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Nicholas John Craddock - One of the best experts on this subject based on the ideXlab platform.
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early postpartum symptoms in Puerperal Psychosis
Obstetrical & Gynecological Survey, 2008Co-Authors: Jessica Heron, Robertson E Blackmore, Mary Mcguinness, Nicholas John Craddock, Ian JonesAbstract:Childbirth is frequently an occasion for the onset of psychiatric symptoms, especially in women who are vulnerable to bipolar disorders. Women with Puerperal Psychosis (PP), the most severe form of postnatal psychiatric illness, are more than 20 times likelier to have the onset of a manic or psychotic episode in the first postpartum month than at any other time in their lives. This retrospective interview study enrolled 127 women who developed bipolar affective PP-strictly defined-within 4 weeks after childbirth. Semistructured interviews were based on the Schedule for Clinical Assessment in Neuropsychiatry, or SCAN). Mania, depression, and Psychosis were estimated by a SCAN-trained psychiatrist or psychologist. The mean age at the time of the interview was 40 years, and the median time from the first episode of PP to the interview was 9 years. A single episode of PP was reported by 70% of the women interviewed. Although individuals with a clear onset of episodes during pregnancy were excluded, 10 women (8% of those interviewed) had experienced mild symptoms in the last few days before childbirth or had noted increasingly intense symptoms over the last trimester. In 51 others (40%), symptoms began on the day of delivery. Nearly three-fourths of women had developed symptoms within 3 days after childbirth. Among the most frequently described symptoms reported by 4 or more women within 3 days of childbirth were feeling excited or elated (52%), not needing (or being able to) sleep (48%), feeling active or energetic (37%), and talking more or feeling "chatty" (31%). Other commonly reported early symptoms included confusion, irritability, anxiety, detachment, and lability. Recognition of potential prodromal signs of PP in postnatal women, along with monitoring of mental status in women at risk, might prevent some psychiatric-related deaths. Hypomanic symptoms in the early postpartum period are characteristic of women who go on to develop PP.
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early postpartum symptoms in Puerperal Psychosis
British Journal of Obstetrics and Gynaecology, 2008Co-Authors: Jessica Heron, Robertson E Blackmore, Mary Mcguinness, Nicholas John Craddock, Ian JonesAbstract:Objective: To examine the nature of the earliest reported symptoms in women who develop a bipolar affective Puerperal Psychosis (PP). Design: A retrospective interview study. Setting: Women were recruited for clinical and molecular genetic studies of PP from a national PP network, articles in the national press and referrals from UK specialist perinatal psychiatry services. Sample: One hundred and twenty-seven women met the criteria for an episode of strictly defined bipolar affective PP developing within 4 weeks of childbirth. Methods: Participants were interviewed using the Schedule for clinical assessment in neuropsychiatry and hospital records were reviewed. Lifetime and Puerperal episode diagnoses were made according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) based on all the available information. During interview, participants were asked to describe the earliest symptoms they believed to be related to their illness onset. The day of onset for each symptom was recorded. Main outcome measures: We present subjectively experienced emotional and behavioural changes occurring within 3 days of childbirth, reported by four or more women. Results: Seventy-three percent of women recalled experiencing an onset of symptoms by day 3. The most commonly recalled symptoms were feeling excited, elated or high (52%), not needing to sleep or not able to sleep (48%), feeling active or energetic (37%) and talking more or feeling very chatty (31%). Conclusions Hypomanic symptoms are particularly characteristic of the early postpartum in women who develop PP. These types of symptoms should be carefully monitored in individuals at high risk of PP episodes.
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no latent period in the onset of bipolar affective Puerperal Psychosis
Archives of Womens Mental Health, 2007Co-Authors: J Heron, Robertson E Blackmore, Mary Mcguinness, Nicholas John Craddock, Ian JonesAbstract:The weeks following childbirth are a period of high risk in bipolar women with manic or mixed affective episodes following 20–30% of deliveries. Although the vast majority of episodes have their onset within 2 weeks of delivery it is commonly believed that there is a “latent” or symptom-free period in the first few days after delivery. We examine the day of onset of clinically significant symptoms in 101 bipolar women who have experienced an episode of Puerperal (postpartum) Psychosis. We find no evidence of a latent period. Over 50% of symptom onsets occur on days 1–3, with over 22% occurring on the first postpartum day.
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searching for the Puerperal trigger molecular genetic studies of bipolar affective Puerperal Psychosis
Psychopharmacology Bulletin, 2007Co-Authors: Ian Jones, Nicholas John CraddockAbstract:The available evidence suggests that the puerperium is a period of increased risk for acute episodes of illness in bipolar (BP) women and points to genetic factors as influencing vulnerability to postpartum triggering of such episodes. We have previously reported compelling evidence of familiarity of vulnerability to Puerperal episodes in female sibs with BP disorder and find similar familial clustering for episodes of narrowly defined postpartum episodes in siblings with major depression. Molecular genetic approaches hold out the promise of uncovering the nature of the Puerperal trigger leading to important improvements in the prevention and treatment of postpartum affective episodes. A research strategy focusing on positional and candidate gene approaches may prove fruitful in the search for susceptibility genes for both postpartum triggering in particular and for the affective disorder diathesis in general. We have identified the subset of families in the Wellcome Trust UK-Irish BP sib-pair molecular genetic linkage genome screen that include at least one female who has suffered an episode of Puerperal Psychosis. Analysis of this more homogeneous subgroup of families resulted in a genome-wide significant linkage signal (LOD = 4.07) on chromosome 16p13 and genome wide suggestive linkage on chromosome 8q24. We are undertaking association studies in women with postpartum Psychosis at a number of candidate genes of interest in BP disorder with an emphasis on those for which the expression is influenced by steroid hormones
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obstetric variables associated with bipolar affective Puerperal Psychosis
British Journal of Psychiatry, 2006Co-Authors: Emma Robertson Blackmore, Ian Jones, Ian Brockington, Monica Doshi, Syeed Haque, Roger Holder, Nicholas John CraddockAbstract:Background Previous cross-sectional studies have highlighted a number of obstetric variables that may be associated with the development of broadly defined Puerperal (post-partum) Psychosis. These include: (a) primiparity, (b) pregnancy complications, (c) delivery complications, (d) Caesarean section, (e) female baby and (f) shorter gestation period. Aims To examine these risk factors in women with well-characterised bipolar affective Puerperal Psychosis. Method A sample of 129 women with bipolar affective Puerperal Psychosis were investigated using a design that takes advantage of within-subject comparisons of affected and unaffected deliveries. Results Two of the variables studied were independently associated with an episode of Puerperal Psychosis: primiparity (odds ratio=3.76, P < 0.001) and delivery complications (odds ratio=2.68, P=0.022). Conclusions This study provides further evidence of the association between primiparity and Puerperal Psychosis and suggests that complications during delivery may be associated with a severe post-partum episode.
Ian Jones - One of the best experts on this subject based on the ideXlab platform.
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Puerperal Psychosis identifying and caring for women at risk
Advances in Psychiatric Treatment, 2009Co-Authors: Ian Jones, Sue SmithAbstract:Puerperal (postpartum) Psychosis – the acute onset of a manic or psychotic episode shortly after childbirth – most commonly occurs in women with a bipolar disorder diathesis who have a vulnerability to a specific childbirth-related trigger. Women with bipolar disorder are at particularly high risk of Puerperal Psychosis, with a severe affective episode following between 25 and 50% of deliveries. Suicide is a leading cause of maternal death in the UK and it is clear that we must do more to identify and better manage women at high risk of illness related to childbirth. The clinical picture of Puerperal Psychosis can vary dramatically from hour to hour and can escalate quickly to a true psychiatric emergency. It is vital that clinical services identify women who are unwell and can respond quickly to the severity of illness, delivering treatment in the most appropriate setting for the mother and her baby.
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early postpartum symptoms in Puerperal Psychosis
Obstetrical & Gynecological Survey, 2008Co-Authors: Jessica Heron, Robertson E Blackmore, Mary Mcguinness, Nicholas John Craddock, Ian JonesAbstract:Childbirth is frequently an occasion for the onset of psychiatric symptoms, especially in women who are vulnerable to bipolar disorders. Women with Puerperal Psychosis (PP), the most severe form of postnatal psychiatric illness, are more than 20 times likelier to have the onset of a manic or psychotic episode in the first postpartum month than at any other time in their lives. This retrospective interview study enrolled 127 women who developed bipolar affective PP-strictly defined-within 4 weeks after childbirth. Semistructured interviews were based on the Schedule for Clinical Assessment in Neuropsychiatry, or SCAN). Mania, depression, and Psychosis were estimated by a SCAN-trained psychiatrist or psychologist. The mean age at the time of the interview was 40 years, and the median time from the first episode of PP to the interview was 9 years. A single episode of PP was reported by 70% of the women interviewed. Although individuals with a clear onset of episodes during pregnancy were excluded, 10 women (8% of those interviewed) had experienced mild symptoms in the last few days before childbirth or had noted increasingly intense symptoms over the last trimester. In 51 others (40%), symptoms began on the day of delivery. Nearly three-fourths of women had developed symptoms within 3 days after childbirth. Among the most frequently described symptoms reported by 4 or more women within 3 days of childbirth were feeling excited or elated (52%), not needing (or being able to) sleep (48%), feeling active or energetic (37%), and talking more or feeling "chatty" (31%). Other commonly reported early symptoms included confusion, irritability, anxiety, detachment, and lability. Recognition of potential prodromal signs of PP in postnatal women, along with monitoring of mental status in women at risk, might prevent some psychiatric-related deaths. Hypomanic symptoms in the early postpartum period are characteristic of women who go on to develop PP.
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early postpartum symptoms in Puerperal Psychosis
British Journal of Obstetrics and Gynaecology, 2008Co-Authors: Jessica Heron, Robertson E Blackmore, Mary Mcguinness, Nicholas John Craddock, Ian JonesAbstract:Objective: To examine the nature of the earliest reported symptoms in women who develop a bipolar affective Puerperal Psychosis (PP). Design: A retrospective interview study. Setting: Women were recruited for clinical and molecular genetic studies of PP from a national PP network, articles in the national press and referrals from UK specialist perinatal psychiatry services. Sample: One hundred and twenty-seven women met the criteria for an episode of strictly defined bipolar affective PP developing within 4 weeks of childbirth. Methods: Participants were interviewed using the Schedule for clinical assessment in neuropsychiatry and hospital records were reviewed. Lifetime and Puerperal episode diagnoses were made according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) based on all the available information. During interview, participants were asked to describe the earliest symptoms they believed to be related to their illness onset. The day of onset for each symptom was recorded. Main outcome measures: We present subjectively experienced emotional and behavioural changes occurring within 3 days of childbirth, reported by four or more women. Results: Seventy-three percent of women recalled experiencing an onset of symptoms by day 3. The most commonly recalled symptoms were feeling excited, elated or high (52%), not needing to sleep or not able to sleep (48%), feeling active or energetic (37%) and talking more or feeling very chatty (31%). Conclusions Hypomanic symptoms are particularly characteristic of the early postpartum in women who develop PP. These types of symptoms should be carefully monitored in individuals at high risk of PP episodes.
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bipolar affective Puerperal Psychosis genome wide significant evidence for linkage to chromosome 16
American Journal of Psychiatry, 2007Co-Authors: Ian Jones, J Heron, Marian L Hamshere, Jeannemarrie Nangle, P Bennett, Elaine K Green, Ricardo Segurado, David Lambert, Peter Holmans, Aiden CorvinAbstract:Objective: Vulnerability to the triggering of bipolar episodes by childbirth aggregates in families and may define a genetically relevant subtype of bipolar disorder. The authors conducted a search by systematic whole genome linkage scan for loci influencing vulnerability to bipolar affective Puerperal Psychosis. Method: The authors selected families with bipolar disorder from their previous bipolar disorder genome scan, in which there was at least one family member with a manic or psychotic episode with an onset within 6 weeks of delivery. Individuals were coded as affected if they had been diagnosed with bipolar I disorder; bipolar II disorder; or schizoaffective disorder, bipolar type, according to DSM-IV. A total of 36 pedigrees contributed 54 affected sibling pairs to the cohort. A genome scan with 494 microsatellite markers was analyzed using GENEHUNTER and MAPMAKER/SIBS. Results: A genome-wide significant linkage signal was observed on chromosome 16p13, and a genome-wide suggestive linkage was obse...
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no latent period in the onset of bipolar affective Puerperal Psychosis
Archives of Womens Mental Health, 2007Co-Authors: J Heron, Robertson E Blackmore, Mary Mcguinness, Nicholas John Craddock, Ian JonesAbstract:The weeks following childbirth are a period of high risk in bipolar women with manic or mixed affective episodes following 20–30% of deliveries. Although the vast majority of episodes have their onset within 2 weeks of delivery it is commonly believed that there is a “latent” or symptom-free period in the first few days after delivery. We examine the day of onset of clinically significant symptoms in 101 bipolar women who have experienced an episode of Puerperal (postpartum) Psychosis. We find no evidence of a latent period. Over 50% of symptom onsets occur on days 1–3, with over 22% occurring on the first postpartum day.
William Davies - One of the best experts on this subject based on the ideXlab platform.
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an analysis of cellular communication network factor proteins as candidate mediators of postpartum Psychosis risk
Frontiers in Psychiatry, 2019Co-Authors: William DaviesAbstract:Postpartum (or Puerperal) Psychosis (PP) is a severe psychiatric condition associated with hallucinations, delusions, cognitive disorganisation and mood problems, which affects approximately 1-2 out of every 1000 new mothers shortly after childbirth. Whilst the risk factors for, and co-morbidities of, PP are relatively well-defined, currently the pathophysiology underlying the disorder is very poorly-specified. Here, I argue, on the basis of multiple lines of new evidence, that altered expression of the Cellular Communication Network (CCN) factor proteins (and of the heterodimerising CCN2 and CCN3 proteins in particular), may be associated with, and possibly causal for, increased PP risk. Future preclinical and clinical studies should aim to test this hypothesis as empirical support for it would provide much-needed clues regarding the biological substrates of PP, and could point to predictive biomarkers for the condition.
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do defective immune system mediated myelination processes increase postpartum Psychosis risk
Trends in Molecular Medicine, 2018Co-Authors: Paola Dazzan, Montserrat Fuste, William DaviesAbstract:Postpartum (or Puerperal) Psychosis (PP) is a rare, severe psychiatric disorder that affects women shortly after childbirth; risk is particularly high in individuals with a history of bipolar disorder or PP, but the underlying pathophysiology remains poorly understood. Emerging evidence suggests that immune system (dys)function plays an important role in disorder onset. On the basis of new findings from clinical and animal model studies, we hypothesise that the abundance and/or activity of regulatory T cells, and the efficacy of consequent (re)myelination processes in the brain mediated by CCN proteins, is perturbed in PP; this pathway may be modulated by risk and protective/treatment factors for the disorder, and identifying abnormalities within it could signpost novel predictive biomarkers and therapeutic targets.
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does steroid sulfatase deficiency influence postpartum Psychosis risk
Trends in Molecular Medicine, 2012Co-Authors: William DaviesAbstract:Postpartum (or Puerperal) Psychosis (PP) occurs shortly after childbirth in 0.1–0.2% of women, and is characterised by delusions, mood swings, confused thinking, and disorganised behaviour. The condition is disturbing for patients and their family members and loved ones, and affected individuals may be at increased risk of harming themselves or their offspring. The features of PP indicate a substantial biological basis to its pathogenesis, although currently little is known about possible risk factors. Based on recent results from animal model and human studies, I propose that reduced function of the enzyme steroid sulfatase in the mother represents a unifying and physiologically plausible candidate mechanism for the neural and endocrinological disturbances seen in cases of PP.
Ian Brockington - One of the best experts on this subject based on the ideXlab platform.
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non reproductive triggers of postpartum Psychosis
Archives of Womens Mental Health, 2017Co-Authors: Ian BrockingtonAbstract:Bipolar disorders, and other psychoses, are known to be triggered by a number of agents apart from the reproductive process. In some women, pregnant or recently delivered, Psychosis may be due to these alternative triggers. There are substantial numbers of mothers suffering from childbearing psychoses, who have been prescribed bromocriptine or steroids, have had surgical operations or developed thyrotoxicosis. It is best to eliminate these episodes and cases from study samples of Puerperal Psychosis.
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obstetric variables associated with bipolar affective Puerperal Psychosis
British Journal of Psychiatry, 2006Co-Authors: Emma Robertson Blackmore, Ian Jones, Ian Brockington, Monica Doshi, Syeed Haque, Roger Holder, Nicholas John CraddockAbstract:Background Previous cross-sectional studies have highlighted a number of obstetric variables that may be associated with the development of broadly defined Puerperal (post-partum) Psychosis. These include: (a) primiparity, (b) pregnancy complications, (c) delivery complications, (d) Caesarean section, (e) female baby and (f) shorter gestation period. Aims To examine these risk factors in women with well-characterised bipolar affective Puerperal Psychosis. Method A sample of 129 women with bipolar affective Puerperal Psychosis were investigated using a design that takes advantage of within-subject comparisons of affected and unaffected deliveries. Results Two of the variables studied were independently associated with an episode of Puerperal Psychosis: primiparity (odds ratio=3.76, P < 0.001) and delivery complications (odds ratio=2.68, P=0.022). Conclusions This study provides further evidence of the association between primiparity and Puerperal Psychosis and suggests that complications during delivery may be associated with a severe post-partum episode.
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molecular genetic approaches to Puerperal Psychosis
Progress in Brain Research, 2001Co-Authors: Ian Jones, Ian Brockington, Emma J Robertson, Corinne Lendon, Natasha Coyle, Nicholas John CraddockAbstract:Puerperal Psychosis, an episode of mania or Psychosis precipitated by childbirth follows approximately one in 1000 deliveries. The evidence of clinical, outcome and genetic studies supports the hypothesis that the majority of Puerperal psychotic episodes are manifestations of an affective disorder diathesis with a Puerperal trigger. Furthermore the available evidence supports the hypothesis that genes are involved in susceptibility to both diathesis and trigger. For complex genetic disorders such as affective illness there are marked benefits in focussing on a homogeneous subtype which allows a subset of hypotheses to be tested. Molecular genetic studies of Puerperal Psychosis provide an excellent example of this strategy, allowing a hierarchy of hypotheses concerning the involvement of neurosteroid pathways in pathophysiology to be tested. Puerperal Psychosis results in considerable suffering to a woman and her family. Elucidating the pathophysiological basis of this disorder will lead to better prevention and treatment and, it is anticipated, inform research on affective disorders more generally.
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molecular genetic studies of bipolar disorder and Puerperal Psychosis at two polymorphisms in the estrogen receptor alpha gene esr 1
American Journal of Medical Genetics, 2000Co-Authors: Ian Jones, Ian Brockington, Emma J Robertson, Corinne Lendon, Natasha Coyle, F Middle, F Mccandless, Nicholas John CraddockAbstract:A number of lines of evidence point to the possible involvement of estrogen pathways in the pathophysiology of bipolar disorder in general and Puerperal Psychosis in particular. There is strong evidence from clinical, follow-up, and genetic studies to support the hypothesis that most cases of Puerperal Psychosis are manifestations of an affective disorder diathesis with a Puerperal trigger and that genes influence susceptibility to both diathesis and trigger. The nature of the trigger is unknown but in view of the abrupt onset at a time of major physiological change it is widely believed that biological, probably hormonal, mechanisms are of paramount importance, with estrogen receiving the most attention to date. We have undertaken a case control association study of bipolar disorder and Puerperal Psychosis at two known polymorphisms within the estrogen receptor alpha gene (ESR 1) in a sample of 219 unrelated bipolar probands and 219 controls. We could exclude these polymorphisms from an important contribution to susceptibility to bipolar disorder with a high level of confidence. We found no support for the hypothesis that they contribute specific susceptibility to the Puerperal trigger, but due to the small numbers of Puerperal probands (n = 26) no firm conclusions can be drawn regarding their involvement in Puerperal Psychosis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:850-853, 2000
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approaches to the ascertainment recruitment and clinical assessment of women with Puerperal Psychosis
Archives of Womens Mental Health, 2000Co-Authors: Emma J Robertson, Ian Jones, Ian Brockington, J Benjamin, C Murdoch, G Pelios, Nicholas John CraddockAbstract:Puerperal Psychosis is the most severe and rare form of postnatal psychiatric disorder. Researchers in Birmingham are currently involved in a wide range of studies into the disorder, which necessitates the recruitment of subjects who have suffered from this relatively uncommon illness, as well as conducting a comprehensive clinical assessment of the phenotype. This paper describes the approaches we have developed for sample ascertainment and the methodology for recruitment and clinical assessment used in research studies of Puerperal Psychosis. These include the establishment of a national panel of women who have suffered from the illness (Action on Puerperal Psychosis) and the use of the media as well as systematic routes of ascertainment. Clinical evaluation includes collection of key social, obstetric, and demographic data, together with life-time assessment of mania, depression and psychotic symptomatology by modified SCAN interview and review of case notes. We believe that the methods employed will be useful to other researchers investigating Puerperal Psychosis, as well as other psychiatric disorders.
Emma J Robertson - One of the best experts on this subject based on the ideXlab platform.
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living with Puerperal Psychosis a qualitative analysis
Psychology and Psychotherapy-theory Research and Practice, 2003Co-Authors: Emma J Robertson, Antonia C LyonsAbstract:Objectives: To explore women's experiences of the relatively uncommon postnatal illness of Puerperal Psychosis, and to gain understanding into living through and past the illness. Design: An interview-based study using grounded theory principles to analyse the qualitative data. Methods: Interviews were conducted with 10 women who had been diagnosed and treated for Puerperal Psychosis (defined according to DSM-IV criteria, with onset within six weeks of childbirth) during the last 10 years. Results: Three main categories were identified from the interviews: Puerperal Psychosis as a separate form of mental illness, loss, and relationships and social rules. Further, two higher order concepts were identified, termed ‘living with emotions’ and ‘regaining and changing sel’. These concepts emerged across, and linked, the categories previously identified. Conclusions: Women felt that the illness took away the ability to experience normal emotions, as affective responses were viewed as potentially pathogenic. Although Puerperal Psychosis was described as a life-changing experience, the women used feeling like their ‘old sense of self’ as a marker for recovery. Anger and frustration were directed towards health services because of their lack of provision of adequate information and support for the women and their families. More support may have alleviated the stresses placed on relationships and informed families about the nature of the illness. Further work is needed to establish the long-term effects of suffering from Puerperal Psychosis.
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no association between two polymorphisms at the 5ht2a gene and bipolar affective Puerperal Psychosis
Acta Psychiatrica Scandinavica, 2003Co-Authors: Emma J Robertson, Ian Jones, F Middle, J Moray, Nicholas John CraddockAbstract:Objective: To examine whether variation at two common polymorphisms, T102C and −1438AG, of the serotonin 2A gene (5HT2A) are involved in the Puerperal triggering mechanism of bipolar affective Puerperal Psychosis. Method: A total of 242 parous women diagnosed with bipolar disorder were genotyped for the two polymorphisms. Of these, 165 women had experienced a manic or psychotic episode, according to DSM-IV criteria, within 6 weeks of childbirth (the Puerperal Psychosis group). The comparison group comprised of 77 parous women who had not experienced psychiatric disturbance following childbirth. Results: No significant differences between genotype or allelic frequencies were found between the two groups for either polymorphism. Conclusion: The results indicate that variation at two common polymorphisms of the 5HT2A gene does not appear to play a major role in the development of bipolar affective Puerperal Psychosis.
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variation in the coding sequence and flanking splice junctions of the estrogen receptor alpha erα gene does not play an important role in genetic susceptibility to bipolar disorder or bipolar affective Puerperal Psychosis
American Journal of Medical Genetics, 2003Co-Authors: F Middle, Nicholas John Craddock, Ian Jones, Emma J Robertson, Corinne Lendon, Jaime MoreyAbstract:Genes involved in estrogen pathways have been proposed as possible candidates influencing susceptibility to bipolar disorder and the affective symptoms suffered by many women during the Puerperal period. The estrogen receptor alpha (ERalpha) gene in particular has been a subject of interest and has recently been intensively screened for variations of potential relevance to psychiatric disorders, resulting in the identification of four mutations in individuals with bipolar disorder or Puerperal Psychosis. We have examined the frequency of these four ERalpha variations in a case control study using a group of mixed gender bipolar individuals (N = 231), further classified into subsets of parous bipolar females with (N = 112) and without (N = 50) Puerperal Psychosis, and a non-psychiatric comparison group (N = 110). We have also investigated the families in which the variations were initially detected, for evidence of co-segregation of the variants with mood disorder. We found no evidence in our case control sample to support the involvement of any of the ERalpha variations in either the aetiology of bipolar disorder or Puerperal triggering of bipolar episodes. Nor did we find co-segregation of ERalpha variants and disease in any of the four families examined. We conclude that variation in the coding sequence and flanking splice junctions of the ERalpha gene does not play an important pathogenic role in the majority of cases of Bipolar Disorder or Bipolar Affective Puerperal Psychosis.
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molecular genetic approaches to Puerperal Psychosis
Progress in Brain Research, 2001Co-Authors: Ian Jones, Ian Brockington, Emma J Robertson, Corinne Lendon, Natasha Coyle, Nicholas John CraddockAbstract:Puerperal Psychosis, an episode of mania or Psychosis precipitated by childbirth follows approximately one in 1000 deliveries. The evidence of clinical, outcome and genetic studies supports the hypothesis that the majority of Puerperal psychotic episodes are manifestations of an affective disorder diathesis with a Puerperal trigger. Furthermore the available evidence supports the hypothesis that genes are involved in susceptibility to both diathesis and trigger. For complex genetic disorders such as affective illness there are marked benefits in focussing on a homogeneous subtype which allows a subset of hypotheses to be tested. Molecular genetic studies of Puerperal Psychosis provide an excellent example of this strategy, allowing a hierarchy of hypotheses concerning the involvement of neurosteroid pathways in pathophysiology to be tested. Puerperal Psychosis results in considerable suffering to a woman and her family. Elucidating the pathophysiological basis of this disorder will lead to better prevention and treatment and, it is anticipated, inform research on affective disorders more generally.
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molecular genetic studies of bipolar disorder and Puerperal Psychosis at two polymorphisms in the estrogen receptor alpha gene esr 1
American Journal of Medical Genetics, 2000Co-Authors: Ian Jones, Ian Brockington, Emma J Robertson, Corinne Lendon, Natasha Coyle, F Middle, F Mccandless, Nicholas John CraddockAbstract:A number of lines of evidence point to the possible involvement of estrogen pathways in the pathophysiology of bipolar disorder in general and Puerperal Psychosis in particular. There is strong evidence from clinical, follow-up, and genetic studies to support the hypothesis that most cases of Puerperal Psychosis are manifestations of an affective disorder diathesis with a Puerperal trigger and that genes influence susceptibility to both diathesis and trigger. The nature of the trigger is unknown but in view of the abrupt onset at a time of major physiological change it is widely believed that biological, probably hormonal, mechanisms are of paramount importance, with estrogen receiving the most attention to date. We have undertaken a case control association study of bipolar disorder and Puerperal Psychosis at two known polymorphisms within the estrogen receptor alpha gene (ESR 1) in a sample of 219 unrelated bipolar probands and 219 controls. We could exclude these polymorphisms from an important contribution to susceptibility to bipolar disorder with a high level of confidence. We found no support for the hypothesis that they contribute specific susceptibility to the Puerperal trigger, but due to the small numbers of Puerperal probands (n = 26) no firm conclusions can be drawn regarding their involvement in Puerperal Psychosis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:850-853, 2000
