Circadian genes and bipolar disorder

Bipolar disorder (BD) is a chronic, potentially disabling illness with a lifetime morbid risk of approximately 1%. There is substantial evidence for a significant genetic etiology, but gene-mapping efforts have been hampered by the complex mode of inheritance and the likelihood of multiple genes of small effect. In view of the complexity, it may be instructive to understand the biological bases for pathogenesis. Extensive disruption in circadian function is known to occur among patients in relapse. Therefore, it is plausible that circadian dysfunction underlies pathogenesis. Evidence for such a hypothesis is mounting and is reviewed here. If circadian dysfunction can be established as an 'endophenotype' for BD, this may not only enable identification of more homogenous sub-groups, but may also facilitate genetic analyses. For example, it would be logical to investigate polymorphisms of genes encoding key proteins that mediate circadian rhythms. Association studies that analyzed circadian genes in BD have been initiated and are reviewed. Other avenues for research are also discussed.     

Circadian genes and bipolar disorder

Bipolar disorder (BD) is a chronic, potentially disabling illness with a lifetime morbid risk of approximately 1%. There is substantial evidence for a significant genetic etiology, but gene‐mapping efforts have been hampered by the complex mode of inheritance and the likelihood of multiple genes of small effect. In view of the complexity, it may be instructive to understand the biological bases for pathogenesis. Extensive disruption in circadian function is known to occur among patients in relapse. Therefore, it is plausible that circadian dysfunction underlies pathogenesis. Evidence for such a hypothesis is mounting and is reviewed here. If circadian dysfunction can be established as an ‘endophenotype’ for BD, this may not only enable identification of more homogenous sub‐groups, but may also facilitate genetic analyses. For example, it would be logical to investigate polymorphisms of genes encoding key proteins that mediate circadian rhythms. Association studies that analyzed circadian genes in BD have been initiated and are reviewed. Other avenues for research are also discussed.     

Lamotrigine for the treatment of bipolar disorder

OBJECTIVE: To describe the available data regarding the clinical efficacy of lamotrigine for the treatment of bipolar disorder. SUMMARY: Anticonvulsants have emerged as alternative mood-stabilizing agents for patients with bipolar disorder who do not respond to lithium. Data regarding the efficacy of lamotrigine have been generated primarily from case reports, small open trials, and one large, randomized, placebo-controlled trial. These reports suggest that lamotrigine may be effective for the management of bipolar disorder. CONCLUSIONS: Although current data are limited, treatment-refractory patients with bipolar disorder may benefit from lamotrigine therapy. Several studies are currently underway to determine the appropriate role of lamotrigine in the treatment of bipolar disorder.     

Psychoeducation for bipolar disorder: A discourse analysis

Psychoeducation has become a common intervention within mental health settings. It aims to increase people's ability to manage a life with a long‐term illness. For people with bipolar disorder, psychoeducation is one of a range of psychosocial interventions now considered part of contemporary mental health practice. It has taken on a ‘common sense’ status that results in little critique of psychoeducation practices. Using a published manual on psychoeducation and bipolar disorder as its data, Foucauldian discourse analysis was used in the present study for a critical perspective on psychoeducation in order to explore the taken‐for‐granted assumptions on which it is based. It identifies that the text produces three key subject positions for people with bipolar disorder. To practice self‐management, a person must: (i) accept and recognize the authority of psychiatry to know them; (ii) come to see that they can moderate themselves; and (iii) see themselves as able to undertake a reflexive process of self‐examination and change. These findings highlight the circular and discursive quality to the construct of insight that is central to how psychoeducation is practiced. Using Foucault's construct of pastoral power, it also draws attention to the asymmetrical nature of power relations between the clinician and the person with bipolar disorder. An effect of the use of medical discourse in psychoeducation is to limit its ability to work with ambivalence and contradiction. A critical approach to psychotherapy and education offers an alternate paradigm on which to basis psychoeducation practices.     

Extended-release carbamazepine (Equetro) for bipolar disorder

An extended-release formulation of carbamazepine, available since 1997 for treatment of epilepsy, has now been approved under a new name, Equetro, for acute mania and mixed episodes of bipolar disorder. Although the drug was effective in some patients for up to 6 months, it has not been approved for maintenance treatment. Carbamazepine has not been shown to be more effective than lithium or valproate, and it can cause serious adverse effects.     

Prevalence, clinical correlates, and treatment of migraine in bipolar disorder

OBJECTIVE: To investigate the prevalence, clinical correlates, and treatment of migraine in bipolar disorder. BACKGROUND: The relationship between migraine and mood disorders has been of long-standing interest to researchers and clinicians. Although a strong association has been demonstrated consistently for migraine and major depression, there has been less systematic research on the links between migraine and bipolar disorder. METHODS: A migraine questionnaire (based on International Headache Society criteria) was administered to 108 outpatients with bipolar disorder. Information on the clinical course of bipolar illness was also collected. RESULTS: The overall lifetime prevalence of migraine was 39.8% (43.8% among women and 31.4% among men). In the subgroup of patients with bipolar II disorder, the lifetime prevalence of migraine was 64.7%. The bipolar with migraine group was younger, tended to be more educated, was more likely to be employed or studying, and had fewer psychiatric hospitalizations. Their initial presentation for psychiatric treatment was more often for symptoms of depression, rather than hypomania or mania. They were more likely to have a family history of migraine and psychiatric disorders, and a greater number of affected relatives. They were less likely to use mood stabilizers, and more likely to use atypical antidepressants. Migraine was assessed by a neurologist in only 16% of affected patients. The prevalence of the use of specific antimigraine medications (triptans) was 27.9%. CONCLUSIONS: This study confirms the higher prevalence of migraine among those with bipolar disorder compared to the general population. Migraine in patients with bipolar disorder is underdiagnosed and undertreated. Bipolar disorder with migraine is associated with differences in the clinical course of bipolar disorder, and may represent a subtype of bipolar disorder.     

Clinical,genetic, and brain imaging predictors of risk for bipolar disorder in high-risk individuals

ABSTRACT

Introduction: Early detection and intervention in bipolar disorder (BD) might reduce illness severity, slow its progression, and, in specific cases, even ward off the full-blown disorder. Therefore, identifying at-risk individuals and targeting them promptly before the illness onset is of the utmost importance. In the last decades, there has been a significant effort aimed at identifying genetic and molecular factors able to modulate risk and pharmacological outcomes.

Areas covered: We performed a narrative review of articles aimed at identifying clinical, genetics, molecular, and brain imaging markers of BD specifically focusing on samples of individuals at high-risk for BD. Special emphasis was put on studies applying an integrative design, e.g. studies combining different markers such as genetic and brain imaging.

Expert opinion: Findings from studies in risk individuals are still too sparse to allow drawing definite conclusions. However, the high potentiality of longitudinal studies in individuals considered at risk to develop BD supports the need for more efforts. Future investigations should focus on more homogeneous subpopulations and evaluate the cross-linking between clinical, genetic, and brain morphostructural/functional neuroimaging characteristics as predictors of risk for BD.     

门诊双相情感障碍临床现象学分析

目的了解门诊双相情感障碍(BPD)患者的临床特征和药物治疗方式。方法采用自编的调查问卷对符合DSM-IV双相情感障碍诊断标准的门诊患者进行研究。结果①入组患者共203例,其中双相I型163例(80.3%),双相Ⅱ型40例(19.7%)。②最主要的治疗药物为心境稳定剂(70.4%),其次为抗精神病药物(63%)。③Ⅰ型患者使用心境稳定剂者、抗精神病药物及苯二氮类药物者多于Ⅱ型患者;Ⅱ型患者使用抗抑郁药多于Ⅰ型患者。④联合2种及以上药物治疗者占72.4%。⑤80.5%的双相情感障碍患者病情处于稳定状态。结论门诊双相情感障碍双相I型多于Ⅱ型,Ⅱ型更容易漏诊。目前临床门诊药物治疗方式与国内外指南推荐方案基本符合,联合用药多,多数患者治疗效果良好。     

Sexual health and women with bipolar disorder

AIM: The aim of this paper is to illustrate the importance of sexual health promotion strategies for women with bipolar disorder in order to stimulate interest and debate in this area of care. BACKGROUND: Sexual health promotion is an important aspect of holistic nursing care. However, the literature indicates that nurses are reluctant to discuss sexual health and sexual behaviour with their clients. People with bipolar disorder warrant special consideration with regards to sexual health because the nature of the manic, or hypomanic, mood state is associated in some cases with sexually risky behaviour. For women with bipolar disorder, the associated risks include the threat of unplanned pregnancy or sexually transmitted diseases. To ignore sexual health and sexual behaviour in mental health care increases the vulnerability of women who may already be at risk of sexual exploitation. CASE EXAMPLE: A brief case example is included to demonstrate how the sexual health of a young woman with bipolar disorder was promoted. The sexual health promotion that was incorporated into her care enabled her to make a choice about appropriate contraception, and also provided her with the opportunity to explore acceptable boundaries in different types of interpersonal relationships. As a result of the episodic nature of Bipolar disorder, it is impossible to state whether the positive outcomes from this strategy will be enduring or not. CONCLUSION: Consideration of sexual health is an essential element of the care of women with Bipolar disorder. To ignore it is to neglect an important sphere of human behaviour that can be affected by the condition.     

认知疗法辅助治疗双相情感障碍系统评价

目的系统评价认知疗法辅助治疗双相情感障碍的临床疗效,为临床有效干预提供依据。方法检索Cochrane图书馆临床对照试验资料库（1980-2008）,MEDLINE（1950-2008）,PubMed（1980-2008）、CBMdise（1979-2008）及同方数据库（1979-2008）,手工检索中、英文已发表的资料,收集所有认知疗法辅助治疗双相情感障碍的随机对照试验,根据纳入和排除标准筛选文献、提取资料,并进行质量评价、结果描述;采用RevMan5．0软件对数据进行Meta分析。结果共纳入有效文献6篇;经文献质量评估,5项研究为A级,1项为B级;3项研究对比了认知疗法与未干预的疗效差异,Meta分析显示认知疗法与未干预相比在减少复发率方面无差异性[RR=0．94,95％CI（0．79,1．12）,P=0．491;另3项研究对比了认知疗法与协同照护,结果不完全一致。结论由于纳入研究数量少,样本量小,数据间异质性高,难以证实认知疗法治疗双相障碍的有效性,因此,有待设计良好的随机对照研究进一步验证。     

Latest therapies for bipolar disorder. Looking beyond lithium

Effective treatments of bipolar disorder now extend to a panoply of choices that include various anticonvulsants and antipsychotics. Although lithium still has an important role, particularly in "classic" mania and suicide prevention, the other FDA-approved agents are better tolerated and more efficacious for mixed states and rapid cycling. It is not uncommon to use combination therapy for this challenging disorder. The FDA has approved olanzapine, risperidone, and quetiapine in combination with either lithium or divalproex for acute mania and the combination medication of olanzapine and fluoxetine for acute bipolar depression. Maintenance treatments that have received FDA approval include olanzapine and lamotrigine. Off-label use of adjunctive medications may be required to target residual symptoms.     

Genome scans for susceptibility genes in bipolar affective disorder

A genome-wide scan for genetic linkage can suggest fresh insights into disease aetiology. However, in the case of complex disorders such as bipolar affective disorder (BPAD), the results of genome-wide scans must be interpreted with caution. We review 10 published and 10 in-progress genome scans of BPAD, encompassing 3536 affected individuals in 1119 pedigrees. We find that ascertainment methods vary widely, with no two studies using identical methods. Sample sizes and marker densities have generally been well below what is now considered adequate, but several in-progress studies are using larger samples and more closely spaced markers. Few findings reach the 'suggestive' threshold, and fewer still reach the 'significant' threshold at genome-wide levels of significance. Strategies for pooling samples or subjecting findings in different samples to meta-analysis are being developed, but differences in ascertainment methods may have a large impact on the uniformity of different samples and hamper efforts at combining data or findings. There is also a need for methods that help define more genetically homogeneous phenotypes, take into account interactions between multiple susceptibility loci, and accommodate additional complexity (eg parent-of-origin effects) in the search for linkage.     

Spectrophotometric analysis of lithium carbonate used for bipolar disorder

Lithium therapy is the gold standard of treatment for patients with Bipolar Disorder. However, despite its effectiveness, it is a potentially hazardous drug requiring regular monitoring of blood levels to ensure toxic levels are not reached. This paper describes the spectrophotometric analysis of Lithium carbonate in solution as a first step in developing a portable home monitoring device for blood lithium analysis.. Using a high-end spectrophotometer, solutions of lithium carbonate (Li₂CO₃) have been optically fingerprinted. Preliminary measurements indicate that the ultraviolet region shows a strong distinction between different lithium concentrations. Utilizing second derivative absorption curves, the region of 220 nm to 230 nm demonstrated the ability to differentiate between concentrations representing those found in patients. Furthermore, the method could determine to within a 1–6% accuracy whether an unknown solution of Li₂CO₃ is either inside or outside the high-end of the therapeutic limit.OCIS codes: (170.0170) Medical optics and biotechnology, (170.1470) Blood or tissue constituent monitoring, (170.6510) Spectroscopy, tissue diagnostics     

Emerging treatments for bipolar disorder: safety and adverse effect profiles

OBJECTIVE: To provide an overview of the safety and tolerability of newer agents used to treat bipolar disorder (BPD) and provide clinicians with management strategies for drug-related toxicity and adverse effects. DATA SOURCES: MEDLINE was searched through July 2005 for BPD treatment, adverse effects, tolerability, safety, emerging agents, atypical antipsychotics, new antiepileptic drugs (AEDs), risperidone, quetiapine, clozapine, ziprasidone, aripiprazole, lamotrigine, topiramate, gabapentin, oxcarbazepine, and olanzapine. STUDY SELECTION AND DATA EXTRACTION: Results from randomized controlled trials, open-label studies, and reviews are described. DATA SYNTHESIS: Emerging agents recently approved for BPD include atypical antipsychotics and new AEDs. Safety and tolerability are as important as efficacy because poor adherence in BPD worsens outcome; metabolic and other comorbidities pose specific challenges; and manic patients often require combination therapy, which increases adverse effects. Most atypical antipsychotics cause fewer extrapyramidal symptoms than conventional antipsychotics, but may cause more weight gain and metabolic complications. The newer AEDs generally cause less weight gain than the older agents, and some even promote weight loss. Several newer AEDs used in BPD also offer the advantages of fewer drug interactions and less need for therapeutic drug monitoring compared with older AEDs. CONCLUSIONS: Pending the results of ongoing controlled studies, several emerging agents may be useful additions to the therapeutic arsenal for BPD.     

抑郁症双相情感障碍精神分裂症药物应用状况调查

目的：了解抑郁症、双相情感障碍及精神分裂症患者的药物应用状况。方法采用自制调查表对34例抑郁症、27例双相情感障碍及88例精神分裂症患者的药物应用状况进行统计分析。结果抑郁症以单一用药为主（94．1％）;双相情感障碍在应用情感稳定剂治疗的基础上常联合抗抑郁药物（37．0％）或抗精神病药（37．0％）治疗;精神分裂症单一用药占51．1％,联合用药占48．9％。结论抑郁症、双相情感障碍及精神分裂症患者的临床用药均符合精神药理学规范。