Ataxia-telangiectasia mutated (ATM), a master kinase of the DNA damage response (DDR), phosphorylates a multitude of substrates to activate signaling pathways after DNA double-strand breaks (DSBs). ATM inhibitors have been evaluated as anticancer drugs to potentiate the cytotoxicity of DNA damage-based cancer therapy. ATM is also involved in autophagy, a conserved cellular process that maintains homeostasis by degrading unnecessary proteins and dysfunctional organelles. In this study, we report that ATM inhibitors (KU-55933 and KU-60019) provoked accumulation of autophagosomes and p62 and restrained autolysosome formation. Under autophagy-inducing conditions, the ATM inhibitors caused excessive autophagosome accumulation and cell death. This new function of ATM in autophagy was also observed in numerous cell lines. Repression of ATM expression using an siRNA inhibited autophagic flux at the autolysosome formation step and induced cell death under autophagy-inducing conditions.Taken together, our results suggest that ATM is involved in autolysosome formation and that the use of ATM inhibitors in cancer therapy may be expanded.

Objective: The Functioning Assessment Short Test (FAST) is a relatively specific test for bipolar disorders designed to assess the main functioning problems experienced by patients. This brief instrument includes 24 items assessing impairment or disability in 6 domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time. It has already been translated into standardized versions in several languages. The aim of this study is to measure the validity and reliability of the Korean version of FAST (K-FAST). Methods: A total of 209 bipolar disorder patients were recruited from 14 centers in Korea. K-FAST, Young Mania Rating Scale (YMRS), Bipolar Depression Rating Scale (BDRS), Global Assessment of Functioning (GAF) and the World Health Organization Quality of Life Assessment Instrument Brief Form (WHOQOL-BREF) were administered, and psychometric analysis of the K-FAST was conducted. Results: The internal consistency (Cronbach’s alpha) of the K-FAST was 0.95. Test-retest reliability analysis showed a strong correlation between the two measures assessed at a 1-week interval (ICC = 0.97; p ＜ 0.001). The K-FAST exhibited significant correlations with GAF (r = −0.771), WHOQOL-BREF (r = −0.326), YMRS (r = 0.509) and BDRS (r = 0.598). A strong negative correlation with GAF pointed to a reasonable degree of concurrent validity. Although the exploratory factor analysis showed four factors, the confirmatory factor analysis of questionnaires had a good fit for a six factors model (CFI = 0.925; TLI = 0.912; RMSEA = 0.078). Conclusion The K-FAST has good psychometric properties, good internal consistency, and can be applicable and acceptable to the Korean context.

The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2022 (KMAP-BP 2022) with other recently published guidelines for treating bipolar disorder. We reviewed a total of six recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2022 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy in a same degree for mania. However, the KMAP-BP 2022 recommended MS + AAP combination therapy for psychotic mania, mixed mania and psychotic depression as treatment of choice. Aripiprazole, quetiapine and olanzapine were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Some guideline suggested olanzapine is a second-line options during maintenance treatment, related to concern about long-term tolerability. Most guidelines advocated newer AAPs (asenapine, cariprazine, long-acting injectable risperidone, and aripiprazole once monthly) as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. KMAP-BP 2022 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2022, predominantly in the treatment of psychotic mania, mixed mania and psychotic depression.

Objective: We revised the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP), first published in 2002 and revised in 2006, 2010, 2014, and 2018, to reflect recent progress in the treatment of bipolar disorder. Methods: The questionnaires consisted of 56 items for adult patients and 7 items for child/adolescent patients, and were used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of bipolar disorder. The review committee included 87 Korean psychiatrists and 40 child and adolescent psychiatry experts. Results: For treatment of manic episodes, a combination of a mood stabilizer (MS) and atypical antipsychotics (AAP), or monotherapy with MS or AAP were recommended as first-line treatments. Combinations of MS and AAP, or AAP and lamotrigine (LMT) were recommended as first-line treatments for depressive episodes regardless of the severity. Monotherapy with MS, AAP, or LMT were also first-line treatments for mild to moderate depressive episodes. For mixed features, a combination of MS and AAP, or monotherapy with AAP or MS were recommended as first-line treatments, and a combination of AAP and LMT, or MS and LMT were the first-line treatments for depressive mixed state. Conclusion The recommendations of the KMAP-BP 2022 have changed from the previous version, to reflect the evolution of the social culture and healthcare system in Korea and recent evidence regarding pharmacotherapy of bipolar disorder. The KMAP-BP 2022 provides clinicians with a wealth of information regarding appropriate strategies to treat patients with bipolar disorder.

The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) first was published in 2002, and has been revised four times, in 2006, 2012, 2017, and 2021. In this review, we compared recommendations from the recently revised KMAP-DD 2021 to four global clinical practice guidelines (CPGs) for depression published after 2010. The recommendations from the KMAP-DD 2021 were similar to those from other CPGs, although there were some differences. The KMAP-DD 2021 reflected social culture and the healthcare system in Korea and recent evidence about pharmacotherapy for depression, as did other recently published evidence-based guidelines. Despite some intrinsic limitations as an expert consensus-based guideline, the KMAP-DD 2021 can be helpful for Korean psychiatrists making decisions in clinical settings by complementing previously published evidence-based guidelines, especially for some clinical situations lacking evidence from rigorously designed clinical trials.

Objectives: This study revised the Korean Medication Algorithm Project for Bipolar Disorder 2018 for rapid cycling. Methods: Questionnaires to survey the expert opinion of medication for rapid cycling were completed by a review committee consisting of 87 Korean expert psychiatrists. The experts’ opinions were classified into three categories based on the lowest category in which the confidence interval fell (6.5≤ for first-line, 3.5≤ for second-line, and 3.5> for third-line treatment). Results: The first-line treatments were a combination of mood stabilizers and atypical antipsychotics, atypical antipsychotics monotherapy, or mood stabilizer monotherapy. Furthermore, a mood stabilizer with lamotrigine therapy and an atypical antipsychotic with lamotrigine combinations was the first-line treatment for a depressive episode. The first-line medications in all episodes were valproate, lithium, quetiapine, olanzapine, and aripiprazole. Risperidone was the first-line medication in manic episodes and mixed states, and lamotrigine was the first-line medication for treating depressive episodes. Conclusion Compared to the surveys in 2018, the preference for atypical antipsychotics and lamotrigine has increased, and the modalities as a second-line treatment are more diversified.

Objectives: The objective of this study was to revise the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) 2022: children and adolescents. Methods: We performed a survey, using a questionnaire comprising 23 questions according to various situations facing children and adolescents with bipolar disorders. A total of 40 of the 60 experts in child and adolescent psychiatry responded to the survey. Results: The first-line pharmacotherapeutic strategies for manic and depressive episodes in children with bipolar disorders were a combination of mood stabilizer (MS) and atypical antipsychotics (AAP). The first-line medications selected for these children were aripiprazole (treatment of choice, TOC) and risperidone. The first-line pharmacotherapeutic strategies for manic episodes in adolescents were a combination of MS and an AAP (TOC), monotherapy with MS, and monotherapy with an AAP. Lithium, valproate, aripiprazole, risperidone, and quetiapine were selected as first-line medications for these adolescents. First-line pharmacotherapeutic strategies for depressive episodes in adolescents were a combination of MS and an AAP, monotherapy with MS, and monotherapy with an AAP. The first-line pharmacotherapeutic strategies for the depressive episodes in adolescents at high risk for bipolar disorder were a combination of MS and AAP and monotherapy with an AAP. Lithium, valproate, aripiprazole (TOC), quetiapine, and risperidone were selected as first-line medications for the treatment of depressive episodes in adolescents with bipolar disorder. Conclusion It is expected that the present KMAP-BP 2022: children and adolescents will give the direction and be usefully applied by clinicians to treat children and adolescents with bipolar disorders.

Objectives: In this study, we investigated and organized the maintenance-treatment strategies for Bipolar I and II disorders outlined in The Korean Medication Algorithm Project for Bipolar disorder 2022 (KMAP-BP 2022). Methods: The questionnaire sought to survey expert opinion on medication for bipolar disorders and was completed by a review committee consisting of 87 experienced Korean psychiatrists. It comprised 56 questions, and each question included various sub-items. The questionnaire for the maintenance treatments covered overall treatment strategies after acute mood episodes in bipolar I and II disorders, the choice of mood stabilizers and atypical antipsychotics and antidepressants, duration of medication, and treatment strategies for breakthrough symptoms. Results: In the case of bipolar I disorder, mood stabilizer monotherapy, atypical antipsychotics monotherapy, and a combination of mood stabilizers and atypical antipsychotics were selected as the first-line treatments. In maintenance management of bipolar II disorder, mood stabilizer monotherapy, atypical antipsychotics monotherapy, and combinations of mood stabilizers were selected as the preferred first-line treatments. Conclusion There has been a growing body of evidence that atypical antipsychotics have a greater preference than observed in the previous KMAP-BP of 2018. Also, monotherapy of mood stabilizers or atypical antipsychotics was more frequently selected in KMAP-BP 2022 than in the KMAP-BP 2018.

Objectives: The safety and tolerability of drugs are very important to ensure compliance and efficacy in the treatment of bipolar disorders. An expert opinion survey was conducted on treatment strategies in various special clinical situations, such as patients with significant weight gain, reporting characteristic drug side effects, low drug adherence, pregnant and reproductive women, and genetic counseling. Methods: A written survey that addressed treatment strategies related to safety and tolerability was prepared. The survey focused on significant weight gain, characteristic drug side effects, low drug adherence, treatment of pregnant and reproductive women, and genetic counseling. Eighty-seven experts in the review committee completed the survey. Results: In the case of weight gain occurring during drug treatment, it was considered preferable to replace the treatment drug with a drug that caused less weight gain, such as lamotrigine, aripiprazole, or ziprasidone. If there was a significant weight gain due to the treatment drug, it was considered preferable to intervene as soon as possible. In the case of hyperprolactinemia, it was considered preferable to change the drug. It was recommended that the drug beto discontinued in case of a benign rash as seen in patients treated with lamotrigine. For improving drug adherence, there was an increased preference for long-acting injections. It was also opined that antipsychotics should be used with great caution in pregnant or reproductive women. Conclusion Treatment strategies in various clinical situations related to the safety and tolerability of drugs for bipolar disorder have been described. It is hoped that this information would be useful in practical clinical situations.

Objectives: The present study was carried out to revise the guidelines for the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) 2018. The revision was carried out based on expert opinions to facilitate clinical decisions related to the treatment of bipolar disorders in patients with comorbid physical illnesses. Methods: A 56-item questionnaire was developed; a consensus was arrived at by 87 out of 93 experts (93.5%), on the pharmacological treatment strategies to be used in cases of comorbid physical illnesses accompanying bipolar disorders. Results: For patients with bipolar disorder exhibiting comorbid conditions, by consensus, lamotrigine, aripiprazole, and ziprasidone were recommended as the first-line strategies for metabolic syndrome; lamotrigine and aripiprazole were the recommended first-line strategies for cardiovascular problems; lithium and aripiprazole were the recommended first-line strategies for haptic problems; valproate, lamotrigine, aripiprazole, and quetiapine were the recommended first-line strategies for renal problems; and valproate and aripiprazole were the recommended first-line strategies for cerebrovascular problems or cerebral damage. Conclusion The present study is the most recent consensus among experts on recommendations for the treatment of bipolar disorders in patients with comorbid physical illnesses. Aripiprazole was recommended as the first-line pharmacotherapeutic agent in five comorbid physical conditions. This recommendation is similar to KMAP-BP 2018. Additionally, lamotrigine has been added as a first -line pharmacotherapeutic agent in patients with the metabolic syndrome, cardiovascular problems, and renal problems in the current algorithm.