A thorough understanding of the role of estrogens on aging-related muscle weakness is lacking. To clarify the molecular mechanisms underlying the effects of hormone replacement therapy (HRT) on skeletal muscle, we analyzed systemic protein and local mRNA levels of factors related to interleukin 6 (IL-6) and insulin-like growth factor 1 (IGF-1) pathways in 30- to 35-year-old (n = 14) women (without hormonal contraceptives) and in 54- to 62-year-old monozygotic female twin pairs discordant for HRT (n = 11 pairs, mean duration of HRT 7.3 ± 3.7 years). Biopsies were taken from vastus lateralis muscle and from abdominal adipose tissue. We found, first, that the systemic levels of IL-6 receptors sIL-6R and sgp130 are sensitive to both age and HRT concomitant with the changes in body composition. The serum levels of sgp130 and sIL-6R were 16% and 52% (p ≤ 0.001 for both variables) higher in postmenopausal women than in premenopausal women, and 10% and 9% lower (p = 0.033 and p < 0.001, respectively) in the HRT using than in their non using co-twins. After adjustment for body fat amount, the differences were no more significant. Second, the transcript analyses emphasize the impact of adipose tissue on systemic levels of IL-6, sgp130 and sIL6R, both at pre- and postmenopausal age. In muscle, the most notable changes were 28% lower gene expression of IGF-1 splice variant Ea (IGF-1Ea) and 40% lower expression of splice variant Ec (IGF-1Ec) in the postmenopausal non-users than in premenopausal women (p = 0.016 and 0.019, respectively), and 28% higher expression of IGF1-receptor in HRT users than in non-users (p = 0.060). The results tend to demonstrate that HRT has positive anti-catabolic effect on aging skeletal muscle.
Aging; Estrogen-based hormone therapy; Inflammation; Skeletal muscle; IL-6; IGF-1
Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants for this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch patients and 4,580 population-matched controls. We selected SNPs from 12 loci with two or more SNPs with P-values < 1 × 10−5 for follow-up in 2,508 patients and 2,652 controls. Two loci, i.e. 1q22 (MEF2D) and 3p24 (near TGFBR2) replicated convincingly (P = 4.9 × 10−4, P = 1.0 × 10−4, respectively). Meta-analysis of the discovery and replication data yielded two additional genome-wide significant (P < 5 × 10−8) loci in PHACTR1 and ASTN2. In addition, SNPs in two previously reported migraine loci in or near TRPM8 and LRP1 significantly replicated. This study reveals the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder.
Secular trends towards earlier puberty, possibly caused by new environmental triggers, provide a basis for periodic evaluation of the influence and interaction of genetic and environmental effects on pubertal timing. In such studies, a practical marker that reflects timing of puberty in both genders needs to be used. We investigated genetic and environmental influences on pubertal timing by using change in the relative height between early and late adolescence (HD:SDS, height difference in standard deviations) as a new marker of pubertal timing. HD:SDS correlated well with age at peak height velocity in a population of men and women with longitudinal growth data. In 2,309 twin girls and 1,828 twin boys, HD:SDS was calculated between height SDs at age 11.5 and 17.5, and 14.0 and 17.5 years, respectively. Quantitative genetic models for twin data were fitted to estimate the genetic contribution to HD:SDS. We also investigated whether the same genetic factors influenced individual differences between HD:SDS and development of secondary sex characteristics prospectively collected by pubertal development scale (PDS). Genetic effects contributed to 86 and 82% of the variance in HD:SDS in girls and boys, respectively, when using the same model including additive genetic and specific environmental factors. In girls, 30% and in boys, 49% of the genetic factors affecting PDS and HD:SDS were the same. Future comparison of the results of periodic evaluations allows estimation of possible changes in the effects of environment on timing of puberty. In such studies, HD:SDS can be used as a practical marker of pubertal timing.
Prospective studies on the risk factors for subarachnoid hemorrhage (SAH) are limited. Moreover, the effect of risk factors on the incidence rates of SAH is not well known about.
In this study, we aimed to identify risk factors for SAH and characterize subgroups in a population with a high incidence of SAH.
After recording multiple potential risk factors for SAH at the time of enrolment, first ever SAH events between 1972 and 2009 were recorded through the nationwide Causes of Death Register and Hospital Discharge Register for the population-based cohort of 64 349 participants, who participated in the National FINRISK Study between 1972 and 2007 in Finland.
During the follow-up time of 1.26 million person-years (median 17.9 years, range 0 to 37.9 years), 437 persons experienced fatal or non-fatal SAH. Crude SAH incidence was 34.8 (95% confidence interval: 31.7–38.2) per 100 000 person-years among ≥25-year-old persons. Female sex, high blood pressure values and current smoking were confirmed as risk factors for SAH. Previous myocardial infarction, history of premature stroke (any kind) in mother and elevated cholesterol levels in men were identified as new risk factors for SAH. Depending on the combination of risk factors, SAH incidence varied between 8 and 171 per 100 000 person-years.
New and previously reported risk factors appear to have a much stronger association with the incidence of SAH than is ordinarily seen in cardiovascular diseases. Risk factor assessments may facilitate the identification of high-risk persons who should be the focus of preventive interventions.
Exploring genetic pleiotropy can provide clues to a mechanism underlying the observed epidemiological association between type 2 diabetes and heightened fracture risk. We examined genetic variants associated with bone mineral density (BMD) for association with type 2 diabetes and glycemic traits in large well-phenotyped and -genotyped consortia. We undertook follow-up analysis in ∼19,000 individuals and assessed gene expression. We queried single nucleotide polymorphisms (SNPs) associated with BMD at levels of genome-wide significance, variants in linkage disequilibrium (r2 > 0.5), and BMD candidate genes. SNP rs6867040, at the ITGA1 locus, was associated with a 0.0166 mmol/L (0.004) increase in fasting glucose per C allele in the combined analysis. Genetic variants in the ITGA1 locus were associated with its expression in the liver but not in adipose tissue. ITGA1 variants appeared among the top loci associated with type 2 diabetes, fasting insulin, β-cell function by homeostasis model assessment, and 2-h post–oral glucose tolerance test glucose and insulin levels. ITGA1 has demonstrated genetic pleiotropy in prior studies, and its suggested role in liver fibrosis, insulin secretion, and bone healing lends credence to its contribution to both osteoporosis and type 2 diabetes. These findings further underscore the link between skeletal and glucose metabolism and highlight a locus to direct future investigations.
We analyzed the association between mean height and old age cognition in two Nordic twin cohorts with different childhood living conditions. The cognitive performance of 4720 twin individuals from Denmark (mean age 81.6 years, SD = 4.59) and Finland (mean age 74.4 years, SD = 5.26) was measured using validated cognitive screens. Taller height was associated with better cognitive performance in Finland (β-estimates 0.18 SD/10cm, p value < .001, for men and 0.13 SD, p = .008, for women), but this association was not significant in Denmark (β-estimates 0.0093 SD, p value = .16, for men and 0.0075 SD, p value = .016, for women) when adjusted for age and education/social class. Among Finnish participants higher variability of cognitive performance within shorter height quintiles was observed. Analysis using gene-environment interaction models showed that environmental factors exerted a greater impact on cognitive performance in shorter participants, whereas in taller participants' it was explained mainly by genetic factors. Our results suggest that shorter participants with childhood adversity are more vulnerable to environmental risk factors for cognitive impairment.
twins; genetics; height; cognition; dementia; risk factor
The CHRNA5-CHRNA3-CHRNB4 gene cluster on chromosome 15q25.1 encoding the cholinergic nicotinic receptor subunits is robustly associated with smoking behavior and nicotine dependence. Only a few studies to date have examined the locus with alcohol related traits and found evidence of association with alcohol abuse and dependence. Our main goal was to examine the role of three intensively studied single nucleotide polymorphisms, rs16969968, rs578776 and rs588765, tagging three distinct loci, in alcohol use. Our sample was drawn from two independent Finnish population-based surveys, the National FINRISK Study and the Health 2000 (Health Examination) Survey. The combined sample included a total of 32,592 adult Finns (54% women) of whom 8,356 were assessed for cigarettes per day (CPD). Data on alcohol use were available for 31,812 individuals. We detected a novel association between rs588765 and alcohol use defined as abstainers and low-frequency drinkers versus drinkers (OR=1.15, p=0.00007). Additionally, we provide precise estimates of strength of the association between the three loci and smoking quantity in a very large population based sample. As a conclusion, our results provide further evidence for the nicotine-specific role of rs16969968 (locus 1). Further, our data suggest that the effect of rs588765 (locus 3) may be specific to alcohol use as the effect is seen also in never smokers.
Nicotinic acetylcholine receptors; 15q25.1; alcohol use; smoking behavior; public health; population-based sample; genetic association
The role of the nicotinic acetylcholine receptor gene cluster on chromosome 15q24-25 in the etiology of nicotine dependence (ND) is still being defined. In this study, we included all 15 tagging single nucleotide polymorphisms (SNPs) within the CHRNA5-CHRNA3-CHRNB4 cluster and tested associations with 30 smoking-related phenotypes.
The study sample was ascertained from the Finnish Twin Cohort study. Twin pairs born 1938–1957 and concordant for a history of cigarette smoking were recruited along with their family members (mainly siblings), as part of the Nicotine Addiction Genetics consortium. The study sample consisted of 1,428 individuals (59% males) from 735 families, with mean age 55.6 years.
We detected multiple novel associations for ND. DSM-IV ND symptoms associated significantly with the proxy SNP Locus 1 (rs2036527, p = .000009) and Locus 2 (rs578776, p = .0001) and tolerance factor of the Nicotine Dependence Syndrome Scale (NDSS) showed suggestive association to rs11636753 (p = .0059), rs11634351 (p = .0069), and rs1948 (p = .0071) in CHRNB4. Furthermore, we report significant association with DSM-IV ND diagnosis (rs2036527, p = .0003) for the first time in a Caucasian population. Several SNPs indicated suggestive association for traits related to ages at smoking initiation. Also, rs11636753 in CHRNB4 showed suggestive association with regular drinking (p = .0029) and the comorbidity of depression and ND (p = .0034).
We demonstrate novel associations of DSM-IV ND symptoms and the NDSS tolerance subscale. Our results confirm and extend association findings for other ND measures. We show pleiotropic effects of this gene cluster on multiple measures of ND and also regular drinking and the comorbidity of ND and depression.
Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in the elderly. It is characterized by changes in joint structure including degeneration of the articular cartilage and its etiology is multifactorial with a strong postulated genetic component. We performed a meta-analysis of four genome-wide association (GWA) studies of 2,371 knee OA cases and 35,909 controls in Caucasian populations. Replication of the top hits was attempted with data from additional ten replication datasets. With a cumulative sample size of 6,709 cases and 44,439 controls, we identified one genome-wide significant locus on chromosome 7q22 for knee OA (rs4730250, p-value=9.2×10−9), thereby confirming its role as a susceptibility locus for OA. The associated signal is located within a large (500kb) linkage disequilibrium (LD) block that contains six genes; PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, beta), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like), and BCAP29 (the B-cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
Early pubertal onset in females is associated with increased risk for adult obesity and cardiovascular disease, but whether this relationship is independent of preceding childhood growth events is unclear. Furthermore, the association between male puberty and adult disease remains unknown. To clarify the link between puberty and adult health, we evaluated the relationship between pubertal timing and risk factors for type 2 diabetes and cardiovascular disease in both males and females from a large, prospective, and randomly ascertained birth cohort from Northern Finland.
RESEARCH DESIGN AND METHODS
Pubertal timing was estimated based on pubertal height growth in 5,058 subjects (2,417 males and 2,641 females), and the relationship between puberty and body weight, glucose and lipid homeostasis, and blood pressure at age 31 years was evaluated with linear regression modeling.
Earlier pubertal timing associated with higher adult BMI, fasting insulin, diastolic blood pressure, and decreased HDL cholesterol in both sexes (P < 0.002) and with higher total serum cholesterol, LDL cholesterol, and triglycerides in males. The association with BMI and diastolic blood pressure remained statistically significant in both sexes, as did the association with insulin levels and HDL cholesterol concentrations in males after adjusting for covariates reflecting both fetal and childhood growth including childhood BMI.
We demonstrate independent association between earlier pubertal timing and adult metabolic syndrome-related derangements both in males and females. The connection emphasizes that the mechanisms advancing puberty may also contribute to adult metabolic disorders.
Nuclear magnetic resonance assays allow for measurement of a wide range of metabolic phenotypes. We report here the results of a GWAS on 8,330 Finnish individuals genotyped and imputed at 7.7 million SNPs for a range of 216 serum metabolic phenotypes assessed by NMR of serum samples. We identified significant associations (P < 2.31 × 10−10) at 31 loci, including 11 for which there have not been previous reports of associations to a metabolic trait or disorder. Analyses of Finnish twin pairs suggested that the metabolic measures reported here show higher heritability than comparable conventional metabolic phenotypes. In accordance with our expectations, SNPs at the 31 loci associated with individual metabolites account for a greater proportion of the genetic component of trait variance (up to 40%) than is typically observed for conventional serum metabolic phenotypes. The identification of such associations may provide substantial insight into cardiometabolic disorders.
Body mass index (BMI) is associated with subjective well-being. Higher BMI is believed to be related with lower well-being. However, the association may not be linear. Therefore, we investigated whether a nonlinear (U-shaped) trend would better describe this relationship, and whether eating disorders might account for the association in young adults.
FinnTwin16 study evaluated multiple measures of subjective well-being, including life satisfaction, General Health Questionnaire (GHQ-20), satisfaction with leisure time, work, and family relationships, and satisfaction with sex life in young adulthood in the 1975–79 birth cohorts of Finnish twins (n=5240). We studied the relationship between indicators of subjective well-being and BMI both in full birth cohorts and in subgroups stratified by lifetime DSM-IV eating disorders.
We found an inverse U-shaped relationship between all indicators of subjective well-being and BMI in men. There was no overall association between BMI and subjective well-being in women. However, there was an inverse U-shaped relationship between BMI and indicators of subjective well-being in women with a lifetime eating disorder and their healthy female co-twins. Subjective well-being was optimal in the overweight category.
Both underweight and obesity are associated with impaired subjective well-being in young men. The BMI reflecting optimal subjective well-being of young men may be higher than currently recognized. Categorization of body weight in terms of BMI may need to be reassessed in young men. BMI and subjective well-being are related in women with a lifetime eating disorder, but not in the general population of young women.
Body mass index; Subjective well-being; Life satisfaction; GHQ-20; Eating disorders; Twin study
We investigated genetic and environmental influences common to adolescent
externalizing behavior (at age 12), smoking (at age 14) and initiation of drug
use (at age 17) using the FinnTwin12 cohort data. Multivariate
Cholesky models were fit to data from 737 monozygotic and 722 dizygotic twin
pairs. Heritability of externalizing behavior was 56%, that of smoking
initiation/amount 20/32%, and initiation of drug use 27%. In the
best-fitting model common environmental influences explained most of the
covariance between externalizing behavior and smoking initiation (69%)
and amount (77%). Covariance between smoking initiation/amount and drug
use was due to additive genetic (42/22%) and common environmental
(58/78%) influences. Half of the covariance between externalizing
behavior and drug use was due to shared genetic and half due to the environments
shared by co-twins. Using a longitudinal, prospective design, our results
indicate that early observed externalizing behavior provides significant
underlying genetic and environmental influences common to later substance use,
here manifested as initiation of drug use in late adolescence.
Externalizing behavior; Smoking; Drugs; Genetic modeling
We examined whether externalizing problem behaviors (hyperactivity–impulsivity, aggressiveness, and inattention) predict illicit drug use independently, or whether their associations with drug use are mediated through cigarette smoking. We used a prospective longitudinal design within the FinnTwin12-17 study among Finnish adolescents with baseline at age 12 and follow-up surveys at ages 14 and 17. Path models were conducted with Mplus and included 1992 boys and 2123 girls. The outcome was self-reported ever use of cannabis or other illicit drugs at age 17. The predictors were: externalizing behaviors (hyperactivity–impulsivity, aggressiveness, and inattention) assessed by teachers and parents (age 12) and self-reported cigarette smoking (age 14). The findings differed across behavior studied. The association of hyperactivity–impulsivity with drug use was mostly mediated through earlier cigarette smoking. Concerning aggressiveness and inattention, the results were different among girls than boys. Among girls no significant mediation occurred, whereas among boys more consistent evidence on mediation was seen. Consistently in all models, the direct association of early cigarette smoking on drug use was strong and highly significant. We conclude that the associations of externalizing problem behaviors with illicit drug use are partially mediated through cigarette smoking. Although interventions targeting externalizing problem behaviors may protect adolescents from early onset smoking and subsequently experimenting with drugs, interventions to prevent cigarette smoking initiation are also important in reducing risk of later drug use.
externalizing behavior; hyperactivity-impulsivity; aggressiveness; inattention; cigarette smoking; tobacco; cannabis; illicit drugs; adolescents
Twin and family studies have demonstrated that adolescent alcohol use and behavior problems are influenced by a combination of genetic and environmental factors. More recently, studies have begun to investigate how genetic and environmental influences may interact, with efforts underway to identify specific environmental variables that moderate the expression of genetic predispositions. Previously, we have reported that community-level factors, including urban/rural residency, migration rates, and prevalence of young adults, moderate the importance of genetic effects on alcohol use in late adolescence (ages 16 to 18). Here, we extend these findings to test for moderating effects of these socioregional factors on alcohol use and behavior problems assessed in a younger sample of adolescent Finnish twins.
Using data from the population-based Finnish twin study, FinnTwin12, biometric twin models were fit to data on >1,400 twin pairs to examine the significance of each of the socioregional moderating variables on alcohol use measured at age 14, and behavior problems, measured at age 12.
We find no evidence of a moderating role of these socioregional variables on alcohol use; however, there was significant moderation of genetic influences on behavior problems, with effects limited to girls. Genetic influences assumed greater importance in urban settings, communities with greater migration, and communities with a higher percentage of slightly older adolescents.
The moderation effects observed on behavior problems in early adolescence paralleled the effects found on alcohol use late in adolescence in an independent sample, providing further support for the idea that behavior problems may represent an earlier manifestation of the predisposition to subsequent alcohol problems. Our findings also support the growing body of evidence suggesting that females may be more susceptible to a variety of environmental influences than males.
Neighborhoods; Community; Genetics; Gene–Environment Interaction; Behavior Problems
Chromosome 20 has previously been associated with nicotine dependence (ND) and smoking cessation. Our aim was to replicate and extend these findings.
First, a total of 759 subjects belonging to 206 Finnish families were genotyped with 18 microsatellite markers residing on chromosome 20, in order to replicate previous linkage findings. Then, the replication data were combined to an existing whole-genome linkage data resulting in a total of 1,302 genotyped subjects from 357 families. ND diagnosed by DSM-IV criteria, the Fagerström Test for Nicotine Dependence (FTND) score, and the lifetime maximum number of cigarettes smoked within a 24-hr period (MaxCigs24) were used as phenotypes in the nonparametric linkage analyses.
We replicated previously reported linkage to DSM-IV ND, with a maximum logarithm of odd (LOD) score of 3.8 on 20p11, with females contributing more (maximum LOD [MLOD] score 3.4 on 20q11) than males (MLOD score 2.6 on 20p11). With the combined sample, a suggestive LOD score of 2.3 was observed for DSM-IV ND on 20p11. Sex-specific analyses revealed that the signal was driven by females with a maximum LOD score of 3.3 (on 20q11) versus LOD score of 1.3 in males (on 20q13) in the combined sample. No significant linkage signals were obtained for FTND or MaxCigs24.
Our results provide further evidence that chromosome 20 harbors genetic variants influencing ND in adult smokers.
Serotonin transporter gene polymorphism (5-HTTLPR polymorphism) predicts the degree of structural and functional connectivity in the brain, and less consistently the degree of vulnerability for anxiety and depressive disorders. It is less known how 5-HTTLPR polymorphism influences on the coupling between brain and neuronal cardiovascular control. The present study demonstrates the impact of 5-HTTLPR polymorphism on the relations between heart rate (HR) corrected cardiac repolarization interval (QTc interval) and the brain 5-HTT binding.
Material and Methods
Thirty healthy young adults (fifteen monozygotic twin pairs) (mean age 26±1.3 years, 16 females) were imagined with single-photon emission computed tomography (SPECT) using iodine-123 labeled 2β-carbomethoxy-3β-(4-iodophenyl) nortropane (nor-β-CIT). Continuous ECG recording was obtained from each participant at supine rest. Signal averaged QTc interval on continuous ECG was calculated and compared with the brain imaging results.
In the two groups [l homozygotes (n = 16, 10 females), s carriers (n = 14, 8 female)] HR and the length of QTc interval were not influenced by 5-HTTLPR polymorphism. There were no significant relations between HR and 5-HTT binding in the brain. There were significant associations between QTc interval and nor-β-CIT binding in the brain in l homozygotes, but not in s carriers (correlations for QTc interval and nor-β-CIT binding of striatum, thalamus and right temporal region were −0.8–−0.9, (p<0.0005), respectively).
The finding of longer QTc interval with less 5-HTT binding availability in major serotonergic binding sites in l homozygotes, but not in s carriers, implicate to differentiated control of QTc interval by 5-HTTLPR polymorphism.
High serum triglyceride (TG) levels is an established risk factor for coronary heart disease (CHD). Fat is stored in the form of TGs in human adipose tissue. We hypothesized that gene co-expression networks in human adipose tissue may be correlated with serum TG levels and help reveal novel genes involved in TG regulation.
Gene co-expression networks were constructed from two Finnish and one Mexican study sample using the blockwiseModules R function in Weighted Gene Co-expression Network Analysis (WGCNA). Overlap between TG-associated networks from each of the three study samples were calculated using a Fisher’s Exact test. Gene ontology was used to determine known pathways enriched in each TG-associated network.
We measured gene expression in adipose samples from two Finnish and one Mexican study sample. In each study sample, we observed a gene co-expression network that was significantly associated with serum TG levels. The TG modules observed in Finns and Mexicans significantly overlapped and shared 34 genes. Seven of the 34 genes (ARHGAP30, CCR1, CXCL16, FERMT3, HCST, RNASET2, SELPG) were identified as the key hub genes of all three TG modules. Furthermore, two of the 34 genes (ARHGAP9, LST1) reside in previous TG GWAS regions, suggesting them as the regional candidates underlying the GWAS signals.
This study presents a novel adipose gene co-expression network with 34 genes significantly correlated with serum TG across populations.
Mexicans; Finns; RNA sequencing; Triglycerides; Adipose tissue; Weighted gene co-expression network analysis
Twin studies demonstrate that measures of alcohol consumption (AC) show evidence of genetic influence, suggesting they may be useful in gene identification efforts. The extent to which these phenotypes will be informative in identifying susceptibility genes involved in alcohol dependence depends on the extent to which genetic influences are shared across measures of AC and alcohol problems. Previous studies have demonstrated that AC reported for the period of heaviest lifetime drinking shows a large degree of genetic overlap with alcohol dependence; however, many studies with genetic material assess current AC. Further, there are many different aspects of AC that can be assessed (e.g., frequency of use, quantity of use, and frequency of intoxication).
Here, we use data from 2 large, independent, population-based twin samples, Finn-Twin 16 and The Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, to examine the extent to which genetic influences are shared across many different measures of AC and alcohol problems.
Genetic correlations across current AC measures and alcohol problems were high across both samples. However, both samples suggest a complex genetic architecture with many different genetic factors influencing various aspects of current AC and problems.
These results suggest that careful attention must be paid to the phenotype in efforts to “replicate” genetic effects across samples or combine samples for meta-analyses of genetic effects influencing susceptibility to alcohol-related outcomes.
Alcohol Consumption; Alcohol Dependence; Gene Finding; Genetic Influence; Twin Studies
Anxiety symptoms are common in chronic pain patients. High levels of anxiety are associated with increased pain experience and disability. Proneness to anxiety has a large interindividual variation. The aim of the study was to determine whether the anxiety-related temperament trait Harm Avoidance (HA), is associated with pain-related anxiety.
One hundred chronic pain patients in a multidisciplinary pain clinic participated in the study. The patients were assessed using the HA scale of the Temperament and Character Inventory (TCI) of Cloninger and Pain Anxiety Symptoms Scale-20 (PASS-20). Both the HA total score and the four subscales of HA were analyzed. Current pain intensity was measured using the Visual Analogue Scale (VAS). The Beck Depression Inventory (BDI) was used to control for the influence of depression on the personality measurement.
The HA total score was associated with PASS-20, but the association became non-significant after controlling for depression. The HA4 Fatigability subscale was associated with the PASS scales. Depression did not influence this association. Pain intensity was not correlated with HA or the PASS scales. However, the association between HA4 Fatigability and PASS was influenced by pain intensity. Higher pain intensity was associated with stronger association between the scales.
Harm Avoidance, representing temperament and trait-related anxiety, has relevance in pain-related anxiety. Assessing personality and temperament may deepen the clinician's understanding of the pain experience and behavior in chronic pain patients.
Prevalence differences in depressive symptoms between the sexes typically emerge in adolescence, with symptoms more prevalent among girls. Some evidence suggests that variation in onset and progression of puberty might contribute to these differences. This study used a genetically informative, longitudinal (assessed at ages 12, 14, and 17) sample of Finnish adolescent twins (N = 1214, 51.6% female) to test whether etiological influences on depressive symptoms differ as a function of pubertal status. These tests were conducted separately by sex, and explored longitudinal relationships. Results indicated that pubertal development moderates environmental influences on depressive symptoms. These factors are more important on age 14 depressive symptoms among more developed girls relative to their less developed peers, but decrease in influence on age 17 depressive symptoms. The same effects are observed in boys, but are delayed, paralleling the delay in pubertal development in boys compared to girls. Thus, the importance of environmental influences on depressive symptoms during adolescence changes as a function of pubertal development, and the timing of this effect differs across the sexes.
Pubertal development; Depressive symptoms; Moderation; Genetics
Callosal volume reduction has been observed in patients with bipolar disorder, but whether these deficits reflect genetic vulnerability to the illness remains unresolved. Here, we used computational methods to map corpus callosum abnormalities in a population-based sample of twin pairs discordant for bipolar disorder. Twenty-one probands with bipolar I disorder (mean age 44.4 ± 7.5 years; 48% female), 19 of their non-bipolar co-twins, and 34 demographically matched control twin individuals underwent magnetic resonance imaging. Three-dimensional callosal surface models were created to visualize its morphologic variability and to localize group differences. Neurocognitive correlates of callosal area differences were additionally investigated in a subsample of study participants. Bipolar (BPI) probands, but not their co-twins, showed significant callosal thinning and area reduction, most pronounced in the genu and splenium, relative to healthy twins. Altered callosal curvature was additionally observed in BPI probands. In bipolar probands and co-twins, genu and splenium midsagittal areas were significantly correlated with verbal processing speed and response inhibition. These findings suggest that aberrant connections between cortical regions—possibly reflecting decreased myelination of white matter tracts—may be involved in bipolar pathophysiology. However, findings of callosal thinning appear to be disease related, rather than reflecting genetic vulnerability to bipolar illness.
magnetic resonance imaging; mood disorders; myelination; processing speed; twin study
The authors tested for genetic linkage of DSM-IV-diagnosed major depressive disorder in families that were ascertained for cigarette smoking.
Within a study that targeted families characterized by a history of smoking, analyses derived a subset of 91 Australian families with two or more offspring with a history of DSM-IV major depressive disorder (affected sibling pairs, N=187) and 25 Finnish families (affected sibling pairs, N=33). Within this affected sibling pair design, the authors conducted nonparametric linkage analysis.
In the Australian heavy smoking families, the authors found a genome-wide significant multipoint LOD score of 4.14 for major depressive disorder on chromosome 3 at 24.9 cM (3p26-3p25).
Genome-wide significant linkage was detected for major depressive disorder on chromosome 3p in a sample ascertained for smoking. A linkage peak at this location was also observed in an independent study of major depressive disorder.
To examine whether smoking habits, nicotine dependence (ND) and plasma cotinine levels differ by diurnal type.
Data originated from the national FINRISK 2007 survey. Regression analyses were calculated to examine the association between diurnal type and smoking status, ND, and nicotine intake.
7091 FINRISK participants with smoking and diurnal type information and a subset of 1746 ever smokers with detailed smoking, and ND assessments.
Diurnal type assessed with a six-item sum scale was categorized as morning, intermediate and evening type. Smoking status was determined as current (daily or occasional), former, and never smokers. ND was measured with the Fagerström Test for Nicotine Dependence (FTND), the Hooked on Nicotine Checklist (HONC), and the Nicotine Dependence Syndrome Scale (NDSS). For current smokers, plasma cotinine was analyzed as biochemical measurement of nicotine intake.
Evening type was associated with current smoking (OR=1.66, 95% CI 1.40, 1.97). A significant association with diurnal type was seen for FTND among men (beta= -0.46, 95% CI -0.72, -0.21), sexes combined for HONC (beta= -0.31, 95% CI -0.52, -0.11) and NDSS (beta= -0.86, 95% CI -1.43, -0.29) and for cotinine among men (beta= -0.73, 95% CI -1.16, -0.29). Adjustment for depressive symptoms attenuated the association of diurnal type with NDSS to be non-significant.
Diurnal type was associated with multiple ND measures and nicotine intake, interestingly more so among men. Evening type persons are at higher risk of dependence, but depressive symptoms attenuates this association clearly.
Adults; Smoking; Nicotine dependence; Diurnal type; Chronotype; Eveningness; Fagerström test for nicotine dependence; Nicotine dependence syndrome scale; Hooked on nicotine checklist; Cotinine