neuropeptide-y and Psychotic-Disorders

The mechanism underlying the weight gain due to treatment with olanzapine and other second generation antipsychotics has not been fully understood. To examine olanzapine's weight gain effects, we accepted first attack psychotic patients with no medication (pre-treatment) (n=22) and the healthy control group (n=26) in this study. After patientś diagnosis, they were hospitalized and then treated for four weeks with olanzapine (post-treatment). We used case-control association design to test body mass index (BMI) and biochemical changes in each group. We also investigated peripheral leptin and neuropeptides/hormones namely, pro-opiomelanocortin (POMC), cocaine and amphetaime regulated transcript (CART), and neuropeptide Y (NPY) levels. These neuropeptides which are synthesized/secreted from arcuate nucleus of hypothalamus affect food intake and therefore, body weight. After 4 weeks of olanzapine treatment; BMI (body mass index), waist circumference, blood triglyceride, total cholesterol, and very low density lipoprotein (VLDL) levels were increased significantly in patients compared to their pre-treatment baseline. In pre-treatment, patients' NPY levels were significantly lower while α-MSH, the anorexigenic product of POMC levels were significantly higher vs. control. Both leptin and NPY levels were significantly increased in patients after the treatment but the NPY levels were also significantly lower in post-treatment vs. the control group. The CART levels did not change after the treatment. We may presume that the antagonist effect of olanzapine on the serotonin (5HT2CR and 5HT1BR) receptors of the arcuate hypothalamic neurons may be a basis for a deregulation of the neurohormones secretion.

Topics: Adult; alpha-MSH; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Cholesterol; Humans; Hypothalamus; Leptin; Male; Nerve Tissue Proteins; Neuropeptide Y; Neuropeptides; Olanzapine; Psychotic Disorders; Waist Circumference

Alterations in the inhibitory circuitry of the dorsolateral prefrontal cortex (DLPFC) in schizophrenia include reduced expression of the messenger RNA (mRNA) for somatostatin (SST), a neuropeptide present in a subpopulation of gamma-aminobutyric acid (GABA) neurons. Neuropeptide Y (NPY) is expressed in a subset of SST-containing interneurons and lower levels of NPY mRNA have also been reported in schizophrenia spectrum disorders. However, whether the alterations in these two transcripts identify the same, particularly vulnerable, subset of GABA neurons has not been examined.. We used in situ hybridization to quantify NPY mRNA levels in DLPFC gray and white matter from 23 pairs of subjects with schizophrenia or schizoaffective disorder and matched normal control subjects; results were compared to those from a previous study of SST mRNA expression in the same subjects.. In contrast to SST mRNA, NPY mRNA levels were not significantly lower in the gray matter of subjects with schizophrenia or schizoaffective disorder. However, NPY, but not SST, mRNA expression was significantly lower in the superficial white matter of subjects with schizoaffective disorder.. These findings suggest that the alterations in SST-containing interneurons in schizophrenia and schizoaffective disorder are selective for the subset that do not express NPY mRNA, and that lower NPY mRNA expression in the superficial white matter may distinguish subjects with schizoaffective disorder from those with schizophrenia.

Topics: Adult; Aged; Analysis of Variance; Case-Control Studies; Female; Gene Expression Regulation; Humans; Male; Middle Aged; Neuropeptide Y; Prefrontal Cortex; Psychotic Disorders; RNA, Messenger; Somatostatin; Young Adult

Acetyl-coenzyme A carboxylase alpha (ACACA) single-nucleotide polymorphism (SNP) (rs2229416) was significantly associated with hypertriglyceridemia, during exploration of antipsychotic direct effects on lipids. Neuropeptide Y (NPY) gene (rs1468271) and ACACB gene (rs2241220) SNPs were significantly associated with severe hypercholesterolemia. In the same sample (173 patients on olanzapine, quetiapine, chlorpromazine or mirtazapine [increasing the risk of hyperlipidemia] and 184 controls taking other antipsychotics), three (rs1266175, rs12453407 and rs9906543) of eight additional ACACA SNPs were significantly associated with hypertriglyceridemia in those taking drugs of interest, but not in controls. Five other ACACA SNPs, three additional NPY SNPs, and seven additional ACACB SNPs were not significant.

Topics: Acetyl-CoA Carboxylase; Adult; Antipsychotic Agents; Cholesterol; Cross-Sectional Studies; Female; Humans; Hypercholesterolemia; Logistic Models; Male; Middle Aged; Neuropeptide Y; Pharmacogenetics; Polymorphism, Single Nucleotide; Psychotic Disorders; Sequence Analysis, DNA; Triglycerides

A number of different gene polymorphisms have been found to dispose for the development of schizophrenia. However, no single gene polymorphism is sufficient for the precipitation of schizophrenia. Swedish psychosis patients (n=103) and control subjects (n=89) were analyzed for 36 single nucleotide polymorphisms in 30 candidate genes for schizophrenia. Evidence of association was analyzed with Bayesian statistical methods. Variants in the genes coding for dopamine-D2 receptor, brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY), neuregulin 1, reelin and synapsin 3 showed association with schizophrenia, although few subjects were found in the minority allele for the two latter variants. The six gene variants, all with suspected connection to schizophrenia, were found to be risk factors when considered in combination, but not separately. The results indicate that the Bayesian statistical method gives additional possibilities in the search for risk factors for schizophrenia or other complex disorders.

Topics: Adult; Alleles; Bayes Theorem; Brain-Derived Neurotrophic Factor; Cell Adhesion Molecules, Neuronal; Chromosome Mapping; Extracellular Matrix Proteins; Female; Genetic Predisposition to Disease; Genetic Variation; Humans; Male; Middle Aged; Nerve Tissue Proteins; Neuregulin-1; Neuropeptide Y; Neuropeptides; Phosphoproteins; Polymorphism, Single Nucleotide; Psychotic Disorders; Receptors, Dopamine D2; Reelin Protein; Risk Factors; Schizophrenia; Serine Endopeptidases; Synapsins