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Aiden Corvin

Publications and source records attributed to Aiden Corvin.

11 recordsLinked to original sources
PubMed2024

BICEP: Bayesian inference for rare genomic variant causality evaluation in pedigrees.

Next-generation sequencing is widely applied to the investigation of pedigree data for gene discovery. However, identifying plausible disease-causing variants within a robust statistical framework is challenging. Here, we introduce BICEP: a Bayesian inference tool for rare variant causality evaluation in pedigree-based cohorts. BICEP calculates the posterior odds that a genomic variant is causal for a phenotype based on the variant cosegregation as well as a priori evidence such as deleteriousness and functional consequence. BICEP can correctly identify causal variants for phenotypes with both Mendelian and complex genetic architectures, outperforming existing methodologies. Additionally, BICEP can correctly down-weight common variants that are unlikely to be involved in phenotypic liability in the context of a pedigree, even if they have reasonable cosegregation patterns. The output metrics from BICEP allow for the quantitative comparison of variant causality within and across pedigrees, which is not possible with existing approaches.

Pedigree↗
PubMed2006

Variance in neurocognitive performance is associated with dysbindin-1 in schizophrenia: a preliminary study.

Susceptibility genes for schizophrenia have been hypothesised to mediate liability for the disorder at least partly by influencing cognitive performance. We investigated the association between genotype and cognitive performance for a Dysbindin risk haplotype which is associated with schizophrenia in our sample. Fifty-two patients with schizophrenia or schizoaffective disorder (24 risk haplotypes carriers versus 28 non-risk haplotype carriers) were assessed in areas of cognition showing evidence of familial deficits in schizophrenia. Verbal and spatial memory, working memory, and attentional control was assessed using selected measures from the Weschler memory scale (WMS), Cambridge automated test battery (CANTAB), continuous performance test (CPT), and a simple go/no-go task. Pre-morbid IQ was also assessed using the Weschler Test of Adult Reading (WTAR). Patients carrying the Dysbindin risk haplotype showed significantly lower spatial working memory performance than patients who were non-risk carriers, with genotype explaining 12% of variance in performance. Our study suggests that the increased risk for schizophrenia associated with dysbindin may be partly mediated by its influence on pre-frontal function.

Adolescent↗
PubMed2006

Are deficits in executive sub-processes simply reflecting more general cognitive decline in schizophrenia?

BACKGROUND: Schizophrenia is associated with both global and specific cognitive deficits. We sought to investigate whether deficits in executive subcomponents differed in their relationship to global cognitive impairments. METHOD: 95 patients were classified according to pre-morbid and current general cognitive ability as having either (a) intact pre-morbid and current general cognitive ability; (b) intact pre-morbid but deteriorated current ability, and (c) deteriorated both pre-morbid and current cognitive ability. All patients completed measures of verbal and spatial working memory, sustained selective attention, attentional set sifting, and inhibitory control. RESULTS: Deficits on both measures of working memory were associated with general cognitive ability. None of the attentional control deficits observed were associated with general ability. Further, spatial working memory deficits were also associated with more severe negative symptoms. CONCLUSIONS: These results provide further evidence of the discreet nature of attentional deficits in schizophrenia. By contrast, this study suggests that working memory deficits may to some extent index more general cognitive decline. Awareness of such overlap is important for schizophrenia genetics studies where working memory measures has been used to index supposedly discreet aspects of cognitive dysfunction.

Adult↗
PubMed2006

Neurocognition and suicidal behaviour in an Irish population with major psychotic disorders.

OBJECTIVES: Although neurocognitive deficits are seen as core to schizophrenia the association between suicidality and neurocognition has received little attention. Our aim was to examine the relationship between neurocognitive variables and suicidal behaviour in patients with schizophrenia and schizoaffective disorder. METHODS: Seventy-eight patients with DSM-IV diagnoses of schizophrenia or schizoaffective disorder were categorised as either having attempted suicide or not having attempted suicide based on clinical interview and chart review. Attempters and non-attempters were compared on an extensive neuropsychological battery examining pre-morbid and current general cognitive functioning, episodic memory, and executive functioning. RESULTS: Suicide attempters tended to out perform non-attempters across all areas of executive functioning, and showed significantly better performances on measures of attention and verbal fluency. After controlling for relevant clinical and demographic variables, the differences between attempters and non-attempters remained significant for measures of attention (F = 4.97, p = 0.03) and verbal fluency (F = 4.28, p = 0.04). CONCLUSION: This study adds to existing data that suicide attempters with schizophrenia or schizoaffective disorder may have higher cognitive functioning than non-attempters. In particular, the preservation of higher executive function may influence the ability to initiate and plan suicidal behaviour.

Adult↗
PubMed2006

Do antisaccade deficits in schizophrenia provide evidence of a specific inhibitory function?

BACKGROUND: Despite its inhibitory control requirements, antisaccade deficits have been consistently associated with working memory impairments in schizophrenia. We investigated whether variance in antisaccade performance could be better accounted for in terms of a specific inhibitory function. METHOD: We assessed 48 clinically stable out-patients with schizophrenia on an antisaccade task, as well as on measures of spatial and verbal working memory, sustained selective attention, and a simple motoric go/no-go measure of response inhibition. RESULTS: In a stepwise multiple regression analysis, go/no-go task performance accounted for a considerably greater percentage of variance in antisaccade performance (25.3%) than either working memory (8.4%) or sustained selective attention task (9.1%). DISCUSSION: We conclude that antisaccade deficits in schizophrenia appear to be better understood in terms of a specific deficit of inhibitory control than in terms of more general difficulties with context maintenance or goal neglect.

Adult↗
PubMed2006

Evidence that specific executive functions predict symptom variance among schizophrenia patients with a predominantly negative symptom profile.

INTRODUCTION: Although deficits in executive functioning in schizophrenia have been consistently reported, their precise relationship to symptomatology remains unclear. Recent approaches to executive functioning in nonschizophrenia studies have aimed to "fractionate" the individual cognitive processes involved. In this study, we hypothesised that if these processes are fractionable, then particular symptom syndromes may be selectively related to executive deficits. In particular, it was hoped that this approach could clarify whether negative and positive symptoms of schizophrenia are differentially related to particular aspects of executive/attentional functions. METHODS: A total of 32 patients with schizophrenia and 16 matched controls were assessed on a series of tasks designed to tap the theoretically derived executive functions of Inhibition, Shifting set, Working memory, and Sustained attention. RESULTS: Negative symptoms were significantly predicted by performance on an "Inhibition" task (Stroop), and not by performance on any other task. Furthermore, for a subgroup of patients with predominantly negative symptoms variance in positive symptoms was only significantly predicted by performance on a set-shifting task (Visual Elevator), and not by performance on other tasks, including inhibition. CONCLUSIONS: Our results support the contention that negative symptoms can, at least partly, be conceived of as cognitive behaviours expressing specific executive deficits. Specifically, we discuss the possibility that negative symptoms may, in part, express a failure in response monitoring. We further suggest that the disordered metacognition resulting in positive symptoms may be mediated by cognitive flexibility in patients with a predominantly negative symptom profile.

Adult↗
PubMed2005

Investigation of the apolipoprotein-L (APOL) gene family and schizophrenia using a novel DNA pooling strategy for public database SNPs.

We performed an extensive genetic association study of the six known apolipoprotein-L (APOL) genes and schizophrenia (SZ) using a novel DNA pooling strategy. The APOL genes are both positional and functional candidate genes for SZ. This gene family maps to chromosome 22q12.3, a region implicated by SZ linkage studies as likely to contain one or more SZ susceptibility genes. A recent gene expression study demonstrated up-regulation of APOL1, 2, and 4 in post-mortem brain samples from SZ patients compared to controls in two independent samples. To test for genetic association with SZ, we analyzed 143 SNPs from dbSNP from across the APOL genes in an Irish sample of 219 cases and 231 controls. Of these 143 SNPs, 51 (36%) were polymorphic in our Irish sample and were genotyped using a novel three-stage DNA pooling strategy. This strategy does not require the identification of a heterozygous individual for DNA pooling association analysis and is therefore very efficient when using public database SNPs. We found no evidence to support the hypothesis that genetic variation at the APOL genes contributes to SZ susceptibility in our sample.

Alleles↗
PubMed2005

Genomewide linkage scan in schizoaffective disorder: significant evidence for linkage at 1q42 close to DISC1, and suggestive evidence at 22q11 and 19p13.

CONTEXT: Traditionally, the search for genes involved in predisposition to major psychoses has proceeded with separate studies of schizophrenia and bipolar disorder. However, twin data suggest that, in addition to genes with specificity for these phenotypes, there exist genes that simultaneously influence susceptibility to schizophrenia, bipolar disorder, and schizoaffective disorder. OBJECTIVE: To undertake, to our knowledge, the first systematic search for such loci. DESIGN: Genomewide linkage scan. SETTING: Affected individuals were ascertained in the United Kingdom and Ireland from general psychiatric inpatient and outpatient services. PARTICIPANTS: The families were selected for linkage studies of either schizophrenia or bipolar disorder. Pedigrees were selected for the current analysis where there was at least 1 member with DSM-IV schizoaffective disorder, bipolar type. Within these pedigrees, individuals were coded as affected if they had been diagnosed with DSM-IV schizophrenia, schizoaffective disorder of bipolar type, or bipolar I disorder. A total of 24 pedigrees contributed 35 affected sibling pairs to the sample. METHOD: A 10-centimorgan genome scan using microsatellite markers was analyzed using MAPMAKER/SIBS software. RESULTS: A genomewide significant signal (LOD = 3.54) was observed at chromosome 1q42 (near D1S2800), and suggestive LOD scores were observed at chromosomes 22q11 (LOD = 1.96) and 19p13 (LOD = 1.85). No linkage was observed in these regions in our original schizophrenia or bipolar scans in individuals from the United Kingdom. CONCLUSIONS: Our linkage findings strongly support the existence of loci that influence susceptibility across the functional psychosis spectrum. The DISC1 gene lies within 2.5 megabases of our peak marker on chromosome 1q42 and has been previously implicated in schizophrenia, bipolar disorder, and, recently, schizoaffective disorder. Follow-up of this region should use samples enriched for cases of schizoaffective disorder. Our findings have similar implications for the search for genetic variation on chromosome 22q11 that influences susceptibility to psychosis.

Bipolar Disorder↗
PubMed2005

Are the cognitive deficits associated with impaired insight in schizophrenia specific to executive task performance?

Although impaired insight in schizophrenia has been associated with deficits in executive task performance, the relationship remains unclear. We aimed to clarify this relationship by fractionating executive functioning into the theoretically derived functions of inhibition, working memory, set shifting, and sustained attention. We compared the performance of patients showing impaired insight, patients showing good insight, and a matched control group on measures of each of these executive functions, along with measures of current cognitive functioning and memory. We found that while patients with impaired insight performed significantly below those with good insight on our working memory task, they also performed poorly on measures of general cognitive functioning and memory. We conclude that while impaired insight does appear to be associated with executive deficits, this association may not be specific but may instead relate to cognitive deficits more generally.

Adult↗