Burden of depressive disorders by country, sex, age, and year : findings from the Global Burden of Disease Study 2010

Background Depressive disorders were a leading cause of burden in the Global Burden of Disease (GBD) 1990 and 2000 studies. Here, we analyze the burden of depressive disorders in GBD 2010 and present severity proportions, burden by country, region, age, sex, and year, as well as burden of depressive disorders as a risk factor for suicide and ischemic heart disease. Methods and Findings Burden was calculated for major depressive disorder (MDD) and dysthymia. A systematic review of epidemiological data was conducted. The data were pooled using a Bayesian meta-regression. Disability weights from population survey data quantified the severity of health loss from depressive disorders. These weights were used to calculate years lived with disability (YLDs) and disability adjusted life years (DALYs). Separate DALYs were estimated for suicide and ischemic heart disease attributable to depressive disorders.Depressive disorders were the second leading cause of YLDs in 2010. MDD accounted for 8.2% (5.9%-10.8%) of global YLDs and dysthymia for 1.4% (0.9%-2.0%). Depressive disorders were a leading cause of DALYs even though no mortality was attributed to them as the underlying cause. MDD accounted for 2.5% (1.9%-3.2%) of global DALYs and dysthymia for 0.5% (0.3%-0.6%). There was more regional variation in burden for MDD than for dysthymia; with higher estimates in females, and adults of working age. Whilst burden increased by 37.5% between 1990 and 2010, this was due to population growth and ageing. MDD explained 16 million suicide DALYs and almost 4 million ischemic heart disease DALYs. This attributable burden would increase the overall burden of depressive disorders from 3.0% (2.2%-3.8%) to 3.8% (3.0%-4.7%) of global DALYs. Conclusions GBD 2010 identified depressive disorders as a leading cause of burden. MDD was also a contributor of burden allocated to suicide and ischemic heart disease. These findings emphasize the importance of including depressive disorders as a public-health priority and implementing cost-effective interventions to reduce its burden.Please see later in the article for the Editors' Summary.

Is disease severity in ankylosing spondylitis genetically determined?

Objective. To assess the role of genes and the environment in determining the severity of ankylosing spondylitis. Methods: One hundred seventy-three families with >1 case of ankylosing spondylitis were recruited (120 affected sibling pairs, 26 affected parent-child pairs, 20 families with both first- and second-degree relatives affected, and 7 families with only second-degree relatives affected), comprising a total of 384 affected individuals. Disease severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and functional impairment was determined using the Bath Ankylosing Spondylitis Functional Index (BASFI). Disease duration and age at onset were also studied. Variance-components modeling was used to determine the genetic and environmental components Contributing to familiality of the traits examined, and complex segregation analysis was performed to assess different disease models. Results. Both the disease activity and functional capacity as assessed by the BASDAI and the BASFI, respectively, were found to be highly familial (BASDAI familiality 0.51 [P = 10-4], BASFI familiality 0,68 [P = 3 × 10-7]). No significant shared environmental component was demonstrated to be associated with either the BASDAI or the BASFI. Including age at disease onset and duration of disease as covariates made no difference in the heritability assessments. A strong correlation was noted between the BASDAI and the BASFI (genetic correlation 0.9), suggesting the presence of shared determinants of these 2 measures. However, there was significant residual heritability for each measure independent of the other (BASFI residual heritability 0.48, BASDAI 0,36), perhaps indicating that not all genes influencing disease activity influence chronicity. No significant heritability of age at disease onset was found (heritability 0.18; P = 0.2). Segregation studies suggested the presence of a single major gene influencing the BASDAI and the BASFI. Conclusion. This study demonstrates a major genetic contribution to disease severity in ankylosing spondylitis. As with susceptibility to ankylosing spondylitis, shared environmental factors play little role in determining the disease severity.

Quality of life in children with Crohn disease

Objectives: Quality of life (QOL) is reportedly poor in children with Crohn disease (CD) but improves with increasing disease duration. This article aims to detail QOL in a cohort of Australian children with CD in relation to disease duration, disease activity, and treatment. MATERIALS AND METHODS: QOL, assessed using the IMPACT-III questionnaire, and disease activity measures, assessed using the Pediatric Crohn's Disease Activity Index (PCDAI), were available in 41 children with CD. For this cohort, a total of 186 measurements of both parameters were available. Results: QOL was found to be significantly lower, and disease activity significantly higher (F = 31.1, P = 0.00), in patients within 6 months of their diagnosis compared with those up to 2.5 years, up to 5 years, and beyond 5 years since diagnosis. Higher disease activity was associated with poorer QOL (r =-0.51, P = 0.00). Total QOL was highest in children on nil medications and lowest in children on enteral nutrition. The PCDAI (t =-6.0, P = 0.00) was a significant predictor of QOL, with the clinical history (t =-6.9, P = 0.00) and examination (t =-2.9, P = 0.01) sections of the PCDAI significantly predicting QOL. Disease duration, age, or sex was neither related to nor significant predictors of QOL, but height z score and type of treatment approached significance. Conclusions: Children with CD within 6 months of their diagnosis have impaired QOL compared with those diagnosed beyond 6 months. These patients, along with those with growth impairment, ongoing elevated disease activity with abdominal pain, diarrhoea and/or perirectal and extraintestinal complications, may benefit from regular assessments of QOL as part of their clinical treatment. © 2010 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Visual sensitivity loss in the central thirty degrees of visual field is associated with diabetic peripheral neuropathy

Aims/hypothesis: Impaired central vision has been shown to predict diabetic peripheral neuropathy (DPN). Several studies have demonstrated diffuse retinal neurodegenerative changes in diabetic patients prior to retinopathy development, raising the prospect that non-central vision may also be compromised by primary neural damage. We hypothesise that type 2 diabetic patients with DPN exhibit visual sensitivity loss in a distinctive pattern across the visual field, compared with a control group of type 2 diabetic patients without DPN. Methods: Increment light sensitivity was measured by standard perimetry in the central 30 degree of visual field for two age-matched groups of type 2 diabetic patients, with and without neuropathy (n=40/30). Neuropathy status was assigned using the neuropathy disability score. Mean visual sensitivity values were calculated globally, for each quadrant and for three eccentricities (0-10 degree , 11-20 degree and 21-30 degree ). Data were analysed using a generalised additive mixed model (GAMM). Results: Global and quadrant between-group visual sensitivity mean differences were marginally but consistently lower (by about 1 dB) in the neuropathy cohort compared with controls. Between-group mean differences increased from 0.36 to 1.81 dB with increasing eccentricity. GAMM analysis, after adjustment for age, showed these differences to be significant beyond 15 degree eccentricity and monotonically increasing. Retinopathy levels and disease duration were not significant factors within the model (p=0.90). Conclusions/interpretation: Visual sensitivity reduces disproportionately with increasing eccentricity in type 2 diabetic patients with peripheral neuropathy. This sensitivity reduction within the central 30 degree of visual field may be indicative of more consequential loss in the far periphery.

Retinal nerve fibre layer thinning associated with diabetic peripheral neuropathy

Aims:  To investigate the relationship between retinal nerve fibre layer thickness and peripheral neuropathy in patients with Type 2 diabetes, particularly in those who are at higher risk of foot ulceration. Methods:  Global and sectoral retinal nerve fibre layer thicknesses were measured at 3.45 mm diameter around the optic nerve head using optical coherence tomography (OCT). The level of neuropathy was assessed in 106 participants (82 with Type 2 diabetes and 24 healthy controls) using the 0–10 neuropathy disability score. Participants were stratified into four neuropathy groups: none (0–2), mild (3–5), moderate (6–8), and severe (9–10). A neuropathy disability score ≥ 6 was used to define those at higher risk of foot ulceration. Multivariable regression analysis was performed to assess the effect of neuropathy disability scores, age, disease duration and retinopathy on RNFL thickness. Results:  Inferior (but not global or other sectoral) retinal nerve fibre layer thinning was associated with higher neuropathy disability scores (P = 0.03). The retinal nerve fibre layer was significantly thinner for the group with neuropathy disability scores ≥ 6 in the inferior quadrant (P < 0.005). Age, duration of disease and retinopathy levels did not significantly influence retinal nerve fibre layer thickness. Control participants did not show any significant differences in thickness measurements from the group with diabetes and no neuropathy (P > 0.24 for global and all sectors). Conclusions:  Inferior quadrant retinal nerve fibre layer thinning is associated with peripheral neuropathy in patients with Type 2 diabetes, and is more pronounced in those at higher risk of foot ulceration.

Retinal nerve fibre layer thickness is associated with higher risk of foot ulceration in diabetic peripheral neuropathy

Purpose To evaluate the association between retinal nerve fibre layer (RNFL) thickness and diabetic peripheral neuropathy in people with type 2 diabetes, and specifically those at higher risk of foot ulceration. Methods RNFL thicknesses was measured globally and in four quadrants (temporal, superior, nasal and inferior) at 3.45 mm diameter around the optic nerve head using optical coherence tomography (OCT). Severity of neuropathy was assessed using the Neuropathy Disability Score (NDS). Eighty-two participants with type 2 diabetes were stratified according to NDS scores (0-10) as: none, mild, moderate, and severe neuropathy. A control group was additionally included (n=17). Individuals with NDS≥ 6 (moderate and severe neuropathy) have been shown to be at higher risk of foot ulceration. A linear regression model was used to determine the association between RNFL and severity of neuropathy. Age, disease duration and diabetic retinopathy levels were fitted in the models. Independent t-test was employed for comparison between controls and the group without neuropathy, as well as for comparison between groups with higher and lower risk of foot ulceration. Analysis of variance was used to compare across all NDS groups. Results RNFL thickness was significantly associated with NDS in the inferior quadrant (b= -1.46, p=0.03). RNFL thicknesses globally and in superior, temporal and nasal quadrants did not show significant associations with NDS (all p>0.51). These findings were independent of the effect of age, disease duration and retinopathy. RNFL was thinner for the group with NDS ≥ 6 in all quadrants but was significant only inferiorly (p<0.005). RNFL for control participants was not significantly different from the group with diabetes and no neuropathy (superior p=0.07, global and all other quadrants: p>0.23). Mean RNFL thickness was not significantly different between the four NDS groups globally and in all quadrants (p=0.08 for inferior, P>0.14 for all other comparisons). Conclusions Retinal nerve fibre layer thinning is associated with neuropathy in people with type 2 diabetes. This relationship is strongest in the inferior retina and in individuals at higher risk of foot ulceration.

Challenging the myth of an "epidemic" of common mental disorders : trends in the global prevalence of anxiety and depression between 1990 and 2010

Background Anxiety disorders and major depressive disorder (MDD) are common and disabling mental disorders. This paper aims to test the hypothesis that common mental disorders have become more prevalent over the past two decades. Methods We conducted a systematic review of prevalence, remission, duration, and excess mortality studies for anxiety disorders and MDD and then used a Bayesian meta-regression approach to estimate point prevalence for 1990, 2005, and 2010. We also conducted a post-hoc search for studies that used the General Health Questionnaire (GHQ) as a measure of psychological distress and tested for trends to present a qualitative comparison of study findings. Results This study found no evidence for an increased prevalence of anxiety disorders or MDD. While the crude number of cases increased by 36%, this was explained by population growth and changing age structures. Point prevalence of anxiety disorders was estimated at 3.8% (3.6-4.1%) in 1990 and 4.0% (3.7-4.2%) in 2010. The prevalence of MDD was unchanged at 4.4% in 1990 (4.2-4.7%) and 2010 (4.1-4.7%). However, 8 of the 11 GHQ studies found a significant increase in psychological distress over time. Conclusions The perceived "epidemic" of common mental disorders is most likely explained by the increasing numbers of affected patients driven by increasing population sizes. Additional factors that may explain this perception include the higher rates of psychological distress as measured using symptom checklists, greater public awareness, and the use of terms such as anxiety and depression in a context where they do not represent clinical disorders.

A clarion call for action based on refined DALY estimates for South Africa

Initial estimates of the burden of disease in South Africa in 20001 have been revised on the basis of additional data to estimate the disability-adjusted life-years (DALYs) for single causes for the first time in South Africa. The findings highlight the fact that despite uncertainty in the estimates, they provide important information to guide public health responses to improve the health of the nation...

Manifestations of type 2 diabetes in corneal endothelial cell density, corneal thickness and intraocular pressure

We sought to evaluate central corneal thickness (CCT), corneal endothelial cell density (ECD) and intraocular pressure (IOP) in patients with type 2 diabetes mellitus (DM) and to associate potential differences with diabetes duration and treatment modality in a prospective, randomized study. We measured ECD, CCT and IOP of 125 patients with type 2 DM (mean age 57.1¡11.5 years) and compared them with 90 age-matched controls. Measured parameters were analyzed for association with diabetes duration and glucose control modalities (insulin injection or oral medication) while controlling for age. In the diabetic group, the mean ECD (2511¡252 cells/mm2), mean CCT (539.7¡33.6 mm) and mean IOP (18.3¡2.5 mmHg) varied significantly from those the control group [ECD: 2713¡132 cells/mm2 (P,0.0001), CCT: 525.0¡45.3 mm (P50.003) and IOP: 16.7¡1.8 mmHg (P,0.0001)]. ECD was significantly reduced by about 32 cell/mm2 for diabetics with duration of .10 years when compared with those with duration of ,10 years (P,0.05). CCT was thicker and IOP was higher for diabetics with duration of .10 years than those with duration of ,10 years (P.0.05). None of the measured parameters was significantly associated with diabetes duration and treatment modality (P.0.05). In conclusion, subjects with type 2 DM exhibit significant changes in ECD, IOP and CCT, which, however, are not correlated with disease duration or if the patients receive on insulin injection or oral medications.

Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis

Objective: To identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS). Method: We studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon-intron boundaries, and 5 kb flanking DNA in the 5' and 3' UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting p<0.05 were genotyped in a further cohort of 830 AS cases; results were analysed both separately and in combination with the discovery phase data. Association was tested by contingency tables after separating the samples into 'mild' and 'severe' groups, defined as the bottom and top 40% by mSASSS, adjusted for gender and disease duration. Results: Experiment-wise association was observed with the SNP rs8092336 (combined OR 0.32, p=1.2×10-5), which lies within RANK (receptor activator of NF?B), a gene involved in osteoclastogenesis, and in the interaction between T cells and dendritic cells. Association was also found with the SNP rs1236913 in PTGS1 (prostaglandin-endoperoxide synthase 1, cyclooxygenase 1), giving an OR of 0.53 (p=2.6×10-3). There was no observed association between radiographic severity and HLA-B*27. Conclusions: These findings support roles for bone resorption and prostaglandins pathways in the osteoproliferative changes in AS.

Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: Results of a randomised placebo-controlled trial (ABILITY-1)

Purpose: To evaluate the efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis (nr-axSpA). Methods: Patients fulfilled Assessment of Spondyloarthritis international Society (ASAS) criteria for axial spondyloarthritis, had a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥ 4, total back pain score of ≥ 4 (10 cm visual analogue scale) and inadequate response, intolerance or contraindication to non-steroidal anti-inflammatory drugs (NSAIDs); patients fulfilling modified New York criteria for ankylosing spondylitis were excluded. Patients were randomised to adalimumab (N=91) or placebo (N=94). The primary endpoint was the percentage of patients achieving ASAS40 at week 12. Efficacy assessments included BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS). MRI was performed at baseline and week 12 and scored using the Spondyloarthritis Research Consortium of Canada (SPARCC) index. Results: Significantly more patients in the adalimumab group achieved ASAS40 at week 12 compared with patients in the placebo group (36% vs 15%, p<0.001). Significant clinical improvements based on other ASAS responses, ASDAS and BASDAI were also detected at week 12 with adalimumab treatment, as were improvements in quality of life measures. Inflammation in the spine and sacroiliac joints on MRI significantly decreased after 12 weeks of adalimumab treatment. Shorter disease duration, younger age, elevated baseline C-reactive protein or higher SPARCC MRI sacroiliac joint scores were associated with better week 12 responses to adalimumab. The safety profile was consistent with what is known for adalimumab in ankylosing spondylitis and other diseases. Conclusions: In patients with nr-axSpA, adalimumab treatment resulted in effective control of disease activity, decreased inflammation and improved quality of life compared with placebo. Results from ABILITY-1 suggest that adalimumab has a positive benefit-risk profile in active nr-axSpA patients with inadequate response to NSAIDs.

Spectrum of ankylosing spondylitis in Portugal. Development of BASDAI, BASFI, BASMI and mSASSS reference centile charts

The availability of population-specific normative data regarding disease severity measures is essential for patient assessment. The goals of the current study were to characterize the pattern of ankylosing spondylitis (AS) in Portuguese patients and to develop reference centile charts for BASDAI, BASFI, BASMI and mSASSS, the most widely used assessment tools in AS. AS cases were recruited from hospital outpatient clinics, with AS defined according to the modified New York criteria. Demographic and clinical data were recorded. All radiographs were evaluated by two independent experienced readers. Centile charts for BASDAI, BASFI, BASMI and mSASSS were constructed for both genders, using generalized linear models and regression models with duration of disease as independent variable. A total of 369 patients (62.3% male, mean ± (SD) age 45.4 ± 13.2 years, mean ± (SD) disease duration 11.4 ± 10.5 years, 70.7% B27-positive) were included. Family history of AS in a first-degree relative was reported in 17.6% of the cases. Regarding clinical disease pattern, at the time of assessment 42.3% had axial disease, 2.4% peripheral disease, 40.9% mixed disease and 7.1% isolated enthesopatic disease. Anterior uveitis (33.6%) was the most common extra-articular manifestation. The centile charts suggest that females reported greater disease activity and more functional impairment than males but had lower BASMI and mSASSS scores. Data collected through this study provided a demographic and clinical profile of patients with AS in Portugal. The development of centile charts constitutes a useful tool to assess the change of disease pattern over time and in response to therapeutic interventions.

ANKH and susceptibility to and severity of ankylosing spondylitis

Objective. Unconfirmed reports describe association of ankylosing spondylitis (AS) with several candidate genes including ANKH. Cellular export of inorganic pyrophosphate is regulated by the ANK protein, and mutant mice (ank/ank), which have a premature stop codon in the 3′ end of the ank gene, develop severe ankylosis. We tested the association between single-nucleotide polymorphisms (SNP) in these genes and susceptibility to AS in a population of patients with AS. We investigated the role of these genes in terms of functional (BASFI) and metrological (BASMI) measures, and the association with radiological severity (mSASSS). Methods. Our study was conducted on 355 patients with AS and 95 ethnically matched healthy controls. AS was defined according to the modified New York criteria. Four SNP in ANKH (rs27356, rs26307, rs25957, and rs28006) were genotyped. Association analysis was performed using Cochrane-Armitage and linear regression tests for dichotomous and quantitative variables. Analyses of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASFI, and mSASSS were controlled for sex and disease duration. Results. None of the 4 markers showed significant single-locus disease associations (p > 0.05), suggesting that ANKH was not a major determinant of AS susceptibility in our population. No association was observed between these SNP and age at symptom onset, BASDAI, BASFI, BASMI, or mSASSS. Conclusion. These results confirm data in white Europeans that ANKH is probably not a major determinant of susceptibility to AS. ANKH polymorphisms do not markedly influence AS disease severity, as measured by BASMI and mSASSS. The Journal of Rheumatology

The effect of transforming growth factor β1 gene polymorphisms in ankylosing spondylitis

Objectives. To determine whether genetic polymorphisms in or near the transforming growth factor β1 (TGFB1) locus were associated d with susceptibility to or severity of ankylosing spondylitis (AS). Methods. Five intragenic single-nucleotide polymorphisms (SNP) and three microsatellite markers flanking the TGFB1 locus were genotyped. Seven hundred and sixty-two individuals from 184 multiplex families were genotyped for the microsatellite markers and two of the promoter SNPs. One thousand and two individuals from 212 English and 170 Finnish families with AS were genotyped for all five intragenic SNPs. A structured questionnaire was used to assess the age of symptom onset, disease duration and disease severity scores, including the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index). Results. A weak association was noted between the rare TGFB1 + 1632 T allele and AS in the Finnish population (P = 0.04) and in the combined data set (P = 0.03). No association was noted between any other SNPs or SNP haplotype and AS, even among those families with positive non-parametric linkage scores. The TGFB1 +1632 polymorphism was also associated with a younger age of symptom onset (English population, allele 2 associated with age of onset greater by 4.2 yr, P = 0.05; combined data set, allele 2 associated with age of onset greater by 3.2 yr, P = 0.02). A haplotype of coding region SNPs (TGFB1 +869/ +915+1632 alleles 2/1/2) was associated with age of symptom onset in both the English parent-case trios and the combined data set (English data set, haplotype 2/1/2 associated with age of onset greater by 4.9 yr, P = 0.03; combined data set, haplotype 2/1/2 associated with greater age of onset by 4.2 yr, P = 0.006). Weak linkage with AS susceptibility was noted and the peak LOD score was 1.3 at distance 2 cM centromeric to the TGFB1 gene. No other linkage or association was found between quantitative traits and the markers. Conclusion. This study suggests that the polymorphisms within the TGFB1 gene play at most a small role in AS and that other genes encoded on chromosome 19 are involved in susceptibility to the disease.

Interleukin 10 polymorphisms in ankylosing spondylitis

Genetic polymorphisms of the IL10 promoter region have been implicated in many autoimmune diseases, including seronegative spondyloarthropathies. We studied three SNPs (IL10-1087,-824, and -597) and two microsafellites(IL10R and IL10G) lying within the promoter region of IL10 for association with susceptibility to and clinical manifestations of ankylosing spondylitis (AS), a common form of spondyloarthritis. Four hundred and sixty-eight individuals from 182 Finnish families affected with AS were studied. No association between individual IL10 promoter region polymorphisms or marker haplotype was observed with susceptibility to AS, but weak association was noted between the IL10-597 and -824 SNPs and age of disease onset (P= 0.01 for each SNP). The IL10.G4 allele was associated with BASFI (corrected for disease duration) (P= 0.03). We conclude that IL10 promoter polymorphisms have no significant effect on susceptibility to AS, but may play a minor role in determining age of disease onset and disease severity. © 2003 Nature Publishing Group All rights reserved.