Efficacy and Safety of Lurasidone vs. Quetiapine XR in Acutely Psychotic Patients With Schizophrenia in Korea: A Randomized, Double-Blind, Active-Controlled Trial

Objective@#This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. @*Methods@#Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. @*Results@#Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. @*Conclusion@#Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Practical Issues With Clonazepam Use / 신경정신의학

Clonazepam, a 7-nitrobenzodiazepine, has been used for the treatment of various neuropsychiatric disorders such as seizures, sleep disorders, panic disorders, anxiety, and movement disorders. However, clonazepam is officially approved as a therapeutic drug only for epilepsy and panic disorders in Korea. This raises ethical issues in clinical practice, as clonazepam is prescribed off-label for most neuropsychiatric disorders in many other countries as well. The misuse and abuse of clonazepam as a recreational drug have also been commonly reported in global literature. In this review, as a therapeutic drug as the authors aim to highlight the pharmacological aspects, clinical effects, and potential addictive risks of clonazepam use, by reviewing the current literature on clonazepam to increase its clinical use by accurately understanding and identifying its psychopharmacological benefits and characteristics. However, establishing the risk/benefit ratio of clonazepam for use in specific clinical situations is difficult because of the lack of adequate updated data. Therefore, the use of clonazepam needs to be approached from the point of view of personalized drug treatment rather than following fixed guidelines which would not reflect the current real-world clinical practices.

Benzodiazepines: Pharmacology Up-to-Date and Practical Issues / 신경정신의학

Benzodiazepines have been widely used as anxiolytics, sedatives, hypnotics, anticonvulsants, or central muscle relaxants since the 1960s despite significant adverse effects, the potential for misuse, and consequent overdose. Benzodiazepines exert their pharmacological action by binding to gamma-aminobutyric acid type A (GABA-A) receptors in the brain and facilitateing the inhibitory actions of the neurotransmitter GABA. Recent findings have also elucidated the effects of benzodiazepines on the allosteric modulation of GABA-A receptors, including receptor subtypes and transmembrane proteins, which is a significant step in our understanding of GABA pharmacology. In clinical practice, the use of benzodiazepines to treat psychiatric disorders has been limited due to the challenges associated with the long-term use, namely the risks of abuse, misuse, and overdose, as well as withdrawal effects. Furthermore, the approval of selective serotonin reuptake inhibitors for anxiety disorders has led to their extensive use as a first-line pharmacological option and they have also been promoted in various practice guidelines for the treatment of anxiety disorders. However, although recent systematic reviews and meta-analyses have shown that benzodiazepines are useful and effective drugs for the treatment of various neuropsychiatric disorders, including anxiety, debates over the clinical use of benzodiazepines continue. More than 60 years after the introduction of benzodiazepines in clinical practice, it is necessary to revisit the controversies associated with benzodiazepine use and to update the discussion current approach to practice with thethrough an understanding of the new data on their pharmacological actions and to identify appropriate indications according to the new diagnostic systems of psychiatric disorders through an extensive literature review.

Optimizing the Efficacy of Electroconvulsive Therapy / 신경정신의학

Modern electroconvulsive therapy (ECT) is a non-pharmacological and biological treatment that is clinically effective and safe. ECT is used in the treatment of many psychiatric disorders, some neurological diseases, and psychiatric emergencies requiring a rapid and life-saving clinical response. Generalized seizures of the central nervous system induced by the electrical stimulation of ECT are an essential component of the therapeutic effects, which are attributed to the various neuronal responses of the brain. Modern ECT is conducted under general anesthesia, given to the extent of loss of consciousness, followed by administration of a muscle relaxant, and ECT with minimally appropriate electrical stimulation. ECT optimization has the main objective of ensuring maximum clinical efficacy and safety with minimal adverse events through adequate generalized seizures. Since its first introduction in clinical practice in 1938, many studies have been carried out and advances made to enhance the therapeutic effects of ECT and address the adverse events associated with it. As a result, there have been developments such as the use of a square wave instead of a sine wave, various electrode placements, dose titration methods, seizure thresholds, general anesthesia with muscle relaxation, session scheduling, monitoring of electroencephalograms (EEG) and electromyograms, etc. and these have been applied to actual clinical practice. Research on the clinical characteristics and the optimal ECT parameters to increase the efficacy of seizures is still ongoing. In this review, various factors associated with ECT such as EEG monitoring, motor seizures, electrode placements, stimulation dose and titration, seizure evaluation and adequacy, and the ECT algorithms are discussed to improve the efficacy of modern ECT as a useful treatment for psychiatric disorders.

Breakthrough Psychosis and Long-Acting Injectable Antipsychotics / 대한정신분열병학회지

“Breakthrough” of psychosis despite good compliance of antipsychotics medication for a long time is a major obstacle to the treatment of schizophrenia, whether the mechanism is caused by dopamine hypersensitivity or insufficient dose of antipsychotics. Researchers advocating “Dopamine Supersensitivity Psychosis” (DSP) emphasize to avoid excessive inhibition of dopamine 2 receptors from the beginning of treatment. On the other hand, researchers advocating “Breakthrough psychosis on Antipsychotic Maintenance Medication” (BAMM) in which psychosis recurs due to insufficient medication despite continuous administration of antipsychotics without non-adherence argue that dose of antipsychotics should be increased to enhance therapeutic effect. In patients using long-acting antipsychotics injection (LAI), non-compliance can be ruled out. We believe that in treating non-affective psychosis, it is necessary to continuously maintain the lowest dose possible using the optimal dose considering the side effects of second-generation antipsychotics and the cycle and stage of psychosis, and the optimal formulation such as LAI.

Development of the Korea-Polyenvironmental Risk Score for Psychosis

Objective@#Comprehensive understanding of polyenvironmental risk factors for the development of psychosis is important. Based on a review of related evidence, we developed the Korea Polyenvironmental Risk Score (K-PERS) for psychosis. We investigated whether the K-PERS can differentiate patients with schizophrenia spectrum disorders (SSDs) from healthy controls (HCs). @*Methods@#We reviewed existing tools for measuring polyenvironmental risk factors for psychosis, including the Maudsley Environmental Risk Score (ERS), polyenviromic risk score (PERS), and Psychosis Polyrisk Score (PPS). Using odds ratios and relative risks for Western studies and the “population proportion” (PP) of risk factors for Korean data, we developed the K-PERS, and compared the scores thereon between patients with SSDs and HCs. In addition, correlation was performed between the K-PERS and Positive and Negative Syndrome Scale (PANSS). @*Results@#We first constructed the “K-PERS-I,” comprising five factors based on the PPS, and then the “K-PERS-II” comprising six factors based on the ERS. The instruments accurately predicted participants’ status (case vs. control). In addition, the K-PERS-I and -II scores exhibited significant negative correlations with the negative symptom factor score of the PANSS. @*Conclusion@#The K-PERS is the first comprehensive tool developed based on PP data obtained from Korean studies that measures polyenvironmental risk factors for psychosis. Using pilot data, the K-PERS predicted patient status (SSD vs. HC). Further research is warranted to examine the relationship of K-PERS scores with clinical outcomes of psychosis and schizophrenia.

Association between Childhood Attention Deficit Hyperactivity Disorder Features and Adulthood Psychological Resilience in Patients with Mood Disorders

Objectives@#Psychological resilience plays a significant role in many aspects of mental health. The aim of this study was to find an association between childhood attention deficit hyperactivity disorder (ADHD) features and adulthood psychological resilience in patients with mood disorders. @*Methods@#A total of 213 patients with mood disorders including major depressive disorder or bipolar I, II disorder and 909 healthy controls were included. We assessed childhood ADHD features using the Wender Utah Rating Scale (WURS), adulthood psychological resilience using the Connor-Davidson Resilience Scale (CD-RISC), and current depressive mood using the Beck Depression Inventory (BDI). Pearson’s correlation, multiple linear regression and a mediation analyses were performed to examine the relationships between three WURS factor (impulsivity, inattention, and mood instability) scores, the BDI score, and the CD-RISC score. @*Results@#The CD-RISC score was negatively correlated with the WURS childhood inattention factor score and current BDI score in patients with mood disorders. BDI score mediated the influence of the inattention factor score on CD-RISC score among patients with mood disorders. The CD-RISC score was significantly lower in patients with mood disorders than in controls even after controlling for age, WURS scores, and the BDI score. @*Conclusions@#An evaluation of psychological resilience is important for enhancing recovery and quality of life in patients with mood disorders. When assessing psychological resilience, current depression and ADHD features in childhood, particularly inattention, should be considered.

Association between Childhood Attention Deficit Hyperactivity Disorder Features and Adulthood Psychological Resilience in Patients with Mood Disorders

Objectives@#Psychological resilience plays a significant role in many aspects of mental health. The aim of this study was to find an association between childhood attention deficit hyperactivity disorder (ADHD) features and adulthood psychological resilience in patients with mood disorders. @*Methods@#A total of 213 patients with mood disorders including major depressive disorder or bipolar I, II disorder and 909 healthy controls were included. We assessed childhood ADHD features using the Wender Utah Rating Scale (WURS), adulthood psychological resilience using the Connor-Davidson Resilience Scale (CD-RISC), and current depressive mood using the Beck Depression Inventory (BDI). Pearson’s correlation, multiple linear regression and a mediation analyses were performed to examine the relationships between three WURS factor (impulsivity, inattention, and mood instability) scores, the BDI score, and the CD-RISC score. @*Results@#The CD-RISC score was negatively correlated with the WURS childhood inattention factor score and current BDI score in patients with mood disorders. BDI score mediated the influence of the inattention factor score on CD-RISC score among patients with mood disorders. The CD-RISC score was significantly lower in patients with mood disorders than in controls even after controlling for age, WURS scores, and the BDI score. @*Conclusions@#An evaluation of psychological resilience is important for enhancing recovery and quality of life in patients with mood disorders. When assessing psychological resilience, current depression and ADHD features in childhood, particularly inattention, should be considered.

Defining Treatment Response, Remission, Relapse, and Recovery in First-Episode Psychosis: A Survey among Korean Experts

Objective@#For the proper treatment of first-episode psychosis, assessment of treatment response, remission, relapse, and recovery is important. Therefore, the present study aimed to develop operational definitions of clinical outcomes in first-episode psychosis. @*Methods@#A questionnaire was developed by a panel of experts and underwent three revisions. The final survey was presented to 150 psychiatrists who were members of the Korean Society for Schizophrenia Research. Respondents selected factors that they believed were important to consider while defining treatment response, remission, relapse, and recovery using a 6-point Likert scale. Selected factors that constituted each definition were statistically extracted, and operational definitions were developed. @*Results@#A total of 91 experts responded to the survey. The extent of reduction in psychopathology, socio-occupational functioning, and duration of each state were the core factors of each definition. Outcomes obtained from discussions and consultations by experts have been summarized and proposed. @*Conclusion@#The criteria developed in this survey tended to be somewhat stricter than those used by other studies. The fundamental reason for this is that this survey focused on first-episode psychosis. A better understanding of each definition in first-episode psychosis is necessary to improve effective treatment outcomes.

Differences in Symptoms, Functions, and Their Outcomes According to the Degree of Trauma in Patients with Early Psychosis / 신경정신의학

Methods@#The study involved 226 people who participated in the Korean Early Psychosis Cohort Study, and we divided the participants into two groups according to the degree of trauma.Positive and Negative Syndrome Scale (PANSS) and Social and Occupational Functioning Assessment Scale (SOFAS) were compared at the start of the study and at 12 months after the treatment using paired t-test and repeated measures analysis of variance. @*Results@#At the beginning of the study, there was no significant difference between the two groups. But after 12 months of treatment, the high trauma group showed less improvement in PANSS negative score, general psychopathological score, total score, and SOFAS than the low trauma group. @*Conclusion@#In patients with early psychosis and at least moderate severity of premorbid trauma, negative symptoms, general psychopathological, and social and occupational functional improvements after treatment are less.

The Effectiveness on Prevention of Rehospitalization with Long-Term Psychosocial Interventions for Patients with Major Psychiatric Disorders / 대한정신분열병학회지

OBJECTIVES: This study aimed to elucidate the effectiveness of long-term psychosocial intervention in reducing the disabling period of patients with major psychiatric disorders by their rehospitalization rate. METHODS: Of the 210 patients with major psychiatric disorders received psychosocial interventions in a Mental Health and Welfare Center, 192 patients (147 with schizophrenia spectrum disorders, 45 with mood disorders) who received interventions more than 6 months were selected. Review of case management records was conducted to obtain information. RESULTS: The number and length of hospitalization and the hospital days per year significantly decreased after psychosocial intervention. Additional analysis of 102 patients followed up for more than 5 years suggested that the effectiveness of the intervention persisted for a sufficient period. However, no significant difference was observed in the number of rehospitalization in 45 patients with mood disorders, though the length of hospitalization significantly decreased. In addition, the hospital days per year of 21 patients with mood disorder followed up for more than 5 years also showed no significant decrease. CONCLUSION: Long-term psychosocial intervention had a significant effect on reducing the number and length of hospitalization for patients with major psychiatric disorder and the effectiveness maintained for more than 5 years.

The Characteristics of REM Sleep-Dependent Obstructive Sleep Apnea and NREM Sleep-Dependent Obstructive Sleep Apnea / 수면정신생리

OBJECTIVES: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder that is characterized by repetitive collapse or partial collapse of the upper airway during sleep in spite of ongoing effort to breathe. It is believed that OSA is usually worsened in REM sleep, because muscle tone is suppressed during REM sleep. However, many cases showed a higher apnea-hypopnea index (AHI) during NREM sleep than during REM sleep. We aimed here to determine the characteristics of REM sleep-dependent OSA (REM-OSA) and NREM sleep-dependent OSA (NREM-OSA). METHODS: Five hundred sixty polysomnographically confirmed adult OSA subjects were studied retrospectively. All patients were classified into 3 groups based on the ratio between REM-AHI and NREM-AHI. REM-OSA was defined as REM-AHI/NREM-AHI > 2, NREM-OSA as NREM-AHI/REM-AHI > 2, and the rest as sleep stage-independent OSA (IND-OSA). In addition to polysomnography, questionnaires related to subjective sleep quality, daytime sleepiness, and emotion were completed. Chi-square test, ANOVA, and ANCOVA were performed. RESULTS: There was no age difference among subgroups. The REM-OSA group was comprised of large proportions of mild OSA and female OSA patients. These patients experienced poor sleep and more negative emotions than other two groups. The AHI and oxygen desaturation index (ODI) were lowest in REM-OSA. Sleep efficiency and N3 percentage of REM-OSA were higher than in NREM-OSA. The percentage of patients who slept in a supine position was higher in REM-OSA than other subgroups. IND-OSA showed higher BMI and larger neck circumference and abdominal circumference than REM-OSA. The patients with IND-OSA experienced more sleepiness than the other groups. AHI and ODI were highest in IND-OSA. NREM-OSA presented the shortest total sleep time and the lowest sleep efficiency. NREM-OSA showed shorter sleep latency and REM latency and higher percentage of N1 than those of REM-OSA and the highest proportion of those who slept in a lateral position than other subgroups. NREM-OSA revealed the highest composite score on the Horne and Östberg questionnaire. With increased AHI severity, the numbers of apnea and hypopnea events during REM sleep decreased, and the numbers of apnea and hypopnea events during NREM sleep increased. The results of ANCOVA after controlling age, sex, BMI, NC, AC, and AHI showed the lowest sleep efficiency, the highest AHI in the supine position, and the highest percentage of waking after sleep onset in NREM-OSA. CONCLUSION: REM-OSA was associated with the mild form of OSA, female sex, and negative emotions. IND-OSA was associated with the severe form of OSA. NREM-OSA was most closely related to position and showed the lowest sleep efficiency. Sleep stage-dependent characteristics could provide better understanding of OSA.

Design and Methodology of the Korean Early Psychosis Cohort Study

The present study details the rationale and methodology of the Korean Early Psychosis Cohort Study (KEPS), which is a clinical cohort investigation of first episode psychosis patients from a Korean population. The KEPS is a prospective naturalistic observational cohort study that follows the participants for at least 2 years. This study includes patients between 18 and 45 years of age who fulfill the criteria for one of schizophrenia spectrum and other psychotic disorders according to the diagnostic criteria of DSM-5. Early psychosis is defined as first episode patients who received antipsychotic treatment for fewer than 4 consecutive weeks after the onset of illness or stabilized patients in the early stages of the disorder whose duration of illness was less than 2 years from the initiation of antipsychotic treatment. The primary outcome measures are treatment response, remission, recovery, and relapse. Additionally, several laboratory tests are conducted and a variety of objective and subjective psychiatric measures assessing early life trauma, lifestyle pattern, and social and cognitive functioning are administered. This long-term prospective cohort study may contribute to the development of early intervention strategies and the improvement of long-term outcomes in patients with schizophrenia.

Prevalence of Metabolic Syndrome in Patients with Schizophrenia in Korea: A Multicenter Nationwide Cross-Sectional Study

OBJECTIVE: We designed a nationwide study with limited exclusion criteria to investigate the prevalence of metabolic syndrome (MetS) in Korea and its relationship with antipsychotic medications. METHODS: This multicenter, cross-sectional, and observational study included patients diagnosed with schizophrenia or schizoaffective disorder. Sixteen hospitals enrolled 845 patients aged 18 to 65 years prescribed any antipsychotic medication between August 2011 and August 2013. MetS was diagnosed using the criteria of the modified Adult Treatment Panel III of the National Cholesterol Education Program with the Korean abdominal obesity definition (waist circumference ≥85 cm in women, ≥90 cm in men). RESULTS: The prevalence of MetS in all patients was 36.5% and was significantly higher in men than women (men, 40.8%; women, 32.2%) and was significantly correlated with age [odds ratio (OR) 1.02] and duration of illness (OR 1.03). The prevalence of MetS across antipsychotic drugs in the major monotherapy group was as follows: 18.8% for quetiapine, 22.0% for aripiprazole, 33.3% for both amisulpride and paliperidone, 34.0% for olanzapine, 35% for risperidone, 39.4% for haloperidol, and 44.7% for clozapine. CONCLUSION: The prevalence of MetS is very high in patients with schizophrenia or schizoaffective disorder. Screening and monitoring of MetS is also strongly recommended.

Association between the 5-HTTLPR Genotype and Childhood Characteristics in Mood Disorders

OBJECTIVE: The features of childhood attention deficit hyperactivity disorder (ADHD) are significantly associated with adult mood disorders. Some genetic factors may be common to both ADHD and mood disorders underlie the association between these two phenotypes. The present study aimed to determine whether a genetic role may be played by the serotonin transporter-linked polymorphic region (5-HTTLPR) in the childhood ADHD features of adult patients with mood disorders. METHODS: The present study included 232 patients with major depressive disorder (MDD), 154 patients with bipolar disorder (BPD), and 1,288 normal controls. Childhood ADHD features were assessed with the Korean version of the Wender Utah Rating Scale (WURS-K). The total score and the scores of three factors (impulsivity, inattention, and mood instability) from the WURS-K were analyzed to determine whether they were associated with the 5-HTTLPR genotype. RESULTS: In the BPD type II group, the 5-HTTLPR genotype was significantly associated with the total score (p=0.029) and the impulsivity factor (p=0.004) on the WURS-K. However, the inattention and mood instability factors were not associated with the 5-HTTLPR genotype. BPD type I, MDD and normal control groups did not exhibit any significant associations between the WURS-K scores and the 5-HTTLPR genotype. CONCLUSION: The findings suggest that the 5-HTTLPR genotype may play a role in the impulsivity component of childhood ADHD in patients with BPD type II. Because of a small sample size and a single candidate gene, further studies investigating other candidate genes using a larger sample are warranted to determine any common genetic links.

Proteomic Analysis of Serum from Patients with Major Depressive Disorder to Compare Their Depressive and Remission Statuses

OBJECTIVE: Currently, there are a few biological markers to aid in the diagnosis and treatment of depression. However, it is not sufficient for diagnosis. We attempted to identify differentially expressed proteins during depressive moods as putative diagnostic biomarkers by using quantitative proteomic analysis of serum. METHODS: Blood samples were collected twice from five patients with major depressive disorder (MDD) at depressive status before treatment and at remission status during treatment. Samples were individually analyzed by liquid chromatography-tandem mass spectrometry for protein profiling. Differentially expressed proteins were analyzed by label-free quantification. Enzyme-linked immunosorbent assay (ELISA) results and receiver-operating characteristic (ROC) curves were used to validate the differentially expressed proteins. For validation, 8 patients with MDD including 3 additional patients and 8 matched normal controls were analyzed. RESULTS: The quantitative proteomic studies identified 10 proteins that were consistently upregulated or downregulated in 5 MDD patients. ELISA yielded results consistent with the proteomic analysis for 3 proteins. Expression levels were significantly different between normal controls and MDD patients. The 3 proteins were ceruloplasmin, inter-alpha-trypsin inhibitor heavy chain H4 and complement component 1qC, which were upregulated during the depressive status. The depressive status could be distinguished from the euthymic status from the ROC curves for these proteins, and this discrimination was enhanced when all 3 proteins were analyzed together. CONCLUSION: This is the first proteomic study in MDD patients to compare intra-individual differences dependent on mood. This technique could be a useful approach to identify MDD biomarkers, but requires additional proteomic studies for validation.

Risk Factors of Socio-Demographic Variables to Depressive Symptoms and Suicidality in Elderly Who Live Alone at One Urban Region / 정신신체의학

OBJECTIVES: To understand the risk factors of demographic data in geriatric depression scale, and suicidality among in elderly who live alone at one urban region. METHODS: In 2009, 589 elderly who live alone(age> or =65) were carried out a survey about several socio-demographic data, Korean version of the Geriatric Depression Scale(SGDS-K) and Suicidal Ideation Questionnaire (SIQ). Statistical analysis was performed for the collected data. RESULTS: Mean age of elderly who live alone is 75.69(SD 6.17). 40.1% of participants uneducated, 31.4% graduate from elementary school, 12.9% graduate from high school, 11.7% graduate from middle school, 3.2% graduate from university. Religionless, having past history of depression or physical diseases, low subjective satisfaction of family situation, and not having any social group activity have significance to depressive symptoms of elderly who live alone. Having past history of depression, religionless, low subjective satisfaction of family situation have significance to suicidality. Especially, low subjective satisfaction of family situation and having past history of depression are powerful demographic factor both depressive symptoms and suicidality of elderly who live alone. CONCLUSIONS: When we take care elderly who live alone, we should consider many things, but especially the social support network such as family satisfaction and past history of depression for reducing or preventing their depression and suicide both elderly depression and suicide who live alone.

Genetic Role of BDNF Val66Met and 5-HTTLPR Polymorphisms on Depressive Disorder

OBJECTIVE: We investigated possible association between depressive disorders and BDNF Val66Met and 5-HTTLPR. Brain derived neurotrophic factor (BDNF) gene and serotonin transporter (SLC6A4) gene are promising candidate genes for depressive disorders. It has been suggested that BDNF promotes the survival and differentiation of serotonergic neurons and that serotonergic transmission exerts powerful control over BDNF gene expression. METHODS: Final analyses were performed on 186 patients with depressive disorders and 1032 controls. Val66Met polymorphism of BDNF gene and 5-HTTLPR polymorphism of serotonin transporter gene were genotyped and allele and genotypic associations on the diagnosis of depression and age at onset of depression were analyzed. RESULTS: The 5-HTTLPR was positively associated with depressive affected status in the total sample and in females (p=0.038 for allelewise, p=0.015 for genotype-wise associations), but, not in males. The BDNF Val66Met showed no association with depression. BDNF Val66Met and 5-HTTLPR alone were not associated with age at onset of depression. Additional analysis on the interaction between BDNF Val66Met and 5-HTTLPR found a significant association with age at onset of depression in the entire patient group. This association was also found in the female but not in the male patient group. None of the positive results survived Bonferroni correction for multiple testing. CONCLUSION: This result suggested that BDNF Val66Met and 5-HTTLPR may contribute to depressive disorders in a complex way and that the genetic effect could differ by gender. Further studies with large number of patients will be necessary.

A Study about Long-Term Effects of Attention-Deficit Hyperactivity Disorder Medication on Height and Weight in the Korean School-Aged Boys with Attention-Deficit Hyperactivity Disorder Based on Observation of Natural Course

OBJECTIVES: This study was conducted naturalistically in order to observe the long-term effects of attention-deficit hyperactivity disorder (ADHD) medications on growth rates among Korean school-aged boys with ADHD. METHODS: Participants in the study were boys with ADHD aged 6 to 11 years who have taken ADHD medication, methylphenidate (extended release) or atomoxetine. They attended scheduled visits monthly or bimonthly for clinical assessment with measurement of height and weight. In this study, 35 boys with ADHD (mean age at baseline=7.90+/-1.77 years ; mean age at endpoint= 12.54+/-1.91 years) were included, with a mean follow-up period of 4.64 years (+/-1.62 years), ranging from 2 to 9.7 years. Height, weight, and body mass index (BMI) measurements were converted to "age-corrected Z-scores" using data from Growth Charts provided by the Korean Center for Disease Control and Prevention from 2007. RESULTS: Age-corrected endpoint growth parameters (height, weight, BMI Z-scores) did not differ significantly from the baseline values (height t=0.027 ; weight t=-0.61 ; BMI t=-1.86, in paired t-test). Especially high correlation was observed between the baseline and endpoint height Z-scores (r=0.876, p<.001), for which the coefficient of determination r2 was 0.767, meaning that the amount of variability in endpoint height Z-scores explained by the baseline height Z-scores was 76.7%. CONCLUSION: Our results suggested that the long-term effects of ADHD medications on growth parameters to be tolerable in Korean school-aged boys with ADHD.

Morningness-Eveningness Affects the Depressive Mood and Day Time Sleepiness of Obstructive Sleep Apnea Syndrome Patient / 수면정신생리

OBJECTIVES: Recent studies have reported a correlation between obstructive sleep apnea syndrome (OSA) and depression. In attempt to verify the suggestion that eveningness is related to depression, we examined the effect of morningness-eveningness on their depressive mood in patinets with OSA. METHODS: The examination was based on the medical records and polysomnography reports of 211 OSA patients. Information was gathered from the patients who filled out the Horne and Ostberg questionnaire (HOQ), profile of mood states-Korean version (K-POMS), and Epworth sleepiness scale (ESS). We compared mean values of K-POMS total, subscales of K-POMS, ESS, and OSA severity variables among the 3 morningness-eveningness groups (morningness, eveningness, and neither groups). Partial correlation analysis was performed between variables and ANCOVA was performed among the 3 groups after adjustment with age and weight. RESULTS: There were significant negative correlations between HOQ and the followings : K-POMS total, POMS-T (tension-anxiety), POMS-D (depression-dejection), POMS-A (anger-hostility), POMS-F (fatigue-inertia), POMS-C (confusion-bewilderment), spontaneous arousal index, average O2 saturation. There were significant positive correlations between HOQ and the followings : POMS-V (vigor-activity), apnea-hypopnea index, respiratory arousal index, snore time. There were significant negative correlations between POMS-D and the followings : HOQ, POMS-V, stage 1 sleep (%), AHI, TAI (total arousal index), oxygen desaturation index, respiratory arousal index, neck circumference, average O2 desaturation, snore time (%). There were significant positive correlations between POMS-D and K-POMS total, POMS-T, POMS-A, POMS-F, POMS-C, sleep latency, stage 2 sleep (%), heart rate, spontaneous arousal index. There were significant differences in K-POMS total, POMS-T, POMS-D, POMS-F, POMS-C, spontaneous arousal index among the three HOQ groups in ANCOVA. CONCLUSION: The depressive correlates of OSA patients might be affected, not by excessive daytime sleepiness or OSA severity indexes, but by eveningness circadian characteristics. It would be important to take into account the morningness-eveningness tendency when we manage the depressive mood of OSA patients.