Epilepsy in Bipolar Disorder: Impact on Clinical Features, Course and Outcome

Background and Aims: It is well recognized that mood disorders and epilepsy commonly co-occur. However, the relationship between epilepsy and the clinical features and course of illness in bipolar disorder (BD) is currently unknown. Here we explore the rate of epilepsy within a large sample of individuals with BD and examine bipolar illness characteristics according to the presence or absence of epilepsy. Methods: 1596 participants recruited to the Bipolar Disorder Research Network; a well-defined sample of UK subjects with a diagnosis of BD, completed a self-report questionnaire to assess lifetime history of epilepsy (Ottman et al., 2010). A subset of participants (n = 29) completed a telephone interview assessment to determine expert-confirmed epilepsy status. Lifetime clinical characteristics of illness were compared between BD subjects with and without a history of epilepsy. Results: 127 individuals (8%) screened positively for lifetime history of epilepsy. Bipolar subjects with epilepsy experienced higher rates of: suicide attempt (64.2% vs. 47.4%, p = 0.000367); panic disorder (29.6% vs. 16.1%, p = 0.001); phobias (13.6% vs. 5.7%, 0.004); alcohol abuse (18.6% vs. 10.6%, p = 0.017); and other substance abuse (10.2% vs. 4%, p = 0.009). History of suicide attempt (OR = 1.79, p = 0.013) remained significant within a multivariate model. Similar trends were observed within bipolar subjects with well-defined, expert-confirmed epilepsy (n = 29). Conclusions: Results demonstrate an increased rate of self-reported epilepsy in the BD sample, compared to the general population, and suggest differences in the clinical course of BD according to the presence of epilepsy. Comorbid epilepsy within BD may provide an attractive opportunity for subcategorising for future genetic studies, potentially identifying common underlying mechanisms.

History of Premenstrual Mood Change and Postpartum Episodes are Associated with Perimenopausal Episodes in Women with Bipolar Disorder

Background and Aims: Reproductive life events are potential triggers of mood episodes in women with bipolar disorder. We aimed to establish whether a history of premenstrual mood change and postpartum episodes are associated with perimenopausal episodes in women who have bipolar disorder. Methods: Participants were 339 post-menopausal women with DSM-IV bipolar disorder recruited into the Bipolar Disorder Research Network (www.bdrn.org). Women self-reported presence (N = 200) or absence (N = 139) of an illness episode during the perimenopausal period. History of premenstrual mood change was measured using the self-report Premenstrual Symptoms Screening Tool (PSST), and history of postpartum episodes was measured via semi-structured interview (Schedules for Clinical Assessment in Neuropsychiatry, SCAN) and inspection of case-notes. Results: History of a postpartum episode within 6 months of delivery (OR = 2.13, p = 0.03) and history of moderate/severe premenstrual syndrome (OR = 6.33, p < 0.001) were significant predictors of the presence of a perimenopausal episode, even after controlling for demographic factors. When we narrowed the definition of premenstrual mood change to premenstrual dysphoric disorder, it remained significant (OR = 2.68, p = 0.007). Conclusions: Some women who have bipolar disorder may be particularly sensitive to reproductive life events. Previous mood episodes in relation to the female reproductive lifecycle may help clinicians predict individual risk for women with bipolar disorder approaching the menopause. There is a need for prospective longitudinal studies of women with bipolar disorder providing frequent contemporaneous ratings of their mood to overcome the limitations of retrospective self-report data.

Autistic and Schizotypal Traits and Global Functioning in Bipolar Disorder

Background and Aims To determine the expression of autistic and positive schizotypal traits in a large sample of adults with bipolar disorder (BD), and the effect of co-occurring autistic and positive schizotypal traits on global functioning in BD. Methods Autistic and positive schizotypal traits were assessed in 797 individuals with BD recruited by the Bipolar Disorder Research Network (BDRN), using the Autism-Spectrum Quotient and Kings Schizotypy Questionnaire (KSQ), respectively. Differences in global functioning (rated using the Global Assessment Scale) during lifetime worst depressive and manic episodes (GASD and GASM respectively) were calculated in groups with high/low autistic and positive schizotypal traits. Regression analyses assessed the interactive effect of autistic and positive schizotypal traits on global functioning. Results 47.2% (CI = 43.7–50.7%) showed clinically significant levels of autistic traits. Mean of sample on the KSQ-Positive scale was 11.98 (95% CI: 11.33–12.62). In the worst episode of mania, the high autistic, high positive schizotypal group had better global functioning than the low autistic, low positive schizotypal group (mean difference = 3.72, p = 0.004). High levels of co-occurring traits were associated with better global functioning in both mood states in individuals with a history of psychosis (GASM: p < 0.001; GASD: p = 0.055). Conclusions Expression of autistic and schizotypal traits in adults with BD is prevalent, and may be important to predict course of illness, prognosis, and in devising individualised therapies. Future work should focus on replicating these findings in independent samples, and on the biological and/or psychosocial mechanisms underlying better global functioning in those who have high levels of both autistic and positive schizotypal traits.

Seasonality Shows Evidence for Polygenic Architecture and Genetic Correlation With Schizophrenia and Bipolar Disorder

OBJECTIVE: To test common genetic variants for association with seasonality (seasonal changes in mood and behavior) and to investigate whether there are shared genetic risk factors between psychiatric disorders and seasonality. METHOD: Genome-wide association studies (GWASs) were conducted in Australian (between 1988 and 1990 and between 2010 and 2013) and Amish (between May 2010 and December 2011) samples in whom the Seasonal Pattern Assessment Questionnaire (SPAQ) had been administered, and the results were meta-analyzed in a total sample of 4,156 individuals. Genetic risk scores based on results from prior large GWAS studies of bipolar disorder, major depressive disorder (MDD), and schizophrenia were calculated to test for overlap in risk between psychiatric disorders and seasonality. RESULTS: The most significant association was with rs11825064 (P = 1.7 × 10⁻⁶, β = 0.64, standard error = 0.13), an intergenic single nucleotide polymorphism (SNP) found on chromosome 11. The evidence for overlap in risk factors was strongest for schizophrenia and seasonality, with the schizophrenia genetic profile scores explaining 3% of the variance in log-transformed global seasonality scores. Bipolar disorder genetic profile scores were also associated with seasonality, although at much weaker levels (minimum P value = 3.4 × 10⁻³), and no evidence for overlap in risk was detected between MDD and seasonality. CONCLUSIONS: Common SNPs of large effect most likely do not exist for seasonality in the populations examined. As expected, there were overlapping genetic risk factors for bipolar disorder (but not MDD) with seasonality. Unexpectedly, the risk for schizophrenia and seasonality had the largest overlap, an unprecedented finding that requires replication in other populations and has potential clinical implications considering overlapping cognitive deficits in seasonal affective disorders and schizophrenia.

Mind games : applying White’s principles of narrative therapy to the creation of a cabaret about depression and bipolar disorder

This PhD represents my attempt to make sense of my personal experiences of depression through the form of cabaret. I first experienced depression in 2006. Previously, I had considered myself to be a happy and optimistic person. I found the experience of depression to be a shock: both in the experience itself, and also in the way it effected my own self image. These personal experiences, together with my professional history as a songwriter and cabaret performer, have been the motivating force behind the research project. This study has explored the question: What are the implications of applying principles of Michael White’s narrative therapy to the creation of a cabaret performance about depression and bipolar disorder? There is a 50 percent weighting on the creative work, the cabaret performance Mind Games, and a 50 percent weighting on the written exegesis. This research has focussed on the illustration of therapeutic principles in order to play games of truth within a cabaret performance. The research project investigates ways of telling my own story in relation to others’ stories through three re-authoring principles articulated in Michael White’s narrative therapy: externalisation, an autonomous ethic of living and rich descriptions. The personal stories presented in the cabaret were drawn from my own experiences and from interviews with individuals with depression or bipolar disorder. The cabaret focussed on the illustration of therapeutic principles, and was not focussed on therapeutic ends for myself or the interviewees. The research question has been approached through a methodology combining autoethnographic, practice-led and action research. Auto ethnographic research is characterised by close investigation of assumptions, attitudes, and beliefs. The combination of autoethnographic, practice-led, action research has allowed me to bring together personal experiences of mental illness, research into therapeutic techniques, social attitudes and public discourses about mental illness and forms of contemporary cabaret to facilitate the creation of a one-woman cabaret performance. The exegesis begins with a discussion of games of truth as informed by Michel Foucault and Michael White and self-stigma as informed by Michael White and Erving Goffman. These concepts form the basis for a discussion of my own personal experiences. White’s narrative therapy is focused on individuals re-authoring their stories, or telling their stories in different ways. White’s principles are influenced by Foucault’s notions of truth and power. Foucault’s term games of truth has been used to describe the effect of a ‘truth in flux’ that occurs through White’s re-authoring process. This study argues that cabaret is an appropriate form to represent this therapeutic process because it favours heightened performativity over realism, and showcases its ‘constructedness’ and artificiality. Thus cabaret is well suited to playing games of truth. A contextual review compares two major cabaret trends, personal cabaret and provocative cabaret, in reference to the performer’s relationship with the audience in terms of distance and intimacy. The study draws a parallel between principles of distance and intimacy in Michael White’s narrative therapy and relates these to performative terms of distance and intimacy. The creative component of this study, the cabaret Mind Games, used principles of narrative therapy to present the character ‘Jo’ playing games of truth through: externalising an aspect of her personality (externalisation); exploring different life values (an autonomous ethic of living); and enacting multiple versions of her identity (rich descriptions). This constant shifting between distance and intimacy within the cabaret created the effect of a truth in ‘constant flux’, to use one of White’s terms. There are three inter-related findings in the study. The first finding is that the application of principles of White’s narrative therapy was able to successfully combine provocative and empathetic elements within the cabaret. The second finding is that the personal agenda of addressing my own self-stigma within the project limited the effective portrayal of a ‘truth in flux’ within the cabaret. The third finding presents the view that the cabaret expressed ‘Jo’ playing games of truth in order to journey towards her own "preferred identity claim" (White 2004b) through an act of "self care" (Foucault 2005). The contribution to knowledge of this research project is the application of therapeutic principles to the creation of a cabaret performance. This process has focussed on creating a self-revelatory cabaret that questions notions of a ‘fixed truth’ through combining elements of existing cabaret forms in new ways. Two major forms in contemporary cabaret, the personal cabaret and the provocative cabaret use the performer-audience relationship in distinctive ways. Through combining elements of these two cabaret forms, I have explored ways to create a provocative cabaret focussed on the act of self-revelation.

Health states for schizophrenia and bipolar disorder within the Global Burden of Disease 2010 Study

A comprehensive revision of the Global Burden of Disease (GBD) study is expected to be completed in 2012. This study utilizes a broad range of improved methods for assessing burden, including closer attention to empirically derived estimates of disability. The aim of this paper is to describe how GBD health states were derived for schizophrenia and bipolar disorder. These will be used in deriving health state-specific disability estimates. A literature review was first conducted to settle on a parsimonious set of health states for schizophrenia and bipolar disorder. A second review was conducted to investigate the proportion of schizophrenia and bipolar disorder cases experiencing these health states. These were pooled using a quality-effects model to estimate the overall proportion of cases in each state. The two schizophrenia health states were acute (predominantly positive symptoms) and residual (predominantly negative symptoms). The three bipolar disorder health states were depressive, manic, and residual. Based on estimates from six studies, 63% (38%-82%) of schizophrenia cases were in an acute state and 37% (18%-62%) were in a residual state. Another six studies were identified from which 23% (10%-39%) of bipolar disorder cases were in a manic state, 27% (11%-47%) were in a depressive state, and 50% (30%-70%) were in a residual state. This literature review revealed salient gaps in the literature that need to be addressed in future research. The pooled estimates are indicative only and more data are required to generate more definitive estimates. That said, rather than deriving burden estimates that fail to capture the changes in disability within schizophrenia and bipolar disorder, the derived proportions and their wide uncertainty intervals will be used in deriving disability estimates.

Defining a developmental subtype of bipolar disorder in a sample of nonreferred adults by age at onset

Objective To test the hypothesis that the age at onset of bipolar disorder would identify a developmental subtype of bipolar disorder in adults characterized by increased levels of irritability, chronic course, rapid cycling, and comorbidity with attention deficit hyperactivity disorder. Methods Forty-four adult subjects diagnosed with bipolar disorder were selected from large family studies of youth with and without attention deficit hyperactivity disorder. These subjects were stratified by the age at onset in childhood (younger than 13 years; n = 8, 18%), adolescence (13–18 years; n = 12, 27%, or adulthood (older than 19 years; n = 24, 55%). All subjects were administered structure diagnostic interviews and a brief cognitive battery. Results In contrast with adult-onset bipolar disorder, child-onset bipolar disorder was associated with a longer duration of illness, more irritability than euphoria, a mixed presentation, a more chronic or rapid-cycling course, and increased comorbidity with childhood disruptive behavior disorders and anxiety disorders. Conclusion Stratification by age at onset of bipolar disorder identified subgroups of adult subjects with differing clinical correlates. This pattern of correlates is consistent with findings documented in children with pediatric bipolar disorder and supports the hypothesis that child-onset bipolar disorder may represent a developmental subtype of the disorder.

The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data

The relationship between major depressive disorder (MDD) and bipolar disorder (BD) remains controversial. Previous research has reported differences and similarities in risk factors for MDD and BD, such as predisposing personality traits. For example, high neuroticism is related to both disorders, whereas openness to experience is specific for BD. This study examined the genetic association between personality and MDD and BD by applying polygenic scores for neuroticism, extraversion, openness to experience, agreeableness and conscientiousness to both disorders. Polygenic scores reflect the weighted sum of multiple single-nucleotide polymorphism alleles associated with the trait for an individual and were based on a meta-analysis of genome-wide association studies for personality traits including 13,835 subjects. Polygenic scores were tested for MDD in the combined Genetic Association Information Network (GAIN-MDD) and MDD2000+ samples (N=8921) and for BD in the combined Systematic Treatment Enhancement Program for Bipolar Disorder and Wellcome Trust Case-Control Consortium samples (N=6329) using logistic regression analyses. At the phenotypic level, personality dimensions were associated with MDD and BD. Polygenic neuroticism scores were significantly positively associated with MDD, whereas polygenic extraversion scores were significantly positively associated with BD. The explained variance of MDD and BD, approximately 0.1%, was highly comparable to the variance explained by the polygenic personality scores in the corresponding personality traits themselves (between 0.1 and 0.4%). This indicates that the proportions of variance explained in mood disorders are at the upper limit of what could have been expected. This study suggests shared genetic risk factors for neuroticism and MDD on the one hand and for extraversion and BD on the other.

Functional and work disability and treatment received by patients with major depressive disorder

This study is one part of a collaborative depression research project, the Vantaa Depression Study (VDS), involving the Department of Mental and Alcohol Research of the National Public Health Institute, Helsinki, and the Department of Psychiatry of the Peijas Medical Care District (PMCD), Vantaa, Finland. The VDS includes two parts, a record-based study consisting of 803 patients, and a prospective, naturalistic cohort study of 269 patients. Both studies include secondary-level care psychiatric out- and inpatients with a new episode of major depressive disorder (MDD). Data for the record-based part of the study came from a computerised patient database incorporating all outpatient visits as well as treatment periods at the inpatient unit. We included all patients aged 20 to 59 years old who had been assigned a clinical diagnosis of depressive episode or recurrent depressive disorder according to the International Classification of Diseases, 10th edition (ICD-10) criteria and who had at least one outpatient visit or day as an inpatient in the PMCD during the study period January 1, 1996, to December 31, 1996. All those with an earlier diagnosis of schizophrenia, other non-affective psychosis, or bipolar disorder were excluded. Patients treated in the somatic departments of Peijas Hospital and those who had consulted but not received treatment from the psychiatric consultation services were excluded. The study sample comprised 290 male and 513 female patients. All their psychiatric records were reviewed and each patient completed a structured form with 57 items. The treatment provided was reviewed up to the end of the depression episode or to the end of 1997. Most (84%) of the patients received antidepressants, including a minority (11%) on treatment with clearly subtherapeutic low doses. During the treatment period the depressed patients investigated averaged only a few visits to psychiatrists (median two visits), but more to other health professionals (median seven). One-fifth of both genders were inpatients, with a mean of nearly two inpatient treatment periods during the overall treatment period investigated. The median length of a hospital stay was 2 weeks. Use of antidepressants was quite conservative: The first antidepressant had been switched to another compound in only about one-fifth (22%) of patients, and only two patients had received up to five antidepressant trials. Only 7% of those prescribed any antidepressant received two antidepressants simultaneously. None of the patients was prescribed any other augmentation medication. Refusing antidepressant treatment was the most common explanation for receiving no antidepressants. During the treatment period, 19% of those not already receiving a disability pension were granted one due to psychiatric illness. These patients were nearly nine years older than those not pensioned. They were also more severely ill, made significantly more visits to professionals and received significantly more concomitant medications (hypnotics, anxiolytics, and neuroleptics) than did those receiving no pension. In the prospective part of the VDS, 806 adult patients were screened (aged 20-59 years) in the PMCD for a possible new episode of DSM-IV MDD. Of these, 542 patients were interviewed face-to-face with the WHO Schedules for Clinical Assessment in Neuropsychiatry (SCAN), Version 2.0. Exclusion criteria were the same as in the record-based part of the VDS. Of these, 542 269 patients fulfiled the criteria of DSM-IV MDE. This study investigated factors associated with patients' functional disability, social adjustment, and work disability (being on sick-leave or being granted a disability pension). In the beginning of the treatment the most important single factor associated with overall social and functional disability was found to be severity of depression, but older age and personality disorders also significantly contributed. Total duration and severity of depression, phobic disorders, alcoholism, and personality disorders all independently contributed to poor social adjustment. Of those who were employed, almost half (43%) were on sick-leave. Besides severity and number of episodes of depression, female gender and age over 50 years strongly and independently predicted being on sick-leave. Factors influencing social and occupational disability and social adjustment among patients with MDD were studied prospectively during an 18-month follow-up period. Patients' functional disability and social adjustment were alleviated during the follow-up concurrently with recovery from depression. The current level of functioning and social adjustment of a patient with depression was predicted by severity of depression, recurrence before baseline and during follow-up, lack of full remission, and time spent depressed. Comorbid psychiatric disorders, personality traits (neuroticism), and perceived social support also had a significant influence. During the 18-month follow-up period, of the 269, 13 (5%) patients switched to bipolar disorder, and 58 (20%) dropped out. Of the 198, 186 (94%) patients were at baseline not pensioned, and they were investigated. Of them, 21 were granted a disability pension during the follow-up. Those who received a pension were significantly older, more seldom had vocational education, and were more often on sick-leave than those not pensioned, but did not differ with regard to any other sociodemographic or clinical factors. Patients with MDD received mostly adequate antidepressant treatment, but problems existed in treatment intensity and monitoring. It is challenging to find those at greatest risk for disability and to provide them adequate and efficacious treatment. This includes great challenges to the whole society to provide sufficient resources.

Suicidal behaviour in bipolar disorder

The Jorvi Bipolar Study (JoBS) is a collaborative ongoing bipolar research project between the Department of Mental Health and Alcohol Research of the National Public Health Institute, Helsinki, and the Department of Psychiatry, Jorvi Hospital, Helsinki University Central Hospital (HUCH), Espoo, Finland. The JoBS is a prospective, naturalistic cohort study of secondary level care psychiatric out-and inpatients with a new episode of Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) bipolar disorder (BD). Altogether, 1630 patients (aged 18-59) years were screened using the Mood Disorder Questionnaire (MDQ) for a possible new episode of DSM-IV BD. 490 patients were interviewed with semi-structured interview [the Structured Clinical Interview for DSM-IV Disorders, research version with Psychotic Screen (SCID-I/P)]. 191 patients with new episode of DSM-IV BD were included in the bipolar cohort study. Psychiatric comorbidity was evaluated using semi-structured interviews. At 6- and 18-month follow-up, the interviews were repeated and life-chart methodology was used to integrate all available information about nature and duration of all different phases. Suicidal behaviour was examined both at intake and follow-up by psychometric scale [Scale for Suicidal Ideation (SSI)], interviewer s questions and medical and psychiatric records. The aim of this thesis was to evaluate prevalence of suicidal behaviour and incidence of suicide attempts, and examine the wide range of risk factors for attempted suicide both, at intake and follow-up, in representative secondary-level sample of psychiatric in- and outpatients with BD. In this study suicidal behaviour was common among psychiatric patients with BD. During the episode when patients were included into cohort study (index episode), 20% of the patients had attempted suicide and 61% had suicidal ideation. Severity of depressive episode and hopelessness were independent risk factors for suicidal ideation, whereas hopelessness, comorbid personality disorder and previous suicide attempt predicted suicide attempts during the index episode. There were no differences in prevalence of suicidal behaviour between bipolar I and II disorder; the risk factors were overlapping but not identical. During the index episode, suicide attempts took place during depressive, mixed and depressive mixed phases. Furthermore, there were marked differences regarding level of suicidal ideation during different phases, with the highest levels during the mixed phases of the illness. Hopelessness was independently associated with suicidal behaviour during the depressive phase. A subjective rating of severity of depression (Beck Depression Inventory) and younger age predicted suicide attempts during mixed phases. During the 18-month follow-up 20% of patients attempted suicide. Previous suicide attempts, hopelessness, depressive phase at index episode and younger age at intake were independent risk factors for suicide attempts during follow-up. Taken altogether, 55% patients attempted suicide before index episode, during index episode or during follow-up. The incidence of suicide attempts was 37-fold during combined mixed and depressive mixed states and 18-fold during major depressive phase as compared with other phases. Prior suicide attempt and time spent in combined mixed phases - mixed and depressive mixed - and depressive phases independently predicted the suicide attempt during follow-up. More than half of the patients have attempted suicide during their lifetime, a finding which highlights the public health importance of suicidal behaviour in bipolar disorder. Clinically, it is crucial to recognize BD and manage the mixed and depressive phases of bipolar patients fast and effectively, as time spent in depressive and mixed phases involves a remarkably high risk of suicide attempts.

The Influence of the Val158Met Catechol-O-Methyltransferase Polymorphism on the Personality Traits of Bipolar Patients

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Bipolar disorder comorbid with alcohol use disorder: Focus on neurocognitive correlates

Bipolar disorder (BD) and alcohol use disorders (AUDs) are usually comorbid, and both have been associated with significant neurocognitive impairment. Patients with the BD-AUD comorbidity (dual diagnosis) may have more severe neurocognitive deficits than those with a single diagnosis, but there is paucity of research in this area. To explore this hypothesis more thoroughly, we carried out a systematic literature review through January 2015. Eight studies have examined the effect of AUDs on the neurocognitive functioning of BD patients. Most studies found that BD patients with current or past history of comorbid AUDs show more severe impairments, especially in verbal memory and executive cognition, than their non-dual counterparts. Greater neurocognitive dysfunction is another facet of this severe comorbid presentation. Implications for clinical practice and research are discussed. Specifically, the application of holistic approaches, such as clinical staging and systems biology, may open new avenues of discoveries related to the BD-AUD comorbidity.

Normal levels of prepulse inhibition in the euthymic phase of bipolar disorder.

BACKGROUND:Deficits in prepulse inhibition (PPI) of the acoustic startle response have been suggested as a potentially useful endophenotype for schizophrenia spectrum disorders and may explain certain symptoms and cognitive deficits observed in the psychoses. PPI deficits have also been found in mania, but it remains to be confirmed whether this dysfunction is present in the euthymic phase of bipolar disorder.METHOD: Twenty-three adult patients with DSM-IV bipolar disorder were compared to 20 controls on tests of acoustic startle reactivity and PPI of the startle response. Sociodemographic and treatment variables were recorded and symptom scores assessed using the Hamilton Depression Inventory and the Young Mania Rating Scale.RESULTS:Overall, the patient and control groups demonstrated similar levels of startle reactivity and PPI, although there was a trend for the inter-stimulus interval to differentially affect levels of PPI in the two groups.CONCLUSIONS: In contrast to bipolar patients experiencing a manic episode, general levels of PPI were normal in this euthymic sample. Further studies are required to confirm this finding and to determine the mechanisms by which this potential disruption/normalization occurs. It is suggested that an examination of PPI in a high-risk group is required to fully discount dysfunctional PPI as a potentially useful endophenotype for bipolar disorder.