Does Post-traumatic Stress Disorder Impact Treatment Outcomes within a Randomised Controlled Trial of Mitochondrial Agents for Bipolar Depression?

Samantha E. Russell,Anna L. Wrobel,Melanie M. Ashton,Alyna Turner,Mohammadreza Mohebbi,MIchael Berk,Sue Cotton,Seetal Dodd,Chee H. Ng,Gin S. Malhi,Olivia M. Dean 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.3

Objective: Bipolar disorder often co-occurs with post-traumatic stress disorder, yet few studies have investigated the impact of post-traumatic stress disorder in bipolar disorder on treatment outcomes. The aim of this sub-analysis was to explore symptoms and functioning outcomes between those with bipolar disorder alone and those with comorbid bipolar disorder and post-traumatic stress disorder. Methods: Participants (n = 148) with bipolar depression were randomised to: (i) N-acetylcysteine alone; (ii) a combination of nutraceuticals; (iii) or placebo (in addition to treatment as usual) for 16 weeks (+4 weeks discontinuation). Differences between bipolar disorder and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning at five timepoints, as well as on the rate of change from baseline to week 16 and baseline to week 20, were examined. Results: There were no baseline differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder apart from the bipolar disorder alone group being significantly more likely to be married (p = 0.01). There were also no significant differences between bipolar disorder alone and comorbid bipolar disorder and post-traumatic stress disorder on symptoms and functioning. Conclusion: There were no differences in clinical outcomes over time within the context of an adjunctive randomised controlled trial between those with bipolar disorder alone compared to those with comorbid bipolar disorder and post-traumatic stress disorder. However, differences in psychosocial factors may provide targets for areas of specific support for people with comorbid bipolar disorder and post-traumatic stress disorder.

Atypical Antipsychotics for Bipolar Disorder: Overblown or Blown Over?

Felicity Ng,Seetal Dodd,Michael Berk 대한정신약물학회 2007 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.5 No.2

Objective:Developments in the pharmacological treatment of bipolar disorder are of much interest, as the chronicity and disability of the disorder become better understood, and as treatment goals have shifted to emphasise early control of illness course and maintenance of euthymia in addition to acute episodic remission. Atypical antipsychotics have emerged as treatment options, and this paper aims to review the evidence for their role in bipolar disorder. Methods:A MEDLINE search was conducted for publications up till October 2006. Results:The search yielded a number of randomised, controlled clinical trials of various atypical antipsychotics as monotherapy or adjunctive therapy in bipolar disorder. The majority of such trials have investigated their efficacy in acute mania, with fewer studies devoted to acute bipolar depression or maintenance treatment. There are no specific trials on mixed states, which have mainly been studied together with bipolar mania. The most robust evidence supports a class effect of atypical agents in the treatment of mania. Conclusions:There are placebo-controlled trials that support the efficacy of olanzapine and quetiapine in bipolar depression, and of olanzapine and aripiprazole as maintenance treatment. There is strong support for the role of atypical antipsychotics in bipolar disorder management despite a relatively narrow literature base, chiefly for the treatment of mania. However, these findings need to be replicated, and further investigation is warranted to clarify their spectrum of efficacy in bipolar disorder. Objective:Developments in the pharmacological treatment of bipolar disorder are of much interest, as the chronicity and disability of the disorder become better understood, and as treatment goals have shifted to emphasise early control of illness course and maintenance of euthymia in addition to acute episodic remission. Atypical antipsychotics have emerged as treatment options, and this paper aims to review the evidence for their role in bipolar disorder. Methods:A MEDLINE search was conducted for publications up till October 2006. Results:The search yielded a number of randomised, controlled clinical trials of various atypical antipsychotics as monotherapy or adjunctive therapy in bipolar disorder. The majority of such trials have investigated their efficacy in acute mania, with fewer studies devoted to acute bipolar depression or maintenance treatment. There are no specific trials on mixed states, which have mainly been studied together with bipolar mania. The most robust evidence supports a class effect of atypical agents in the treatment of mania. Conclusions:There are placebo-controlled trials that support the efficacy of olanzapine and quetiapine in bipolar depression, and of olanzapine and aripiprazole as maintenance treatment. There is strong support for the role of atypical antipsychotics in bipolar disorder management despite a relatively narrow literature base, chiefly for the treatment of mania. However, these findings need to be replicated, and further investigation is warranted to clarify their spectrum of efficacy in bipolar disorder.

주요우울장애 환자에서 기분장애 질문지를 이용한 양극성 스펙트럼장애 선별에 관한 연구

김원우,권영준,심세훈,정희연,권완준,이화영 대한신경정신의학회 2012 신경정신의학 Vol.51 No.5

ObjectivesZZThis study was performed to evaluate the frequency of bipolar spectrum disorder (BSD) among patients who have been diagnosed with major depressive disorder. In addition, authors assessed the practical usefulness of the Mood Disorder Questionnaire (MDQ) to investigate the frequency of bipolar spectrum disorder in major depressive disorder. MethodsZZThe participants were 70 depressive patients who have never been diagnosed with bipolar disorders. The subjects were interviewed for diagnosis using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision criteria and the Mini-International Neuropsychiatric Interview to exclude bipolar disorders from the subjects. BSD criteria (as defined by Ghaemi, et al. 2002), and Korean version of the Mood Disorder Questionnaire (K-MDQ) was used to investigate their bipolarity. Data were collected including family history of affective disorder, number of previous depressive episode, age of onset, history of suicide attempt, comorbid psychiatric illness, and drug and alcohol use. ResultsZZAmong 70 subjects, 25 patients (35.7%) were classified as having bipolar spectrum disorder on BSD criteria, while other 45 patients (64.3%) as unipolar depression. Among the 25 patients who meet the BSD criteria, 24 patients (34.3%) scored more than 7 and only 1 patient (1.4%) scored less than 6 on K-MDQ. Among the 45 patients who don’t meet BSD criteria, 40 patients (57.1%) scored less than 6 and only 5 patients (7.1%) scored more than 7 on K-MDQ. Early age of onset, recurrent depressive episode, brief depressive episode, bipolar family history, history of suicide attempt, antidepressant induced hypomania, hyperthymic temperament, atypical depressive symptom, psychotic depressive symptom, and antidepressant “wear off” were found to be highly related with MDQ positive subjects and BSD subjects among the depressive subjects. ConclusionZZThe result of this study demonstrates the high frequency of BSD in depressive patients who have never been diagnosed with bipolar disorders. Some BSD criteria can be used to differentiate BSD subjects from the subjects with major depressive disorder. Also these results indicate that K-MDQ is useful for screening of bipolar spectrum disorder.

양극성 장애에도 정신치료가 필요한가? : 양극성 장애의 정신치료적 접근의 개요와 전망

김원 대한우울조울병학회 2011 우울조울병 Vol.9 No.3

Bipolar disorder is a severe and recurrent mood disorder. The proper pharmacotherapy is essential to the treatment of bipolar disorder. Then, how about psychotherapy? Is psychotherapy necessary to patients with bipolar disorder? The goal of this review is to present an overview of psychotherapy for bipolar disorder, updated results of clinical trial, and the implication of psychotherapy for bipolar disorder. There are several empirically supported psychotherapies for adjunctive treatment to pharmacotherapy of bipolar disorder. Cognitive-behavioral therapy (CBT), interpersonal social rhythm therapy (IPSRT), and Family-focused therapy (FFT) are well-organized branded psychotherapies and psychoeducation is one of the traditional methods for communicating with patients. With respect to the updated results of clinical trials, CBT is efficacious as adjunctive treatment to medication in acute depression and in preventing depressive episodes, but not clear in preventing manic episode. IPSRT is possibly efficacious as adjuncts to medication in acute depression and in preventing bipolar episodes. FFT is efficacious as adjuncts to medication in acute depression and in preventing both depressive and manic episodes. The psychotherapy for bipolar disorder is necessary to improve patients’ medication compliance, reduce residual symptoms, prevent relapse, and then restoring their life. Future research of psychotherapy for bipolar disorder will improve the treatment of bipolar disorder and patients’ qualities of life. (J of Kor Soc for Dep and Bip Disorders 2011;9:154-161)

한국형 양극성 장애 약물치료 알고리듬 2010 : 유지치료

이정구,박원명,윤보현,전덕인,김원,서정석,민경준,이은,주연호,안용민,김병수,신영철 대한우울조울병학회 2011 우울조울병 Vol.9 No.3

Objective : After announcement of Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) in 2006, there has been an increasing need for the revision of treatment algorithm due to rapid changes in the management for bipolar disorder. In this study, we evaluated the maintenance treatment of bipolar I and bipolar II disorders of KMAP-BP 2010. Method : The questionnaire to survey the expert opinion of medication for bipolar disorder was completed by the review committee consisting of 65 experienced psychiatrists. It is composed of 37 questions, and each question includes various sub-items. We classified the expert opinion to 3 categories (the first-line treatment, the second-line, the third-line) by χ2 test. A part of this revision regarding maintenance treatment had 7 items ; 5 on bipolar I and 2 on bipolar II disorder. Results : In case of bipolar I disorder, mood stabilizer monotherapy and combination of mood stabilizer and atypical antipsychotic drugs were 1st-line treatment. In maintenance management for bipolar II disorder, two treatment options were recommended. Treatment with MS alone or combinations of MS and atypical antipsychotic drugs were preferred. Atypical antipsychotic drugs and lamotrigine were more favored in the maintenance treatment for bipolar I and II disorders than previous KAMP-BP 2006. Conclusions : There have been growing body of tendency that atypical antipsychotics are more preferred than the previous KMAP-BP. Also there is an increasing interest on the maintenance use of lamotrigine in the maintenance treatment of bipolar disorder. (J of Kor Soc for Dep and Bip Disorders 2011;9:162-170)

양극성 장애 환자의 소아기 주의력결핍과 CHRNA7 유전자 다형성

정성훈,김의중,이규영,구영진,송주연,송혜진,이주은,주은정 대한정신약물학회 2011 대한정신약물학회지 Vol.22 No.4

Objective Patients with bipolar disorder have attention deficit during even euthymic status. Bipolar disorder patients showed more childhood attention deficit and other ADHD like feature. Alpha 7 nicotinic receptor (CHRNA7) gene has been known to play roles in attention and sensory gating, and association between CHRNA7 gene and bipolar disorder has been reported. Therefore, we investigated a possible association between childhood attention deficit of bipolar disorder and CHRNA7 gene polymorphisms. Methods We included 122 patients with bipolar disorder (89 subjects of bipolar disorder type I, 33 subjects of bipolar disorder type II). Childhood attention deficit was measured by Wender Utah Rating Scale (WURS). Factor analysis was done for WURS to extract inattention factor from childhood ADHD like feature. Three factors were extracted: Impulsivity, Inattention, and Mood instability. All subjects were ethnically Korean. Genotyping was done for three intronic Single Nucleotide Polymorphism (SNPs) of CHRNA7 gene: rs2337506 (A/G), rs6494223 (C/T), and rs12916879 (A/G). Analysis of association was done by UNPHASED version 3.1.4, a free software for genetic statistics. Results Genetic association tests found no association between factor score of inattention and any SNP or combination of SNPs of CHRNA7. Positive association between WURS total score and SNP rs6494223 (p=0.043), factor score of impulsivity and SNP rs2337506 (p=0.038) as well as SNP rs6494223 (p=0.043) was revealed. These positive associations were survived after 1,000 permutation tests. Combination of SNPs association tests performed for total WURS and factor scores could not find any significant association. Conclusion We could not find association between CHRNA7 gene and childhood attention deficit in bipolar disorder. However,we found CHRNA7 gene involved in childhood impulsivity of bipolar disorder, another ADHD like feature. Further studies with larger sample and denser polymorphisms are necessary to clarify genetic role of CHRNA7 in attention and impulsivity of bipolar disorder. 양극성 장애 환자에서 관찰되는 주의력저하에 대한 유전학적 탐구의 일환으로 본 연구에서는 양극성 장애 환자의 소아기 특성으로 나타나는 주의력결핍과 여러 측면에서 양극성 장애의 주의력과 관련이 깊을 것으로 보이는 후보유전자인 CHR-NA7 유전자와의 관련성을 살펴보았다. 122명의 DSM-IV 양극성 장애 환자(양극성 장애 1형 89명, 양극성 장애 2형 33명)를 대상으로 소아기 ADHD 특성을 조사하는 WURS를 적용하고 요인분석을 시행하여 주의력결핍, 충동성, 기분불안정의 3 가지 요인을 추출하였고 각각을 표현형으로 하여 CHRNA7 유전자 내 3개의 SNP 부위와의 관련성을 분석하였다. UNPHASED 를 이용한 개별 SNP 분석 및 SNP 들의 조합을 분석한 결과 소아기 주의력결핍과는 아무런 관련성을 찾을 수 없었고 소아기 충동성 특성에 대해서는 rs2337506와 rs6494223이 개별적으로 유의하게 관련됨을 발견할 수 있었다. 향후 CHRNA7 유전자의 양극성 장애 환자의 주의력 및 소아기 특성에 미치는 역할을 규명하기 위한 후속 연구들이 필요할 것으로 사료된다.

양극성 장애 1형에서 종양괴사인자 베타 유전자 다형성

전태연,이경욱,배치운,김원,우영섭,채정호,박원명 大韓神經精神醫學會 2005 신경정신의학 Vol.44 No.6

Objectives : Bipolar disorder is known to have a high genetic predisposition. Recently, the main focus of etiologic studies in bipolar disorder has been concentrated on molecular genetic approach including gene polymorphism analysis. The present study was conducted to investigate whether TNFB polymorphism is associated with bipolar I disorder in the Korean population. Methods : 89 bipolar I disorder patients diagnosed by DSM-IV criteria were assigned as the patient group and 202 normal population, matched on age and sex from Catholic hemopoietic stem cell bank (Seoul, Korea), were enrolled as the control group in this study. Genotyping was performed by a polymerase chain reaction-restriction fragment length polymorphism method. All data was analyzed by x² test. Results : There were no significant differences in frequency of TNFB*1/1,TNFB*1/2 and TNFB*2/2 between bipolar I disorder patient group and normal control group. The frequency of TNFB*1 was not statistically different between bipolar I disorder patient group and normal control group. Conclusion : The difference of frequency in TNFB*1/TNFB*2 gene between the bipolar I disorder gropup and the normal contro1 could not be verified. The present result suggested that the gene polymorphism of TNFB may not play a significant role in susceptibility to bipolar I disorder. Studies with a larger number of subjects from different ethnic backgrounds, considring clinical phenotype and controlling various factors, should be launched to further determine the role of TNFB in bipolar I disorder.

The Neurobiology of Bipolar Disorder: An Integrated Approach

Ather Muneer 전남대학교 의과학연구소 2016 전남의대학술지 Vol.52 No.1

Bipolar disorder is a heterogeneous condition with myriad clinical manifestations andmany comorbidities leading to severe disabilities in the biopsychosocial realm. The objectiveof this review article was to underline recent advances in knowledge regardingthe neurobiology of bipolar disorder. A further aim was to draw attention to new therapeutictargets in the treatment of bipolar disorder. To accomplish these goals, an electronicsearch was undertaken of the PubMed database in August 2015 of literature publishedduring the last 10 years on the pathophysiology of bipolar disorder. A wide-rangingevaluation of the existing work was done with search terms such as “mood disordersand biology,” “bipolar disorder and HPA axis,” “bipolar disorder and cytokines,” “mooddisorders and circadian rhythm,” “bipolar disorder and oxidative stress,” etc. This endeavorshowed that bipolar disorder is a diverse condition sharing neurobiologicalmechanisms with major depressive disorder and psychotic spectrum disorders. Thereis convincing evidence of crosstalk between different biological systems that act in adeleterious manner causing expression of the disease in genetically predisposedindividuals. Inflammatory mediators act in concert with oxidative stress to dysregulatehormonal, metabolic, and circadian homeostasis in precipitating and perpetuating theillness. Stress, whether biologically or psychologically mediated, is responsible for theinitiation and progression of the diathesis. Bipolar spectrum disorders have a stronggenetic component; severe life stresses acting through various paths cause the illnessphenotype.

Clinical Usefulness of Loudness Dependence of Auditory Evoked Potentials (LDAEP) in Patients with Bipolar Disorder

박영민,이승환 대한신경정신의학회 2013 PSYCHIATRY INVESTIGATION Vol.10 No.3

While it has been reported previously that the loudness dependence of auditory evoked potentials (LDAEP) is a putative biological marker or a predictor of treatment response, there have been few studies of LDAEP in bipolar disorder. However, a recent study by Park and colleagues raised the possibility that the LDAEP could be useful as a biological marker of bipolar disorder. They found that the LDAEP was significantly higher in normal controls than in patients with either bipolar disorder or schizophrenia. Lee and colleagues also examined the LDAEP in bipolar disorder and normal controls, and found that it differed according to the bipolar phase, being significantly higher in cases of euthymic bipolar disorder, bipolar depression, and bipolar mania. With regard to treatment response, early clinical findings were that a higher LDAEP and a stronger intensity dependence of visual evoked potentials were related to a favorable response to lithium treatment. Juckel and colleagues recently demonstrated that the pretreatment LDAEP could be a predictor of successful prophylactic lithium treatment. The present article reviews the literature in order to determine whether the LDAEP can be used as a biological marker or a predictor of treatment response in patients with bipolar disorder and of manic switch or treatment resistance in patients with major depressive episode(s).

한국형 양극성장애 약물치료 알고리듬 2014 : 소아 청소년

심세훈,박원명,손인기,김문두,이정구,윤보현,정종현,왕희령,우영섭,전덕인,서정석,신영철,민경준 대한우울조울병학회 2014 우울조울병 Vol.12 No.2

Objectives : Clinicians who treat children and adolescents with bipolar disorder desperately need current treatment guidelines. Therefore, we decided to develop first the algorithms for children and adolescents with bipolar disorder when we revise the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) 2010. Method : We performed the survey using questionnaire comprising 16 questions according to each situation in children and adolescents with bipolar disorder. Twenty-three members of the review committee completed the survey. The executive committee analyzed the results and discussed the final production of algorithm considering scientific evidences. Results : The first-line strategy for manic episode in children and adolescents with bipolar disorder is combina-tion of mood stabilizer and an atypical antipsychotic. There was no first-line strategy including expert consensus for depressive episode in children and adolescents with bipolar disorder and at high risk for bipolar disorder. Conclusion : We developed the algorithm for children and adolescents with bipolar disorder first in KMAP-BP 2014. We expect this algorithm may provide clinicians good information and help about the treatment of children and adolescents with bipolar disorder.