[show abstract][hide abstract] ABSTRACT: Activation of one or more serotonin (5-HT) receptors may play a role in mediating the antidepressant effects of serotonergic antidepressants. The serotonin 2C (5HT 2C) receptor is known to be associated with antidepressant action and weight gain. We sought to determine whether the 5-HTR 2C receptor -759C/T polymorphism was associated with weight gain and treatment response to mirtazapine in major depressive disorder (MDD) patients.
The 5-HT 2C receptor -759C/T polymorphism was analyzed in 323 MDD patients. All patients were evaluated using the 21-item Hamilton Depression Rating Scale at the beginning of the study and at 1, 2, 4, and 8 weeks of mirtazapine treatment.
There was no significant difference in the 5-HT 2C receptor -759C/T genotype distribution between responder and non-responder groups. The 5-HT 2C receptor -759C/T polymorphism was not associated with weight change over time after mirtazapine administration.
The 5-HT 2C receptor -759C/T polymorphism does not appear to be a predictor of treatment response to mirtazapine. This polymorphism was not associated with weight change after 8 weeks of mirtazapine treatment. Further investigation on other polymorphisms of the 5-HT 2C gene is required to determine whether the 5-HT 2C gene influences treatment response and weight change after mirtazapine administration in patients with major depressive disorder.
[show abstract][hide abstract] ABSTRACT: Subpopulations of patients with adjustment disorder are at increased risk for suicide. The current study investigated whether personality traits, including alexithymia, temperament, and character, are associated with an increased risk of suicide in individuals with adjustment disorder. Age and sex-matched patients meeting the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for adjustment disorder with (n=92) and without (n=92) a history of suicide attempts were recruited for the present study. Ninety-two healthy individuals who did not meet diagnostic criteria for Axis I or II diagnoses were used as controls. The Toronto Alexithymia Scale-20 (TAS-20) and the Temperament and Character Inventory (TCI) were used to assess personality traits. Significantly higher total and subscale scores on the TAS-20, including on the difficulty-identifying-feelings (DIF) and difficulty-describing-feelings (DDF) subscales, and lower scores on the TCI cooperativeness subscale were noted in adjustment-disorder patients with previous suicide attempts. In the multivariate regression analysis, high DDF and DIF and low cooperativeness increased the risk of suicide attempts in adjustment-disorder patients. A subsequent path analysis revealed that high DDF had a direct effect on suicide attempts, whereas high DIF had an indirect effect on suicide attempts via low cooperativeness.
[show abstract][hide abstract] ABSTRACT: Personality is an important clinical factor for successful adjustment in stressful situations. The aim of this study was to examine possible differences in temperament and character dimensions between patients with adjustment disorder with depressed mood and healthy controls. Among the young male conscripts, 86 subjects with adjustment disorder with depressed mood and 86 healthy controls were included. The mean scores in the 7 dimensions and 25 subscales of the Temperament and Character Inventory were compared between the patients with adjustment disorder with depressed mood and the control group by an independent t-test. The patients with adjustment disorder with depressed mood had significantly higher scores on harm-avoidance and lower scores on self-directedness, cooperativeness, and self-transcendence than did the controls. There were no differences in novelty seeking, reward dependence, and persistence in temperament between the two groups. The results of this study suggest that the personality traits of the subjects with adjustment disorder with depressed mood would make them vulnerable to stressful situations and less skilled in coping with conscription.
The Journal of nervous and mental disease 11/2012; 200(11):973-7. · 1.77 Impact Factor
[show abstract][hide abstract] ABSTRACT: The primary aim of this study was to compare electronic monitoring with other measures of adherence to antipsychotic medication in outpatients with schizophrenia. The secondary aim of the study was to analyze the relationships between adherence and other clinical parameters.
Fifty-one patients diagnosed with schizophrenia were monitored over an eight-week period. Medication adherence was assessed using the Medication Event Monitoring System (MEMS), which is a bottle cap with a microprocessor that records the occurrence and times of bottle opening, patient self-reports, a clinician rating scale, and pill counts. Agreements among adherence measures and the relationships between adherence and other clinical factors were assessed.
The rate of non-adherence according to the MEMS was 41.2%, considerably higher than those of pill counting (7.8%), clinician rating scale (7.8%), or self-reporting (25.5%). Excitement, impulse control, and preoccupation symptoms on the Positive and Negative Syndrome Scale (PANSS) were higher in the non-adherent patients than in the adherent patients. The full Drug Attitude Inventory (DAI) score was higher in adherent versus non-adherent patients and the significant other subscale of the Multidimensional Scale of Perceived Social Support score was lower in the adherent patients. The Clinical Global Impression-Severity score was negatively correlated with adherence as measured by the MEMS (r=-0.426, p<0.05) and DAI scores were positively correlated with adherence according to the MEMS and the clinician rating scale (r=0.498, p<0.01 and r=0.387, p<0.05). Multivariate analysis showed that PANSS and DAI scores significantly contributed to MEMS adherence.
Adherence as measured by the MEMS showed a discrepancy with other measures of adherence in patients with schizophrenia. The severity of disease and attitudes toward medication were related to adherence. Further studies are needed to evaluate the impacts of medication adherence in schizophrenia.
Schizophrenia Research 11/2011; 134(2-3):226-31. · 4.59 Impact Factor
[show abstract][hide abstract] ABSTRACT: Previous neuroimaging studies in patients with major depressive disorder (MDD) have reported changes in several brain areas, such as the medial and dorsolateral orbital cortex, amygdala, hippocampus, and basal ganglia. However, the results of these studies are inconsistent, and relatively few studies have been conducted using voxel-based morphometry (VBM) to detect gray matter concentration (GMC) abnormalities in patients with MDD.
We examined 47 MDD patients and 51 healthy controls to investigate structural abnormalities using a 1.5 T magnetic resonance imaging system, which was normalized to a customized T1 template and segmented with optimized VBM. Analysis of covariance with age and gender as covariates was adopted for the VBM statistics; the level of statistical significance was set at P<0.05 for the corrected false discovery rate.
Decreased GMC was found in MDD patients in the bilateral amygdalae, hippocampi, fusiform gyri, lingual gyri, insular gyri, middle-superior temporal gyri, thalami, cingulate gyri, the central lobule of the cerebellum, and the midbrain encompassing the dorsal raphe nuclei (DRN).
Half of our study subjects were taking antidepressants. This may have been a potential confounding factor if any of the medications affected cortical volume.
The results suggest that the GMC of several regions associated with emotion regulation was lower in MDD patients. In particular, we found decreased GMC in the DRN. These findings may provide a better understanding of the anatomical properties of the neural mechanisms underlying the etiology of MDD.
Journal of affective disorders 05/2011; 133(1-2):128-36. · 3.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Adrenergic alpha2a receptors (ADRA2A) are expressed in the central nervous system and peripheral tissues. The primary mechanism of action of mirtazapine is the antagonism of central presynaptic alpha2 receptors. Mirtazapine is reportedly associated with weight gain. Our objective was to determine whether the ADRA2A -1291C/G polymorphism is associated with weight gain and treatment response to mirtazapine in patients with major depressive disorder (MDD).
The ADRA2A -1291C/G polymorphism was analyzed in 314 MDD patients and 162 control subjects. All patients were evaluated using the 21-item Hamilton Depression Rating Scale at the beginning of the study and at 1, 2, 4, and 8 weeks of mirtazapine treatment.
No relationship was observed between the ADRA2A -1291C/G polymorphism and MDD. No significant difference was found between responder and non-responder groups when comparing the ADRA2A genotype distribution with treatment response to mirtazapine. Repeated measures ANOVA with the last observation carry-forward test indicated that after adjusting for baseline body weight, age, and gender, the subjects with the C/C genotype exhibited a greater mean body weight gain than the subjects with the C/G or G/G genotype after 8 weeks of mirtazapine treatment (p=0.052).
The ADRA2A -1291C/G polymorphism does not appear to be a predictor of treatment response to mirtazapine. This polymorphism was weakly associated with weight change after 8 weeks of mirtazapine treatment. Further investigation is required to determine whether other polymorphisms of this gene influence treatment response and weight change in patients receiving mirtazapine.
Brain research 02/2009; 1262:1-6. · 2.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: Objective: Major depressive disorder (MDD) is closely related to stress reactions and serotonin probably underpins the pathophysiology of MDD. Alterations of the hypothalamic-pituitary-adrenal axis at the gene level have reciprocal consequences on serotonin neurotransmission. Glucocorticoid receptor (GR) polymorphisms affect glucocorticoid sensitivity, which is associated with cortisol feedback effects. Therefore, we hypothesised that GR polymorphisms are associated with the susceptibility to MDD and predict the treatment response.Method: Ninety-six subjects with a minimum score of 17 on the 21-item Hamilton Depression Scale (HAMD) at baseline were enrolled into the present study. The genotypes of GR (N363S, ER22/23EK, Bcl1, and TthIII1 polymorphisms) were analysed. The HAMD score was again measured after 1, 2, 4 and 8 weeks of antidepressant treatment to detect whether the therapeutic effects differed with the GR genotype.Results: Our subjects carried no N363S or ER22/23EK genetic polymorphisms and three types of Bcl1 and TthIII1 genetic polymorphisms. The C/C genotype and C allele at Bcl1 polymorphism were more frequent in MDD patients than in normal controls (p < 0.01 and p = 0.01, respectively). The genotype distributions did not differ significantly between responders and non-responders.Conclusion: These results suggest that GR polymorphism cannot predict the therapeutic response after antidepressant administration. However, GR polymorphism (Bcl1) might play a role in the pathophysiology of MDD. Future studies should check this finding in larger populations with different characteristics.
[show abstract][hide abstract] ABSTRACT: Hwa-Byung (HB) is a Korean culture-bound psychiatric syndrome caused by the suppression of anger. HB patients have various psychological and somatic symptoms, such as chest discomfort, a sensation of heat, and the sensation of having an epigastric mass. In this study, we measured brain activity in HB patients and healthy individuals in response to affective facial stimuli. Using functional magnetic resonance imaging (fMRI), the current study measured neural responses to neutral, sad, and angry facial stimuli in 12 healthy individuals and 12 patients with HB. In response to all types of facial stimuli, HB patients showed increased activations in the lingual gyrus and fusiform gyrus compared with healthy persons, but they showed relatively lower activation in the thalamus. We also found that patients with HB showed lower activity in response to the neutral condition in the right ACC than healthy controls. The current study indicates that the suppression of affect results in aberrant function of the brain regions of the visual pathway, and functional impairment in the ACC may contribute to the pathophysiology of HB.
The World Journal of Biological Psychiatry 06/2008; 10(4 Pt 2):552-9. · 3.57 Impact Factor
[show abstract][hide abstract] ABSTRACT: Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic. We evaluated candidate functional polymorphism of the G protein beta3 subunit (GNB3) gene for association with drug-induced TD in the Korean schizophrenic patients.
We investigated whether the C825T polymorphism of the GNB3 gene is associated with the TD in a Korean sample of schizophrenic patients with (n = 83) and without TD (n = 126), matched for antipsychotic drug exposure and other relevant variables.
The distribution of genotypes and allele frequencies of GNB3 were not different between schizophrenic patients with TD and without TD (p > 0.05).
Within the limitations imposed by the size of the clinical sample, these findings suggest that the GNB3 825 C/T single nucleotide polymorphism (SNP) does not contribute significantly to risk for TD.
Human Psychopharmacology Clinical and Experimental 12/2007; 22(8):501-4. · 2.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: Modulations of serotonergic and noradrenergic systems are thought to be critical to the therapeutic effect of most antidepressants, and their efficacies have been shown to depend on a functional polymorphism within the promoter region of the serotonin transporter gene (5-HTTLPR). Mirtazapine has a dual-action profile, combining the enhancement of the noradrenergic neurotransmitter system with specific actions on particular serotonergic receptor subtypes. The goal of this study was to elucidate whether the 5-HTTLPR polymorphism is associated with the mirtazapine antidepressant response in subjects with major depressive disorder (MDD). One hundred and one MDD patients were evaluated during 4 weeks of mirtazapine treatment. The severity of depression was assessed with the 21-item Hamilton Depression Rating scale, and the 5-HTTLPR genotypes in the patients were determined using the polymerase chain reaction. Our results showed that responses at the 2nd and 4th weeks were significantly better for the s/s genotype of the 5-HTTLPR polymorphism than for l-allele carriers. These results support our hypothesis that the response to noradrenergic and specific serotonergic antidepressants is significantly associated with the 5-HTTLPR polymorphism.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 09/2007; 31(6):1317-21. · 3.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: The present study tested the potential association between the 3111C/T polymorphism of the CLOCK gene and seasonal variations in mood and behavior. A total of 297 Korean college students were genotyped for the CLOCK polymorphism and the seasonal variation was evaluated using the Seasonal Pattern Assessment Questionnaire (SPAQ). The seasonality scores were not different between CLOCK gene variants (P > 0.05). Comparison between seasonals (syndromal plus subsyndromal seasonal affective disorder according to SPAQ) and non-seasonals found no significant difference in frequencies of genotypes (P > 0.05). These findings suggest that the CLOCK polymorphism does not play a major role in susceptibility to seasonal variations in a Korean population.
Psychiatry and Clinical Neurosciences 03/2007; 61(1):124-6. · 2.04 Impact Factor
[show abstract][hide abstract] ABSTRACT: The 3111 C/T single nucleotide polymorphism (SNP) in the CLOCK gene and the 825C/T SNP in the G-protein beta3 subunit gene (GNB3) have been reported to influence diurnal preference. This study has attempted to characterize the association between the CLOCK gene and GNB3 polymorphisms and diurnal preference in healthy Korean college students. All subjects completed the 13-item Composite Scale for Morningness (CSM). The interaction between the 3111 C/T SNP in the CLOCK gene and the 825 C/T SNP in the GNB3 gene significantly influenced diurnal preference, according to the CSM Performance subscore (F=10.94, p=0.001). However, when the different polymorphisms of the two genes were analyzed independently, no direct correlations with diurnal preference were detected. The CLOCK gene 3111 C/T SNP and GNB3 gene 825 C/T SNP were found to manifest a gene-gene interaction that affects diurnal preference.
Chronobiology International 02/2007; 24(4):589-97. · 4.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotics. We evaluated whether a candidate functional polymorphism of the dopamine D4 receptor (DRD4) gene is associated with drug-induced TD in 209 Korean schizophrenic patients with TD (n = 83) and without TD (n = 126) who were matched for antipsychotic drug exposure and other relevant variables. There was no significant association of the genotype and allele frequencies determined by the -521 C/T SNP of DRD4 between TD and non-TD patients. In addition, there was no significant difference in terms of total Abnormal Involuntary Movement Scale scores among the 3 genotype groups. Within the limitations imposed by the size of the clinical sample, these findings suggest that the DRD4 -521 C/T SNP does not contribute significantly to the risk for TD.
[show abstract][hide abstract] ABSTRACT: Tryptophan hydroxylase-1 (TPH1) is the rate-limiting enzyme in serotonin biosynthesis, and selective serotonin reuptake inhibitors (SSRIs) exert their activity enhancing the general serotonergic tone. Citalopram is the most selective SSRI, with little or no affinity for a variety of receptor types. The goal of this study was to investigate whether the A218C polymorphism of the TPH1 gene is associated with the citalopram antidepressant response in subjects with major depressive disorder (MDD). All of the patients were evaluated using the 21-item Hamilton Depression Rating Scale before beginning and after 8 weeks of citalopram treatment. Genotyping was performed with the polymerase chain reaction. The remission rate to citalopram treatment was worse in MDD subjects with the TPH1 A/A and A/C genotypes than in those with the TPH1 C/C genotype. Our results suggest that the A218C polymorphism of the TPH1 gene serves as a modulator of antidepressant activity, especially in terms of treatment remission.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 02/2007; 31(1):104-7. · 3.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: The 5-HTR2A gene is a candidate gene for influencing the clinical response to treatment with antidepressants. The purpose of this study was to determine the relationship between the -1438A/G polymorphism of the 5-HTR2A gene and the response to mirtazapine in a Korean population with major depressive disorder. Mirtazapine was administered for eight weeks to the 101 patients who completed the study, during which we evaluated the clinical outcome using repeated-measures ANCOVA. A main effect of genotype or an effect of genotype-time interactions on the decrease in HAMD score during the eight-week follow-up was not found, which suggests that the 5-HTR2A -1438A/G polymorphism does not affect the clinical outcome to mirtazapine administration. However, significant effects of genotype and allele carriers on the decrease in the sleep score over the eight weeks were found (genotype: F = 4.093, p = 0.017; allele: F = 4.371, p = 0.037), whereas no effect of genotype-time interactions on the decrease in the HAMD score over the eight-week follow-up was found. These observations suggest that the -1438A/G polymorphism on the sleep improvement at each time period revealed significant differences in the sleep scores after two weeks of mirtazapine administration. The sleep scores were lower for carriers of the A+ allele than of the A- allele after two weeks of mirtazapine administration (p = 0.041), which means that the -1438GG genotype is associated with less improvement in sleep, and suggests that the effect of mirtazapine on improving the sleep quality differs with the 5-HTR2A -1438A/G polymorphism within two weeks of mirtazapine treatment. In conclusion, although the -1438A/G polymorphism affects the sleep improvement resulting from the administration of mirtazapine to Korean patients with major depressive disorder, our results do not support the hypothesis that this polymorphism of the 5-HTR2A gene is involved in the therapeutic response to mirtazapine.
The International Journal of Psychiatry in Medicine 02/2007; 37(3):315-29. · 1.15 Impact Factor
[show abstract][hide abstract] ABSTRACT: Seasonal affective disorder and seasonal rhythms in mood and behavior (seasonality) have been reported to be associated with serotonergic system. In this study we investigated the relationship between the serotonin 2A receptor (5HTR2A) -1438 A/G polymorphism and seasonal variation in a young Korean healthy population.
297 young Korean medical students were recruited for this study. They were genotyped for the 5HTR2A -1438 A/G polymorphism and evaluated the seasonal variation in mood and behavior by the Seasonality Pattern Assessment Questionnaire (SPAQ).
The Global Seasonality Score of the SPAQ among three genotypes were not different. However, the comparison between seasonals and non-seasonals showed significant difference in the genotype distribution. The winter-type seasonals showed a significantly higher frequency of the 5HTR2A -1438 A allele compared with non-seasonals (chi2 = 6.80, p = 0.009; OR = 1.79; 95% CI, 1.15-2.78).
These results suggest that the 5HTR2A -1438 A/G polymorphism is possibly related to seasonality in the Korean population.
Journal of Affective Disorders 11/2006; 95(1-3):145-8. · 3.30 Impact Factor
[show abstract][hide abstract] ABSTRACT: Nitric oxide (NO) is known to influence cerebral monoaminergic activity, including the activity of serotonin. We evaluated plasma NO metabolite (NO(x)) levels in depressive patients with and without a recent history of suicide attempt.
Plasma NO(x) levels were measured in 39 depressive patients who had recently attempted suicide, 44 non-suicidal depressed patients, and 70 normal controls. The severity of depression was measured with the Hamilton's Depression Rating Scale. The lethality of the suicide attempt was scored using Weisman and Worden's risk-rescue rating scale and Lethality Suicide Attempt Rating Scale.
Plasma NO(x) levels were significantly higher in suicidal depressive patients than non-suicidal depressive patients or normal control subjects (Z=-2.472, p=0.013). However, higher plasma NO(x) levels in suicidal depressive patients were significantly related to a lower lethality of suicide attempts and lower severity of depression.
Our study suggests that increased plasma NO(x) level is associated with suicide attempts in depressive patients. Moreover, higher plasma NO(x) level is related with suicide attempts in mild depressed patients. However, further studies are required to understand the role of NO system in depression and suicidal behavior.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 09/2006; 30(6):1091-6. · 3.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: Weight gain can be an adverse effect of antipsychotics and is an important factor for long-term health and treatment compliance. Many reports have shown that the alpha(2)-adrenergic receptor may be related to eating behaviors or lipolytic activities, both associated with body weight change. We hypothesized that there might be a relationship between the alpha(2a)-adrenergic receptor -1,291 C/G polymorphism and olanzapine-induced weight gain. A group of 62 Korean schizophrenic patients participated in a study; weight and height measurements were obtained prior to starting olanzapine and measured again after long-term treatment. Genotyping for the -1291 C/G polymorphism was performed on all participants. Body weight changes from baseline to endpoint were significantly associated with genotypes (P = 0.028). The frequency of the G allele was significantly higher in subjects who had severe weight gain (defined as a more than 10% weight gain from baseline) compared to subjects who did not have extreme weight gain (less than 10% weight gain from baseline) (X(2) = 6.120, P = 0.013; OR = 2.58, 95% CI = 1.21-5.51). Therefore, the findings from this study support a relationship between the -1291 C/G polymorphism of the alpha(2a)-adrenergic receptor and weight gain in Korean schizophrenic patients receiving olanzapine treatment.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics 07/2006; 141B(4):394-7. · 3.23 Impact Factor
[show abstract][hide abstract] ABSTRACT: ObjectiveㅋThe present study examined the possible association between the serotonin 2A receptor (5-HTR2A)-1438 A/G polymorphism and post-traumatic stress disorder (PTSD). MethodsㅋThe genotype, allele and allele carrier frequencies of the 5-HTR2A gene poly-morphism were analyzed in 107 PTSD patients and 161 unrelated healthy controls using a case-control design. ResultsㅋWhile there was no difference in the genotype and allele distribution of the 5-HTR2A gene polymorphism between the PTSD patients and normal controls, there was a marginal difference in the allele carrier frequency between the two groups (χ 2 =2.82, df=1, p=0.093), that is the GG genotype frequency tended to be higher in the PTSD samples. When the analyses were conducted separately by gender, the frequency of the GG genotype was significantly higher in the female PTSD patients than in the female normal controls (χ 2 = 4.38, df=1, p=0.036; OR=2.21, 95% confidence interval: 1.04-4.71). ConclusionㅋThese findings suggest that the 5-HTR2A GG genotype is one of the possible genetic factors for susceptibility to PTSD, especially in the female population. Further inves-tigations are required into the influence of gene polymorphisms on the biological mechanisms of PTSD.