living alone was linked with higher ND. Longitudinal studies are warranted to further explore these associations. As lower SES smokers are more addicted they may need more targeted cessation services to succeed in quitting smoking. [Copyright &y& Elsevier]

B Background: b DNA methylation changes may play a role in progression from normative to problematic drinking and underlie adverse health outcomes associated with alcohol misuse. First, we analyzed the association between alcohol consumption and DNA methylation at individual CpG sites using the lme4 R package. [Extracted from the article]

Linkage and association studies of major mental illness in Finland have continually identified the 1q42 region, and the Disrupted in Schizophrenia 1 (DISC1) gene in particular, as being a key locus of interest. Haplotypes and variants in the DISC1 gene have been associated with Schizophrenia (SCZ), bipolar disorder, and autism spectrum disorders, as well as to variations in related endophenotypes such as visual working memory, anhedonia, and gray matter volume in the dorsal lateral prefrontal cortex. Despite this consistent line of evidence for these loci in the Finnish population, any true causal variants within the DISC1 gene are yet to be identified. To identify any potential mutations, a subset of families ascertained for SCZ (n=20 families, 96 individuals) were sequenced using Nimblegen SeqCap EZ for the DISC1 gene locus, including TSNAX. All identified variants were then prioritized using association analysis (p<0.05) combined with bioinformatic prediction of function, with major focus on exonic and regulatory variants. Selected variants (n=28) were then genotyped in a larger sub-cohort of the familial SCZ cohort (n=1,133 individuals in 301 families), alongside population based controls (n=323), to verify these observations we obtained in the small discovery sample. Verification of both the variants existence and association (p<0.05) to SCZ, or alternative phenotypes available in these families, led to the selection of 7 variants to be genotyped across Finnish cohorts for different major mental illnesses. Including the rest of the SCZ cohort (n= 2,837), a family cohort for bipolar disorder (n=650), twin pairs concordant and discordant for SCZ (n=303), a population cohort for anxiety disorders (n=823), a cohort for psychosis (n=125) and population based controls (n=1,117). With the aid of this three-step sequencing and genotyping approach, we identified 1,828 variants in the DISC1 gene, of which 28 variants were identified as associated (p<0.05) and located in potentially functional regions. Of these, 7 variants could be verified in a larger cohort, and thus studied across multiple cohorts. Preliminary results highlight a specific 5' exonic variant associating to both schizophrenia and anxiety disorders (pscz=3.24×10–11; panxiety=0.011), and a 3' intronic variant associated with schizophrenia and bipolar disorder (pscz=0.0024; pbipolar=0.031). We aim to identify the potential mutations within the DISC1 gene which have been alluded to through our previous studies of Finnish cohorts for major mental illness. Our initial findings confirm the observation of association for several variants in the DISC1 gene for varied phenotypes, while focusing on the specific variants that have potential functional consequences. The variants we report may represent the principal major mental illness mutations within the DISC1 gene in the Finnish population. Once the relevance of these mutations to multiple diagnostic criteria is determined, we will study these mutations with respect to alternative phenotypes to the diagnoses available in these cohorts, including neuropsychological endophenotypes, neuroimaging, gene expression levels from lymphocytes, and medication usage. [ABSTRACT FROM AUTHOR]

Depression has been suggested to hinder smoking cessation, especially when co-occurring with nicotine dependence. The study aimed to examine the longitudinal association of depressive symptoms with smoking cessation among daily smokers. The study utilized adult Finnish twin cohort where 1438 daily smokers (mean age: 38.3, range: 33-45) in 1990 were re-examined for their smoking status in 2011. We assessed baseline depressive symptoms with the Beck Depression Inventory, and the self-reported smoking status at follow-up. The methods included multinomial logistic regression and time to event analyses, adjusted for multiple covariates (age, sex, marital status, social class, heavy drinking occasions, and health status) and smoking heaviness at baseline assessed by cigarettes per day (CPD). Additionally, within-twin-pair analyses were conducted. Results indicated that moderate/severe depressive symptoms at baseline were associated with a lower likelihood of smoking cessation two decades later. Adjusting for covariates, those with moderate/severe depressive symptoms (vs. no/minimal depressive symptoms) had 46% lower likelihood of quitting (relative risk ratio, RRR = 0.54, 95% CI: 0.30-0.96). After including CPD, the association of depressive symptoms with smoking cessation attenuated modestly (RRR = 0.62, 95% CI: 0.34-1.12). Further, time to event analysis for quitting year since baseline yielded similar findings. In the within-pair analysis, depressive symptoms were not associated with quitting smoking. The results suggest that reporting more depressive symptoms is associated with a lower likelihood of smoking cessation during a 20-year period. The baseline amount of smoking and familial factors partly explain the observed association. Smoking cessation programs should monitor depressive symptoms. [ABSTRACT FROM AUTHOR]

Background The genetic etiology of schizophrenia (SCZ) has been studied in a familial Finnish cohort since the late 1980s. Over the years, linkage and association studies of these families have continually identified the 1q42 region, and the Disrupted in Schizophrenia 1 (DISC1) gene in particular, as being a key locus of interest. Haplotypes and variants in the DISC1 gene have also been noted to associate with the risk to other mental illnesses in the Finnish population, including bipolar disorder and autism spectrum disorders, as well as to variations in phenotypes such as visual working memory, anhedonia, and gray matter volume in the dorsal lateral prefrontal cortex. Furthermore, studies in the SCZ family cohort have also observed association at genes for DISC1 interacting partners, the DISC1 network, including NDE1, PDE4D, PDE4B, and NDEL1. Despite this consistent line of evidence for these loci in the Finnish population, any true causal variants have yet to be identified. Methods To identify any potential mutations a subset of SCZ families (n=20 families, 96 individuals) were sequenced at 24 genes from the extended DISC1 network. All identified variants were then prioritized using association analysis (p<0.05) combined with bioinformatic prediction of function, focusing on exonic and regulatory variants. These selected 67 variants were then genotyped in a larger sub-cohort of the SCZ families (n=1415 individuals in 420 families), alongside population based controls (n=359 individuals), in order to verify the observations in the small discovery sample. Verification of both the variants existence and association (p<0.05) to SCZ, or alternative phenotypes available in these families, led to the selection of those variants to be genotyped across a combined Finnish cohort featuring individual data sets for different major mental illnesses. This includes the rest of the SCZ cohort (n= 2,289), a family cohort for bipolar disorder (n=683), twin pairs concordant and discordant for SCZ (n=307), a selection of a population cohort based on anxiety (n=974), three small cohorts for psychosis (n=825) and population based controls (n=1,406). Results With the aid of the three step sequencing and genotyping approach, we identified 12,795 variants in the DISC1 gene network, of which 67 variants from 9 genes were identified as associated (p<0.05) and genotyped in the verification stage. This additional genotyping step validated association (p<0.05) findings for 26 variants in 8 genes, which have been genotyped across the combined cohort with major mental illness in Finland. Preliminary results from the validation stage highlight a specific exonic variant in DISC1 (p = 0.0000051), a regulatory variant in NDE1 (p = 0.011), and an exonic variant in PDE4D as being the main variants of interest at these loci. Discussion This research aims to identify the potential mutations within the DISC1 network which have been alluded to through our previous studies of Finnish cohorts for major mental illness. Our initial findings confirm the observation of association at a number of DISC1 network genes, including DISC1 itself, while focusing on the specific variants at these loci that have potential functional consequences. Thus, the variants we are observing may represent the principal mutations at these loci in the Finnish population, and predispose to psychiatric disorders beyond schizophrenia. [ABSTRACT FROM AUTHOR]