• Molecular & Cellular Toxicology
• /
• 제5권4호
• /
• pp.346-353
• /
• 2009

Drug metabolism is a critical determinant of the therapeutic and adverse effects of many psychotropic drugs. The metabolism depends on the pharmacokinetics of a drug, which includes its absorption, distribution, and elimination. Psychotropic drugs are metabolized mainly by cytochrome P450 (CYP) enzymes; about 20 of these enzymes exist and they are often responsible for the rate-limiting step of drug metabolism. CYP2D6 is the best-characterized P450 enzyme that exhibits polymorphism in humans. This study determined the relationship between the CYP2D6*10 (P34S) polymorphism and the response to mirtazapine in 153 Koreans with major depressive disorder (MDD). The genotype frequencies were compared using logistic regression analysis, and between-genotype differences in the decrease in the 21-item Hamilton Depression (HAMD21) score over the 12-week treatment period were analyzed using a linear regression analysis. The proportion of remitters was lower in patients with MDD possessing the S allele than in P allele carriers after 2 weeks of mirtazapine treatment. Similarly, the reductions in the HAMD21 and Clinical Global Impression (CGI) scores in S allele carriers were smaller than those in patients with the P allele after 2 weeks of mirtazapine treatment. In the analysis of depression symptoms, the sleep and delusion scores had smaller reductions in S allele carriers. Based on the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS), the psychic adverse effects of mirtazapine were associated with CYP2D6 P34S, while weight gain was not. These results suggest that CYP2D6 P34S affects the outcome of mirtazapine treatment in patients with MDD, and that this polymorphism may be a good genetic marker for predicting the clinical outcome of mirtazapine treatment.

• 대한불안의학회지
• /
• 제16권1호
• /
• pp.32-40
• /
• 2020

Objective : The purpose of this study was to investigate the cognitive performance of major depressive disorder (MDD) in military service/conscription personnel who visited the psychiatric clinic for a medical certificate to consider the situation from the perspective of Korea's unique compulsory military system. We used the Korean Wechsler Adult Intelligence Scale-IV (K-WAIS-IV) as the test for verifying the suitable level of cognitive functioning for military service and as the embedded measure with reflecting suboptimal effort. Methods : The study was conducted on 56 (28 males, age 19-34) in/out-patients admitted to the psychiatry department and diagnosed with MDD (DSM-IV). All participants completed a structured clinical interview (MINI-Plus), as well as self-report questionnaires related to demographics and severity of clinical symptoms. K-WAIS-IV was administered to each subject to assess cognitive characteristics. Results : Military group showed significantly lower processing speed index (PSI) score including subtests of symbol search (SS) and coding (CD) score, compared to the control group. There was no other significant differences in the Full Scale IQ (FSIQ), Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working Memory Index (WMI) scores including sub-tests comprised of the above indices, and Reliable Digit Span (RDS), Enhanced-RDS-Revised (E-RDS-R) between the study and control groups. Conclusion : This study was the first effort to verify the characteristics of Korea's military group with MDD and suggest the applicability of PSI and processing speed of K-WAIS-IV as an embedded performance index to test sub-optimal effort or low motivation beyond the purpose of testing cognitive deficits.

• 생물정신의학
• /
• 제18권1호
• /
• pp.15-24
• /
• 2011

Mood disorder is unlikely to be a disease of a single brain region or a neurotransmitter system. Rather, it is now generally viewed as a multidimensional disorder that affects many neural pathways. Growing neuroimaging evidence suggests the anterior cingulate-pallidostriatal-thalamic-amygdala circuit as a putative cortico-limbic mood regulating circuit that may be dysfunctional in mood disorders. Brain-imaging techniques have shown increased activation of mood-generating limbic areas and decreased activation of cortical areas in major depressive disorder(MDD). Furthermore, the combination of functional abnormalities in limbic subcortical neural regions implicated in emotion processing together with functional abnormalities of prefrontal cortical neural regions probably result in the emotional lability and impaired ability to regulate emotion in bipolar disorder. Here we review the biological correlates of MDD and bipolar disorder as evidenced by neuroimaging paradigms, and interpret these data from the perspective of endophenotype. Despite possible limitations, we believe that the integration of neuroimaging research findings will significantly advance our understanding of affective neuroscience and provide novel insights into mood disorders.

• 생물정신의학
• /
• 제23권4호
• /
• pp.140-147
• /
• 2016

Objectives To determine the relationship between the Alu insertion/deletion (I/D) polymorphism in the tissue-type plasminogen activator (tPA) gene and the clinical outcome of mirtazapine treatment in Korean major depressive disorder (MDD) patients. Methods We enrolled 422 patients in this study. Symptoms were evaluated using the 21-item Hamilton Depression Rating (HAMD-21) Scale. After 1, 2, 4, and 8 weeks of mirtazapine treatment, the association between the Alu I/D polymorphism in the tPA gene and remission/response outcomes were evaluated. Results The proportion of I/I homozygotes in responders was higher than that in non-responders, whereas the proportion of D/D homozygotes in responders was lower than that in non-responders at 8 weeks of treatment (p = 0.032, OR = 1.57). The percentage decline of HAMD-21 scores in I allele carriers was larger than that of D/D homozygotes at 2 and 8 weeks of treatment (p = 0.035 and 0.007, respectively). I allele carriers were associated with remission at 8 weeks of treatment (p = 0.047, OR = 2.2). Conclusions These results show that treatment response and remission to mirtazapine were associated with the Alu I/D polymorphism of the tPA gene. This suggests the Alu I/D polymorphism may be a potential genetic marker for the prediction of therapeutic response to mirtazapine treatment in patients with MDD.

• 대한불안의학회지
• /
• 제20권1호
• /
• pp.8-16
• /
• 2024

Objective : The purpose of this study is to compare the signal obtained from the frontal 2-electrodes EEG with that obtained from the temporal, central, and parietal 2 electrodes. Methods : EEGs were recorded in a total of 67 patients with major depressive disorder (MDD), 104 patients with schizophrenia (SCZ), and 29 patients with Alzheimer's disease (AD). For each disease group, there were healthy controls (HC) that were paired accordingly (HC1=69, HC2=104, HC3=27). The following measurements were compared across electrodes: band power, alpha peak frequency (APF), APF power, alpha asymmetry (AA), and Kolmogorov complexity (KC). Results : Statistically significant differences were found in band power measured from frontal electrodes compared to electrodes placed in other locations. Specifically, the power of theta waves was measured higher in the temporal electorodes, alpha 1 and alpha 2 waves in the parietal, beta 1 and beta 2 in the central, and gamma waves in the temporal electrodes. Both SCZ and AD patients showed increased theta power in all electrodes. In SCZ patients, APF decreased in the central and temporal electrodes, but the APF power analysis showed no difference between the patients and controls. Additionally, AD patients exhibited increased AA in the central EEG, while SCZ patients showed decreased KC in the parietal and temporal electrodes. Conclusion : Depending on the electrode location, sensitive EEG frequencies differed. Compared with signals from other electrodes, frontal EEG in MDD patients revealed generally constant signal values, though the temporo-parieto-central electrodes appeared to be more reliable in SCZ and AD patients.

• Clinical Psychopharmacology and Neuroscience
• /
• 제16권4호
• /
• pp.469-480
• /
• 2018

Objective: Pharmacogenomic-based antidepressant treatment (PGATx) may result in more precise pharmacotherapy of major depressive disorder (MDD) with better drug therapy guidance. Methods: An 8-week, randomized, single-blind clinical trial was conducted to evaluate the effectiveness and tolerability of PGATx in 100 patients with MDD. All recruited patients were randomly allocated either to PGATx (n=52) or treatment as usual (TAU, n=48) groups. The primary endpoint was a change of total score of the Hamilton Depression Rating Scale-17 (HAMD-17) from baseline to end of treatment. Response rate (at least 50% reduction in HAMD-17 score from baseline), remission rate (HAMD-17 score ${\leq}7$ at the end of treatment) as well as the change of total score of Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER) from baseline to end of treatment were also investigated. Results: The mean change of HAMD-17 score was significantly different between two groups favoring PGATx by -4.1 point of difference (p=0.010) at the end of treatment. The mean change in the FIBSER score from baseline was significantly different between two treatment groups favoring PGATx by -2.5 point of difference (p=0.028). The response rate (71.7 % vs. 43.6%, p=0.014) were also significantly higher in PGATx than in TAU at the end of treatment, while the remission rate was numerically higher in PGATx than in TAU groups without statistical difference (45.5% vs. 25.6%, p=0.071). The reason for early drop-out associated with adverse events was also numerically higher in TAU (n=9, 50.0%) than in PGATx (n=4, 30.8%). Conclusion: The present study clearly demonstrate that PGATx may be a better treatment option in the treatment of MDD in terms of effectiveness and tolerability; however, study shortcomings may limit a generalization. Adequately-powered, well-designed, subsequent studies should be mandatory to prove its practicability and clinical utility for routine practice.

• 생물정신의학
• /
• 제15권4호
• /
• pp.303-309
• /
• 2008

Objectives : Some reports have suggested that 5-HT5A polymorphism allelic association was associated with depression, however, there has been no report about relationship between the 5-HT5A gene and antidepressant response. We conducted the association study of the 5-HT5A receptor gene polymorphisms (-19G/C,12A/T) and response to citalopram in Korean patients with major depressive disorder(MDD). Methods : A total of 106 patients with major depressive disorder were included in this study. The patient's symptoms were measured by 21-item Hamilton Depression Rating Scale(HAMD) at baseline, week 1, week 2, week 4 and week 8 during citalopram treatment. A Responder to citalopram was defined by 50% reduction of total HAMD scores. To analyze genetic polymorphisms, a polymerase chain reaction based method was used. Results : At week 8, responders were 62, non-responders were 44. No significant differences of genotypes or allelic association in 19G/C and 12A/T polymorphisms were observed between responsive and non-responsive patients. Conclusion : These results do not support the hypothesis that this polymorphism of the HT5A receptor gene is involved in the therapeutic response to citalopram.

• Journal of Ginseng Research
• /
• 제45권3호
• /
• pp.420-432
• /
• 2021

Background: Many ginsenosides have been shown to be efficacious for major depressive disorder (MDD), which is a highly recurrent disorder, through several preclinical studies. We aimed to review the literature assessing the antidepressant effects of ginsenosides on MDD animal models, to establish systematic scientific evidence in a rigorous manner. Methods: We performed a systematic review on the antidepressant effects of ginsenoside evaluated in in vivo studies. We searched for preclinical trials from inception to July 2019 in electronic databases such as Pubmed and Embase. In vivo studies examining the effect of a single ginsenoside on animal models of primary depression were included. Items of each study were evaluated by two independent reviewers. A meta-analysis was conducted to assess behavioral changes induced by ginsenoside Rg1, which was the most studied ginsenoside. Data were pooled using the random-effects models. Results: A total of 517 studies were identified, and 23 studies were included in the final analysis. They reported on many ginsenosides with different antidepressant effects and biological mechanisms of action. Of the 12 included articles assessing ginsenoside Rg1, pooled results of forced swimming test from 9 articles (mean difference (MD): 20.50, 95% CI: 16.13-24.87), and sucrose preference test from 11 articles (MD: 28.29, 95% CI: 22.90-33.69) showed significant differences compared with vehicle treatment. The risk of bias of each study was moderate, but there was significant heterogeneity across studies. Conclusion: These estimates suggest that ginsenosides, including ginsenoside Rg1, reduces symptoms of depression, modulates underlying mechanisms, and can be a promising antidepressant.

• 생물정신의학
• /
• 제20권2호
• /
• pp.45-53
• /
• 2013

Objectives Non-major depression with fewer symptoms than required for a Diagnostic and Statistical Manual of Mental Disorders-4th edition diagnosis of major depressive disorder (MDD) has consistently been found to be associated with functional impairment. In this study, we aim to estimate the cognitive impairment and the quality of life in elderly patients with subsyndromal depression (SSD) compared with non-depressive elderly (NDE). Methods The Korean version of Mini International Neuropsychiatric Interview was administered to 194 outpatients with depression and 108 normal controls. SSD is defined as having five or more current depressive symptoms with core depressive symptoms (depressive mood or loss of interest or pleasure) during more than half a day and more than seven days over two weeks. Depression was evaluated by the Korean form of Geriatric Depression Scale of a 15-item short version. Global cognition was assessed by Mini-Mental State Examination in the Korean version of CERAD assessment packet (MMSE-KC). Subjective cognitive impairment was assessed by the Subjective Memory Complaint Questionnaire. Quality of life was evaluated by the Korean Version of Short-Form 36-Item Health Survey. Results The mean score of the MMSE-KC in the SSD group was lower than that in the NDE group with adjustment for age, gender, and education [F = 4.270, p = 0.04, analysis of covariance (ANCOVA)]. If we defined those having Z-score of MMSE-KC < -1.5 as a high risk group of cognitive impairment, the odds ratio for the high risk group of cognitive impairment was 1.86 [95% confidence intervals (CI) 1.04-3.34] in SSD and 7.57 (95% CI 3.50-16.40) in MDD compared to NDE. The scores of physical component summary (F = 9.274, p = 0.003, ANCOVA) and mental component summary (F = 53.166, p < 0.001, ANCOVA) in the SSD group were lower than those in the NDE group with adjustment for age, gender, and education. Conclusions The subjects with SSD, as well as those with MDD, showed impairment of global cognition and also experienced low quality of life in both physical and mental aspects, compared to the NDE group.

• 생물정신의학
• /
• 제21권3호
• /
• pp.107-113
• /
• 2014

Objectives Restless legs syndrome (RLS) is a sleep disorder characterized by uncomfortable and unpleasant sensations in the legs and an urge to move the legs, usually at night. The aim of this study is to investigate the incidence of RLS in patients with late life depression and its influence on various clinical outcomes such as severity of depression, sleep quality, cognitive function, and quality of life and accordingly, to elucidate the clinical significance of RLS in patients with late life depression (LLD). Methods This study enlisted 170 depressive patients aged 65 years or older from an outpatient clinic. Structured diagnostic interviews were performed using the Korean version of the Mini-International Neuropsychiatric Interview. All patients completed the questionnaires, including the International RLS Severity Scale, the Korean version of Short-Form 36-Item Health Survey (SF-36), and the Pittsburgh Sleep Quality Index (PSQI). The severity of depression was evaluated by the Korean form of the Geriatric Depression Scale (KGDS) and the level of global cognition was assessed by the Mini-Mental State Examination in the Korean version of The Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (MMSE-KC). Results The incidence of RLS was 17.6% in LLD patients. RLS was more prevalent among the subjects with major depressive disorder (MDD) than those with minor depressive disorder or subsyndromal depressive disorder. The RLS group showed higher score in the KGDS than the Non-RLS group but the difference did not reach the statistical significance (p = 0.095, Student t-test). The mean PSQI score was significantly higher in the RLS group than in the Non-RLS group (p = 0.001, Student t-test). The MMSE-KC score was also lower in the RLS group than in Non-RLS group (p = 0.009, analysis of covariance). But, there was no difference in the score of SF-36 between the RLS group and the Non-RLS group. Conclusions RLS is common in LLD patients, especially in the patients with MDD and is associated with poor sleep quality and cognitive dysfunction, indicating that RLS is clinically significant in patients with LLD. Therefore, RLS should be considered as an important clinical issue in the management of LLD.