双相及相关障碍的核心特征与治疗

《精神障碍诊断与统计手册(第5版)》(DSM-5)将双相及相关障碍从心境障碍中独立出来,与抑郁障碍分为两章。双相障碍是一类受遗传因素影响较大的精神障碍,其代表性疾病是双相Ⅰ型障碍、双相Ⅱ型障碍和环性心境障碍。躁狂发作是双相Ⅰ型障碍诊断的必要条件,且不再要求个体必须有重性抑郁发作史。双相Ⅱ型障碍需有轻躁狂发作和重性抑郁发作史。环性心境障碍从开始发病,至少有半数时间经历多次轻躁狂期和抑郁期,但未符合轻躁狂发作或重性抑郁发作的诊断标准。双相及相关障碍的治疗方法包括心境稳定剂治疗、心理咨询、电休克治疗等。     

双相障碍的早期识别

双相障碍是一种高复发率(＞90％的患者反复发作)、高自杀率(25％～50％的患者自杀未遂,11％～19％的患者自杀死亡)、高共病率(46％的患者伴酒依赖,60％的患者伴药物依赖)的临床常见病[1].双相障碍的自然病程中,始终仅有躁狂或轻躁狂发作者很少(单纯躁狂约占双相障碍的1％),这些患者的家族史、病前人格、生物学特征、治疗原则及预后等与兼有抑郁发作的双相障碍相似[2].Akiskal[3]疾呼:双相障碍,尤其是双相抑郁大多被临床医生所忽略.     

抗抑郁药物用于双相抑郁的治疗：一个有争议的临床问题

双相障碍是一种慢性致残性疾病。以往治疗的重点在于控制躁狂或轻躁狂症状,然而由于双相障碍患者处于抑郁状态的时间远多于躁狂或轻躁狂状态,近期更多关注的是双相抑郁状态。很多双相障碍患者持续存在阈下抑郁症状。然而,有关双相抑郁药物治疗的循证依据十分有限。     

奥氮平与碳酸锂对双相情感障碍患者躁狂症状、血清尿酸水平的影响及安全性比较

目的比较奥氮平与碳酸锂对双相情感障碍躁狂发作患者症状、血清尿酸水平的影响及安全性。方法对我院治疗的72例双相情感障碍躁狂发作患者进行研究。按照随机数字表发将患者分为观察组和对照组,对照组给予碳酸锂治疗,观察组给予奥氮平治疗。比较两组患者治疗前后的Beck-Rafaelsen躁狂量表(BRMS)评分、血清尿酸水平以及不良反应发生情况。结果两组患者治疗后,BRMS评分较治疗前均有显著降低(P0.05),且观察组患者各时间段的BRMS评分均显著低于对照组各时间段的BRMS评分(P0.05)。两组患者治疗前后及各时间点的血清尿酸水平比较差异均无统计学意义(P0.05)。对两组患者随访8周,对照组的不良反应发生率与观察组相比无显著差异(P0.05)。结论奥氮平治疗双相情感障碍躁狂发作的疗效确切,安全性较高。未发现其对血清尿酸水平的显著影响。     

双相抑郁的药物治疗现状及新探索

对双相障碍中抑郁发作的研究尤为重要,其原因在于:①躁狂发作往往为时短暂,且现有的治疗相当有效,可使患者短时间内缓解;②抑郁发作更为常见,在双相障碍发作周期中所占的时间远远长于躁狂,且往往缺乏有效的治疗[1-2]. 在过去10余年里,双相障碍的治疗取得一些积极进展,但总的状况依然不尽如人意.研究表明,大多数接受规范治疗的双相障碍患者很难达到临床痊愈水平.     

丙戊酸盐治疗急性躁狂症

近几十年,由于神经阻滞剂、锂盐及卡马西平等药物的应用,双相障碍的治疗已经取得了很大进展。但是有相当一部分双相障碍患者用这些药无效或不能耐受其副作用,例如双相障碍躁狂相病人至少有30%碳酸锂治疗无效或不能耐受其副作用,需要寻找一种新药。丙戊酸盐(valproate)以往主要用于治疗癫癎,也有文献报道其对精神疾患、尤其是双相障碍的躁狂相有效。本文对36例符合DSM-Ⅲ-R双相障碍躁狂相标准的病人进行双盲安慰剂对照研究。方法:病人年龄18～65岁,符合DSM-Ⅲ-R双相障碍躁狂相诊断标准,锂盐治疗无效或不能耐受,以往未一次性服过超过     

提高对双相抑郁的诊断认识和药物治疗水平

对双相情感障碍的研究，以往更多的兴趣集中在双相躁狂和单相抑郁的急性期和长期治疗上，而对双相抑郁的研究则较少。但在临床实践中，双相抑郁的药物治疗更为复杂，长期治疗的时间也远长于躁狂。近年来通过对双相抑郁的研究发现，临床上常出现由于对双相抑郁的诊断意识低而引起的误诊问题，     

奥氮平单药与联合碳酸锂治疗双相障碍躁狂发作患者的对照研究

目的:比较奥氮平单药与奥氮平联合碳酸锂治疗双相躁狂或混合发作患者的疗效与安全性. 方法:60例双相障碍Ⅰ型躁狂发作或混合性发作患者随机分为单用药组29例和合用药组31例.分别给予奥氮平单药和奥氮平联合碳酸锂治疗.疗程4周.于基线时,治疗l,2,3和4周,分别采用临床总体印象量表-双相障碍版、Young躁狂量表(YMR...     

双相障碍治疗前后催乳素、雌二醇水平的改变 及其与临床疗效的关系

目的 探讨双相障碍治疗前后催乳素（PRL）、雌二醇（E2）水平变化及其与临床疗效的关 联。方法 选取2014年1月—2015年5月收住北京回龙观医院的符合ICD-10标准的双相障碍患者57例（男 36 例,女21 例）,其中双相躁狂39 例,双相抑郁18 例。入组后患者接受药物治疗,治疗时间为6 周,采用 汉密尔顿抑郁量表24项版（HAMD-24）评估抑郁症状,采用贝克-拉范森躁狂量表（BRMS）评估躁狂症状。 使用化学发光免疫分析法检测研究对象周围血中E2、PRL水平。结果 与基线相比,治疗后双相障碍患 者PRL浓度降低,差异有统计学意义（P=0.01）,E2浓度未见明显升高（P＞0.05）。双相躁狂组PRL水平降 低,差异有统计学意义（P=0.01）。双相抑郁组PRL、E2浓度变化均不明显（P＞0.05）。双相躁狂组治疗前 BRMS评分及双相抑郁组治疗后HAMD-24评分均下降,差异有统计学意义（均P＜0.01）。躁狂组治疗前 PRL水平与BRMS评分呈正相关（r=0.41,P＜0.01）,躁狂组治疗前后PRL变化值及E2变化值与BRMS减分 值呈正相关（r=0.39,P＜0.01;r=0.33, P=0.03）。结论 双相障碍、躁狂发作患者治疗后PRL均下降,躁狂 发作患者的症状、疗效与PRL水平的变化可能存在一定相关性。     

不同临床相双相障碍患者甲状腺功能的回顾性研究

目的探究双相障碍患者甲状腺功能的临床相和性别差异,以期为双相障碍的诊断和治疗提供参考。方法采用回顾性研究方法,收集河南省精神病医院2015年9月-2018年1月的住院患者甲状腺功能生化指标,包括促甲状腺素(TSH)、三碘甲状腺原氨酸(T_3)、甲状腺素(T_4)、游离三碘甲状腺原氨酸(FT_3)和游离甲状腺素(FT_4),筛选符合《国际疾病分类(第10版)》(ICD-10)诊断标准的双相障碍躁狂发作(双相躁狂)和双相障碍抑郁发作(双相抑郁)患者2 207例,同期选择415例体检人员作为正常对照组,比较不同临床相和不同性别的双相障碍患者甲状腺功能的差异。结果①双相躁狂患者的T_3、FT_3水平高于双相抑郁患者,TSH、T_4水平低于正常对照组;双相抑郁患者的TSH、T_3、T_4、FT_3水平均低于正常对照组(P0. 05或0. 01);②在双相躁狂患者中,男性T_3、FT_3和FT_4水平高于女性,而TSH、T_4水平低于女性,在双相抑郁患者中,男性T_3、FT_3和FT_4水平高于女性,而TSH水平低于女性(P0. 05或0. 01);③在男性患者中,双相躁狂患者的T_3和FT_3水平均高于双相抑郁患者,双相抑郁患者的T_3水平低于正常对照组(P0. 05或0. 01);在女性患者中,双相躁狂患者的T_3和FT_3水平高于双相抑郁患者,双相抑郁患者的T_3、T_4、FT_3水平均低于正常对照组(P0. 05或0. 01)。结论双相障碍患者的甲状腺功能可能存在临床相和性别的差异。     

Staging Bipolar Disorder

The purpose of this study was to analyze the evidence supporting a staging model for bipolar disorder. The authors conducted an extensive Medline and Pubmed search of the published literature using a variety of search terms (staging, bipolar disorder, early intervention) to find relevant articles, which were reviewed in detail. Only recently specific proposals have been made to apply clinical staging to bipolar disorder. The staging model in bipolar disorder suggests a progression from prodromal (at-risk) to more severe and refractory presentations (Stage IV). A staging model implies a longitudinal appraisal of different aspects: clinical variables, such as number of episodes and subsyndromal symptoms, functional and cognitive impairment, comorbidity, biomarkers, and neuroanatomical changes. Staging models are based on the fact that response to treatment is generally better when it is introduced early in the course of the illness. It assumes that earlier stages have better prognosis and require simpler therapeutic regimens. Staging may assist in bipolar disorder treatment planning and prognosis, and emphasize the importance of early intervention. Further research is required in this exciting and novel area.     

The mood spectrum: improving the diagnosis of bipolar disorder

Although the distinction between bipolar and unipolar disorders served our field well in the early days of psychopharmacology, in clinical practice it is apparent that their phenotypes are only partially described by current diagnostic classification systems. A substantial body of evidence has accrued suggesting that clinical variability needs to be viewed in terms of a broad conceptualization of mood disorders and their common threshold or subthreshold comorbidity. The spectrum model provides a useful dimensional approach to psychopathology and is based on the assumption that early-onset and enduring symptoms shape the adult personality and establish a vulnerability to the subsequent development of Axis-I disorders. To obtain a clearer understanding of the depressive phenotype, it is pivotal that we increase our detection of hypomanic symptoms so that clinicians can better distinguish bipolar II disorder from unipolar depression. Diagnostic criteria sensitive to hypomanic symptoms have been identified that suggest bipolar II disorder is at least as prevalent as major depression. Moreover, the comorbidities of these illnesses are very different and alcoholism in particular appears to be a greater problem in bipolar II disorder than in unipolar depression. Structured clinical interviews and patient self-report questionnaires have also successfully identified the presence of hypomanic symptoms in patients with unipolar disorder and support the concept of a spectrum of bipolar illness. In conclusion, the importance of subthreshold syndromes should not be underestimated as failure to recognize bipolar spectrum disorder could delay treatment and worsen prognosis.     

Bipolar disorder, schizoaffective disorder and schizophrenia: epidemiologic, clinical and prognostic differences.

The validity and nosologic status of schizoaffective disorder is still a controversial issue. This study was conducted to analyze the demographic, clinical and prognostic variables that determine the validity of the diagnosis of schizoaffective disorder bipolar type. We analyzed and compared 138 outpatients: 67 with type I bipolar disorder, 34 with schizoaffective disorder bipolar type and 37 with schizophrenia. They were all diagnosed following research diagnostic criteria and assessed according to the Schedule for Affective Disorders and Schizophrenia. Schizoaffective unipolar patients were excluded. The results reaffirmed that, from the standpoints of demographics, clinical features and prognosis, schizoaffective disorders bipolar type can be classified as a phenotypic form at an intermediate point between bipolar I disorder and schizophrenia. These results emphasize the importance of longitudinal follow-up in the diagnosis and assessment of psychotic syndromes. Although cross-sectional symptoms were closer to the schizophrenia spectrum, the course of the illness resembled more that of bipolar patients, resulting in an intermediate outcome.     

Is there an association between duration of untreated psychosis and 24-month clinical outcome in a first-admission series?

OBJECTIVE: The authors examined the duration of untreated psychosis, defined as the interval from first psychotic symptom to first psychiatric hospitalization, in a county-wide sample of first-admission inpatients who had received no previous antipsychotic medication. Differences between diagnostic groups in 24-month illness course and clinical outcomes as well as relationships between outcomes and duration of untreated psychosis were evaluated. METHOD: The data were derived from subjects in the Suffolk County Psychosis Project who were diagnosed at 24-month follow-up according to DSM-IV as having schizophrenia or schizoaffective disorder (N=155), bipolar disorder with psychotic features (N=119), or major depressive disorder with psychotic features (N=75). Duration of untreated psychosis was derived from the Structured Clinical Interview for DSM-III-R, medical records, and information from significant others. Measures at 24-month follow-up included consensus ratings of illness course, Global Assessment of Functioning Scale scores for the worst week in the month before interview, and current affective and psychotic symptoms. RESULTS: The median duration of untreated psychosis was 98 days for schizophrenia, 9 days for psychotic bipolar disorder, and 22 days for psychotic depression. Duration of untreated psychosis was not significantly associated with 24-month illness course or clinical outcomes in any of the diagnostic subgroups. CONCLUSIONS: Although these findings require replication in other epidemiologically based first-admission samples, at face value they do not support the suggestion of a psychotoxic effect of prolonged exposure to untreated psychosis.     

双相障碍早期识别的诊断和评估工具的开发与应用

双相障碍以反复出现的躁狂或抑郁发作为典型特点,但其临床表现复杂,病程演变多样,起病初期与单相抑郁难以区分,易造成临床诊断困难。该病共患病多,自杀风险高,预后不良,严重的社会负担使其日益受到重视,如何早期识别双相障碍是国内外研究的热点之一。近年来,随着对双相障碍临床现象学研究的不断深入,具有临床早期识别和诊断价值的评估工具相继问世,有效地提高了临床医生对双相障碍的早期识别能力,为后续规范化治疗、改善预后提供了有力保障。针对双相障碍的早期识别,本文对新近开发的一些具有较高临床应用价值的诊断与评估工具进行介绍与评述。     

Presence of co-morbid substance use disorder in bipolar patients worsens their social functioning to the level observed in patients with schizophrenia

Bipolar disorder has been considered to have a better prognosis than schizophrenia at the very beginning of its definition. However, psychosocial functioning may vary not only because of the characteristics of the disorder, but also of co-morbid conditions, especially regarding substance use disorder (SUD). The purpose of this study was to compare the social adjustment level of patients with bipolar disorder with that observed in patients with schizophrenia, taking into account substance use disorder (SUD). Forty subjects with schizophrenia and 40 subjects with bipolar disorder, in the stable phase of the disorder, were matched for age, gender and presence of SUD (DSM-IV criteria). The social adjustment scale was completed with socio-demographic and clinical characteristics of illness. The global adaptation score of bipolar patients with SUD was poorer than bipolar patients without SUD, but was not observed as being significantly different from that of patients with schizophrenia, with or without associated SUD. Suicide attempts, poor compliance, longer hospitalisation, shorter remissions and criminal activity were also more frequently observed in the group of patients with bipolar disorder and SUD. Presence of substance use disorder seems to have a greater weight than the main diagnostic (schizophrenia versus bipolar disorder) to predict worse social adjustment and poorer outcome.     

Abnormalities of cyclic adenosine monophosphate signaling in platelets from untreated patients with bipolar disorder

BACKGROUND: Abnormalities in the cyclic adenosine monophosphate (cAMP)-dependent phosphorylation system have been recently reported in patients with bipolar disorder. We evaluated the immunoreactivity of the regulatory and catalytic subunits of cAMP-dependent protein kinase (protein kinase A) and 1 of its substrates, Rap1, in platelets from untreated euthymic, manic, and depressed patients with bipolar disorder and healthy subjects. METHODS: Platelets were collected from 112 drug-free patients with bipolar disorder (52 euthymic, 29 depressed, and 31 manic) and 62 healthy subjects. The levels of cAMP-dependent protein kinase and Rap1 were assessed by Western blot analysis, immunostaining, and computer-assisted imaging. RESULTS: The immunolabeling of the catalytic subunit of cAMP-dependent protein kinase was significantly different among groups (P<.001), with higher values in untreated depressed and manic patients with bipolar disorder compared with untreated euthymic patients with bipolar disorder and healthy subjects. No significant differences were found in the immunolabeling of the regulatory subunits (type I and type II) of cAMP-dependent protein kinase. The immunolabeling of Rap1 was significantly higher (P<.001) in untreated euthymic, depressed, and manic patients than in healthy persons. CONCLUSIONS: Levels of Rap1 and the catalytic subunit of cAMP-dependent protein kinase are altered in the platelets of bipolar patients. These findings may provide clues toward understanding the involvement of cAMP signaling in the pathogenesis of bipolar disorder.     

青少年期起病的双相障碍与强迫症共病研究

目的：探讨青少年期起病的双相障碍与强迫症共病患者的临床特征。方法：选择双相障碍和强迫症共病患者（共病组）36例及强迫症患者（OCD组）31例，完成自编调查问卷、强迫症量表（Y-BOCS）测评。结果：OCD组的男性比例高于共病组；共病组的强迫症病程、平均治疗时间长于OCD组。结论：双相障碍与强迫症共病是常见的临床现象，共病对患者的病程及疗效均有影响。     

Unmet needs in bipolar depression

Bipolar disorders, particularly bipolar spectrum disorders, frequently go unrecognized and undiagnosed by clinicians and thus remain untreated or inappropriately treated. Although the symptoms of bipolar I disorder are widely acknowledged and recognized among clinicians, epidemiology sampling studies over the past several years have found that bipolar II disorder and bipolar spectrum disorders are likely to be more prevalent and more challenging to diagnose, particularly as depressive presentations are far more common in these groups. Bipolar disorder is associated with increased morbidity and mortality, as well as higher healthcare costs, but it is unclear how much of the consequences of bipolar disorder are unrecognized in the face of poor recognition of bipolar II and bipolar spectrum disorders. This article addresses challenges in diagnosing and treating bipolar disorder in the face of a depressive episode, and offers guidelines for recognizing and appropriately managing these patients. Studies with the newer anticonvulsant mood stabilizer lamotrigine have shown antidepressant effects in bipolar disorder, and may fill an unmet need for treatment options in patients who present with depression in the context of bipolar disorder.