Hsien-Yuan Lane

Bio: Hsien-Yuan Lane is an academic researcher from China Medical University (Taiwan). The author has contributed to research in topics: Schizophrenia & Risperidone. The author has an hindex of 44, co-authored 258 publications receiving 6583 citations. Previous affiliations of Hsien-Yuan Lane include Taipei Medical University & China Medical University (PRC).

Sarcosine or D-Serine Add-on Treatment for Acute Exacerbation of Schizophrenia: A Randomized, Double-blind, Placebo-Controlled Study

Abstract: Context Agents that enhance N -methyl-D-aspartate (NMDA) function through the glycine modulatory site (D-serine, glycine, orD-cycloserine) or through glycine transporter 1 (sarcosine) improve the symptoms of patients with stable chronic schizophrenia. Objective To determine whether NMDA-glycine site agonists or glycine transporter-1 inhibitors have better efficacy and whether NMDA receptor−enhancing agents have beneficial effects for acute exacerbation of schizophrenia. Design Randomized, double-blind, placebo-controlled trial. Setting Inpatient units of 2 major medical centers in Taiwan. Patients Sixty-five schizophrenic inpatients with acute exacerbation. Interventions Six weeks of treatment with sarcosine (2 g/d),D-serine (2 g/d), or placebo and concomitant optimal risperidone therapy. Main Outcome Measures Positive and Negative Syndrome Scale (PANSS) and Scale for the Assessment of Negative Symptoms (SANS) (20 and 17 items) total scores. Results The sarcosine group revealed more reductions in PANSS total scores than the placebo ( P = .04) andD-serine ( P P = .007) and SANS-17 ( P = .003) scores and toD-serine in decreasing SANS-20 ( P = .006) and SANS-17 ( P = .002) scores. The PANSS-general, PANSS-cognitive, and PANSS-depressive symptoms scores and SANS-alogia and SANS−blunted affect scores improved significantly more in sarcosine-cotreated patients than in risperidone monotherapy patients ( P ≤.02 for all). Sarcosine adjunctive therapy also surpassedD-serine in terms of PANSS-general, PANSS-positive, PANSS-negative, and PANSS-depressive symptoms scores ( P ≤.04 for all).D-Serine and risperidone cotreatment did not differ significantly from risperidone monotherapy in all efficacy domains. Conclusions This first short-term treatment study on NMDA receptor−enhancing agents suggests that sarcosine, superior toD-serine, can benefit not only patients with long-term stable disease but also acutely ill persons with schizophrenia. This finding indicates that a glycine transporter 1 inhibitor may be more efficacious than NMDA-glycine site agonists for adjuvant treatment of schizophrenia, at least during the acute phase. Further studies are needed.

Add-on Treatment of Benzoate for Schizophrenia: A Randomized, Double-blind, Placebo-Controlled Trial of d-Amino Acid Oxidase Inhibitor

Abstract: Importance In addition to dopaminergic hyperactivity, hypofunction of the N -methyl-d-aspartate receptor (NMDAR) has an important role in the pathophysiology of schizophrenia. Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach. To date, several trials on adjuvant NMDA-enhancing agents have revealed beneficial, but limited, efficacy for positive and negative symptoms and cognition. Another method to enhance NMDA function is to raise the levels ofd-amino acids by blocking their metabolism. Sodium benzoate is ad-amino acid oxidase inhibitor. Objective To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia. Design, Setting, and Participants A randomized, double-blind, placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer. Interventions Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo. Main Outcomes and Measures The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score. Clinical efficacy and adverse effects were assessed biweekly. Cognitive functions were measured before and after the add-on treatment. Results Benzoate produced a 21% improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the PANSS total and subscales, Scales for the Assessment of Negative Symptoms–20 items, Global Assessment of Function, Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health’s Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, including the domains of processing speed and visual learning. Benzoate was well tolerated without significant adverse effects. Conclusions and Relevance Benzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia. The preliminary results show promise ford-amino acid oxidase inhibition as a novel approach for new drug development for schizophrenia. Trial Registration clinicaltrials.gov Identifier:NCT00960219

Type 2 Diabetes Mellitus in Youth Exposed to Antipsychotics: A Systematic Review and Meta-analysis

Abstract: Importance Antipsychotics are used increasingly in youth for nonpsychotic and off-label indications, but cardiometabolic adverse effects and (especially) type 2 diabetes mellitus (T2DM) risk have raised additional concern. Objective To assess T2DM risk associated with antipsychotic treatment in youth. Data Sources Systematic literature search of PubMed and PsycINFO without language restrictions from database inception until May 4, 2015. Data analyses were performed in July 2015, and additional analyses were added in November 2015. Study Selection Longitudinal studies reporting on T2DM incidence in youth 2 to 24 years old exposed to antipsychotics for at least 3 months. Data Extraction and Synthesis Two independent investigators extracted study-level data for a random-effects meta-analysis and meta-regression of T2DM risk. Main Outcomes and Measures The coprimary outcomes were study-defined T2DM, expressed as cumulative T2DM risk or as T2DM incidence rate per patient-years. Secondary outcomes included the comparison of the coprimary outcomes in antipsychotic-treated youth with psychiatric controls not receiving antipsychotics or with healthy controls Results Thirteen studies were included in the meta-analysis, including 185 105 youth exposed to antipsychotics and 310 438 patient-years. The mean (SD) age of patients was 14.1 (2.1) years, and 59.5% were male. The mean (SD) follow-up was 1.7 (2.3) years. Among them, 7 studies included psychiatric controls (1 342 121 patients and 2 071 135 patient-years), and 8 studies included healthy controls (298 803 patients and 463 084 patient-years). Antipsychotic-exposed youth had a cumulative T2DM risk of 5.72 (95% CI, 3.45-9.48; P P P P P P P P P = .002) ( r 2 = 1.00, P P ≤ .050) and less autism spectrum disorder diagnosis ( P = .048) ( r 2 = 0.21, P = .044). Conclusions and Relevance Although T2DM seems rare in antipsychotic-exposed youth, cumulative risk and exposure-adjusted incidences and IRRs were significantly higher than in healthy controls and psychiatric controls. Olanzapine treatment and antipsychotic exposure time were the main modifiable risk factors for T2DM development in antipsychotic-exposed youth. Antipsychotics should be used judiciously and for the shortest necessary duration, and their efficacy and safety should be monitored proactively.

Human biochemical genetics

Abstract: So far in this course we have dealt entirely with the evolution of characters that are controlled by simple Mendelian inheritance at a single locus. There are notes on the course website about gametic disequilibrium and how allele frequencies change at two loci simultaneously, but we didn’t discuss them. In every example we’ve considered we’ve imagined that we could understand something about evolution by examining the evolution of a single gene. That’s the domain of classical population genetics. For the next few weeks we’re going to be exploring a field that’s actually older than classical population genetics, although the approach we’ll be taking to it involves the use of population genetic machinery. If you know a little about the history of evolutionary biology, you may know that after the rediscovery of Mendel’s work in 1900 there was a heated debate between the “biometricians” (e.g., Galton and Pearson) and the “Mendelians” (e.g., de Vries, Correns, Bateson, and Morgan). Biometricians asserted that the really important variation in evolution didn’t follow Mendelian rules. Height, weight, skin color, and similar traits seemed to

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

Abstract: The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.

A rating scale for drug-induced akathisia

Abstract: A rating scale for drug-induced akathisia has been derived that incorporates diagnostic criteria for pseudoakathisia, and mild, moderate, and severe akathisia. It comprises items for rating the observable, restless movements which characterise the condition, the subjective awareness of restlessness, and any distress associated with the akathisia. In addition, there is an item for rating global severity. A standard examination procedure is recommended. The inter-rater reliability for the scale items (Cohen's kappa) ranged from 0.738 to 0.955. Akathisia was found in eight of 42 schizophrenic in-patients, and nine had pseudoakathisia, where the typical sense of inner restlessness was not reported.

Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand

Abstract: We evolved muscarinic receptors in yeast to generate a family of G protein-coupled receptors (GPCRs) that are activated solely by a pharmacologically inert drug-like and bioavailable compound (clozapine-N-oxide) Subsequent screening in human cell lines facilitated the creation of a family of muscarinic acetylcholine GPCRs suitable for in vitro and in situ studies We subsequently created lines of telomerase-immortalized human pulmonary artery smooth muscle cells stably expressing all five family members and found that each one faithfully recapitulated the signaling phenotype of the parent receptor We also expressed a Gi-coupled designer receptor in hippocampal neurons (hM4D) and demonstrated its ability to induce membrane hyperpolarization and neuronal silencing We have thus devised a facile approach for designing families of GPCRs with engineered ligand specificities Such reverse-engineered GPCRs will prove to be powerful tools for selectively modulating signal-transduction pathways in vitro and in vivo