An investigation of memory deficits and executive function in adults reporting high checking behaviours

Cognitive-behavioural models have been proposed to explain the development and maintenance of Obsessive Compulsive Disorder (OCD) and checking symptoms. Previous research has examined models relating to cognitive dysfunction, including the memory deficits and executive impairments. Evidence to support these models is inconclusive. Researchers suggest that it may be more fruitful to examine memory and executive function as involving several independent processes rather than treating them as unitary processes. It has also been suggested that memory impairments may be secondary to executive dysfunction. Reported work examining this relationship is limited. Studies investigating checking behaviours have highlighted the role of belief and appraisal models. In particular, memory confidence and perceived responsibility has been examined. The relative contribution of these variables, when examining memory deficits and executive dysfunction, is uncertain. This work programme had the objective of examining the relative contribution of different cognitive-behavioural models to checking symptoms across four different studies. Prospective memory deficits and familiarity biases were found to be related to checking symptom severity. These findings suggest that, when examining memory deficits, independent memory processes should be considered. Inhibitory function was shown to consistently predict checking symptom severity, suggesting that executive dysfunction is related to a specific dimension of cognitive regulation. Inhibitory impairments were not shown to be solely related to the presence of OCD symptoms, with similar inhibition deficits in an OCD and anxiety group. Additionally, inhibition was demonstrated to independently contribute to compulsive but not obsessive symptoms, when anxiety was taken into account. These findings highlighted the role of anxiety and inhibition in relation to compulsive symptoms. Correlation and mediation analyses across this work demonstrated that there is no relationship between memory impairments and inhibition. It was concluded that both memory deficits and inhibition independently contribute to the checking symptom profile. When memory confidence and perceived responsibility were examined in the same model as memory and inhibition, only perceived responsibility was found to be an independent predictor of checking symptom severity. The results from each of the four studies reported here have potential implications for future research examining cognitive-behavioural models of checking. It is suggested that an integrated model of checking may be useful in helping to develop a better understanding of the onset and maintenance of the disorder.Cognitive-behavioural models have been proposed to explain the development and maintenance of Obsessive Compulsive Disorder (OCD) and checking symptoms. Previous research has examined models relating to cognitive dysfunction, including the memory deficits and executive impairments. Evidence to support these models is inconclusive. Researchers suggest that it may be more fruitful to examine memory and executive function as involving several independent processes rather than treating them as unitary processes. It has also been suggested that memory impairments may be secondary to executive dysfunction. Reported work examining this relationship is limited. Studies investigating checking behaviours have highlighted the role of belief and appraisal models. In particular, memory confidence and perceived responsibility has been examined. The relative contribution of these variables, when examining memory deficits and executive dysfunction, is uncertain. This work programme had the objective of examining the relative contribution of different cognitive-behavioural models to checking symptoms across four different studies. Prospective memory deficits and familiarity biases were found to be related to checking symptom severity. These findings suggest that, when examining memory deficits, independent memory processes should be considered. Inhibitory function was shown to consistently predict checking symptom severity, suggesting that executive dysfunction is related to a specific dimension of cognitive regulation. Inhibitory impairments were not shown to be solely related to the presence of OCD symptoms, with similar inhibition deficits in an OCD and anxiety group. Additionally, inhibition was demonstrated to independently contribute to compulsive but not obsessive symptoms, when anxiety was taken into account. These findings highlighted the role of anxiety and inhibition in relation to compulsive symptoms. Correlation and mediation analyses across this work demonstrated that there is no relationship between memory impairments and inhibition. It was concluded that both memory deficits and inhibition independently contribute to the checking symptom profile. When memory confidence and perceived responsibility were examined in the same model as memory and inhibition, only perceived responsibility was found to be an independent predictor of checking symptom severity. The results from each of the four studies reported here have potential implications for future research examining cognitive-behavioural models of checking. It is suggested that an integrated model of checking may be useful in helping to develop a better understanding of the onset and maintenance of the disorder

Checking behaviours, prospective memory and executive functions

Explanations implicating memory in the causes and severity of checking symptoms have focused primarily on retrospective memory, and relatively little attention has been paid to prospective memory. Limited research has examined the relationship between prospective memory and executive functions. We assessed whether impairments in prospective memory and executive function predict checking symptoms in a sample of 106 adults. Checking symptoms were assessed using the Padua Inventory Washington State University Revision (PI-WSUR). All participants completed the prospective memory questionnaire (PMQ) and four computerised executive function tasks from the CANTAB, measuring inhibition, planning, attention set-shifting and working memory. Prospective memory and inhibition predicted checking symptom severity. Importantly, there were no correlations between internally cued prospective memory and inhibition or between prospective memory aiding strategies and inhibition. These variables appear to have an independent role in checking. The current findings highlight prospective memory and inhibition as key contributors to the checking symptom profile and provide the first evidence that these cognitive processes may independently contribute to checking symptoms. These findings have implications for a model in which memory performance is thought to be secondary to impairments in executive functions

Genome-wide association study confirms lung cancer susceptibility loci on chromosomes 5p15 and 15q25 in an African-American population.

ObjectivesGenome-wide association studies (GWAS) of lung cancer have identified regions of common genetic variation with lung cancer risk in Europeans who smoke and never-smoking Asian women. This study aimed to conduct a GWAS in African Americans, who have higher rates of lung cancer despite smoking fewer cigarettes per day when compared with Caucasians. This population provides a different genetic architecture based on underlying African ancestry allowing the identification of new regions and exploration of known regions for finer mapping.Materials and methodsWe genotyped 1,024,001 SNPs in 1737 cases and 3602 controls in stage 1, followed by a replication phase of 20 SNPs (p<1.51×10(-5)) in an independent set of 866 cases and 796 controls in stage 2.Results and conclusionIn the combined analysis, we confirmed two loci to be associated with lung cancer that achieved the threshold of genome-wide significance: 15q25.1 marked by rs2036527 (p=1.3×10(-9); OR=1.32; 95% CI=1.20-1.44) near CHRNA5, and 5p15.33 marked by rs2853677 (p=2.8×10(-9); OR=1.28; 95% CI=1.18-1.39) near TERT. The association with rs2853677 is driven by the adenocarcinoma subtype of lung cancer (p=1.3×10(-8); OR=1.37; 95% CI=1.23-1.54). No SNPs reached genome-wide significance for either of the main effect models examining smoking - cigarettes per day and current or former smoker. Our study was powered to identify strong risk loci for lung cancer in African Americans; we confirmed results previously reported in African Americans and other populations for two loci near plausible candidate genes, CHRNA5 and TERT, on 15q25.1 and 5p15.33 respectively, are associated with lung cancer. Additional work is required to map and understand the biological underpinnings of the strong association of these loci with lung cancer risk in African Americans

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) \u3c 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p \u3c 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations