Leen Kim

D2 and D4 dopamine receptor gene polymorphisms and personality traits in a young Korean population

The correlation between the D4 dopamine receptor gene (DRD4) and the D2 dopamine receptor gene (DRD2) polymorphisms was investigated with personality traits. For this study, homogeneous population consisting of 243 young alcohol‐ and drug‐naive Koreans who were blood‐unrelated with a mean age (±SD) of 13.87 (±0.30) years old was analyzed for the DRD4 and the DRD2 polymorphisms with their personality trait by Temperament and character inventory (TCI). The association between Novelty seeking (NS) score and DRD4 long alleles was only observed among the female subjects (t = 2.11, P = 0.037), but not in the male counter part. Female subjects who carried the DRD2 less frequent alleles (TaqI A1, TaqI B1, and Intron6 1) showed higher RD4 scores (dependence vs. independence) of Reward dependence (RD) than those without these alleles (P < 0.05). There was no interaction between DRD4 and DRD2 on the personality traits. These results, thus, confirmed the previous findings in which the long repeats of the DRD4‐exon III polymorphism are related to NS personality trait, and also suggested that the DRD2 less frequent alleles were also associated with the reward‐dependent trait.

Brain-derived neurotrophic factor gene polymorphisms and mirtazapine responses in Koreans with major depression

Brain-derived neurotrophic factor (BDNF) is a candidate molecule for influencing the clinical response to antidepressant treatment. The aims of this study were to determine the relationship between the Val66Met polymorphism in the BDNF gene and the response to mirtazapine in 243 Korean subjects with major depressive disorder (MDD). The reduction in the Hamilton Depression score over the 8-week treatment period was not influenced by BDNF V66M genotypes. A marginal effect of genotype on somatic anxiety score was observed at baseline (P = 0.047 in the dominant model). However, genotype–time interaction had no effect on somatic anxiety score after the 8-week a treatment period. Plasma BDNF levels tended to increase during mirtazapine treatment, although without statistical significance (P = 0.055). After 8 weeks of mirtazapine treatment, plasma BDNF levels were higher in Met allele homozygotes (1499.7 ± 370.6 ng/mL) than in Val allele carriers (649.7 ± 158.5 ng/mL, P = 0.049). Our results do not support the hypothesis that the Val66Met promoter polymorphism in the BDNF gene influences the therapeutic response to mirtazapine in Korean MDD patients. However, our data indicate that this polymorphism results in increased plasma BDNF after mirtazapine treatment.

Characteristics and clinical correlates of restless legs syndrome in schizophrenia

OBJECTIVE The cause of restless legs syndrome (RLS) has not yet been ascertained, but one of the most promising theories involves dopaminergic deficiency. In accordance with this theory, we assumed that the prevalence of RLS would be higher among schizophrenics treated with antipsychotics than in the normal population. The purpose of this study was to establish the prevalence, characteristics, and clinical correlates of RLS in schizophrenic patients undergoing treatment with antipsychotics. METHODS A total of 182 hospitalized schizophrenic patients and 108 age- and sex-matched normal controls were enrolled. The presence of RLS and its severity were assessed using the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria and the IRLSSG rating scale, respectively. The Athens Insomnia Scale (AIS), Brief Psychiatric Rating Scale (BPRS), and Barnes Akathisia Rating Scale (BARS) were used to evaluate insomnia, global psychiatric symptoms, and akathisia, respectively, in schizophrenic patients. RESULTS Of the 182 schizophrenic patients, 39 (21.4%) were found to have RLS and 87 (47.8%) met at least one of the RLS diagnostic criteria. The prevalence of RLS was significantly higher in the schizophrenia group than in the control group (p=0.009), as were the RLS scores (p<0.001). The BPRS (p=0.001) and the AIS (p<0.001) scores were higher in the RLS group than in the group with no RLS symptoms. CONCLUSION We conclude that it is important to consider the diagnosis of RLS when schizophrenic patients complain of insomnia, and that RLS symptoms could be associated with more severe psychiatric symptoms and insomnia.

Cognitive deterioration and changes of P300 during total sleep deprivation

The study was conducted to evaluate the cognitive deteriorations induced by sleep deprivation with the computerized neurocognitive tests and the P300 event‐related potential. Thirty healthy college students (22 men, eight women) participated in the present study. Subjects remained awake for 38 h under continuous surveillance. In the morning and the evening of the two study days, the computerized neurocognitive tests and the P300 were performed. In vigilance test and reaction unit test, there were significant cognitive impairments during sleep deprivation. However, in the cognitrone test there was significant functional improvement, which might be due to the practice effect. The P300 latency was significantly prolonged and the amplitudes decreased during sleep deprivation. The cognitive impairment during 38 h of sleep deprivation was mainly in terms of vigilance and reaction time. In contrast, higher complex cognitive function such as fine perceptual analyses, visual discrimination and working memory might be not affected by 38 h of total sleep deprivation. The changes of P300 were significantly correlated with the results of vigilance and reaction unit tests but not with the cognitrone test. Taken together, these results suggest that the P300 changes that occur during sleep deprivation are a reflection of the decrement in vigilance, which prolongs reaction time.

Estrogen, Cognitive Function and Negative Symptoms in Female Schizophrenia

The aim of this study was to evaluate the relationship of serum reproductive hormone levels with cognitive function and negative symptoms in schizophrenic women during the follicular phase of the menstrual cycle. Thirty-five women with chronic schizophrenia who had minimal positive symptoms participated in this study. We evaluated the correlation of serum reproductive hormone levels with the Scale for the Assessment of Negative Symptoms (SANS) and cognitive function tests such as the Immediate Visual Recognition Scale, Oral Fluency Test, List Recall Scale with List Acquisition Scale, Trail Making Tests A and B, and Digit Symbol Test. The patients were divided into two subgroups (low estradiol group and normal estradiol group) using the normal serum reference range for estradiol. Significant correlation between SANS subcategories, such as Alogia and Attention Impairment, and estradiol were found. Moreover, significant relationships between the estradiol level and the Oral Fluency Test, List Recall Scale with List Acquisition Scale, Trail Making Test B and Digit Symbol Test were observed. In the low estradiol group, the SANS scores, except for Anhedonia-Asociality and Avolition-Apathy, were significantly higher than those in the normal estradiol group. Patients in the low estradiol group had a significantly lower performance in the cognitive function tests, except Visual Recognition Scale, when compared to patients in the normal estradiol group. These results suggest that for schizophrenic women of reproductive age, lower levels of estrogen are associated with more severe negative symptomatology as well as reduced performance in cognitive function, especially verbal performance and executive functioning.

Antipsychotics and dopamine transporter gene polymorphisms in delirium patients

Abstract  The main objective of the present study was to determine the relationship between treatment responses of delirium and genetic polymorphisms in the dopamine transporter. The optimal dosages of haloperidol and risperidone in the treatment of delirium were also investigated. Either haloperidol or risperidone was administered to delirium patients, and delirium symptoms were measured daily until remission. Variable number of tandem repeat (VNTR) polymorphisms of the dopamine transporter were determined using the polymerase chain reaction. Among 42 subjects, symptoms of delirium appeared a mean of 9.68 days after hospitalization. A majority of the subjects (83.3%) had the type 10/10 polymorphism. Dosages of haloperidol and risperidone at the day of recovery were 1.67 mg/day (SD = 1.32; range 0.5–2.5 mg/day) and 1.19 mg/day (SD = 1.14; range 0.5–5.0 mg/day), respectively. The mean drug response time was 8.5 days in the haloperidol group and 4.8 days in the risperidone group (no significant difference). The response rates at the 3rd and 7th days after medication did not differ with either the drug group or the dopamine transporter polymorphism. Relatively low doses of risperidone and haloperidol exhibited similar efficacies, and dopamine transporter polymorphisms do not appear to play a major role in the action of antipsychotics on delirium.

Auditory Event-Related Potentials and Psychological Changes during Sleep Deprivation

This study investigated the psychophysiological effects of sleep deprivation on auditory event-related potentials (AERPs) and their relationship with psychological parameters. Twenty-four subjects remained awake for 37 h under continuous surveillance. In the mornings and the evenings of 2 consecutive study days, AERPs were recorded and 4 self-rated scales (sleepiness, fatigue, anxiety, and mood) were quantified. The latencies of P300 and N200 were significantly prolonged (p < 0.001) and their amplitudes decreased (p < 0.05) as a consequence of sleep deprivation. However, the only significant change in N100 and P200 was an increase in the P200 amplitude (p < 0.05). The increase in the latencies of P300 and N200 were correlated with increased sleepiness (p < 0.05), and the increase in P200 amplitude was correlated with negative mood, anxiety, and fatigue (p < 0.05). Although the changes in P300 and N200 induced by sleep deprivation are due to sleepiness, which may slow cognitive processing and decrease the efficiency of mental processing, the increase in P200 may be related with increased anxiety, negative mood, and fatigue.

Allelic Variants Interaction of Dopamine Receptor D4 Polymorphism Correlate With Personality Traits in Young Korean Female Population

Polymorphism in exon III of the dopamine D4 receptor (DRD4) gene has been implicated to be associated with the human personality trait of novelty seeking (NS). For this study, we have investigated the possible association between 48‐bp VNTR in exon III and −521 C/T SNP of the DRD4 and personality traits among young (≈14 years of age) Korean female population. We found that the interaction between the two alleles of DRD4 polymorphism, 48‐bp VNTR and −521 C/T, were significantly high on NS (F = 4.88, P = 0.029) and persistence (P) (F = 5.05, P = 0.027) personality scores, suggesting that the variants of DRD4 gene influence the NS and P (persistent) personality traits. When analyzed independently, however, the two different alleles of DRD4 polymorphisms, 48‐bp VNTR and −521 C/T, there was no direct correlation with the personality traits.

Effects of season and climate on the first manic episode of bipolar affective disorder in Korea

The purpose of this study was to determine if a seasonal pattern existed for the first manic episodes in Korea. The first manic episodes out of 152 bipolar disorder patients were investigated, in subjects who were admitted in two hospitals in Seoul between 1996 and 1999. Correlations between the monthly climate variables and the first monthly manic episodes indicated that the first manic episodes peaked in 25 cases during March. The mean monthly hours of sunshine and sunlight radiation correlated significantly with manic episodes. Separating the patients into two groups, namely, with and without major depressive episode, only the occurrence of manic episodes with major depressive episode was significantly correlated with mean monthly hours of sunshine. Separating the subjects by gender, the monthly first manic episodes was significantly correlated with the intensity of sunlight radiation in female patients only. These findings suggested that increasing the duration and intensity of sunlight could facilitate breakdown into the manic episodes.

Role of cytokines in atypical depression

Background: Atypical depression (AD) is considered a biologically and psychologically distinct subtype of depression. AD, contrary to melancholic depression (MD), may have different alteration in cytokine activity. Aims: We aimed to investigate the differences of cytokine activity between AD patients and MD patients. Among psychiatric patients visited to the Psychiatry Department, Korea University Medical Center, 105 patients with major depression who met the Diagnostic and Statistical Manual (DSM-IV) criteria based on clinical interviews using a Structured Clinical Interview for DSM-IV were recruited. Among 105 patients, 35 patients had atypical feature. We measured in vitro cytokines (interleukins) IL-2, IL-4, IL-6 and tumor necrosis factor-α (TNF-α). Results: Decreased IL-4 and increased IL-2 was observed in AD patients. IL-6 and TNF-α level of AD patients showed no difference from the controls. Conclusions: Contrary to MD, AD has reversed vegetative symptoms, i.e. hypersomnia and hyperphagia. It is assumed that the phenotype difference between AD and MD might be related to Th1 cytokines (IL-2) and Th2 cytokines (IL-4) and not related to monocytic cytokines (IL-6, and TNF-α).