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E Cummings,
G Donohoe,
A Hargreaves,
S Moore,
C Fahey,
T G Dinan,
C McDonald,
E O'Callaghan,
F A O'Neill,
J L Waddington,
K C Murphy,
D W Morris,
M Gill, A Corvin
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[hide abstract]
ABSTRACT: OBJECTIVE: The Schizophrenia Psychiatric Genome-wide Association (GWAS) Consortium recently reported on five novel schizophrenia susceptibility loci. The most significant finding mapped to a micro-RNA, MIR-137, which may be involved in regulating the function of other schizophrenia and bipolar disorder susceptibility genes. METHOD: We genotyped 821 patients with confirmed DSM-IV diagnoses of schizophrenia, bipolar affective disorder I and schizoaffective disorder for the risk SNP (rs1625579) and investigated the clinical profiles of risk allele carriers using a within-case design. We also assessed neurocognitive performance in a subset of cases (n=399) and controls (n=171). RESULTS: Carriers of the risk allele had lower scores for an OPCRIT-derived positive symptom factor (p=0.04) and lower scores on a lifetime measure of psychosis incongruity (p=0.017). Risk allele carriers also had more cognitive deficits involving episodic memory and attentional control. CONCLUSION: This is the first evidence that the MIR-137 risk variant may be associated with a specific subgroup of psychosis patients. Although the effect of this single SNP was not clinically relevant, investigation of the impact of carrying multiple risk SNPs in the MIR-137 regulatory network on diagnosis and illness profile may be warranted.
Neuroscience Letters 09/2012; · 2.11 Impact Factor
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ABSTRACT: Suicide is the leading cause of death in schizophrenia. An association between suicidal behavior and both higher and lower cognitive ability in schizophrenia has been reported. To clarify this relationship, we investigated whether the relationship between suicidality and neurocognition varied according to differences in suicidal ideation and behavior.
Three hundred and ten patients with DSM-IV diagnoses of schizophrenia or schizoaffective disorder were categorized based on patient and staff interviews as either non-suicide attempters, non-attempters expressing suicidal ideation, single suicide attempters, or multiple suicide attempters. These groups were compared on a neuropsychological battery examining current general cognitive ability, episodic and working memory, and attentional control.
Neuropsychological performance in those with a history of suicidal ideation (n=63), and those who had made one suicide attempt (n=48) was comparable. Together, these groups outperformed patients with no history of either suicidal behavior or ideation (n=172) on measures of IQ, episodic memory and working memory. Only differences in global cognition remained significant after controlling for between-group differences in depressive symptoms. Those who had either expressed suicidal ideation and/or made a single suicide attempt demonstrated trend level advantages in neuropsychological tests over those that had made multiple suicide attempts.
These findings support earlier evidence of an association between suicidality and neurocognitive ability in schizophrenia. Specifically, these data suggest that patients who have contemplated suicide or made a single suicide attempt have better cognitive functioning than those who have not. Suicidality in multiple attempters, who do not perform better in neurocognitive tests than those who have neither contemplated nor attempted suicide, is likely to be influenced by factors other than neurocognitive ability.
Biological Psychiatry 07/2012; 140(1-3):232-6. · 8.28 Impact Factor
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X Chen,
G Lee,
B S Maher,
A H Fanous,
J Chen,
Z Zhao,
A Guo,
E van den Oord,
P F Sullivan,
J Shi, [......],
A McQuillin,
J Pimm,
C Hultman,
P Lichtenstein,
P Sklar,
S M Purcell,
E Scolnick,
D St Clair,
D H R Blackwood,
K S Kendler
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ABSTRACT: We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values ≤0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3 828 611-rs10043986, r(2)=0.008; rs10043986-rs4704591, r(2)=0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case-control samples, 11 380 cases and 15 021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR)=1.11, 95% confidence interval (CI)=1.04-1.18, P=8.2 × 10(-4) and rs4704591, OR=1.07, 95% CI=1.03-1.11, P=3.0 × 10(-4)). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR=1.11, 95% CI=1.03-1.17, P=0.0026 and rs4704591, OR=1.07, 95% CI=1.02-1.11, P=0.0015). Furthermore, haplotype conditioned analyses indicated that the association signals observed at these two markers are independent. On the basis of these results, we concluded that CMYA5 is associated with schizophrenia and further investigation of the gene is warranted.
Molecular psychiatry 11/2011; 16(11):1117-29. · 15.05 Impact Factor
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A Jablensky,
D Angelicheva,
G J Donohoe,
M Cruickshank,
D N Azmanov,
D W Morris,
A McRae,
C S Weickert,
K W Carter,
D Chandler, [......],
M Cooper,
M Phillips,
J Badcock,
E Bramon-Bosch,
O P Almeida,
L Flicker,
M Gill, A Corvin,
S Macgregor,
L Kalaydjieva
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ABSTRACT: In a previous study, we detected a 6p25-p24 region linked to schizophrenia in families with high composite cognitive deficit (CD) scores, a quantitative trait integrating multiple cognitive measures. Association mapping of a 10 Mb interval identified a 260 kb region with a cluster of single-nucleotide polymorphisms (SNPs) significantly associated with CD scores and memory performance. The region contains two colocalising genes, LYRM4 and FARS2, both encoding mitochondrial proteins. The two tagging SNPs with strongest evidence of association were located around the overlapping putative promoters, with rs2224391 predicted to alter a transcription factor binding site (TFBS). Sequencing the promoter region identified 22 SNPs, many predicted to affect TFBSs, in a tight linkage disequilibrium block. Luciferase reporter assays confirmed promoter activity in the predicted promoter region, and demonstrated marked downregulation of expression in the LYRM4 direction under the haplotype comprising the minor alleles of promoter SNPs, which however is not driven by rs2224391. Experimental evidence from LYRM4 expression in lymphoblasts, gel-shift assays and modelling of DNA breathing dynamics pointed to two adjacent promoter SNPs, rs7752203-rs4141761, as the functional variants affecting expression. Their C-G alleles were associated with higher transcriptional activity and preferential binding of nuclear proteins, whereas the G-A combination had opposite effects and was associated with poor memory and high CD scores. LYRM4 is a eukaryote-specific component of the mitochondrial biogenesis of Fe-S clusters, essential cofactors in multiple processes, including oxidative phosphorylation. LYRM4 downregulation may be one of the mechanisms involved in inefficient oxidative phosphorylation and oxidative stress, increasingly recognised as contributors to schizophrenia pathogenesis.Molecular Psychiatry advance online publication, 4 October 2011; doi:10.1038/mp.2011.129.
Molecular psychiatry 10/2011; · 15.05 Impact Factor
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Molecular psychiatry 08/2011; 17(2):118-9. · 15.05 Impact Factor
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E Cummings,
G Donohoe,
C McDonald,
T G Dinan,
F A O'Neill,
E O'Callaghan,
J L Waddington,
K C Murphy,
M Gill,
D W Morris, A Corvin
Biological Psychiatry 09/2010; 122(1-3):273-5. · 8.28 Impact Factor
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H J Williams,
N Norton,
S Dwyer,
V Moskvina,
I Nikolov,
L Carroll,
L Georgieva,
N M Williams,
D W Morris,
E M Quinn, [......],
P Sklar,
S Purcell,
V L Nimgaonkar,
G Kirov,
P Holmans, A Corvin,
D Rujescu,
N Craddock,
M J Owen,
M C O'Donovan
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ABSTRACT: A recent genome-wide association study (GWAS) reported evidence for association between rs1344706 within ZNF804A (encoding zinc-finger protein 804A) and schizophrenia (P=1.61 × 10(-7)), and stronger evidence when the phenotype was broadened to include bipolar disorder (P=9.96 × 10(-9)). In this study we provide additional evidence for association through meta-analysis of a larger data set (schizophrenia/schizoaffective disorder N=18 945, schizophrenia plus bipolar disorder N=21 274 and controls N=38 675). We also sought to better localize the association signal using a combination of de novo polymorphism discovery in exons, pooled de novo polymorphism discovery spanning the genomic sequence of the locus and high-density linkage disequilibrium (LD) mapping. The meta-analysis provided evidence for association between rs1344706 that surpasses widely accepted benchmarks of significance by several orders of magnitude for both schizophrenia (P=2.5 × 10(-11), odds ratio (OR) 1.10, 95% confidence interval 1.07-1.14) and schizophrenia and bipolar disorder combined (P=4.1 × 10(-13), OR 1.11, 95% confidence interval 1.07-1.14). After de novo polymorphism discovery and detailed association analysis, rs1344706 remained the most strongly associated marker in the gene. The allelic association at the ZNF804A locus is now one of the most compelling in schizophrenia to date, and supports the accumulating data suggesting overlapping genetic risk between schizophrenia and bipolar disorder.
Molecular psychiatry 04/2010; 16(4):429-41. · 15.05 Impact Factor
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ABSTRACT: Susceptibility to schizophrenia and bipolar disorder may involve a substantial, shared contribution from thousands of common genetic variants, each of small effect. Identifying whether risk variants map to specific molecular pathways is potentially biologically informative. We report a molecular pathway analysis using the single-nucleotide polymorphism (SNP) ratio test, which compares the ratio of nominally significant (P<0.05) to nonsignificant SNPs in a given pathway to identify the 'enrichment' for association signals. We applied this approach to the discovery (the International Schizophrenia Consortium (n=6909)) and validation (Genetic Association Information Network (n=2729)) of schizophrenia genome-wide association study (GWAS) data sets. We investigated each of the 212 experimentally validated pathways described in the Kyoto Encyclopaedia of Genes and Genomes in the discovery sample. Nominally significant pathways were tested in the validation sample, and five pathways were found to be significant (P=0.03-0.001); only the cell adhesion molecule (CAM) pathway withstood conservative correction for multiple testing. Interestingly, this pathway was also significantly associated with bipolar disorder (Wellcome Trust Case Control Consortium (n=4847)) (P=0.01). At a gene level, CAM genes associated in all three samples (NRXN1 and CNTNAP2), which were previously implicated in specific language disorder, autism and schizophrenia. The CAM pathway functions in neuronal cell adhesion, which is critical for synaptic formation and normal cell signaling. Similar pathways have also emerged from a pathway analysis of autism, suggesting that mechanisms involved in neuronal cell adhesion may contribute broadly to neurodevelopmental psychiatric phenotypes.
Molecular psychiatry 02/2010; 16(3):286-92. · 15.05 Impact Factor
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ABSTRACT: There have been nearly 400 genome-wide association studies (GWAS) published since 2005. The GWAS approach has been exceptionally successful in identifying common genetic variants that predispose to a variety of complex human diseases and biochemical and anthropometric traits. Although this approach is relatively new, there are many excellent reviews of different aspects of the GWAS method. Here, we provide a primer, an annotated overview of the GWAS method with particular reference to psychiatric genetics. We dissect the GWAS methodology into its components and provide a brief description with citations and links to reviews that cover the topic in detail.
Psychological Medicine 11/2009; 40(7):1063-77. · 6.16 Impact Factor
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ABSTRACT: Despite the substantial heritability of the psychoses and their genuine public health burden, the applicability of the genomic approach in psychiatry has been strongly questioned or prematurely dismissed.
selective review of the recent literature on molecular genetic and genomic approaches to the psychoses including the early output from genome-wide association studies and the genomic analysis of DNA structural variation.
Susceptibility variants at strong candidate genes have been identified including neuregulin, dysbindin, DISC1 and neurexin 1. Rare but highly penetrant copy number variants and new mutations affecting genes involved in neurodevelopment, cell signalling and synaptic function have been described showing some overlapping genetic architecture with other developmental disorders including autism. The de-novo mutations described offer an explanation for the familial sporadic divide and the persistence of schizophrenia in the population. The functional effects of risk variants at the level of cognition and connectivity has been described and recently, ZNF804A has been identified, and the MHC re-identified as risk loci, and it has been shown that at least a third of the variation in liability is due to multiple common risk variants of small effect with a substantial shared genetic liability between schizophrenia and bipolar affective disorder.
The genomics have done much for the psychoses to date and more is anticipated.
Psychological Medicine 10/2009; 40(4):529-40. · 6.16 Impact Factor
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ABSTRACT: Post hoc analysis of occupational attainment and performance on a standard neurocognitive battery suggests that performance on letter-number sequencing is strongly associated with work attainment. Letter-number sequencing may warrant further investigation as a clinically useful tool to inform decisions around vocational rehabilitation.
European Psychiatry 09/2009; 25(2):101-4. · 2.77 Impact Factor
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L S Carroll,
N M Williams,
V Moskvina,
E Russell,
N Norton,
H J Williams,
T Peirce,
L Georgieva,
S Dwyer,
D Grozeva, [......], A Corvin,
M Gill,
D Rujescu,
P Sham,
P Holmans,
I Jones,
G Kirov,
N Craddock,
M C O'Donovan,
M J Owen
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[hide abstract]
ABSTRACT: We earlier reported a genome-wide significant linkage to schizophrenia at chromosome 17 that was identified in a single pedigree (C702) consisting of six affected, male siblings with DSM-IV schizophrenia and prominent mood symptoms. In this study, we adopted several approaches in an attempt to map the putative disease locus. First, mapping the source of linkage to chromosome 17 in pedigree C702. We refined the linkage region in family C702 to a 21-marker segment spanning 11.7 Mb at 17q23-q24 by genotyping a total of 50 microsatellites across chromosome 17 in the pedigree. Analysis of data from 1028 single nucleotide polymorphisms (SNPs) across the refined linkage region identified a single region of homozygosity present in pedigree C702 but not in 2938 UK controls. This spanned ~432 kb of the gene encoding protein kinase C, alpha (PRKCA), the encoded protein of which has been implicated in the pathogenesis of psychiatric disorders. Analysis of pedigree C702 by oligonucleotide-array comparative genome hybridization excluded the possibility that this region of homozygosity was because of a deletion. Mutation screening of PRKCA identified a rare, four-marker haplotype (C-HAP) in the 3' untranslated region of the gene, which was present in the homozygous state in all six affected members of pedigree C702. No other homozygotes were observed in genotype data for a total of 6597 unrelated Europeans (case N=1755, control N=3580 and parents of probands N=1262). Second, association analysis of C702 alleles at PRKCA. The low-frequency haplotype (C-HAP) showed a trend for association in a study of unrelated schizophrenia cases and controls from the UK (661 cases, 2824 controls, P=0.078 and odd ratio (OR)=1.9) and significant evidence for association when the sample was expanded to include cases with bipolar (N=710) and schizoaffective disorder (N=50) (psychosis sample: 1421 cases, 2824 controls, P=0.037 and OR=1.9). Given that all the affected members of C702 are male, we also undertook sex-specific analyses. This revealed that the association was strongest in males for both schizophrenia (446 male cases, 1421 male controls, P=0.008 and OR=3.9) and in the broader psychosis group (730 male cases, 1421 male controls, P=0.008 and OR=3.6). Analysis of C-HAP in follow-up samples from Ireland and Bulgaria revealed no evidence for association in either the whole sample or in males alone, and meta-analysis of all male psychosis samples yielded no significant evidence of association (969 male cases, 1939 male controls, 311 male probands P=0.304 and OR=1.4). Third, association mapping of the pedigree C702 linkage region. Independent of pedigree C702, genotype data from the Affymetrix 500k GeneChip set were available for 476 patients with schizophrenia and 2938 controls from the United Kingdom. SNPs in PRKCA showed evidence for association with schizophrenia that achieved gene-wide significance (P=0.027). Moreover, the same SNP was the most significantly associated marker out of the 1028 SNPs genotyped across the linkage region (rs873417, allelic P=0.0004). Follow-up genotyping in samples from Ireland, Bulgaria and Germany did not show consistent replication, but meta-analysis of all samples (4116 cases and 6491 controls) remained nominally significant (meta-analysis P=0.026, OR=1.1). We conclude that, although we have obtained convergent lines of evidence implicating both rare and common schizophrenia risk variants at PRKCA, none of these is individually compelling. However, the evidence across all approaches suggests that further study of this locus is warranted.
Molecular psychiatry 09/2009; 15(11):1101-11. · 15.05 Impact Factor
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A Corvin,
K A McGhee,
K Murphy,
G Donohoe,
J M Nangle,
S Schwaiger,
N Kenny,
S Clarke,
D Meagher,
J Quinn,
P Scully,
P Baldwin,
D Browne,
C Walsh,
J L Waddington,
D W Morris,
M Gill
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ABSTRACT: The D-amino acid oxidase (DAO) signaling pathway has been implicated in schizophrenia pathogenesis. This may be mediated through modulation of NMDA function by DAO, which is in turn activated by DAO activator (DAOA, formerly G72). Chumakov et al. (2002); PNAS 99: 13675-13680, identifying the novel schizophrenia susceptibility gene DAOA/G30 and a number of independent studies have since reported evidence of association between the DAOA and DAO genes and schizophrenia. However, at least two studies have failed to replicate the epistatic interaction between these loci described in the original report and there have been differences in the associated alleles/haplotypes reported at each locus. In this study, we performed association and epistasis analyses of the DAOA/G30 and DAO loci in a sample of 373 cases with DSM-IV schizophrenia/schizoaffective disorder and 812 controls from the Republic of Ireland. Corrected for the number of tests performed, we found evidence for association between markers at both genes and schizophrenia: DAOA/G30 (P = 0.005, OR = 1.34 (1.09, 1.65)) and DAO (P = 0.003, OR = 1.43 (1.12, 1.84). The data suggest that evidence for association at DAO (marker rs2111902) is more consistent than previously realized, particularly in Caucasian schizophrenia populations. We identified evidence for epistatic interaction between the associated SNPs at DAOA and DAO genes in contributing to schizophrenia risk (OR = 9.3 (1.4, 60.5). Based on these data, more systematic investigation of genes involved in DAO signaling is required.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 11/2007; 144B(7):949-53. · 3.70 Impact Factor
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D Lambert,
F Middle,
M L Hamshere,
R Segurado,
R Raybould, A Corvin,
E Green,
E O'Mahony,
I Nikolov,
T Mulcahy, [......],
P Bennett,
N Norton,
M J Owen,
G Kirov,
C Lendon,
L Jones,
I Jones,
P Holmans,
M Gill,
N Craddock
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[hide abstract]
ABSTRACT: Bipolar affective disorder (BPAD) is a common psychiatric disorder with complex genetic aetiology. We have undertaken a genome-wide scan in one of the largest samples of bipolar affected sibling pairs (ASPs) using a two-stage approach combining sample splitting and marker grid tightening. In this second stage analysis, we have examined 17 regions that achieved a nominally significant maximum likelihood LOD score (MLS) threshold of 0.74 (or 1.18 for the X-chromosome) in stage one. The second stage has added 135 ASP families to bring the total stage 2 sample to 395 ASPs. In total, 494 microsatellite markers have been used to screen the human genome at a density of 10 cM in the first stage sample (260 ASPs) and 5 cM in the second stage. Under the broad diagnostic model, two markers gave LOD scores exceeding 3 with two-point analysis: D4S392 (LOD=3.30) and D10S197 (LOD=3.18). Multipoint analysis demonstrated suggestive evidence of linkage between BPAD and chromosomal regions 6q16-q21 (MLS=2.61) and 4q12-q21 (MLS=2.38). 6q16-q21 is of particular interest because our data, together with those from two recent genome scans, make this the best supported linkage region in BPAD. Further, our data show evidence of a gender effect at this locus with increased sharing predominantly within the male-male pairs. Our scan also provides support for linkage (MLS> or =1.5) at several other regions that have been implicated in meta-analyses of bipolar disorder and/or schizophrenia including 9p21, 10p14-p12 and 18q22.
Molecular Psychiatry 10/2005; 10(9):831-41. · 13.67 Impact Factor
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Irish medical journal 04/2004; 97(3):70-2.
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P Bennett,
R Segurado,
I Jones,
S Bort,
F McCandless,
D Lambert,
J Heron,
C Comerford,
F Middle, A Corvin, [......],
B Larsen,
T Mulcahy,
N Williams,
R O'Connell,
E O'Mahony,
A Payne,
M Owen,
P Holmans,
N Craddock,
M Gill
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[hide abstract]
ABSTRACT: We have completed the first stage of a two-stage genome wide screen designed to identify chromosomal regions that may harbour susceptibility genes for bipolar affective disorder. The first stage screening sample included 509 subjects from 151 nuclear families recruited within the United Kingdom and Republic of Ireland. This sample contained 154 narrowly defined affected sibling pairs (DSM-IV BPI) and 258 broadly defined affected sibling pairs (DSM-IV BPI, SABP, BPII, BPNOS or MDD(R)), approximately two thirds of all families contained at least one other additional typed individual. All individuals were genotyped using 398 highly polymorphic microsatellite markers from Applied Biosystems's Linkage Mapping Set Version 2. The average inter-marker distance was 9.6 cM and the mean heterozygosity was 0.78. Analysis of these data using non-parametric linkage methods (MAPMAKER/SIBS) found no evidence for loci of major effect and no regions reached genome-wide significance for either suggestive or significant linkage. We identified 19 points across the genome where the MLS exceeded a value set for follow up in our second stage screen (MLS > or = 0.74 (equivalent to a nominal pointwise significance of 5%) under the narrowest diagnostic model). These points were on chromosomes 2, 3, 4, 6, 7, 9, 10, 12, 17, 18 & X. Some of these points overlapped with previous linkage reports both within bipolar affective disorder and other psychiatric illnesses. Under the narrowest diagnostic model, the single most significant multipoint linkage was on chromosome 18 at marker D18S452 (MLS=1.54). Overall the highest MLS was 1.70 on chromosome 2 at marker D2S125, under the broadest diagnostic model.
Molecular Psychiatry 02/2002; 7(2):189-200. · 13.67 Impact Factor
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E O'Mahony, A Corvin,
R O'Connell,
C Comerford,
B Larsen,
R Jones,
F McCandless,
G Kirov,
A G Cardno,
N Craddock,
M Gill
[show abstract]
[hide abstract]
ABSTRACT: As part of a collaborative linkage study, the authors obtained clinical and demographic data on 160 families in which more than one sibling was affected with a bipolar illness. The aim of the study was to identify clinical characteristics that had a high degree of familiality.
Data on age at onset, gender, frequency of illness-episodes and proportion of manic to depressive episodes were examined to determine intra-pair correlations in affected sibling pairs. Dimension scales were developed measuring frequency and severity of lifetime mania, depression, psychosis and mood-incongruence of psychotic symptoms; degree of familial aggregation for scores on these dimensions was calculated.
Sibling pairs correlated significantly for age at onset (p = 0.293, P < 0 001); dimension scores for psychosis (p = 0.332, P < 0.001); and proportion of manic to depressive episodes (p = 0.184, P = 0.002). These findings remained significant when correcting for multiple testing. Of the other test variables; mania (p = 0.171, P = 0.019); incongruence dimensions (p = 0.242, P = 0.042); .frequency of manic episodes (p = 0.152, P = 0.033); and frequency of depressive episodes (p = 0.155, P = 0.028) were associated with modest correlations but these were not significant after correction. Degree of familial aggregation was not significant for sex (kappa = 0.084) or dimension scores for depression (p = 0.078, P = 0.300).
Significant but modest familial resemblance has been shown for some specific features of bipolar illness, particularly age at onset and degree of psychosis. Further research may establish the extent to which these findings are mediated by genetic and/or environmental factors.
Psychological Medicine 01/2002; 32(1):55-61. · 6.16 Impact Factor
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[hide abstract]
ABSTRACT: An association exists between smoking and schizophrenia, independent of other factors and related to psychotic symptomatology.
To determine whether smoking is associated with psychosis in bipolar affective disorder.
Smoking data were collected from 92 unrelated patients with bipolar affective disorder. An ordinal logistic regression analysis tested the relationship between smoking severity and psychotic symptomatology, allowing for potential confounders.
A significant relationship was detected between smoking/heavy smoking and history of psychosis (68.7%, n=44). Smoking was less prevalent in patients who were less symptomatic (56.5%, n=13) than in patients with a more severe psychosis (75.7, n=31). Prevalence and severity of smoking predicted severity of psychotic symptoms (P=0.001), a relationship independent of other variables (P=0.0272).
A link between smoking and psychosis exists in bipolar affective disorder and may be independent of categorical diagnosis.
The British Journal of Psychiatry 08/2001; 179:35-8. · 6.62 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Low cholesterol may act as a peripheral marker for parasuicide.
To examine the relationship between total serum cholesterol and psychological parameters in parasuicide.
Total serum cholesterol and self-rated scores for impulsivity, depression and suicidal intent were measured in 100 consecutive patients following parasuicide, pair-matched with normal and psychiatric control groups.
Backward, stepwise multiple regression analysis revealed a significantly lower mean cholesterol in the parasuicide population (P < 0.01). Across all groups there was an independent significant (P < 0.01) negative correlation between cholesterol and self-reported scores of impulsivity. No correlation existed between cholesterol and scores for depression or suicidal intent.
The data confirm previous reports of low cholesterol in parasuicide. This is the first reported investigation of the construct of impulsivity in relation to cholesterol. We hypothesise that the reported increased mortality in populations with low cholesterol may derive from increased suicide and accident rates consequent on increased tendencies to impulsivity in these populations.
The British Journal of Psychiatry 07/2000; 177:77-83. · 6.62 Impact Factor
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D Lambert,
F Middle,
Marian Lindsay Hamshere,
Ricardo Segurado,
Rachel Elizabeth Raybould, A Corvin,
Elaine Karen Green,
E O'Mahony,
Ivan Nikolov,
T Mulcahy, [......],
P Bennett,
Nadine Norton,
Michael John Owen,
George Kirov,
C Lendon,
L Jones,
Ian Richard Jones,
Peter Alan Holmans,
M Gill,
Nicholas John Craddock
[show abstract]
[hide abstract]
ABSTRACT: Bipolar affective disorder (BPAD) is a common psychiatric disorder with complex genetic aetiology. We have undertaken a genome-wide scan in one of the largest samples of bipolar affected sibling pairs (ASPs) using a two-stage approach combining sample splitting and marker grid tightening. In this second stage analysis, we have examined 17 regions that achieved a nominally significant maximum likelihood LOD score (MLS) threshold of 0.74 (or 1.18 for the X-chromosome) in stage one. The second stage has added 135 ASP families to bring the total stage 2 sample to 395 ASPs. In total, 494 microsatellite markers have been used to screen the human genome at a density of 10 cM in the first stage sample (260 ASPs) and 5 cM in the second stage. Under the broad diagnostic model, two markers gave LOD scores exceeding 3 with two-point analysis: D4S392 (LOD=3.30) and D10S197 (LOD=3.18). Multipoint analysis demonstrated suggestive evidence of linkage between BPAD and chromosomal regions 6q16–q21 (MLS=2.61) and 4q12–q21 (MLS=2.38). 6q16–q21 is of particular interest because our data, together with those from two recent genome scans, make this the best supported linkage region in BPAD. Further, our data show evidence of a gender effect at this locus with increased sharing predominantly within the male–male pairs. Our scan also provides support for linkage (MLS1.5) at several other regions that have been implicated in meta-analyses of bipolar disorder and/or schizophrenia including 9p21, 10p14–p12 and 18q22.
