Novel Risk Loci Associated With Genetic Risk for Bipolar Disorder Among Han Chinese Individuals: A Genome-Wide Association Study and Meta-analysis.

Importance: The genetic basis of bipolar disorder (BD) in Han Chinese individuals is not fully understood. Objective: To explore the genetic basis of BD in the Han Chinese population. Design, Setting, and Participants: A genome-wide association study (GWAS), followed by independent replication, was conducted to identify BD risk loci in Han Chinese individuals. Individuals with BD were diagnosed based on DSM-IV criteria and had no history of schizophrenia, mental retardation, or substance dependence; individuals without any personal or family history of mental illnesses, including BD, were included as control participants. In total, discovery samples from 1822 patients and 4650 control participants passed quality control for the GWAS analysis. Replication analyses of samples from 958 patients and 2050 control participants were conducted. Summary statistics from the European Psychiatric Genomics Consortium 2 (PGC2) BD GWAS (20 352 cases and 31 358 controls) were used for the trans-ancestry genetic correlation analysis, polygenetic risk score analysis, and meta-analysis to compare BD genetic risk between Han Chinese and European individuals. The study was performed in February 2020. Main Outcomes and Measures: Single-nucleotide variations with P < 5.00 × 10-8 were considered to show genome-wide significance of statistical association. Results: The Han Chinese discovery GWAS sample included 1822 cases (mean [SD] age, 35.43 [14.12] years; 838 [46%] male) and 4650 controls (mean [SD] age, 27.48 [5.97] years; 2465 [53%] male), and the replication sample included 958 cases (mean [SD] age, 37.82 [15.54] years; 412 [43%] male) and 2050 controls (mean [SD] age, 27.50 [6.00] years; 1189 [58%] male). A novel BD risk locus in Han Chinese individuals was found near the gene encoding transmembrane protein 108 (TMEM108, rs9863544; P = 2.49 × 10-8; odds ratio [OR], 0.650; 95% CI, 0.559-0.756), which is required for dendritic spine development and glutamatergic transmission in the dentate gyrus. Trans-ancestry genetic correlation estimation (ρge = 0.652, SE = 0.106; P = 7.30 × 10-10) and polygenetic risk score analyses (maximum liability-scaled Nagelkerke pseudo R2 = 1.27%; P = 1.30 × 10-19) showed evidence of shared BD genetic risk between Han Chinese and European populations, and meta-analysis identified 2 new GWAS risk loci near VRK2 (rs41335055; P = 4.98 × 10-9; OR, 0.849; 95% CI, 0.804-0.897) and RHEBL1 (rs7969091; P = 3.12 × 10-8; OR, 0.932; 95% CI, 0.909-0.956). Conclusions and Relevance: This GWAS study identified several loci and genes involved in the heritable risk of BD, providing insights into its genetic architecture and biological basis.

Ethnicity and impact on the receipt of cognitive-behavioural therapy in people with psychosis or bipolar disorder: an English cohort study.

OBJECTIVES: (1) To explore the role of ethnicity in receiving cognitive-behavioural therapy (CBT) for people with psychosis or bipolar disorder while adjusting for differences in risk profiles and symptom severity. (2) To assess whether context of treatment (inpatient vs community) impacts on the relationship between ethnicity and access to CBT. DESIGN: Cohort study of case register data from one catchment area (January 2007-July 2017). SETTING: A large secondary care provider serving an ethnically diverse population in London. PARTICIPANTS: Data extracted for 30 497 records of people who had diagnoses of bipolar disorder (International Classification of Diseases (ICD) code F30-1) or psychosis (F20-F29 excluding F21). Exclusion criteria were: <15 years old, missing data and not self-defining as belonging to one of the larger ethnic groups. The sample (n=20 010) comprised the following ethnic groups: white British: n=10 393; Black Caribbean: n=5481; Black African: n=2817; Irish: n=570; and 'South Asian' people (consisting of Indian, Pakistani and Bangladeshi people): n=749. OUTCOME ASSESSMENTS: ORs for receipt of CBT (single session or full course) as determined via multivariable logistic regression analyses. RESULTS: In models adjusted for risk and severity variables, in comparison with White British people; Black African people were less likely to receive a single session of CBT (OR 0.73, 95% CI 0.66 to 0.82, p<0.001); Black Caribbean people were less likely to receive a minimum of 16-sessions of CBT (OR 0.83, 95% CI 0.71 to 0.98, p=0.03); Black African and Black Caribbean people were significantly less likely to receive CBT while inpatients (respectively, OR 0.76, 95% CI 0.65 to 0.89, p=0.001; OR 0.83, 95% CI 0.73 to 0.94, p=0.003). CONCLUSIONS: This study highlights disparity in receipt of CBT from a large provider of secondary care in London for Black African and Caribbean people and that the context of therapy (inpatient vs community settings) has a relationship with disparity in access to treatment.

The physical health of Maori with bipolar disorder.

AIMS: There is very little empirical evidence about the relationship between severe mental illness and the physical health of Indigenous peoples. This paper aims to compare the physical health of Maori and non-Maori with a diagnosis of bipolar disorder in contact with NZ mental health services. METHODS: A cohort of Maori and non-Maori with a current bipolar disorder diagnosis at 1 January 2010 were identified from routine mental health services data and followed up for non-psychiatric hospital admissions and deaths over the subsequent 5 years. RESULTS: Maori with bipolar disorder had a higher level of morbidity and a higher risk of death from natural causes compared to non-Maori with the same diagnosis, indicating higher levels of physical health need. The rate of medical and surgical hospitalisation was not higher among Maori compared to non-Maori (as might be expected given increased health needs) which suggests under-treatment of physical health conditions in this group may be a factor in the observed higher risk of mortality from natural causes for Maori. CONCLUSION: This study provides the first indication that systemic factors which cause health inequities between Maori and non-Maori are compounded for Maori living with severe mental illness. Further exploration of other diagnostic groups and subgroups is needed to understand the best approach to reducing these inequalities.

Double-blind, placebo-controlled study of lurasidone monotherapy for the treatment of bipolar I depression.

AIM: Previous studies conducted primarily in the USA and Europe have demonstrated the efficacy and safety of lurasidone 20-120 mg/day for the treatment of bipolar I depression. The aim of the current study was to evaluate the efficacy and safety of lurasidone monotherapy for the treatment of bipolar I depression among patients from diverse ethnic backgrounds, including those from Japan. METHODS: Patients were randomly assigned to double-blind treatment for 6 weeks with lurasidone, 20-60 mg/day (n = 184) or 80-120 mg/day (n = 169), or placebo (n = 172). The primary end-point was change from baseline to Week 6 on the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Lurasidone treatment significantly reduced mean MADRS total scores from baseline to Week 6 for the 20-60-mg/day group (-13.6; adjusted P = 0.007; effect size = 0.33), but not for the 80-120-mg/day group (-12.6; adjusted P = 0.057; effect size = 0.22) compared with placebo (-10.6). Treatment with lurasidone 20-60 mg/day also improved MADRS response rates, functional impairment, and anxiety symptoms. The most common adverse events associated with lurasidone were akathisia and nausea. Lurasidone treatments were associated with minimal changes in weight, lipids, and measures of glycemic control. CONCLUSION: Monotherapy with once daily doses of lurasidone 20-60 mg, but not 80-120 mg, significantly reduced depressive symptoms and improved functioning in patients with bipolar I depression. Results overall were consistent with previous studies, suggesting that lurasidone 20-60 mg/day is effective and safe in diverse ethnic populations, including Japanese.

A Randomized Controlled Trial of Transcultural Validation of Group-Based Psychosocial Intervention for Patients with Bipolar Disorder.

Adjunctive psychosocial interventions are part of the preferred method to treat bipolar disorder (BD). This study aimed to conduct a randomized control and protocol-guided trial, in order to evaluate the feasibility and effectiveness of adjunctive group-based treatments for Chinese outpatients with BD. A single-blind trial in which 68 outpatients with BD were randomly assigned to either treatment as usual (TAU) or to an experimental group with 12 additional weekly sessions and 3 monthly booster sessions. Participants were assessed at baseline for mood condition, suicidal ideation, medication adherence, and quality of life (QoL), with follow-up assessments every 3 months over a 1-year period. The overall retention rate of this study was 89.7%. The results showed significant differences between groups for the variables evaluated, which included achieving euthymia, decrease of depression symptoms, and improvement of QoL. No improvements in medication adherence, reduction in manic symptoms, or suicidal ideation was observed. The results of this study support the transcultural validity and efficacy of group-based psychosocial intervention as anadjunct to TAU among Chinese outpatients with BD to promote improvements during the course of the illness including achieving euthymia, reducing depressive symptoms, and improving QoL.

Polygenetic Risk Scores for Major Psychiatric Disorders Among Schizophrenia Patients, Their First-Degree Relatives, and Healthy Participants.

BACKGROUND: The genetic etiology of schizophrenia (SCZ) overlaps with that of other major psychiatric disorders in samples of European ancestry. The present study investigated transethnic polygenetic features shared between Japanese SCZ or their unaffected first-degree relatives and European patients with major psychiatric disorders by conducting polygenic risk score (PRS) analyses. METHODS: To calculate PRSs for 5 psychiatric disorders (SCZ, bipolar disorder [BIP], major depressive disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder) and PRSs differentiating SCZ from BIP, we utilized large-scale European genome-wide association study (GWAS) datasets as discovery samples. PRSs derived from these GWASs were calculated for 335 Japanese target participants [SCZ patients, FRs, and healthy controls (HCs)]. We took these PRSs based on GWASs of European psychiatric disorders and investigated their effect on risk in Japanese SCZ patients and unaffected first-degree relatives. RESULTS: The PRSs obtained from European SCZ and BIP patients were higher in Japanese SCZ patients than in HCs. Furthermore, PRSs differentiating SCZ patients from European BIP patients were higher in Japanese SCZ patients than in HCs. Interestingly, PRSs related to European autism spectrum disorder were lower in Japanese first-degree relatives than in HCs or SCZ patients. The PRSs of autism spectrum disorder were positively correlated with a young onset age of SCZ. CONCLUSIONS: These findings suggest that polygenic factors related to European SCZ and BIP and the polygenic components differentiating SCZ from BIP can transethnically contribute to SCZ risk in Japanese people. Furthermore, we suggest that reduced levels of an ASD-related genetic factor in unaffected first-degree relatives may help protect against SCZ development.

Decreased core symptoms of mania and utilization of lithium/mood stabilizing anticonvulsants in U.S. bipolar I patients of African vs European ancestry.

OBJECTIVE: Misdiagnosis is common in bipolar disorder and disproportionally affects racial and ethnic minorities. There is interest in better understanding the contribution of differential symptomatic illness presentation to misdiagnosis. METHODS: Utilizing the Genetic Association Information Network (GAIN) public database, this study compared clinical phenomenology between bipolar patients of African vs European ancestry (AA = 415 vs EA = 480). The Diagnostic Interview for Genetic Studies (DIGS) was utilized to evaluate symptom endorsement contributing to diagnostic confirmation of bipolar I disorder (BPI) and lifetime medication use. RESULTS: Elevated/euphoric mood was less endorsed in AA vs EA participants (p = 0.03). During the most severe episode of mania, AA participants, in comparison to EA participants, had a lower sum of manic symptoms (p = 0.006) and a higher rate of hallucinations (p = 0.01). During lifetime psychosis, AA participants, in comparison to EA participants, had a higher lifetime sum of delusions (p = 0.01) and hallucinations (p < 0.0001). AA participants reported lower use of lithium (p < 0.0001) and mood stabilizing anticonvulsants (p = 0.0003). CONCLUSIONS: The differential rate of manic and psychotic symptom endorsement from a semi-structured diagnostic interview may represent differential illness presentation based on biological differences or racial or study biases (e.g. ascertainment). Increased minority recruitment in bipolar research is therefore a necessary future direction. LIMITATIONS: Recall and interviewer bias may affect study results, but are likely diminished by the alignment of symptom endorsement and medication use.

Do Asian and North American patients with bipolar disorder have similar efficacy, tolerability, and safety profile during clinical trials with atypical antipsychotics?

BACKGROUND: The approvals of psychotropics for bipolar disorder (BD) are mainly based on randomized, double-blind, placebo-controlled trials (RCTs) from North America. It remains unknown whether approved psychotropics have similar efficacy, tolerability, and safety for Asians with BD. The aim of this systematic review was to compare those differences of psychotropics between Asians and North Americans with BD. METHODS: MEDLINE, EMBASE, and PsycINFO were searched for RCTs studied in two regions. The effect size, remission/response rate, and risk for discontinuation due to adverse events (AEs), weight gain (WG), nervous systems and gastrointestinal AEs were assessed and compared between two regions with Cohen's d or number needed to treat/harm. RESULTS: Eleven studies of aripiprazole, olanzapine, risperidone, and quetiapine in BD were included. Similar efficacy and relatively benign tolerability of atypical antipsychotics (AAPs) between Asians and Americans with BD were observed in most studies. The risk for AAP-related WG was similar between two regions. Asians with mania or bipolar depression were more vulnerable to akathisia/tremor or constipation. Japanese and Chinese with bipolar depression were more sensitive to somnolence and dizziness, respectively. Americans were more likely to have dry mouth, nausea, and vomiting. LIMITATIONS: The number of included psychotropics and papers was small. CONCLUSIONS: Differences in AAP-related efficacy and tolerability were minimal between the two regions, but some AEs appeared to be different. Clinicians should pay attention to these differences to optimize treatment strategies in different races/ethnicities with BD.

Uma etnografia virtual em um grupo sobre o transtorno bipolar: sociabilidades e saberes produzidos no meio on-line / Virtual ethnography in a group about bipolar disorder: sociabilities and knowledge produced in the online environment / Una etnografía virtual en un grupo sobre el trastorno bipolar: sociabilidades y saberes producidos en el medio on-line

Publicado pela primeira vez no Manual Diagnóstico e Estatístico de Transtornos Mentais (DSM) III, o transtorno bipolar trouxe uma nova maneira de entender e vivenciar as oscilações emocionais, fortemente imbuída dos referenciais da psicofarmacologia, neurociências e novas conceituações sobre as variações afetivas. Com o objetivo de investigar os sentidos, as sociabilidades e os modos de ser constituídos a partir desse diagnóstico, foi feita uma etnografia no grupo brasileiro do Facebook mais numeroso sobre a bipolaridade, que identificou o seguinte: a rede facilita a produção de uma expertise experiencial; a ideia de que "apenas quem sofre entende" fortalece a identificação mútua; em contraposição à antiga psicose maníaco-depressiva, o transtorno bipolar adquire certa positividade, tornando-se fonte de humor; a química medicamentosa é o principal recurso usado para gerir a vida afetiva, tornando os pacientes parcialmente independentes do médico ao manejarem esses recursos entre si; e o transtorno bipolar é dissociado do Eu.(AU)

Published for the first time in DSM IIII, bipolar disorder has brought a new way of understanding and experiencing emotional oscillations, strongly impregnated with the frameworks of psychopharmacology, neurosciences, and with new conceptualizations of affective variations. Aiming to investigate the meanings, sociabilities and ways of being constituted from this diagnosis, an ethnography was performed in the most numerous Brazilian Facebook group about bipolar disorder, which identified the following aspects: the network facilitates the production of an experiential expertise; the idea that "only those who suffer from it can understand it" strengthens mutual identification; in opposition to manic depression, as it was formerly called, bipolar disorder acquires a certain positivity, becoming a source of humor; drug therapy is the main resource used to manage affective life, making patients partially independent from the physician when they handle these resources among themselves; bipolar disorder is dissociated from the "self".(AU)

Publicado por primera vez en el DSM III, el trastorno bipolar proporcionó una nueva manera de entender y experimentar las oscilaciones emocionales, fuertemente basada en los referenciales de la psicofarmacología, neurociencias y nuevas conceptuaciones sobre las variaciones afectivas. Con el objetivo de investigar los sentidos, sociabilidades y modos de ser constituidos a partir de este diagnóstico, se realizó una etnografía en el grupo brasileño del Facebook más numeroso sobre la bipolaridad que identificó lo siguiente: la red facilita la producción de una expertise con base en la experiencia; la idea de que "solamente quien lo sufre entiende" fortalece la identificación mutua; en contraposición a la antigua psicosis maníaco-depresiva, el trastorno bipolar adquiere cierta positividad, convirtiéndose en fuente de humor; la química medicamentosa es el principal recurso utilizado para administrar la vida afectiva, haciendo que los pacientes sean parcialmente independientes del médico al manejar estos recursos entre sí; el trastorno bipolar se disocia del "yo".(AU)

Postmortem brain tissue as an underutilized resource to study the molecular pathology of neuropsychiatric disorders across different ethnic populations.

In recent years, large scale meta-analysis of genome-wide association studies (GWAS) have reliably identified genetic polymorphisms associated with neuropsychiatric disorders such as schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD). However, the majority of disease-associated single nucleotide polymorphisms (SNPs) appear within functionally ambiguous non-coding genomic regions. Recently, increased emphasis has been placed on identifying the functional relevance of disease-associated variants via correlating risk polymorphisms with gene expression levels in etiologically relevant tissues. For neuropsychiatric disorders, the etiologically relevant tissue is brain, which requires robust postmortem sample sizes from varying genetic backgrounds. While small sample sizes are of decreasing concern, postmortem brain databases are composed almost exclusively of Caucasian samples, which significantly limits study design and result interpretation. In this review, we highlight the importance of gene expression and expression quantitative loci (eQTL) studies in clinically relevant postmortem tissue while addressing the current limitations of existing postmortem brain databases. Finally, we introduce future collaborations to develop postmortem brain databases for neuropsychiatric disorders from Chinese and Asian subpopulations.

[An evolutionist approach of mood disorders from a transcultural perspective]. / Une approche évolutionniste de la manie dans une perspective transculturelle.

INTRODUCTION: The objective of this paper is to verify if traits and symptoms defined as pathological and maladjusted in certain contexts may produce adaptive effects in other contexts, especially if they occur in sub-threshold forms. METHODS: A historical examination of how the symptoms of depression have changed in front of great social changes and an analysis of Sardinian migrants' thymic profiles toward several metropolises. RESULTS AND CONCLUSIONS: Mood disorders have been increasing since the "English malady" in the 17th century, and we suppose that some forms of mood disorders might have an adaptive advantage. Otherwise, the increase of such an epidemic would have been self-limited. From a sociobiological point of view, it is highly probable that the environment of a rapidly evolving society can select people who are explorers and able to support accelerated biorhythms and that the condition of social change stimulates psychological and psychopathologic changes. It is also possible that hyperthymic persons modulate and create the new environment. If this model can explain the epidemic of mood disorders, its verification should guide future research.

Substance Use and Psychiatric Disorders Among Mexican Americans and Non-Hispanic Whites by Immigration Status.

OBJECTIVE: To compare prevalence rates of alcohol, nicotine, and other drug use and major psychiatric disorders (major depressive disorder, persistent depression, bipolar I disorder, agoraphobia, social and specific phobias, and antisocial, schizotypal, and borderline personality disorders) between US-born and foreign-born Mexican Americans and non-Hispanic whites and between early entry versus later-entry foreign-born Mexican Americans and non-Hispanic whites. METHODS: Data were derived from face-to-face interviews in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions-III (N = 36,309). RESULTS: US-born Mexican Americans and US-born non-Hispanic whites were at greater risk (P < .05) of alcohol, nicotine, and any drug use and their associated disorders and other DSM-5 psychiatric disorders relative to their foreign-born counterparts. US-born non-Hispanic whites were more likely (P < .05) to use substances and develop many psychiatric disorders relative to US-born Mexican Americans. Foreign-born Mexican Americans < 18 years old at immigration were at greater risk of drug use, drug use disorders, and nicotine use disorder compared with foreign-born Mexican Americans ≥ 18 years old at immigration. Foreign-born non-Hispanic whites < 18 years old at immigration were more likely to use substances and to develop many psychiatric disorders relative to foreign-born non-Hispanic whites ≥ 18 years old at immigration. CONCLUSIONS: Taken together, the findings of this study support the healthy immigrant hypothesis and adverse role of acculturation for US-born and foreign-born Mexican Americans and non-Hispanic whites. Further research is warranted on immigration status and age at arrival into the United States and those processes underlying differential exposure to substances and development of psychiatric conditions. An understanding of these processes can be invaluable to clinicians in guiding culturally sensitive and informed prevention and intervention efforts.

Effective care for Maori with bipolar disorder: A qualitative study.

Maori have high rates of bipolar disorder (BD) and mental health service use. Despite the high prevalence and the impact on functioning and whanau (family), there is limited research on treatment interventions for Maori with bipolar disorder and indeed on Maori and indigenous mental health generally. A qualitative study combining individual interviews and focus groups was conducted with the aim to explore mental health clinicians' and Maori mental health workers' perspectives of effective treatment for Maori with BD. Sixteen participants took part in either individual interviews, focus groups or both. The study found the importance of a Maori worldview; tikanga Maori (rituals); understanding the whanau context, whakawhanaugatanga (connection), the powhiri (introduction) process, and whakarongo (listening) were key to working effectively with Maori who had BD. Both the interviews and focus groups identified similar concepts. The concept of whakawhanaungatanga (connection) captures the themes from the individual interviews and focus groups. The participants in this study identified the person and their culture rather than the psychiatric diagnosis as crucial to providing effective care to Maori with BD. Without a foundation in whakawhanaungatanga, engagement, diagnosis, treatment adherence, and the process of recovery are unlikely to be as effective for Maori with BD. It was evident from the findings that it was the person not the diagnosis that was central to therapeutic engagement.

The associations between subjective and objective cognitive functioning across manic or hypomanic, depressed, and euthymic states in Chinese bipolar patients.

BACKGROUND: Patients may present cognitive deficits during all stages of bipolar disorder (BD). Few studies have examined self-reported cognitive difficulties and its relation to neurocognitive dysfunction during symptomatic periods of BD. This study aimed to compare subjective cognitive functioning and explore associations between subjective and objective cognitive functioning across different BD clinical states, and investigate the predicting and moderating roles of mood symptoms. METHODS: Subjective cognitive functioning (measured by Cognitive Complaints in Bipolar Disorder Rating Assessment, COBRA) and several domains of cognitive functioning (assessed by a neuropsychological battery), including executive functions, attention and processing speed, and visual memory, were examined in 48 hypomanic or manic patients, 42 depressed bipolar patients, 50 euthymic bipolar patients and 60 healthy comparisons. RESULTS: All patients exhibited subjective and objective cognitive deficits in relation to healthy comparisons. There was a significant association between subjective and objective cognitive functioning in euthymic group, but the association was not significant in acute symptomatic groups, which could be moderated by depressive or manic symptoms in depressive or manic group, respectively. Subjective cognitive functioning was significantly correlated with mood symptoms, and the best predictor of subjective cognitive functioning was depressive symptoms. LIMITATIONS: This was a cross-sectional study with a mixed sample of inpatients and outpatients. The medication effect was not adjusted. CONCLUSIONS: The associations between subjective and objective cognitive dysfunction varied in clinical states, and mood symptoms moderated the associations. A neuropsychological test battery is required to substantiate actual cognitive dysfunction in clinical settings, irrespective of subjective cognitive deficits.

Risk of schizophrenia, schizoaffective, and bipolar disorders by migrant status, region of origin, and age-at-migration: a national cohort study of 1.8 million people.

BACKGROUND: We assessed whether the risk of various psychotic disorders and non-psychotic bipolar disorder (including mania) varied by migrant status, a region of origin, or age-at-migration, hypothesizing that risk would only be elevated for psychotic disorders. METHODS: We established a prospective cohort of 1 796 257 Swedish residents born between 1982 and 1996, followed from their 15th birthday, or immigration to Sweden after age 15, until diagnosis, emigration, death, or end of 2011. Cox proportional hazards models were used to model hazard ratios by migration-related factors, adjusted for covariates. RESULTS: All psychotic disorders were elevated among migrants and their children compared with Swedish-born individuals, including schizophrenia and schizoaffective disorder (adjusted hazard ratio [aHR]migrants: 2.20, 95% CI 1.96-2.47; aHRchildren : 2.00, 95% CI 1.79-2.25), affective psychotic disorders (aHRmigrant1.42, 95% CI 1.25-1.63; aHRchildren: 1.22 95% CI 1.07-1.40), and other non-affective psychotic disorders (aHRmigrant: 1.97, 95% CI 1.81-2.14; aHRchildren: 1.68, 95% CI 1.54-1.83). For all psychotic disorders, risks were generally highest in migrants from Africa (i.e. aHRschizophrenia: 5.24, 95% CI 4.26-6.45) and elevated at most ages-of-migration. By contrast, risk of non-psychotic bipolar disorders was lower for migrants (aHR: 0.58, 95% CI 0.52-0.64) overall, and across all ages-of-migration except infancy (aHR: 1.20; 95% CI 1.01-1.42), while risk for their children was similar to the Swedish-born population (aHR: 1.00, 95% CI 0.93-1.08). CONCLUSIONS: Increased risk of psychiatric disorders associated with migration and minority status may be specific to psychotic disorders, with exact risk dependent on the region of origin.

Neuroplasticity, Neurotransmission and Brain-Related Genes in Major Depression and Bipolar Disorder: Focus on Treatment Outcomes in an Asiatic Sample.

INTRODUCTION: Mood disorders are common and disabling disorders. Despite the availability of over 100 psychotropic compounds, only one-third of patients benefit from first-line treatments. Over the past 20 years, many studies have focused on the biological factors modulating disease risk and response to treatments, but with still inconclusive data. In order to improve our current knowledge, in this study, we investigated the role of a set of genes involved in different pathways (neurotransmission, neuroplasticity, circadian rhythms, transcription factors, signal transduction and cellular metabolism) in the treatment outcome of major depressive disorder (MDD) and bipolar disorder (BD) after naturalistic pharmacological treatment. METHODS: Totals of 242 MDD, 132 BD patients and 326 healthy controls of Asian ethnicity (Koreans) were genotyped for polymorphisms within 19 genes. Response and remission after 6-8 weeks of treatment with antidepressants and mood stabilizers were evaluated. In secondary analyses, genetic associations with disease risk and some disease-associated features (age of onset, suicide attempt and psychotic BD) were also tested. RESULTS: None of the variants within the investigated genes was significantly associated with treatment outcomes. Some marginal association (uncorrected p < 0.01) was observed for HTR2A, BDNF, CHL1, RORA and HOMER1 SNPs. In secondary analyses, HTR2A (rs643627, p = 0.002) and CHL1 (rs4003413, p = 0.002) were found associated with risk for BD, HOMER1 (rs6872497, p = 0.002) with lifetime history of suicide attempt in patients, and RORA with early onset and presence of psychotic features in BD. Marginal results were also observed for ST8SIA2 and COMT. DISCUSSION: Despite limitations linked to multiple testing on small samples, methodological shortcomings and small significance of the findings, this study may support the involvement of some candidate genes in the outcomes of treatments for mood disorders, as well as in BD risk and other disease features.

Metacognition in schizophrenia disorders: Comparisons with community controls and bipolar disorder: Replication with a Spanish language Chilean sample.

Metacognition refers to the activities which allow for the availability of a sense of oneself and others in the moment. Research mostly in North America with English-speaking samples has suggested that metacognitive deficits are present in schizophrenia and are closely tied to negative symptoms. Thus, replication is needed in other cultures and groups. The present study accordingly sought to replicate these findings in a Spanish speaking sample from Chile. Metacognition and symptoms were assessed among 26 patients with schizophrenia, 26 with bipolar disorder and 36 community members without serious mental illness. ANCOVA controlling for age and education revealed that the schizophrenia group had greater levels of metacognitive deficits than the bipolar disorder and community control groups. Differences in metacognition between the clinical groups persisted after controlling for symptom levels. Spearman correlations revealed a unique pattern of associations of metacognition with negative and cognitive symptoms. Results largely support previous findings and provide added evidence of the metacognitive deficits present in schizophrenia and the link to outcome cross culturally. Implications for developing metacognitively oriented interventions are discussed.

Angry characters and frightened souls: Patients and family explanatory models of bipolar disorder in Taiwan.

Bipolar disorder (BD) affects a significant proportion of Taiwanese individuals (Weissman et al., 1996; Yang, Yeh, & Hwu, 2012). Psychotropic medications are typically the mainstay of treatment for BD, and there is an abundance of international research on biological etiology and medication options. However, there is comparatively little research on psychosocial aspects of BD, including how it is understood and managed within families. As culture provides the context in which psychiatric disease is managed, there is a need to identify distinct Chinese psychosocial perspectives that might shed light on intervention options. This research explored how Taiwanese patients and family members comprehend and cope with BD. A sample of 42 participants, including 20 Taiwanese patients diagnosed with Bipolar Disorder-I (BD-I) for at least 4 years, and 22 family members, participated in separate interviews on explanatory models of illness. Qualitative thematic analysis focused on features that were distinct from those in current Western research literature. Five themes were identified that represented Taiwanese conceptualizations of BD, notions of etiology, views regarding treatment, and the difficulties in managing the disorder. Participants used Chinese language terms and descriptions of BD that reflected greater concerns about irritability, anger, and family conflict than about other symptoms, and participants also emphasized characterological trait descriptions of the condition. Their responses reflected their acceptance of lifelong family responsibility for caretaking, clashing beliefs regarding biomedical versus traditional Chinese medical and spiritual models of etiology and cure, profound concerns about the effects of psychiatric medication on the liver and kidney systems, and a focus on stress rather than genetic or biological models of etiology.

Racial disparities in bipolar disorder treatment and research: a call to action.

OBJECTIVES: Health disparities between individuals of African and European ancestry are well documented. The disparities in bipolar disorder may be driven by racial bias superimposed on established factors contributing to misdiagnosis, including: evolving empirically based diagnostic criteria (International Classification of Diseases [ICD], Research Diagnostic Criteria [RDC] and Diagnostic and Statistical Manual [DSM]), multiple symptom domains (i.e. mania, depression and psychosis), and multimodal medical and additional psychiatric comorbidity. METHODS: For this paper, we reviewed the phenomenological differences between bipolar individuals of African and European ancestry in the context of diagnostic criteria and clinical factors that may contribute to a potential racial bias. RESULTS: Published data show that bipolar persons of African ancestry, compared with bipolar persons of non-African ancestry, are more often misdiagnosed with a disease other than bipolar disorder (i.e. schizophrenia). Additionally, studies show that there are disparities in recruiting patients of African ancestry to participate in important genomic studies. This gap in biological research in this underrepresented minority may represent a missed opportunity to address potential racial differences in the risk and course of bipolar illness. CONCLUSION: A concerted effort by the research community to increase inclusion of diverse persons in studies of bipolar disorder through community engagement may facilitate fully addressing these diagnostic and treatment disparities in bipolar individuals of African ancestry.