Prevalence and Comorbidities of Adult Attention-deficit/hyperactivity Disorder in a Community Sample from Korea.

Objective: : Attention-deficit/hyperactivity disorder (ADHD) is prevalent in adults, and psychiatric comorbidities are common in adults with ADHD. We aimed to examine the prevalence of adult ADHD with several common psychiatric conditions in a community sample in Korea and the association between adult ADHD and risk of psychiatric comorbidities. Methods: : This study used a cross-sectional survey design. We provided supplementary and optional self-report questionnaires, including the Korean version of the World Health Organization Adult ADHD Self-Report Scale (ASRS) short screening scale, Patient Health Questionnaire-9 for screening for depression, Alcohol Use Disorders Identification Test alcohol consumption questions, and the Korean version of the Mood Disorders Questionnaire, to Korean adults who visited one of six centers of a large private healthcare company for the National General Health Examination. Results: : A total of 17,799 subjects included in this study, and 430 (2.4%) were positive on the ASRS screen. ADHD was significantly associated with the 19-30-year-old age group (odds ratio [OR] = 3.938), lower income (OR = 1.298), depression (OR = 11.563), and bipolar disorder (OR = 3.162). Conclusion: : Adult ADHD was highly associated with depression and bipolar disorder, suggesting that clinicians should carefully evaluate and treat such psychiatric disorders in adults with ADHD symptoms.

Characteristics of Cognitive Function Changes and Related Factors in Individuals With Cognitive Impairment During the Pandemic of COVID-19: A Retrospective Chart Review Study.

OBJECTIVE: This study aimed to explore the characteristics and factors related to changes in cognitive function in vulnerable individuals with cognitive impairment during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Among patients who visited a local university hospital with subjective cognitive complaints, those who had been tested for cognitive function at least once after the onset of COVID-19 and tested regularly at least three times within the last 5 years were included (1st, the initial screening; 2nd, the test immediately before the COVID-19 pandemic; 3rd, the most recent test after the pandemic). Finally, 108 patients were included in this study. They were divided into groups according to whether the Clinical Dementia Rating (CDR) was maintained/improved and deteriorated. We investigated the characteristics of the changes in cognitive function and related factors during COVID-19. RESULTS: When comparing CDR changes before and after COVID-19, there was no significant difference between the two groups (p=0.317). Alternatively, the main effect of the time when the test was conducted was significant (p<0.001). There was also a significant difference in the interaction between the groups and time. When the effect of the interaction was analyzed, the CDR score of the maintained/ improved group significantly decreased before COVID-19 (1st-2nd) (p=0.045). After COVID-19 (2nd-3rd), the CDR score of the deteriorated group was significantly higher than that of the maintained/improved group (p<0.001). Mini-Mental State Examination recall memory and changes in activity during COVID-19 were significantly associated with CDR deterioration. CONCLUSION: Memory dysfunction and decreased activity during the COVID-19 pandemic are strongly related to the deterioration of cognitive impairment.

Psychometric Properties of the Korean Version of Functioning Assessment Short Test in Bipolar Disorder.

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 Korean Medication Algorithm Project for Depressive Disorder 2021: Comparisons with Other Treatment Guidelines.

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.

Prevalence and Comorbidities of Attention Deficit Hyperactivity Disorder Among Adults and Children/Adolescents in Korea.

OBJECTIVE: This study investigated the prevalence and comorbidities of attention deficit hyperactivity disorder (ADHD) among adults and children/adolescents in Korea. METHODS: This study used data from the Korea Health Insurance Review and Assessment Service collected from 2008 to 2018. Study participants comprised patients with at least one diagnosis of ADHD (International Statistical Classification of Diseases and Related Health Provisions, 10th revision code F90.0). Prevalence rates and psychiatric comorbidities were also analyzed. RESULTS: We identified 878,996 patients diagnosed with ADHD between 2008 and 2018. The overall prevalence rate of diagnosed ADHD increased steeply from 127.1/100,000 in 2008 to 192.9/100,000 in 2018; it increased 1.47 times in children/adolescents (≤ 18 years) and 10.1 times in adults (＞ 18 years) during this period. Among adult and children/ adolescent ADHD patients, 61.84% (95% confidence interval [95% CI] 61.74-61.93) and 78.72% (95% CI 78.53- 78.91) had at least one psychiatric comorbidity, respectively. CONCLUSION: Our results showed that the prevalence rate of diagnosed ADHD has increased in Korea; however, it is lower than the global average. Further studies are required to identify and treat vulnerable populations appropriately.

Comparison between Atomoxetine and OROS Methylphenidate as an Adjunctive to SSRIs in Attention-deficit/Hyperactivity Disorder Adults with Comorbid Partially Responsive Major Depressive Disorder: A Head-to-head, 12-week, Randomized, Rater-blinded Clinical Trial.

OBJECTIVE: This study aimed to compare the efficacy and safety of atomoxetine (ATX) and OROS methylphenidate (MPH) as adjunctive to selective serotonin reuptake inhibitors (SSRIs) in adults with attention-deficit hyperactivity disorder (ADHD) with comorbid partially responsive major depressive disorder (MDD). METHODS: Sixty Korean adults with ADHD and comorbid partially responsive MDD were recruited in a 12-week, randomized, rater-blinded, active-controlled trial and were evenly randomized to ATX or OROS MPH treatment. RESULTS: Depressive symptoms measured using the Hamilton Depression Rating Scale and Clinically Useful Depression Outcome Scale, and ADHD symptoms measured using the Adult ADHD Self-Report Scale, as well as the Clinical Global Impression-Severity, Clinical Global Impression-Improvement, and the Sheehan Disability Scale scores were significantly improved in both groups during the 12 weeks of treatment. The changes in all outcome measures during the 12-week treatment were not significantly different between the two groups (all p > 0.05). No serious adverse events were reported and there were no significant differences in systolic and diastolic blood pressure, pulse rate, weight, or body mass index between the ATX and MPH groups. CONCLUSION: Our findings suggest that ATX and MPH can be used as adjunctive treatments in adults with ADHD and comorbid partially responsive MDD. The efficacy and tolerability of ATX and MPH in adults with ADHD did not differ significantly. Further studies should be conducted to draw a definitive conclusion.

Korean Medication Algorithm for Depressive Disorder 2021, Fourth Revision: An Executive Summary.

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.

Validation of the Korean Version of the Depression in Old Age Scale and Comparison with Other Depression Screening Questionnaires Used in Elderly Patients in Medical Settings.

OBJECTIVE: The Depression in Old Age Scale (DIA-S) is a new screening tool for assessing depression in the elderly. The primary aims of this study were to describe the validation of the Korean version of the DIA-S (K-DIA-S) and to compare its validity with that of other depression screening questionnaires used in elderly outpatients in medical settings. METHODS: A total of 385 elderly outpatients completed the K-DIA-S and underwent the Mini International Neuropsychiatric Interview to diagnose depressive disorders. Other measures included the 15-item short form of the Geriatric Depression Scale (SGDS), the 9-item depression module of the Patient Health Questionnaire (PHQ-9), and the Montgomery-Asberg Depression Rating Scale (MADRS). Reliability and validity tests, an optimal cutoff point estimate, and receiver operating characteristic curve analysis were performed to investigate the diagnostic validity of the K-DIA-S. Areas under the curves (AUCs) for the K-DIA-S, SGDS, and PHQ-9 were compared statistically. RESULTS: The K-DIA-S showed good internal consistency and strong correlations with the SGDS (r = 0.853), PHQ-9 (r= 0.739), and MADRS (r= 0.772). The cut-off point of the K-DIA-S that can be recommended for screening depressive symptoms was a score of 4. For "any depressive disorder", the AUC (standard error) for the K-DIA-S was 0.896 (0.015), which was significantly larger than that for the PHQ-9 (p= 0.033). CONCLUSION: The present findings suggest that the K-DIA-S has good psychometric properties and is a valid and reliable tool for assessing depressive symptoms in elderly populations and medically ill patients.

Screening with the Korean Version of the Mood Disorder Questionnaire for Bipolar Disorders in Adolescents: Korean Validity and Reliability Study.

OBJECTIVE: This study aimed to evaluate the validity and reliability of a Korean version of the Mood Disorder Questionnaire-Adolescent version (K-MDQ-A) as a screening instrument for bipolar disorders in adolescents. METHODS: One hundred two adolescents with bipolar disorders and their parents were recruited from November 2014 to November 2016 at 7 training hospitals. One hundred six controls were recruited from each middle school in two cities of South Korea. The parent version of the original MDQ-A was translated into Korean. The parents of all participants completed the K-MDQ-A. The diagnoses of bipolar disorders were determined based on the Korean version of K-SADS-PL. The test-retest reliability with a 10-month interval was investigated in 33 bipolar adolescents. RESULTS: K-MDQ-A yielded a sensitivity of 0.90 and a specificity of 0.92 when using a cut-off score of endorsement of 5 items, indicating that symptoms occurred in the same time period and caused moderate or serious problems. The internal consistency of the K-MDQ-A was good. The correlations between each item and the total score ranged from 0.40 to 0.76 and were all statistically significant. Factor analysis revealed 3 factors that explained 61.25% of the total variance. The mean total score was significantly higher in bipolar adolescents (7.29) than in controls (1.32). The Pearson correlation coefficient for the total test-retest score was 0.59 (p＜0.001). CONCLUSION: The K-MDQ-A completed by parents showed the excellent validity and reliability and may be a useful screening tool for adolescents with bipolar disorders attending in- and outpatient psychiatric clinics.

Comparison of the Efficacy and Safety of Aripiprazole Versus Bupropion Augmentation in Patients With Major Depressive Disorder Unresponsive to Selective Serotonin Reuptake Inhibitors: A Randomized, Prospective, Open-Label Study.

PURPOSE: The purpose of this study was to compare the efficacy and safety of aripiprazole versus bupropion augmentation in patients with major depressive disorder (MDD) unresponsive to selective serotonin reuptake inhibitors (SSRIs). METHODS: This is the first randomized, prospective, open-label, direct comparison study between aripiprazole and bupropion augmentation. Participants had at least moderately severe depressive symptoms after 4 weeks or more of SSRI treatment. A total of 103 patients were randomized to either aripiprazole (n = 56) or bupropion (n = 47) augmentation for 6 weeks. Concomitant use of psychotropic agents was prohibited. Montgomery Asberg Depression Rating Scale, 17-item Hamilton Depression Rating scale, Iowa Fatigue Scale, Drug-Induced Extrapyramidal Symptoms Scale, Psychotropic-Related Sexual Dysfunction Questionnaire scores were obtained at baseline and after 1, 2, 4, and 6 weeks of treatment. RESULTS: Overall, both treatments significantly improved depressive symptoms without causing serious adverse events. There were no significant differences in the Montgomery Asberg Depression Rating Scale, 17-item Hamilton Depression Rating scale, and Iowa Fatigue Scale scores, and response rates. However, significant differences in remission rates between the 2 groups were evident at week 6 (55.4% vs 34.0%, respectively; P = 0.031), favoring aripiprazole over bupropion. There were no significant differences in adverse sexual events, extrapyramidal symptoms, or akathisia between the 2 groups. CONCLUSIONS: The present study suggests that aripiprazole augmentation is at least comparable to bupropion augmentation in combination with SSRI in terms of efficacy and tolerability in patients with MDD. Both aripiprazole and bupropion could help reduce sexual dysfunction and fatigue in patients with MDD. Aripiprazole and bupropion may offer effective and safe augmentation strategies in patients with MDD who are unresponsive to SSRIs. Double-blinded trials are warranted to confirm the present findings.

Genetic findings in obsessive-compulsive disorder connect to brain-derived neutrophic factor and mammalian target of rapamycin pathways: implications for drug development.

Traditional pharmacological approaches to the treatment of obsessive-compulsive disorder (OCD) are based on affecting serotonergic and dopaminergic transmission in the central nervous system. However, genetic epidemiology findings are pointing to glutamate pathways and developmental genes as etiological in OCD. A review of recent genetic findings in OCD is conducted, and bioinformatics approaches are used to locate pathways relevant to neuroprotection. The OCD susceptibility genes DLGAP1, RYR3, PBX1-MEIS2, LMX1A and candidate genes BDNF and GRIN2B are components of the neuronal growth, differentiation and neurogenesis pathways BDNF-mTOR. These pathways are emerging as a promising area of research for the development of neuroprotective pharmaceuticals. Emergent genetic epidemiologic data on OCD and repetitive behaviors may support new approaches for pharmacological discovery. Neuroprotective approaches that take into consideration glutamate-mediated BDNF-mTOR pathways are suggested by OCD susceptibility genes.

Glutamate drugs and pharmacogenetics of OCD: a pathway-based exploratory approach.

INTRODUCTION: Neuropharmacology research in glutamate-modulating drugs supports their development and use in the management of neuropsychiatric disorders, including major depression, Alzheimer's disorder and schizophrenia. Concomitantly, there is a growing use of these agents used in the treatment of obsessive-compulsive disorder (OCD). AREAS COVERED: This article provides a review of glutamate-modulating drugs used in the treatment of OCD. Specifically, the authors examine riluzole, N-acetylcysteine, d-cycloserine, glycine, ketamine, memantine and acamprosate as treatments. Furthermore, recent genetic epidemiology research findings are presented with a focus on the positional candidate genes SLC1A1 (a glutamate transporter), ADAR3 (an RNA-editing enzyme), RYR3 (a Ca(2+) channel), PBX1 (a homeobox transcription factor) and a GWAS candidate gene, DLGAP1 (a protein interacting with post-synaptic density). These genetic findings are submitted to a curated bioinformatics database to conform a biological network for discerning potential pharmacological targets. EXPERT OPINION: In the genetically informed network, known genes and identified key connecting components, including DLG4 (a developmental gene), PSD-95 (a synaptic scaffolding protein) and PSEN1 (presenilin, a regulator of secretase), conform a group of potential pharmacological targets. These potential targets can be explored, in the future, to deliver new therapeutic approaches to OCD. There is also the need to develop a better understanding of neuroprotective mechanisms as a foundation for future OCD drug discovery.

Effect of methylphenidate on sleep parameters in children with ADHD.

OBJECTIVE: The primary aim of this study was to investigate the acute impact of methylphenidate (MPH) on sleep parameters in attention-deficit/hyperactivity disorder (ADHD) children. The second aim was to investigate the different effects of intermediate- and longacting MPH on sleep parameters. The third aim was to test the different effects of dose and age on sleep parameters. METHODS: Ninety-three ADHD children were enrolled and randomized to two different MPH preparations. Baseline and daily sleep diaries were evaluated for four weeks after taking medication. Weekday and weekend bedtimes, wake-up times, sleep latencies and total sleep times were compared by weeks. RESULTS: After taking MPH, there was a significant delay in bedtimes and a significant reduction of total sleep time (TST) both on weekdays and at weekends. There was also a significant delay in wake-up time on weekdays. However, the difference was applied to younger age group children only. There was no difference in changes of TST between metadate-CD and OROS-MPH. There also was no difference in changes of TST with different doses of MPH. CONCLUSION: MPH had negative impacts on sleep among young ADHD children, but different preparations and doses did not affect the result.

Factors associated with subjective quality of life in Korean patients with depressive disorders: the CRESCEND study.

PURPOSE: A number of studies suggest that depression is associated with the significant disability and the poorer subjective quality of life (QOL). We aimed to assess subjective QOL in Korean patients with depression and explore the factors (sociodemographic characteristics and clinical features) associated with subjective QOL. METHODS: We obtained the data from 808 depressive patients who entered the Clinical Research Center for Depression (CRESCEND) study and evaluated the relationship between subjective QOL and personal sociodemographics, and various clinical features, including depressive severity, and subjective QOL. We assessed subjective QOL using the 26-item abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF) instrument. RESULTS: Decrements in patients' physical health, psychological health, social relationships, and environment domains of subjective QOL were all strongly associated with the greater depressive symptom severity. After controlling for age and depressive symptom severity, the lower subjective QOL was independently related to being divorced or separated, the less monthly household income, and having no religious practices. CONCLUSION: Our results suggest the importance of sociodemographic characteristics in addition to symptoms for the understanding of subjective QOL in depressed patients. The prospective studies to compare the different treatments' effects on various subjective QOL domains are needed.

Current use of depression rating scales in mental health setting.

OBJECTIVE: This study was to investigate the current use of depression rating scales by psychiatrists and clinical psychologists in Korea. METHODS: The questionnaires from many psychiatrists and clinical psychologists were included in the analysis. The questionnaire was composed of items about examining the percentage of patients clinically using depression rating scales, reasons for not use of them, the degree of satisfaction, the perceived agreement rate between the result of depression rating scales and doctor's clinical interview in the evaluation of patients with depressive symptoms. Data were analyzed by χ(2) and independent t-test. RESULTS: The clinical use of depression rating scales was more frequent in the psychologists than in the psychiatrists. The purposes for using depression rating scales were assessed into six areas, there was no significant difference in between two groups, and both groups pointed out their purpose as rating of severity and screening. The reasons for not using scales were that their interview may be sufficient for diagnosis and assessment of depressive patients and they are not familiar with the use of depression rating scales. The psychiatrists usually prefer the Beck Depression Inventory (BDI), Hamilton Depression Rating Scale and Symptom Checklist 90-Revision (SCL-90-R) in order of frequency, and the clinical psychologists are more likely to use the BDI, Minnesota Multiphasic Personality Inventory and SCL-90-R. Overall rate of satisfaction in the use of the scales was 67.29±14.45% and overall perceived agreement rate was 70.89±16.45%. CONCLUSION: Currently used depression rating scales at the clinical practice were not various. Therefore, to heighten clinicians' utility of these depression rating scales measures, either educational efforts or advertisements, or both, will be necessary to spread them wildly.

Sleep patterns and their age-related changes in elementary-school children.

OBJECTIVES: This study aimed to evaluate children's bedtime, wake-up time, total sleep duration (TSD), sleep latency, and daytime napping by age and gender. Its secondary aim was to compare sleep duration among demographic and lifestyle factors. METHODS: We performed a cross-sectional study of 3639 children in Daegu, Korea, comparing bedtimes, wake-up times, TSDs, daytime naps, and sleep latency according to age and gender, as well as comparing sleep duration according to the children's demographic and lifestyle factors. RESULTS: Bedtime and TSD varied significantly by age. But wake-up time differences were not as large, as the differences in bedtimes and TSDs. There were no gender differences in any sleep parameters. The percentage of the children who took naps decreased until age 9 and began increasing again at age 10. Children who lived in apartments got less sleep than did those living in other types of housing. Extracurricular academic activities, duration and timing of television-watching, and computer playing were also related to the children's sleep duration. CONCLUSIONS: Older children sleep less than younger children; the main reason is late bedtimes. Late bedtimes may be due to socio-cultural factors, high levels of nighttime and recreational activities, and/or excessive academic activities.

Aripiprazole treatment of children and adolescents with Tourette disorder or chronic tic disorder.

OBJECTIVE: This study was conducted to evaluate the effectiveness of aripiprazole to reduce the severity and frequency of tic symptoms and to evaluate the additional effects of aripiprazole on weight changes in children and adolescents with Tourette disorder (TD) or chronic tic disorders. METHODS: A 12-week, open-label trial with flexible dosing strategy of aripiprazole was performed with 15 participants, aged 7-19 years. The Yale Global Tic Severity Scale was applied and the baseline, week 3, 5, 9, and end point scores were compared. The mean body mass index (BMI) at baseline and end point were also compared. RESULTS: Significant decreases in the scores of motor and phonic tics, global impairment, and global severity were demonstrated between baseline and week 3, and the scores continued to improve thereafter. No difference was observed between the baseline and end point BMI. CONCLUSION: This study demonstrates that a relatively low dose of aripiprazole can be used to control tic symptoms effectively in children and adolescents with TD and chronic tic disorders without causing significant weight gain. Additional double-blind studies are needed to establish the definitive efficacy of aripiprazole in treating children and adolescents with chronic tic symptoms.