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Women with bipolar disorder have a high recurrence rate in the perinatal period. However, the use of prophylactic medication can be a concern during pregnancy and breastfeeding. There are few studies looking at the impact of prophylactic medication on the risk of recurrence.The aims of this study are to describe the use of medication in women with bipolar disorder in the perinatal period and the impact of that prophylactic medication on the rate of postnatal recurrence.
The BDRN (Bipolar Disorder Research Network Study) is the largest individual network of individuals with bipolar disorder and related mood disorders in the world. The BDRN pregnancy study is a prospective observational study which took place in the UK. We collected sociodemographic, clinical and medication data from pregnant women with a diagnosis of bipolar disorder and who were euthymic entering the postpartum period. The clinical data were collected via interviews during pregnancy and the postpartum and access to clinical records where those were available.
Data were analysed for association using χ2 tests and logistic regression.
Our total sample for this analysis comprised of 103 women who met the criteria.
We found that 71 (70%) were taking medication at delivery: 43 (43%) antipsychotics, 9 (9%) antidepressants, 10 (10%) mood stabilisers, (6 lithium, 4 anticonvulsants and 9 multiple medication classes).
Of the total sample, 44 (43%) experienced a postpartum recurrence: 21 (20%) had an episode of postpartum psychosis, 15 (15%) of non-psychotic depression and 8 (8%) of hypomania. Of the postpartum psychotic episodes 11 were of mania with psychosis, 8 of mania without psychosis and 2 of psychotic depression.
There was no significant association between taking medication at delivery and postpartum recurrence χ2 (1)=0.116, p=0.73.
In a multivariable analysis there continued to be no association when adjusted for age, ethnicity, parity, severity (previous admissions, age at impairment, bipolar subtype) and previous psychotic symptoms aOR 1.35 95%CI [0.45; 4.00], p=0.59.
A high number of bipolar women are taking medication at delivery and in the majority, antipsychotics are prescribed. The postnatal recurrence rate in both medicated and unmedicated women is high.
Our findings align with recent electronic health records and observational studies, but differ from older clinical cohort and higher Lithium-prescribing sample studies. Limitations include the study design and confounding by indication. Further research in larger populations is necessary to inform clinical decision-making for women and their healthcare providers.
Bipolar disorder is a chronic and severe mental health disorder. Early stratification of individuals into subgroups based on age at onset (AAO) has the potential to inform diagnosis and early intervention. Yet, the psychosocial predictors associated with AAO are unknown.
We aim to identify psychosocial factors associated with bipolar disorder AAO.
Using data from the Bipolar Disorder Research Network UK, we employed least absolute shrinkage and selection operator regression to identify psychosocial factors associated with bipolar disorder AAO. Twenty-eight factors were entered into our model, with AAO as our outcome measure.
We included 1022 participants with bipolar disorder (μ = 23.0, s.d. ± 9.86) in our model. Six variables predicted an earlier AAO: childhood abuse (β = −0.2855), regular cannabis use in the year before onset (β = −0.2765), death of a close family friend or relative in the 6 months before onset (β = −0.2435), family history of suicide (β = −0.1385), schizotypal personality traits (β = −0.1055) and irritable temperament (β = −0.0685). Five predicted a later AAO: the average number of alcohol units consumed per week in the year before onset (β = 0.1385); birth of a child in the 6 months before onset (β = 0.2755); death of parent, partner, child or sibling in the 6 months before onset (β = 0.3125); seeking work without success for 1 month or more in the 6 months before onset (β = 0.3505) and a major financial crisis in the 6 months before onset (β = 0.4575).
The identified predictor variables have the potential to help stratify high-risk individuals into likely AAO groups, to inform treatment provision and early intervention.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
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.
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.
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.
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.
Pregnancy and childbirth are a period of high risk for women with bipolar disorder and involve difficult decisions particularly about continuing or stopping medications.
To explore what clinical predictors may help to individualise the risk of perinatal recurrence in women with bipolar disorder.
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.
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.
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.
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) = 143, 95% CI 1.17–1.75, P<0.001) and BD-I subtype (OR=2.81, 95% CI 2.26–3.50, P<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.
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.
To determine the prevalence and distribution of problem gambling in
people with bipolar disorder in the UK.
The Problem Gambling Severity Index was used to measure gambling problems
in 635 participants with bipolar disorder.
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).
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
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.
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.
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.
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.
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
Individuals with a mental health disorder appear to be at increased risk of medical illness.
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.
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.
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.
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.
Increasing the conditionality of welfare benefits is a growing trend in many developed countries, particularly in relation to some groups who may be perceived as undeserving of state support. Problem drug users (PDUs) are one such group, and in the UK most PDUs do not work and a high proportion claim benefits. Facilitating the movement of these individuals into employment is a policy aim, because it is believed to improve the circumstances of drug users (and promote future abstinence) and because moving all groups off benefits and into work is a primary purpose of recent welfare reforms. Yet little is known about the interactions of PDUs with the UK benefits system or how recent moves to increase the conditionality of benefits are likely to affect this vulnerable group. This paper begins to address this gap by exploring the perceptions that PDUs and relevant frontline staff have of drug users’ interactions with the welfare system and the factors affecting their prospects for employment. The findings suggest some aspects of recent welfare reforms, notably the simplification of benefits, may help PDUs interact with the system. However, the data also reinforce claims that the increased use of sanctions is unlikely to succeed in improving employment rates amongst this group without intensive support and demand-side interventions.
Only some women with recurrent major depressive disorder experience
postnatal episodes. Personality and/or cognitive styles might increase
the likelihood of experiencing postnatal depression.
To establish whether personality and cognitive style predicts
vulnerability to postnatal episodes over and above their known
relationship to depression in general.
We compared personality and cognitive style in women with recurrent major
depressive disorder who had experienced one or more postnatal episodes
(postnatal depression (PND) group, n=143) with healthy
female controls (control group, n=173). We also examined
parous women with recurrent major depressive disorder who experienced no
perinatal episodes (non-postnatal depression (NPND) group,
The PND group had higher levels of neuroticism and dysfunctional beliefs,
and lower self-esteem than the control group. However, there were no
significant differences between the PND and NPND groups.
Established personality and cognitive vulnerabilities for depression were
reported by women with a history of postnatal depression, but there was
no evidence that any of these traits or styles confer a specific risk for
the postnatal onset of episodes.
It is commonly – but wrongly – assumed that there are no important
differences between the clinical presentations of major depressive disorder
and bipolar depression. Here we compare clinical course variables and
depressive symptom profiles in a large sample of individuals with major
depressive disorder (n=593) and bipolar disorder
(n=443). Clinical characteristics associated with a
bipolar course included the presence of psychosis, diurnal mood variation
and hypersomnia during depressive episodes, and a greater number of shorter
depressive episodes. Such features should alert a clinician to a possible
bipolar course. This is important because optimal management is not the same
for bipolar and unipolar depression.
Bulk samples of six Ln2TiO5 compounds with Ln = La, Pr, Nd, Eu, Gd and Tb were prepared and characterised. Most of the samples have a phase purity of ∼95% (based on BEI and EDS) with the predominant secondary phase primarily being Ln2Ti2O7. Using XRD, TEM selected area diffraction and high resolution imaging techniques, we have confirmed the results of previous studies which showed that at room temperature Pr2TiO5, Nd2TiO5, Eu2TiO5 and Tb2TiO5 have orthorhombic structures with Pnma symmetry. The structure of Tb2TiO5 was further monitored as a function of temperature. The relevance of Ln2TiO5 compounds to advanced nuclear fuel cycles is discussed.
Abnormalities of cognitive style in bipolar disorder are of both clinical and theoretical importance.
To compare cognitive style in people with affective disorders and in healthy controls.
Self-rated questionnaires were administered to 118 individuals with bipolar I disorder, 265 with unipolar major recurrent depression and 268 healthy controls. Those with affective disorder were also interviewed using the Schedules for Clinical Assessment in Neuropsychiatry and case notes were reviewed.
Those with bipolar disorder and those with unipolar depression demonstrated different patterns of cognitive style from controls; negative self-esteem best discriminated between those with affective disorders and controls; measures of cognitive style were substantially affected by current levels of depressive symptomatology; patterns of cognitive style were similar in bipolar and unipolar disorder when current mental state was taken into account.
Those with affective disorder significantly differed from controls on measures of cognitive style but there were no differences between unipolar and bipolar disorders when current mental state was taken into account.
Synroc containing 20 wt% simulated high level waste (HLW) was subjected to
two sets of leach tests at 150°C where the leachant was and was not replaced
during the test (replacement and non-replacement testing). The leachant was
a KH-phthalate buffered solution (pH 4.2). Samples were characterised before
and after leach testing using SEM, AEM and SIMS. Elemental concentrations in
leachates were measured using ICP-MS. In concert with the findings of i) a
dissolution study of perovskite in a flowing leachant and ii) a previous
Synroc dissolution study (wherein Synroc containing 10 wt% simulated HLW was
subjected to periodic replacement, leach testing in deionised water at
150°C), the results of this study show that when the leachant replacement
frequency is varied from 7 d to the duration of the test, there is no effect
on leach rate or leaching mechanisms.
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