Cross-sectional analysis of depressive symptom profiles and serum C-reactive protein levels: data from the Northern Finland 1966 birth cohort.

PURPOSE: Individuals with depression exhibit significantly higher levels of systemic inflammation than those without depression, particularly among those with atypical depression. However, this association has been less convincing at the population level among individuals without a formal depression diagnosis but with suggestive symptoms. Our aim was to clarify this association. MATERIALS AND METHODS: In a large birth cohort sample of the Finnish general population, we examined the cross-sectional association between high-sensitivity C-reactive protein (hsCRP) levels in venous blood samples and atypical/non-atypical depressive symptoms using the Beck Depression Inventory-II to screen 5443 middle-aged participants. RESULTS: As expected, depressive symptoms associated to elevated hsCRP-levels compared to non-depressed. Participants with the atypical subtype of depressive symptoms (n = 84) had an odds ratio (OR) of 2.59 (95% CI 1.40-4.81) for elevated hsCRP levels compared to the non-depressed group. Similarly, our findings indicate that participants with non-atypical symptoms (n = 440) also showed an OR of 1.42 (95% CI 1.05-1.92) when compared to the non-depressed group (n = 4919). CONCLUSIONS: These results provide additional support for previous research linking depression and inflammation and add to the field with a unique and sizeable study population. Furthermore, the current results support the notion that different types of depressive symptoms may be associated with inflammatory markers in slightly different ways.

Glucose status and depressive symptoms: a cohort study of elderly people in northwest Finland.

Objective: To assess the association between depressive symptoms and impaired glucose metabolism in the elderly population in arctic latitudes. Design: A population-based study. Setting. Community. Subjects: The study population consisted of 1,830 subjects born between the years 1915 and 1958 in the northernmost part of Finland, the Muonio-Enontekiö district, who participated in a health survey during 1974-1984. In 2014, a health questionnaire was sent to 1,037 subjects, and 757 participants (73%) answered it. Those (n = 629) living in the Muonio-Enontekiö district undergone a clinical examination in 2014 and 2015 including blood collections. Main outcome measures: Depressive symptoms defined by the Beck Depression Inventory II (BDI II) with a cut-off point of 14. Different diabetic states based on WHO's classification criteria defined by fasting plasma glucose and ADA's criteria by glycosylated haemoglobin (HbA1c) values. Results: According to logistic regression analysis, depressive symptoms (BDI-II ≥ 14) were associated statistically significantly with previously known type 2 diabetes, the odds ratio (OR) being 4.33 (95% CI 1.53-14.14). Regarding prediabetic fasting glucose/HbA1c values, the corresponding OR was 2.94 (95% CI 1.17-8.94). The prevalence of depressive symptoms (BDI-II ≥ 14) was 7.1%, (men 9.7% and women 5.4%) and 13.7% (men 9.9% and women 17.0%) in subjects living in Muonio-Enontekiö district and in those who had moved away from there, respectively. Conclusions: The association of depressive symptoms between prediabetes and diabetes seems to be present also in the northernmost latitudes of the world.

ÖMPSQ-Short Score and determinants of chronic pain: cross-sectional results from a middle-aged birth cohort.

BACKGROUND: The Örebro Musculoskeletal Pain Screening Questionnaire (ÖMPSQ) was developed to identify patients at risk of developing work disability due to pain. So far, neither the ÖMPSQ or its short version (ÖMSPQ-short) have been tested in population-based samples. AIM: We examined the associations between several well-known determinants for chronic pain and ÖMPSQ-Short Score. DESIGN: Cross-sectional study. SETTING: All measurements and tests were made at the University of Oulu. POPULATION: Subjects belonging to the Northern Finland Birth Cohort 1966 answered a questionnaire at the age of 46 years (N.=5637). METHODS: The questionnaire included the ÖMPSQ-short as well as questions about smoking, education, location, number of pain sites, and physical activity. In addition, body weight and height were measured in order to calculate the Body Mass Index. RESULTS: In multivariate logistic regression analysis, reporting 4-5 pain sites (females OR 3.4; males 3.0), ≥6 pain sites (females OR 12.4; males 7.4) and current smoking (females 1.8; males 2.6) were associated with being classified into the ÖMPSQ high risk group. In females, also obesity (OR 1.6) and less than 9 years of education (2.7) were associated with higher ÖMPSQ Score. The frequency of physical activity was not associated with the ÖMPSQ Score. CONCLUSIONS: High number of pain sites and smoking among both genders, and obesity and low education level among females is associated with higher ÖMPSQ scores. Therefore, the ÖMPSQ-short may be a working instrument for also screening the general population. CLINICAL REHABILITATION IMPACT: Results of this study may improve the detection of patients at high risk of developing work disability due to pain.

Association between height and osteoarthritis of the knee and hip: The Northern Finland Birth Cohort 1966 Study.

OBJECTIVES: To investigate whether height at the age of 31 is associated with the incidence of knee and hip osteoarthritis (OA) in the following 15 years. METHODS: Participants in The Northern Finland Birth Cohort 1966 (NFBC1966) diagnosed with knee or hip OA between the ages of 31 and 46 were used as OA cases. Study subjects without knee and hip OA were used as the controls. Height and weight were measured in a clinical examination at the age of 31 (baseline). Mean heights for the OA cases and the controls were compared by an independent samples t-test. Cox regression analysis was performed to calculate the risk for OA for different height quartiles. The results were adjusted for body mass index/weight, education, smoking and leisure-time physical activity at baseline. Additionally, a Kaplan-Meier analysis was performed. RESULTS: Men with knee OA were 2.6 cm taller (P < 0.001) and women with knee OA 1.2 cm taller (P = 0.048) than the controls. Hip OA cases were found to be slightly shorter than the controls, but no statistically significant differences were observed. The adjusted hazard ratios (HRs) for knee OA and hip OA in the highest quartile were 2.5 (95% CI 1.4-4.5) and 1.0 (95% CI 0.3-3.4) for men and 1.8 (95% CI 1.0-3.1) and 0.7 (95% CI 0.2-2.3) for women. CONCLUSIONS: Height at the age of 31 was associated with incidence of early knee OA, diagnosed prior to age 46. However, the low incidence of hip OA made our results for hip OA inconclusive.

Long-term adolescent multi-site musculoskeletal pain is associated with psychological distress and anxiety.

OBJECTIVE: Although several studies have shown that adolescent musculoskeletal pain is associated with psychological problems in a cross-sectional setting, the associations of long-term musculoskeletal pain with psychological distress and anxiety are not known. METHODS: The study included 1773 adolescents belonging to the Northern Finland Birth Cohort 1986. They received a postal questionnaire at the age of 16years and a follow-up questionnaire two years later. The first inquiry contained questions about the sites of musculoskeletal pain; the second had the same pain questions, along with measures of distress and anxiety. Risk ratios (RR) were assessed by log-linear regression analysis. RESULTS: Multi-site musculoskeletal pain (in ≥2 body locations) at both 16 and 18years was common, reported by 53% of girls and 30% of boys. Multi-site pain at both ages, compared to those with multi-site pain neither at 16 nor 18years, was associated with psychological distress at the age of 18 among both girls (RR 1.8 95% CI 1.2-2.7) and boys (RR 3.5 95% CI 2.1-5.9). For anxiety, the corresponding relative risks were 1.5 (95% CI 1.0-2.2) and 1.8 (95% CI 1.4-2.3), respectively. For short-term multi-site pain (prevalent only at the age of 16 or 18), these relative risks were between 0.8 and 2.3. CONCLUSIONS: Adolescents with long-term multi-site pain have higher levels of distress and anxiety than those without or with only short-term multi-site pain. Associations were found in both genders, but the relationship between pain and distress was more pronounced among boys. The associations had modest effect strength.

Lumbar disc degeneration is linked to a carbohydrate sulfotransferase 3 variant.

Lumbar disc degeneration (LDD) is associated with both genetic and environmental factors and affects many people worldwide. A hallmark of LDD is loss of proteoglycan and water content in the nucleus pulposus of intervertebral discs. While some genetic determinants have been reported, the etiology of LDD is largely unknown. Here we report the findings from linkage and association studies on a total of 32,642 subjects consisting of 4,043 LDD cases and 28,599 control subjects. We identified carbohydrate sulfotransferase 3 (CHST3), an enzyme that catalyzes proteoglycan sulfation, as a susceptibility gene for LDD. The strongest genome-wide linkage peak encompassed CHST3 from a Southern Chinese family­based data set, while a genome-wide association was observed at rs4148941 in the gene in a meta-analysis using multiethnic population cohorts. rs4148941 lies within a potential microRNA-513a-5p (miR-513a-5p) binding site. Interaction between miR-513a-5p and mRNA transcribed from the susceptibility allele (A allele) of rs4148941 was enhanced in vitro compared with transcripts from other alleles. Additionally, expression of CHST3 mRNA was significantly reduced in the intervertebral disc cells of human subjects carrying the A allele of rs4148941. Together, our data provide new insights into the etiology of LDD, implicating an interplay between genetic risk factors and miRNA.

Genetic association studies in lumbar disc degeneration: a systematic review.

OBJECTIVE: Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans. METHODS: A systematic literature search was conducted in MEDLINE, MEDLINE In-Process, SCOPUS, ISI Web of Science, The Genetic Association Database and The Human Genome Epidemiology Network for information published between 1990-2011 addressing genes and lumbar disc degeneration. Two investigators independently identified studies to determine inclusion, after which they performed data extraction and analysis. The level of cumulative genetic association evidence was analyzed according to The HuGENet Working Group guidelines. RESULTS: Fifty-two studies were included for review. Forty-eight studies reported at least one positive association between a genetic marker and lumbar disc degeneration. The phenotype definition of lumbar disc degeneration was highly variable between the studies and replications were inconsistent. Most of the associations presented with a weak level of evidence. The level of evidence was moderate for ASPN (D-repeat), COL11A1 (rs1676486), GDF5 (rs143383), SKT (rs16924573), THBS2 (rs9406328) and MMP9 (rs17576). CONCLUSIONS: Based on this first extensive systematic review on the topic, the credibility of reported genetic associations is mostly weak. Clear definition of lumbar disc degeneration phenotypes and large population-based cohorts are needed. An international consortium is needed to standardize genetic association studies in relation to disc degeneration.

Gender difference in genetic association between IL1A variant and early lumbar disc degeneration: a three-year follow-up.

OBJECTIVE: The purpose of the present study was to analyze the associations between specific genetic markers and early disc degeneration (DD) or early disc degeneration progression (DDP) defined by magnetic resonance imaging (MRI). METHODS: We selected eleven of the most promising single nucleotide polymorphisms (SNP) and compared the distributions of these genetic markers between groups defined by MRI in a Danish adolescent population (N=166) over a three-year follow-up period. RESULTS: We observed a ten-fold higher annual incidence of endplate changes than previously reported in adults. The gender difference in IL1A rs1800587 association with DD remained significant and another association with DDP emerged in follow-up assessment. Among girls, the rs1800587 T-allele was associated both with DD (OR 2.82 [95% CI 1.29-6.16]) and with DDP (OR 2.45 [95% CI 1.03-5.82]). Among boys, the IL6 rs1800795 genotype G/C was protective in both DD (OR 0.26 [95% CI 0.09-0.72]) and DDP (OR 0.32 [95% CI 0.12-0.88]) with the IL6 rs1800797 genotype G/A was associated with a decreased likelihood of DD (OR 0.27 [95% CI 0.10-0.77]). Gender-genotype interactions were significant for polymorphisms in both IL1A and IL6. Correction for multiple testing weakened the associations for IL6 polymorphisms. CONCLUSION: We conclude that gender specific effects in lumbar disc degeneration and its progression are possible. However, further evaluations in larger populations are needed. Our results provide some support to the hypothesis that early disc degeneration is an especially important phase in the cascade of degenerative disc disease.

Genetic susceptibility of intervertebral disc degeneration among young Finnish adults.

BACKGROUND: Disc degeneration (DD) is a common condition that progresses with aging. Although the events leading to DD are not well understood, a significant genetic influence has been found. This study was undertaken to assess the association between relevant candidate gene polymorphisms and moderate DD in a well-defined and characterized cohort of young adults. Focusing on young age can be valuable in determining genetic predisposition to DD. METHODS: We investigated the associations of existing candidate genes for DD among 538 young adults with a mean age of 19 belonging to the 1986 Northern Finland Birth Cohort. Nineteen single nucleotide polymorphisms (SNP) in 16 genes were genotyped. We evaluated lumbar DD using the modified Pfirrmann classification and a 1.5-T magnetic resonance scanner for imaging. RESULTS: Of the 538 individuals studied, 46% had no degeneration, while 54% had DD and 51% of these had moderate DD. The risk of DD was significantly higher in subjects with an allele G of IL6 SNPs rs1800795 (OR 1.45, 95% CI 1.07-1.96) and rs1800797 (OR 1.37, 95% CI 1.02-1.85) in the additive inheritance model. The role of IL6 was further supported by the haplotype analysis, which resulted in an association between the GGG haplotype (SNPs rs1800797, rs1800796 and rs1800795) and DD with an OR of 1.51 (95% CI 1.11-2.04). In addition, we observed an association between DD and two other polymorphisms, SKT rs16924573 (OR 0.27 95% CI 0.07-0.96) and CILP rs2073711 in women (OR 2.04, 95% CI 1.07-3.89). CONCLUSION: Our results indicate that IL6, SKT and CILP are involved in the etiology of DD among young adults.

Genetic risk factors of disc degeneration among 12-14-year-old Danish children: a population study.

The objective of the present study was to examine the associations between eleven putative predisposing single nucleotide polymorphisms (COL9A3, COL11A2, IL1A, IL1B, IL6 and VDR) and early disc degeneration (DD). The population consisted of 12 to 14-year-old Danish children (N=352). DD was evaluated from magnetic resonance images (MRI). We analysed the association between DD and single nucleotide polymorphisms or haplotypes using logistic regression analyses. Of the 352 children studied, 73 boys and 81 girls had no MRI changes, while 30 boys and 36 girls had lumbar DD. Among girls, IL1A rs1800587 in CT/TT compared to CC resulted in OR 2.85 [1.19-6.83]. In IL6 promoter polymorphism rs1800796, the C-allele was more frequent among the subjects with DD, OR 6.71 [1.71-26.3]. Of the IL6 haplotypes, GCG was associated with DD, OR 6.46 [1.61 - 26.0]. No associations were observed among boys. Our results suggest possible roles for IL1A and IL6 in early DD among girls.