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Continuous use of antidepressants can relieve depressive symptoms and prevent recurrence in people with depression; however, many studies have reported low drug compliance rates. This study aimed to investigate the relationship between the type of initial antidepressants and treatment adherence in outpatients with new onset depression.This was a retrospective cohort study using National Health Insurance claim data for services provided in 2012. We examined data from 142,336 individuals aged 18 years or older, who were continuously enrolled in treatment after a new episode of depression, and had initiated antidepressant treatment. A new diagnosis of depression, is defined as a first reported diagnosis of depression in the preceding five years. Adherence was operationally defined as the antidepressant being dispensed to the patient at least 80% of the time during the first three- and six-month treatment periods. To investigate the relationship between the initial type of antidepressants and treatment adherence, we estimated adjusted odds ratios and 95% confidence intervals using logistic regression analysis, adjusting for socio-demographic and health care utilization characteristics.A statistically significant association was found between initial antidepressant type and adherence in the first three- and six-month treatment periods for employed and self-employed patients newly diagnosed with major depression. In addition, patients with starting prescriptions for tricyclic antidepressants had significantly lower adherence compared to selective serotonin reuptake inhibitors.This study used national insurance data; therefore, only variables on the claim form were available, and psychological and environmental factors were not considered.This was the first study to demonstrate the relationship between initial antidepressant type and treatment adherence among Korean outpatients with new onset depression.

This study aimed to evaluate whether somatic symptoms in adolescents with attention deficit hyperactivity disorder (ADHD) are associated with a dissociative pattern of functional connectivity (FC) within the default mode network (DMN) and whether methylphenidate administration can improve clinical and somatic symptoms. We also evaluated whether the improvement of somatic symptoms is associated with increased FC within the DMN in response to methylphenidate treatment.Fifteen male adolescents with somatic symptoms of ADHD and 15 male adolescents with ADHD without somatic symptoms were included. At baseline and after 6 months of methylphenidate treatment, all adolescents were asked to complete questionnaires for the Korean version of the Dupaul's ADHD rating scale, the symptom checklist-90- revised-somatization subscales, the Beck Depression Inventory, and the Beck Anxiety Inventory. Additionally, a resting- state functional magnetic resonance imaging scan was conducted.Methylphenidate treatment improved clinical and somatic symptoms in adolescents with ADHD. In addition, it increased brain FC within the DMN from the posterior cingulate cortex (posterior DMN) to the middle prefrontal cortex (anterior DMN). The improvement of somatic symptoms was associated with FC within the DMN from the posterior cingulate cortex to the middle prefrontal cortex in ADHD adolescents with somatic symptoms.Methylphenidate increased brain FC between the anterior and posterior DMN. The improvement of somatic symptoms in adolescents with ADHD was associated with FC within the DMN. The DMN in adolescents with ADHD seems to be associated with the severity of the clinical and somatic symptoms of ADHD.

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.

Background. The Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) is an expert consensus guideline for depressive disorder created in 2002, and since then, four revisions (2006, 2012, 2017, 2021) have been published. In this study, changes in the content of the KMAP-DD survey and recommendations for each period were examined. Methods. The development process of the KMAP-DD was composed of two stages. First, opinions from experts with abundant clinical experience were gathered through surveys. Next, a final guideline was prepared through discussion within the working committee regarding the suitability of the results with reference to recent clinical studies or other guidelines. Results. In mild depressive symptoms, antidepressant (AD) monotherapy was preferred, but when severe depression or when psychotic features were present, a combination of AD and atypical antipsychotics (AD + AAP) was preferred. AD monotherapy was preferred in most clinical subtypes. AD monotherapy was preferred for mild depressive symptoms, and AD + AAP was preferred for severe depression and depression with psychotic features in children, adolescents, and the elderly. Conclusions. This study identified the changes in the KMAP-DD treatment strategies and drug preferences in each period over the past 20 years. This work is expected to aid clinicians in establishing effective treatment strategies.

Objectives The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) is based on expert consensus and has been revised five times since 2002. This study evaluated the changes in treatment strategies advocated by the KMAP-BP over time. Methods The five editions of the KMAP-BP were reviewed, and the recommendations of the KMAP-BP were compared with those of other bipolar disorder (BP) treatment guidelines. Results The most preferred option for the initial treatment of mania was a combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP). Either MS or AAP monotherapy was also considered a first-line strategy for mania, but not for all types of episodes, including mixed/psychotic mania. In general, although lithium and valproic acid were commonly recommended, valproic acid has been increasingly preferred for all phases of BP. The most notable changes over time included the increasing preference for AAPs for all phases of BP, and lamotrigine for the depressive and maintenance phases. The use of antidepressants for BP has gradually decreased, but still represents a first-line option for severe and psychotic depression. Conclusions In general, the recommended strategies of the KMAP-BP were similar to those of other guidelines, but differed in terms of the emphasis on rapid effectiveness, which is often desirable in actual clinical situations. The major limitation of the KMAP-BP is that it is a consensus-based rather than an evidence-based tool. Nevertheless, it may confer advantages in actual clinical practice.

Objective In this study we investigated whether current mood states of patients with bipolar disorder have an influence on the screening accuracy of the Mood Disorder Questionnaire (MDQ). Methods A total of 452 patients with mood disorder (including 192 with major depressive disorder and 260 with bipolar disorder completed the Korean version of the MDQ. Patients with bipolar disorder were subdivided into three groups (bipolar depressed only, bipolar euthymic only, bipolar manic/hypomanic only) according to current mood states. The screening accuracy of the MDQ including sensitivity, specificity and area under the curve (AUC) of receiver operating characteristic (ROC) curves were evaluated according to current mood states. Results The optimal cutoff of MDQ was 5 in this study sample. Sensitivity and specificity were not significantly different according to current mood states. Significant differences in AUCs of four independent ROC curves were not found (ROC 1st curve included all bipolar patients; ROC 2nd curve included only bipolar depressed patients; ROC 3rd curve included only bipolar manic/hypomanic patients; ROC 4th curve included only bipolar euthymic patients). Conclusion The study results showed that current mood states (either euthymic state, depressed or manic/hypomanic) did not significantly influence the screening accuracy of the MDQ suggesting that the MDQ could be a useful screening instrument for detecting bipolar disorder in clinical practice regardless of the current mood symptoms of subjects.

Objective In the 19 years since the Korean College of Neuropsychopharmacology and the Korean Society for Affective Disorders developed the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) in 2002, four revisions have been conducted. Methods To increase survey efficiency in this revision, to cover the general clinical practice, and to compare the results with previous KMAP-DD series, the overall structure of the questionnaire was maintained. The six sections of the questionnaire were as follows: 1) pharmacological treatment strategies for major depressive disorder (MDD) with/without psychotic features; 2) pharmacological treatment strategies for persistent depressive disorder and other depressive disorder subtypes; 3) consensus for treatment-resistant depression; 4) the choice of an antidepressant in the context of safety, adverse effects, and comorbid physical illnesses; 5) treatment strategies for special populations (children/adolescents, elderly, and women); and 6) non-pharmacological biological therapies. Recommended first-, second-, and third-line strategies were derived statistically. Results There has been little change in the four years since KMAP-DD 2017 due to the lack of newly introduced drug or treatment strategies. However, shortened waiting time between the initial and subsequent treatments, increased preference for atypical antipsychotics (AAPs), especially aripiprazole, and combination strategies with AAPs yield an active and somewhat aggressive treatment trend in Korea. Conclusion We expect KMAP-DD to provide clinicians with useful information about the specific strategies and medications appropriate for treating patients with MDD by bridging the gap between clinical real practice and the evidence-based world.

The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2018 (KMAP-BP 2018) with other recently published guidelines for treating bipolar disorder. We reviewed a total of five recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2018 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 for mania. However, the KMAP-BP 2018 did not prefer monotherapy with MS or AAP for psychotic mania. Quetiapine, olanzapine and aripiprazole were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Most guidelines advocated newer AAPs 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. As research evidence accumulated over time, recommendations of newer AAPs (such as asenapine, cariprazine, paliperidone, lurasidine, long-acting injectable risperidone and aripiprazole once monthly) became prominent. KMAP-BP 2018 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 2018, predominantly in the treatment of psychotic mania and severe depression. Further studies were needed to address several issues identified in our review.

Objective The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was first published in 2002 through an expert consensus of opinion, and updated in 2006, 2010, and 2014. This study constitutes the fourth revision of the KMAP-BP. Methods A 50-item questionnaire was used to obtain the consensus of experts regarding pharmacological treatment strategies for various phases of adult bipolar disorder and six items for pediatric bipolar disorder. The review committee included 84 Korean psychiatrists and 43 child and adolescent psychiatry experts. Results The preferred first-step strategies for acute mania were the combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP), MS monotherapy, and AAP monotherapy. A combination of a MS and an AAP, and AAP monotherapy were preferred for psychotic mania. The first-step strategies for mild to moderate bipolar depression were monotherapy with MS, AAP, or lamotrigine (LMT), and the combination of a MS and an AAP or LMT, or a combination of an AAP and LMT. The combination of two among a MS, AAP, and LMT were preferred for non-psychotic severe depression. A combination of a MS and an AAP or the combination of an AAP with an antidepressant or LMT were the first-line options for psychotic severe depression. Conclusion The recommendations of the KMAP-BP 2018 have changed from the previous version by reflecting recent developments in pharmacotherapy for bipolar disorder. KMAP-BP 2018 provides clinicians with a wealth of information regarding appropriate strategies for treating patients with bipolar disorder.

Objective In 2002, the Korean Society for Affective Disorders developed the guidelines for the treatment of major depressive disorder (MDD), and revised it in 2006 and 2012. The third revision of these guidelines was undertaken to reflect advances in the field. Methods Using a 44-item questionnaire, an expert consensus was obtained on pharmacological treatment strategies for MDD 1) without or 2) with psychotic features, 3) depression subtypes, 4) maintenance, 5) special populations, 6) the choice of an antidepressant (AD) regarding safety and adverse effects, and 7) non-pharmacological biological therapies. Recommended first, second, and third-line strategies were derived statistically. Results AD monotherapy is recommended as the first-line strategy for non-psychotic depression in adults, children/adolescents, elderly adults, patient with persistent depressive disorder, and pregnant women or patients with postpartum depression or premenstrual dysphoric disorder. The combination of AD and atypical antipsychotics (AAP) was recommended for psychotic depression in adult, child/adolescent, postpartum depression, and mixed features or anxious distress. Most experts recommended stopping the ongoing initial AD and AAP after a certain period in patients with one or two depressive episodes. As an MDD treatment modality, 92% of experts are considering electroconvulsive therapy and 46.8% are applying it clinically, while 86% of experts are considering repetitive transcranial magnetic stimulation but only 31.6% are applying it clinically. Conclusion The pharmacological treatment strategy in 2017 is similar to that of Korean Medication Algorithm for Depressive Disorder 2012. The preference of AAPs was more increased.

Background Treatment using aversive conditioning has been suggested for smoking cessation. The efficacy of this method is thought to be associated with cognitive avoidance. We compare differences in avoidance traits and patterns of associated brain activation in response to cues that induce cravings versus aversion between smokers and non-smokers. Methods Fifteen smokers and fifteen non-smokers completed cue reactivity tasks while undergoing functional magnetic resonance imaging (fMRI) to examine brain responses to craving-inducing cues (Cr) and aversion-inducing cues (Av). Participant avoidant traits were also assessed. Results Activation of the left frontal subcallosal gyrus in response to Cr was greater in smokers than in non-smokers. Smokers showed less activation in the right temporal lobe in response to Av than did non-smokers. Brain activation in response to Cr in the left frontal subcallosal gyrus was positively correlated with Fagerstrom Test for Nicotine Dependence (FTND) scores in smokers. Brain activation in response to Av in the right temporal lobe was negatively correlated with the Korean Version of the Cognitive Avoidance Questionnaire (KCAQ) scores in non-smokers. Conclusions Cognitive avoidance in smokers during aversive stimulation might result in sustaining addictive behaviors. On the other hand, non-smokers may be able to emotionally confront the adverse effects of smoking.

In this review, we compared recommendations from the Korean Medication Algorithm Project for Depressive Disorder 2017 (KMAP-DD 2017) to other global treatment guidelines for depression. Six global treatment guidelines were reviewed; among the six, 4 were evidence-based guidelines, 1 was an expert consensus-based guideline, and 1 was an amalgamation of both evidence and expert consensus-based recommendations. The recommendations in the KMAP-DD 2017 were generally similar to those in other global treatment guidelines, although there were some differences between the guidelines. The KMAP-DD 2017 appeared to reflect current changes in the psychopharmacology of depression quite well, like other recently published evidence-based guidelines. As an expert consensus-based guideline, the KMAP-DD 2017 had some limitations. However, considering there are situations in which clinical evidence cannot be drawn from planned clinical trials, the KMAP-DD 2017 may be helpful for Korean psychiatrists making decisions in the clinical settings by complementing previously published evidence-based guidelines.

In order to compare patterns of connectivity between affective and attention networks in adolescents with bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD), we investigated differences in resting state functional connectivity (RSFC) between these populations. Study participants were medication-naïve adolescents (aged 13-18 years) with BD (N=22) or ADHD (N=25) and age- and sex-matched healthy adolescents (healthy controls [HC]) (N=22). Forty-seven adolescents with mood fluctuation and attention problems showed increased functional correlation (FC) between two pairs of regions within the affective network (AFN), compared to 22 HC: the left orbitofrontal cortex (OFC) to the left thalamus and the left OFC to the right thalamus. In post-hoc testing, adolescents with BD showed increased FC between two pairs of regions compared to ADHD: the right amygdala to the left temporoparietal junction (TPJ) and the right amygdala to the right TPJ. Adolescents with BD showed increased FC within the attention network (ATN) as well as increased FC between the ATN and the AFN, while those with ADHD showed decreased FC within the ATN. The current suggests that these features could be used as biomarkers for differentiating BD from ADHD in adolescents.

Objective The aim of the present study was to evaluate the role of comorbid psychiatric symptoms on quantitative electroencephalogram (QEEG) activities in boys with the attention deficit/hyperactivity disorder (ADHD). Methods All participants were male students in the second, third or fourth grade in elementary school. Therefore, there were no significant differences in age or sex. Participants with ADHD were assigned to one of three groups: pure ADHD (n=22), ADHD with depressive symptoms (n=11), or ADHD with problematic internet use (n=19). The Korean version of the Children's Depression Inventory and the Korean Internet Addiction Self-scale were used to assess depressive symptoms and problematic internet use, respectively. Resting-state EEG during eyes closed was recorded, and the absolute power of five frequency bands was analyzed: delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), and gamma (30-50 Hz). Results The ADHD with problematic internet use group showed decreased absolute theta power at the central and posterior region compared with the pure ADHD group. However, The ADHD with depressive symptoms group showed no significant differences compared with the other groups. Conclusion These findings will contribute to a better understanding of brain-based electrophysiological changes in children with ADHD in accordance with comorbid psychiatric symptoms.

Objectives The purpose of this study was to evaluate the prevalence of mixed features using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and to examine how patients with mixed states would be classified using the DSM-5. Methods In total, 12 hospitals participated in this study, and data on the demographic characteristics and clinical diagnoses of patients treated between October 2013 and September 2016 were obtained. We reviewed the data for opposite-polarity symptoms according to the DSM-5 criteria and the research-based diagnostic criteria. Results Of the 859 patients included in the final analysis, the prevalence of mixed features in patients with major depressive episodes based on the DSM-5 remained low. Patients with major depressive disorder were more likely to be classified as experiencing anxious distress and/or a cluster-B personality disorder in mixed state patients not diagnosed with DSM-5 mixed features, whereas more mixed state patients with bipolar disorder were diagnosed with mixed features using the DSM-5. Conclusions The prevalence of mixed features did not increase significantly when the DSM-5 was used, and patients with mixed states were more likely to be classified as having anxious distress and/or a cluster-B personality disorder in addition to mixed features.

Objective Dopamine plays a significant role in working memory by acting as a key neuromodulator between brain networks. Additionally, treatment of patients with schizophrenia using amisulpride, a pure dopamine class 2/3 receptor antagonist, improves their clinical symptoms with fewer side effects. We hypothesized that patients with schizophrenia treated with amisulpride and aripiprazole show increased working memory and glucose metabolism compared with those treated with cognitive behavioral therapy (CBT) and aripiprazole instead. Methods Sixteen patients with schizophrenia (eight in the amisulpride group [aripiprazole+amisulpride] and eight in the CBT group [aripiprazole+CBT]) and 15 age- and sex-matched healthy control subjects were recruited for a 12-week-long prospective trial. An [18F]-fluorodeoxyglucose-positron emission tomography/computerized tomography scanner was used to acquire the images. Results After 12 weeks of treatment, the amisulpride group showed greater improvement in the Letter-Number Span scores than the CBT group. Additionally, although brain metabolism in the left middle frontal gyrus, left occipital lingual gyrus, and right inferior parietal lobe was increased in all patients with schizophrenia, the amisulpride group exhibited a greater increase in metabolism in both the right superior frontal gyrus and right frontal precentral gyrus than the CBT group. Conclusion This study suggests that a small dose of amisulpride improves the general psychopathology, working memory performance, and brain glucose metabolism of patients with schizophrenia treated with aripiprazole.

Objective It is not easy to diagnose bipolar disorders accurately in the clinical setting. Although Korean version of the Mood Disorder Questionnaire (K-MDQ) is easily administered, it still has weakness regarding case finding. In this study, we suggest a new weighted version of the K-MDQ to increase its screening power. Methods Ninety-five patients with bipolar disorders and 346 controls (patients with schizophrenia, patients with depressive disorders, patients with anxiety disorders, and subjects without any psychiatric disease) were enrolled in this study. The subjects received brief information on the K-MDQ, and then independently completed the questionnaire. Results Using odds ratios, we constructed a new weighted K-MDQ (W-K-MDQ). Item 1 (feel so good or hyper) was weighted 7 times and item 4 (less sleep) 3.5 times. Item 7 (easily distracted) and item 11 (more interested in sex) were excluded. Part 2 (simultaneity) and 3 (functional impairment) were also excluded as in the original K-MDQ. The sensitivity of the W-K-MDQ with a cutoff value of 10 was enhanced to 0.789. The area under the receiver operating characteristic curve was increased to 0.837. Conclusion We suggested a new formula for K-MDQ using 11 of its items. The W-K-MDQ can be easily applied with good sensitivity to screen for bipolar disorders in clinical settings in Korea. Further evaluations with larger samples are needed to establish the usefulness of the W-K-MDQ.

Theta-phase gamma-amplitude coupling (TGC) between slow and fast oscillations is considered to represent cortico-subcortical interactions. The purpose of this electroencephalographic (EEG) study was to evaluate the diagnostic utility of TGC by comparing the power spectra and TGC at rest between ADHD and control children. Nineteen-channel EEGs were recorded from 97 volunteers (including 53 subjects with ADHD attending a camp for hyperactive children). The EEG power spectra and TGC data were analyzed. Analysis of covariance (ANCOVA) was conducted on the quantitative EEG results between the groups to adjust for sex. Receiver operator characteristic (ROC) analysis was conducted to examine the discriminating ability of each parameter for ADHD diagnosis. The ADHD group exhibited significantly decreased TGC in multiple areas, including frontal (Fp1, F3, F7, F6), temporal (T3), and occipital (O2) areas, compared with the control group. The ROC analysis performed on the TGC data generated the most accurate result among the EEG measures, with an overall classification accuracy of 71.7%. TGC, which reflects the degree of neuronal interactions between functional systems, provides information about an individual's attentional network. Therefore, resting-state TGC is a promising neurophysiological marker of ADHD in children.

OBJECTIVE: Mirtax is a generic mirtazapine widely used since 2003. We conducted an open-label, uncontrolled 6-week study to evaluate the efficacy and safety of Mirtax for major depressive disorder (MDD). METHODS: Ninety three MDD patients with the diagnosis of MDD and 17-item Hamilton Depression Rating Scale (HDRS) score ≥14 were recruited. The HDRS, Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions-Severity Scale (CGI-S) were administered at baseline, 1, 2, 4 and 6 weeks. Response (≥50% decrease in the HDRS or MADRS score), remission (absolute HDRS score ≤7 or MADRS score ≤10) and CGI-I score ≤2 were also calculated. Adverse event (AE) frequency and severity, weight, blood pressure, and pulse rate were checked to assess safety. RESULTS: The starting dosage was 11.5±6.4 mg/day, and the maintenance dosage was 23.1±9.4 mg/day. During 6 weeks, HDRS, MADRS and CGI-S scores decreased from 25.1±5.6 to 11.9±8.6 (mean change -13.1±8.3, p

The Continuous Performance Test (CPT) is a valuable tool for assessing behavior in attention-deficit/hyperactivity disorder (ADHD). Quantitative electroencephalography (QEEG) is a promising tool for the diagnosis of ADHD. Recently, theta-phase gamma-amplitude coupling (TGC) measurement has received attention because it is a feasible method of assessing brain function. We investigated the relationship between CPT performance and EEG measures such as TGC and theta and gamma activity. EEGs were recorded from 68 volunteers from a camp for hyperactive children using a 19-electrode system. Their TGC, theta and 40 Hz gamma activity were estimated and compared with results obtained on the Korean ADHD Rating Scale (KARS) and the Intermediate Visual and Auditory (IVA) CPT. The results demonstrated significant negative partial correlations between TGC and the IVA CPT, such as the Response Control Quotient (RCQ) and Attention Quotient (AQ). TGC successfully identified the level of dysfunctional interaction of the attention/arousal system at a multi-scale large network level. It is thought that as the TGC increases, the efficacy of the system is very low or dysfunctional. Compensatory hyper-arousal patterns of the dysfunctional attention/arousal system may account for this effect. TGC is a promising neurophysiological marker for ADHD behavior in children.

Objective This study investigated the clinical utility of quantitative electroencephalography (QEEG) and the Integrated Visual and Auditory Continuous Performance Test (IVA + CPT) as auxiliary tools for assessing Attention Deficit Hyperactivity Disorder (ADHD). Methods All of 157 subjects were assessed using the Korean version of the Diagnostic Interview Schedule for Children Version IV (DISC-IV). We measured EGG absolute power in 21 channels and conducted IVA + CPT. We analyzed QEEG according to the Hz range: delta (1–4 Hz), theta (4–8 Hz), slow alpha (8–10 Hz), fast alpha (10–13.5 Hz), and beta (13.5–30 Hz). To remove artifacts, independent component analysis was conducted (ICA), and the tester confirmed the results again. Results All of the IVA + CPT quotients showed significant differences between the ADHD and control groups. The ADHD group showed significantly increased delta and theta activity compared with the control group. The z -scores of theta were negatively correlated with the scores of IVA + CPT in ADHD combined type, and those of beta were positively correlated. Conclusions IVA + CPT and QEEG significantly discriminated between ADHD and control groups. The commission error of IVA + CPT showed an accuracy of 82.1%, and the omission error of IVA + CPT showed an accuracy of 78.6%. Significance The IVA + CPT and QEEG are expected to be valuable tools for aiding ADHD diagnosis accurately.

Objective The aim of this study was to examine the validity of the Korean version of the Hypomania Checklist-32, second revision (HCL-32-R2) in mood disorder patients. Methods A total of 454 patients who diagnosed as mood disorder according to Structured Clinical Interview for DSM-IV Axis I Disorders, clinician version (SCID-CV) (bipolar disorder [BD] I, n=190; BD-II, n=72; and major depressive disorder [MDD], n=192) completed the Korean module of the HCL-32-R2 (KHCL-32-R2). Results The KHCL-32-R2 showed a three-factorial structure (eigenvalue ＞2) that accounted for 43.26% of the total variance. Factor 1 was labeled "active/elated" and included 16 items; factor 2, "irritable/distractible" and included 9 items; and factor 3 was labeled "risk-taking/indulging" and included 9 items. A score of 16 or more on the KHCL-32-R2 total scale score distinguished between BD and MDD, which yielded a sensitivity of 70% and a specificity of 70%. MDD and BD-II also could be differentiated at a cut-off of 15 with maximized sensitivity (0.67) and specificity (0.66). Cronbach's alpha of KHCL-32-R2 and its subsets (factors 1, 2, and 3) were 0.91, 0.89, 0.81 and 0.79, respectively. Correlations between KHCL-32-R2 and Montgomery- Asberg Depression Rating Scale, Young Mania Rating Scale and Korean version of Mood Disorder Questionnaire were -0.66 (p=0.41), -0.14 (p=0.9), and 0.61 (p＜0.001), respectively. Conclusion The KHCL-32-R2 may be a useful tool in distinguishing between bipolar and depressive patients in clinical settings.

Theta-phase gamma-amplitude coupling (TGC) was used as an evidence-based tool to reflect the dysfunctional cortico-thalamic interaction in patients with schizophrenia. The aim of the present study was to evaluate the diagnostic utility of TGC. The subjects included 90 patients with schizophrenia and 90 healthy controls. We compared the TGC results between the groups using an analysis of covariance (ANCOVA) to adjust for age and sex and receiver operator characteristic (ROC) curve analyses to examine the discrimination ability of delta to gamma frequency bands and TGC. Patients with schizophrenia showed a significant increase in the resting-state TGC at all 19 electrodes. The analysis of the ROC curves for each frequency band exhibited relatively low classification accuracies for the delta, theta, slow alpha, fast alpha, and beta power. The TGC generated the most accurate results among the electroencephalography (EEG) measures, with an overall classification accuracy of 92.5%. The resting-state TGC value was increased in patients with schizophrenia compared to that in healthy controls and had a higher discriminating ability than the other parameters. These findings may be related to the compensatory hyper-arousal patterns of the dysfunctional default-mode network (DMN) in schizophrenia. Therefore, resting-state TGC is a promising neurophysiological marker of schizophrenia.

Aim This study constitutes a revision of the guidelines for the treatment of major depressive disorder (MDD) issued by the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) 2006. In incorporates changes in the experts׳ consensus that occurred between 2006 and 2012 as well as information regarding newly developed and recently published clinical trials. Methods Using a 44-item questionnaire, an expert consensus was obtained on pharmacological treatment strategies for (1) non-psychotic MDD, (2) psychotic MDD, (3) dysthymia and depression subtypes, (4) continuous and maintenance treatment, and (5) special populations; consensus was also obtained regarding (6) the choice of an antidepressant (AD) in the context of safety and adverse effects, and (7) non-pharmacological biological therapies. Results AD monotherapy was recommended as the first-line strategy for nonpsychotic depression in adults, children and adolescents, elderly adults, and patients with postpartum depression or premenstrual dysphoric disorder. The combination of AD and atypical antipsychotics (AAP) was recommended for psychotic depression. The duration of the initial AD treatment for psychotic depression depends on the number of depressive episodes. Most experts recommended stopping the initial AD and AAP therapy after a certain period in patients with one or two depressive episodes. However, for those with three or more episodes, maintenance of the initial treatment was recommended for as long as possible. Monotherapy with various selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) was recommended for dysthymic disorder and melancholic type MDD. Conclusion The pharmacological treatment strategy of KMAP-DD 2012 is similar to that of KMAP-DD 2006; however, the preference for the first-line use of AAPs was stronger in 2012 than in 2006.

Background Episodes of alcohol consumption produce use-limiting aversive effects as well as use-promoting euphoric effects. The brain regions associated with the reward circuit in patients with alcohol dependence (PAD) show signs of conditioning for alcohol craving. Alternatively, brain structures in the medial temporal region are known to be crucial for aversive conditioning. In this study, we compare differences in patterns of brain activation in response to cues that induce cravings versus aversion in PAD. Methods Thirty-eight PAD and 26 healthy volunteers were administered cue reactivity tasks while undergoing functional magnetic resonance imaging (fMRI) to examine brain response to craving-inducing cues (CIC) and aversion-inducing cues (AIC). Results Activation of the right medial frontal gyrus (right orbitofrontal cortex) during CIC was greater in PAD than in healthy volunteers. Participants in the PAD group displayed less activation in the right amygdala and the right middle temporal gyrus during AIC than did the healthy volunteers. Brain reactivity within the right medial frontal gyrus in response to CIC was positively correlated with the scores of PAD on the Korean Alcohol Urge Questionnaire (AUQ-K) and the Michigan Alcohol Screening Test (MAST). Reactivity within the amygdala in response to AIC was negatively correlated with AUQ-K scores among PAD. Conclusion The dysfunction of the orbitofrontal cortex that results from repeated exposure to alcohol accounts for craving and relapse in PAD. Additionally, PAD seem to be less sensitive to cues related to aversive consequences of alcohol overuse in comparison with healthy individuals.

Aim We compared the 1-year rehospitalization rates of first-episode bipolar manic patients who were discharged while being treated with lithium or valproate in combination with an atypical antipsychotic. Methods We investigated the rehospitalization status of first-episode bipolar manic patients who were discharged between 1 January 2003 and 31 December 2010 while they were taking lithium or valproate in combination with aripiprazole, olanzapine, quetiapine, or risperidone. Rehospitalization rates during a 1-year period after discharge were compared between the group receiving lithium plus an atypical antipsychotic and the group receiving valproate plus an atypical antipsychotic using the Kaplan–Meier method. A Cox regression model was used to analyze covariates hypothesized to affect time to rehospitalization. Results The rehospitalization rate was 17.3% during the 1-year follow-up period. We found significant differences in the rehospitalization rates of patients in the lithium (23.1%) and the valproate (13.3%) groups using the Kaplan–Meier formula. According to Cox proportional hazards regression analysis, higher Clinical Global Impression–Bipolar Version–Severity score at discharge (P = 0.005) and lithium treatment (P = 0.055) contributed to the risk of rehospitalization. Conclusion Treatment with valproate and an atypical antipsychotic can be more effective than treatment with lithium and an atypical antipsychotic in preventing rehospitalization during the 1 year after hospitalization due to a first manic episode in patients with bipolar I disorder. Higher Clinical Global Impression–Bipolar Version–Severity scores at discharge also negatively affected rehospitalization rates.

BACKGROUND: Many treatment guidelines for bipolar disorders have been introduced to assist clinical decision. Majority of these guidelines are based on evidences from clinical trials. The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed to adopt and maintain an expert-consensus paradigm which was more practical and specific to the atmosphere in Korea. In this research, preferred medication strategies for acute mania over four consecutively published KMAP-BP guidelines (2002, 2006, 2010, 2014, and 2018) were investigated. METHODS: The KMAP-BP questionnaire using a nine-point scale had covered some specific clinical situations divided into subsections with many treatment options. A written survey asked about the appropriateness of various treatment strategies and treatment agents commonly used by clinicians as the first-line. RESULTS: The most preferred initial treatment strategy for all subtypes of mania was a combination of mood stabilizer (MS) and atypical antipsychotic (AAP) in every edition. In contrast to MS monotherapy, the preference of combination therapy has been increased over time. Among MSs, lithium and valproic acid are almost equally preferred except in the mixed subtype where valproic acid is the most recommended MS. Carbamazepine was the first-line MS only in the first edition. Olanzapine, quetiapine, and aripiprazole were the preferred AAP for acute manic episode in later editions. This change might depend on the recent research results and safety profile. In cases of unsatisfactory response to the first-line medications, we recommended switching or adding another first-line agent. In KMAP-BP 2018, MS (more preferred as treatment of choice) or AAP monotherapy was first-line medication. DISCUSSION: The Korean experts have been increasingly convinced of the effectiveness of a combination therapy for acute manic episode. There have been evident preference changes: increased for AAP and decreased for carbamazepine.

Introduction The Feasibility Study of the Korean Medication Algorithm Project for Bipolar Disorder 2002 (KMAP-BP 2002) revealed its clinical usefulness in 2005. Since much more data had become available since 2002, it was revised in 2006 as KMAP-BP 2006. For the same reason, revision of KMAP-BP 2006 is now necessary. Methods The questionnaire, amended on the basis of KMAP-BP 2006 and new data, was sent to 94 experts, 65 of whom replied. Results In an acute manic episode, a combination of a mood stabilizer (MS) with an atypical antipsychotic (AAP) is recommended as first-line strategy. Monotherapy with MS is first-line in a hypomanic episode. Triple combination of a MS, an AAP, and an antidepressant (AD), is the first-line strategy in non-psychotic severe depression. Also MS+AAP and MS+AD are recommended as first-line. In psychotic bipolar depression, MS+AAP+AD, MS+AAP and AAP+AD are first-line strategies. In bipolar depression, lithium, lamotrigine and valproic acid are selected as first-line MS and quetiapine, olanzapine and aripiprazole are preferred antipsychotics. In maintenance treatment, a combination of MS with AAP and monotherapy of MS are recommended as first-line. Discussion In treating bipolar disorder, even the first step of treatment, the expert consensus has changed from our studies in 2002 and 2006.

Objective Metabolic syndrome and antipsychotic medications are associated with inflammation. This study investigated the relationship between inflammation and metabolic syndrome in patients with schizophrenia. It also examined the effects of paliperidone extended release (ER) treatment on metabolic parameters. Methods Data were analyzed from schizophrenic patients who participated in a multi-center, open-label, non-comparative clinical trial. Anthropomorphic measurements ( i.e. , weight, waist circumference, and blood pressure) were assessed along with fasting laboratory values, including white blood cell (WBC) count, glucose, high-density lipoprotein, and triglycerides. Results Among the 225 patients at baseline, the group with the highest WBC count displayed a 5.9-fold risk for metabolic syndrome compared with that of the lowest group. An increase of 10 3 WBCs/μL was associated with a 1.4-fold increased risk for metabolic syndrome. After 24 weeks of treatment with paliperidone ER, significant increases were observed in waist circumference and body weight. Changes in WBC count were positively correlated with changes in waist circumference. Conclusions Schizophrenic patients with high levels of inflammation should be carefully monitored for metabolic syndrome. Moreover, strategies to reduce inflammation and obesity may prevent metabolic syndrome in patients with schizophrenia who take atypical antipsychotic medication.

Introduction Bipolar disorders are relatively frequent but easily misdiagnosed. The Korean version of the Mood Disorder Questionnaire (K-MDQ) is a screening instrument for bipolar disorders. The aim of this study was to establish the pattern of responses to the K-MDQ for several psychiatric disorders. Methods The subjects for this study were 345 patients with bipolar disorders, schizophrenia, depressive disorders or anxiety disorders, as determined using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and 96 controls from five hospitals. The subjects completed the questionnaire by themselves. Results The total K-MDQ score was higher in the bipolar disorder group than the other groups. Although the mean K-MDQ score differed significantly between the bipolar disorder group and the other groups, the distributions of total scores for the groups overlapped, and in particular with the schizophrenia group. The area under the receiver operating characteristics curve was relatively high for the bipolar disorder group and the other subjects, but it was less than 0.8 between the bipolar disorder group, and the schizophrenia and control groups. Discussion There are some distinguishing features of the K-MDQ pattern for each disorder, but their similarities were significant. This made it difficult to differentially diagnose the disorder using only the total K-MDQ score. The diagnostic power of the K-MDQ can only be improved in the clinical setting by utilizing reinforcing criteria to diagnose bipolar disorders. Clinicians should be cautious in their interpretation of the K-MDQ, and the use of additional data is essential.

Objective We investigated the efficacy and tolerability of ziprasidone combined with divalproex to determine the relationship between the initial dose of ziprasidone and the treatment effect among Korean patients with acute bipolar manic or mixed disorders. Methods This study was a 6-week, open-label, prospective investigation of Korean patients with an acute manic or mixed episode of bipolar disorder. Sixty-five patients were recruited. The patients were categorized based on the initial dose of ziprasidone as follows: low (20-79 mg/day) and standard (80 mg/day). Ziprasidone was given in combination with divalproex in flexible doses, according to the clinical response and tolerability. Results The response and remission rates were significantly higher in the standard-dose group than the low-dose group. The combination of ziprasidone and divalproex was well-tolerated and adverse events were mostly mild with no statistically significant increase in body weight. Conclusion The results of this study showed that a standard starting dose of ziprasidone in combination with divalproex for bipolar disorder is more effective than a low starting dose.

BACKGROUND Craving for alcohol and food has been studied in association with alcohol dependence and eating disorders, respectively. One subclass of the gamma-aminobutyric acid (GABA) receptor, 1519T>C GABA(A)alpha6 has been reported to be associated with both alcohol dependence and weight gain. In this study, we hypothesized that patients being treated for alcohol dependence would report decreased craving for alcohol, but an increased craving for food during a 4-week treatment period. We further hypothesized that the T allele of the 1519T>C GABA(A)alpha6 gene would modulate the extent of changes in craving for alcohol and food. METHODS This study included 98 male inpatients being treated for alcohol dependence. A 7-point visual analog scale was applied to evaluate relative levels of alcohol and food craving at baseline and again 4 weeks later. Body weight was also checked at the same periods. Genotyping of the 1519T>C SNP in GABA(A)alpha6 was carried out by restriction fragment length polymorphism. RESULTS There were significant changes in craving for alcohol and food in all patients with alcohol dependence. During the treatment period, body weight increased in all patients with alcohol dependence. Changes in alcohol and food craving in T-allele carriers (CT + TT) of 1519T>C GABA(A)alpha6 were greater than those observed in CC homozygotes. In T-allele carriers, body weight significantly increased and the changes in weight showed a negative correlation with the change in the craving for alcohol and a positive correlation with the changes in craving for food. DISCUSSION The current results suggest that in T-allele carriers the change in craving for alcohol during treatment for alcohol dependence is negatively associated with changes in craving for food. The T allele of the 1519T>C GABA(A)alpha6 gene may be one of the modulating factors associated with changes in craving for alcohol and food during treatment of patients with alcohol dependence.

Sun Mi Kim,1 Sung Yong Park,1 Young In Kim,1 Young Don Son,2 Un-Sun Chung,3,4 Kyung Joon Min,1 Doug Hyun Han1 1Department of Psychiatry, School of Medicine, Chung-Ang University, Seoul, 2Department of Biomedical Engineering, Gachon University of Medicine and Science, Incheon, 3Department of Psychiatry, School of Medicine, Kyungpook National University, 4School Mental Health Resources and Research Center, Kyungpook National University Children’s Hospital, Daegu,SouthKorea Aim: Disruptive behaviors are thought to affect the progress of major depressive disorder (MDD) in adolescents. In resting-state functional connectivity (RSFC) studies of MDD, the affective network (limbic network) and the default mode network (DMN) have garnered a great deal of interest. We aimed to investigate RSFC in a sample of treatment-naïve adolescents with MDD and disruptive behaviors.Methods: Twenty-two adolescents with MDD and disruptive behaviors (disrup-MDD) and 20 age- and sex-matched healthy control (HC) participants underwent resting-state functional magnetic resonance imaging (fMRI). We used a seed-based correlation approach concerning two brain circuits including the affective network and the DMN, with two seed regions ­including the bilateral amygdala for the limbic network and the bilateral posterior cingulate cortex (PCC) for the DMN. We also observed a correlation between RSFC and severity of depressive symptoms and disruptive behaviors.Results: The disrup-MDD participants showed lower RSFC from the amygdala to the orbitofrontal cortex and parahippocampal gyrus compared to HC participants. Depression scores in disrup-MDD participants were negatively correlated with RSFC from the amygdala to the right orbitofrontal cortex. The disrup-MDD participants had higher PCC RSFC compared to HC participants in a cluster that included the left precentral gyrus, left insula, and left parietal lobe. Disruptive behavior scores in disrup-MDD patients were positively correlated with RSFC from the PCC to the left insular cortex.Conclusion: Depressive mood might be correlated with the affective network, and disruptive behavior might be correlated with the DMN in adolescent depression. Keywords: resting-state functional connectivity, major depressive disorder, disruptive behaviors, limbic network, default mode network

Introduction Social network analysis has emerged as a promising tool in modern social psychology. This method can be used to examine friend-based social relationships in terms of network theory, with nodes representing individual students and ties representing relationships between students (e.g., friendships and kinships). Using social network analysis, we investigated whether greater severity of ADHD symptoms is correlated with weaker peer relationships among elementary school students. Methods A total of 562 sixth-graders from two elementary schools (300 males) provided the names of their best friends (maximum 10 names). Their teachers rated each student’s ADHD symptoms using an ADHD rating scale. Results The results showed that 10.2% of the students were at high risk for ADHD. Significant group differences were observed between the high-risk students and other students in two of the three network parameters (degree, centrality and closeness) used to assess friendship quality, with the high-risk group showing significantly lower values of degree and closeness compared to the other students. Moreover, negative correlations were found between the ADHD rating and two social network analysis parameters. Conclusion Our findings suggest that the severity of ADHD symptoms is strongly correlated with the quality of social and interpersonal relationships in students with ADHD symptoms.

Jinuk Song,1 Doug Hyun Han,1 Sun Mi Kim,1 Ji Sun Hong,1 Kyung Joon Min,1 Jae Hoon Cheong,2 Bung Nyun Kim3 1Department of Psychiatry, Chung Ang University Hospital, 2Uimyung Research Institute for Neuroscience, Samyook University, 3Department of Psychiatry, Seoul National Hospital, Seoul, South Korea Background: Although schizophrenia and bipolar disorder (BD) are classified as different disease entities, they share critical pathognomonic symptoms in terms of hallucination and delusion. Because the characteristics of clinical symptoms are not sufficient to differentiate schizophrenia from BD, several studies have applied brain imaging methods to provide biological evidence of differences. We compared gray matter (GM) volume differences in schizophrenia and BD patients and examined volumetric differences associated with hallucination and delusion in these two groups.Methods: Ninety-three schizophrenia patients and 75 BD patients who were followed for at least 3 years in an outpatient department were recruited for this study. Magnetic resonance data from 71 schizophrenia patients and 44 BD patients were obtained using a 3.0 T scanner. Volumetric differences were analyzed using Matlab 8.0.0 and SPM8 software.Results: The results showed that delusion symptoms were negatively correlated with GM volume within both frontal and both temporal cortices in the schizophrenia group and were negatively correlated with GM volume within the bilateral frontal cortices in the BD group. Hallucination symptoms were negatively correlated with GM volume within the bilateral frontal, bilateral temporal, and left parietal cortices in the schizophrenia group and were negatively correlated with GM volume within the bilateral frontal, right parietal, occipital, and insular cortices in the BD group.Conclusion: Delusions in schizophrenia were correlated with GM volume in multiple brain regions, including the frontal, temporal, and parietal cortices, compared to those in patients with BD. Hallucination was associated with temporal lobe GM volume in patients with schizophrenia and with insular cortex GM volume in patients with BD. Keywords: schizophrenia, bipolar disorder, delusion, hallucination, voxel-based morphometry