Trends of Mental Disorders and Treatment Continuity Predictors of New Patients in the Paediatric Psychiatry Clinic of a University Hospital.

This study analysed trends of first-time patients visiting the paediatric psychiatry clinic in a university hospital. The medical records from 2009 to 2016 of first-time patients visiting the Kyung Hee University Hospital were reviewed, focusing on children in grades 1-12. We analysed the clinical diagnosis rate of mental disorders per 100,000 in the general population by gender and grade, and the characteristics of patients who sought outpatient care more than three times. The study included 1467 participants, of which 931 were males (63.5%). The number of male patients per 100,000 population significantly decreased from 4.14 in 2009 to 2.03 in 2016. While hyperkinetic disorders had the highest prevalence in males, neurotic disorders were most frequent in females. The rate of disruptive behaviour disorders in males and mental retardation in females decreased significantly during the data collecting period. The factors affecting treatment continuity were being female, 7th-12th graders, and diagnosis of depressive, hyperkinetic, and tic disorders. Physicians should consider the new paediatric patients' gender, grade, and expected diagnosis from their first visit to improve treatment compliance.

Preliminary Study of ADHD Biomarkers in Adults with Focus on Serum Iron and Transcranial Sonography of the Substantia Nigra.

As previous studies have reported abnormalities in the iron indices of peripheral blood and hyperechogenicity of the substantia nigra (SN) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD), we aimed to examine the same in adults with ADHD using transcranial Doppler sonography (TCS). In addition, we compared the iron indices and TCS findings before and after methylphenidate (MPH) treatment. A total of 39 participants aged ≥19 years (13 patients and 26 healthy controls) were recruited from Kyung Hee University Hospital between October 2018 and September 2019. All subjects were clinically evaluated based on the ADHD diagnostic criteria in the DSM-5, the Adult ADHD Self-Report Scale, and the Diagnostic Interview for ADHD in Adults (DIVA-5). Further, the iron indices including serum iron, ferritin, and mean platelet volume were determined. Additionally, TCS focused on the midbrain and echogenicity of the SN was conducted. Follow-up for all items was conducted for five ADHD patients after MPH treatment. Patients with ADHD had significantly lower education levels (number of years) than controls. There were no statistically significant differences in serum iron indices or the echogenic area between ADHD and control groups. Further, there were no significant changes in iron indices or TCS findings after MPH medication. Unlike previous studies, this study showed no differences between patients with ADHD and controls. Therefore, it is important to determine if these null findings were due to different target populations (children vs. adults) or other factors, including ADHD subtypes.

Age as a Moderator of Social Skills Intervention Response Among Korean Adolescents with Autism Spectrum Disorder.

Few studies have investigated the effect of age on treatment effectiveness of evidence-based social skills training in autism spectrum disorder (ASD) adolescents. This study evaluated the effectiveness of Program for the Education and Enrichment of Relational Skills (PEERS®) in different ages of ASD adolescents. A total of 110 ASD adolescents aged 11-19 years were divided into early, middle, and late adolescence groups, and the changes in outcome measures following intervention were compared among the three groups. We found that the improvements in social competence after PEERS® were significant, but the treatment effects were not significantly different among the three age groups. The findings suggest that PEERS® is beneficial for ASD adolescents regardless of patient age and adolescence stage.

A randomized controlled trial of the Korean version of the PEERS(®) parent-assisted social skills training program for teens with ASD.

Impaired social functioning is a hallmark feature of autism spectrum disorder (ASD), often requiring treatment throughout the life span. PEERS(®) (Program for the Education and Enrichment of Relational Skills) is a parent-assisted social skills training for teens with ASD. Although PEERS(®) has an established evidence base in improving the social skills of adolescents and young adults with ASD in North America, the efficacy of this treatment has yet to be established in cross-cultural validation trials. The objective of this study is to examine the feasibility and treatment efficacy of a Korean version of PEERS(®) for enhancing social skills through a randomized controlled trial (RCT).The English version of the PEERS(®) Treatment Manual (Laugeson & Frankel, 2010) was translated into Korean and reviewed by 21 child mental health professionals. Items identified as culturally sensitive were surveyed by 447 middle school students, and material was modified accordingly. Participants included 47 teens between 12 and 18 years of age with a diagnosis of ASD and a verbal intelligence quotient (IQ) ≥ 65. Eligible teens were randomly assigned to a treatment group (TG) or delayed treatment control group (CG). Primary outcome measures included questionnaires and direct observations quantifying social ability and problems directly related to ASD. Secondary outcome measures included scales for depressive symptoms, anxiety, and other behavioral problems. Rating scales for parental depressive symptoms and anxiety were examined to detect changes in parental psychosocial functioning throughout the PEERS(®) treatment. Independent samples t-tests revealed no significant differences at baseline across the TG and CG conditions with regard to age (14.04 ± 1.64 and 13.54 ± 1.50 years), IQ (99.39 ± 18.09 & 100.67 ± 16.97), parental education, socioeconomic status, or ASD symptoms (p < 0.05), respectively. Results for treatment outcome suggest that the TG showed significant improvement in communication and social interaction domain scores on the Autism Diagnostic Observation Schedule, interpersonal relationship and play/leisure time on the subdomain scores of the Korean version of the Vineland Adaptive Behavior Scale (p's < 0.01), social skills knowledge total scores on the Test of Adolescent Social Skills Knowledge-Revised (p < 0.01), and decreased depressive symptoms on the Child Depression Inventory following treatment (p < 0.05). Analyses of parental outcome reveal a significant decrease in maternal state anxiety in the TG after controlling for potential confounding variables (p < 0.05). Despite cultural and linguistic differences, the PEERS(®) social skills intervention appears to be efficacious for teens with ASD in Korea with modest cultural adjustment. In an RCT, participants receiving the PEERS(®) treatment showed significant improvement in social skills knowledge, interpersonal skills, and play/leisure skills, as well as a decrease in depressive symptoms and ASD symptoms. This study represents one of only a few cross-cultural validation trials of an established evidence-based treatment for adolescents with ASD.

Valproic Acid Regulates α-Synuclein Expression through JNK Pathway in Rat Primary Astrocytes.

Although the role of α-synuclein aggregation on Parkinson's disease is relatively well known, the physiological role and the regulatory mechanism governing the expression of α-synuclein are unclear yet. We recently reported that α-synuclein is expressed and secreted from cultured astrocytes. In this study, we investigated the effect of valproic acid (VPA), which has been suggested to provide neuroprotection by increasing α-synuclein in neuron, on α-synuclein expression in rat primary astrocytes. VPA concentrationdependently increased the protein expression level of α-synuclein in cultured rat primary astrocytes with concomitant increase in mRNA expression level. Likewise, the level of secreted α-synuclein was also increased by VPA. VPA increased the phosphorylation of Erk1/2 and JNK and pretreatment of a JNK inhibitor SP600125 prevented the VPA-induced increase in α-synuclein. Whether the increased α-synuclein in astrocytes is involved in the reported neuroprotective effects of VPA awaits further investigation.

Proteinase 3 induces oxidative stress-mediated neuronal death in rat primary cortical neuron.

The recruitment of neutrophils into the cerebral microcirculation occurs, especially, in acute brain diseases like a focal cerebral ischemia and plays important role in pathological processes. Proteinase 3 is one of the three major proteinases expressed in neutrophils but no reports are available whether proteinase 3 can modulate neuronal survival. In this study, treatment of cultured rat primary cortical neuron with proteinase 3 induced overt reactive oxygen species production and decreased total glutathione contents as well as disruption of mitochondrial transmembrane potential. Proteinase 3 induced neuronal cell death as evidenced by MTT analysis as well as propidium iodide staining, which was prevented by pretreatment with an antioxidant, N-acetyl cysteine. Proteinase 3 increased activation of procaspase-3 and altered expression level of apoptotic regulator proteins, such as Bcl-2, Bax, and Bcl-xL. Similar to in vitro data, a direct microinjection of proteinase 3 into striatum of rat brain induced neuronal death, which was mediated by reactive oxygen species. These results suggest that proteinase 3 is new essential regulator of neuronal cell death pathway in a condition of excess neutrophil encounter in neuroinflammatory conditions.

The phosphodiesterase type-5 inhibitor, tadalafil, improves depressive symptoms, ameliorates memory impairment, as well as suppresses apoptosis and enhances cell proliferation in the hippocampus of maternal-separated rat pups.

Early adverse experiences resulting from maternal separation may lead to neuronal cell death and eventually cause memory impairment. Maternal separation has been used to create a valid animal model of early life stress and a depression-like syndrome. The phosphodiesterase (PDE)-5 inhibitor, tadalafil (Cialis), is a widely prescribed agent for the treatment of erectile dysfunction. In this study, we investigated the effects of tadalafil on apoptosis and cell proliferation in the hippocampal dentate gyrus of rat pups following maternal separation. Specifically, the immobility time in the forced swim test was increased in the maternal-separated rat pups, and tadalafil treatment decreased the immobility time. The rat pups in the maternal separation group had deceased memory function compared to the rat pups in the maternal care group, and tadalafil treatment increased memory function of the rat pups in the maternal separation group. Apoptotic cell death in the hippocampal dentate gyrus was significantly increased in the maternal-separated rat pups, and tadalafil treatment suppressed maternal separation-induced apoptosis. In contrast, cell proliferation in the dentate gyrus was significantly decreased in the maternal-separated rat pups, and taldalafil treatment increased cell proliferation. The present results suggest that tadalafil improves depressive symptoms and alleviates memory impairment by suppressing apoptotic neuronal cell death and enhancing cell proliferation in maternal-separated rat pups.

Liuweidihuang-tang improves spatial memory function and increases neurogenesis in the dentate gyrus in rats.

The aqueous extract of Liuweidihuang-tang given to rats at doses of 100 mg/kg/day for 10 days induced a reduction in the frequency of error and increased neurogenesis in the hippocampal dentate gyrus. Our data suggest that Liuweidihuang-tang improves spatial learning ability by increasing neurogenesis in the dentate gyrus.

Protective effect of shenqi-wan against H2O2-induced apoptosis in hippocampal neuronal cells.

The present study investigated whether Shenqi-wan possesses a protective effect against hydrogen peroxide (H2O2)-induced apoptosis of the hippocampal cell line HiB5. Through morphological and biochemical analyses, it was demonstrated that HiB5 cells treated with H2O2 exhibited several apoptotic features, while cells pre-treated with Shenqi-wan prior to H2O2 exposure showed a decrease in the occurrence of apoptosis. In addition, a patch clamp study revealed that Shenqi-wan inhibited profoundly N-methyl-D-aspartic acid (NMDA) receptor-activated ion current in acutely dissociated hippocampal CA1 neurons. These results suggest that Shenqi-wan may exert its protective effect against H2O2-induced apoptosis via inhibition of NMDA receptors in hippocampal neuronal cells.

Effect of Puerariae radix on c-Fos expression in hippocampus of alcohol-intoxicated juvenile rats.

Alcohol consumption is known to cause substantial neuronal loss in several regions of the brain. In Oriental medicine, medications based on Puerariae radix have been known to be of efficacy in the treatment of alcohol-related problems. In the present study, the effect of the aqueous extract of Puerariae radix on the expression of c-Fos, an immediate early gene whose expression is sometimes used as a marker for stimulus-induced changes in the metabolic activity of neurons, in the hippocampus of acutely alcohol-intoxicated juvenile rats was investigated via immunohistochemistry. In the first part of the experiment, Sprague-Dawley rats were divided into six groups: the control group, the alcohol-treated group, the alcohol- and 0.3 mg/kg Puerariae radix-treated group, the alcohol- and 3 mg/kg Puerariae radix-treated group, the alcohol- and 30 mg/kg Puerariae radix-treated group, and the alcohol- and 300 mg/kg Puerariae radix-treated group. In the second part of the experiment, animals were divided into four groups: the control group, the 30 mg/kg Puerariae radix-treated group, the alcohol-treated group, and the alcohol- and 30 mg/kg Puerariae radix-treated group. From the results, it was demonstrated that alcohol administration significantly decreases the number of Fos-positive cells in the various regions of the hippocampus, and Puerariae radix treatment inhibits the alcohol-induced suppression of the expression of Fos in the hippocampus in a dose-dependent manner. Puerariae radix exerted no significant effect on Fos expression in the hippocampus of normal rats. The results presented in this study suggest that Puerariae radix may alleviate alcohol-induced disruption of hippocampal functions.

Alcohol and nicotine reduce cell proliferation and enhance apoptosis in dentate gyrus.

It is generally accepted that alcohol and nicotine affect learning ability and memory functions, especially in adolescents. In the present study, the effects of alcohol and nicotine on cell proliferation and apoptosis in the dentate gyrus of young rats were investigated. The results show that cell proliferation is suppressed by alcohol and nicotine. Furthermore, alcohol and nicotine increase the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells. Based on the results presented in this study, it can be suggested that alcohol- and nicotine-related impairment in learning and memory functions may be due to alcohol- and nicotine-induced suppression of new cell formation and acceleration of apoptosis, especially during adolescence.

Protective effect of Hypericum perforatum Linn (St. John's wort) against hydrogen peroxide-induced apoptosis on human neuroblastoma cells.

The medicinal plant Hypericum perforatum Linn, commonly known as St. John's wort, has been used as an antidepressant. To investigate whether St. John's wort possesses a protective effect against hydrogen peroxide (H(2)O(2))-induced cytotoxicity in neuronal cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 4,6-diamidino-2-phenylindole staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay, flow cytometry analysis, DNA fragmentation assay, and caspase-3 enzyme assay were performed on SK-N-MC human neuroblastoma cells. Cells treated with H(2)O(2) exhibited several apoptotic features, while those pre-treated with St. John's wort prior to H(2)O(2) exposure showed a decreased occurrence of apoptotic features. In addition, pre-treatment with St. John's wort inhibited H(2)O(2)-induced increase in caspase-3 enzyme activity. These results suggest that St. John's wort may exert a protective effect against H(2)O(2)-induced apoptosis in human neuroblastoma cells.