Temperature- and sex-related effects of serine protease alleles on larval development in the Glanville fritillary butterfly.

The body reserves of adult Lepidoptera are accumulated during larval development. In the Glanville fritillary butterfly, larger body size increases female fecundity, but in males fast larval development and early eclosion, rather than large body size, increase mating success and hence fitness. Larval growth rate is highly heritable, but genetic variation associated with larval development is largely unknown. By comparing the Glanville fritillary population living in the Åland Islands in northern Europe with a population in Nantaizi in China, within the source of the post-glacial range expansion, we identified candidate genes with reduced variation in Åland, potentially affected by selection under cooler climatic conditions than in Nantaizi. We conducted an association study of larval growth traits by genotyping the extremes of phenotypic trait distributions for 23 SNPs in 10 genes. Three genes in clip-domain serine protease family were associated with larval growth rate, development time and pupal weight. Additive effects of two SNPs in the prophenoloxidase-activating proteinase-3 (ProPO3) gene, related to melanization, showed elevated growth rate in high temperature but reduced growth rate in moderate temperature. The allelic effects of the vitellin-degrading protease precursor gene on development time were opposite in the two sexes, one genotype being associated with long development time and heavy larvae in females but short development time in males. Sexually antagonistic selection is here evident in spite of sexual size dimorphism.

Smoking and cognitive deficits in schizophrenia: a pilot study.

The cross-sectional study assessed the associations among smoking status, number of cigarettes smoked per day, and psychiatric symptoms in 88 chronic schizophrenic outpatients with a stable psychic condition. Among the 49 smokers, the number of cigarettes smoked per day was associated with the severity of cognitive symptoms of the Positive and Negative Syndrome Scale. The authors suggest that smoking may alleviate cognitive deficits in schizophrenia by increasing dopaminergic neurotransmission in the prefrontal areas of the brain.

Citalopram as an adjuvant in schizophrenia: further evidence for a serotonergic dimension in schizophrenia.

There is increasing evidence suggesting that symptoms of depression and anxiety may also be associated with serotonergic dysfunction in schizophrenic patients. The effect of the adjuvant selective serotonin reuptake inhibitor citalopram was assessed regarding the symptom dimensions of schizophrenia measured with the Positive and Negative Syndrome Scale (PANSS) and with the Hamilton Rating Scale for Depression (HRSD). Citalopram alleviated symptoms of the depression/anxiety dimension of the PANSS, but not the symptoms of the four other PANSS domains or depressive symptoms measured with the HRSD. The results support the hypothesis of a serotonergic dimension in schizophrenia.

Citalopram causes no significant alterations in plasma neuroleptic levels in schizophrenic patients.

Steady-state plasma concentrations of commonly used neuroleptic drugs were measured in 90 schizophrenic patients before and after adding placebo or citalopram (40 mg/day) to their treatment regimen. Plasma concentrations of citalopram and its main metabolite, desmethylcitalopram, were also measured. In addition, patients with exceptionally high neuroleptic levels or an increase in adverse effects during the 12-week study period were evaluated for their debrisoquine/sparteine hydroxylase (CYP2D6) genotype, an enzyme responsible for oxidative metabolism of several neuroleptics and selective serotonin re-uptake inhibitors. There were no significant changes in plasma concentrations of haloperidol, chlorpromazine, zuclopenthixol, levomepromazine, thioridazine or perphenazine during the study. Plasma concentrations of citalopram and desmethylcitalopram were well within the levels reported previously with monotherapy, and remained stable throughout the study. None of the 15 patients analysed for the CYP2D6 genotype was a poor metabolizer. It is concluded that clinically important pharmacokinetic drug interactions do not play a crucial role when citalopram is used as an augmentation therapy in neuroleptic-treated schizophrenic patients.

Effect of smoking on neuroleptics in schizophrenia.

OBJECTIVE: The effect of smoking on daily doses and plasma levels of neuroleptics prescribed for schizophrenic patients was studied. METHODS: 90 outpatients with schizophrenic disorder (DSM-III-R) who were on a stable regimen of psychotropic medication and showed a stable clinical state were included in a double-blind placebo-controlled trial. Data were collected and blood tests taken at the baseline interview. The plasma levels were obtained for 52 patients. RESULTS: Daily neuroleptic doses converted to chlorpromazine equivalents correlated significantly (r = 0.436) with the plasma levels of their unmetabolised fractions. The neuroleptic doses increased with age in smokers, while in nonsmokers they decreased. Neither sex, age nor smoking had a significant association with the neuroleptic plasma levels. CONCLUSIONS: Smoking seems to lead to increased neuroleptic dosages in postmenopausal schizophrenics by increasing hepatic metabolism and renal excretion of the drugs and possibly enhancing dopamine release. It is also possible that older smoking patients form a selected group of heavy smoker and they, therefore, need exceptionally high neuroleptic doses.

Citalopram as an adjuvant in chronic schizophrenia: a double-blind placebo-controlled study.

The effects of citalopram--the most selective serotonin reuptake inhibitor on the market--on psychopathological symptoms were studied in chronic schizophrenic patients on a stable regimen of neuroleptic medication. Outpatients suffering from schizophrenic disorder (DSM-III-R) with Positive and Negative Symptom Scale (PANSS) scores higher than 50 were included in a double-blind placebo-controlled add-on study. The daily dose of citalopram was 20 mg in the first week and 40 mg for the remaining period. A total of 90 patients (45 patients receiving citalopram and 45 receiving placebo) completed the 12-week trial. There were no changes in neuroleptic plasma levels during the trial. There was a significant decrease in total PANNS scores during the trial, although no statistically significant differences between the citalopram group and the placebo group were revealed. The number of responders in terms of severity of illness (CGI) was higher and the increase in subjective well-being (VAS) was greater in patients on citalopram than in those receiving placebo. There were no significant differences in the occurrence of side-effects. It is concluded that, in chronic schizophrenic out-patients, citalopram has no clear effect on the psychopathological symptoms; it may improve the general clinical condition, and it appears to increase the subjective well-being of these patients. Citalopram appears to be safe when used to treat schizophrenic patients who are receiving concomitant neuroleptic treatment.

Prediction of positive placebo response among chronic schizophrenic outpatients.

We undertook this study to determine whether predictors of positive placebo response in chronic schizophrenic outpatients could be identified. Twelve placebo responders and 33 placebo nonresponders who participated in a parallel-group, double-blind, 12-week clinical drug trial were compared. No significant differences between the groups were found with regard to 16 anamnestic and symptom variables. To investigate further which variables at baseline predicted positive placebo response, a stepwise linear regression model was created. Of the seven variables entered into the model, only high scores in the positive domain of the Positive and Negative Syndrome Scale (delusions, unusual thought content, grandiosity, and suspiciousness/persecution) at baseline predicted significantly positive placebo response (p = .0047). Because the onset of placebo response was gradual, the authors hypothesize that placebo response in chronic schizophrenia consists mainly of two ingredients: nonspecific psychotherapeutic effect caused by the several assessments carried out during the study, and regression toward the mean.