Bipolar Subtypes Research Articles

Childhood and adolescence outcomes in offspring to parents with bipolar disorder: the impact of lifetime parental comorbidity, parental sex, and bipolar subtype.

Offspring of parents with bipolar disorder have increased risks of their own psychopathology. However, a large-scale survey of psychiatric, somatic, and adverse social outcomes up to adulthood, which could aid in prioritizing and tailoring prevention, is lacking. It also remains to clarify how risks are modified by other parental factors. Swedish population registers were linked to compare offspring having (N = 24,788) and not having (N = 247,880) a parent with bipolar disorder with respect to psychiatric diagnoses and psychotropic medication, birth-related and somatic conditions, social outcomes, accidents, suicide attempts, and mortality. Individuals were followed until age 18. We estimated the influence of lifetime parental psychiatric comorbidity, bipolar disorder subtype, and sex on outcomes. Children of parents with bipolar disorder had 2-3 times higher risks of all psychiatric diagnoses, except for bipolar disorder, for which the risk was 11-fold. Significantly increased risks were also found for several somatic conditions, low school grades, criminal behavior, victimization, accidents, and suicidal behavior. Adjusting for lifetime parental psychiatric comorbidity attenuated most associations. Offspring of a parent with bipolar disorder type 2 had statistically significantly higher risks of attention deficit hyperactivity disorder, respiratory tract conditions, and accidents compared with offspring of a parent with bipolar disorder type 1. Offspring of mothers with bipolar disorder had higher risks of several psychiatric diagnoses, respiratory tract conditions, low school grades, and accidents compared with offspring of fathers with bipolar disorder. Having two parents with bipolar disorder entailed the highest risks of psychiatric outcomes in offspring. Early intervention and family support are particularly warranted for the offspring of a parent with bipolar disorder in the presence of lifetime parental psychiatric comorbidity, when the parent has bipolar disorder type 2, or when the mother or both parents have bipolar disorder.

Genomic SEM applied to explore etiological divergences in bipolar subtypes.

Bipolar disorder (BD) is an overarching diagnostic class defined by the presence of at least one prior manic episode (BD I) or both a prior hypomanic episode and a prior depressive episode (BD II). Traditionally, BD II has been conceptualized as a less severe presentation of BD I, however, extant literature to investigate this claim has been mixed. We apply genomic structural equation modeling (Genomic SEM) to investigate divergent genetic pathways across BD's two major subtypes using the most recent GWAS summary statistics from the PGC. We begin by identifying divergences in genetic correlations across 98 external traits using a Bonferroni-corrected threshold. We also use a theoretically informed follow-up model to examine the extent to which the genetic variance in each subtype is explained by schizophrenia and major depression. Lastly, transcriptome-wide SEM (T-SEM) was used to identify neuronal gene expression patterns associated with BD subtypes. BD II was characterized by significantly larger genetic overlap across non-psychiatric medical and internalizing traits (e.g. heart disease, neuroticism, insomnia), while stronger associations for BD I were absent. Consistent with these findings, follow-up modeling revealed a substantial major depression component for BD II. T-SEM results revealed 35 unique genes associated with shared risk across BD subtypes. Divergent patterns of genetic relationships across external traits provide support for the distinction of the bipolar subtypes. However, our results also challenge the illness severity conceptualization of BD given stronger genetic overlap across BD II and a range of clinically relevant traits and disorders.

The impact of body mass index on the clinical features of bipolar disorder: A STEP-BD study.

The effects of body mass index (BMI) on the core symptoms of bipolar disorder (BD) and its implications for disease trajectory are largely unexplored. To examine whether BMI impacted hospitalization rate, medical and psychiatric comorbidities, and core symptom domains such as depression and suicidality in BD. Participants (15 years and older) were 2790 BD outpatients enrolled in the longitudinal STEP-BD study; all met DSM-IV criteria for BD-I, BD-II, cyclothymia, BD NOS, or schizoaffective disorder, bipolar subtype. BMI, demographic information, psychiatric and medical comorbidities, and other clinical variables such as bipolarity index, history of electroconvulsive therapy (ECT), and history of suicide attempts were collected at baseline. Longitudinal changes in Montgomery-Åsberg Depression Rating Scale (MADRS) score, Young Mania Rating Scale (YMRS) score, and hospitalizations during the study were also assessed. Depending on the variable of interest, odds-ratios, regression analyses, factor analyses, and graph analyses were applied. A robust increase in psychiatric and medical comorbidities was observed, particularly for baseline BMIs >35. A significant relationship was noted between higher BMI and history of suicide attempts, and individuals with BMIs >40 had the highest prevalence of suicide attempts. Obese and overweight individuals had a higher bipolarity index (a questionnaire measuring disease severity) and were more likely to have received ECT. Higher BMIs correlated with worsening trajectory of core depression symptoms and with worsening lassitude and inability to feel. In BD participants, elevated BMI was associated with worsening clinical features, including higher rates of suicidality, comorbidities, and core depression symptoms.

Phase-based concerns of caregivers for individuals with a bipolar disorder.

Caregivers have a key role in providing social and practical support for individuals with bipolar disorder. As such, their perspectives are uniquely important when collaborative decisions are made on management priorities and potential treatment options. This study aims to identify common concerns that caregivers have in the management of an individual with a bipolar disorder. 111 caregivers were recruited from online advertisements and social media support groups. They completed a questionnaire that obtained demographic and clinical feature details, in addition to whether a series of generic and phase-specific (i.e. depressive or hypo/manic) management concerns reflected their experiences of caregiving. Concerns about work capacity and family impacts were almost ubiquitous, as were general feelings of ineffectiveness and irritation. Depressive phases were more likely to elicit fears of suicide by caregivers, while during hypo/manic phases caregivers were more likely to be angered, have concerns for their own safety, call emergency services or to take safety precautions. There were no differences between bipolar subtypes with regards to concerns during depressive phases, but concerns around safety, reputational damage and risky behaviours were more likely in relation to those experiencing bipolar I manic phases compared to bipolar II hypomanic phases. The concerns identified by caregivers in this paper are consistent with clinical expectations, with concerns regarding insularity and externalisation being prominent for depression and hypo/mania respectively. Not all of these caregivers' concerns would necessarily be communicated in a healthcare setting, highlighting the need for an embracive approach to improve management outcomes. Additionally, caregivers' emphasis on their distinctive altruistic concerns highlights their commitment to care despite the challenges, and thus further highlights the potential for clinicians to implement a more proactive role for them in patient care.

Mixed States and Suicidality in Bipolar Disorder: Results from the Stanley Foundation Bipolar Treatment Network

IntroductionMixed states in bipolar disorder (BD) are characterized by the simultaneous occurrence of both manic and depressive features. Growing evidence suggests that they are associated with longer duration of illness, increased relapse risk, and higher prevalence of comorbidities. Suicide risk among BD patients is up to 20–30 times greater than in the general population, although there is not a univocal consensus in whether mixed states should be considered as a high-risk state for suicide.ObjectivesThe objective of this study was to identify whether depressive and hypo/manic episodes with mixed features, are associated with more frequent suicidal behavior or ideation when compared to pure hypo/manic and depressive ones. We hypothesized that suicidal ideation or behavior would be more common in those experiencing mixed symptoms. We subsequently also tested whether gender or bipolar subtype moderated the relation between mood and suicidality.MethodsIn a naturalistic study, 903 adult BD outpatients participating in the Stanley Foundation Bipolar Network were followed longitudinally across 14,213 visits for 7 years. The scores at the Inventory of Depressive Symptomatology–Clinician-Rated Version (IDS-C) and at the Young Mania Rating Scale (YMRS), administered at each visit, were used to define the mood episode. Given partial overlap of items between these scales, analyses were also conducted by removing overlapping items. The presence of suicidality was evaluated through the 18th item of the IDS-C (Suicidal Ideation).ResultsDuring the observation period, up to 60.7% of subjects had at least one visit with suicidal ideation or behavior, broadly defined as a score ≥ 1 at the 18th item of the IDS-C. The distribution of suicidality among visits in different mood states is reported in Figure 1 (N° of visits in which suicidality was detected by mood state at the time of visit). Depressive symptoms were associated with suicidal ideation and behavior either during mixed depression and hypo/mania (p < 0.0001). Hypomanic or manic symptoms appeared to be related to suicidality only during hypo/mania, either pure or mixed (p 0.007). When overlapping items between the two psychometric scales were removed results seemed to confirm these hypotheses. Moreover, male gender appeared to have a protective role against suicidal ideation when hypo/manic (p 0.002).Image:ConclusionsThe primary role of depressive symptoms in predicting suicidal risk was confirmed by our results, which however suggest that mixed symptoms relate to suicidal ideation and behavior more intensely than pure hypo/manic symptoms. More importantly, hypo/manic symptoms did not appear to have a protective role during mixed episodes. Future studies considering also deaths by suicide are required in order to better clarify the role of mixity on suicidality.Disclosure of InterestNone Declared

Association of premorbid intelligence with level of functioning and illness severity in bipolar disorder

BackgroundBipolar disorder is a severe psychiatric syndrome defined by periodic mood shifts. Patients with bipolar disorder show cognitive impairments relative to healthy controls. The risk of developing schizophrenia, and partially also bipolar disorder, has previously been shown to increase with lower premorbid intelligence. It is not known if premorbid intelligence is associated with level of functioning and illness severity of people having developed bipolar disorder. MethodsWe used multiple linear and ordinal regression to analyze how premorbid intelligence, as measured at conscription, associate with functional outcome and illness severity in Swedish male bipolar disorder patients (n = 788). ResultsWe found that lower premorbid intelligence is associated with lower percentage of time in work, after adjusting for age and bipolar subtype, and correcting for multiple comparisons. We also found a strong negative association with the total number of inpatient episodes and psychiatric comorbidity, but not with interepisodic remission, treatment with psychotherapy or lithium or the presence of any complicating socioeconomical factors. Adjusting for confounding genetic factors using polygenic risk scores for bipolar disorder and schizophrenia had no effect on the associations. LimitationsThis study lacks females and controls and may thus have lower generalizability. ConclusionIn conclusion, premorbid intelligence is associated with both level of functioning and illness severity as well as comorbidity in bipolar disorder patients. Further research is needed to develop targeted interventions for this subgroup of bipolar disorder patients.

The AREDOC project and its implications for the definition and measurement of the bipolar disorders: A summary report

Judging that the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria for defining mania/hypomania (and thus bipolar I/II disorders, respectively) would benefit from review, we formed an expert taskforce to derive modified criteria for consideration. The aim of this paper is to summarise the component stages and detail the final recommended criteria. We first sought taskforce members' views on the Diagnostic and Statistical Manual of Mental Disorders criteria and how they might be modified. Next, members recruited patients with a bipolar I or II disorder, and who were asked to judge new definitional options and complete a symptom checklist to determine the most differentiating items. The latter task was also completed by a small comparison group of unipolar depressed patients to determine the mood state items that best differentiate unipolar from bipolar subjects. Subsequent reports overviewed analyses arguing for bipolar I and II as being categorically distinct and generated empirically derived diagnostic criteria. Alternatives to all the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) criteria were generated. Modifications included recognising that impairment is not a necessary criterion, removing hospitalisation as automatically assigning bipolar I status, adding an irritable/angry symptom construct to the symptom list, deleting a mandatory duration period for manic/hypomanic episodes, and requiring a greater number of affirmed symptoms for a bipolar diagnosis to manage the risk of overdiagnosis. Granular symptom criteria were identified by analyses and constructed to assist clinician assessment. A potential bipolar screening measure was developed with analyses showing that it could clearly distinguish bipolar versus unipolar status, whether symptom items were assigned as having equal status or weighted by their quantified diagnostic contribution. While requiring further validation, we suggest that the revised criteria overcome several current Diagnostic and Statistical Manual of Mental Disorders (5th ed.) limitations to defining and differentiating the two bipolar sub-types, while still respecting and preserving the Diagnostic and Statistical Manual of Mental Disorders template. It will be necessary to determine whether the bipolar screening measure has superiority to currently accepted measures.

Are there clinical and sociodemographic differences between bipolar i and ii disorders?

IntroductionBipolar disorder is a serious mental disorder. Although bipolar disorder I (BDI) might seem to have a more complex evolution and severe prognosis than bipolar disorder II (BDII) because of cross-sectional symptom severity, BDII has a high episode frequency, high rates of psychiatric comorbidities and recurrent suicidal behaviours that impair functioning and quality of life.ObjectivesTo explore whether there are differences between patients with BDI and BDII concerning sociodemographic and clinical variables of interest.MethodsA sample of 407 euthymic patients with bipolar disorder (307 BDI and 100 BDII) being age 18 or older was recruited from the Bipolar and Depressive Disorders Unit of the Hospital Clinic of Barcelona. Sociodemographic and clinical variables were collected through the administration of semi-structured interview and clinical scales. Differences between groups in these variables were analysed using the Mann-Whitney U and Chi-square tests, as appropriate. The level of significance was set at p <0.05.ResultsWe found statistically significant differences between both groups. Patients with BD II were older (p<0.001), presented a longer illness duration (p=0,001) and a greater subsyndromal depressive symptomatology (p=0,010). Patients with BDI had a higher number of previous hospitalizations (p<0,001) and higher rates of psychotic symptoms (p<0,001) even during the first episode (p<0,001).ConclusionsOur data suggests that clinical differences exist between both bipolar subtypes. The episodes may be more serious, with a greater presence of a history of psychosis, and require more hospitalizations in BDI patients. In the BDII group, persistent subsyndromal symptoms may predominate, especially of the depressive pole.DisclosureNo significant relationships.

Differences in perceived life stress in bipolar I and II disorder: Implications for future epigenetic quantification

ObjectiveFew instruments measuring life events over the course of bipolar disorder distinguish the valence of events or consider cumulative stress burden. In the current study, we used a valence-focused life event questionnaire to assess stress in the last 12 months in patients with bipolar I (n = 863) and bipolar II (n = 362) disorder. MethodsAssociations between recent stress and lifetime illness severity features were evaluated via linear and logistic regression, adjusting for age and gender. We additionally investigated the feasibility of quantifying recent stress burden by measuring methylation at a known bipolar susceptibility locus, SLC1A2 in a subset of bipolar I patients (n = 150) with or without comorbid substance use. ResultsBipolar II patients endorsed higher total, negative, and positive stress burden than their bipolar I counterparts, but the latter displayed more significant stress-illness severity associations, notably to all forms of substance abuse (e.g., alcohol, nicotine, food, other drugs). Irrespective of bipolar subtype, negative stress burden was significantly associated with illness severity features. High versus low total stress predicted hypomethylation of the SLC1A2 promoter (p < 0.05). ConclusionTogether, these findings reveal substantial differences in how bipolar subtypes experience and perceive stress. The observed degree of association between recent stress and substance abuse in bipolar I lend further support to the multidirectional effects of stress, affective episodes, and substance abuse on illness severity. Quantification of recent total stress using the methylation status of the SLC1A2 promoter is feasible, although a whole-methylome approach will likely prove more effective in disaggregating other environmental influences.

Clinical Phenotype of Tardive Dyskinesia in Bipolar Disorder.

Recognizing the negative impact that antipsychotic-induced movement disorders have on the quality of life and treatment outcomes in bipolar disorder (BD), this study aimed to assess clinical correlates and antipsychotic use patterns of tardive dyskinesia (TD+) in BD. Participants with and without TD were included. Clinical variables were compared using t-test and χ2 test. Antipsychotic use patterns in TD+, including number of trials, mean doses, and estimated cumulative exposure, were assessed in a case-only analysis. The prevalence rate of TD was 5.1%. In comparison to the TD- group (n = 1074), TD+ participants (n = 58) were older, more likely to be female and have type I bipolar illness. There were 60.3% of the TD+ group that continued using antipsychotics at study entry and had a mean cumulative exposure to antipsychotics of 18.2 ± 15.6 years. Average dose, in haloperidol equivalents, was 5.9 ± 3.5 mg and 77.7% of the trials were second-generation antipsychotics. This study confirms previously identified TD risk factors, such as age, sex, and bipolar subtype in a large BD cohort. Limitations included a cross-sectional design and the lack of tardive illness severity assessment. As atypical antipsychotics continue to be primary mood stabilization treatment, attempting to harmonize large data sets to identify additional biomarkers of tardive risk will optimize individualized care for patients with BD.

The dynamic interplay between sleep and mood: an intensive longitudinal study of individuals with bipolar disorder.

Sleep disturbances are important symptoms to monitor in people with bipolar disorder (BD) but the precise longitudinal relationships between sleep and mood remain unclear. We aimed to examine associations between stable and dynamic aspects of sleep and mood in people with BD, and assess individual differences in the strength of these associations. Participants (N = 649) with BD-I (N = 400) and BD-II (N = 249) provided weekly self-reports of insomnia, depression and (hypo)mania symptoms using the True Colours online monitoring tool for 21 months. Dynamic structural equation models were used to examine the interplay between weekly reports of insomnia and mood. The effects of clinical and demographic characteristics on associations were also assessed. Increased variability in insomnia symptoms was associated with increased mood variability. In the sample as a whole, we found strong evidence of bidirectional relationships between insomnia and depressive symptoms but only weak support for bidirectional relationships between insomnia and (hypo)manic symptoms. We found substantial variability between participants in the strength of prospective associations between insomnia and mood, which depended on age, gender, bipolar subtype, and a history of rapid cycling. Our results highlight the importance of monitoring sleep in people with BD. However, researchers and clinicians investigating the association between sleep and mood should consider subgroup differences in this relationship. Advances in digital technology mean that intensive longitudinal data on sleep and mood are becoming increasingly available. Novel methods to analyse these data present an exciting opportunity for furthering our understanding of BD.

Spatiotemporal patterns of neuronal subtype genesis suggest hierarchical development of retinal diversity.

How do neuronal subtypes emerge during development? Recent molecular studies have profiled existing neuronal diversity, but neuronal subtype genesis remains elusive. The 15 types of mouse retinal bipolar interneurons are characterized by distinct functions, morphologies, and transcriptional profiles. Here, we develop a comprehensive spatiotemporal map of bipolar subtype genesis in the murine retina. Combining multiplexed detection of 16 RNA markers with timed delivery of 5-ethynyl uridine (EdU) and bromodeoxyuridine (BrdU), we analyze more than 30,000 single cells in full retinal sections to classify all bipolar subtypes and their birthdates. We find that bipolar subtype birthdates are ordered and follow a centrifugal developmental axis. Spatial analysis reveals a striking wave pattern of bipolar subtype birthdates, and lineage analyses suggest clonal restriction on homotypic subtype production. These results inspire a hierarchical developmental model, with ordered subtype genesis within lineages. Our results provide insight into neuronal subtype development and establish a framework for studying subtype diversification.

Altered dynamic amplitude of low-frequency fluctuation between bipolar type I and type II in the depressive state

BackgroundBipolar disorder is a chronic and highly recurrent mental disorder that can be classified as bipolar type I (BD I) and bipolar type II (BD II). BD II is sometimes taken as a milder form of BD I or even doubted as an independent subtype. However, the fact that symptoms and severity differ in patients with BD I and BD II suggests different pathophysiologies and underlying neurobiological mechanisms. In this study, we aimed to explore the shared and unique functional abnormalities between subtypes. MethodsThe dynamic amplitude of low-frequency fluctuation (dALFF) was performed to compare 31 patients with BD I, 32 with BD II, and 79 healthy controls (HCs). Global dALFF was calculated using sliding-window analysis. Group differences in dALFF among the 3 groups were compared using analysis of covariance (ANCOVA), with covariates of age, sex, years of education, and mean FD, and Bonferroni correction was applied for post hoc analysis. Pearson and Spearman's correlations were conducted between clusters with significant differences and clinical features in the BD I and BD II groups, after which false error rate (FDR) was used for correction. ResultsWe found a significant decrease in dALFF values in BD patients compared with HCs in the following brain regions: the bilateral-side inferior frontal gyrus (including the triangular, orbital, and opercular parts), inferior temporal gyrus, the medial part of the superior frontal gyrus, middle frontal gyrus, anterior cingulum, insula gyrus, lingual gyrus, calcarine gyrus, precuneus gyrus, cuneus gyrus, left-side precentral gyrus, postcentral gyrus, inferior parietal gyrus, superior temporal pole gyrus, middle temporal gyrus, middle occipital gyrus, superior occipital gyrus and right-side fusiform gyrus, parahippocampal gyrus, hippocampus, middle cingulum, orbital part of the medial frontal gyrus and superior frontal gyrus. Unique alterations in BD I were observed in the right-side supramarginal gyrus and postcentral gyrus. In addition, dALFF values in BD II were significantly higher than those in BD I in the right superior temporal gyrus and middle temporal gyrus. The variables of dALFF correlated with clinical characteristics differently according to the subtypes, but no correlations survived after FDR correction. LimitationsOur study was cross-sectional. Most of our patients were on medication, and the sample was limited. ConclusionsOur findings demonstrated neurobiological characteristics of BD subtypes, providing evidence for BD II as an independent existence, which could be the underlying explanation for the specific symptoms and/or severity and point to potential biomarkers for the differential diagnosis of bipolar subtypes.

Development and diversification of bipolar interneurons in the mammalian retina

The bipolar interneurons of the mammalian retina have evolved as a diverse set of cells with distinct subtype characteristics, which reflect specialized contributions to visual circuitry. Fifteen subtypes of bipolar interneurons have been identified in the mouse retina, each with characteristic gene expression, morphology, and light responses. This review provides an overview of the developmental events that underlie the generation of the diverse bipolar cell class, summarizing the current knowledge of genetic programs that establish and maintain bipolar subtype fates, as well as the events that shape the final distribution of bipolar subtypes. With much left to be discovered, bipolar interneurons present an ideal model system for studying the interplay between cell-autonomous and non-cell-autonomous mechanisms that influence neuronal subtype development within the central nervous system.

Handedness in bipolar disorders is associated with specific neurodevelopmental features: results of the BD-FACE cohort.

High rates of non-right-handedness (NRH) and mixed-handedness exist in neurodevelopmental disorders. Dysfunctional neurodevelopmental pathways may be implicated in the underlying pathophysiology of bipolar disorders (BD), at least in some subgroups. Yet little is known about correlates of NRH and mixed-handedness in BD. The objectives of this national study are to determine (i) the prevalence of NRH and mixed-handedness in a well-stabilized sample of BD individuals; (ii) if NRH/mixed-handedness in BD is associated with a different clinical, biological and neurocognitive profile. We included 2174 stabilized individuals. Participants were tested with a comprehensive battery of neuropsychological tests. Handedness was assessed using a single oral question. Learning and/or language disorders and obstetrical complications were recorded using childhood records. Common environmental, clinical and biological parameters were assessed. The prevalence of NRH and mixed-handedness were, respectively, 11.6 and 2.4%. Learning/language disorders were found in 9.7% out of the total sample and were associated with atypical handedness (only dyslexia for mixed-handedness (p < 0.01), and dyslexia and dysphasia for NRH (p = 0.01 and p = 0.04, respectively). In multivariate analyses, NRH was associated with a younger age of BD onset (aOR 0.98 (95% CI 0.96-0.99) and lifetime substance use disorder (aOR 1.40 (95% CI 1.03-1.82) but not with any of the cognitive subtasks. Mixed-handedness was associated in univariate analyses with lifetime substance use disorder, lifetime cannabis use disorder (all p < 0.01) and less mood stabilizer prescription (p = 0.028). No association was found between NRH or mixed-handedness and the following parameters: trauma history, obstetrical complications, prior psychotic symptoms, bipolar subtype, attention deficit/hyperactivity disorder, peripheral inflammation or body mass index. Handedness may be associated with specific features in BD, possibly reflecting a specific subgroup with a neurodevelopmental load.

Is the 4-factor model of symptomology equivalent across bipolar disorder subtypes?

BackgroundResearch with the BDSx (Bipolar Disorder Symptom Scale) suggests a 4-factor structure of responses: two depression (cognitive, somatic) and two hypo/mania factors (elation/loss of insight, affrontive symptoms). The two depression and two hypo/mania factors are correlated; and affrontive symptoms of hypo/mania (e.g., furious, disgusted, argumentative) are positively correlated with both depression factors suggesting pathways for mixed symptom presentation. This grouping of affrontive symptoms of hypo/mania organically emerged in exploratory research and has subsequently been supported in confirmatory analyses between samples and over time. The BDSx has been clinically validated with BD outpatients.ResultsOver 19 days, we recruited an international sample of 784 adults with BD using micro-targeted, social media advertising (M = 44.48 years, range 18–82). All participants indicated that they had BD (subtype, if known) and had been diagnosed with BD (month, year). This sample size was sufficient to confirm the 4-factor model across subtypes and compare the three (BD I, BD II, BD NOS). Responses to 19 of 20 BDSx items were psychometrically consistent across BD subtypes. Only responses to the ‘hopeless’ item were significantly higher for those with BD II.ConclusionsWhen comparing models, it appears that affrontive symptoms are significantly and uniformly associated with hypo/mania and both depression factors across subtypes. In contrast to BD diagnostic criteria, this suggests that affrontive symptoms are central to the clinical presentation of hypo/mania and mixed symptomology across BD subtypes.

Multicentre evaluation of the pharmacological management of women with bipolar disorder in the perinatal period

AimsThe pharmacological management of women with bipolar disorder in the perinatal period is challenging. This population has a high recurrence rate, but some medications can be a concern in pregnancy and breastfeeding. Little is known about prescribing practices in perinatal services, and the impact of medication on recurrence rates.The aims of this study are: 1) to describe the use of medication in women with bipolar disorder in the perinatal period and 2) to evaluate the impact of medication on the rate of postpartum recurrence.MethodClinical data were collected from pregnant women with a diagnosis of bipolar disorder in the nine participating centres in the UK and who were not experiencing an episode of illness entering the postpartum period. Using a proforma, data were collected for the period between conception and three months postpartum: sociodemographic, reproductive, the severity of illness, medication and recurrence.Data were analysed for association using χ2 tests and logistic regression.ResultIn this sample of 167 women, 91 (55%) were taking medication at delivery: 62 (37%) antipsychotics, 41 (25%) antidepressants, and 25 (15%) mood stabilisers. In 12 cases medication was reduced before delivery. Of those who were taking medication at delivery six decreased of stopped after delivery and one increased the dose. 42% of women in this sample experienced a recurrence, with 30% of the sample experiencing a manic/psychotic episode. There was no significant association between taking medication and recurrence χ 2(1) = 0.07, p = 0.79. There continued to be no association in a multivariable analysis when adjusted for parity, severity (previous admissions, age at first treatment, bipolar subtype), type of medication during pregnancy and immediate postpartum changes aOR 0.33 95%CI [0.03; 3.40], p = 0.35.ConclusionA high number of women with bipolar disorder are taking medication before delivery and in the majority, antipsychotics are prescribed. The postnatal recurrence rate in both medicated and unmedicated women is high. These results are in line with existing literature. Further work is needed in larger samples to provide clinical guidance for women and their clinicians.

Regional lithium prescription rates and recurrence in bipolar disorder

BackgroundLithium is the best documented maintenance treatment in bipolar disorder, but its use varies considerably across and within countries. It is not known whether regional differences in lithium prescription rates translate to differing regional outcomes.AimsTo estimate associations between county specific lithium prescription rates and county specific recurrence odds of bipolar disorder in Sweden.MethodData from 14,616 patients with bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified were extracted from the Swedish national quality assurance register for bipolar disorders (BipoläR). Lithium prescription frequencies were calculated for 21 counties. Logistic regression analyses were run adjusted for confounders, with any type of recurrence as primary outcome, and incident elated and depressive episodes as secondary outcomes. Subsets of patients with bipolar I, II and not otherwise specified disorder were also analysed separately.ResultsLithium prescription rates for populations with all bipolar subtypes ranged across counties from 37.7 to 84.9% (mean 52.4%). Higher regional prescription rates were significantly associated with lower rate of any type of recurrence. The association was stronger when bipolar I disorder was analysed separately.ConclusionsThe advantages for lithium use long acknowledged for bipolar I disorder are also seen for the rest of the bipolar spectrum. Results suggest that population level outcomes of bipolar disorder could be improved by increasing the number of patients using lithium.

Multicentre evaluation of perinatal pharmacological management in women with bipolar disorder

IntroductionThe pharmacological management of women with bipolar disorder in the perinatal period is challenging. This population has a high recurrence rate, but some medications can be a concern in pregnancy and breastfeeding. Little is known about prescribing practices in perinatal services, and the impact of medication on recurrence rates.ObjectivesTo describe 1. the use of medication in women with bipolar disorder in the perinatal period and 2. the impact of medication on the rate of recurrence.MethodsClinical data was collected from pregnant women with diagnosis of bipolar disorder in the nine participating centres and who were not experiencing an episode of illness entering the postpartum period. Data were analysed for association using χ2 tests and logistic regression.ResultsIn this sample of 167 women, 55% were taking medication at delivery: 37% antipsychotics, 15% mood stabilisers, 25% antidepressants. In 12 cases medication was reduced before delivery. 42% experienced a recurrence, with 30% being a manic/psychotic episode. There was no significant association between taking medication and recurrence c2(1)=0.72, p=0.79. There continued to be no association when adjusted for severity (previous admissions, age at first treatment, bipolar subtype) and type of medication OR 0.57 95%CI [0.08; 4.29], p=0.59.ConclusionsA high number of bipolar women are taking medication before delivery and in the majority antipsychotics are prescribed. The postnatal recurrence rate in both medicated and unmedicated women is high. Further work is needed in larger samples to provide clinical guidance for women and their clinicians.DisclosureNo significant relationships.

Pharmacological treatment profiles in the FACE-BD cohort: An unsupervised machine learning study, applied to a nationwide bipolar cohort✰

BackgroundDespite thorough and validated clinical guidelines based on bipolar disorders subtypes, large pharmacological treatment heterogeneity remains in these patients. There is limited knowledge about the different treatment combinations used and their influence on patient outcomes. We attempted to determine profiles of patients based on their treatments and to understand the clinical characteristics associated with these treatment profiles. MethodsThis multicentre longitudinal study was performed on a French nationwide bipolar cohort database. We performed hierarchical agglomerative clustering to search for clusters of individuals based on their treatments during the first year following inclusion. We then compared patient clinical characteristics according to these clusters. ResultsFour groups were identified among the 1795 included patients: group 1 (“heterogeneous” n = 1099), group 2 (“lithium” n = 265), group 3 (“valproate” n = 268), and group 4 (“lamotrigine” n = 163). Proportion of bipolar 1 disorder, in groups 1 to 4 were: 48.2%, 57.0%, 48.9% and 32.5%. Groups 1 and 4 had greater functional impact at baseline and a less favorable clinical and functioning evolution at one-year follow-up, especially on GAF and FAST scales. LimitationsThe one-year period used for the analysis of mood stabilizing treatments remains short in the evolution of bipolar disorder. ConclusionsTreatment profiles are associated with functional evolution of patients and were not clearly determined by bipolar subtypes. These profiles seem to group together common patient phenotypes. These findings do not seem to be influenced by the duration of disease prior to inclusion and neither by the number of treatments used during the follow-up period.