Brown adipose tissue is specialized to burn lipids for thermogenesis and energy expenditure. Second-generation antipsychotics (SGA) are the most commonly used drugs for schizophrenia with several advantages over first-line drugs, however, it can cause clinically-significant weight gain. To reveal the involvement of brown adipocytes in SGA-induced weight gain, we compared the effect of clozapine, quetiapine, and ziprasidone, SGA with different propensities to induce weight gain, on the differentiation and the expression of brown fat-specific markers, lipogenic genes and adipokines in a mouse brown preadipocyte cell line. On Oil Red-O staining, the differentiation was inhibited almost completely by clozapine (40 microM) and partially by quetiapine (30 microM). Clozapine significantly down-regulated the brown adipogenesis markers PRDM16, C/EBPbeta, PPARgamma2, UCP-1, PGC-1alpha, and Cidea in dose- and time-dependent manners, whereas quetiapine suppressed PRDM16, PPARgamma2, and UCP-1 much weakly than clozapine. Clozapine also significantly inhibited the mRNA expressions of lipogenic genes ACC, SCD1, GLUT4, aP2, and CD36 as well as adipokines such as resistin, leptin, and adiponectin. In contrast, quetiapine suppressed only resistin and leptin but not those of lipogenic genes and adiponectin. Ziprasidone (10 microM) did not alter the differentiation as well as the gene expression patterns. Our results suggest for the first time that the inhibition of brown adipogenesis may be a possible mechanism to explain weight gain induced by clozapine and quetiapine.
Adipocytes, Brown/drug effects ; Adipogenesis/drug effects ; Adipokines/metabolism ; Animals ; *Antipsychotic Agents/administration & dosage/adverse effects ; Cell Differentiation/drug effects ; Cell Line ; Cell Survival/drug effects ; *Clozapine/administration & dosage/adverse effects ; *Dibenzothiazepines/administration & dosage/adverse effects ; Gene Expression Regulation/drug effects ; Humans ; Mice ; *Piperazines/administration & dosage/adverse effects ; Schizophrenia/drug therapy ; *Thiazoles/administration & dosage/adverse effects ; Weight Gain/*drug effects

Clozapine ; adverse effects ; Haloperidol ; adverse effects ; Humans ; Infant, Newborn ; Male ; Neonatal Abstinence Syndrome ; etiology

This report describes the efficacy of combined use of aripiprazole in the treatment of a patient with clozapine induced enuresis. Aripiprazole acts as a potential dopamine partial agonist and the dopamine blockade in the basal ganglia might be one of the causes of urinary incontinence and enuresis. We speculate that aripiprazole functioned as a D2 agonist in hypodopaminergic state of basal ganglia caused by clozapine and maintained dopamine level that would improve enuresis ultimately.
Adult ; Antipsychotic Agents/*adverse effects ; Clozapine/*adverse effects ; Dopamine/metabolism ; Dopamine Agonists/*therapeutic use ; Drug Therapy, Combination ; Enuresis/chemically induced/*drug therapy ; Humans ; Male ; Middle Aged ; Piperazines/*therapeutic use ; Quinolones/*therapeutic use ; Schizophrenia, Paranoid/drug therapy

OBJECTIVE: To explore the correlation between signs similar to schizophrenia in mice after ketamine administration and the expressions of NRG1 and ErbB4 mRNA in order to explain the possible pathogenesis of schizophrenia. METHODS: Fifty KM mice were randomly divided into 5 groups which were administered intraperitoneally with saline, clozapine and different dosages ketamine. The ketamine groups were administered intraperitoneally with low dosage (25 mg/kg), middle dosage (50 mg/kg) and high dosage (100 mg/kg) one time every day for 7 days. After administration of 100 mg/kg ketamine for 7 days, the clozapine group was introgastrically administered 20 mg/kg with clozapine one time every day for 7 days. The pathological changes of hippocampus neurons were observed by HE stain. The expressions of the NRG1 and ErbB4 mRNA in hippocampus were detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: In the group with high dosage of ketamine, the levels of NRG1 and ErbB4 mRNA were significantly lower than that of the group with saline. CONCLUSION Ketamine may induce signs similar to schizophrenia in KM mice. The mechanism may be involved in the reduction of NRG1 and ErbB4 mRNA expression.
Animals ; Clozapine/therapeutic use* ; Disease Models, Animal ; Dose-Response Relationship, Drug ; ErbB Receptors/metabolism* ; Hippocampus/pathology* ; Ketamine/adverse effects* ; Male ; Mice ; Neuregulin-1/metabolism* ; Neurons/metabolism* ; RNA, Messenger/metabolism* ; Random Allocation ; Receptor, ErbB-4 ; Reverse Transcriptase Polymerase Chain Reaction ; Schizophrenia/genetics*

OBJECTIVETo compare the short-term curative effect of clozapine (CZ) and its combination with electroacupuncture (EA) in treating schizophrenia.

METHODSNinety schizophrenia patients were randomly divided into two groups equally: the EA group treated with combination of CZ (200 - 300 mg/d in mean) and EA, and the CZ group treated with CZ alone. The effects of treatment were evaluated with PANSS, CGI and TESS before and at the 2th, 4th, 6th and 8th weekend of the treatment.

RESULTSThe initiation of effect in the two groups was the same, the total effective rate was 75% in the EA group and 73% in the CZ group. However, somatic complaint was lower and compliance was higher in the EA group than that in the CZ group respectively.

CONCLUSIONWith the effect equal to CZ, combination of CZ and EA shows higher compliance in treating schizophrenia, which would be beneficial in the later stage treatment for consolidation.

Acupuncture Therapy ; Adolescent ; Adult ; Clozapine ; adverse effects ; therapeutic use ; Combined Modality Therapy ; Electroacupuncture ; Female ; Humans ; Male ; Middle Aged ; Schizophrenia ; therapy