Publications by authors named "Liz Forty"

43 Publications

Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology.

Nat Genet 2021 Jun 17;53(6):817-829. Epub 2021 May 17.

Department of Neuroscience, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
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http://dx.doi.org/10.1038/s41588-021-00857-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192451PMC
June 2021

Symptom profile of postpartum and non-postpartum manic episodes in bipolar I disorder: a within-subjects study.

Psychiatry Res 2020 02 2;284:112748. Epub 2020 Jan 2.

National Centre for Mental Health, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, 3.06, Hadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK. Electronic address:

The relationship of postpartum mania to episodes of mania occurring outside the perinatal period among women with bipolar disorder remains controversial. Previous studies have used between-subjects designs to compare the clinical presentations of these episodes meaning the differences, in part, may reflect between-group differences. To overcome this we have undertaken within-subject comparisons of the symptom profile of postpartum and non-postpartum manic episodes in 50 women with DSM-IV bipolar I disorder. For each woman detailed symptom information on a postpartum episode of mania and a comparison non-postpartum manic episode was collected. The occurrence of manic, psychotic and depressive symptoms in these episodes were compared. Postpartum manic episodes had a significantly higher incidence of perplexity and excessive self-reproach. Classic manic symptoms, specifically pressured speech and increased sociability, were significantly less frequent in postpartum manic episodes. Overall there were significantly fewer manic symptoms and significantly more depressive symptoms in the postpartum episodes than in the non-postpartum episodes. The mixed presentation of postpartum manic episodes suggests childbirth may act as a pathoplastic trigger in women with bipolar disorder. The differences in symptom profiles suggests further research is warranted into whether differences in treatment response exist among women experiencing postpartum and non-postpartum manic episodes.
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http://dx.doi.org/10.1016/j.psychres.2020.112748DOI Listing
February 2020

International Consortium on the Genetics of Electroconvulsive Therapy and Severe Depressive Disorders (Gen-ECT-ic).

Eur Arch Psychiatry Clin Neurosci 2020 Oct 4;270(7):921-932. Epub 2019 Dec 4.

Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alliance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts.
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http://dx.doi.org/10.1007/s00406-019-01087-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7385979PMC
October 2020

Comparison of Genetic Liability for Sleep Traits Among Individuals With Bipolar Disorder I or II and Control Participants.

JAMA Psychiatry 2020 03;77(3):303-310

Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom.

Importance: Insomnia, hypersomnia, and an evening chronotype are common in individuals with bipolar disorder (BD), but whether this reflects shared genetic liability is unclear. Stratifying by BD subtypes could elucidate this association and inform sleep and BD research.

Objective: To assess whether polygenic risk scores (PRSs) for sleep traits are associated with BD subtypes I and II.

Design, Setting, And Participants: This case-control study was conducted in the United Kingdom and Sweden with participants with BD and control participants. Multinomial regression was used to assess whether PRSs for insomnia, daytime sleepiness, sleep duration, and chronotype are associated with BD subtypes compared with control participants. Affected individuals were recruited from the Bipolar Disorder Research Network. Control participants were recruited from the 1958 British Birth Cohort and the UK Blood Service. Analyses were repeated in an independent Swedish sample from August 2018 to July 2019. All participants were of European ancestry.

Exposures: Standardized PRSs derived using alleles from genome-wide association studies of insomnia, sleep duration, daytime sleepiness, and chronotype. These were adjusted for the first 10 population principal components, genotyping platforms, and sex.

Main Outcomes And Measures: Association of PRSs with BD subtypes, determined by semistructured psychiatric interview and case notes.

Results: The main analysis included 4672 participants with BD (3132 female participants [67.0%]; 3404 with BD-I [72.9%]) and 5714 control participants (2812 female participants [49.2%]). Insomnia PRS was associated with increased risk of BD-II (relative risk [RR], 1.14 [95% CI, 1.07-1.21]; P = 8.26 × 10-5) but not BD-I (RR, 0.98 [95% CI, 0.94-1.03]; P = .409) relative to control participants. Sleep-duration PRS was associated with BD-I (RR, 1.10 [95% CI, 1.06-1.15]; P = 1.13 × 10-5) but not BD-II (RR, 0.99 [95% CI, 0.93-1.06]; P = .818). Associations between (1) insomnia PRS and BD-II and (2) sleep-duration PRS and BD-I were replicated in the Swedish sample of 4366 individuals with BD (2697 female participants [61.8%]; 2627 with BD-I [60.2%]) and 6091 control participants (3767 female participants [61.8%]). Chronotype and daytime-sleepiness PRS were not associated with BD subtypes.

Conclusions And Relevance: Per this analysis, BD subtypes differ in genetic liability to insomnia and hypersomnia, providing further evidence that the distinction between BD-I and BD-II has genetic validity. This distinction will be crucial in selecting participants for future research on the role of sleep disturbance in BD.
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http://dx.doi.org/10.1001/jamapsychiatry.2019.4079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902167PMC
March 2020

Genome-wide association study identifies 30 loci associated with bipolar disorder.

Nat Genet 2019 05 1;51(5):793-803. Epub 2019 May 1.

Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA.

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.
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http://dx.doi.org/10.1038/s41588-019-0397-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6956732PMC
May 2019

Contribution of Rare Copy Number Variants to Bipolar Disorder Risk Is Limited to Schizoaffective Cases.

Biol Psychiatry 2019 07 20;86(2):110-119. Epub 2018 Dec 20.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Background: Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood.

Methods: Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis.

Results: CNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p = .001), BD I (p = .0003), and BD II (p = .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p = .0007, PRS p = .004), and BD I without psychosis (CNV p = .0004, PRS p = 3.9 × 10). Within BD I, psychosis was associated with increased schizophrenia PRSs (p = .005) but not CNV burden.

Conclusions: CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.
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http://dx.doi.org/10.1016/j.biopsych.2018.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586545PMC
July 2019

Stratification of the risk of bipolar disorder recurrences in pregnancy and postpartum.

Br J Psychiatry 2018 09;213(3):542-547

Institute of Psychological Medicine and Clinical Neurosciences,Cardiff University,UKandDepartment of Psychological Medicine,University of Worcester,UK.

Background: 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.

Method: 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.

Results: 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 psychosis.

Conclusions: Previous perinatal history of affective psychosis or depression is the most important predictor of perinatal recurrence in women with bipolar disorder and can be used to individualise risk assessments.Declaration of interestNone.
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http://dx.doi.org/10.1192/bjp.2018.92DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429257PMC
September 2018

A data-driven investigation of relationships between bipolar psychotic symptoms and schizophrenia genome-wide significant genetic loci.

Am J Med Genet B Neuropsychiatr Genet 2018 06 19;177(4):468-475. Epub 2018 Apr 19.

MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University Institute of Psychological Medicine and Clinical Neurosciences, Cardiff, United Kingdom.

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 subjects). As a secondary analysis, we applied sCCA to larger groups of SNPs, and also to groups of symptoms defined according to a published factor analyses of schizophrenia. sCCA analysis based on individual psychotic symptoms revealed a significant association (p = .033), with the largest weights attributed to a variant on chromosome 3 (rs11411529), chr3:180594593, build 37) and delusions of influence, bizarre behavior and grandiose delusions. sCCA analysis using the same set of SNPs supported association with the same SNP and the group of symptoms defined "factor 3" (p = .012). A significant association was also observed to the "factor 3" phenotype group when we included a greater number of SNPs that were less stringently associated with schizophrenia; although other SNPs contributed to the significant multivariate association result, the greatest weight remained assigned to rs11411529. Our results suggest that the canonical correlation is a useful tool to explore phenotype-genotype relationships. To the best of our knowledge, this is the first study to apply this approach to complex, polygenic psychiatric traits. The sparse canonical correlation approach offers the potential to include a larger number of fine-grained systematic descriptors, and to include genetic markers associated with other disorders that are genetically correlated with BD.
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http://dx.doi.org/10.1002/ajmg.b.32635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001555PMC
June 2018

Association Between Schizophrenia-Related Polygenic Liability and the Occurrence and Level of Mood-Incongruent Psychotic Symptoms in Bipolar Disorder.

JAMA Psychiatry 2018 01;75(1):28-35

Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, Wales.

Importance: 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.

Objective: To investigate the association between common-variant liability for schizophrenia, indexed by polygenic risk scores (PRSs), and psychotic presentations of BD.

Design, Setting, And Participants: 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 February 28, 2017.

Exposures: Standardized PRSs, calculated using alleles with an association threshold of P < .05 in the second Psychiatric Genomics Consortium genome-wide association study of schizophrenia, were adjusted for the first 10 population principal components and genotyping platforms.

Main Outcomes And Measures: Multinomial logit models estimated PRS associations with BD stratified by Research Diagnostic Criteria subtypes of BD, by lifetime occurrence of psychosis, and by lifetime mood-incongruent psychotic features. Ordinal logistic regression examined PRS associations across levels of mood incongruence. Ratings were derived from the Schedules for Clinical Assessment in Neuropsychiatry interview and the Bipolar Affective Disorder Dimension Scale.

Results: Of the 4436 cases of BD, 2966 (67%) were female patients, and the mean (SD) age at interview was 46 [12] years. Across clinical phenotypes, there was an exposure-response gradient, with the strongest PRS association for schizophrenia (risk ratio [RR] = 1.94; 95% CI, 1.86-2.01), followed by schizoaffective BD (RR = 1.37; 95% CI, 1.22-1.54), bipolar I disorder subtype (RR = 1.30; 95% CI, 1.24-1.36), and bipolar II disorder subtype (RR = 1.04; 95% CI, 0.97-1.11). Within BD cases, there was an effect gradient, indexed by the nature of psychosis. Prominent mood-incongruent psychotic features had the strongest association (RR = 1.46; 95% CI, 1.36-1.57), followed by mood-congruent psychosis (RR = 1.24; 95% CI, 1.17-1.33) and BD with no history of psychosis (RR = 1.09; 95% CI, 1.04-1.15).

Conclusions And Relevance: For the first time to date, a study shows a polygenic-risk gradient across schizophrenia and BD, indexed by the occurrence and level of mood-incongruent psychotic symptoms.
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http://dx.doi.org/10.1001/jamapsychiatry.2017.3485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833541PMC
January 2018

Mania triggered by sleep loss and risk of postpartum psychosis in women with bipolar disorder.

J Affect Disord 2018 01 18;225:624-629. Epub 2017 Aug 18.

Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Hadyn Ellis Building, Maindy Road, CF24 4HQ Cardiff, UK. Electronic address:

Background: 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).

Methods: 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.

Results: 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 = 1.47-2.97, p < 0.001) compared to women who did not report this. There was no significant association between depression triggered by sleep loss and PP (p = 0.526).

Limitations: Data were cross-sectional therefore may be subject to recall bias. We also did not have objective data on sleep disruption that had occurred during the postpartum period or prior to mood episodes.

Conclusions: In clinical practice, a history of mania following sleep loss could be a marker of increased vulnerability to PP, and should be discussed with BD women who are pregnant or planning to conceive.
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http://dx.doi.org/10.1016/j.jad.2017.08.054DOI Listing
January 2018

Genome-wide significant locus for Research Diagnostic Criteria Schizoaffective Disorder Bipolar type.

Am J Med Genet B Neuropsychiatr Genet 2017 Dec 29;174(8):767-771. Epub 2017 Aug 29.

MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.

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 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 ). 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 schizoaffective disorder.
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http://dx.doi.org/10.1002/ajmg.b.32572DOI Listing
December 2017

Changes to the Diagnostic Criteria for Bipolar Disorder in DSM-5 Make Little Difference to Lifetime Diagnosis: Findings From the U.K. Bipolar Disorder Research Network (BDRN) Study.

Am J Psychiatry 2017 08;174(8):803

From the Department of Psychological Medicine, University of Worcester, Worcester, U.K.; and the Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cardiff, U.K.

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http://dx.doi.org/10.1176/appi.ajp.2017.17010109DOI Listing
August 2017

Sleep loss as a trigger of mood episodes in bipolar disorder: individual differences based on diagnostic subtype and gender.

Br J Psychiatry 2017 Sep 6;211(3):169-174. Epub 2017 Jul 6.

Katie Swaden Lewis, BSc, Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatry Genetics and Genomics, Cardiff University, Cardiff; Katherine Gordon-Smith, PhD, Institute of Health & Society, University of Worcester, Worcester; Liz Forty, PhD, National Centre for Mental Health, Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff; Arianna Di Florio, PhD, MD, Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff; Nick Craddock, PhD, FRCPsych, National Centre for Mental Health, Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff; Lisa Jones, PhD, Institute of Health & Society, University of Worcester, Worcester; Ian Jones, PhD, MRCPsych, National Centre for Mental Health, Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK

Sleep loss may trigger mood episodes in people with bipolar disorder but individual differences could influence vulnerability to this trigger.To 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.During 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.Sleep loss triggering episodes of high mood was associated with female gender (odds ratio (OR) = 1.43, 95% CI 1.17-1.75, < 0.001) and BD-I subtype (OR = 2.81, 95% CI 2.26-3.50, < 0.001). Analyses on sleep loss triggering low mood were not significant following adjustment for confounders.Gender and bipolar subtype may increase vulnerability to high mood following sleep deprivation. This should be considered in situations where patients encounter sleep disruption, such as shift work and international travel.
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http://dx.doi.org/10.1192/bjp.bp.117.202259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579327PMC
September 2017

Autistic and schizotypal traits and global functioning in bipolar I disorder.

J Affect Disord 2017 Jan 3;207:268-275. Epub 2016 Oct 3.

Department of Psychological Medicine, University of Worcester, Worcester, United Kingdom. Electronic address:

Objective: To determine the expression of autistic and positive schizotypal traits in a large sample of adults with bipolar I disorder (BD I), and the effect of co-occurring autistic and positive schizotypal traits on global functioning in BD I.

Method: Autistic and positive schizotypal traits were self-assessed in 797 individuals with BD-I recruited by the Bipolar Disorder Research Network. Differences in global functioning (rated using the Global Assessment Scale) during lifetime worst depressive and manic episodes (GASD and GASM respectively) were calculated in groups with high/low autistic and positive schizotypal traits. Regression analyses assessed the interactive effect of autistic and positive schizotypal traits on global functioning.

Results: 47.2% (CI=43.7-50.7%) showed clinically significant levels of autistic traits, and 23.22% (95% CI=20.29-26.14) showed clinically significant levels of positive schizotypal traits. In the worst episode of mania, the high autistic, high positive schizotypal group had better global functioning compared to the other groups. Individual differences analyses showed that high levels of both traits were associated with better global functioning in both mood states.

Limitations: Autistic and schizotypal traits were assessed using self-rated questionnaires.

Conclusions: Expression of autistic and schizotypal traits in adults with BD I is prevalent, and may be important to predict illness aetiology, prognosis, and diagnostic practices in this population. Future work should focus on replicating these findings in independent samples, and on the biological and/or psychosocial mechanisms underlying better global functioning in those who have high levels of both autistic and positive schizotypal traits.
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http://dx.doi.org/10.1016/j.jad.2016.09.059DOI Listing
January 2017

Genome-wide association study identifies SESTD1 as a novel risk gene for lithium-responsive bipolar disorder.

Mol Psychiatry 2016 09 27;21(9):1290-7. Epub 2015 Oct 27.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Lithium is the mainstay prophylactic treatment for bipolar disorder (BD), but treatment response varies considerably across individuals. Patients who respond well to lithium treatment might represent a relatively homogeneous subtype of this genetically and phenotypically diverse disorder. Here, we performed genome-wide association studies (GWAS) to identify (i) specific genetic variations influencing lithium response and (ii) genetic variants associated with risk for lithium-responsive BD. Patients with BD and controls were recruited from Sweden and the United Kingdom. GWAS were performed on 2698 patients with subjectively defined (self-reported) lithium response and 1176 patients with objectively defined (clinically documented) lithium response. We next conducted GWAS comparing lithium responders with healthy controls (1639 subjective responders and 8899 controls; 323 objective responders and 6684 controls). Meta-analyses of Swedish and UK results revealed no significant associations with lithium response within the bipolar subjects. However, when comparing lithium-responsive patients with controls, two imputed markers attained genome-wide significant associations, among which one was validated in confirmatory genotyping (rs116323614, P=2.74 × 10(-8)). It is an intronic single-nucleotide polymorphism (SNP) on chromosome 2q31.2 in the gene SEC14 and spectrin domains 1 (SESTD1), which encodes a protein involved in regulation of phospholipids. Phospholipids have been strongly implicated as lithium treatment targets. Furthermore, we estimated the proportion of variance for lithium-responsive BD explained by common variants ('SNP heritability') as 0.25 and 0.29 using two definitions of lithium response. Our results revealed a genetic variant in SESTD1 associated with risk for lithium-responsive BD, suggesting that the understanding of BD etiology could be furthered by focusing on this subtype of BD.
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http://dx.doi.org/10.1038/mp.2015.165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995544PMC
September 2016

Epilepsy and bipolar disorder.

Epilepsy Behav 2015 Nov 25;52(Pt A):267-74. Epub 2015 Aug 25.

MRC Centre for Neuropsychiatric Genetics and Genomics, Haydn Ellis Building, Maindy Road, Cardiff CF24 4HQ, UK. Electronic address:

It is well recognized that mood disorders and epilepsy commonly co-occur. Despite this, our knowledge regarding the relationship between epilepsy and bipolar disorder is limited. Several shared features between the two disorders, such as their episodic nature and potential to run a chronic course, and the efficacy of some antiepileptic medications in the prophylaxis of both disorders, are often cited as evidence of possible shared underlying pathophysiology. The present paper aims to review the bidirectional associations between epilepsy and bipolar disorder, with a focus on epidemiological links, evidence for shared etiology, and the impact of these disorders on both the individual and wider society. Better recognition and understanding of these two complex disorders, along with an integrated clinical approach, are crucial for improved evaluation and management of comorbid epilepsy and mood disorders.
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http://dx.doi.org/10.1016/j.yebeh.2015.07.003DOI Listing
November 2015

Affective temperaments and concomitant alcohol use disorders in bipolar disorder.

J Affect Disord 2015 Nov 29;186:226-31. Epub 2015 Jul 29.

Institute of Health and Wellbeing, University of Glasgow, 1 Lilybank Gardens, Glasgow G12 8RZ, UK. Electronic address:

Background: Alcohol misuse (AM) is more common in bipolar disorder (BD) than within the general population but the mechanisms of this association are unclear. We hypothesized that certain affective temperaments (including hyperthymic, cyclothymic, anxious, depressive and/or irritability) might represent 'fundamental states' contributing to risk of both AM and BD and we aimed to assess whether extremes of these five affective temperaments were associated with BD and concomitant AM status.

Methods: Our sample comprised 1420 individuals with BD who were recruited into a clinical-genetic study conducted by the Bipolar Disorder Research Network. Phenotypic assessments, including evaluation for AM and the 32-item TEMPS-A questionnaire, were conducted. Binary logistic regression was used to determine the effect of TEMPS-A scores on the likelihood of concomitant AM, with adjustment for confounders.

Results: Mean scores for four affective temperaments (hyperthymic, cyclothymic, depressive and irritable) were higher in cases (BD+AMs) than controls (BD only) (p<0.001). Hyperthymic and irritable temperaments in particular significantly increased the odds of concomitant AM within the BD sample after adjustment for potential confounders.

Limitations: The definition of AM was not directly based on formal diagnostic classification systems. A retrospective, cross-sectional design was used. Our findings may not generalize to other countries and cultures.

Conclusions: Higher scores on measures of hyperthymic and irritable temperament may contribute to the association between AM and BD. Assessing affective temperaments early in the course of BD may help to predict the development of an AM problem in vulnerable individuals.
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http://dx.doi.org/10.1016/j.jad.2015.07.027DOI Listing
November 2015

Smoking and postpartum psychosis.

Bipolar Disord 2015 Aug 9;17(5):572-3. Epub 2015 Jun 9.

Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.

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http://dx.doi.org/10.1111/bdi.12314DOI Listing
August 2015

Gambling problems in bipolar disorder in the UK: prevalence and distribution.

Br J Psychiatry 2015 Oct 18;207(4):328-33. Epub 2015 Jun 18.

Lisa Jones, PhD, Alice Metcalf, Department of Psychiatry, University of Birmingham; Katherine Gordon-Smith, PhD, Department of Psychiatry, University of Birmingham, and National Centre for Mental Health, Medical Research Council (MRC) Centre for Neuropsychiatric Genetics and Genomics, Cardiff University; Liz Forty, PhD, National Centre for Mental Health, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University; Amy Perry, BSc, Department of Psychiatry, University of Birmingham; Joanne Lloyd, PhD, School of Psychology, Sport and Exercise Health, Staffordshire University, Stoke-on-Trent; John R. Geddes, MD, FRCPsych, Guy M. Goodwin, FMedSci, DPhil, FRCPsych, Department of Psychiatry, University of Oxford; Ian Jones, PhD, MRCPsych, Nick Craddock, PhD, FRCPsych, National Centre for Mental Health, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University; Robert D. Rogers, PhD, Department of Psychiatry, University of Oxford, and School of Psychology, Bangor University, UK

Background: North American studies show bipolar disorder is associated with elevated rates of problem gambling; however, little is known about rates in the different presentations of bipolar illness.

Aims: To determine the prevalence and distribution of problem gambling in people with bipolar disorder in the UK.

Method: The Problem Gambling Severity Index was used to measure gambling problems in 635 participants with bipolar disorder.

Results: Moderate to severe gambling problems were four times higher in people with bipolar disorder than in the general population, and were associated with type 2 disorder (OR = 1.74, P = 0.036), history of suicidal ideation or attempt (OR = 3.44, P = 0.02) and rapid cycling (OR = 2.63, P = 0.008).

Conclusions: Approximately 1 in 10 patients with bipolar disorder may be at moderate to severe risk of problem gambling, possibly associated with suicidal behaviour and a rapid cycling course. Elevated rates of gambling problems in type 2 disorder highlight the probable significance of modest but unstable mood disturbance in the development and maintenance of such problems.
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http://dx.doi.org/10.1192/bjp.bp.114.154286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589664PMC
October 2015

Authors' reply.

Br J Psychiatry 2015 Jun;206(6):523

Liz Forty, Nick Craddock (on behalf of the authors), Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, UK. Email:

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http://dx.doi.org/10.1192/bjp.206.6.523DOI Listing
June 2015

Adverse childhood events and psychosis in bipolar affective disorder.

Br J Psychiatry 2015 Mar 22;206(3):191-7. Epub 2015 Jan 22.

Rachel Upthegrove, MRCPsych, PhD, Department of Psychiatry, School of Clinical & Experimental Medicine, University of Birmingham, Birmingham, Bipolar Disorder Research Network and Early Intervention Service, Birmingham and Solihull Mental Health Foundation Trust, Birmingham; Christine Chard, BMedSc, Lisa Jones, PhD, Department of Psychiatry, School of Clinical & Experimental Medicine, University of Birmingham, Birmingham and Bipolar Disorder Research Network; Katherine Gordon-Smith, PhD, Department of Psychiatry, School of Clinical & Experimental Medicine, University of Birmingham, Birmingham, National Centre for Mental Health, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff and Bipolar Disorder Research Network, UK; Liz Forty, PhD, Ian Jones, MRCPsych, PhD, Nick Craddock, FRCPsych, PhD, FMedSci, National Centre for Mental Health, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff and Bipolar Disorder Research Network, UK.

Background: There has been increasing interest in the association between childhood trauma and psychosis. Proposals for potential mechanisms involved include affective dysregulation and cognitive appraisals of threat.

Aims: To establish if, within bipolar disorder, childhood events show a significant association with psychosis, and in particular with symptoms driven by dysregulation of mood or with a persecutory content.

Method: Data on lifetime-ever presence of psychotic symptoms were determined by detailed structured interview with case-note review (n = 2019). Childhood events were recorded using a self-report questionnaire and case-note information.

Results: There was no relationship between childhood events, or childhood abuse, and psychosis per se. Childhood events were not associated with an increased risk of persecutory or other delusions. Significant associations were found between childhood abuse and auditory hallucinations, strongest between sexual abuse and mood congruent or abusive voices. These relationships remain significant even after controlling for lifetime-ever cannabis misuse.

Conclusions: Within affective disorder, the relationship between childhood events and psychosis appears to be relatively symptom-specific. It is possible that the pathways leading to psychotic symptoms differ, with delusions and non-hallucinatory symptoms being influenced less by childhood or early environmental experience.
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http://dx.doi.org/10.1192/bjp.bp.114.152611DOI Listing
March 2015

Comorbid medical illness in bipolar disorder.

Br J Psychiatry 2014 Dec 30;205(6):465-72. Epub 2014 Oct 30.

Liz Forty, PhD, Anna Ulanova, MD, MSc Psych, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK; Lisa Jones, PhD, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK; Ian Jones, MRCPsych, PhD, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK; Katherine Gordon-Smith, PhD, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff and School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK; Christine Fraser, BSc, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK; Anne Farmer, FRCPsych, PhD, Peter McGuffin, FRCPsych, PhD, Cathryn M. Lewis, PhD, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK; Georgina M. Hosang, PhD, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London and Department of Psychology, Goldsmiths University of London, UK; Margarita Rivera, PhD, MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK and Institute of Neurosciences, Biomedical Research Centre (CIBM), University of Granada, Spain; Nick Craddock, FRCPsych, PhD, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.

Background: Individuals with a mental health disorder appear to be at increased risk of medical illness.

Aims: To examine rates of medical illnesses in patients with bipolar disorder (n = 1720) and to examine the clinical course of the bipolar illness according to lifetime medical illness burden.

Method: Participants recruited within the UK were asked about the lifetime occurrence of 20 medical illnesses, interviewed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and diagnosed according to DSM-IV criteria.

Results: We found significantly increased rates of several medical illnesses in our bipolar sample. A high medical illness burden was associated with a history of anxiety disorder, rapid cycling mood episodes, suicide attempts and mood episodes with a typically acute onset.

Conclusions: Bipolar disorder is associated with high rates of medical illness. This comorbidity needs to be taken into account by services in order to improve outcomes for patients with bipolar disorder and also in research investigating the aetiology of affective disorder where shared biological pathways may play a role.
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http://dx.doi.org/10.1192/bjp.bp.114.152249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248234PMC
December 2014

Bipolar disorder, miscarriage, and termination.

Bipolar Disord 2015 Feb 10;17(1):102-5. Epub 2014 Jun 10.

National Centre for Mental Health, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff.

Objectives: To compare rates of bipolar episodes following miscarriage and termination with those occurring in the postpartum period.

Methods: Information in relation to pregnancy and childbirth was gathered retrospectively for 1,283 women with broadly defined bipolar disorder by interview and case-notes review.

Results: Rates of mania or affective psychosis were significantly higher after full-term delivery than after termination (p < 0.001) or miscarriage (p < 0.001). Rates of non-psychotic major depression were similar following full-term deliveries, miscarriages (p = 0.362), and terminations (p = 0.301).

Conclusions: While women with bipolar disorder and their clinicians should be aware of the possible onset of depression in the weeks following miscarriage or termination, episodes of mania or affective psychosis are less common in comparison with the high rates observed in the postpartum period.
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http://dx.doi.org/10.1111/bdi.12217DOI Listing
February 2015

Mood disorders and parity - a clue to the aetiology of the postpartum trigger.

J Affect Disord 2014 Jan;152-154:334-9

Background: Episodes of postpartum psychosis have been associated with first pregnancies in women with bipolar I disorder. It is unclear, however, if the effect extends to episodes at other times in relation to childbirth and to women with other mood disorders such as major depression and bipolar II disorder. This primiparity effect, which is also seen in other pregnancy related conditions such as pre-eclampsia, is a potentially important clue to the aetiology of childbirth related mood episodes.

Methods: Participants were interviewed and case notes reviewed. Best-estimate diagnoses were made according to DSM-IV criteria. Data on the occurrence of episodes in pregnancy and the postpartum were available on 3345 full term deliveries from 1667 participants, 934 with bipolar I disorder (BD-I), 278 with bipolar II disorder (BD-II) and 455 with recurrent major depression (RMD).

Results: Onsets of psychosis/mania within 6 weeks of childbirth were overrepresented in primiparae (p=0.007) with BD-I. Although primiparity was not associated with perinatal bipolar depression, there was an association with the onset of depression within 6 weeks in women with RMD (p=0.035). Whilst women experiencing a postpartum episode were less likely to go on to have further children, this did not account for the association with primiparity.

Limitations: Data were collected retrospectively. Information on pharmacological treatment was not available.

Conclusions: Primiparity is associated not only with postpartum psychosis/mania in BD-I, but also with postpartum depression in RMD. Psychosocial factors and biological differences between first and subsequent pregnancies may play a role and are candidates for examination in further studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025607PMC
http://dx.doi.org/10.1016/j.jad.2013.09.034DOI Listing
January 2014

Improving the psychometric utility of the hypomania checklist (HCL-32): a Rasch analysis approach.

J Affect Disord 2014 Jan 16;152-154:448-53. Epub 2013 Oct 16.

Institute of Health and Wellbeing, University of Glasgow, UK. Electronic address:

Background: The HCL-32 is a widely-used screening questionnaire for hypomania. We aimed to use a Rasch analysis approach to (i) evaluate the measurement properties, principally unidimensionality, of the HCL-32, and (ii) generate a score table to allow researchers to convert raw HCL-32 scores into an interval-level measurement which will be more appropriate for statistical analyses.

Methods: Subjects were part of the Bipolar Disorder Research Network (BDRN) study with DSM-IV bipolar disorder (n=389). Multidimensionality was assessed using the Rasch fit statistics and principle components analysis of the residuals (PCA). Item invariance (differential item functioning, DIF) was tested for gender, bipolar diagnosis and current mental state. Item estimates and reliabilities were calculated.

Results: Three items (29, 30, 32) had unacceptable fit to the Rasch unidimensional model. Item 14 displayed significant DIF for gender and items 8 and 17 for current mental state. Item estimates confirmed that not all items measure hypomania equally.

Limitations: This sample was recruited as part of a large ongoing genetic epidemiology study of bipolar disorder and may not be fully representative of the broader clinical population of individuals with bipolar disorder.

Conclusion: The HCL-32 is unidimensional in practice, but measurements may be further strengthened by the removal of four items. Re-scored linear measurements may be more appropriate for clinical research.
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http://dx.doi.org/10.1016/j.jad.2013.10.014DOI Listing
January 2014

Perinatal episodes across the mood disorder spectrum.

JAMA Psychiatry 2013 Feb;70(2):168-75

Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for NeuropsychiatricGenetics and Genomics, Cardiff University, Cardiff, Wales, United Kingdom.

CONTEXT Affective disorders are common in women, with many episodes having an onset in pregnancy or during the postpartum period. OBJECTIVE To investigate the occurrence and timing of perinatal mood episodes in women with bipolar I disorder, bipolar II disorder, and recurrent major depression (RMD). SETTING AND PATIENTS Women were recruited in our ongoing research on the genetic and nongenetic determinants of major affective disorders. Participants were interviewed and case notes were reviewed. Best-estimate diagnoses were made according to DSM-IV criteria. The 1785 parous women identified included 1212 women with bipolar disorder (980 with type I and 232 with type II) and 573 with RMD. Data were available on 3017 live births. MAIN OUTCOME MEASURES We report the lifetime occurrence of perinatal mood episodes, the rates of perinatal episodes per pregnancy/postpartum period, and the timing of the onset of episodes in relation to delivery. RESULTS More than two-thirds of all diagnostic groups reported at least 1 lifetime episode of illness during pregnancy or the postpartum period. Women with bipolar I disorder reported an approximately 50% risk of a perinatal major affective episode per pregnancy/postpartum period. Risks were lower in women with RMD or bipolar II disorder, at approximately 40% per pregnancy/postpartum period. Mood episodes were significantly more common in the postpartum period in bipolar I disorder and RMD. Most perinatal episodes occurred within the first postpartum month, with mania or psychosis having an earlier onset than depression. CONCLUSIONS Although episodes of postpartum mood disorder are more common in bipolar I disorder and manic and psychotic presentations occur earlier in the postpartum period, perinatal episodes are highly prevalent across the mood disorder spectrum.
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http://dx.doi.org/10.1001/jamapsychiatry.2013.279DOI Listing
February 2013

Variation at the GABAA receptor gene, Rho 1 (GABRR1) associated with susceptibility to bipolar schizoaffective disorder.

Am J Med Genet B Neuropsychiatr Genet 2010 Oct;153B(7):1347-9

Department of Psychological Medicine and Neurology, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.

We have previously reported evidence that variation at GABA(A) receptor genes is associated with susceptibility to bipolar disorder with schizophrenia-like psychotic features (Research Diagnostic Criteria (RDC) schizoaffective disorder, bipolar type) with gene-wide significance at GABRB1, GABRA4, GABRB3, GABRA5, and GABRR3. Here we provide suggestive evidence implicating a sixth member of the gene family, GABRR1 (gene-wide P = 0.0058; experiment-wide corrected significance P = 0.052).
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http://dx.doi.org/10.1002/ajmg.b.31108DOI Listing
October 2010

Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls.

Nature 2010 Apr;464(7289):713-20

Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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http://dx.doi.org/10.1038/nature08979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2892339PMC
April 2010

Cognitive style, personality and vulnerability to postnatal depression.

Br J Psychiatry 2010 Mar;196(3):200-5

Department of Psychiatry, School of Clinical and Experimental Medicine, University of Birmingham, UK.

Background: Only some women with recurrent major depressive disorder experience postnatal episodes. Personality and/or cognitive styles might increase the likelihood of experiencing postnatal depression.

Aims: To establish whether personality and cognitive style predicts vulnerability to postnatal episodes over and above their known relationship to depression in general.

Method: We compared personality and cognitive style in women with recurrent major depressive disorder who had experienced one or more postnatal episodes (postnatal depression (PND) group, n=143) with healthy female controls (control group, n=173). We also examined parous women with recurrent major depressive disorder who experienced no perinatal episodes (non-postnatal depression (NPND) group, n=131).

Results: The PND group had higher levels of neuroticism and dysfunctional beliefs, and lower self-esteem than the control group. However, there were no significant differences between the PND and NPND groups.

Conclusions: Established personality and cognitive vulnerabilities for depression were reported by women with a history of postnatal depression, but there was no evidence that any of these traits or styles confer a specific risk for the postnatal onset of episodes.
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http://dx.doi.org/10.1192/bjp.bp.109.064683DOI Listing
March 2010

Reducing the Hypomania Checklist (HCL-32) to a 16-item version.

J Affect Disord 2010 Aug 2;124(3):351-6. Epub 2010 Feb 2.

Department of Psychological Medicine, School of Medicine, Cardiff University, University Hospital of Wales, Cardiff, CF14 4XN, UK.

Background: The under-recognition of hypomanic symptoms by both clinicians and patients is a major clinical problem which contributes to misdiagnosis and diagnostic delay in patients with bipolar disorder. The recent development of validated screening instruments for hypomania, such as the Hypomania Checklist (HCL-32), may help to improve the detection of bipolar disorder. In this study, we assess whether it is possible to reduce the number of items on the HCL-32 without any loss in the screening tool's ability to reliably differentiate between bipolar disorder (BD) and major depressive disorder (MDD).

Methods: Using our large samples of patients with DSM-IV defined bipolar I disorder (BD-I) (n=230) and recurrent MDD (n=322), we performed item correlations in order to identify potentially redundant items in the HCL-32. We then tested the performance of a shortened 16-item HCL questionnaire within a separate sample of patients with BD (including BD-I, BD-II and BD-NOS) (n=59) and MDD (n=76).

Results: The structure of the 16-item HCL demonstrated two main factors similar to those identified for the HCL-32 (an 'active-elated' factor and a 'risk-taking/irritable' factor). A score of 8 or more on a shortened 16-item version of the HCL had excellent ability to distinguish between BD and MDD. The sensitivity (83%) and specificity (71%) of the 16-item version were very similar to those for the full 32-item HCL.

Limitations: The HCL-16 was derived after subjects had completed the full HCL-32. It will be important to test the validity of a 'stand-alone' 16-item HCL questionnaire.

Conclusions: A shortened 16-item HCL (the HCL-16) is potentially a useful screening tool for hypomania within busy clinical settings.
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http://dx.doi.org/10.1016/j.jad.2010.01.004DOI Listing
August 2010