[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: The nosology of postpartum depression (PPD) is controversial. We review the evidence and arguments for and against the recognition of PPD as a distinct disorder and discuss the etiopathogenic and diagnostic validity of PPD as a distinct disorder, including its utility and indications for further research. Although multiple epidemiological and clinical studies have found that depression is more common following childbirth than at other times in a woman's life, there is conflicting evidence for the validity of PPD as a distinct disorder. PPD is likely to be a complex phenotype, encompassing several disorders with different disease pathways. It is plausible that for a sub-group of vulnerable women, childbirth triggers episodes of depression. However, even within this group, the mechanisms underpinning the mood disturbances are likely complex and heterogeneous. The distinction between depression occurring in the perinatal period and depression at other times is important for both research and clinical practice. Research should differentiate between episodes that begin during pregnancy and postpartum, as the pathogenetic factors involved may differ and require specialized treatment.
Current Psychiatry Reports 10/2015; 17(10):617. DOI:10.1007/s11920-015-0617-6 · 3.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives:
To compare rates of bipolar episodes following miscarriage and termination with those occurring in the postpartum period.
Information in relation to pregnancy and childbirth was gathered retrospectively for 1,283 women with broadly defined bipolar disorder by interview and case-notes review.
Rates of mania or affective psychosis were significantly higher after full-term delivery than after termination (p < 0.001) or miscarriage (p < 0.001). Rates of non-psychotic major depression were similar following full-term deliveries, miscarriages (p = 0.362), and terminations (p = 0.301).
While women with bipolar disorder and their clinicians should be aware of the possible onset of depression in the weeks following miscarriage or termination, episodes of mania or affective psychosis are less common in comparison with the high rates observed in the postpartum period.
[Show abstract][Hide abstract] ABSTRACT: Background
Episodes of postpartum psychosis have been associated with first pregnancies in women with bipolar I disorder. It is unclear, however, if the effect extends to episodes at other times in relation to childbirth and to women with other mood disorders such as major depression and bipolar II disorder. This primiparity effect, which is also seen in other pregnancy related conditions such as pre-eclampsia, is a potentially important clue to the aetiology of childbirth related mood episodes.
Participants were interviewed and case notes reviewed. Best-estimate diagnoses were made according to DSM-IV criteria. Data on the occurrence of episodes in pregnancy and the postpartum were available on 3345 full term deliveries from 1667 participants, 934 with bipolar I disorder (BD-I), 278 with bipolar II disorder (BD-II) and 455 with recurrent major depression (RMD).
Onsets of psychosis/mania within 6 weeks of childbirth were overrepresented in primiparae (p=0.007) with BD-I. Although primiparity was not associated with perinatal bipolar depression, there was an association with the onset of depression within 6 weeks in women with RMD (p=0.035). Whilst women experiencing a postpartum episode were less likely to go on to have further children, this did not account for the association with primiparity.
Data were collected retrospectively. Information on pharmacological treatment was not available.
Primiparity is associated not only with postpartum psychosis/mania in BD-I, but also with postpartum depression in RMD. Psychosocial factors and biological differences between first and subsequent pregnancies may play a role and are candidates for examination in further studies.
Journal of Affective Disorders 01/2014; s 152–154(100):334–339. DOI:10.1016/j.jad.2013.09.034 · 3.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the comorbidity rates of alcohol use disorders (AUDs) in bipolar disorder (BD) and to explore possible sources of heterogeneity.
Studies were identified through database searches. Meta-analytic techniques were employed to aggregate data on lifetime comorbidity and to explore possible sources of heterogeneity. Funnel plots were used to detect publication bias.
In clinical studies, AUDs affected more than one in three subjects with BD. Significant heterogeneity was found, which was largely explained by the geographical location of study populations and gender ratio of participants. AUDs affected more than one in five women and two in five men.
AUDs are highly prevalent in BD. Our study revealed a substantial heterogeneity across studies. Further research including control groups is needed. Patients with BD should be assessed for current and previous AUDs.
European Psychiatry 09/2013; 29(3). DOI:10.1016/j.eurpsy.2013.07.004 · 3.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Key contentPostpartum psychosis is a severe mental illness with a dramatic onset shortly after childbirth.All women should be screened antenatally for the known risk factors.Women with bipolar disorder have at least a 1 in 4 risk and need close contact and review during the perinatal period even if they are well.Prompt recognition of the illness and rapid institution of treatment are of vital importance. Learning objectivesTo recognise women at high risk for severe postpartum mental illness.To recognise and appreciate the severity of postpartum psychosis and the need for prompt assessment and treatment. Ethical issuesWho should ultimately make decisions about taking medications in pregnancy – the clinician or the woman and her family?What advice should a woman at high risk of postpartum psychosis be given if she is considering pregnancy?
The Obstetrician & Gynaecologist 07/2013; 15(3). DOI:10.1111/tog.12041
[Show abstract][Hide abstract] ABSTRACT: CONTEXT Affective disorders are common in women, with many episodes having an onset in pregnancy or during the postpartum period. OBJECTIVE To investigate the occurrence and timing of perinatal mood episodes in women with bipolar I disorder, bipolar II disorder, and recurrent major depression (RMD). SETTING AND PATIENTS Women were recruited in our ongoing research on the genetic and nongenetic determinants of major affective disorders. Participants were interviewed and case notes were reviewed. Best-estimate diagnoses were made according to DSM-IV criteria. The 1785 parous women identified included 1212 women with bipolar disorder (980 with type I and 232 with type II) and 573 with RMD. Data were available on 3017 live births. MAIN OUTCOME MEASURES We report the lifetime occurrence of perinatal mood episodes, the rates of perinatal episodes per pregnancy/postpartum period, and the timing of the onset of episodes in relation to delivery. RESULTS More than two-thirds of all diagnostic groups reported at least 1 lifetime episode of illness during pregnancy or the postpartum period. Women with bipolar I disorder reported an approximately 50% risk of a perinatal major affective episode per pregnancy/postpartum period. Risks were lower in women with RMD or bipolar II disorder, at approximately 40% per pregnancy/postpartum period. Mood episodes were significantly more common in the postpartum period in bipolar I disorder and RMD. Most perinatal episodes occurred within the first postpartum month, with mania or psychosis having an earlier onset than depression. CONCLUSIONS Although episodes of postpartum mood disorder are more common in bipolar I disorder and manic and psychotic presentations occur earlier in the postpartum period, perinatal episodes are highly prevalent across the mood disorder spectrum.
Archives of general psychiatry 12/2012; 70(2):1-8. DOI:10.1001/jamapsychiatry.2013.279 · 14.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Psychoeducational approaches are promising interventions for the long-term management of bipolar disorder. In consultation with professionals, patients, and their families we have developed a novel web-based psychoeducational intervention for bipolar disorder called Beating Bipolar. We undertook a preliminary exploratory randomized trial to examine efficacy, feasibility and acceptability.
This was an exploratory randomized controlled trial of Beating Bipolar (current controlled trials registration number: ISRCTN81375447). The control arm was treatment-as-usual and the a priori primary outcome measure was quality of life [measured by the brief World Health Organization Quality of Life (WHOQOL-BREF) scale]. Secondary outcomes included psychosocial functioning, insight, depressive and manic symptoms and relapse, and use of healthcare resources. Fifty participants were randomized to either the Beating Bipolar intervention plus treatment-as-usual or just treatment-as-usual. The intervention was delivered over a four-month period and outcomes were assessed six months later.
There was no significant difference between the intervention and control groups on the primary outcome measure (total WHOQOL-BREF score) but there was a modest improvement within the psychological subsection of the WHOQOL-BREF for the intervention group relative to the control group. There were no significant differences between the groups on any of the secondary outcome measures.
Beating Bipolar is potentially a safe and engaging intervention which can be delivered remotely to large numbers of patients with bipolar disorder at relatively low cost. It may have a modest effect on psychological quality of life. Further work is required to establish the impact of this intervention on insight, knowledge, treatment adherence, self-efficacy and self-management skills.
[Show abstract][Hide abstract] ABSTRACT: There is currently a great deal of interest in the use of affective temperaments as possible intermediate phenotypes for bipolar disorder. However, much of the literature in this area is conflicting. Our aims were to test the hypothesis of a gradient in affective temperament scores, as measured by the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A), from bipolar disorder type I (BP-I), through bipolar disorder type II (BP-II), recurrent major depressive disorder (MDD-R), and a control group (CG) in the largest sample to date of 927 subjects.
Non parametric tests were used to compare TEMPS-A scores between diagnostic groups and multinomial logistic regression was used to test the association between TEMPS-A scores and diagnosis while controlling for current mood state, age and gender.
Although the BP-II group scored higher than the BP-I and MDD-R groups on several TEMPS-A subscales, these differences were not significant when confounding variables were controlled for. The dysthymic subscale differentiated between affected and controls and the anxious subscale differentiated the MDD-R group from controls.
The cross-sectional design did not allow us to evaluate potential longitudinal changes of temperament scores, which were assessed only with a self-report questionnaire.
We failed to find evidence of a gradient in affective temperament scores. Both unipolar and bipolar patients reported high dysthymic scores relative to controls, perhaps supporting a unitary view of depression across the bipolar-unipolar spectrum. Taking account of potential confounders will be important in future studies which seek to use affective temperaments as intermediate phenotypes in genetic research.