Publications by authors named "Katherine Gordon-Smith"

51 Publications

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

Nat Genet 2021 06 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

Migraine associated with early onset postpartum depression in women with major depressive disorder.

Arch Womens Ment Health 2021 Apr 21. Epub 2021 Apr 21.

Psychological Medicine, University of Worcester, Henwick Grove, Worcester, WR2 6AJ, UK.

Major depressive disorder (MDD) and migraine are both more common among women than men. Women's reproductive years are associated with increased susceptibility to recurrence of both conditions, suggesting a potential role of sex hormones in aetiology. We examined associations between comorbid migraine and clinical features of MDD in women, including relationships with lifetime reproductive events such as childbirth. Lifetime clinical characteristics and reproductive events in a well-characterised sample of 222 UK women with recurrent MDD, with (n = 98) and without (n = 124) migraine were compared. Women had all been recruited as part of a UK-based ongoing programme of research into the genetic and non-genetic determinants of mood disorders. Multivariate analysis showed a specific association between the lifetime presence of migraine and postpartum depression (PPD) within 6 weeks of delivery (OR = 2.555; 95% CI: 1.037-6.295, p = 0.041). This association did not extend to a broader definition of PPD with onset up to 6 months postpartum. All other factors included in the analysis were not significantly associated with the presence of migraine: family history of depression, younger age at depression onset, history of suicide attempt and severe premenstrual syndrome symptoms. The finding that women with MDD and comorbid migraine may be particularly sensitive to hormonal changes early in the postpartum period leads to aetiological hypotheses and suggests this group may be useful for future studies attempting to characterise PPD and MDD phenotypes. The refinement of such phenotypes has implications for individualising risk and treatment and for future biological and genetic studies.
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http://dx.doi.org/10.1007/s00737-021-01131-6DOI Listing
April 2021

Phenomenology, Epidemiology and Aetiology of Postpartum Psychosis: A Review.

Brain Sci 2021 Jan 4;11(1). Epub 2021 Jan 4.

National Centre for Mental Health, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff CF24 4HQ, UK.

Postpartum psychoses are a severe form of postnatal mood disorders, affecting 1-2 in every 1000 deliveries. These episodes typically present as acute mania or depression with psychosis within the first few weeks of childbirth, which, as life-threatening psychiatric emergencies, can have a significant adverse impact on the mother, baby and wider family. The nosological status of postpartum psychosis remains contentious; however, evidence indicates most episodes to be manifestations of bipolar disorder and a vulnerability to a puerperal trigger. While childbirth appears to be a potent trigger of severe mood disorders, the precise mechanisms by which postpartum psychosis occurs are poorly understood. This review examines the current evidence with respect to potential aetiology and childbirth-related triggers of postpartum psychosis. Findings to date have implicated neurobiological factors, such as hormones, immunological dysregulation, circadian rhythm disruption and genetics, to be important in the pathogenesis of this disorder. Prediction models, informed by prospective cohort studies of high-risk women, are required to identify those at greatest risk of postpartum psychosis.
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http://dx.doi.org/10.3390/brainsci11010047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824357PMC
January 2021

Have I argued with my family this week?": What questions do those with lived experience choose to monitor their bipolar disorder?

J Affect Disord 2021 02 11;281:918-925. Epub 2020 Nov 11.

Psychological Medicine, University of Worcester, Henwick Grove, Worcester, WR2 6AJ, UK. Electronic address:

Background: Electronic self-report mood monitoring tools for individuals with bipolar disorder (BD) are rapidly emerging and predominately employ predefined symptom-based questions. Allowing individuals to additionally choose what they monitor in relation to their BD offers the unique opportunity to capture and gain a deeper insight into patient priorities in this context.

Methods: In addition to monitoring mood symptoms with two standardised self-rated questionnaires, 308 individuals with BD participating in the Bipolar Disorder Research Network True Colours electronic mood-monitoring tool for research chose to create and complete additional personalised questions. A content analysis approach was used to analyse the content of these questions.

Results: 35 categories were created based on the personalised questions with the most common being physical activity and exercise, anxiety and panic, sleep and coping/stress levels. The categories were grouped into six overarching themes 1) mental health; 2) behaviour and level of functioning; 3) physical wellbeing; 4) health behaviours; 5) active self-management; and, 6) interpersonal.

Limitations: The average age of the sample was around 50 years meaning our findings may not be generalisable to younger individuals with BD.

Conclusions: Aspects of BD important to patients in relation to longitudinal monitoring extend well beyond mood symptoms, highlighting the limitations of solely relying on standardised questions/mood rating scales based on symptoms primarily used for diagnosis. Additional symptoms and aspects of life not necessarily useful diagnostically for BD may be more important for individuals themselves to monitor and have more meaning in capturing their own experience of changes in BD severity.
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http://dx.doi.org/10.1016/j.jad.2020.11.034DOI Listing
February 2021

The influence of borderline personality traits on clinical outcomes in bipolar disorder.

Bipolar Disord 2021 Jun 25;23(4):368-375. Epub 2020 Jul 25.

Psychological Medicine, University of Worcester, Worcester, UK.

Objectives: Systematic reviews suggest comorbid borderline personality disorder is present in approximately 20% of individuals who have bipolar disorder, but current diagnostic systems demonstrate a move towards dimensional rather than categorical approaches to classifying personality pathology. We aimed to examine the presence and severity of borderline personality traits in bipolar I and bipolar II disorder, and to explore associations between the presence/severity of borderline personality traits and clinical outcomes in bipolar disorder.

Methods: Borderline personality traits were measured in 1447 individuals with DSM-IV bipolar disorder (1008 bipolar I disorder and 439 bipolar II disorder) using the Borderline Evaluation of Severity over Time (BEST) questionnaire. Lifetime clinical outcomes were assessed via Schedules for Clinical Assessment in Neuropsychiatry (SCAN) semi-structured interview and clinical case notes.

Results: Borderline personality traits were common in both bipolar disorder groups, with 86.2% participants reporting at least one trait. These included traits that overlap with (eg mood instability) and those that are distinct from the symptoms of bipolar disorder (eg fear of abandonment). Borderline personality traits were significantly more frequent and more severe in bipolar II disorder compared to bipolar I disorder. More severe borderline traits, and even the presence of a single borderline personality trait, were significantly associated with younger age of bipolar disorder onset and higher prevalence of lifetime alcohol misuse in both bipolar disorder groups.

Conclusions: The presence of comorbid borderline personality traits should be considered in the management of all patients with bipolar disorder irrespective of whether criteria for a categorical borderline personality disorder diagnosis are met.
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http://dx.doi.org/10.1111/bdi.12978DOI Listing
June 2021

Patterns and clinical correlates of lifetime alcohol consumption in women and men with bipolar disorder: Findings from the UK Bipolar Disorder Research Network.

Bipolar Disord 2020 11 13;22(7):731-738. Epub 2020 Apr 13.

Psychological Medicine, University of Worcester, Worcester, UK.

Objectives: Despite previous literature on comorbid alcohol use disorders (AUDs) in bipolar disorder (BD), little is known about patterns of alcohol use more widely in this population. We have examined lifetime heaviest average weekly alcohol consumption levels in a large well-characterised UK sample including lifetime clinical correlates of increasing levels of alcohol use.

Methods: Participants were 1203 women and 673 men with bipolar I disorder interviewed by semi-structured interview who had consumed alcohol regularly at any point in their life.

Results: Over half of both women (52.3%) and men (73.6%) had regularly consumed over double the current UK recommended guideline for alcohol consumption. In women and men increasing levels of lifetime alcohol consumption were significantly associated with the presence of suicide attempts (women: OR 1.82, P < .001; men: OR 1.48, P = .005) and rapid cycling (women: OR 1.89, P < .001; men: OR 1.88, P < .001). In women only, increasing levels of alcohol consumption were significantly associated with more episodes of depression (OR 1.35, P < .001) and mania (OR 1.30, P < .004) per illness year, less impairment in functioning during the worst episode of mania (OR 1.02, P < .001), fewer psychiatric admissions (OR 0.51, P < .001), comorbid panic disorder (OR 2.16, P < .001) and eating disorder (OR 2.37, P < .001).

Conclusions: Our results highlight the clinical importance of obtaining detailed information on levels of alcohol consumption among patients with BD. Increased levels of alcohol use, not necessarily reaching criteria for AUD, may be helpful in predicting BD illness course, in particular eating disorders comorbidity in women.
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http://dx.doi.org/10.1111/bdi.12905DOI Listing
November 2020

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

Adverse childhood experiences and postpartum depression in bipolar disorder.

J Affect Disord 2020 02 11;263:661-666. Epub 2019 Nov 11.

Institute of Psychological Medicine & Clinical Neurosciences, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK.

Background: Women are particularly vulnerable to recurrence of bipolar disorder (BD) following childbirth. Risk of postpartum psychosis (PP) is especially high, but postpartum depression (PPD) is also common. Adverse childhood experiences (ACEs) have not been associated with PP, but have been associated with PPD in non-bipolar samples. The relationship between ACEs and PPD within BD remains to be investigated. Here, we examined this association in a large, well-defined sample of women with BD.

Methods: Participants were 575 parous women with DSM-IV BD. Lifetime psychopathology, including perinatal, was assessed via semi-structured interview and case-notes. ACEs, assessed via self-report and case-notes, were compared between women with lifetime PPD (n = 368) and those without a lifetime history of perinatal mood episodes (n = 207).

Results: In univariate analysis exposure to 3 or more ACEs, and to childhood abuse specifically, was significantly associated with PPD (p = 0.026 and 0.041 respectively), but this did not remain significant after adjusting for lifetime number of episodes of depression and parity. Post-hoc analysis revealed more frequent episodes of depression to be associated with both a history of 3 or more ACEs and of childhood abuse.

Limitations: Limited range of ACEs assessed and potential recall bias.

Conclusions: Increased frequency of ACEs and particularly childhood abuse was associated with more frequent lifetime episodes of depression, but not specifically episodes with postpartum onset. Understanding factors that mediate the pathway between ACEs and PPD in BD has implications for risk prediction of PPD.
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http://dx.doi.org/10.1016/j.jad.2019.11.042DOI Listing
February 2020

Explaining why childhood abuse is a risk factor for poorer clinical course in bipolar disorder: a path analysis of 923 people with bipolar I disorder.

Psychol Med 2020 10 18;50(14):2346-2354. Epub 2019 Sep 18.

Psychological Medicine, University of Worcester, Worcester, UK.

Background: Childhood abuse is a risk factor for poorer illness course in bipolar disorder, but the reasons why are unclear. Trait-like features such as affective instability and impulsivity could be part of the explanation. We aimed to examine whether childhood abuse was associated with clinical features of bipolar disorder, and whether associations were mediated by affective instability or impulsivity.

Methods: We analysed data from 923 people with bipolar I disorder recruited by the Bipolar Disorder Research Network. Adjusted associations between childhood abuse, affective instability and impulsivity and eight clinical variables were analysed. A path analysis examined the direct and indirect links between childhood abuse and clinical features with affective instability and impulsivity as mediators.

Results: Affective instability significantly mediated the association between childhood abuse and earlier age of onset [effect estimate (θ)/standard error (SE): 2.49], number of depressive (θ/SE: 2.08) and manic episodes/illness year (θ/SE: 1.32), anxiety disorders (θ/SE: 1.98) and rapid cycling (θ/SE: 2.25). Impulsivity significantly mediated the association between childhood abuse and manic episodes/illness year (θ/SE: 1.79), anxiety disorders (θ/SE: 1.59), rapid cycling (θ/SE: 1.809), suicidal behaviour (θ/SE: 2.12) and substance misuse (θ/SE: 3.09). Measures of path analysis fit indicated an excellent fit to the data.

Conclusions: Affective instability and impulsivity are likely part of the mechanism of why childhood abuse increases risk of poorer clinical course in bipolar disorder, with each showing some selectivity in pathways. They are potential novel targets for intervention to improve outcome in bipolar disorder.
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http://dx.doi.org/10.1017/S0033291719002411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610181PMC
October 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

Agitated depression in bipolar disorder.

Bipolar Disord 2019 09 6;21(6):547-555. Epub 2019 May 6.

Psychological Medicine, University of Worcester, UK.

Objectives: It has been suggested that agitated depression (AD) is a common, severe feature in bipolar disorder. We aimed to estimate the prevalence of AD and investigate whether presence of AD was associated with episodic and lifetime clinical features in a large well-characterized bipolar disorder sample.

Method: The prevalence of agitation, based on semi-structured interview and medical case-notes, in the most severe depressive episode was estimated in 2925 individuals with DSM-IV bipolar disorder recruited into the UK Bipolar Disorder Research Network. Predictors of agitation were ascertained using symptoms within the same episode and lifetime clinical features using multivariate models.

Results: 32.3% (n = 946) experienced agitation during the worst depressive episode. Within the same episode, significant predictors of presence of agitation were: insomnia (OR 2.119, P < 0.001), poor concentration (OR 1.966, P = 0.027), decreased libido (OR 1.960, P < 0.001), suicidal ideation (OR 1.861, P < 0.001), slowed activity (OR 1.504, P = 0.001), and poor appetite (OR 1.297, P = 0.029). Over the lifetime illness course, co-morbid panic disorder (OR 2.000, P < 0.001), suicide attempt (OR 1.399, P = 0.007), and dysphoric mania (OR 1.354, P = 0.017) were significantly associated with AD.

Conclusions: Agitation accompanied bipolar depression in at least one-third of cases in our sample and was associated with concurrent somatic depressive symptoms, which are also common features of mixed manic states. Furthermore, AD in our sample was associated with lifetime experience of mixed mania, in addition to severe lifetime illness course including comorbid panic disorder and suicidal behavior. Our results have implications for the diagnosis and treatment of agitated features in bipolar depression.
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http://dx.doi.org/10.1111/bdi.12778DOI Listing
September 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

Large-scale roll out of electronic longitudinal mood-monitoring for research in affective disorders: Report from the UK bipolar disorder research network.

J Affect Disord 2019 03 25;246:789-793. Epub 2018 Dec 25.

Psychological Medicine, University of Worcester, Henwick Grove, Worcester, WR2 6AJ, UK. Electronic address:

Background: Electronic longitudinal mood monitoring has been shown to be acceptable to patients with affective disorders within clinical settings, but its use in large-scale research has not yet been established.

Methods: Using both postal and email invitations, we invited 4080 past research participants with affective disorders who were recruited into the Bipolar Disorder Research Network (BDRN) over a 10 year period to participate in online weekly mood monitoring. In addition, since January 2015 we have invited all newly recruited BDRN research participants to participate in mood monitoring at the point they were recruited into BDRN.

Results: Online mood monitoring uptake among past participants was 20%, and among new participants to date was 46% with participants recruited over the last year most likely to register (61%). More than 90% mood monitoring participants engaged for at least one month, with mean engagement period greater than one year (58 weeks) and maximum engagement for longer than three years (165 weeks). There were no significant differences in the proportion of past and new BDRN participants providing data for at least 4 weeks (91%, 92% respectively), 3 months (78%, 82%), 6 months (65%, 54%) or one year (51%, 44%).

Limitations: Our experiences with recruiting participants for electronic prospective mood monitoring may not necessarily generalise fully to research situations that are very different from those we describe.

Conclusions: Large-scale electronic longitudinal mood monitoring in affective disorders for research purposes is feasible with uptake highest among newly recruited participants.
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http://dx.doi.org/10.1016/j.jad.2018.12.099DOI Listing
March 2019

Genotype-phenotype correlations in Darier disease: A focus on the neuropsychiatric phenotype.

Am J Med Genet B Neuropsychiatr Genet 2018 12 22;177(8):717-726. Epub 2018 Oct 22.

Department of Psychological Medicine, University of Worcester, Worcester, United Kingdom.

Darier disease (DD) is an autosomal dominant skin disorder caused by mutations in ATP2A2 encoding the sarco/endoplasmic reticulum Ca ATPase Isoform 2 (SERCA2). Evidence of a population-level association between DD and psychiatric disorders suggests that mutations in ATP2A2 may have pleiotropic effects on the brain as well as skin. Evidence of genotype-phenotype relationships between ATP2A2 mutations and neuropsychiatric phenotypes would further support this suggestion. We investigated genotype-phenotype correlations between lifetime neuropsychiatric features and ATP2A2 mutation type (dichotomized into likely gene disrupting [LGD] or protein altering) in 75 unrelated individuals with DD. We also looked for evidence of clustering of mutations within SERCA2 according to neuropsychiatric features. Combining our data with the existing literature, the rate of LGD mutations was found to be significantly higher among DD cases/families with bipolar disorder, schizophrenia, or affective psychosis (p = .011). We also found a significant relationship between mutations located in the S4-M4 region of the protein and the presence of a severe neuropsychiatric phenotype (p = .032). Our findings add support to the hypothesis that Darier-causing mutations in ATP2A2 confer susceptibility to neuropsychiatric dysfunction, in particular severe psychiatric illness. This, together with evidence from research on common polymorphisms confirms ATP2A2 as a gene at which variation influences susceptibility to major psychiatric illness.
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http://dx.doi.org/10.1002/ajmg.b.32679DOI Listing
December 2018

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

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

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
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