Association study of arcuate nucleus neuropeptide Y neuron receptor gene variation and serum NPY levels in clozapine treated patients with schizophrenia.

BACKGROUND: Antipsychotic-induced weight gain (AIWG) leads to metabolic consequences and comorbidity, social stigmatization and nonadherence in patients with schizophrenia. Neuropeptide Y (NPY) has an important role in appetite and body weight regulation. Associations between AIWG and serum NPY levels, and genetic polymorphisms (SNPs) associated with its serum levels have been little studied in these patients. SUBJECTS AND METHODS: Associations between serum NPY concentration and other metabolic and inflammatory markers, and 215 SNPs in 21 genes (NPY gene, NPY receptor genes and genes encoding arcuate nucleus NPY neuron receptors) were studied in 180 patients with schizophrenia on clozapine treatment. RESULTS: The serum levels of NPY correlated with levels of resistin (r=0.31, P<0.001) and age (r=0.22, P=0.003). In the general linear univariate model the best-fitting model with explanatory factors age, serum resistin level, serum insulin level, BMI and gender explained 18.0% (P<0.001) of the variance of serum NPY. Genetic risk score (GRSNPY) analysis found twelve significant (P<0.05) serum NPY concentration related SNPs among α7 nicotinic acetylcholine receptor gene CHRNA7, insulin receptor gene INSR, leptin receptor gene LEPR, glucocorticoid receptor (GR) gene NR3C1, and NPY gene. However, after permutation test of gene score the predictive value of GRSNPY remained non-significant (P=0.078). CONCLUSIONS: Serum NPY level does not seem to be a feasible biomarker of AIWG. Serum NPY level alterations are not significantly associated with the candidate gene polymorphisms studied.

Association study of the HTR2C, leptin and adiponectin genes and serum marker analyses in clozapine treated long-term patients with schizophrenia.

Clozapine treatment is associated with weight gain and cardio-metabolic consequences among patients with schizophrenia. Polymorphisms of leptin, serotonin receptor HTR2C and adiponectin genes have been associated with antipsychotic-induced weight gain and metabolic comorbidity. However, the results of the studies so far are inconclusive. The aim of the present study was first to test for a possible role of serum leptin and adiponectin levels as a marker of weight gain in association with inflammatory cytokines/adipokines (IL-6, IL-1Ra, hs-CRP and adipsin), and second to study associations between SNPs LEP rs7799039 (-2548 A/G), ADIPOQ rs1501299 and HTR2C rs1414334 and weight gain and levels of leptin and adiponectin, in 190 patients with schizophrenia on clozapine treatment, with retrospectively assessed weight change and cross-sectionally measured cytokine levels. A strong association was found between serum levels of leptin and weight gain and cytokines/adipokines related to metabolic comorbidity, especially among female patients (in women leptin vs. weight gain, IL-6 and IL-1Ra, P<0.001; in men leptin vs. weight gain, P=0.026, leptin vs. IL-1Ra, P<0.001). In male patients low adiponectin level was a more specific marker of clozapine-induced weight gain (P=0.037). The results of the present study do not support a major role of SNPs LEP rs7799039, ADIPOQ rs1501299 and HTR2C rs1414334 in the regulation of weight gain or association of serum levels of leptin and adiponectin and corresponding studied SNPs in patients with schizophrenia on clozapine treatment.

Unusual presentation of pulmonary tumor thrombotic microangiopathy with no detectable primary tumor.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare condition characterized by the presence of diffuse thrombotic microthrombi and fibrocellular intimal proliferation in the pulmonary vasculature. Its development is linked to the presence of pulmonary tumor microemboli (PTM) and should be suspected in patients with unexplained dyspnea, especially in the presence of adenocarcinoma. PTTM presents in a similar fashion to respiratory disease such as pulmonary embolism, pulmonary hypertension or pneumonia and is usually only diagnosed post-mortem. We report a case of PTTM identified ante-mortem by bronchial biopsy in an 82-year-old woman presenting with a clinical picture of atypical pneumonia. Autopsy confirmed PTTM, from an unknown primary neoplasm.

Seven-year outcome of depression in primary and psychiatric outpatient care: results of the TADEP (Tampere Depression) II Study.

The objective of this article was to determine a 7-year naturalistic progression of depression as well as a number of potential prognostic factors among Finnish primary care and psychiatric care patients. Depression-screened patients from primary care and psychiatric care, aged 18-64, were interviewed in 1991-92 with the Present State Examination (PSE) as the diagnostic instrument. The patients were re-contacted in 1998-99, and their depression at final assessment (FinalA) and during the follow-up period (F-up) was assessed by telephone interview using the Composite International Diagnostic Interview--Short Form (CIDI-SF). 250 primary care (58.1%) and 170 (40.2%) psychiatric care patients were successfully followed. Of the primary care patients with severe depression at baseline, 42.4% had had depression during F-up and 21.2% had depression at FinalA. For the patients with mild depression at baseline, the corresponding figures were nearly the same, but for the patients with depressive symptoms clearly lower. Of the psychiatric care patients with severe depression at baseline, 61.0% had had depression during F-up and 26.2% had depression at FinalA. As with primary care patients, the corresponding figures were nearly the same for mild depression at baseline but clearly lower for depressive symptoms. Experienced lifetime mood elevation was associated with having depression during F-up in both primary care and psychiatric care patients. High Depression Scale (DEPS) score at baseline was associated with having depression at FinalA in primary care patients, but in psychiatric care patients, it was the high Hamilton Rating Scale for depression (HAM-D) and drinking problems. Severe depression and mild depression are predictive for subsequent depression at both levels of care. The long-term prognosis for depression is better in primary care. DEPS and HAM-D are useful, prognostic instruments.

Clozapine serum concentrations are lower in smoking than in non-smoking schizophrenic patients.

Serum concentrations of clozapine and its main metabolite demethylclozapine were measured in 44 schizophrenic inpatients, of whom ten were non-smokers and 34 smokers. When comparing their clozapine dose and body weight-related serum drug levels, we found that clozapine and demethylclozapine concentrations were about 40% lower in the smoking than in the non-smoking group, probably due to an inducing effect of smoking on the cytochrome P450 (CYP) 1A2, which is involved in the metabolism of clozapine. We conclude that dosage adjustment may be necessary in clozapine-treated smokers.