Estimating the diagnostic accuracy of the ankle-brachial pressure index for detecting peripheral arterial disease in people with diabetes: A systematic review and meta-analysis.

AIM: To systematically evaluate research investigating the accuracy of the ankle-brachial index (ABI) for diagnosing peripheral artery disease (PAD) in people with diabetes, as the accuracy is thought to be reduced in this cohort. METHODS: A database search of EBSCO Megafile Premier, Embase and The Cochrane Library was conducted to 28 February 2019. Prospective and retrospective investigations of the diagnostic accuracy of the ABI for PAD in people with diabetes using an imaging reference standard were eligible. Sensitivity and specify of the ABI and bivariate meta-analysis against reference tests, or a standard summary receiver operating curve analysis (SROC) was performed. RESULTS: Thirty-three studies met the inclusion criteria. ABI was compared with angiography in 12 studies and with colour duplex ultrasound (CDUS) in 21 studies. A SROC analysis of studies using angiography as the reference standard found a diagnostic odds ratio (DOR) of 9.06 [95% confidence interval (CI) 3.61 to 22.69], and area under the curve (AUC) of 0.76 (95% CI 0.66 to 0.86). Bivariate analysis of studies using CDUS demonstrated mean sensitivity of 0.60 (95% CI 0.48 to 0.71; P = 0.097) and mean specificity of 0.87 (95% CI 0.78 to 0.92; P < 0.001) with a DOR of 9.76 (95% CI 5.24 to 18.20; P < 0.0001) and AUC 0.72. CONCLUSIONS: These results suggest the ABI has a high specificity but lower sensitivity in detecting imaging diagnosed PAD in people with diabetes. The low probability of the testing being able to rule diagnosis in or out suggest that the ABI has limited effectiveness for early detection of PAD in this cohort.

CD36 polymorphisms and the age of disease onset in patients with pathogenic variants within the mutation cluster region of APC.

BACKGROUND: Familial adenomatous polyposis (FAP) is an autosomal dominant condition that predisposes patients to colorectal cancer. FAP is the result of a loss of APC function due to germline pathogenic variants disrupting gene expression. Genotype-phenotype correlations are described for FAP. For example attenuated forms of the disease are associated with pathogenic variants at the 5' and 3' ends of APC whilst severe forms of the disease appear to be linked to variants occurring in the mutation cluster region (MCR) of the gene. Variants occurring in the MCR are phenotypically associated with hundreds to thousands of adenomas carpeting the colon and rectum and patients harbouring changes in this region have a high propensity to develop colorectal cancer. Not all patients who carry pathogenic variants in this region have severe disease which may be a result of environmental factors. Alternatively, phenotypic variation observed in these patients could be due to modifier genes that either promote or inhibit disease expression. Mouse models of FAP have provided several plausible candidate modifier genes, but very few of these have survived scrutiny. One such genetic modifier that appears to be associated with disease expression is CD36. We previously reported a weak association between a polymorphism in CD36 and a later age of disease onset on a relatively small FAP patient cohort. METHODS: In the current study, we enlarged the FAP cohort. 395 patients all carrying pathogenic variants in APC were tested against three CD36 Single Nucleotide Polymorphisms (SNP)s (rs1049673, rs1761667 rs1984112), to determine if any of them were associated with differences in the age of disease expression. RESULTS: Overall, there appeared to be a statistically significant difference in the age of disease onset between carriers of the variant rs1984112 and wildtype. Furthermore, test equality of survivor functions for each SNP and mutation group suggested an interaction in the Log Rank, Wilcoxon, and Tarone-Ware methods for rs1049673, rs1761667, and rs1984112, thereby supporting the notion that CD36 modifies disease expression. CONCLUSIONS: This study supports and strengthens our previous findings concerning CD36 and an association with disease onset in FAP, AFAP and FAP-MCR affected individuals. Knowledge about the role CD36 in adenoma development may provide greater insight into the development of colorectal cancer.

The duration of intrapartum maternal hyperglycaemia predicts neonatal hypoglycaemia in women with pre-existing diabetes.

AIM: There is a high incidence of neonatal hypoglycaemia in neonates born to mothers with pre-existing diabetes. This often necessitates admission to the neonatal intensive care. Guidelines suggest maintaining intrapartum blood glucose levels (BGLs) of 4-7 mmol/l in women with diabetes to reduce the risk of neonatal hypoglycaemia. This study assessed whether intrapartum BGLs in women with pre-gestational Type 1 and 2 diabetes were predictive of neonatal hypoglycaemia. METHODS: A retrospective analysis of 261 births delivered at a tertiary hospital in Australia from 2009 to 2014. RESULTS: There were 122 cases of neonatal hypoglycaemia (glucose ≤ 2.6 mmol/l) in 261 births (47%). The mothers in the neonatal hypoglycaemia group spent less time with BGL in the range 4-7 mmol/l [55 ± 37% vs. 65 ± 35%, P = 0.02; odds ratio (OR) 0.992, P = 0.03] and more time with BGL in the 7-10 mmol/l range (31 ± 34% vs. 18 ± 27%, P = 0.003; OR 1.013, P = 0.003) compared with those without neonatal hypoglycaemia. Although statistically significant, receiver operating characteristic (ROC) curve analysis showed that time spent with maternal BGLs in the range 4-7 mmol/l [area under the curve (AUC) = 0.58] or 7-10 mmol (AUC = 0.60) was not strong enough to be a useful clinical predictor of neonatal hypoglycaemia. HbA1c in the second trimester of pregnancy (P = 0.02, OR 1.42) and percentage time spent in BGL range of 7-10 mmol/l (P = 0.001, OR 1.02) were both associated with a risk of neonatal hypoglycaemia in a logistic regression model. HbA1c in the third trimester (P = 0.07, OR 1.28) approached, but did not reach, significance. CONCLUSIONS: These data support a BGL range of 4-7 mmol/l as an intrapartum target. Glycaemic control in the second trimester is associated with neonatal hypoglycaemia. Improvement in ante- and intrapartum glycaemic control may reduce neonatal hypoglycaemia in women with pre-existing diabetes.

GWAS for executive function and processing speed suggests involvement of the CADM2 gene.

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.

Reduced prevalence of pain and distress during 4 years of screening with QUICATOUCH in Australian oncology patients.

While psychosocial screening has been recommended in oncology for some time, widespread adoption in clinical practice has lagged. The QUICATOUCH program is one example of sustained clinic-level screening, assessment and referral. We examined whether this program was associated with reductions in pain or distress. Oncology outpatients completed a brief, computerised assessment using Distress and Pain Thermometers. We describe population levels of pain and distress and model pain and distress scores over 4 years of the program. 9,133 patients were screened on 26,385 occasions over 48 months (October 2007-September 2011). Pain over threshold (1/10) reduced over time, from 33% in the first 3 months to 16% in the final quarter of the evaluation. Distress over threshold (4/10) reduced from 28% to 10%. A reduction was also observed when restricted to patients screened for the first time. Our analysis demonstrated this effect was not explained by measured potential confounders (gender, age, treatment status) and was unlikely to be attributable to regression to the mean. Observational studies cannot prove causation. However, the significant reduction in pain and distress levels in the 48 months following commencement of QUICATOUCH is consistent with a beneficial effect of the program.

Predicting type 2 diabetes using genetic and environmental risk factors in a multi-ethnic Malaysian cohort.

OBJECTIVE: Malaysia has a high and rising prevalence of type 2 diabetes (T2D). While environmental (non-genetic) risk factors for the disease are well established, the role of genetic variations and gene-environment interactions remain understudied in this population. This study aimed to estimate the relative contributions of environmental and genetic risk factors to T2D in Malaysia and also to assess evidence for gene-environment interactions that may explain additional risk variation. STUDY DESIGN: This was a case-control study including 1604 Malays, 1654 Chinese and 1728 Indians from the Malaysian Cohort Project. METHODS: The proportion of T2D risk variance explained by known genetic and environmental factors was assessed by fitting multivariable logistic regression models and evaluating McFadden's pseudo R2 and the area under the receiver-operating characteristic curve (AUC). Models with and without the genetic risk score (GRS) were compared using the log likelihood ratio Chi-squared test and AUCs. Multiplicative interaction between genetic and environmental risk factors was assessed via logistic regression within and across ancestral groups. Interactions were assessed for the GRS and its 62 constituent variants. RESULTS: The models including environmental risk factors only had pseudo R2 values of 16.5-28.3% and AUC of 0.75-0.83. Incorporating a genetic score aggregating 62 T2D-associated risk variants significantly increased the model fit (likelihood ratio P-value of 2.50 × 10-4-4.83 × 10-12) and increased the pseudo R2 by about 1-2% and AUC by 1-3%. None of the gene-environment interactions reached significance after multiple testing adjustment, either for the GRS or individual variants. For individual variants, 33 out of 310 tested associations showed nominal statistical significance with 0.001 < P < 0.05. CONCLUSION: This study suggests that known genetic risk variants contribute a significant but small amount to overall T2D risk variation in Malaysian population groups. If gene-environment interactions involving common genetic variants exist, they are likely of small effect, requiring substantially larger samples for detection.

Effects of a 'school-based' physical activity intervention on adiposity in adolescents from economically disadvantaged communities: secondary outcomes of the 'Physical Activity 4 Everyone' RCT.

BACKGROUND/OBJECTIVES: Obesity prevention during adolescence is a health priority. The 'Physical Activity 4 Everyone' (PA4E1) study tested a multi-component physical activity intervention in 10 secondary schools from socio-economically disadvantaged communities. This paper aimed to report the secondary outcomes of the study; to determine whether the intervention impacted on adiposity outcomes (weight, body mass index (BMI), BMI z-score), and whether any effect was moderated by sex, baseline BMI and baseline physical activity level, at 12 and 24 months. SUBJECTS/METHODS: A cluster randomised controlled trial was conducted in New South Wales, Australia. The school-based intervention included seven physical activity strategies targeting the following: curriculum (strategies to maximise physical activity in physical education, student physical activity plans, an enhanced school sport programme); school environment (physical activity during school breaks, modification of school policy); and parents and the community (parent engagement, links with community physical activity providers). Students' weight (kg), BMI and BMI z-score, were collected at baseline (Grade 7), 12 and 24 months. Linear Mixed Models were used to assess between-group mean difference from baseline to 12 and 24 months. Exploratory sub-analyses were undertaken according to three moderators of energy balance. RESULTS: A total of 1150 students (mean age=12 years) provided outcome data at baseline, 1051 (91%) at 12 months and 985 (86%) at 24 months. At 12 months, there were group-by-time effects for weight (mean difference=-0.90 kg (95% confidence interval (CI)=-1.50, -0.30), P<0.01) and BMI (-0.28 kg m-2 (-0.50, -0.06), P=0.01) in favour of the intervention group, but not for BMI z-score (-0.05 (-0.11; 0.01), P=0.13). These findings were consistent for weight (-0.62 kg (-1.21, 0.03), P=0.01) and BMI (-0.28 kg m-2 (-0.49, -0.06), P=0.01) at 24 months, with group-by-time effects also found for BMI z-score (-0.08 (-0.14; -0.02), P=0.02) favouring the intervention group. CONCLUSION: The PA4E1 school-based intervention achieved moderate reductions in adiposity among adolescents from socio-economically disadvantaged communities. Multi-component interventions that increase adolescents' engagement in moderate-to-vigorous physical activity (MVPA) may assist in preventing unhealthy weight gain.

Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949).

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.

The association between cannabis use and motivation and intentions to quit tobacco within a sample of Australian socioeconomically disadvantaged smokers.

This study aimed to (i) describe concurrent and simultaneous tobacco and cannabis use and (ii) investigate the association between cannabis use and motivation and intentions to quit tobacco in a sample of socioeconomically disadvantaged smokers. A cross-sectional survey was conducted in 2013 and 2014 with current tobacco smokers receiving aid from two community service organizations in New South Wales, Australia. At least weekly cannabis use for the month prior to survey, motivation to quit tobacco and intentions to quit tobacco were measured in 369 participants (77% consent rate). Regressions were carried out to investigate associations between weekly cannabis use and motivation and intentions to quit tobacco.Concurrent tobacco and cannabis use was reported by 19% (n = 71) of the sample and of these users, 100% reported simultaneous use. Although regular cannabis use was significantly associated with lower motivation to quit tobacco, it was not significantly associated with intentions to quit tobacco in the next 30 days. Concurrent cannabis use is common in disadvantaged smokers and may play a role in decreased motivation to quit tobacco; however, it does not appear to be associated with intentions to quit in a sample of disadvantaged smokers.

Characterizing the genetic risk for Type 2 diabetes in a Malaysian multi-ethnic cohort.

AIMS: To characterize the association with Type 2 diabetes of known Type 2 diabetes risk variants in people in Malaysia of Malay, Chinese and Indian ancestry who participated in the Malaysian Cohort project. METHODS: We genotyped 1604 people of Malay ancestry (722 cases, 882 controls), 1654 of Chinese ancestry (819 cases, 835 controls) and 1728 of Indian ancestry (851 cases, 877 controls). First, 62 candidate single-nucleotide polymorphisms previously associated with Type 2 diabetes were assessed for association via logistic regression within ancestral groups and then across ancestral groups using a meta-analysis. Second, estimated odds ratios were assessed for excess directional concordance with previously studied populations. Third, a genetic risk score aggregating allele dosage across the candidate single-nucleotide polymorphisms was tested for association within and across ancestral groups. RESULTS: After Bonferroni correction, seven individual single-nucleotide polymorphisms were associated with Type 2 diabetes in the combined Malaysian sample. We observed a highly significant excess in concordance of effect directions between Malaysian and previously studied populations. The genetic risk score was strongly associated with Type 2 diabetes in all Malaysian groups, explaining from 1.0 to 1.7% of total Type 2 diabetes risk variance. CONCLUSION: This study suggests there is substantial overlap of the genetic risk alleles underlying Type 2 diabetes in Malaysian and other populations.

The iTreAD project: a study protocol for a randomised controlled clinical trial of online treatment and social networking for binge drinking and depression in young people.

BACKGROUND: Depression and binge drinking behaviours are common clinical problems, which cause substantial functional, economic and health impacts. These conditions peak in young adulthood, and commonly co-occur. Comorbid depression and binge drinking are undertreated in young people, who are reluctant to seek help via traditional pathways to care. The iTreAD project (internet Treatment for Alcohol and Depression) aims to provide and evaluate internet-delivered monitoring and treatment programs for young people with depression and binge drinking concerns. METHODS: Three hundred sixty nine participants will be recruited to the trial, and will be aged 18-30 years will be eligible for the study if they report current symptoms of depression (score 5 or more on the depression subscale of the Depression Anxiety Stress Scale) and concurrent binge drinking practices (5 or more standard drinks at least twice in the prior month). Following screening and online baseline assessment, participants are randomised to: (a) online monthly self-assessments, (b) online monthly self-assessments + 12-months of access to a 4 week online automated cognitive behaviour therapy program for binge drinking and depression (DEAL); or (c) online monthly assessment + DEAL + 12-months of access to a social networking site (Breathing Space). Independent, blind follow-up assessments occur at 26, 39, 52 and 64-weeks post-baseline. DISCUSSION: The iTreAD project is the first randomised controlled trial combining online cognitive behaviour therapy, social networking and online monitoring for young people reporting concerns with depression and binge drinking. These treatments represent low-cost, wide-reach youth-appropriate treatment, which will have significantly public health implications for service design, delivery and health policy for this important age group. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12614000310662. Date registered 24 March 2014.

VRE acquisition in hospital and its association with hospital antimicrobial usage -a non-linear analysis of an extended time series.

BACKGROUND: Vancomycin resistant enterococci (VRE) have become endemic pathogens in many Australian hospitals causing significant morbidity. There are few observational studies that have evaluated the effect of antibiotic usage on VRE acquisition. This study examined VRE acquisition and its association with antimicrobial use. The setting was a NSW tertiary hospital with 800 beds over a 63 month period up to March 2020, straddling piperacillin-tazobactam (PT) shortages that occurred from in September 2017. METHODS: The primary outcome was monthly inpatient hospital onset Vancomycin-resistant Enterococci (VRE) acquisitions. Multivariate adaptive regression splines (MARS) were used to estimate hypothetical thresholds, where antimicrobial use above threshold is associated with increased incidence of hospital onset VRE acquisition. Specific antimicrobials and categorised usage (broad, less broad and narrow spectrum) were modelled. RESULTS: There were 846 hospital onset VRE detections over the study period. Hospital onset vanB and vanA VRE acquisitions fell significantly by 64% and 36% respectively after the PT shortage. MARS modelling indicated that PT usage was the only antibiotic found to exhibit a meaningful threshold. PT usage greater than 17.4 defined daily doses/1000 occupied bed-days (95%C I: 13.4, 20.5) was associated with higher onset of hospital VRE. CONCLUSIONS: This paper highlights the large, sustained impact that reduced broad spectrum antimicrobial use had on VRE acquisition and showed that PT use in particular was a major driver with a relatively low threshold. It raises the question as to whether hospitals should be determining local antimicrobial usage targets based on direct evidence from local data analysed with non-linear methods.

Percentage grade 4 tumour predicts outcome for prostate adenocarcinoma in needle biopsies from patients with advanced disease: 10-year data from the TROG 03.04 RADAR trial.

Previous reports have shown that quantification of high tumour grade is of prognostic significance for patients with prostate cancer. In particular, percent Gleason pattern 4 (GP4) has been shown to predict outcome in several studies, although conflicting results have also been reported. A major issue with these studies is that they rely on surrogate markers of outcome rather than patient survival. We have investigated the prognostic predictive value of quantifying GP4 in a series of prostatic biopsies containing Gleason score 3+4=7 and 4+3=7 tumours. It was found that the length of GP4 tumour determined from the measurement of all biopsy cores from a single patient, percent GP4 present and absolute GP4 were all significantly associated with distant progression of tumour, all-cause mortality and cancer-specific mortality over a 10-year follow-up period. Assessment of the relative prognostic significance showed that these parameters outperformed division of cases according to Gleason score (3+4=7 versus 4+3=7). International Society of Urological Pathology (ISUP) Grade Groups currently divide these tumours, according to Gleason grading guidelines, into grade 2 (3+4=7) and grade 3 (4+3=7). Our results indicate that this simple classification results in the loss of important prognostic information. In view of this we would recommend that ISUP Grade Groups 2 and 3 be amalgamated as grade 2 tumour with the percentage of GP4 carcinoma being appended to the final grade, e.g., 3+4=7 carcinoma with 40% pattern 4 tumour would be classified as ISUP Grade Group 2 (40%).

Liquor legislation, last drinks, and lockouts: the Newcastle (Australia) solution.

The aim of this study was to determine whether the regional implementation of prohibitive liquor legislation, introduced in order to limit the sale of and access to alcohol, can lead to a sustained reduction in the incidence of assault occasioning facial injury, as seen in patients presenting to a level 1 trauma hospital. A retrospective observational cohort study was conducted to document patients who were identified as an acute hospital presentation of assault occasioning facial injury. The period of study was 2003-2015; this ensured a similar period of time before and after the implementation of the legislation in 2008. A statistical analysis was undertaken to assess the rates of change in oral and maxillofacial (OMF) assault admissions pre and post legislation. The study found that pre-legislation numbers of OMF assaults increased at a rate of 14% per annum and then decreased at a rate of 21% per annum post legislation (31% relative rate ratio reduction). Similar trends were seen for all males, males aged 18-35 years, and males where alcohol was recorded at clinical presentation. The introduction of 'last drinks' and 'lock out' legislation has led to a significant and sustained reduction in assaultive alcohol-related facial injury in Newcastle.

Elevation of post mortem vitreous humour sodium and chloride levels can be used as a reliable test in cases of suspected salt water drowning when the immersion times are less than one hour.

BACKGROUND: Previous studies in salt water drowning deaths (SWD) demonstrated an observable elevation of post mortem vitreous sodium and chloride (PMVSC) levels. It remains unclear what the underlying mechanism responsible for this change is: whether this is due to rapid electrolyte changes from salt water inhalation/ingestion during drowning or from electrolyte diffusion and/or osmosis across the outer coats of the eyeballs during immersion. A recent animal study using sacrificed bovine eyeballs immersed in salt water demonstrated no significant elevations in PMVSC when immersed for less than one hour. Assuming similar physical properties between human and bovine, we extrapolate that an elevation in PMVSC in SWD with immersion times of less than one hour (SWD-1) would not be from immersion, but from drowning. AIM: Investigate whether there is an elevation in PMVSC in SWD-1. METHODS: Retrospective study comparing PMVSC in SWD-1 with controls from 2012 to 2015 inclusive. RESULTS: PMVSC in SWD-1 was significantly elevated compared with controls. A PMVSC of 259mmol/L has a sensitivity, specificity and likelihood ratio of 0.9, 0.9 and 7.6, respectively. CONCLUSION: The elevation in PMVSC in SWD-1 is due to drowning. A PMVSC of 259mmol/L and above is a reliable ancillary test in diagnosing drowning in bodies immersed in salt water for less than one hour.

Autoantibodies are not predictive markers for the development of depressive symptoms in a population-based cohort of older adults.

BACKGROUND: Autoantibodies have been implicated in the etiologic pathway of depressive disorders. Here, we determine the association between the presence of a panel of autoantibodies at baseline and change in depression symptom score over 5-year follow-up in a cohort of healthy elderly Australians. METHODS: Serum samples from 2049 randomly selected subjects enrolled in the Hunter Community Study (HCS) aged 55-85 years were assayed for a range of autoimmune markers (anti-nuclear autoantibodies, extractable nuclear antigen autoantibodies, anti-neutrophil cytoplasmic autoantibodies, thyroid peroxidase autoantibodies, tissue transglutaminase autoantibodies, anti-cardiolipin autoantibodies, rheumatoid factor and cyclic citrullinated peptide autoantibodies) at baseline. Depression symptom score was assessed using the Centre for Epidemiological Study (CES-D) scale at baseline and 5 years later. RESULTS: Autoantibody prevalence varied amongst our sample with ANA being the most prevalent; positive in 16% and borderline in 36% of study population. No evidence for a relationship was found between change in CES-D score over time and any autoimmune marker. Statins and high cholesterol were significantly associated with change in CES-D score over time in univariate analysis; however, these were probably confounded since they failed to remain significant following multivariable analysis. CONCLUSIONS: Autoantibodies were not associated with change in CES-D score over time. These findings point to an absence of autoimmune mechanisms in the general population or in moderate cases of depression.