Neuropsychiatric phenotype in Darier's Disease

Darier's Disease (DD) is a rare autosomal dominantly inherited skin disorder in which co-occurrence of neuropsychiatric abnormalities has been frequently reported by dermatologists. The disease is caused by mutations in a single gene, ATP2A2, which maps to 12q23-q24.1 and is expressed in the skin and brain. This gene encodes SERCA2 (sarco/endoplasmic reticulum Ca 2+ ATPase isoform 2), a calcium pump involved in intracellular calcium transport. This study aimed to conduct the first systematic investigation of the neuropsychiatric phenotype in DD, investigate possible genotype-phenotype correlations, and compare the neuropsychiatric features in DD individuals and their first-degree unaffected relatives. One hundred unrelated individuals with DD and 24 of their unaffected relatives were assessed using a battery of standardised neuropsychiatric measures. The relationship between the mutations detected in iheATP2A2 gene and the presence/severity of neuropsychiatric phenotypes was examined. DD individuals reported high rates of mood disorders, specifically major depression (30%), suicide attempts (13%) and suicidal thoughts (31%), and these were significantly more common in DD when compared with normative population data. Further, individuals with DD reported higher scores on measures of neuropsychiatric dysfunction than their unaffected relatives. These associations cannot be explained by psychosocial factors. Mutations found among individuals with similar neuropsychiatric phenotypes clustered in certain locations within the SERCA2b protein. Together, these findings support the hypothesis that mutations mATP2A2 confer susceptibility to neuropsychiatric dysfunction, in particular mood disorders, in individuals with DD. These findings highlight the need for assessment and recognition of psychiatric symptoms in DD. The findings may also have implications for identification of other genetic factors involved in conferring susceptibility to neuropsychiatric features in individuals without DD. Further research is needed into other neuropsychiatric phenotypes in DD and into the specific functional effects of mutations in ATP2A2 and the relationship of these to the presence of certain neuropsychiatric phenotypes.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Neuropsychiatric phenotype in Darier's Disease

Darier's Disease (DD) is a rare autosomal dominantly inherited skin disorder in which co-occurrence of neuropsychiatric abnormalities has been frequently reported by dermatologists. The disease is caused by mutations in a single gene, ATP2A2, which maps to 12q23-q24.1 and is expressed in the skin and brain. This gene encodes SERCA2 (sarco/endoplasmic reticulum Ca 2+ ATPase isoform 2), a calcium pump involved in intracellular calcium transport. This study aimed to conduct the first systematic investigation of the neuropsychiatric phenotype in DD, investigate possible genotype-phenotype correlations, and compare the neuropsychiatric features in DD individuals and their first-degree unaffected relatives. One hundred unrelated individuals with DD and 24 of their unaffected relatives were assessed using a battery of standardised neuropsychiatric measures. The relationship between the mutations detected in iheATP2A2 gene and the presence/severity of neuropsychiatric phenotypes was examined. DD individuals reported high rates of mood disorders, specifically major depression (30%), suicide attempts (13%) and suicidal thoughts (31%), and these were significantly more common in DD when compared with normative population data. Further, individuals with DD reported higher scores on measures of neuropsychiatric dysfunction than their unaffected relatives. These associations cannot be explained by psychosocial factors. Mutations found among individuals with similar neuropsychiatric phenotypes clustered in certain locations within the SERCA2b protein. Together, these findings support the hypothesis that mutations mATP2A2 confer susceptibility to neuropsychiatric dysfunction, in particular mood disorders, in individuals with DD. These findings highlight the need for assessment and recognition of psychiatric symptoms in DD. The findings may also have implications for identification of other genetic factors involved in conferring susceptibility to neuropsychiatric features in individuals without DD. Further research is needed into other neuropsychiatric phenotypes in DD and into the specific functional effects of mutations in ATP2A2 and the relationship of these to the presence of certain neuropsychiatric phenotypes.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Neuropsychiatric phenotype in Darier's Disease

Darier's Disease (DD) is a rare autosomal dominantly inherited skin disorder in which co-occurrence of neuropsychiatric abnormalities has been frequently reported by dermatologists. The disease is caused by mutations in a single gene, ATP2A2, which maps to 12q23-q24.1 and is expressed in the skin and brain. This gene encodes SERCA2 (sarco/endoplasmic reticulum Ca 2+ ATPase isoform 2), a calcium pump involved in intracellular calcium transport. This study aimed to conduct the first systematic investigation of the neuropsychiatric phenotype in DD, investigate possible genotype-phenotype correlations, and compare the neuropsychiatric features in DD individuals and their first-degree unaffected relatives. One hundred unrelated individuals with DD and 24 of their unaffected relatives were assessed using a battery of standardised neuropsychiatric measures. The relationship between the mutations detected in iheATP2A2 gene and the presence/severity of neuropsychiatric phenotypes was examined. DD individuals reported high rates of mood disorders, specifically major depression (30%), suicide attempts (13%) and suicidal thoughts (31%), and these were significantly more common in DD when compared with normative population data. Further, individuals with DD reported higher scores on measures of neuropsychiatric dysfunction than their unaffected relatives. These associations cannot be explained by psychosocial factors. Mutations found among individuals with similar neuropsychiatric phenotypes clustered in certain locations within the SERCA2b protein. Together, these findings support the hypothesis that mutations mATP2A2 confer susceptibility to neuropsychiatric dysfunction, in particular mood disorders, in individuals with DD. These findings highlight the need for assessment and recognition of psychiatric symptoms in DD. The findings may also have implications for identification of other genetic factors involved in conferring susceptibility to neuropsychiatric features in individuals without DD. Further research is needed into other neuropsychiatric phenotypes in DD and into the specific functional effects of mutations in ATP2A2 and the relationship of these to the presence of certain neuropsychiatric phenotypes

Large-scale Roll Out of Electronic Longitudinal Mood-Monitoring for Research in Affective Disorders: Report From the UK Bipolar Disorder Research Network

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

Adverse Childhood Life Events and Postpartum Mood Episodes in Bipolar Disorder

Background: The early postpartum has been established as a period of increased vulnerability for psychiatric mood illness. Women with bipolar disorder (BD) in particular are at elevated risk of postnatal depression (PND) and of postpartum psychosis (PP). Though adverse childhood life events (ACLEs) have been implicated in the aetiology of PND, this has rarely been studied in relation to PP. Furthermore, despite being at high risk of relapse following childbirth, little research has assessed the relationship between ACLEs and postnatal mood episodes (PNEs) exclusively in women with BD. Therefore, our aim was to explore associations between ACLEs and occurrence of both PND and PP in a large sample of women with BD. Methods: Participants were 665 parous women with BD who had been recruited into the Bipolar Disorder Research Network study. Diagnoses and lifetime psychopathology were obtained via a semi-structured interview (SCAN). Postnatal psychiatric history and experience of 7 ACLEs were also assessed. Where available, all information obtained at interview was confirmed from psychiatric case notes. Women were classified into three groups according to postnatal psychiatric history: 1) those who had experienced no postnatal mood episode (no PNE, n=224), 2) women with a history of PND (n=223) and 3) women who had experienced PP (n=208). A Pearson’s chi-square test was used to compare the prevalence of each type of ACLE between women in the no PNE group and those with a history of PND or PP. Results: Women with PND were significantly more likely to have experienced emotional, sexual or physical abuse in childhood compared with women who had no history of a PNE (p<0.05). In particular, childhood sexual abuse was reported significantly more in the PND than the no PNE group (P<0.05). In contrast, there were no significant differences in the frequency of reporting of any ACLEs between women who had no PNE and those with PP. Conclusions: Our findings indicate that childhood abuse, sexual abuse in particular, is associated with PND among women with BD. In contrast, we found no evidence for an association between any ACLE and PP, suggesting that biological factors are likely to play a more important role in the aetiology of psychosis in the early postpartum

Agitated Depression in Bipolar Disorder

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‐characterised 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<.001), poor concentration (OR 1.966, p=.027), decreased libido (OR 1.960, p<.001), suicidal ideation (OR 1.861, p<.001), slowed activity (OR 1.504, p=.001), and poor appetite (OR 1.297, p=.029). Over the lifetime illness course, co‐morbid panic disorder (OR 2.000, p<.001), suicide attempt (OR 1.399, p=.007), and dysphoric mania (OR 1.354, p=.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 behaviour. Our results have implications for the diagnosis and treatment of agitated features in bipolar depression

Molecular Genetic Investigation of Bipolar Disorder: Recruitment and Data Collection

Bipolar disorder is a common psychiatric condition with episodes of extreme mood disturbance ranging from mania to depression. We are currently collecting clinically rich data from a large group of individuals with bipolar disorder as part of our ongoing research into the genetic and environmental causes of bipolar disorder. Participants are being recruited to our study with the help of a number of Clinical Studies Officers throughout the UK. Participants are visited in their own homes by a member of our research team. A semi-structured psychiatric interview, Schedules for Clinical Assessment in Neuropsychiatry, is administered and a blood sample collected at the time of interview. Participants are left with a pack of self-rate questionnaires to complete in their own time, which measure psychological aspects of bipolar disorder. We also ask for participants’ consent to gather further information from their case notes to supplement the information provided at interview. Collecting rich clinical data is essential for molecular genetic studies investigating how genetic and environmental factors interact and influence susceptibility to bipolar disorder. We hope the findings of our research will enable a better understanding of the causes of bipolar disorder and will lead to improved treatments in the future

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Stratification of the Risk of Bipolar Disorder Recurrences in Pregnancy and Postpartum

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. Aims To 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 bipola