Mental health pharmacists views on shared decision-making for antipsychotics in serious mental illness

Background People diagnosed with serious mental illnesses (SMIs) such as schizophrenia and bipolar affective disorder are frequently treated with antipsychotics. National guidance advises the use of shared decision-making (SDM) in antipsychotic prescribing. There is currently little data on the opinions of health professionals on the role of SDM. Objective To explore the views and experiences of UK mental health pharmacists regarding the use of SDM in antipsychotic prescribing in people diagnosed with SMI. Setting The study was conducted by interviewing secondary care mental health pharmacists in the UK to obtain qualitative data. Methods Semi-structured interviews were recorded. An inductive thematic analysis was conducted using the method of constant comparison. Main outcome measure Themes evolving from mental health pharmacists on SDM in relation to antipsychotic prescribing in people with SMI. Results Thirteen mental health pharmacists were interviewed. SDM was perceived to be linked to positive clinical outcomes including adherence, service user satisfaction and improved therapeutic relations. Despite more prescribers and service users supporting SDM, it was not seen as being practised as widely as it could be; this was attributed to a number of barriers, most predominantly issues surrounding service user’s lacking capacity to engage in SDM and time pressures on clinical staff. The need for greater effort to work around the issues, engage service users and adopt a more inter-professional approach was conveyed. Conclusion The mental health pharmacists support SDM for antipsychotic prescribing, believing that it improves outcomes. However, barriers are seen to limit implementation. More research is needed into overcoming the barriers and measuring the benefits of SDM, along with exploring a more inter-professional approach to SDM.

A Utilitarian Perspective of Social and Medical Contributions to Three Illustrative Conditions, and Recent UK NHS Policy Initiatives

Background: To date debate concerning the relative merits of social and medical sciences has been largely academic. Aims: To outline and critically appraise a utilitarian approach to mental health research that reflects a critical realist perspective. Method: Consideration of the relative utility of differing approaches to illustrative ‘‘psychiatric’’ disorders, and recent policy initiatives. Results: Socially relevant outcomes of Bipolar Affective Disorder are determined by influences that operate independently of the characteristic instability of mood. There is now a highly specific and effective psychological treatment for Panic Disorder. Its benefits are still not fully exploited because of continuing lay and professional focus upon the condition’s social manifestations. Great numbers of people presenting in primary care are unhelpfully caused to adopt the role of ‘‘patient’’ due to practices limiting the professional response to a medical one. Such practices reflect public and professional perceptions of the nature of ‘‘mental health difficulties’’ much more than they do the achievements of medicine. Recent policy-supporting initiatives influencing UK NHS mental health services are much more likely to be supported by social sciences than by medical research. Conclusions: There is considerable scope for a contribution to applied mental health research from frameworks and methodologies that are rooted in a social sciences perspective.

Impact of sunlight on the age of onset of bipolar disorder

Bauer M, Glenn T, Alda M, Andreassen OA, Ardau R, Bellivier F, Berk M, Bjella TD, Bossini L, Del Zompo M, Dodd S, Fagiolini A, Frye MA, Gonzalez-Pinto A, Henry C, Kapczinski F, Kliwicki S, Konig B, Kunz M, Lafer B, Lopez-Jaramillo C, Manchia M, Marsh W, Martinez-Cengotitabengoa M, Melle I, Morken G, Munoz R, Nery FG, ODonovan C, Pfennig A, Quiroz D, Rasgon N, Reif A, Rybakowski J, Sagduyu K, Simhandl C, Torrent C, Vieta E, Zetin M, Whybrow PC. Impact of sunlight on the age of onset of bipolar disorder. Bipolar Disord 2012: 14: 654663. (c) 2012 The Authors. Journal compilation (c) 2012 John Wiley & Sons A/S. Objective: Although bipolar disorder has high heritability, the onset occurs during several decades of life, suggesting that social and environmental factors may have considerable influence on disease onset. This study examined the association between the age of onset and sunlight at the location of onset. Method: Data were obtained from 2414 patients with a diagnosis of bipolar I disorder, according to DSM-IV criteria. Data were collected at 24 sites in 13 countries spanning latitudes 6.3 to 63.4 degrees from the equator, including data from both hemispheres. The age of onset and location of onset were obtained retrospectively, from patient records and/or direct interviews. Solar insolation data, or the amount of electromagnetic energy striking the surface of the earth, were obtained from the NASA Surface Meteorology and Solar Energy (SSE) database for each location of onset. Results: The larger the maximum monthly increase in solar insolation at the location of onset, the younger the age of onset (coefficient= -4.724, 95% CI: -8.124 to -1.323, p = 0.006), controlling for each countrys median age. The maximum monthly increase in solar insolation occurred in springtime. No relationships were found between the age of onset and latitude, yearly total solar insolation, and the maximum monthly decrease in solar insolation. The largest maximum monthly increases in solar insolation occurred in diverse environments, including Norway, arid areas in California, and Chile. Conclusion: The large maximum monthly increase in sunlight in springtime may have an important influence on the onset of bipolar disorder.

Relationship between sunlight and the age of onset of bipolar disorder:an international multisite study

Background - The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. Methods - Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. Results - There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. Limitations - Recall bias for onset and family history data. Conclusions - A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.

Clinical guidelines on long-term pharmacotherapy for bipolar disorder in children and adolescents

Bipolar disorder is a severe affective disorder which can present in adolescence, or sometimes earlier, and often requires a pharmacotherapeutic approach. The phenomenology of bipolar disorder in children and adolescents appears to differ from that of adult patients, prompting the need for specific pharmacotherapy guidelines for long-term management in this patient population. Current treatment guidelines were mainly developed based on evidence from studies in adult patients, highlighting the requirement for further research into the pharmacotherapy of children and adolescents with bipolar disorder. This review compares and critically analyzes the available guidelines, discussing the recommended medication classes, their mechanisms of action, side effect profiles and evidence base

Adverse Childhood Life Events and Postpartum Psychosis in Bipolar Disorder

Background Women with bipolar disorder are at increased risk of postpartum psychosis. Adverse childhood life events have been associated with depression in the postpartum period, but have been little studied in relation to postpartum psychosis. In this study we investigated whether adverse childhood life events are associated with postpartum psychosis in a large sample of women with bipolar I disorder. Methods Participants were 432 parous women with DSM-IV bipolar I disorder recruited into the Bipolar Disorder Research Network (www.BDRN.org). Diagnoses and lifetime psychopathology, including perinatal episodes, were obtained via a semi-structured interview (Schedules for Clinical Assessment in Neuropsychiatry; Wing et al., 1990) and case-notes. Adverse childhood life events were assessed via self-report and case-notes, and compared between women with postpartum psychosis (n=208) and those without a lifetime history of perinatal mood episodes (n=224). Results There was no significant difference in the rate of any adverse childhood life event, including childhood sexual abuse, or in the total number of adverse childhood life events between women who experienced postpartum psychosis and those without a lifetime history of perinatal mood episodes, even after controlling for demographic and clinical differences between the groups. Limitations Adverse childhood life events were assessed in adulthood and therefore may be subject to recall errors. Conclusions We found no evidence for an association between adverse childhood life events and the occurrence of postpartum psychosis. Our data suggest that, unlike postpartum depression, childhood adversity does not play a significant role in the triggering of postpartum psychosis in women with bipolar disorder.

Identifying Risk Factors for Postpartum Mood Episodes in Bipolar Disorder – A UK Prospective Study

Background and Aims: Women with bipolar disorder are vulnerable to episodes postpartum, but risk factors are poorly understood. We are exploring risk factors for postpartum mood episodes in women with bipolar disorder using a prospective longitudinal design. Methods: Pregnant women with lifetime DSM-IV bipolar disorder are being recruited into the Bipolar Disorder Research Network (www.BDRN.org). Baseline assessments during late pregnancy include lifetime psychopathology and potential risk factors for perinatal episodes such as medication use, sleep, obstetric factors, and psychosocial factors. Blood samples are taken for genetic analysis. Perinatal psychopathology is assessed via follow-up interview at 12-weeks postpartum. Interview data are supplemented by clinician questionnaires and case-note review. Potential risk factors will be compared between women who experience perinatal episodes and those who remain well. Results: 80 participants have been recruited to date. 32/61 (52%) women had a perinatal recurrence by follow-up. 16 (26%) had onset in pregnancy. 21 (34%) had postpartum onset, 19 (90%) within 6-weeks of delivery: 11 (18%) postpartum psychosis, 5 (8%) postpartum hypomania, 5 (8%) postpartum depression. Postpartum relapse was more frequent in women with bipolar-I than bipolar-II disorder (45% vs 17%). 62% women with postpartum relapse took prophylactic medication peripartum and almost all received care from secondary psychiatric services (95%). Conclusions: Rate of postpartum relapse is high, despite most women receiving specialist care and medication perinatally. A larger sample size will allow us to examine potential risk factors for postpartum episodes, which will assist in providing accurate and personalised advice to women with bipolar disorder who are considering pregnancy.

Postpartum Psychosis in Bipolar Disorder: No Association with Personality, Cognitive Style and Temperament

Background and Aims: Bipolar disorder has been associated with a number of personality traits, cognitive styles and affective temperaments. Women who have bipolar disorder are at increased risk of experiencing postpartum psychosis, however no previous research has investigated these traits in relationship to postpartum episodes. Our aim was to establish whether aspects of personality, cognitive style and affective temperament, that have been associated with bipolar disorder, confer vulnerability to postpartum psychosis over and above their known association with bipolar disorder. Methods: Participants were 552 parous women with DSM-IV bipolar I disorder recruited into the Bipolar Disorder Research Network (www.bdrn.org). Postpartum psychosis group: lifetime episode of postpartum psychosis within 6 weeks of delivery (N = 284). Non-postpartum psychosis group: no history of any perinatal mood episodes (N = 268). Bipolar disorder-associated personality traits (neuroticism, extraversion, schizotypy and impulsivity), cognitive styles (low self-esteem and dysfunctional attitudes) and affective temperaments were measured using well validated self-report questionnaire measures. Results: After controlling for key demographic, clinical and pregnancy-related variables, and measures of current mood state, there were no statistically significant differences between the postpartum psychosis group and non-postpartum psychosis group on any of the personality, cognitive style or affective temperament measures. Conclusions: Personality traits, cognitive styles and affective temperaments associated with the bipolar disorder diathesis in general were not associated with the onset of postpartum psychosis specifically. We have found no evidence that these traits should play a key role when evaluating risk of postpartum psychosis in women with bipolar I disorder considering pregnancy.

The Influence of Borderline Personality Traits on the Course of Bipolar Disorder

Background and Aims: Bipolar disorder and borderline personality disorder are commonly comorbid. Borderline personality disorder is diagnosed categorically, but personality pathology may be better characterised dimensionally. The impact of borderline personality traits (not diagnosis) on the course of bipolar disorder is unknown. We examined the presence and severity of borderline personality traits in a large UK sample of bipolar disorder, and the impact of these traits on illness course. Methods: Borderline Evaluation of Severity over Time (BEST) was used to measure presence and severity of borderline traits in 1447 individuals with DSM-IV bipolar I disorder (n = 1008) and bipolar II disorder (n = 439) recruited into the Bipolar Disorder Research Network (www.bdrn.org). Clinical course was measured via semi-structured interview (Schedules for Clinical Assessment in Neuropsychiatry) and case-notes. Results: BEST score was higher in bipolar II than bipolar I (36 v 27, p < 0.001) and 9/12 individual BEST traits were significantly more common in bipolar II than bipolar I. Within both bipolar I and bipolar II higher BEST score was associated with younger age of bipolar onset (p < 0.001), history of alcohol misuse (p < 0.010), and history of suicide attempt (p < 0.001). Conclusions: Borderline personality traits are common in bipolar disorder, and more severe in bipolar II than bipolar I disorder. Borderline trait severity was associated with more severe bipolar illness course; younger age of onset, alcohol misuse and suicidal behaviour. Clinicians should be vigilant for borderline personality traits irrespective of whether criteria for diagnosis are met, particularly in those with bipolar II disorder and younger age of bipolar onset.

Genome-wide association study of major depressive disorder: New results, meta-analysis, and lessons learned

Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were: (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10), and; (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.

Genetic background of bipolar disorder and related cognitive impairments

Bipolar disorder (BP) is a complex psychiatric disorder characterized by episodes of mania and depression. BP affects approximately 1% of the world’s population and shows no difference in lifetime prevalence between males and females. BP arises from complex interactions among genetic, developmental and environmental factors, and it is likely that several predisposing genes are involved in BP. The genetic background of BP is still poorly understood, although intensive and long-lasting research has identified several chromosomal regions and genes involved in susceptibility to BP. This thesis work aims to identify the genetic variants that influence bipolar disorder in the Finnish population by candidate gene and genome-wide linkage analyses in families with many BP cases. In addition to diagnosis-based phenotypes, neuropsychological traits that can be seen as potential endophenotypes or intermediate traits for BP were analyzed. In the first part of the thesis, we examined the role of the allelic variants of the TSNAX/DISC1 gene cluster to psychotic and bipolar spectrum disorders and found association of distinct allelic haplotypes with these two groups of disorders. The haplotype at the 5’ end of the Disrupted-in-Schizophrenia-1 gene (DISC1) was over-transmitted to males with psychotic disorder (p = 0.008; for an extended haplotype p = 0.0007 with both genders), whereas haplotypes at the 3’ end of DISC1 associated with bipolar spectrum disorder (p = 0.0002; for an extended haplotype p = 0.0001). The variants of these haplotypes also showed association with different cognitive traits. The haplotypes at the 5’ end associated with perseverations and auditory attention, while the variants at the 3’ end associated with several cognitive traits including verbal fluency and psychomotor processing speed. Second, in our complete set of BP families with 723 individuals we studied six functional candidate genes from three distinct signalling systems: serotonin-related genes (SLC6A4 and TPH2), BDNF -related genes (BDNF, CREB1 and NTRK2) and one gene related to the inflammation and cytokine system (P2RX7). We replicated association of the functional variant Val66Met of BDNF with BP and better performance in retention. The variants at the 5’ end of SLC6A4 also showed some evidence of association among males (p = 0.004), but the widely studied functional variants did not yield any significant results. A protective four-variant haplotype on P2RX7 showed evidence of association with BP and executive functions: semantic and phonemic fluency (p = 0.006 and p = 0.0003, respectively). Third, we analyzed 23 bipolar families originating from the North-Eastern region of Finland. A genome-wide scan was performed using the 6K single nucleotide polymorphism (SNP) array. We identified susceptibility loci at chromosomes 7q31 with a LOD score of 3.20 and at 9p13.1 with a LOD score of 4.02. We followed up both linkage findings in the complete set of 179 Finnish bipolar families. The finding on chromosome 9p13 was supported (maximum LOD score of 3.02), but the susceptibility gene itself remains unclarified. In the fourth part of the thesis, we wanted to test the role of the allelic variants that have associated with bipolar disorder in recent genome-wide association studies (GWAS). We could confirm findings for the DFNB31, SORCS2, SCL39A3, and DGKH genes. The best signal in this study comes from DFNB31, which remained significant after multiple testing corrections. Two variants of SORCS2 were allelic replications and presented the same signal as the haplotype analysis. However, no association was detected with the PALB2 gene, which was the most significantly associated region in the previous GWAS. Our results indicate that BP is heterogeneous and its genetic background may accordingly vary in different populations. In order to fully understand the allelic heterogeneity that underlies common diseases such as BP, complete genome sequencing for many individuals with and without the disease is required. Identification of the specific risk variants will help us better understand the pathophysiology underlying BP and will lead to the development of treatments with specific biochemical targets. In addition, it will further facilitate the identification of environmental factors that alter risk, which will potentially provide improved occupational, social and psychological advice for individuals with high risk of BP.

Affective disorders, hospital admissions, and seasonal variation of mania in a subtropical area, southern hemisphere

Hospital admissions (n = 15,450) to a state psychiatric hospital in Botucatu, São Paulo State, Brazil, over a 10-year period (1982-1991) were reviewed. 157 (1%) patients received a probable diagnosis of affective disorder according to DSM-III-R criteria. Among them, 46% had been diagnosed by the staff psychiatrists, and their diagnoses were sustained by the researchers, whereas 54% were diagnosed only by one of the researchers (F.K.C.). These last patients had previously received a diagnosis of paranoid schizophrenia or unspecified psychosis (ICD-9). Most of the patients with affective disorders were bipolar: 72 and 8%, respectively, presented manic and depressive episodes. Thus, only 20% received a diagnosis of major depression. A seasonal pattern in hospital admission was observed only for mania in women, their episodes occurring more often (p < 0.02) in spring and summer. No significant seasonal pattern in hospital admission for depression was found.

A complete genome screen for genes predisposing to severe bipolar disorder in two Costa Rican pedigrees

Bipolar mood disorder (BP) is a debilitating syndrome characterized by episodes of mania and depression. We designed a multistage study to detect all major loci predisposing to severe BP (termed BP-I) in two pedigrees drawn from the Central Valley of Costa Rica, where the population is largely descended from a few founders in the 16th–18th centuries. We considered only individuals with BP-I as affected and screened the genome for linkage with 473 microsatellite markers. We used a model for linkage analysis that incorporated a high phenocopy rate and a conservative estimate of penetrance. Our goal in this study was not to establish definitive linkage but rather to detect all regions possibly harboring major genes for BP-I in these pedigrees. To facilitate this aim, we evaluated the degree to which markers that were informative in our data set provided coverage of each genome region; we estimate that at least 94% of the genome has been covered, at a predesignated threshold determined through prior linkage simulation analyses. We report here the results of our genome screen for BP-I loci and indicate several regions that merit further study, including segments in 18q, 18p, and 11p, in which suggestive lod scores were observed for two or more contiguous markers. Isolated lod scores that exceeded our thresholds in one or both families also occurred on chromosomes 1, 2, 3, 4, 5, 7, 13, 15, 16, and 17. Interesting regions highlighted in this genome screen will be followed up using linkage disequilibrium (LD) methods.

Age-at-first-registration and heterogeneity in affective psychoses

Background: Previous research into age of onset in affective disorders has produced conflicting results. This paper examines the influence of heterogeneity on the age-at-first-registration distribution for the ICD-9 diagnostic group 'affective psychosis'. Method: For 1979-1991, data for age-at-first-registration for 4985 individuals diagnosed with affective psychosis (ICD-9 296.x) were extracted from a name-linked mental health register. These data were divided into (i) '296.1 only', a category used to code unipolar depression (males = 700; females = 1321); and (ii) '296 other', all 296 cases other than 296.1 (males = 1280; females = 1684). Inception rates for each 5-year age division were adjusted for the background population age-structure as a rate per 100 000 population. Results: The age-at-first-registration distribution for affective psychosis has a wide age range, with women outnumbering men. There is a near-linear increase in inception rates for both men and women with 296.1 only, while the bulk of those with affective psychoses (296 other) have an inverted U-shaped age distribution. Males have an earlier modal age-at-first-registration for 296 other compared to females. Conclusion: The heterogeneity in terms of subtypes and sex in affective psychosis clouds the interpretation of age-at-first-registration. Separating those with unipolar psychotic depression from other subclassifications and differentiating by sex may provide clues to factors that precipitate the onset of affective psychosis.

Influence of light exposure during early life on the age of onset of bipolar disorder

Background: Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. Methods: Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4N and 70.7N, and 1.2S and 41.3S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation. Results: More hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. Conclusions: Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life.