Prescription Trends of Psychotropics in Children and Adolescents with Autism Based on Nationwide Health Insurance Data.

Children with autism are often medicated to manage emotional and behavioral symptoms; yet, data on such pharmacotherapy is insufficient. In this study, we investigated the Korean National Health Insurance Claims Database (NHICD) information related to autism incidence and psychotropic medication use. From the 2010-2012 NHICD, we selected a total of 31,919,732 subjects under 19 years old. To examine the diagnostic incidence, we selected patients who had at least one medical claim containing an 10th revision of International Statistical Classification of Diseases and Related Health Problems (ICD-10) code for pervasive developmental disorder, F84, not diagnosed in the previous 360 days. Psychotropics were categorized into seven classes. Then, we analyzed the data to determine the mean annual diagnostic incidence and psychotropic prescription trends. Diagnostic incidence was 17,606 for the 3 years, with a mean annual incidence per 10,000 population of 5.52. Among them, 5,348 patients were prescribed psychotropics. Atypical antipsychotics were the most commonly used, followed by antidepressants. An older age, male sex, and the availability of medical aid were associated with a higher rate of prescription than observed for a younger age, female sex, and the availability of health insurance. Psychotropic drugs were used for less than one-third of patients newly diagnosed with autism, and prescription differed by sex and age. Increased diagnostic incidence is associated with an increased prescription of psychotropic drugs. Therefore, medication-related safety data and policies for psychotropic drugs in autism should be prepared.

The transgenerational inheritance of autism-like phenotypes in mice exposed to valproic acid during pregnancy.

Autism spectrum disorder (ASD) is a heterogeneously pervasive developmental disorder in which various genetic and environmental factors are believed to underlie its development. Recently, epigenetics has been suggested as a novel concept for ASD aetiology with a proposition that epigenetic marks can be transgenerationally inherited. Based on this assumption of epigenetics, we investigated the transgenerational inheritance of ASD-like behaviours and their related synaptic changes in the VPA animal model of ASD. The first generation (F1) VPA-exposed offspring exhibited autistic-like impaired sociability and increased marble burying. They also showed increased seizure susceptibility, hyperactivity and decreased anxiety. We mated the VPA-exposed F1 male offspring with naïve females to produce the second generation (F2), and then similarly mated the F2 to deliver the third generation (F3). Remarkably, the autism-like behavioural phenotypes found in F1 persisted to the F2 and F3. Additionally, the frontal cortices of F1 and F3 showed some imbalanced expressions of excitatory/inhibitory synaptic markers, suggesting a transgenerational epigenetic inheritance. These results open the idea that E/I imbalance and ASD-like behavioural changes induced by environmental insults in mice can be epigenetically transmitted, at least, to the third generation. This study could help explain the unprecedented increase in ASD prevalence.

Utilization of Western and Traditional Korean Medicine for Children and Adolescents with Mental Disorders: a Nationwide Population-based Study from 2010 to 2012.

When in need of medical treatment, Korean citizens have a choice of practitioners of western medicine (WM) or Traditional Korean Medicine (TKM). However, the two branches frequently conflict with one another, particularly with regard to mental disorders. This study was designed to compare the utilization of WM and TKM, focusing on child/adolescent patients with mental disorders. We analyzed F-code (Mental and behavioral disorders) claims from the Korean Health Insurance Review and Assessment Service, including data from 0-18-year-old patients from 2010 to 2012. Slightly more men than women utilized WM, while TKM use was almost evenly balanced. WM claims increased with advancing age, whereas utilization of TKM was common for the 0-6 age group. In WM and TKM, the total number of claims relying on the National Health Insurance Service (NHIS) was 331,154 (92.78%) and 73,282 (97.85%), respectively, and the number of claims relying on medical aid was 25,753 (7.22%) and 1,610 (2.15%), respectively. The most frequent F-coded claim in WM was F90 (Hyperkinetic disorders), with 64,088 claims (17.96%), and that in TKM was F45 (Somatoform disorders), with 28,852 claims (38.52%). The prevalence of a single disorder without comorbidities was 168,764 (47.29%) in WM and 52,615 (70.25%) in TKM. From these data, we conclude that WM takes prevalence over TKM in cases of attention deficit/hyperactivity disorder (ADHD), as well as in psychological problems such as depression and anxiety. On the other hand, patients utilizing TKM more commonly present with physical health problems including somatoform problems, sleep, and eating disorders.

Advanced pharmacotherapy evidenced by pathogenesis of autism spectrum disorder.

In clinical practice, pharmacological treatment is mostly focused on behavioral symptoms in everyday life. Nevertheless, persistent effort continues to develop medication for causal treatment. Recent changes in diagnostic criteria from Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) to DSM-5 would affect not only diagnosing approaches, but also therapeutic approaches. Because previous pervasive developmental disorders have been integrated into a single entity, the autism spectrum disorder (ASD), we have to prepare for what medications are valuable for the ASD. In this article, we reviewed the following etiological treatment: acetylcholine and glutamate related medicine; amino acid medicine such as secretin, endogenous opioid, and oxytocin; complementary and alternative medicine such as chelating agents, vitamins, and omega-3; promising drugs related to the scope of pharmacogenetics currently under study.

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.

Nicotine administration decreases neuropeptide Y expression and increases leptin receptor expression in the hypothalamus of food-deprived rats.

The effects of nicotine on the expressions of neuropeptide Y (NPY) and leptin receptor in the rat hypothalamus were investigated via immunohistochemistry. The results show that NPY expression is not affected in the arcuate nucleus (ARN) and is increased only slightly in the paraventricular nucleus (PVN) by nicotine administration under normal (i.e. fed) conditions and that leptin receptor expression is decreased slightly in the ARN and not affected in the PVN following nicotine treatment under the same conditions. Food deprivation enhanced NPY and suppressed leptin receptor expression in the ARN and PVN of the hypothalamus. Nicotine administration resulted in decreased NPY and increased leptin receptor levels.

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.

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.