精神病学及临床心理学进展专栏（征译稿）

精神病学及临床心理学进展专栏（征译稿） 大家可以动态报道最新的psychiarty and clinical psychology方面的临床和基础实验，首先包括新英格兰杂志，柳叶刀，JAMA，BMJ等医学综合类杂志和专业杂志如：ACTA PSYCHIAT SCAND，AM J PSYCHIAT，ANNU REV PSYCHOL，ARCH GEN PSYCHIAT，BIOL PSYCHIAT，BRIT J PSYCHIAT，J CLIN PSYCHIAT，MOL PSYCHIATR等。 主要以摘要为主，也欢迎全文。 文章可以由我选取，也可以由战友提供，并鼓励由战友提供。为保持本栏目的权威性，对于科学性相对较差的临床/基础实验文献（impact factor)低于4分的文献原则上控制登出。临床病例、病理讨论除外。 加分规则： 1，同时提供文献和摘要译稿的最低分1分，根据文献质量和译文质量加分，最高分4分。 2，对于仅提供文献无译文者，将由斑竹决定是否加分，最高分1分。对于灌水低质量文献求分者扣分。 3，推荐大家跟贴，也可以自行发帖。 希望大家多支持。 This is a sample TIncreased cerebrospinal fluid glutamine levels in depressed patients. SO: Biol-Psychiatry. 2000 Apr 1; 47(7): 586-93 BACKGROUND: There is increasing evidence for an association between alterations of brain glutamatergic neurotransmission and the pathophysiology of affective disorders. METHODS: We studied the association between cerebrospinal fluid (CSF) metabolites, including glutamine, in unipolar and bipolar depressed patients versus control subjects using a proton magnetic resonance spectroscopy technique. Cerebrospinal fluid samples were obtained from 18 hospitalized patients with acute unmedicated severe depression without medical problems and compared with those of 22 control subjects. RESULTS: Compared with the control group, the depressed patient group had significantly higher CSF glutamine concentrations, which correlated positively with CSF magnesium levels. CONCLUSIONS: These findings suggest an abnormality of the brain glial-neuronal glutamine/glutamate cycle associated with N-methyl-D-aspartate receptor systems in patients with depression. 背景：越来越多的证据表明情感性精神障碍的病理生理学与大脑谷氨酸能递质的改变之间存在联系。 方法：使用质子磁共振波谱（MRS）研究单相抑郁和双相障碍抑郁相患者及对照组个体包括谷氨酸在内的脑脊液代谢物之间的联系。脑脊液样本取自18例未经药物治疗的无躯体合并症的住院急性重症抑郁症患者和22例对照组个体。 结果：与对照组个体相比，抑郁症患者脑脊液谷氨酸浓度显著要高，且与脑脊液镁的浓度呈正相关。 结论：这些发现说明抑郁症患者大脑神经胶质-谷氨酰胺/谷氨酸循环的异常与N-甲基-D-天冬氨酸（***A）受体系统有关。为保持本栏目的权威性，对于科学性相对较差的临床/基础实验文献（impact factor)低于4分的文献原则上控制登出。 怎样知道文献的影响因子？影响因子是由杂志决定的吗？还是由文章本身决定的？ 首先包括新英格兰杂志，柳叶刀，JAMA，BMJ等医学综合类杂志和专业杂志如：ACTA PSYCHIAT SCAND，AM J PSYCHIAT，ANNU REV PSYCHOL，ARCH GEN PSYCHIAT，BIOL PSYCHIAT，BRIT J PSYCHIAT，J CLIN PSYCHIAT，MOL PSYCHIATR等。 上述杂志的影响因子都大于4吧。[翻译][摘要]分析性心理治疗的适应症 1: Acta Psychiatr Scand. 2004 Mar;109(3):164-78. Suitability for psychoanalytic psychotherapy: a review. Valbak K. Department North, Psychiatric Hospital in Aarhus, The Aarhus University Hospital, Risskov, Denmark. kv@psykiatri.aaa.dk OBJECTIVE: To review empirical studies on outpatients' pretherapy suitability for psychoanalytic psychotherapy. METHOD: A literature search for studies in English was made in the databases MEDLINE, PsychInfo and EM-base. Forty-one studies spanning 20 years were selected for a thorough evaluation. RESULTS: Seventy-five per cent of the studies concerned brief dynamic psychotherapy. In general, application of single measures of suitability had a modest predictive value with correlations in the range of 0.17-0.73. There was no consistent difference between various formats of therapies. Most promising variables with the highest correlations with good outcome were: 'good quality of object relations', 'psychological mindedness' and 'motivation for change'. Some clinical guidelines can be drawn from quantitative research to provide the therapist with best method and format. CONCLUSION: The importance of psychological variables known from the development of the brief dynamic therapies and earlier research was confirmed. Most correlations were modest and single factors could not be identified. Multivariate designs that combine different methods and formats with patient characteristics seem most promising in future predictor-outcome research. Publication Types: Review Review, Tutorial PMID: 14984388 [PubMed - indexed for MEDLINE] 综述：分析性心理治疗的适应症。 丹麦澳尔胡斯大学医院精神科 Valbak K. 目的：回顾对于门诊病人是否适合精神分析治疗的的经验性研究。 方法：查阅MEDLINE, PsychInfo and EM-base三个数据库的英文文献。选出20多年内的41个研究进行彻底评估。 结果：75%的研究与短期动力学治疗有关。总的来看，单一标准对于适应症有一个中等程度的预测值，在0.17-0.73之间。不同形式的分析性治疗的效果没有一致的差异。与取得好的治疗效果最密切的变量是“好的客体关系”，“心理学头脑”，“改变自己的动机” 。通过定量研究可以给治疗师选择最佳治疗方法和治疗形式写一些临床的指导手册。 结论：短期动力学治疗的早期研究和发展过程中提出的与疗效有关的变量得到了证实。多数的相关性为中等程度，单一因子还不能被确认。根据病人特质用多元的设计结合不同的治疗方法和治疗形式看上去在将来预测心理治疗结果的研究中是最有前途的。jeansjan wrote: 为保持本栏目的权威性，对于科学性相对较差的临床/基础实验文献（impact factor)低于4分的文献原则上控制登出。 怎样知道文献的影响因子？影响因子是由杂志决定的吗？还是由文章本身决定的？ 首先包括新英格兰杂志，柳叶刀，JAMA，BMJ等医学综合类杂志和专业杂志如：ACTA PSYCHIAT SCAND，AM J PSYCHIAT，ANNU REV PSYCHOL，ARCH GEN PSYCHIAT，BIOL PSYCHIAT，BRIT J PSYCHIAT，J CLIN PSYCHIAT，MOL PSYCHIATR等。 上述杂志的影响因子都大于4吧。 一般指某个杂志的影响因子（impact factor）特指科学引文索引（science citation index）即SCI收录的期刊。简单的说，IF衡量依据是根据刊登的论文被引用的频率，有专门的机构负责评价。 影响因子是杂志的质量好坏的重要衡量指标，每年都要重新评定，当然杂志刊登的文章的质量对杂志的IF非常重要。这也是顶级杂志据稿率高的原因。 我举例的这些杂志不都是IF大于4分的，但考虑ACTA PSYCHIAT SCAND和BRIT J PSYCHIAT国内可以获得全文，且质量相当也较高，所以也欢迎以上杂志的文摘翻译。 想了解IF的更具体信息，及某个杂志的IF可以到DXY文献求助区检索相关知识，或参考相关书籍。Depression in Schizophrenia: Perspective in the Era of "Atypical" Antipsychotic Agents Samuel G. Siris, M.D Am J Psychiatry 157:1379-1389, September 2000 © 2000 American Psychiatric Association ABSTRACT OBJECTIVE: The author sought to provide a contemporary understanding of depression in schizophrenia and promote a treatment orientation. METHOD: Computer and library-based resources were used to review the literature on depression in schizophrenia. RESULTS: Despite multiple definitions of "depression," a substantial rate of depression has consistently been found in patients with schizophrenia. A differential diagnosis can be used to advance the understanding and treatment of depression in schizophrenia, and changes in response to the advent of atypical antipsychotic agents can be understood in the context of this differential diagnosis paradigm. CONCLUSIONS: Depression is an important co-occurring syndrome in schizophrenia. In at least some schizophrenic patients, the stress-vulnerability model has potential as an integrating concept concerning the relationship between depression and psychosis. 目的：作者旨在提供对精神分裂症抑郁的当代理解，促进治疗。方法：利用图书馆和计算机资源对精神分裂症抑郁的文献评述。结果：尽管诊断标准不同，但精神分裂症常伴抑郁却是肯定的，鉴别诊断有助于理解和治疗，在鉴别诊断范例的背景下，对于非典型抗精神病药带来的变化更易理解，结论：抑郁是精神分裂症的常见伴发症状，至少部分病人表现出来的应激易感性对于抑郁和精神病的关系而言可以作为一个整合概念。Am J Psychiatry. 2004 Nov;161(11):2108-14. Related Articles, Links Axis I comorbidity in patients with borderline personality disorder: 6-year follow-up and prediction of time to remission. Zanarini MC, Frankenburg FR, Hennen J, Reich DB, Silk KR. McLean Hospital, 115 Mill St., Belmont, MA 02478, USA. zanarini@mclean.harvard.edu OBJECTIVE: The purpose of this study was to assess the prevalence of axis I disorders among patients with borderline personality disorder over 6 years of prospective follow-up. METHOD: A semistructured interview of demonstrated reliability was used to assess presence or absence of comorbid axis I disorders in 290 patients who met Revised Diagnostic Interview for Borderlines criteria and DSM-III-R criteria for borderline personality disorder and 72 patients who did not meet these criteria but did meet DSM-III-R criteria for another axis II disorder. Over 94% of surviving patients were reinterviewed about their axis I disorders at 2-year, 4-year, and 6-year follow-up periods. RESULTS: Although the patients with borderline personality disorder experienced declining rates of many axis I disorders over time, the rates of these disorders remained high, particularly the rates of mood and anxiety disorders. Patients whose borderline personality disorder remitted over time experienced substantial decline in all comorbid disorders assessed, but those whose borderline personality disorder did not remit over time reported stable rates of comorbid disorders. When the absence of comorbid axis I disorders was used to predict time to remission, the absence of substance use disorders was a far stronger predictor of remission from borderline personality disorder than was the absence of posttraumatic stress disorder, mood disorders, other anxiety disorders, or eating disorders, respectively. CONCLUSIONS: The results of this study suggest that axis I disorders are less common over time in patients with initially severe borderline personality disorder, particularly for patients whose borderline personality disorder remits over time. The findings also suggest that substance use disorders are most closely associated with the failure to achieve remission from borderline personality disorder. PMID: 15514413 [PubMed - indexed for MEDLINE]J Clin Psychol. 2004 Dec;60(12):1291-315. Related Articles, Links How does psychotherapy influence personality? A theoretical integration. Mayer JD. Department of Psychology, University of New Hampshire, Durham, NH 03824, USA. jack.mayer@unh.edu A given type of psychotherapy (e.g., psychodynamic) is associated with a set of specific change techniques (e.g., interpreting defenses, identifying relationship themes). Different change techniques can be conceived of as influencing different parts of personality (e.g., interpreting defense increases conscious awareness). An integrated model of personality is presented. Then, change techniques from different theoretical perspectives are assigned by judges to areas of personality the techniques are believed to influence. The results suggest that specific change techniques can be reliably sorted into the areas of personality. Thinking across theoretical perspectives leads to important new opportunities for assessment, therapy outcome research, and communication with patients concerning personality change. 2004 Wiley Periodicals, Inc. PMID: 15470725 [PubMed - in process]太晚了,暂时只提供摘要,明天再组织翻译.Arch Gen Psychiatry. 2004 Sep;61(9):866-76. Related Articles, Links Cognitive enhancement therapy for schizophrenia: effects of a 2-year randomized trial on cognition and behavior. Hogarty GE, Flesher S, Ulrich R, Carter M, Greenwald D, Pogue-Geile M, Kechavan M, Cooley S, DiBarry AL, Garrett A, Parepally H, Zoretich R. University of Pittsburgh Medical Center, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA. hogartyje@upmc.edu BACKGROUND: Deficits in social cognition and neurocognition are believed to underlie schizophrenia disability. Attempts at rehabilitation have had circumscribed effects on cognition, without concurrent improvement in broad aspects of behavior and adjustment. OBJECTIVE: To determine the differential effects of cognitive enhancement therapy (a recovery-phase intervention) on cognition and behavior compared with state-of-the-art enriched supportive therapy. DESIGN: A 2-year, randomized controlled trial with neuropsychological and behavioral assessments completed at baseline and at 12 and 24 months. SETTING: An outpatient research clinic housed in a medical center's comprehensive care service for patients with severe mental illness. PATIENTS: A total of 121 symptomatically stable, non-substance-abusing but cognitively disabled and chronically ill patients with schizophrenia or schizoaffective disorder. INTERVENTIONS: Cognitive enhancement therapy is a multidimensional, developmental approach that integrates computer-assisted training in neurocognition with social cognitive group exercises. Enriched supportive therapy fosters illness management through applied coping strategies and education. MAIN OUTCOME MEASURES: Six highly reliable summary measures--Processing Speed, Neurocognition, Cognitive Style, Social Cognition, Social Adjustment and Symptoms--were tested using analysis of covariance and linear trend analysis. RESULTS: At 12 months, robust cognitive enhancement therapy effects were observed on the Neurocognition and Processing Speed composites (P<.003), with marginal effects observed on the behavioral composites. By 24 months, differential cognitive enhancement therapy effects were again observed for the 2 neuropsychological composites and for Cognitive Style (P=.001), Social Cognition (P=.001), and Social Adjustment (P=.01). As expected, no differences were observed on the residual Symptoms composite. Effects were unrelated to the type of antipsychotic medication received. Enriched supportive therapy also demonstrated statistically significant within-group effect sizes, suggesting that supportive psychotherapy can also have positive, although more modest, effects on cognitive deficits. CONCLUSION: Many cognitive deficits and related behaviors of patients with stable schizophrenia are improved when sufficient exposure to relevant rehabilitation is provided. Publication Types: Clinical Trial Randomized Controlled Trial PMID: 15351765 [PubMed - indexed for MEDLINE]Am J Psychiatry. 2004 Sep;161(9):1665-71. Related Articles, Links Long-term changes in defense styles with psychodynamic psychotherapy for depressive, anxiety, and personality disorders. Bond M, Perry JC. Department of Psychiatry, Sir Mortimer B.Davis-Jewish General Hospital and McGill University, Quebec, Canada. michael.bond@mcgill.ca OBJECTIVE: This study examined 1) whether patients with chronic and recurrent anxiety and depressive disorders and/or personality disorders demonstrate improvement in their defense styles with long-term dynamic psychotherapy and 2) what the relationship is between defense style change and symptomatic change. METHOD: Measures of defense (Defense Style Questionnaire) and symptoms and functioning were administered at regular intervals over the course of 3-5 years to adults who entered a naturalistic study of long-term psychodynamic psychotherapy. With hierarchical linear regression, the relative contributions of change in variables on the Defense Style Questionnaire to change in other outcome variables were calculated. RESULTS: Those with high initial scores on the maladaptive and self-sacrificing defense styles improved, with effect sizes of 0.80 and 0.67, while overall defensive functioning improved, with an effect size of 0.43. The effect size of the change in score on the Global Assessment of Functioning scale was 0.82. Depressed subjects improved their scores significantly on the Hamilton Depression Rating Scale, and there was a significant improvement in distress, as measured by the SCL-90-R. Changes in score on the Defense Style Questionnaire added substantially to the prediction of variance in these three outcomes above their initial levels. A higher level of defensive functioning also predicted a better self-reported therapeutic alliance. CONCLUSIONS: Defense styles became more adaptive and symptoms improved over time in patients who started with scores in the clinical range. Change in defense style predicts symptomatic change, but causation has not been established. PMID: 15337658 [PubMed - indexed for MEDLINE]请不要只提供摘要，否则就变成PUBMED的题录展示厅了， 给出翻译，最好还能评论下研究的缺陷和进一步研究的方向等 （当然只根据文摘做出以上评价较难）。平一指1974 wrote: Am J Psychiatry. 2004 Sep;161(9):1665-71. Related Articles, Links Long-term changes in defense styles with psychodynamic psychotherapy for depressive, anxiety, and personality disorders. Bond M, Perry JC. Department of Psychiatry, Sir Mortimer B.Davis-Jewish General Hospital and McGill University, Quebec, Canada. michael.bond@mcgill.ca OBJECTIVE: This study examined 1) whether patients with chronic and recurrent anxiety and depressive disorders and/or personality disorders demonstrate improvement in their defense styles with long-term dynamic psychotherapy and 2) what the relationship is between defense style change and symptomatic change. METHOD: Measures of defense (Defense Style Questionnaire) and symptoms and functioning were administered at regular intervals over the course of 3-5 years to adults who entered a naturalistic study of long-term psychodynamic psychotherapy. With hierarchical linear regression, the relative contributions of change in variables on the Defense Style Questionnaire to change in other outcome variables were calculated. RESULTS: Those with high initial scores on the maladaptive and self-sacrificing defense styles improved, with effect sizes of 0.80 and 0.67, while overall defensive functioning improved, with an effect size of 0.43. The effect size of the change in score on the Global Assessment of Functioning scale was 0.82. Depressed subjects improved their scores significantly on the Hamilton Depression Rating Scale, and there was a significant improvement in distress, as measured by the SCL-90-R. Changes in score on the Defense Style Questionnaire added substantially to the prediction of variance in these three outcomes above their initial levels. A higher level of defensive functioning also predicted a better self-reported therapeutic alliance. CONCLUSIONS: Defense styles became more adaptive and symptoms improved over time in patients who started with scores in the clinical range. Change in defense style predicts symptomatic change, but causation has not been established. PMID: 15337658 [PubMed - indexed for MEDLINE] 精神动力治疗引起抑郁、焦虑和人格障碍患者心理防御方式的长期改变 目的 首先，本研究考察了具有或不具有人格障碍的长期、周期性的焦虑症和抑郁症患者经过长期的精神动力治疗能否引起心理防御方式的改变；其次，考察心理防御方式的变化和患者症状的变化两者之间的关系。方法 在3-5年内，对参加精神动力治疗研究的成年人定期评定他们的心理防御方式（心理防御方式问卷）、症状和技能，用分级线性回归分析评价其他因果变量引起心理防御方式问卷中变量变化的相对贡献。结果 那些在心理防御方式问卷中适应不良和自我牺牲的初始分数高的人群有明显变化，统计效应大小分别是0.80和0.67，而整体的心理防御机能变化的统计效应大小是0.43。整体性机能评价量表得分改变的统计效应大小是0.82。抑郁症患者的汉密尔顿抑郁量表得分明显改变，SCL-90修订版的抑郁因子分也有显著变化。心理防御方式问卷分数的变化与那些高出初始水平的三项结果的变化明显相关。较高水平的心理防御机能也预示着更好的心理治疗联盟。结论 在经过一段时间的精神动力治疗后，患者的心理防御方式变的更具适应性，症状也得到改善。心理防御方式的改变预示着症状上的变化，但其因果关系有待于进一步确定。 翻译的不好，拿出来献丑了，请大家指正。蓝色标记的，是自己感觉最糟糕的。其余的还有很多错误或不当之处。不过，整个译文可能说出了大体意思吧。^_^Have schizophrenia genes been found? Amanda Elkina,b, Sridevi Kalidindia,b and Peter McGuffina Purpose of review The understanding of the molecular genetics of schizophrenia has advanced considerably in recent years. New findings are scrutinized, particularly concentrating on progress since mid-2002. Recent findings Recent studies have focused on positional and functional candidate genes postulated to be associated with schizophrenia. These include neuregulin, dysbindin, G72/Damino acid oxidase, proline dehydrogenase (PRODH), catechol-O-methyltransferase (COMT), regulator of G protein signalling (RGS-4), 5HT2A and dopamine D3 receptor. There is also a promising newcomer, PPP3CC. Three new studies support the role of neuregulin. Similarly, associations with dysbindin are present in all samples reported to date, although with different haplotypes. As yet, there is one study implicating G72 and this has also just been implicated with bipolar affective disorder. COMT and PRODH are both genes located within the linkage/Velo-Cardio Facial Syndrome (VCFS) microdeletion region of chromosome 22q. COMT seems likely to play an etiological role in schizophrenia although whether a high or lowactivity variant is responsible is currently unclear. The evidence for PRODH is equivocal, with several positive studies but one larger negative one. RGS-4 has also received recent support and a metaanalysis continues to support an association between schizophrenia and the functional candidate genes, 5HT2A and dopamine D3 receptor. Summary Schizophrenia genes have been found at last. A potentially exciting phase of research is imminent. It is likely that more susceptibility genes and the functional significance of variations within them will be identified. Potentially, this has implications for future treatments. We also suggest that, in light of further genetic evidence, a re-evaluation of psychiatric classification may be required. Keywords genetics, schizophrenia Current Opinion in Psychiatry 2004, 17:107–113 精神分裂症基因被发现了吗？ 综述目的 近年来，对精神分裂症的分子遗传学的研究已获得较大的进展。本文回顾了该领域的新成果，尤其是2002年下半年之后的研究进展。 近来的研究成果 近来与精神分裂症相关的位置的和功能的候选基因的研究受到关注。包括神经调节蛋白, dysbindin, G72/D氨基酸氧化酶,脯氨酸脱氢酶(PRODH), 儿茶酚-O-甲基转移酶（catechol-O-methyltransferase，COMT）, G蛋白信号调节体（regulator of G protein signalling，RGS-4), 5HT2A 和多巴胺D3受体。还有一个有希望的新成员，PPP3CC. 这些新的研究支持神经调节蛋白的作用。同样，尽管单倍型不同，至今为止发表的所有样本都显示dysbindin与精神分裂症的相关性。一项研究支持G72的作用并且它涉及到双相情感障碍。 COMT和PRODH均定位于22q的microdeletion区的linkage/Velo-Cardio Facial Syndrome (VCFS) 。 尽管不清楚发挥作用时COMT的活性是增高还是降低，COMT仍可能对精神分裂症具有致病作用。 对PRODH的作用尚无定论，几项研究得出了阳性结果而一项更大的研究得出了阴性结果。近来的研究也支持RGS-4，并且一项meta分析支持精神分裂症与功能性候选基因5HT2A和多巴胺D3受体有关。 摘要 最终精神分裂症的基因会被发现。激动人心的时刻即将来临。更多的易感基因和它们的功能有望被发现。因而，这对将来的治疗具有指导意义。我们也希望，根据将来的基因信息重新对精神障碍进行分类。 关键词 遗传学，精神分裂症 缺文献出处，这是哪个杂志上的文献？ Current Opinion in Psychiatry 2004, 17:107–113Am J Psychiatry. 2004 Nov;161(11):2108-14. Related Articles, Links Axis I comorbidity in patients with borderline personality disorder: 6-year follow-up and prediction of time to remission. Zanarini MC, Frankenburg FR, Hennen J, Reich DB, Silk KR. McLean Hospital, 115 Mill St., Belmont, MA 02478, USA. zanarini@mclean.harvard.edu OBJECTIVE: The purpose of this study was to assess the prevalence of axis I disorders among patients with borderline personality disorder over 6 years of prospective follow-up. METHOD: A semistructured interview of demonstrated reliability was used to assess presence or absence of comorbid axis I disorders in 290 patients who met Revised Diagnostic Interview for Borderlines criteria and DSM-III-R criteria for borderline personality disorder and 72 patients who did not meet these criteria but did meet DSM-III-R criteria for another axis II disorder. Over 94% of surviving patients were reinterviewed about their axis I disorders at 2-year, 4-year, and 6-year follow-up periods. RESULTS: Although the patients with borderline personality disorder experienced declining rates of many axis I disorders over time, the rates of these disorders remained high, particularly the rates of mood and anxiety disorders. Patients whose borderline personality disorder remitted over time experienced substantial decline in all comorbid disorders assessed, but those whose borderline personality disorder did not remit over time reported stable rates of comorbid disorders. When the absence of comorbid axis I disorders was used to predict time to remission, the absence of substance use disorders was a far stronger predictor of remission from borderline personality disorder than was the absence of posttraumatic stress disorder, mood disorders, other anxiety disorders, or eating disorders, respectively. NCLUSIONS: The results of this study suggest that axis I disorders are less common over time in patients with initially severe borderline personality disorder, particularly for patients whose borderline personality disorder remits over time. The findings also suggest that substance use disorders are most closely associated with the failure to achieve remission from borderline personality disorder. PMID: 15514413 [PubMed - indexed for MEDLINE] 目的:本研究对边缘性人格障碍患者进行为期6年的前瞻性随访研究，评估这些患者的轴I障碍的发病率。方法：用已证实可靠的半结构面谈，对290例符合边缘标准和DSM-III-R标准的修订诊断面谈的边缘性人格障患者及72例不符合上述标准但满足另一个轴II障碍的患者，进行评估共病轴I障碍的存在与否。对轴I障碍在随访2年，4年及6年，再次94%具有残存症状的患者进行面谈。结果：尽管随着随访时间的过去，边缘性人格障碍患者经历许多轴I障碍的下降率，但是这些障碍的出现率仍很高，尤其是心境障碍和焦虑障碍。在所有的评估的共病障碍中边缘性人格障碍患者忽轻忽重，随着时间的推移，这些患者基本上下降。但是随着时间的过去，没有忽轻忽重的边缘性人格障碍患者，被报道具有共病障碍的稳定比率。当消失被用来预言疾病缓和的时间，应用精神作用物质所致精神障碍的轴I共病障碍消失，分别与创伤性应激障碍、心境障碍，其他的焦虑障碍、或者饮食障碍的轴I共病障碍消失比较，是边缘性人格障碍缓和的更强烈预测指标。本研究结果表明：随着随访时间的过去，在最初具有严重边缘性人格障碍患者中，轴I障碍是很不普遍的，尤其在随着时间忽轻忽重的边缘性人格障碍患者。本研究也表明：应用精神作用物质所致精神障碍与边缘性人格障碍不能获得症状减轻紧密地相联系。J Clin Psychol. 2004 Dec;60(12):1291-315. Related Articles, Links How does psychotherapy influence personality? A theoretical integration. Mayer JD. Department of Psychology, University of New Hampshire, Durham, NH 03824, USA. jack.mayer@unh.edu A given type of psychotherapy (e.g., psychodynamic) is associated with a set of specific change techniques (e.g., interpreting defenses, identifying relationship themes). Different change techniques can be conceived of as influencing different parts of personality (e.g., interpreting defense increases conscious awareness). An integrated model of personality is presented. Then, change techniques from different theoretical perspectives are assigned by judges to areas of personality the techniques are believed to influence. The results suggest that specific change techniques can be reliably sorted into the areas of personality. Thinking across theoretical perspectives leads to important new opportunities for assessment, therapy outcome research, and communication with patients concerning personality change. 2004 Wiley Periodicals, Inc. 心理治疗如何影响人格？一个理论分析应为理论整合[摘要] 某种特定类型的心理治疗（如，精神动力学）与一套特别的变化应为改变技巧（如，解释过程的防御，关系主体应该是解释防御，关系主题的识别的识别）相联系。不同的变化技巧能被想像为影响人格的不同部分（如，解释过程的防御应为防御过程增加有意识的觉醒）。已经存在一种人格的整合模型。而且，来自不同理论前景的变化技巧通过判断指定到所谓的影响人格的技巧领域不通顺。结果表明：特定的变化技巧可靠地分类到人格领域。交叉理论应为跨越理论的思考前景的思维导致重要的新的评估机会、治疗结果研究以及与有关人格改变患者的交流。 其他两篇也存在一定的问题，还是先校正矫正吧！Arch Gen Psychiatry. 2004 Sep;61(9):866-76. Related Articles, Links Cognitive enhancement therapy for schizophrenia: effects of a 2-year randomized trial on cognition and behavior. Hogarty GE, Flesher S, Ulrich R, Carter M, Greenwald D, Pogue-Geile M, Kechavan M, Cooley S, DiBarry AL, Garrett A, Parepally H, Zoretich R. University of Pittsburgh Medical Center, Western Psychiatric Institute and Clinic, Pittsburgh, PA 15213, USA. hogartyje@upmc.edu BACKGROUND: Deficits in social cognition and neurocognition are believed to underlie schizophrenia disability. Attempts at rehabilitation have had circumscribed effects on cognition, without concurrent improvement in broad aspects of behavior and adjustment. OBJECTIVE: To determine the differential effects of cognitive enhancement therapy (a recovery-phase intervention) on cognition and behavior compared with state-of-the-art enriched supportive therapy. DESIGN: A 2-year, randomized controlled trial with neuropsychological and behavioral assessments completed at baseline and at 12 and 24 months.SETTING: An outpatient research clinic housed in a medical center's comprehensive care service for patients with severe mental illness. PATIENTS: A total of 121 symptomatically stable, non-substance-abusing but cognitively disabled and chronically ill patients with schizophrenia or schizoaffective disorder. INTERVENTIONS: Cognitive enhancement therapy is a multidimensional, developmental approach that integrates computer-assisted training in neurocognition with social cognitive group exercises. Enriched supportive therapy fosters illness management through applied coping strategies and education. MAIN OUTCOME MEASURES: Six highly reliable summary measures--Processing Speed, Neurocognition, Cognitive Style, Social Cognition, Social Adjustment and Symptoms--were tested using analysis of covariance and linear trend analysis. RESULTS: At 12 months, robust cognitive enhancement therapy effects were observed on the Neurocognition and Processing Speed composites (P<.003), with marginal effects observed on the behavioral composites.By 24 months, differential cognitive enhancement therapy effects were again observed for the 2 neuropsychological composites and for Cognitive Style (P=.001), Social Cognition (P=.001), and Social Adjustment (P=.01). As expected, no differences were observed on the residual Symptoms composite. Effects were unrelated to the type of antipsychotic medication received.Enriched supportive therapy also demonstrated statistically significant within-group effect sizes, suggesting that supportive psychotherapy can also have positive, although more modest, effects on cognitive deficits. CONCLUSION: Many cognitive deficits and related behaviors of patients with stable schizophrenia are improved when sufficient exposure to relevant rehabilitation is provided. 精神分裂症的认知改善治疗：2年的随机试验对认知和行为的影响 [摘要] 背景：社会认知和神经认知缺陷被认为是精神分裂症残疾的基础。康复方面的尝试对认知产生了局限的影响，没有共同发生的行为和调节广泛方面的改善。目的：通过与工艺水平浓缩的支持治疗相比，测定认知改善治疗（恢复其干预）对认知和行为的影响。设计：具有神经心理学和行为评估的为期两年的随机对照实验，分别在治疗初，治疗12个月及治疗24个月进行。 场地：一个门诊科学研究诊所位于一个医疗中心，具有为严重精神疾病患者提供广泛的照料服务。患者：总数为121例，具有症状稳定、无物质依赖、有认知缺损和具有精神分裂症或情感分裂性精神障碍的慢性病患者。干预：认知改善疗法是***的、进化方法，即整合神经认知的计算机辅助训练和社会认知的集体操练。浓缩的支持疗法通过应用心里应对策略培养疾病处理。主要的项目测量：6个非常可靠的概括的措施-处理速度、神经认知、认知方式、社会认知、社会调整和症状-通过用协方差分析和线性确实分析来进行检测的。结果：在治疗的12个月后，在神经认知和处理速度混合方面有显著的认知改善治疗效应（P<.003),在行为方面有显著的边缘效果。在治疗24个月后，，不同的认知改善治疗效果即2个神经心理学成分、认知方式(P=.001)、社会认知(P=.001)及社会调整(P=.01)等再次被观察。像预期的那样，在残留症状方面没有差别，效果与所接受的抗精神病药物的类型无关。浓缩的支持治疗统计学上也显著地阐明了组内效应大小，表明支持性心理治疗尽管作用不大，但对认知缺陷也有积极的影响。结论：当提供给稳定的精神分裂症患者充分的有关的康复暴露，它们的许多认知缺陷和相关的行为都被改善。The New England Journal of Medicine Vol 352(11) pp1112-1120 Title: Current Concepts: The Serotonin Syndrome Author: Boyer, Edward W.; Shannon, Michael From the Division of Medical Toxicology, Department of Emergency Medicine, University of Massachusetts, Worcester (E.W.B.); and the Program in Medical Toxicology, Division of Emergency Medicine, Children's Hospital, Boston (E.W.B., M.S.). Address reprint requests to Dr. Boyer at IC Smith Bldg., Children's Hospital, 300 Longwood Ave., Boston, MA 02115, or at edward.boyer@tch.harvard.edu. The serotonin syndrome is a potentially life-threatening adverse drug reaction that results from therapeutic drug use, intentional self-poisoning, or inadvertent interactions between drugs. Three features of the serotonin syndrome are critical to an understanding of the disorder. First, the serotonin syndrome is not an idiopathic drug reaction; it is a predictable consequence of excess serotonergic agonism of central nervous system (CNS) receptors and peripheral serotonergic receptors. [1,2] Second, excess serotonin produces a spectrum of clinical findings. [3] Third, clinical manifestations of the serotonin syndrome range from barely perceptible to lethal. The death of an 18-year-old patient named Libby Zion in New York City more than 20 years ago, which resulted from coadminstration of meperidine and phenelzine, remains the most widely recognized and dramatic example of this preventable condition. 5-羟色胺综合症是一种潜在威胁生命的不良药物反应，这种反应是由治疗性药物使用、故意自我中毒或是疏忽的药物间的相互反应而引起的。理解5-羟色胺综合症的关键的三个特征是：一、5-羟色胺综合症不是一种先天性的药物反应，它是中枢神经系统和外周神经系统5-羟色胺能受体的拮抗过剩的一种可预测的结果。二、过剩的-羟色胺产生一系列的临床发现。三、5-羟色胺综合症的临床显示从仅仅可觉察到致命。20年前在纽约城的一个叫Libby Zion的十八岁的病人的死亡，是由于度冷丁和苯乙肼同时服用引起的，留下了这种可预防的条件的被最广泛认可的和戏剧性的例子。D-serine efficacy as add-on pharmacotherapy to risperidone and olanzapine for treatment-refractory schizophrenia. Heresco-Levy U, Javitt DC, Ebstein R, Vass A, Lichtenberg P, Bar G, Catinari S, Ermilov M. Ezrath Nashim-Herzog Memorial Hospital, Jerusalem, Israel; Department of Psychiatry, Hadassah Medical School, Hebrew University, Jerusalem, Israel. BACKGROUND: D-serine, a selective full agonist at the glycine site of N-methyl-d-aspartate glutamate receptor, might presently be the compound of choice for counteracting the hypothesized dysfunction of this receptor class in schizophrenia. Studies performed with Taiwanese patients indicate that D-serine significantly improves schizophrenia symptoms when used as adjuvant to conventional neuroleptics but not to clozapine. We assessed the efficacy and safety of D-serine adjuvant treatment for Occidental schizophrenia patients treated with newer atypical antipsychotics. METHODS: Thirty-nine risperidone- or olanzapine-treated schizophrenia patients participated in a double-blind, placebo-controlled, 6-week crossover trial with 30 mg/kg/day D-serine added to their antipsychotic medication. Measures of clinical efficacy and side effects were determined biweekly throughout the study. Clinical laboratory parameters and amino acid serum levels were monitored. RESULTS: D-serine administration induced increased serine serum levels (p < .001) and resulted in significant (p < .001) improvements in negative, positive, cognitive, and depression symptoms, as measured by the Positive and Negative Syndrome Scale. For approximately one third of the sample, D-serine treatment resulted in significant (>20%) reductions in Brief Psychiatric Rating Scale total scores. D-serine was well tolerated, and no detrimental changes in clinical laboratory parameters were noted. CONCLUSIONS: These findings 1) indicate that risperidone and olanzapine efficacy might be augmented with D-serine adjuvant treatment; 2) confirm D-serine efficacy against main schizophrenia symptom domains; and 3) warrant the assessment of D-serine antipsychotic monotherapy for this illness. PMID: 15780844 [PubMed - in process] D－丝氨酸作为维思通和奥氮平的辅助药治疗难治性精神分裂症的疗效 研究背境：D－丝氨酸是谷氨酸***A受体甘氨酸结合位点的选择性完全激动剂，它可能会成为逆转精神分裂症病人***A受体功能低下的一个选择。在中国台湾精神分裂症病人中所进行的实验表明，在传统抗精神病药治疗同时，联用D－丝氨酸可明显改善精神分裂症的症状，但氯氮平除外。我们在欧美精神分裂症病人中对非典型抗精神病药联用D－丝氨酸治疗的疗效和安全性进行了评定。方法：实验共纳入39个服用维思通或奥氮平的精神分裂症病人。采用双盲、对照、6周的交叉实验设计，在原用药的基础上加用30mg/kg/天的D－丝氨酸。每两周对疗效和付反应进行一次评定，并监测临床实验室指标和血清氨基酸水平。 结果：服用D－丝氨酸可提高血清丝氨酸浓度（p<0.01）,通过对PANSS的分析，发现可明显改善阴性症状，阳性症状，认知功能和抑郁症状（p<0.01）。约有1/3的病人经D－丝氨酸治疗后BPRS总分明显降低(>20%)。病人对D－丝氨酸的耐受性良好，没有监测到显著的临床实验室指标的变化。结论： 我们研究提示：1，D－丝氨酸可增强维思通和奥氮平的疗效；2，D－丝氨酸可改善精神分裂症的主要症状；3，为评价D－丝氨酸单一用药治疗精神分裂症的疗效提供依据。ＡＰＯＥ的基因分布在分裂症病人和正常对照间存在差异。ＡｐｏＥ２和３基因在分裂症病人的出现频率不同于对照组。研究结果提示ＡｐｏＥ基因可能在精神分裂症的发病机理起一定的作用。―――――Apolipoprotein E genotype in Korean schizophrenic patients.　J Korean Med Sci (Korea 2001 Dec;16:781-3 (ISSN: 1011-8934)　Lee MK; Park AJ; Nam BY; Min KJ; Kee BS; Park DB 　Department of Clinical Pathology, Chung-Ang University College of Medicine, Seoul, Korea. cpworld@hananet.net. 在ＡｐｏＥ多态性、精神分裂症风险、对传统抗精神病药的治疗反应性和分裂症的发病年龄之间的关系研究中，没有发现ＡｐｏＥ基因出现的频率（基因２、３、４）与对照组间有统计学差异，在治疗反应性和ＡｐｏＥ基因间也没有发现有联系；但是研究发现ＡｐｏＥ４或Ｅ４基因型患者的发病年龄明显小于其他患者，在排除了性别因素的干扰后仍然具有显著性，Ｅ３基因的数目与分裂症发病年龄间有一个渐增的线性趋势，而在Ｅ４基因数目和发病年龄间则有一种负性线性趋势；未能发现ＡｐｏＥ多态性与分裂症风险间相关性；研究结果提示ＡｐｏＥ４基因可能与早发精神分裂症有关系，而ＡｐｏＥ３可能在分裂症的发病机制中起保护功能。―――Apolipoprotein E polymorphism is associated with age of onset in schizophrenia.　J Hum Genet 2004;49(7):355-9 (ISSN: 1434-5161)　Kampman O; Anttila S; Illi A; Mattila KM; Rontu R; Leinonen E; Lehtimaki T 　Medical School, University of Tampere, 33014 Tampere, Finland. olli.kampman@uta.fi. 动物模型研究结果支持高水平的ＡｐｏＥ可能参与了分裂症的发病机制，而抗精神病药物使ＡｐｏＥ的水平减低可能是它的治疗作用之一。――――Increased levels of apolipoprotein E in the frontal cortex of subjects with schizophrenia.　Biol Psychiatry 2003 Sep 15;54:616-22 (ISSN: 0006-3223)　Dean B; Laws SM; Hone E; Taddei K; Scarr E; Thomas EA; Harper C; McClean C; Masters C; Lautenschlager N; Gandy SE; Martins RN 　Rebecca L. Cooper Research Laboratories, the Mental Health Research Institute of Victoria, Parkville, Victoria, Australia. 中国上海精神卫生中心的一项2007人的研究表明：精神分裂症病人和正常对照比较其ApoE4/基因型和等位基因频率显著增高，而ApoE3/3基因型和等位基因频率低，这个效应不受性别和发病年龄的影响，但受出生日期的影响明显，因为在研究中发现和正常对照出现显著差异的个例不是出生在1949年之前就是出生在1958年－1967之间，这两个时期都是严重的食物短缺时期或营养不良时期。由此推论ApoE可能是那些在胎儿期和或幼年遭受营养不良的个体患精神分裂症的一个附加风险因素。――Association of APOE gene with schizophrenia in Chinese: a possible risk factor in times of malnutrition. Schizophr Res 2003 Aug 1;62(3):225-30 (ISSN: 0920-9964) Liu W; Breen G; Zhang J; Li S; Gu N; Feng G; Bai S; Shen T; Yu A; Xue H; St Clair D; He L Bio-X Life Science Research Center, Shanghai Jiao Tong University, 200030 Shanghai, PR China. 精神分裂症是复杂的遗传性疾病，它可能涉及到多个基因的微小效应，ApoE基因与大脑功能的改变有关，并且是AD的风险因素。但ApoE与精神分裂症的关系研究中很多结果是相互矛盾的。Schurhoff F研究了114例法国白人精神分裂症患者与91例正常对照，没有发现ApoE基因或等位基因频率在两组间有显著性差异。另外他们还对2003年以前已经发表的有关ApoE和精神分裂症的病例对照研究进行了分析，分析结果总体上不支持ApoE作为精神分裂症的一个主要影响因素，ApoE有可能与精神分裂症的个别类型有关系。Apolipoprotein E in schizophrenia: a French association study and meta-analysis. Am J Med Genet B Neuropsychiatr Genet 2003 May 15;119(1):18-23 (ISSN: 1552-4841) Schurhoff F; Krebs MO; Szoke A; Loze JY; Goldberger C; Quignon V; Tignol J; Rouillon F; Laplanche JL; Leboyer M Service de Psychiatrie Adulte, Hopital Albert Chenevier, Creteil, France. schurhof@ext.jussieu.fr. 日本熊本大学的一项314例精神分裂症病人和188例对照的研究发现在精神分裂症患者和对照组间ApoE基因频率没有显著性差异，这与之前台湾报道说中国台湾ApoE3基因是精神分裂症的风险因素的结果正好相反。――Apolipoprotein E epsilon3 allele is not a risk factor of schizophrenia: a study of 314 Japanese patients. Neuropsychobiology 2000;42(2):66-8 (ISSN: 0302-282X) Kimura T; Shono M; Yokota S; Igata-Yi R; Takamatsu J; Miyakawa T Department of Neuropsychiatry, Kumamoto University School of Medicine, Kumamoto, Japan. tkimura@kaiju.medic.kumamoto-u.ac.jp. ApoE4基因对精神分裂症患者的海马体积和双侧不对称性的可能的影响。 ――Possible effect of the APOE epsilon 4 allele on the hippocampal volume and asymmetry in schizophrenia. Am J Med Genet 2002 Aug 8;114:641-2 (ISSN: 0148-7299) Hata T; Kunugi H; Nanko S; Fukuda R; Kaminaga T 西班牙Martorell L对365例分裂症病人和584例对照进行的ApoE的研究发现：两组间的基因分布和等位基因频率没有差别，但在对ApoE4基因与临床因素间的分析中发现，ApoE4＋（有1个或2个ApoE4基因）的分裂症女性的发病年龄（AAO）比那些ApoE－的女性要早4年，并且她们出现阴性症状群的风险要高4倍多，而在男性病人中没有发现这个现象。这个结果提示ApoE基因不是精神分裂症的发病的风险因素，但它可能通过与性别相连锁的方式来调制它的基因表型的表达。――Schizophrenic women with the APOE epsilon 4 allele have a worse prognosis than those without it. Mol Psychiatry 2001 May;6(3):307-10 (ISSN: 1359-4184) Martorell L; Virgos C; Valero J; Coll G; Figuera L; Joven J; Pocovi M; Labad A; Vilella E Departament de Formacio i Investigacio, Hospital Psiquiatric Universitari Institut Pere Mata, Ctra de I'Institut Pere Mata s/n, 43206 Reus, Spain. ApoE是中枢神经系统的一种脂蛋白，它被认为在神经生长和修复过程中起作用。ApoE有三种异构体（ApoE2、ApoE3和ApoE4），它们分别由三个不同的等位基因（Epsilon2、Epsilon3和Epsilon4）编码。来自双生子研究、家族研究和抽样研究的证据提示ApoE在精神分裂症的病因机制中有着重要的基因遗传作用。在一些精神分裂症病例中存在着类似于AD病人的认知损害，而ApoE基因在AD中的作用已经研究的比较清楚，所以我们可以假设ApoE可能也与精神分裂症有关。我们对114例西班牙分裂症病人和94例健康匹配对照的ApoE基因研究没有发现在ApoE基因型和分裂症之间的联系。而在临床分型中的一部分早发病例中ApoE有轻微的增高，而在有阳性家族史的病例中有轻微的减低，那些对抗精神病药反应不敏感的病例中ApoE2等位基因的出现频率较低，但所有这些高低不同差异都没有达到统计学水平，我们不能说这些差异有什么意义。我们的阴性结果不支持ApoE与分裂症有关，这提示精神分裂症对认知功能的损害的不明机制与AD病人的认知损害机制没有联系，与高水平ApoE4基因也没有关系。－――――Apolipoprotein E genotype in Spanish schizophrenic patients. Psychiatr Genet 2000 Jun;10(2):73-7 (ISSN: 0955-8829) Durany N; Riederer P; Cruz-Sanchez FF Institute of Neurological and Gerontological Sciences, International University of Catalunya, Barcelona, Spain. ndurany@csc.unica.edu. 在以往的报道中，有报道说带有ApoE4等位基因的分裂症病人比那些不带ApoE4等位基因的病人有更少的精神病得分。台湾一项研究就针对分裂症的临床表现或对氯氮平的反应与ApoE4基因的关系对95例难治性分裂症病人进行对照研究显示ApoE4基因并不影响分裂症病人对氯氮平的反应，而且与其精神病理学基线也没有关系，由于ApoE蛋白在大脑中有着多项功能作用，需要进一步研究ApoE基因的影响及对中枢神经系统药物的反应。――Association study of apolipoprotein E epsilon4 with clinical phenotype and clozapine response in schizophrenia. Neuropsychobiology 2000;42(4):172-4 (ISSN: 0302-282X) Hong CJ; Yu YW; Lin CH; Song HL; Lai HC; Yang KH; Tsai SJ Department of Psychiatry, Veterans General Hospital-Taipei, Taipei, Taiwan, ROC. Saiz PA等对106名分裂症门诊病人和250健康对照进行了ApoE基因研究，他们用PCR扩增技术、限制性内切酶分解方法和4％琼糖脂凝胶电泳方法对ApoE基因（E2、E3、E4等位基因）分析，结果显示在两组间ApoE等位基因频率分布没有统计学差异，但ApoE基因在病人组中多出64次记录（9.0％－6.2％，P＝0124，OR＝1.49，95％可信区间CI＝0.82～2.70）。ApoE基因型在两组间也没有差别。携带有ApoE4等位基因的分裂症病人发病年龄与未携带者发病年龄间没有差别。结果提示ApoE变量与分裂症没有关联，ApoE基因型对分裂症发病年龄也没有影响。――Apolipoprotein E genotype and schizophrenia: further negative evidence. Acta Psychiatr Scand 2002 Jan;105(1):71-5 (ISSN: 0001-690X) Saiz PA; Morales B; G-Portilla MP; Alvarez V; Coto E; Fernandez JM; Bousono M; Bobes J Department of Psychiatry, School of Medicine, University of Oviedo, Spain. 自由基在迟发性运动障碍（TD）的发生机制中起着根本性的作用，而ApoE4可以减弱抗氧化剂的活性提示在TD和ApoE等位基因间可能存在一定的联系。日本的Kimura T对62例分裂症患者TD者和271例未患TD者、191例健康对照的ApoE基因进行了凝胶电泳分析发现：TD组和非TD组的ApoE基因频率没有差别，但女性TD组ApoE基因频率比男性TD组低。这个结果并没有证明TD与ApoE4基因间的联系，但却可能揭示在男女性之间ApoE基因对TD的发生发展的不同影响。―――Apolipoprotein E epsilon4 and tardive dyskinesia in a Japanese population. J Psychiatr Res 2000 Jul-Oct;34(4-5):329-32 (ISSN: 0022-3956) Kimura T; Shono M; Yokota S; Ishizuka K; Watanabe M; Takamatsu J; Miyakawa T Department of Neuropsychiatry, Kumamoto University School of Medicine, Honjo 1-1-1, Kumamoto 860-8556, Japan. tkimura@kaiju.medic.kumamoto-u.ac.jp. 我们筛选出一个特定的由300个基因组成的候选cDNA基因序列。这些被选择的基因不是与精神分裂症有关，并且基于目前对精神分裂症的理解这些基因具有概念上的意义，就是位于染色体上的高敏感区域。这些筛选的基因序列采样来自于10个精神分裂症患者和10个对照的大脑前额叶皮质组织，结果提示前者ApoL1的表达上调了2.6倍。这个结果通过与来自Stanley 基金会捐赠的大脑前额叶皮质进行盲法PCR定量分析发现是交叉有效的（cross-validated）。捐赠的样本是由15例分裂症、15例双相障碍、15例重症抑郁和15例对照个例组成。这60例大脑样本是经过严格按照通常的参数因子匹配好的，其中在分裂症组和双相障碍组都有抗精神病药物的应用。目前已经证实分裂症组中的ApoL1基因的表达显著上调了。应用PCR定量技术，ApoL基因家族（ApoL1－L6）的其他基因的表达廓图也被研究了，结果显示在分裂症组中ApoL2和ApoL4的基因表达也被非常显著地上调了。这个结果被日本和新西兰的一个20例分裂症和对照样本的独立的研究证实了。ApoL蛋白属于高密度脂蛋白，所有6个ApoL基因都在染色体22q12的位置，而且相互间非常靠近，这个区域已经被证实具有高度易感性，精神分裂症的基因位点即在此区域，并且它紧靠着与velocardiofacial综合症（包含着分裂症的症状）有关的区域。―――Gene expression analysis in schizophrenia: reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22. Proc Natl Acad Sci U S A 2002 Apr 2;99(7):4680-5 (ISSN: 0027-8424) Mimmack ML; Ryan M; Baba H; Navarro-Ruiz J; Iritani S; Faull RL; McKenna PJ; Jones PB; Arai H; Starkey M; Emson PC; Bahn S Department of Neurobiology, Babraham Institute, Cambridge CB2 4AT, United Kingdom. We screened a custom-made candidate gene cDNA array comprising 300 genes. Genes chosen have either been implicated in schizophrenia, make conceptual sense in the light of the current understanding of the disease, or are located on high-susceptibility chromosome locations. The array screen using prefrontal cortex tissue from 10 schizophrenia and 10 control brains revealed robust up-regulation of apolipoprotein L1 (apo L1) by 2.6-fold. The finding was cross-validated in a blinded quantitative PCR study using prefrontal cortex tissue from the Stanley Foundation brain collection, Bethesda, MD. This collection consists of 15 schizophrenia, 15 bipolar disorder, 15 major depression, and 15 control individuals, all 60 brains being well-matched on conventional parameters, with antipsychotic drug exposure in the schizophrenia and bipolar disorder groups. Significant up-regulation of apo L1 gene expression in schizophrenia was confirmed. Using quantitative PCR, expression profiles of other members of the apo L family (apo L2-L6) were investigated, showing that apo L2 and L4 were highly significantly up-regulated in schizophrenia. Results were then confirmed in an independent set of 20 schizophrenia and 20 control brains from Japan and New Zealand. Apo L proteins belong to the group of high density lipoproteins, with all six apo L genes located in close proximity to each other on chromosome 22q12, a confirmed high-susceptibility locus for schizophrenia and close to the region associated with velocardiofacial syndrome that includes symptoms of schizophrenia. 有人对晚发精神分裂症的认知衰退与AD的认知衰退在神经心理学和神经病理学方面进行了总结比较发现：晚发分裂症患者临床表现常有认知损害症状，但这些损害症状并不具有象AD这类的进行性衰退性疾病样的特点，而且认知损害的速度是非常缓慢的。神经病理学研究显示在分裂症病人里类AD的大脑病理损害并不比普通人群多。所以一旦做出AD的诊断那即意味着在未来的几年里可以预测到不仅仅认知功能还有躯体功能也存在进行性衰退，同时还伴随着中枢神经系统的衰退，而且开始需要有人适当的照顾和护理了。所以对于有认知损害的晚发分裂症患者诊断AD时应当非常慎重。――――Cognitive decline in schizophrenics with Alzheimer's disease: a mini-review of neuropsychological and neuropathological studies. Prog Neuropsychopharmacol Biol Psychiatry 2001 Oct;25(7):1359-66 (ISSN: 0278-5846) Niizato K; Genda K; Nakamura R; Iritani S; Ikeda K Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Japan. kazu@matsuzawa-hp.metro.tokyo.jp. 神经细胞中的ApoE被认为在神经衰退和再生过程中起重要作用。在脑梗死组织中ApoE的累积可能与神经轴突急性损伤后的再生过程有关，而在慢性衰退病变过程中再生可能受到一定的减缓。―――Expression of apolipoprotein E in ballooned neurons-comparative immunohistochemical study on neurodegenerative disorders and infarction. Acta Neuropathol (Berl) 2003 Nov;106(5):436-40 (ISSN: 0001-6322) Aoki K; Uchihara T; Nakamura A; Komori T; Arai N; Mizutani T Department of Neurology, Metropolitan Fuchu Medical Center for Severe Motor and Intellectual Disabilities, 2-9-2 Musashi-dai, Fuchu, 183-0042 Tokyo, Japan.J Neurosci. 2005 Jan 12;25(2):524-31. Ketamine induces dopamine-dependent depression of evoked hippocampal activity in the nucleus accumbens in freely moving rats. Hunt MJ, Kessal K, Garcia R. Neurobiologie Comportementale, Institut National de la Sante et de la Recherche Medicale, Universite de Nice-Sophia Antipolis, 06108 Nice, France. hunt@unice.fr Noncompetitive ***A receptor antagonists, such as ketamine, induce a transient schizophrenia-like state in healthy individuals and exacerbate psychosis in schizophrenic patients. In rodents, noncompetitive ***A receptor antagonists induce a behavioral syndrome that represents an experimentally valid model of schizophrenia. Current experimental evidence has implicated the nucleus accumbens in the pathophysiology of schizophrenia and the psychomimetic actions of ketamine. In this study, we have demonstrated that acute systemic administration of ketamine, at a dose known to produce hyperlocomotion and stereotypy, depressed the amplitude of the monosynaptic component of fimbria-evoked field potentials recorded in the nucleus accumbens. A similar effect was observed using the more selective antagonist dizocilpine maleate, indicating the depression was ***A receptor dependent. Paired-pulse facilitation was enhanced concomitantly with, and in proportion to, ketamine-induced depressed synaptic efficacy, indicative of a presynaptic mechanism of action. Notably, the depression of field potentials recorded in the nucleus accumbens was markedly reduced after a focal 6-hydroxydopamine lesioning procedure in the nucleus accumbens. More specifically, pretreatment with the D2/D4 antagonist haloperidol, but not the D1 antagonist SCH23390 blocked ketamine-induced depression of nucleus accumbens responses. Our findings provide supporting evidence for the contemporary theory of schizophrenia as aberrant excitatory neurotransmission at the level of the nucleus accumbens. KETAMINE诱导自由活动大鼠伏隔核中的诱发的海马活动的DA依赖性抑制作用 非竞争性***AR拮抗剂，如KETAMINE，可诱导健康个体出现短暂的精神分裂样状态，并恶化精神分裂症病人的精神症状。在啮齿类，非竞争性***AR拮抗剂诱导代表实验性精神分裂症真实模型的行为学症状。最近的实验性证据，涉及到精神分裂症病理生理学中伏隔核，和KETAMINE拟精神病性作用。在此研究中，我们已阐明，急性全身性给予KETAMINE，已知剂量来产生活动过度和刻板行为，可抑制伏隔核中所记录的FIMBRIA诱发的场电位的单突触部位的振幅。用更具选择性的拮抗剂DIZOCILPINE MALEATE，可观察到相似的作用，并表现***AR依赖性抑制作用。我们的发现提供了支持性证据，对于当今精神分裂症的理论，在伏隔核水平存在着异常的兴奋性神经传递。Am J Psychiatry 2003;160: 1223-1232 The Effectiveness of Psychodynamic Therapy and Cognitive Behavior Therapy in the Treatment of Personality Disorders: A Meta-Analysis Falk Leichsenring, D.Sc. & Eric Leibing , D.Sc Objective: The authors conducted a meta-analysis to address the effectiveness of psychodynamic therapy and cognitive behavior therapy in the treatment of personality disorders. Method: Studies of psychodynamic therapy and cognitive behavior therapy that were published between 1974 and 2001 were collected. Only studies that 1) used standardized methods to diagnose personality disorders, 2) applied reliable and valid instruments for the assessment of outcome, and 3) reported data that allowed calculation of within-group effect sizes of assessment of personality disorder recovery rate were included. Fourteen studies of psychodynamic therapy and 11 studies of cognitive behavior therapy were included. Fourteen studies of psychodynamic therapy and 11 studies of cognitive behavior therapy were included. Results: Psychodynamic therapy yielded a large overall effect size (1.46), with effect sizes of 1.08 found for self-report measures and 1.79 for observer-rated measures. For cognitive behavior therapy, the corresponding values were 1.00,1.20,and 0.87. For more specific measures of personality disorder pathology, a large overall effect size (.56) was seen for psychodynamic therapy. Two cognitive behavior therapy studies reported significant effects for more specific measures of personality disorder pathology. For psychodynamic therapy, the effect sizes indicate long-term rather than short-term change in personality disorders. Conclusions: There is evidence that both psychodynamic therapy and cognitive behavior therapy are effective treatments of personality disorders. Since the number of studies that could be included in this meta-analysis was limited, the conclusions that can be drawn are only preliminary. Further studies are necessary that examine specific forms of psychotherapy for specific types of personality disorders and that use measures of core psychopathology. Both longer treatments and follow-up studies should be included. 题目：关于心理动力疗法和认知行为疗法在人格障碍治疗中疗效的元分析 目的：作者做了元分析，旨在提出心理动力疗法和认知行为治疗在人格障碍治疗中的有效性 方法：搜集在1974和2001年期间出版的关于心理动力疗法和认知行为疗法的研究。只有满足以下三个要求的研究才选入：1）运用标准化方法诊断人格障碍；2）运用有信效度的工具评估结果；3）报告的数据中有组内效果量的计算或人格障碍康复率的评估。符合以上三条件的有14篇关于心理动力疗法的研究和11篇关于认知行为疗法的研究。 结果：心理动力疗法具有更大的总效果量（1.46），而采用自我报告测量的效果量是1.08，采用观察者评估的效果量是1.79。对于认知行为疗法而言，对应的效果量分别是1.00, 1.20,0.87。对于人格障碍病理学更特殊的评估，心理动力疗法的总效果量是0.56。两篇认知行为疗法的研究表明，对于人格障碍病理学更特殊的评估，具有明显的效果。对于心理动力疗法，效果量表明，在人格障碍治疗中长程疗法胜于短程有效。 结论：很明显，心理动力疗法和认知行为疗法对人格障碍患者的治疗都是有效的。由于在此元分析中所包含的研究很有限，因此得出的结论只不过是初步的。未来研究有必要考察，明确类型的人格障碍的特效心理疗法和核心的精神病理学的评估工具。研究中还应包括更长的治疗和追踪研究。[翻译][全文]谷氨酸与焦虑 （中文）Chronic Depression Medication (Nefazodone) or Psychotherapy (CBASP) Is Effective When the Other Is Not Alan F. Schatzberg, MD et al Arch Gen Psychiatry. 2005;62:513-520. Context Although various strategies are available to manage nonresponders to an initial treatment for depression, no controlled trials address the utility of switching from an antidepressant medication to psychotherapy or vice versa. Objective To compare the responses of chronically depressed nonresponders to 12 weeks of treatment with either nefazodone or cognitive behavioral analysis system of psychotherapy (CBASP) who were crossed over to the alternate treatment (nefazodone, n = 79; CBASP, n = 61). Design Crossover trial. Setting Twelve academic outpatient psychiatric centers. Patients There were 140 outpatients with chronic major depressive disorder; 92 (65.7%) were female, 126 (90.0%) were white, and the mean age was 43.1 years. Thirty participants dropped out of the study prematurely, 22 in the nefazodone group and 8 in the CBASP group. Interventions Treatment lasted 12 weeks. The dosage of nefazodone was 100 to 600 mg/d; CBASP was provided twice weekly during weeks 1 through 4 and weekly thereafter. Main Outcome Measures The 24-item Hamilton Rating Scale for Depression, administered by raters blinded to treatment, the Clinician Global Impressions–Severity scale, and the 30-item Inventory for Depressive Symptomatology–Self-Report. Results Analysis of the intent-to-treat sample revealed that both the switch from nefazodone to CBASP and the switch from from CBASP to nefazodone resulted in clinically and statistically significant improvements in symptoms. Neither the rates of response nor the rates of remission were significantly different when the groups of completers were compared. However, the switch to CBASP following nefazodone therapy was associated with significantly less attrition due to adverse events, which may explain the higher intent-to-treat response rate among those crossed over to CBASP (57% vs 42%). Conclusions Among chronically depressed individuals, CBASP appears to be efficacious for nonresponders to nefazodone, and nefazodone appears to be effective for CBASP nonresponders. A switch from an antidepressant medication to psychotherapy or vice versa appears to be useful for nonresponders to the initial treatment. 题目：慢性抑郁接受奈法唑酮或心理治疗，一种无效时换用另一种仍然有效 目的：比较接受12周奈法唑酮或认知行为分析性心理治疗（CBASP）无效的慢性抑郁病人换用另外一种治疗后的效果，奈法唑酮组79人，CBASP组61人 交叉设计试验，在12个门诊中心进行 病人：140个病人，女92人，平均年龄43岁。30人脱落，其中奈法唑酮组22人，CBASP8人。 治疗干预：治疗持续12周，奈法唑酮量100－－600mg/d; CBASP第一到四周每周2次，以后每周1次。 主要预后评估：24题HAMD, CGI，30题抑郁症状－自我报告。 结果：无论是从奈法唑酮转到CBASP或从CBASP转到奈法唑酮治疗的病人从临床和统计学都表现出显著改善。 结论：在慢性抑郁病人，奈法唑酮治疗无效的病人用CBASP可能有效。而CBASP无效者使用奈法唑酮也可能有效。 Archives of General Psychiatry 2005,62(5), 513-520Pharmacogenetics of treatment in first-episode schizophrenia: D3 and 5-HT2C receptor polymorphisms separately associate with positive and negative symptom response. Reynolds GP, Yao Z, Zhang X, Sun J, Zhang Z. Eur Neuropsychopharmacol. 2005 Mar;15(2):143-51. Department of Mental Health, Queen's University Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL, UK. g.reynolds@qub.ac.uk We have been studying the pharmacogenetic correlates of side effects and early response to antipsychotic treatment in a series of Chinese Han first-episode drug-naive patients with schizophrenia. Here, we report the association of three functional polymorphisms of receptor genes on initial symptom severity and outcome in these patients. We studied the dopamine D3 receptor ser9gly, the dopamine D2 receptor Taq IA and the 5-HT2C receptor promoter -759C/T polymorphisms in 117 patients who had symptoms assessed by Positive and Negative Syndrome Scale (PANSS) on admission and following 10-week antipsychotic treatment, primarily with risperidone or chlorpromazine. The D2 polymorphism was found not to be significantly associated with baseline levels or changes in total PANSS in these patients. The D3 genotype is associated with the change in total PANSS (p<0.01), an effect reflecting positive and general (each p<0.01) but not negative symptom improvement. However, symptom improvement at 10 weeks strongly correlates with total PANSS score on admission, in which the greater improvement is seen with the more severe initial symptom score. The D3 genotype is also related to severity on admission, i.e. to total baseline PANSS (p<0.05), including baseline PANSS score as a covariate, the association of the genotype to change over 10 weeks remains significant for total PANSS (p<0.05) and for positive and general, but not negative, symptom scores. The 5-HT2C promoter polymorphism was also associated with improvement in PANSS (p<0.05), but reflecting effects on negative and general, but not positive, symptom scores. This polymorphism was not associated with PANSS score on admission, although after controlling for the effect of this parameter on 10-week outcome, a stronger association with change in total PANSS (p<0.01) was apparent, again reflecting improvements in negative and general symptoms but not changes in positive symptoms. 题目： 首发精神分裂症治疗的药物遗传学：D3和5-HT2C受体多态性分别与阳性和阴性症状的治疗反应相关。 内容： 我们曾经研究过一系列中国汉族首发精神分裂症患者治疗的副反应和抗精神病药物早期的治疗反应与药物遗传学的相关性。在此，再报道受体基因的三个功能多态性对这些患者的起始症状严重程度和预后的关系。我们以117名精神分裂症患者为研究对象，研究了多巴胺D3受体ser9gly，多巴胺D2受体Taq IA和5-HT2C受体启动子区 -759C/T多态性。这些患者主要选用利培酮或氯丙嗪治疗，在入院时和随后的10周用PANSS量表来对症状进行评估。研究并未发现D2多态性与这些患者的基线分数或PANSS总分的改变有关联。D3基因型与PANSS总分的改变有关，对阳性症状和一般病理学症状的改善有影响，但对阴性症状无改善。然而，10周时的症状改善与入院时的PANSS总分密切相关，起始症状越严重，症状的改善越明显。D3基因型与入院时疾病的严重程度相关，即与基线PANSS总分相关，包括作为相关变异的基线PANSS评分，D3基因型与10周时PANSS总分、阳性症状评分和一般病理学评分的改变有关，而与阴性症状评分无关。5-HT2C启动子多态性也与PANSS评分的改善有关，但只是对阴性症状和一般病理学评分有影响，而与阳性症状评分无关。并且5-HT2C启动子多态性与入院时PANSS评分无关，虽然控制了该参数对10周时预后的影响以后，仍然发现与PANSS总分的改变密切相关，也对阴性症状和一般病理学症状的改善有影响，而对阳性症状的改善无关。Identification of polymorphic loci in the promoter region of the serotonin 5-HT2C receptor gene and association with obesity and Type II diabetes 假说：5－HT2C受体上游多态性在肥胖发展中发挥一定的作用。 对象：466非肥胖（体重指数<28kg/m2）和138肥胖（≥28），其中2型糖尿病（非胰岛素依赖型）138名。 结果：三个单核苷酸置换位点(G→A at －995, C→T at －759, G→C at －697)和一个（GT）缺陷单核苷酸重复多态性在－1027被发现。－995/－759和－697变异频率在非肥胖者中较高，且－995/－759变异在非糖尿病受试者中较高。在缺陷单核苷酸重复位点中，5个位点包括Z17种重复。Z－6等位基因在非肥胖受试中较常见，Z＋2则在肥胖者中常见。单倍型3（Z－6，－995A，－759T，－697C）与瘦（P＝0.02）和糖尿病的少发生（P＝0.033）有关。单倍型9（Z＋2，－995G，－759C，－697G）与肥胖相关（P＝0.007）。单倍型2（Z－6，－995G，－759C，－697C）在非肥胖者中有更常见的趋势。有荧光(素)酶文献报道单倍体2和3较最常见的单倍体6（Z，－995G，－759C，－697G）有1.44—2.58倍的启动活性。 结论：保持核苷酸置换的单倍体与较高基因转录水平有关，并因而具有抵制肥胖和2型糖尿病的作用。5—HT2C受体基因在启动子的多态性可能在糖尿病的遗传素质中扮演一个重要角色。 Keywords ：Serotonin, 5-HT2C receptor, promoter,polymorphism, obesity. association with obesity and Type II diabetes.pdf (53.01k)The Journal of Neuroscience, January 1, 2003 • 23(1):349 –357 • 349 Activation of the TrkB Neurotrophin Receptor Is Induced by Antidepressant Drugs and Is Required for Antidepressant-Induced Behavioral Effects Recent studies have indicated that exogenously administered neurotrophins produce antidepressant-like behavioral effects. We have here investigated the role of endogenous brain-derived neurotrophic factor (BDNF) and its receptor trkB in the mechanism of action of antidepressant drugs. We found that trkB.T1-overexpressing transgenic mice, which show reduced trkB activation in brain, as well as heterozygous BDNF null (BDNF＋/—) mice, were resistant to the effects of antidepressants in the forced swim test, indicating that normal trkB signaling is required for the behavioral effects typical- ly produced by antidepressants. In contrast, neurotrophin-3
/mice showed a normal behavioral response to antidepressants. Furthermore, acute as well as chronic anti- depressant treatment induced autophosphorylation and activation of trkB in cerebral cortex, particularly in the prefrontal and anterior cingulate cortex and hippocampus. Tyrosines in the trkB autophosphorylation site were phosphorylated in response to antidepressants, but phosphorylation of the shc binding site was not observed. Never- theless, phosphorylation of cAMP response element-binding protein was increased by antidepressants in the prefrontal cortex concomitantly with trkB phosphorylation and this responsewas reduced in trkB.T1-overexpressing mice.Our data suggest that anti- depressants acutely increase trkB signaling in a BDNF-dependent manner in cerebral cortex and that this signaling is required for the behavioral effects typical of anti- depressant drugs. Neurotrophin signaling increased by antidepressants may induce formation and stabilization of synaptic connectivity, which gradually leads to the clinical antidepressive effects and mood recovery 抗抑郁剂能诱导神经营养因子的trkB受体激活，并且这种激活是抗抑郁剂发挥药理效应所必需 近来有研究显示外源性给予的神经营养因子可以使动物出现类似服用抗抑郁剂后的行为变化。在此我们研究了内源性的神经营养因子（BDNF）以及它的受体trkB在抗抑郁剂作用机制中的地位。我们发现在进行强迫游泳试验时抗抑郁剂对trkB.T1过表达的转基因大鼠（其大脑中trkB活性降低）和BDNF杂合子（BDNF+/-）大鼠不产生抗抑郁效应，这显示正常的trkB信号传导系统对抗抑郁剂诱导行为学改变是必要的。另外，我们发现急性或慢性给予抗抑郁剂都可以使大脑皮层特别是前额叶、前扣带回皮质和海马的trkB自身磷酸化而激活。在给予抗抑郁剂后trkB自身磷酸化位点处的酪氨酸发生磷酸化，而trkB的shc结合位点并没有出现磷酸化。cAMP反应结合蛋白（CREB）伴随者trkB的磷酸化而出现磷酸化增加，而这个变化在trkB.T1过表达大鼠中是减弱的。我们的数据提示，急性给予抗抑郁剂能在大脑皮质中引起BDNF依赖性的trkB信号传导增加，而此信号传导变化是抗抑郁剂产生行为学效应所必需的。抗抑郁剂导致的神经营养因子信号传导增强可能诱导新突触的形成并使其保持稳定，而这种突触变化积累到一定程度就表现为抗抑郁疗效的发挥和情绪状态的恢复，这与抗抑郁剂通常数周才起效是一致的。为什么不搞点原创性的东西，中国人的心理与外国存在很大的差异，我认为，心理学这一块是最最模仿不得的。请各位同道注意。我非常认同心理治疗在临床上的作用，而且深深感觉到我们的临床治疗存在重大的心理误区，但是我不认为翻译几篇文章就能解决问题，如果说国外的东西我们在这方面有什么要学习的话，那就是思想方法和工作态度。这是我的临床体会，请各位同道方正。我们一百多年来一直在做的事情就是西方思想的中国化，我认为，现在应该是我们搞原创的时候了。没有思想的支持，我们就不能称其为一个伟大的独立的民族。医学界的对西方的崇拜和依赖是极其严重的，希望我们的年轻人在这方面多做工作。我觉得这个专栏并不是否定原创，而是促使大家更多地关注国外的进展，搞原创不是闭门造车。分子生物学的发展、认知神经科学的崛起，已经令神经、精神、心理领域的面貌焕然一新，ERP、fMRI 等新的研究手段令精神心理的研究大为改观，新的成果不断涌现，而我国在这些方面还比较落后，因此关注国外的动态是重要的工作之一。说实话，搞原创很难很难，而且原创的前提是全面了解国内外的发展现状，希望各位战友能够继续支持！Mol Psychiatry. 2002;7(10):1120-6. Combined action of the ACE D- and the G-protein beta3 T-allele in major depression: a possible link to cardiovascular disease? Bondy B, Baghai TC, Zill P, Bottlender R, Jaeger M, Minov C, Schule C, Zwanzger P, Rupprecht R, Engel RR. Psychiatric Department of University Munich, Nussbaumstrasse 7, D-80336 Munich, Germany. bb@psy.med.uni-muenchen.de Although it is well established that depression is a major risk factor for the development of coronary artery disease and that cerebrovascular disease can be a major contributing factor for the development of depression, the information about the interplay between the central nervous system and cardiovascular disease is still limited. We investigated the angiotensin I converting enzyme (ACE) ID and the G-protein beta3-subunit (Gbeta3) C825T polymorphism in 201 patients with unipolar major depression and 161 ethnically and age-matched controls. Both gene variants have earlier been associated with either cardiovascular disease or affective disorders, making them good candidates for a combined analysis. We found a significant increase in the Gbeta3 T allele (OR = 1.61, 95% CI 1.17-2.2, P = 0.0035) and a marginal altered genotype distribution of the ACE ID polymorphism with decrease in the II genotypes (chi(2) = 6.43, df=3, P = 0.04) in the patients' group. Analysing the data for both genes we found that the combined actions of ACE and Gbeta3 genotypes accumulate in carriers of the ACE D allele (ID and DD) and Gbeta3 TT homozygotes with ID/DD-TT carriers showing a more than five-fold increase in risk for major depression (crude OR = 5.83, 95% CI 1.99-17.08, P = 0.0002). As our study was carried out with depressive patients without serious cardiac impairment at the time of the investigation, we are presently unable to predict whether this combined action of the ACE ID/DD-Gbeta3 TT genotype is increasing the risk for both disorders. Nevertheless our study reports for the first time that the same allelic combination of two genes that have been shown to increase the risk for myocardial infarction (Naber et al, 2000) increase the vulnerability for depressive disorder. PMID: 12476328 [PubMed - indexed for MEDLINE] 尽管已经明确抑郁是冠心病的一个独立的危险因素，脑血管疾病则是导致抑郁的一个重要原因，但中枢神经系统和心血管疾病的相互关系还知之有限。我们对201名单相重性抑郁患者和161名对照的血管紧张素I转化酶 ID和G-蛋白β3-亚基 (Gbeta3) C825T的基因多态性进行了研究。两者的变化都较早地同心血管疾病和情感障碍相关，从而使两者的联合分析成为可能。我们发现患者组Gbeta3 T等位基因显著增高 (OR = 1.61, 95% CI 1.17-2.2, P = 0.0035)，ACE ID(插入/删除）基因型分布略有变化，表现为 II 基因型的减低 (chi(2) = 6.43, df=3, P = 0.04) 。通过对两组基因的数据分析我们发现ACE D等位（ID和DD）载体中ACE、Gbeta3关联发生累积，以及ID/DD-TT中Gbeta3 TT纯合子使得重性抑郁的发病风险升高5倍(crude OR = 5.83, 95% CI 1.99-17.08, P = 0.0002)。由于我们研究实施时抑郁症患者并没有严重的心血管损害，我们暂时还难以预测是否 ACE ID/DD-Gbeta3 TT基因型的关联同时增加了抑郁和心血管疾病的风险。然而，我们的研究首次报告了两个基因的相同基因型的关联，增加了心梗的风险和抑郁障碍的易感性。Authors Cabrera-Vera TM. Battaglia G. Institution Department of Pharmacology and Experimental Therapeutics, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois, USA. Title Prenatal exposure to fluoxetine (Prozac) produces site-specific and age-dependent alterations in brain serotonin transporters in rat progeny: evidence from autoradiographic studies. Source Journal of Pharmacology & Experimental Therapeutics. 286(3):1474-81, 1998 Sep. Local Messages Held by a Lilly Library. Check > Abstract The present study provides the first autoradiographic evidence of age-dependent regional changes in the density of serotonin (5-HT) transporters in offspring following prenatal exposure to fluoxetine. Pregnant rats received either saline or fluoxetine (10 mg/kg, s.c.) daily from gestational day 13 through 20. The density of [3H]citalopram-labeled 5-HT transporters was determined in forebrain regions and in midbrain raphe nuclei of prepubescent and adult male offspring. Brain regions representing integral components of the limbic system were particularly sensitive to the prenatal treatment. For example, prenatal fluoxetine exposure significantly altered the density of 5-HT transporters in subregions of the hypothalamus (dorsomedial nucleus, -21%; lateral hypothalamus, +21%), hippocampus (CA2, +47%; CA3, +38%), and amygdala (basolateral nucleus, +32%; medial nucleus, +44%) in prepubescent offspring. However, 5-HT transporter density in the dorsal and median raphe was unaltered in this same group of offspring. In adult offspring, 5-HT transporter densities, in all brain regions examined, were not significantly altered by prenatal exposure to fluoxetine. The present study also identifies significant age-related differences in 5-HT transporter densities between prepubescent and adult control offspring. For example, in adult control offspring, densities of 5-HT transporters were significantly greater in the cingulate cortex (+33%), basolateral amygdala (+58%), and CA1 area of the hippocampus (+78%); but significantly lower in the temporal cortex (-65%) and median raphe (-25%). The age-dependent and site-specific alterations in the density of 5-HT transporters suggests that either 5-HT innervation and/or 5-HT neuron function in various forebrain regions may be altered by prenatal exposure to fluoxetine. 放射自显影研究：孕期暴露于氟西汀（百优解）引起大鼠后代脑5-羟色胺转运体的位点和年龄相关的改变。 此研究首次提供了孕期暴露于氟西汀的后代中5-羟色胺转运体密度的与年龄和区域相关变化的放射自显影资料。从怀孕13到20天时孕鼠每日使用盐水或氟西汀（皮下使用10mg/kg）。在青春期前和成年期的雄性后代大鼠的前脑和中脑缝核区域检测〔H3〕西酞普兰标记的5-羟色胺转运体。对孕期暴露特别敏感的是涉及边缘系统的整合部分。比如，孕期氟西汀的使用显著地改变了青春期前后代大鼠的下列区域的5-羟色胺转运体密度：下丘脑（背内侧核，-21%，外侧下丘脑，+21%），海马（CA2，+47%；CA3，+38%）和杏仁核（底侧核，+32%，内侧核，+44%）。但是，同一组大鼠的背侧和内侧核的5-羟色胺转运体密度没有改变。在成年大鼠，孕期使用氟西汀对已检测的所有脑区的5-羟色胺转运体密度都没有影响。此研究还发现了在对照组的青春期前和成年大鼠之间的年龄相关的5-羟色胺转运体密度的显著差异。比如，在对照的成年大鼠，5-羟色胺转运体密度在下列区域显著地高：扣带回皮质（+33%），底侧杏仁核（+58%），海马CA1区域（+78%），但在颞叶（-65%）和内侧缝核（-25%）显著地低。这种年龄和区域相关的5-羟色胺转运体密度改变提示：孕期使用氟西汀可以改变不同前脑区域的5-羟色胺神经支配或5-羟色胺神经元的功能。Authors Maes M. Van Gastel A. Delmeire L. Meltzer HY. Institution Clinical Research Center for Mental Health, Antwerp, Belgium. Title Decreased platelet alpha-2 adrenoceptor density in major depression: effects of tricyclic antidepressants and fluoxetine. Source Biological Psychiatry. 45(3):278-84, 1999 Feb 1. Abstract BACKGROUND: It has been suggested that major depression is accompanied by a subsensitivity of central alpha 2-adrenoceptors (alpha 2-ARs) and, consequently, by an impaired negative feedback on the presynaptic catecholaminergic neuron, which, in turn, may induce a disinhibition of noradrenergic output and norepinephrine release in response to any activation. METHODS: The maximum number of platelet binding sites (Bmax) and their affinity for [3H]-rauwolscine, a selective alpha 2-AR antagonist, were measured in unmedicated and medicated major depressed patients and in normal volunteers. Specific binding was defined as that inhibited by idazoxan, another alpha 2-AR antagonist. RESULTS: Unmedicated major depressed patients had significantly decreased platelet [3H]-rauwolscine binding Bmax values compared to normal volunteers. [3H]-rauwolscine binding Kd values did not differ significantly between unmedicated major depressed patients and normal controls. [3H]-rauwolscine binding Kd values were significantly higher in depressed patients treated with tricyclic antidepressants than in unmedicated patients. Subchronic treatment with fluoxetine did not significantly alter either [3H]-rauwolscine binding Bmax or Kd values. [3H]-rauwolscine binding Bmax values were significantly greater in men than in women. CONCLUSIONS: The results suggest that i) major depression is accompanied by decreased platelet alpha 2-AR density; and that ii) subchronic treatment with tricyclic antidepressants, but not fluoxetine, results in a decreased affinity of rauwolscine for platelet alpha 2-ARs. 抑郁症血小板α2肾上腺素受体密度的减少：三环类抗抑郁剂和氟西汀的作用。 背景：曾认为抑郁症可以伴随中枢α2肾上腺素受体密度的降低，继发突触前儿茶酚胺神经元负性反馈的损害，导致刺激后去甲肾上腺素输出和释放去抑制功能的减弱。方法：在药物治疗和未治疗过的抑郁症患者和健康志愿者，测量其血小板结合位点的最大数量（Bmax）和他们对[3H]-α-育亨宾（一种选择性α2肾上腺素拮抗剂）的亲和力。结果：与健康志愿者比，未用药的抑郁症患者血小板[3H]-α-育亨宾和Bmax 都显著降低，而[3H]-α-育亨宾的结合常数没有区别。使用三环类抗抑郁剂治疗的抑郁症患者与未用药患者比，其 [3H]-α-育亨宾的结合常数有明显更高。使用氟西汀亚慢性治疗者的[3H]-α-育亨宾的结合常数和Bmax没有显著改变。男性的[3H]-α-育亨宾的Bmax明显比女性高。结论：结果提示i) 抑郁症存在血小板α2肾上腺素受体密度的降低。 ii) 使用氟西汀亚慢性治疗者可以引起α-育亨宾对血小板α2肾上腺素受体亲和力的降低，但这种改变不见于使用氟西汀的患者。Authors Jackson IM. Luo LG. Institution Division of Endocrinology, Rhode Island Hospital, Brown University School of Medicine, Providence 02903, USA. Title Antidepressants inhibit the glucocorticoid stimulation of thyrotropin releasing hormone expression in cultured hypothalamic neurons. Source Journal of Investigative Medicine. 46(9):470-4, 1998 Dec. Abstract BACKGROUND: The pituitary thyroid axis is frequently effected in human depression possibly due to alteration in hypothalamic thyrotropin releasing hormone (TRH) secretion. Since clinical recovery is associated with normalization of thyroid function, the direct effect of antidepressants on TRH expression in a well established fetal rat hypothalamic neuronal culture system was investigated. METHODS: Fetal rat hypothalamic neurons (day 17) in culture were treated with different concentrations of antidepressants with or without glucocorticoids for 7 days following which TRH content was measured by radioimmunoassay (RIA). RESULTS: The results showed that Imipramine (IMIP), a tricyclic antidepressant (TCA), decreased the TRH content in a dose-dependent manner (from 80.7 +/- 4.9, at 10(-9) mol/L, to 14.1 +/- 0.6, at 10(-5) mol/L, fmol/well; P < 0.05). Desipramine (DESI), another tricyclic antidepressant, also decreased the TRH content (from 63.6 +/- 2.5, at 10(-9) mol/L, to 12.6 +/- 0.4, at 10(-5) mol/L, fmol/well; P < 0.05). Sertraline (SERT) and Fluoxetine (FLUO), serotonin selective reuptake inhibitors (SSRI), also decreased TRH content in a dose dependent manner (from 83.9 +/- 7.9, at 10(-10) mol/L, to 7.6 +/- 0.4, at 10(-5) mol/L, and from 41.66 +/- 2.5, at 10(-8) mol/L, to 17.54 +/- 0.92, at 10(-6) mol/L, fmol/well, respectively; both P < 0.05). We then tested the effect of these antidepressants on the Dex stimulation of TRH content. IMIP, DESIP and FLUO at 10(-6) mol/L reduced the TRH response to glucocorticoid stimulation (36.4 +/- 4.0, 56.6 +/- 2.4, 23.75 +/- 4.0, respectively vs 107 +/- 7.5 fmol/well; P < 0.05). CONCLUSION: This raises the possibility that the enhanced thyroid function in depression, which we postulate, may result in part from glucocorticoid stimulation of TRH gene expression, can be reversed by antidepressants through a direct effect on the TRH neuron. However, other mechanisms may need to be invoked in addition since basal TRH content was also reduced. 抗抑郁剂对培养的丘脑神经元糖皮质激素引起的促甲状腺激素释放激素的表达的抑制。 背景：抑郁时垂体甲状腺轴经常受到影响，其原因可能是下丘脑促甲状腺激素释放激素（TRH）分泌的改变。由于临床康复与甲状腺功能的正常化有关，所以在胎鼠下丘脑神经元模型中检验抗抑郁剂对TRH表达的直接作用。方法：对培养的胎鼠（17天）下丘脑神经元连续使用不同浓度的抗抑郁剂（合并或不合并使用糖皮质激素）7天，之后使用放射免疾分析法测量其 TRH情况。结果：结果发现三环类抗抑郁剂丙咪嗪可以线性地降低TRH 的含量(从 10(-9) mol/L 时的80.7 +/- 4.9，降到10(-5) mol/L 时的14.1 +/- 0.6　fmol/well; P < 0.05)。另一种三环类抗抑郁剂去甲丙咪嗪也可以降低TRH 的含量(从10(-9) mol/L时的63.6 +/- 2.5到10(-5) mol/L时的12.6 +/- 0.4fmol/well; P < 0.05)。SSRI中的色曲林和氟西汀也可以线性地降低TRH 的含量(分别从10(-10) mol/L时的 83.9 +/- 7.9降到10(-5) mol/L 时的7.6 +/- 0.4及从10(-8) mol/L 时的41.66 +/- 2.5降到10(-6) mol/L时的17.54 +/- 0.92fmol/well，P < 0.05)。之后检测这些抗抑郁剂对地塞米松刺激后的TRH含量。在10(-6) mol/L时丙咪嗪，去甲丙咪嗪和氟西汀都可以降低对糖皮质激素的TRH反应 (分别为36.4 +/- 4.0, 56.6 +/- 2.4和 23.75 +/- 4.0对107 +/- 7.5 fmol/well; P < 0.05). 结论：本研究的结果提示抑郁症甲状腺功能的增强，可能会糖皮质激素引起的TRH基因表达，并能够被抗抑郁剂对TRH神经元的直接作用而逆转。但是，因为基础的TRH水平较低，所以其他机制可能也有作用。

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