Background and Aims: Bipolar disorder and borderline personality disorder are commonly comorbid. ... more Background and Aims: Bipolar disorder and borderline personality disorder are commonly comorbid. Borderline personality disorder is diagnosed categorically, but personality pathology may be better characterised dimensionally. The impact of borderline personality traits (not diagnosis) on the course of bipolar disorder is unknown. We examined the presence and severity of borderline personality traits in a large UK sample of bipolar disorder, and the impact of these traits on illness course. Methods: Borderline Evaluation of Severity over Time (BEST) was used to measure presence and severity of borderline traits in 1447 individuals with DSM-IV bipolar I disorder (n = 1008) and bipolar II disorder (n = 439) recruited into the Bipolar Disorder Research Network (www.bdrn.org). Clinical course was measured via semi-structured interview (Schedules for Clinical Assessment in Neuropsychiatry) and case-notes. Results: BEST score was higher in bipolar II than bipolar I (36 v 27, p < 0.001) ...
Background: Medical student attitudes to mental illness are significantly influenced by their und... more Background: Medical student attitudes to mental illness are significantly influenced by their undergraduate educational experience. Medical education therefore has a key role to play in challenging the stigma associated with mental illness. We developed a short educational film aimed at challenging stigmatising attitudes to mental illness and explored its effects on undergraduate medical student attitudes. We hypothesised that levels of stigmatising attitudes in medical students would reduce after students viewed the educational film. Method: We used a validated scale (Mental Illness: Clinician Attitudes, MICA) to examine undergraduate medical student attitudes to mental illness at two time points - prior to (T1) and following (T2) viewing the short film. The film focused on patient experiences and was designed to highlight personal experiences of mental illness. Results: 92 students completed the MICA before the film and 73 students at both time points. Having a personal history of...
Background and Aims: True Colours is an online prospective mood-monitoring system developed at th... more Background and Aims: True Colours is an online prospective mood-monitoring system developed at the University of Oxford to assist local patients and clinicians with monitoring course of illness in bipolar disorder. We report our initial experiences of using True Colours for research purposes in the Bipolar Disorder Research Network (BDRN; www.bdrn.org), a large research network of individuals with mood disorders spread throughout the UK. Methods: After initial piloting to ensure the practicality/acceptability of using True Colours within BDRN, we invited all BDRN participants (n = 7000) to participate in weekly True Colours ratings via three postal invitations sent over an 8-month period. Results: Following the three postal invitations, 915 individuals have so far expressed an interest in joining True Colours, and, of these, 662 (72.3%) have registered. 32 of those who registered for True Colours (5%) have so far asked to leave the system. Positive feedback from participants has foc...
Background The aetiology of Bipolar Disorder (BD) and Schizophrenia (SZ) involves a complex gene-... more Background The aetiology of Bipolar Disorder (BD) and Schizophrenia (SZ) involves a complex gene-environment interplay and this involves common risk alleles that are shared across the disorders. Bipolar disorder is heterogeneous in presentation and we and others have postulated that the particular clinical presentation is in part determined by the particular risk alleles carried. To investigate this, we have employed sparse Canonical Correlation Analysis (sCCA), to seek patterns of correlation between psychotic symptoms and schizophrenia risk alleles in a large (N=3903) deeply phenotyped sample of subjects with BD. Methods Canonical Correlation Analysis (CCA) seeks linear relationships between two sets of multi-dimensional variables. In the psychiatric genetics field, this approach can be adapted to enable the analysis of both phenotype and genetic variables in one framework. This has the advantage of minimizing the number of statistical tests required. A recent extension of CCA to sparse canonical correlation analysis (sCCA) allows application of the general approach to high dimensional genomic data (Witten et al., 2009). sCCA has advantages compared to CCA in terms of precision of parameter estimates and statistical power. We employed sCCA to analyse 30 psychotic symptoms assessed with the OPerational CRITeria checklist (OPCRIT) and 82 independent genome-wide significant SNPs that were identified by the SZ PGC2 study (The Psychiatric Genomics Consortium, 2014) for which we had data in our BD sample. We applied the sCCA as a purely data driven approach to individual OPCRIT psychotic symptoms and also to groups of OPCRIT psychotic symptoms (“positive”, “negative”, “disorganised”) defined by a previously published factor analysis study of schizophrenia. Results sCCA analysis of the individual OPCRIT items with the set of significantly associated with SZ 82 sCCA analysis based on individual psychotic symptoms revealed a significant association (p=0.045) with the largest weights attributed to delusions of influence, bizarre behaviour and grandiose delusions and an indel SNP on chromosome 3 (3:180594593, build 37). sCCA analysis on the same set of SNPs and OPCRIT symptom groups confirmed association with the same SNP and the “disorganised” group of OPCRIT symptoms (p=0.01). The results also show significant association when we use less stringent p-value thresholds in SZ. In this case the most heavily weighted SNP remains 3:180594593, but other SNPs also contribute to the analysis. Discussion Our results suggest the CCA canonical correlation approach might be a useful tool to explore phenotype-genotype relationships. It can be applied to generate data-driven hypotheses with the potential to provide further insights into the complex architecture of psychiatric disorders. To the best of our knowledge, this is the first study to apply this approach in analysing phenotypes and genotypes together. sCCA offers the potential to be extended to include a larger number of fine grained systematic descriptors of BD, and for testing for correlation with genetic profiles from other co-morbid disorders.
Mood disorders affect 10-20% of the population, ranging from brief, mild episodes to severe, inca... more Mood disorders affect 10-20% of the population, ranging from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of genetic risk factors between unipolar and bipolar mood disorders. We use data from the largest genome-wide association studies of major depression (MD) and bipolar disorder (BD) to investigate the molecular basis of the shared genetic liability to mood disorders. We meta-analysed the Psychiatric Genomics Consortium (PGC) MD and BD cohorts, and an additional MD cohort from UK Biobank (185,285 cases, 439,741 controls, non-overlapping N = 609,424). 73 loci reached genome-wide significance in the meta-analysis, with additional loci significant in subtype and depression-only analyses. More genome-wide significant loci from PGC MD (39/44, 89% of the PGC MD loci) than PGC BD (4/19, 21%) reached genome-wide significance in the meta-analysis. Genetic correlations calculated between MD and BD s...
The British journal of psychiatry : the journal of mental science, 2018
Pregnancy and childbirth are a period of high risk for women with bipolar disorder and involve di... more Pregnancy and childbirth are a period of high risk for women with bipolar disorder and involve difficult decisions particularly about continuing or stopping medications.AimsTo explore what clinical predictors may help to individualise the risk of perinatal recurrence in women with bipolar disorder. Information was gathered retrospectively by semi-structured interview, questionnaires and case-note review from 887 women with bipolar disorder who have had children. Clinical predictors were selected using backwards stepwise logistic regression, conditional permutation random forests and reinforcement learning trees. Previous perinatal history of affective psychosis or depression was the most significant predictor of a perinatal recurrence (odds ratio (OR) = 8.5, 95% CI 5.04-14.82 and OR = 3.6, 95% CI 2.55-5.07 respectively) but even parous women with bipolar disorder without a previous perinatal mood episode were at risk following a subsequent pregnancy, with 7% developing postpartum ps...
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2018
The etiologies of bipolar disorder (BD) and schizophrenia include a large number of common risk a... more The etiologies of bipolar disorder (BD) and schizophrenia include a large number of common risk alleles, many of which are shared across the disorders. BD is clinically heterogeneous and it has been postulated that the pattern of symptoms is in part determined by the particular risk alleles carried, and in particular, that risk alleles also confer liability to schizophrenia influence psychotic symptoms in those with BD. To investigate links between psychotic symptoms in BD and schizophrenia risk alleles we employed a data-driven approach in a genotyped and deeply phenotyped sample of subjects with BD. We used sparse canonical correlation analysis (sCCA) (Witten, Tibshirani, & Hastie, ) to analyze 30 psychotic symptoms, assessed with the OPerational CRITeria checklist, and 82 independent genome-wide significant single nucleotide polymorphisms (SNPs) identified by the Schizophrenia Working group of the Psychiatric Genomics Consortium for which we had data in our BD sample (3,903 subje...
Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. ... more Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes and mechanisms. To investigate the association between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRSs), and psychotic presentations of BD. This case-control study in the United Kingdom used multinomial logistic regression to estimate differential PRS associations across categories of cases and controls. Participants included in the final analyses were 4436 cases of BD from the Bipolar Disorder Research Network. These cases were compared with the genotypic data for 4976 cases of schizophrenia and 9012 controls from the Type 1 Diabetes Genetics Consortium study and the Generation Scotland study. Data were collected between January 1, 2000, and December 31, 2013. Data analysis was conducted from March 1, 2016, to ...
Background Bipolar disorder (BD) includes a broad range of phenotypic features – most research ex... more Background Bipolar disorder (BD) includes a broad range of phenotypic features – most research examining its genetic underpinning focuses on the overall syndrome rather than its subphenotypic components. BD is a highly heritable disorder and while its genetic architecture is not fully elucidated there is increasingly strong support for a very polygenic component with partial polygenic overlap with schizophrenia (SZ). Here we present preliminary results from an analysis examining the association of SZ derived polygenic risk scores (PRS) across different BD subtypes (Bipolar Type 1(BPI), Bipolar Type 2 (BPII) and Schizoaffective disorder (SAD), and subphenotypes defined by the presence of psychosis and its associated level of mood incongruence. Methods We used a UK sample of 3101 BP cases, collected using a consistently administrated interview protocol with OPCRIT confirmed lifetime diagnosis of Research Diagnostic Criteria (RDC - BPI, BPII or SAD). PRS were generated using 1000 genomes (phase3, 2014) imputed genetic data (INFO score>0.8, HWE>1e-6, MAF>0.01) trained on the results from Psychiatric Genetic Consortium (PGC2) SZ GWAS, pruned r2 Results PRS with the SZ association p-value cut-off of 0.5, have shown significant association across the BD subtypes with relative risk ratios RRR = 1.28 (95%CI: 1.18-1.39, p Discussion Preliminary analyses show a genetic - phenotypic association, between polygenic features of schizophrenia and BP characterised by the presence of psychosis, suggesting the phenotypic overlap between SZ and BD may in part be driven by polygenic overlap. This finding is further supported by the association of PRS and level of mood incongruence in the content of psychotic symptoms. These results suggest the PRS effect is not solely mediated though the psychosis subphenotype, at least in the BPI group. Our analyses show promise for the strategy of examining polygenic/phenotypic associations based on fine grained clinical characterisations
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, Jan 29, 2017
Studies have suggested that Research Diagnostic Criteria for Schizoaffective Disorder Bipolar typ... more Studies have suggested that Research Diagnostic Criteria for Schizoaffective Disorder Bipolar type (RDC-SABP) might identify a more genetically homogenous subgroup of bipolar disorder. Aiming to identify loci associated with RDC-SABP, we have performed a replication study using independent RDC-SABP cases (n = 144) and controls (n = 6,559), focusing on the 10 loci that reached a p-value <10(-5) for RDC-SABP in the Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder sample. Combining the WTCCC and replication datasets by meta-analysis (combined RDC-SABP, n = 423, controls, n = 9,494), we observed genome-wide significant association at one SNP, rs2352974, located within the intron of the gene TRAIP on chromosome 3p21.31 (p-value, 4.37 × 10(-8) ). This locus did not reach genome-wide significance in bipolar disorder or schizophrenia large Psychiatric Genomic Consortium datasets, suggesting that it may represent a relatively specific genetic risk for the bipolar subtype of...
Women with bipolar disorder are at high risk of affective psychoses following childbirth (i.e. &q... more Women with bipolar disorder are at high risk of affective psychoses following childbirth (i.e. "postpartum psychosis", PP) and there is a need to identify which factors underlie this increased risk. Vulnerability to mood dysregulation following sleep loss may influence risk of PP, as childbirth is typified by sleep disruption. We investigated whether a history of mood episodes triggered by sleep loss was associated with PP in women with bipolar disorder (BD). Participants were 870 parous women with BD recruited to the Bipolar Disorder Research Network. Lifetime diagnoses of BD and perinatal episodes were identified via interview and case notes. Information on whether mood episodes had been triggered by sleep loss was derived at interview. Rates of PP were compared between women who did and did not report mood episodes following sleep loss. Women who reported sleep loss triggering episodes of mania were twice as likely to have experienced an episode of PP (OR = 2.09, 95% CI...
The British journal of psychiatry : the journal of mental science, Jan 6, 2017
BackgroundSleep loss may trigger mood episodes in people with bipolar disorder but individual dif... more BackgroundSleep loss may trigger mood episodes in people with bipolar disorder but individual differences could influence vulnerability to this trigger.AimsTo determine whether bipolar subtype (bipolar disorder type I (BP-I) or II (BD-II)) and gender were associated with vulnerability to the sleep loss trigger.MethodDuring a semi-structured interview, 3140 individuals (68% women) with bipolar disorder (66% BD-I) reported whether sleep loss had triggered episodes of high or low mood. DSM-IV diagnosis of bipolar subtype was derived from case notes and interview data.ResultsSleep loss triggering episodes of high mood was associated with female gender (odds ratio (OR) = 1.43, 95% CI 1.17-1.75, P < 0.001) and BD-I subtype (OR = 2.81, 95% CI 2.26-3.50, P < 0.001). Analyses on sleep loss triggering low mood were not significant following adjustment for confounders.ConclusionsGender and bipolar subtype may increase vulnerability to high mood following sleep deprivation. This should be...
Background and Aims: Bipolar disorder and borderline personality disorder are commonly comorbid. ... more Background and Aims: Bipolar disorder and borderline personality disorder are commonly comorbid. Borderline personality disorder is diagnosed categorically, but personality pathology may be better characterised dimensionally. The impact of borderline personality traits (not diagnosis) on the course of bipolar disorder is unknown. We examined the presence and severity of borderline personality traits in a large UK sample of bipolar disorder, and the impact of these traits on illness course. Methods: Borderline Evaluation of Severity over Time (BEST) was used to measure presence and severity of borderline traits in 1447 individuals with DSM-IV bipolar I disorder (n = 1008) and bipolar II disorder (n = 439) recruited into the Bipolar Disorder Research Network (www.bdrn.org). Clinical course was measured via semi-structured interview (Schedules for Clinical Assessment in Neuropsychiatry) and case-notes. Results: BEST score was higher in bipolar II than bipolar I (36 v 27, p < 0.001) ...
Background: Medical student attitudes to mental illness are significantly influenced by their und... more Background: Medical student attitudes to mental illness are significantly influenced by their undergraduate educational experience. Medical education therefore has a key role to play in challenging the stigma associated with mental illness. We developed a short educational film aimed at challenging stigmatising attitudes to mental illness and explored its effects on undergraduate medical student attitudes. We hypothesised that levels of stigmatising attitudes in medical students would reduce after students viewed the educational film. Method: We used a validated scale (Mental Illness: Clinician Attitudes, MICA) to examine undergraduate medical student attitudes to mental illness at two time points - prior to (T1) and following (T2) viewing the short film. The film focused on patient experiences and was designed to highlight personal experiences of mental illness. Results: 92 students completed the MICA before the film and 73 students at both time points. Having a personal history of...
Background and Aims: True Colours is an online prospective mood-monitoring system developed at th... more Background and Aims: True Colours is an online prospective mood-monitoring system developed at the University of Oxford to assist local patients and clinicians with monitoring course of illness in bipolar disorder. We report our initial experiences of using True Colours for research purposes in the Bipolar Disorder Research Network (BDRN; www.bdrn.org), a large research network of individuals with mood disorders spread throughout the UK. Methods: After initial piloting to ensure the practicality/acceptability of using True Colours within BDRN, we invited all BDRN participants (n = 7000) to participate in weekly True Colours ratings via three postal invitations sent over an 8-month period. Results: Following the three postal invitations, 915 individuals have so far expressed an interest in joining True Colours, and, of these, 662 (72.3%) have registered. 32 of those who registered for True Colours (5%) have so far asked to leave the system. Positive feedback from participants has foc...
Background The aetiology of Bipolar Disorder (BD) and Schizophrenia (SZ) involves a complex gene-... more Background The aetiology of Bipolar Disorder (BD) and Schizophrenia (SZ) involves a complex gene-environment interplay and this involves common risk alleles that are shared across the disorders. Bipolar disorder is heterogeneous in presentation and we and others have postulated that the particular clinical presentation is in part determined by the particular risk alleles carried. To investigate this, we have employed sparse Canonical Correlation Analysis (sCCA), to seek patterns of correlation between psychotic symptoms and schizophrenia risk alleles in a large (N=3903) deeply phenotyped sample of subjects with BD. Methods Canonical Correlation Analysis (CCA) seeks linear relationships between two sets of multi-dimensional variables. In the psychiatric genetics field, this approach can be adapted to enable the analysis of both phenotype and genetic variables in one framework. This has the advantage of minimizing the number of statistical tests required. A recent extension of CCA to sparse canonical correlation analysis (sCCA) allows application of the general approach to high dimensional genomic data (Witten et al., 2009). sCCA has advantages compared to CCA in terms of precision of parameter estimates and statistical power. We employed sCCA to analyse 30 psychotic symptoms assessed with the OPerational CRITeria checklist (OPCRIT) and 82 independent genome-wide significant SNPs that were identified by the SZ PGC2 study (The Psychiatric Genomics Consortium, 2014) for which we had data in our BD sample. We applied the sCCA as a purely data driven approach to individual OPCRIT psychotic symptoms and also to groups of OPCRIT psychotic symptoms (“positive”, “negative”, “disorganised”) defined by a previously published factor analysis study of schizophrenia. Results sCCA analysis of the individual OPCRIT items with the set of significantly associated with SZ 82 sCCA analysis based on individual psychotic symptoms revealed a significant association (p=0.045) with the largest weights attributed to delusions of influence, bizarre behaviour and grandiose delusions and an indel SNP on chromosome 3 (3:180594593, build 37). sCCA analysis on the same set of SNPs and OPCRIT symptom groups confirmed association with the same SNP and the “disorganised” group of OPCRIT symptoms (p=0.01). The results also show significant association when we use less stringent p-value thresholds in SZ. In this case the most heavily weighted SNP remains 3:180594593, but other SNPs also contribute to the analysis. Discussion Our results suggest the CCA canonical correlation approach might be a useful tool to explore phenotype-genotype relationships. It can be applied to generate data-driven hypotheses with the potential to provide further insights into the complex architecture of psychiatric disorders. To the best of our knowledge, this is the first study to apply this approach in analysing phenotypes and genotypes together. sCCA offers the potential to be extended to include a larger number of fine grained systematic descriptors of BD, and for testing for correlation with genetic profiles from other co-morbid disorders.
Mood disorders affect 10-20% of the population, ranging from brief, mild episodes to severe, inca... more Mood disorders affect 10-20% of the population, ranging from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Multiple approaches have shown considerable sharing of genetic risk factors between unipolar and bipolar mood disorders. We use data from the largest genome-wide association studies of major depression (MD) and bipolar disorder (BD) to investigate the molecular basis of the shared genetic liability to mood disorders. We meta-analysed the Psychiatric Genomics Consortium (PGC) MD and BD cohorts, and an additional MD cohort from UK Biobank (185,285 cases, 439,741 controls, non-overlapping N = 609,424). 73 loci reached genome-wide significance in the meta-analysis, with additional loci significant in subtype and depression-only analyses. More genome-wide significant loci from PGC MD (39/44, 89% of the PGC MD loci) than PGC BD (4/19, 21%) reached genome-wide significance in the meta-analysis. Genetic correlations calculated between MD and BD s...
The British journal of psychiatry : the journal of mental science, 2018
Pregnancy and childbirth are a period of high risk for women with bipolar disorder and involve di... more Pregnancy and childbirth are a period of high risk for women with bipolar disorder and involve difficult decisions particularly about continuing or stopping medications.AimsTo explore what clinical predictors may help to individualise the risk of perinatal recurrence in women with bipolar disorder. Information was gathered retrospectively by semi-structured interview, questionnaires and case-note review from 887 women with bipolar disorder who have had children. Clinical predictors were selected using backwards stepwise logistic regression, conditional permutation random forests and reinforcement learning trees. Previous perinatal history of affective psychosis or depression was the most significant predictor of a perinatal recurrence (odds ratio (OR) = 8.5, 95% CI 5.04-14.82 and OR = 3.6, 95% CI 2.55-5.07 respectively) but even parous women with bipolar disorder without a previous perinatal mood episode were at risk following a subsequent pregnancy, with 7% developing postpartum ps...
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2018
The etiologies of bipolar disorder (BD) and schizophrenia include a large number of common risk a... more The etiologies of bipolar disorder (BD) and schizophrenia include a large number of common risk alleles, many of which are shared across the disorders. BD is clinically heterogeneous and it has been postulated that the pattern of symptoms is in part determined by the particular risk alleles carried, and in particular, that risk alleles also confer liability to schizophrenia influence psychotic symptoms in those with BD. To investigate links between psychotic symptoms in BD and schizophrenia risk alleles we employed a data-driven approach in a genotyped and deeply phenotyped sample of subjects with BD. We used sparse canonical correlation analysis (sCCA) (Witten, Tibshirani, & Hastie, ) to analyze 30 psychotic symptoms, assessed with the OPerational CRITeria checklist, and 82 independent genome-wide significant single nucleotide polymorphisms (SNPs) identified by the Schizophrenia Working group of the Psychiatric Genomics Consortium for which we had data in our BD sample (3,903 subje...
Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. ... more Bipolar disorder (BD) overlaps schizophrenia in its clinical presentation and genetic liability. Alternative approaches to patient stratification beyond current diagnostic categories are needed to understand the underlying disease processes and mechanisms. To investigate the association between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRSs), and psychotic presentations of BD. This case-control study in the United Kingdom used multinomial logistic regression to estimate differential PRS associations across categories of cases and controls. Participants included in the final analyses were 4436 cases of BD from the Bipolar Disorder Research Network. These cases were compared with the genotypic data for 4976 cases of schizophrenia and 9012 controls from the Type 1 Diabetes Genetics Consortium study and the Generation Scotland study. Data were collected between January 1, 2000, and December 31, 2013. Data analysis was conducted from March 1, 2016, to ...
Background Bipolar disorder (BD) includes a broad range of phenotypic features – most research ex... more Background Bipolar disorder (BD) includes a broad range of phenotypic features – most research examining its genetic underpinning focuses on the overall syndrome rather than its subphenotypic components. BD is a highly heritable disorder and while its genetic architecture is not fully elucidated there is increasingly strong support for a very polygenic component with partial polygenic overlap with schizophrenia (SZ). Here we present preliminary results from an analysis examining the association of SZ derived polygenic risk scores (PRS) across different BD subtypes (Bipolar Type 1(BPI), Bipolar Type 2 (BPII) and Schizoaffective disorder (SAD), and subphenotypes defined by the presence of psychosis and its associated level of mood incongruence. Methods We used a UK sample of 3101 BP cases, collected using a consistently administrated interview protocol with OPCRIT confirmed lifetime diagnosis of Research Diagnostic Criteria (RDC - BPI, BPII or SAD). PRS were generated using 1000 genomes (phase3, 2014) imputed genetic data (INFO score>0.8, HWE>1e-6, MAF>0.01) trained on the results from Psychiatric Genetic Consortium (PGC2) SZ GWAS, pruned r2 Results PRS with the SZ association p-value cut-off of 0.5, have shown significant association across the BD subtypes with relative risk ratios RRR = 1.28 (95%CI: 1.18-1.39, p Discussion Preliminary analyses show a genetic - phenotypic association, between polygenic features of schizophrenia and BP characterised by the presence of psychosis, suggesting the phenotypic overlap between SZ and BD may in part be driven by polygenic overlap. This finding is further supported by the association of PRS and level of mood incongruence in the content of psychotic symptoms. These results suggest the PRS effect is not solely mediated though the psychosis subphenotype, at least in the BPI group. Our analyses show promise for the strategy of examining polygenic/phenotypic associations based on fine grained clinical characterisations
American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, Jan 29, 2017
Studies have suggested that Research Diagnostic Criteria for Schizoaffective Disorder Bipolar typ... more Studies have suggested that Research Diagnostic Criteria for Schizoaffective Disorder Bipolar type (RDC-SABP) might identify a more genetically homogenous subgroup of bipolar disorder. Aiming to identify loci associated with RDC-SABP, we have performed a replication study using independent RDC-SABP cases (n = 144) and controls (n = 6,559), focusing on the 10 loci that reached a p-value <10(-5) for RDC-SABP in the Wellcome Trust Case Control Consortium (WTCCC) bipolar disorder sample. Combining the WTCCC and replication datasets by meta-analysis (combined RDC-SABP, n = 423, controls, n = 9,494), we observed genome-wide significant association at one SNP, rs2352974, located within the intron of the gene TRAIP on chromosome 3p21.31 (p-value, 4.37 × 10(-8) ). This locus did not reach genome-wide significance in bipolar disorder or schizophrenia large Psychiatric Genomic Consortium datasets, suggesting that it may represent a relatively specific genetic risk for the bipolar subtype of...
Women with bipolar disorder are at high risk of affective psychoses following childbirth (i.e. &q... more Women with bipolar disorder are at high risk of affective psychoses following childbirth (i.e. "postpartum psychosis", PP) and there is a need to identify which factors underlie this increased risk. Vulnerability to mood dysregulation following sleep loss may influence risk of PP, as childbirth is typified by sleep disruption. We investigated whether a history of mood episodes triggered by sleep loss was associated with PP in women with bipolar disorder (BD). Participants were 870 parous women with BD recruited to the Bipolar Disorder Research Network. Lifetime diagnoses of BD and perinatal episodes were identified via interview and case notes. Information on whether mood episodes had been triggered by sleep loss was derived at interview. Rates of PP were compared between women who did and did not report mood episodes following sleep loss. Women who reported sleep loss triggering episodes of mania were twice as likely to have experienced an episode of PP (OR = 2.09, 95% CI...
The British journal of psychiatry : the journal of mental science, Jan 6, 2017
BackgroundSleep loss may trigger mood episodes in people with bipolar disorder but individual dif... more BackgroundSleep loss may trigger mood episodes in people with bipolar disorder but individual differences could influence vulnerability to this trigger.AimsTo determine whether bipolar subtype (bipolar disorder type I (BP-I) or II (BD-II)) and gender were associated with vulnerability to the sleep loss trigger.MethodDuring a semi-structured interview, 3140 individuals (68% women) with bipolar disorder (66% BD-I) reported whether sleep loss had triggered episodes of high or low mood. DSM-IV diagnosis of bipolar subtype was derived from case notes and interview data.ResultsSleep loss triggering episodes of high mood was associated with female gender (odds ratio (OR) = 1.43, 95% CI 1.17-1.75, P < 0.001) and BD-I subtype (OR = 2.81, 95% CI 2.26-3.50, P < 0.001). Analyses on sleep loss triggering low mood were not significant following adjustment for confounders.ConclusionsGender and bipolar subtype may increase vulnerability to high mood following sleep deprivation. This should be...
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