Min-Hyeon Park

Thrombospondin-1, vascular endothelial growth factor expression and their relationship with p53 status in prostate cancer and benign prostatic hyperplasia

Objective To evaluate the expression of thrombospondin‐1 (TSP‐1, a potent inhibitor of angiogenesis) and vascular endothelial growth factor (VEGF, an important angiogenic factor in solid tumours) in prostate cancer, and their relationship with p53 status.

Connectomic Disturbances in Attention-Deficit/Hyperactivity Disorder: A Whole-Brain Tractography Analysis

BACKGROUND Few studies have sought to identify, in a regionally unbiased way, the precise cortical and subcortical regions that are affected by white matter abnormalities in attention-deficit/hyperactivity disorder (ADHD). This study aimed to derive a comprehensive, whole-brain characterization of connectomic disturbances in ADHD. METHODS Using diffusion tensor imaging, whole-brain tractography, and an imaging connectomics approach, we characterized altered white matter connectivity in 71 children and adolescents with ADHD compared with 26 healthy control subjects. White matter differences were further delineated between patients with (n = 40) and without (n = 26) the predominantly hyperactive/impulsive subtype of ADHD. RESULTS A significant network comprising 25 distinct fiber bundles linking 23 different brain regions spanning frontal, striatal, and cerebellar brain regions showed altered white matter structure in ADHD patients (p < .05, family-wise error-corrected). Moreover, fractional anisotropy in some of these fiber bundles correlated with attentional disturbances. Attention-deficit/hyperactivity disorder subtypes were differentiated by a right-lateralized network (p < .05, family-wise error-corrected) predominantly linking frontal, cingulate, and supplementary motor areas. Fractional anisotropy in this network was also correlated with continuous performance test scores. CONCLUSIONS Using an unbiased, whole-brain, data-driven approach, we demonstrated abnormal white matter connectivity in ADHD. The correlations observed with measures of attentional performance underscore the functional importance of these connectomic disturbances for the clinical phenotype of ADHD. A distributed pattern of white matter microstructural integrity separately involving frontal, striatal, and cerebellar brain regions, rather than direct frontostriatal connectivity, appears to be disrupted in children and adolescents with ADHD.

COMT genotype affects brain white matter pathways in attention‐deficit/hyperactivity disorder

Increased dopamine availability may be associated with impaired structural maturation of brain white matter connectivity. This study aimed to derive a comprehensive, whole‐brain characterization of large‐scale axonal connectivity differences in attention‐deficit/hyperactivity disorder (ADHD) associated with catechol‐O‐methyltransferase gene (COMT) Val158Met polymorphism. Using diffusion tensor imaging, whole‐brain tractography, and an imaging connectomics approach, we characterized altered white matter connectivity in youth with ADHD who were COMT Val‐homozygous (N = 29) compared with those who were Met‐carriers (N = 29). Additionally, we examined whether dopamine transporter gene (DAT1) and dopamine D4 receptor gene (DRD4) polymorphisms were associated with white matter differences. Level of attention was assessed using the continuous performance test before and after an 8‐week open‐label trial of methylphenidate (MPH). A network of white matter connections linking 18 different brain regions was significantly weakened in youth with ADHD who were COMT Met‐carriers compared to those who were Val‐homozygous (P < 0.05, family‐wise error‐corrected). A measure of white matter integrity, fractional anisotropy, was correlated with impaired pretreatment performance in continuous performance test omission errors and response time variability, as well as with improvement in continuous performance test response time variability after MPH treatment. Altered white matter connectivity was exclusively based on COMT genotypes, and was not evident in DAT1 or DRD4. We demonstrated that white matter connectivity in youth with ADHD is associated with COMT Val158Met genotypes. The present findings suggest that different layers of dopamine‐related genes and interindividual variability in the genetic polymorphisms should be taken into account when investigating the human connectome. Hum Brain Mapp, 36:367–377, 2015.

A retrospective comparison of BMI changes and the potential risk factors among schizophrenic inpatients treated with aripiprazole, olanzapine, quetiapine or risperidone

The objective of this study was to evaluate weight gain and its potential risk factors among different second generation antipsychotics (SGAs). The study was conducted for Korean inpatients with schizophrenia in a university hospital in Seoul, between Jan 2000 and Dec 2007. Data were collected by reviewing the medical records of the patients, who were prescribed to one of the SGAs among aripiprazole, olanzapine, quetiapine or risperidone. The changes of weight and body mass index (BMI); risk of clinically significant weight gain (>7% gain to initial weight) and their associations with various clinical characteristics of such patients were analyzed. Five hundred and eighty-eight (588) and 294 subjects treated with one of the four SGAs for a duration of 1 month and 2 months were included, respectively. Olanzapine showed significantly greater weight and BMI increase at month 1 (p=0.028 for weight; p=0.019 for BMI) and month 2 (p=0.032 for weight; p=0.029 for BMI) than others. Females showed greater BMI increase change (0.70±0.91 kg/m(2), p=0.008) and were also more likely to experience clinically significant weight gain (odd ratio=1.846, 95% CI=1.098 to 3.105, p=0.021) at month 1. Younger patients (<45 years old) had significantly greater weight and BMI increase at both months 1 and 2. Younger patients also showed greater risk for clinically significant weight gain at month 2 (odd odd ratio=2.567, 95% CI=1.196 to 5.508, p=0.016). Low baseline BMI (<25 kg/m(2)) was associated with greater weight gain at month 1 (1.92±2.29 kg, p<0.001) and month 2 (4.07±3.56 kg, p<0.001) and BMI increase at month 1 and month 2 (p<0.001 for both). Patients with low baseline BMI showed higher risk of clinically significant weight gain at both months 1 and 2 (p<0.001 for both). Olanzapine was shown to have higher metabolic risk than other SGAs in inpatients with schizophrenia. The individuals own clinical characteristics also exerted influence on weight gain effects of SGAs. Younger patients with lower baseline BMI were under greater risk of antipsychotic-induced weight gain. More studies are required to verify the role of gender on weight gain.

Clinical characteristics of depressed patients with a history of suicide attempts: results from the CRESCEND study in South Korea.

South Korea is a country with one of the highest suicide rates in the world, and the suicide rate is still on the rise. The purpose of this study was to determine the sociodemographic and clinical characteristics of suicide attempts and risk factors related to suicide attempts among depressed patients in South Korea. Among the 1183 participants, 21.4% had a history of a suicide attempt. When the severity of depression was controlled, the risk factors for patients who attempted suicide included younger age, experienced significant life events before 12 years of age, psychotic symptoms, and previous depressive episodes. The characteristics of attempted suicide in depressed patients in South Korea can be summarized as a high suicide attempt rate with no difference in the number of suicide attempts and lethality between males and females. This unique tendency is probably related to the sociodemographic and cultural characteristics of South Korea.

Possible effect of norepinephrine transporter polymorphisms on methylphenidate-induced changes in neuropsychological function in attention-deficit hyperactivity disorder

BackgroundDysregulation of noradrenergic system may play important roles in pathophysiology of attention-deficit/hyperactivity disorder (ADHD). We examined the relationship between polymorphisms in the norepinephrine transporter SLC6A2 gene and attentional performance before and after medication in children with ADHD.MethodsFifty-three medication-naïve children with ADHD were genotyped and evaluated using the continuous performance test (CPT). After 8-weeks of methylphenidate treatment, these children were evaluated by CPT again. We compared the baseline CPT measures and the post-treatment changes in the CPT measures based on the G1287A and the A-3081T polymorphisms of SLC6A2.ResultsThere was no significant difference in the baseline CPT measures associated with the G1287A or A-3081T polymorphisms. After medication, however, ADHD subjects with the G/G genotype at the G1287A polymorphism showed a greater decrease in the mean omission error scores (p = 0.006) than subjects with the G/A or A/A genotypes, and subjects with the T allele at the A-3081T polymorphism (T/T or A/T) showed a greater decrease in the mean commission error scores (p = 0.003) than those with the A/A genotypes.ConclusionsOur results provide evidence for the possible role of the G1287A and A-3081T genotypes of SLC6A2 in methylphenidate-induced improvement in attentional performance and support the noradrenergic hypothesis for the pathophysiology of ADHD.

Regional brain perfusion before and after treatment with methylphenidate may be associated with the G1287A polymorphism of the norepinephrine transporter gene in children with attention-deficit/hyperactivity disorder.

The noradrenergic system modulates attention and arousal. Dysregulation of the noradrenergic system may be involved in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). This study intended to examine the differences in methylphenidate (MPH) treatment response and pre- and post-treatment cerebral perfusion associated with the G1287A and -3081(A/T) polymorphisms of the norepinephrine transporter (NET) gene in ADHD children. Thirty-seven drug-naïve ADHD children (8.9±1.8 years old, M=32, F=5) were genotyped. Next, baseline single-photon emission computed tomography (SPECT) and clinical assessments were carried out for ADHD subjects. After 8 weeks of MPH treatment, SPECT and clinical assessment were repeated. There were no differences in baseline clinical assessments or cerebral perfusion based on genotype. However, after treatment, ADHD children with the G/G genotype at the G1287A polymorphism showed more improvement in symptoms than children without the G/G genotype as evaluated by the Clinical Global Impressions-Improvement scale (p=0.022). Furthermore, ADHD children with the G/G genotype at the G1287A polymorphism showed hyperperfusion in the right inferior temporal gyrus (p<0.001, uncorrected) and middle temporal gyrus (p=0.001, uncorrected) compared to children without the G/G genotype. Although the results of this study should be interpreted cautiously, they suggest that polymorphisms of the NET gene may contribute to an intermediate phenotype. Further studies should clearly elucidate the relationship between treatment response and functional connectivity in the brain according to this genetic polymorphism.

Aripiprazole treatment for patients with schizophrenia: from acute treatment to maintenance treatment

The most current treatment guidelines for schizophrenia recommend more than 1 year of maintenance therapy after the first psychotic episode, and more than 5 years of maintenance therapy after multiple psychotic episodes. Approximately two-thirds of such patients are known to relapse within 1 year and almost 90% of such patients may recur within 2 years. To maintain adequate consistent treatment, balancing the efficacy and safety/tolerability should be one of the most important clinical issues. In this respect, aripiprazole appears to be a good treatment option owing to its comparable efficacy, favorable safety and tolerability profile, including low incidence of parkinsonian symptoms, lack of prolactin elevation, decreased adrenergic and anticholinergic side effects, less weight gain and low incidence of metabolic syndrome. Hence this article aims to summarize the currently available clinical trial data of aripiprazole published from a number of large-scale randomized controlled studies, including a newer formulation of intramuscular injection as well as a once-monthly intramuscular depot formulation, to update knowledge of treatment options in patients with schizophrenia.

The effect of ziprasidone on body weight and energy expenditure in female rats.

Ziprasidone, a novel antipsychotic agent with a unique receptor-binding profile, has been reported to have lower propensity for weight gain compared with other atypical antipsychotics. Here, we examined the effects of ziprasidone on resting energy expenditure, physical activity, thermogenesis, food intake, and weight gain in female Sprague-Dawley rats. Ziprasidone (20 mg/kg) or vehicle was administered once daily for 7 weeks; and body weight, food intake, resting energy expenditure, locomotor activity, colonic temperature on cold exposure, and abdominal fat were measured. Compared with control animals, ziprasidone-treated rats gained significantly less weight (P = .031), had a lower level of physical activity (P = .016), showed a higher resting energy expenditure (P < .001), and displayed a greater capacity for thermogenesis when subjected to cold (P < .001). In addition, ziprasidone-treated rats had a lower level of abdominal fat than did controls, although the difference was not significant. Ziprasidone had no effect on food intake. Our results indicate that, in female Sprague-Dawley rats, a 7-week treatment regimen of ziprasidone induces a significant decrease in weight gain by increasing resting energy expenditure without decreasing food intake and even with a lower level of physical activity. Further studies are needed to elucidate the precise mechanism of lower propensity of weight gain of ziprasidone.

White-Matter Connectivity and Methylphenidate-Induced Changes in Attentional Performance According to α2A-Adrenergic Receptor Gene Polymorphisms in Korean Children With Attention-Deficit Hyperactivity Disorder

The authors examined the association between the MspI C/G and DraI C/T genotypes of the α2A-adrenergic receptor gene and white-matter connectivity and attentional performance before and after medication in 53 children with attention-deficit hyperactivity disorder. Subjects who carried the T allele at the DraI polymorphism showed fewer changes in the mean commission error scores after 8 weeks of medication and decreased fractional anisotropy (FA) values in the right middle frontal cortex than subjects without the T allele. Subjects with the C allele at the MspI polymorphism showed decreased FA values in the right postcentral gyrus than subjects without.