Biomedical subjects

Young-Chul Chung

Publications and source records attributed to Young-Chul Chung.

4 recordsLinked to original sources

PubMed2006

Pharmacological treatment of primary negative symptoms in schizophrenia: a systematic review.

BACKGROUND: Optimal treatment of primary negative symptoms is important because their presence is associated with poor outcome. AIMS: To systematically review all studies dealing with the efficacy of pharmacological agents on primary negative symptoms. METHOD: A comprehensive search of the relevant literature was undertaken using electronic database, reference lists and personal contact. RESULTS: There is a lack of standardized research designs. Amisulpride is the most extensively studied drug with respect to efficacy against primary negative symptoms. At low doses it demonstrates a consistent, modest effect compared to placebo, though not to conventional antipsychotics and has yet to be tested against other atypicals. Evidence from multiple studies that used simple statistical analyses and inclusion criteria for patients with primary negative symptoms does not support a direct effect for clozapine. Path-analysis studies support the direct effects of risperidone, olanzapine, sertindole and aripiprazole, however, different statistical analyses of the same risperidone study produced conflicting results and the direct effects of olanzapine were not confirmed in selected patients with primary negative symptoms. There are no studies supporting the use of ziprasidone or quetiapine. The effects of typical antipsychotics on primary negative symptoms are inconclusive and likely to depend on drug dosages. Selective serotonin reuptake inhibitors (SSRIs), mirtazepine and NMDA agonists show early promise but require further study. Novel agents such as selegiline, naltrexone, dehydroepiandrosterone, galantamine, Ginkgo, nitric oxide, L-deprenyl and pergolide show positive effects on general negative symptoms but remain untested against primary negative symptoms. CONCLUSIONS: Further studies using standardized selective inclusion criteria and controlling for chronicity are needed. Research guidelines are discussed.

Affect↗

PubMed2005

Valproic acid potentiates both typical and atypical antipsychotic-induced prefrontal cortical dopamine release.

Antipsychotic drugs (APD)s and anticonvulsant mood-stabilizers are now frequently used in combination with one another in treating both schizophrenia and bipolar disorder. We have recently reported that the atypical APDs, e.g. clozapine and risperidone, as well as the anticonvulsant mood-stabilizers, valproic acid (VPA), zonisamide, and carbamazepine, but not the typical APD haloperidol, increase dopamine (DA) release in rat medial prefrontal cortex (mPFC). The increased DA release was partially (atypical APDs) or completely (mood-stabilizers) blocked by the serotonin (5-HT)1A receptor antagonist WAY100635. Diminished prefrontal cortical DA activity may contribute to cognitive impairment in virtually all the patients with schizophrenia and, perhaps, bipolar disorder. Thus, the enhanced release of cortical DA by these agents may be beneficial in this regard. It is, therefore, of considerable interest to determine whether combined administration of these agents augments prefrontal cortical DA release, and if so, whether the increase is dependent upon 5-HT1A receptor activation. VPA (50 mg/kg), which was insufficient by itself to increase prefrontal cortical DA release, potentiated the ability of clozapine (20 mg/kg) and risperidone (1 mg/kg) to increase DA release in the mPFC, but not in the nucleus accumbens (NAC). VPA (50 mg/kg) also potentiated haloperidol (0.5 mg/kg)-induced DA release in the mPFC; this increase was completely abolished by WAY100635 (0.2 mg/kg). These results suggest that, in combination with VPA, both typical and atypical APDs produce greater increases in prefrontal cortical DA release than either type of drug alone via a mechanism dependent upon 5-HT(1A) receptor activation. Furthermore, they provide a strong rationale for testing for possible clinical synergism of an APD and anticonvulsant mood-stabilizer in improving the cognitive deficits present in patients with schizophrenia and bipolar disorder.

Animals↗

PubMed2004

Clozapine increases both acetylcholine and dopamine release in rat ventral hippocampus: role of 5-HT1A receptor agonism.

Atypical antipsychotic drugs (APDs) such as clozapine, but not the typical APD haloperidol, improve some aspects of cognition in schizophrenia. This advantage has been attributed, in part, to the ability of the atypical APDs to markedly increase acetylcholine (ACh) and dopamine (DA) release in rat medial prefrontal cortex (mPFC), while producing a minimal effect in the nucleus accumbens (NAC) or striatum. The atypical APD-induced preferential release of DA, but not ACh, in the mPFC is partially inhibited by the selective 5-HT(1A) antagonist WAY100635. However, little is known about these effects of atypical APDs in the ventral hippocampus (vHIP), another possible site of action of atypical APDs with regard to cognitive enhancement. The present study demonstrates that clozapine (10 mg/kg) comparably increases both ACh and DA release in the vHIP and mPFC. The increases in DA, but not ACh, release in both regions were partially attenuated by WAY100635 (0.2 mg/kg), which had no effect by itself on the release of either neurotransmitter in either region. Tetrodotoxin (TTX; 1 microM), a Na(+) channel blocker, in the perfusion medium, eliminated the clozapine (10 mg/kg)-induced ACh and DA release in the vHIP, indicating their neuronal origin. Haloperidol produced a slight increase in ACh release in the vHIP at 1 mg/kg, and DA release in the mPFC at 0.1 mg/kg. In conclusion, clozapine increases ACh and DA release in the vHIP and mPFC, whereas haloperidol has minimal effects on the release of these two neurotransmitters in either region. These differences may contribute, at least in part, to the superior ability of clozapine, compared to haloperidol, to improve cognition in schizophrenia. 5-HT(1A) agonism is important to the ability of clozapine and perhaps other atypical APDs to increase DA, but not ACh, release in the vHIP, as well as the mPFC. The role of hippocampus in the cognitive effects of atypical APDs warrants more intensive study.

Acetylcholine↗

PubMed1998

Hyperprolactinaemia induced by risperidone.

Risperidone is a potent antagonist of both dopamine (D2) and serotonin (5-HT2) receptors, demonstrating improvement of both positive and negative symptoms and a lower propensity for inducing extrapyramidal symptoms (EPS) than typical neuroleptics. Its most common side-effects, found in the Canadian multi-centre trial (Chouinard et al., 1993), were agitation, anxiety, insomnia, EPS, headache and nausea, in order of frequency. With regard to endocrine effects, risperidone causes an increase in prolactin levels similar to that of other neuroleptics (Claus et al., 1992). In open clinical trials (De Cuyper, 1991), the overall incidence of risperidone-induced endocrine side-effects was quite low: 2.9 % for amenorrhoea and 1-2% for galactorrhoea. However, it is assumed that the incidence can vary depending upon the characteristics of patients and the drug regimen, i.e. dosage and titration schedule. In our experience, hyperolactinaemia is likely to occur when prescribing risperidone to female or first-onset psychotic patients: we are reporting 5 cases of risperidone-induced hyperprolactinaemia with these characteristics.

Journal Article↗