Masamichi Ishioka

Dietary patterns are associated with obesity in Japanese patients with schizophrenia

BackgroundObesity among patients with schizophrenia is a growing concern because being overweight is widely regarded as a major risk factor for cardiovascular disease and premature death. Dietary patterns have been suggested as one modifiable factor that may play a role in development of obesity. The objective of this study was to examine the association between dietary patterns and obesity among patients with schizophrenia in Japan.MethodsWe recruited patients (n = 338) aged 44.0 ± 13.2 (mean ± SD) years with a DSM-IV diagnosis of schizophrenia who were admitted to four psychiatric hospitals using a cross-sectional design. Diet was assessed with a validated brief-type self-administered diet history questionnaire (BDHQ). Dietary patterns from 52 predefined food groups were extracted by principal component analysis.ResultsA total of 61 subjects (18.0%) were classified as obese. Three dietary patterns were identified: the healthy dietary pattern, the processed food dietary pattern, and the alcohol and accompanying dietary patterns. After adjusting for age and gender, patients within the high tertile of each healthy dietary pattern (OR = 0.29, 95% CI = 0.13 to 0.62) and processed food dietary pattern (OR = 0.44, 95% CI = 0.22 to 0.89) had a significantly lower risk for obesity compared with low tertile of dietary pattern.ConclusionsOur findings suggest that dietary patterns, including higher intake of protein, fat, n-3 polyunsaturated fatty acids, n-6 polyunsaturated fatty acids, and vitamins, may be related to a decreased prevalence of obesity within patients with schizophrenia. Future longitudinal research exploring dietary patterns and obesity among patients with schizophrenia is warranted.

Preanalysis Storage Conditions Influence the Measurement of Brain-Derived Neurotrophic Factor Levels in Peripheral Blood

Background: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a pivotal role in regulating neuronal function throughout life, and this factor is regarded as a potential biomarker of mental disorders. However, previous studies have suggested that plasma BDNF levels are more variable than serum BDNF levels. Methods: We determined the influence of time and temperature on the measurement of peripheral blood BDNF levels. Blood samples were aliquoted into four types of tubes, including tubes containing heparin, ethylenediaminetetraacetic acid (EDTA), and citrate for plasma, and anticoagulant-free tubes for serum. The samples were stored at 4 or 25°C for 0, 1, 2, 4, 6, 24 or 48 h, and the plasma and serum BDNF levels were measured using enzyme-linked immunosorbent assay. Results: There were interindividual and interanticoagulant compound variability in the plasma BDNF levels. The measured plasma BDNF levels increased over time, whereas the serum BDNF levels remained unchanged. Furthermore, the BDNF levels detected in plasma stored in heparin tubes at 4°C and those for samples stored in EDTA tubes at 25°C were much higher than those of the other samples. Conclusion: This study indicates that measurements of plasma BDNF levels are dependent not only on the anticoagulant compounds but also on the storage time and temperature conditions used after blood sampling.

Interaction between paliperidone and carbamazepine.

Background: This aim of this study was to determine the impact of carbamazepine on the pharmacokinetics of paliperidone. Methods: Six schizophrenic patients initially received a 6–12 mg/d dose of paliperidone alone. Subsequently, a 200 mg/d dose of carbamazepine was administered, and the carbamazepine dose was increased to 400 mg/d and then 600 mg/d. Plasma concentrations of paliperidone before and after carbamazepine coadministration were quantified using liquid chromatography tandem mass spectrometry (LC–MS/MS). Results: Carbamazepine significantly reduced the plasma concentration of paliperidone. The plasma concentration of paliperidone at baseline and with coadministration of 200, 400, and 600 mg/d were 45.8 ± 11.7, 26.9 ± 13.7, 17.1 ± 8.2, and 15.9 ± 7.6 ng/mL, respectively. The concentration of paliperidone with carbamazepine coadministration at doses of 200, 400, and 600 mg/d were 55.7% ± 20.7%, 36.1% ± 12.2%, and 33.6% ± 10.4%, respectively, of baseline. This effect occurred even at the carbamazepine dose of 200 mg/d and reached a plateau at doses higher than 400 mg/d. However, carbamazepine coadministration exacerbated the psychotic symptoms in some patients. Conclusions: The results of the present study suggest that adjunctive treatment with carbamazepine reduces the concentration of paliperidone in a dose-dependent manner, most likely because of the induction of several drug-metabolizing enzymes and several drug transporters.

Association between plasma brain-derived neurotrophic factor levels and personality traits in healthy Japanese subjects

Although depression has been associated with decreased brain-derived neurotrophic factor (BDNF) levels for specific personality traits, there is a little information regarding the association between peripheral BDNF levels and such traits. The sample consisted of 178 healthy Japanese subjects (age range, 37.4 ± 11.5 years). All subjects filled out the Temperament and Character Inventory (TCI). Plasma BDNF levels were measured using the enzyme-linked immunosorbent assay. A simple regression analysis revealed that plasma BDNF levels were significantly correlated with harm avoidance (r=-0.177, p=0.018) and self-directedness scores (r=0.165, p=0.028). Our findings suggest that plasma BDNF levels are associated with depression-related personality traits.

Neuroleptic Malignant Syndrome Induced by Lamotrigine

This case report describes a 54-year-old man with bipolar I disorder who was treated with aripiprazole (ARP) and lithium. The patient was admitted to our hospital because of aggravation of depressive symptoms, and treatment with lamotrigine (LTG) was initiated. Two weeks after admission, we discontinued administration of ARP after the appearance of a tremor. Three weeks after discontinuing ARP, the patient developed a high fever, rigidity of the arms, diarrhea, dysphagia, and diaphoresis. We suspected these symptoms were consistent with neuroleptic malignant syndrome and therefore removed the application of LTG. After 2 days, most of the patients symptoms and blood results had improved, leading us to conclude that the LTG treatment had induced neuroleptic malignant syndrome. Thus, the purpose of this case report was to warn psychiatrists against therapy with LTG, as it may be conducive to neuroleptic malignant syndrome.

Therapeutic reference range for plasma concentrations of paroxetine in patients with major depressive disorders.

Background: We investigated the relationship between plasma concentrations of paroxetine and the therapeutic effect of the drug, and we evaluated the therapeutic reference range for plasma concentration of paroxetine in patients with major depressive disorders (MDD). Methods: In this study, 120 patients with MDD were treated with 10–40 mg/d of paroxetine for 6 weeks, and 89 patients completed the protocol. The Montgomery–Asberg Depression Rating Scale (MADRS) was used to evaluate the patients at 0, 1, 2, 4, and 6 weeks. At the 6-week treatment time point, the patients were divided into 7 groups according to their paroxetine plasma concentrations in increments of 20 ng/mL. We used an analysis of variance and a &khgr;2 test to define the therapeutic reference range for plasma paroxetine concentrations. Results: We used 50% as the cutoff values for the percentage of MADRS improvement to determine the responder rates, and we defined remitters as patients with MADRS scores <10 at the 6-week treatment time point. We analyzed the responder and remitter rates of the patients according to their plasma paroxetine concentrations: 20 ng/mL, 40 ng/mL, and 60 ng/mL using the &khgr;2 test. According to the results of the &khgr;2 test in the responder rates, the 20–60 ng/mL plasma paroxetine group showed the highest effect size. Conclusions: The results of this study suggested that a range of 20–60 ng/mL is the therapeutic reference range for concentrations of paroxetine in plasma in patients with MDD.

Hyperprolactinemia during antipsychotics treatment increases the level of coagulation markers

Objective The strong association between psychiatric patients who receive antipsychotics and the incidence of venous thromboembolism (VTE) is known. Although previous reports suggest that hyperprolactinemia often increases markers of activated coagulation, few studies have examined the direct relationship between the prolactin level elevated by antipsychotics and activated markers of activated coagulation. Method The participants included 182 patients with schizophrenia (male =89, female =93) who received antipsychotic treatments for at least 3 months. Markers of VTE (D-dimer, fibrin/fibrinogen degradation products, and thrombin–antithrombin complex) and serum prolactin concentrations were measured. Results Prolactin levels were significantly correlated with the logarithmic transformation of the D-dimer (r=0.320, P=0.002) and fibrin/fibrinogen degradation product levels (r=0.236, P=0.026) but not of the thrombin–antithrombin complex level (r=0.117, ns) among men. However, no correlations were found between the VTE markers and prolactin levels among women. These results were confirmed using multiple regression analyses that included demographic factors and antipsychotic dosages. Conclusion The current study indicates that hyperprolactinemia is associated with an increase in markers of activated coagulation among men receiving antipsychotics. This finding clinically implies that monitoring and modulating prolactin levels among men are important to decrease the risk of VTE.

An investigation of temperament and character inventory items for predicting the response to paroxetine treatment in patients with major depressive disorder.

BACKGROUND Previous studies have reported associations between Temperament and Character Inventory (TCI) dimension scores and the response to treatment in patients with major depressive disorder (MDD). We aimed to determine which TCI items could predict the response to treatment with paroxetine in patients with MDD. METHODS Seventy-three patients were enrolled in this study. The participants were treated with 10-40mg/day of paroxetine for six weeks; they then completed the TCI. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate the patients. The participants were divided into two groups (responders and non-responders). We used a chi-squared test to identify the 10 items with the strongest association with treatment response from among all 240 items on the TCI, and we used a multiple logistic regression analysis to confirm the validity of these 10 items. RESULTS Among the TCI dimension scores, only the C score differed significantly between the two groups. We analyzed 10 models using each of the 10 best items. All the models significantly predicted treatment response. The TCI dimensions model also significantly predicted treatment response, but its predictive value was lower than those of the other 10 models. LIMITATIONS The responders included the early responders. The results lacked information about responders whose responses were not predicted by the logistic regression models and TCI items. CONCLUSIONS Some TCI items showed significant associations with the response to paroxetine treatment in the patients with MDD. Treatment response in patients with MDD may be predicted using only 10 items from the TCI.

Glutathione S-transferase K1 genotype and overweight status in schizophrenia patients: A pilot study

Elevated oxidative stress in mitochondria and mitochondrial dysfunction are associated with weight gain in schizophrenia (SCZ) patients. Glutathione S-transferase kappa 1 (GSTK1) protects cells against exogenous and endogenous oxidative stress in the mitochondria. This exploratory study investigated the possible effects of a common GSTK1 polymorphism (rs1917760, G-1308T) on the risk for overweight status among 329 SCZ patients and 305 age- and gender-matched controls and on the GSTK1 mRNA level in peripheral blood mononuclear cells among 14 SCZ patients. The GSTK1 T/T genotype was associated with having a higher BMI value among SCZ male patients, whereas this genotype tended to be associated with a lower BMI value among female patients. Conversely, these associations were not observed among the controls. The GSTK1 T/T genotype was associated with decreased GSTK1 mRNA level among SCZ patients. The GSTK1 T/T genotype may be a novel risk factor for the prediction of overweight status in SCZ male patients, although the results of this pilot study should be verified by a larger study.

Characteristics of Escitalopram Discontinuation Syndrome: A Preliminary Study.

BackgroundAntidepressant discontinuation syndrome (ADS) frequently occurs in patients who undergo an abrupt discontinuation of their antidepressant medication. MethodsWe evaluated 25 consecutive outpatients with depression who discontinued their use of escitalopram. The presence of ADS was evaluated according to the Antidepressants Discontinuation Syndrome checklist. ResultsAntidepressant discontinuation syndrome was observed in 14 of 25 patients. Frequent symptoms were dizziness (44%), muscle tension (44%), chills (44%), confusion or trouble concentrating (40%), amnesia (28%), and crying (28%). The treatment doses and plasma concentrations of escitalopram were significantly higher in patients with ADS than in patients without ADS. No group differences were observed regarding age, sex, or duration of escitalopram treatment before the discontinuation. ConclusionsThese findings suggest that a higher dose and lower clearance of escitalopram lead to a higher risk of ADS. Very slow tapering is recommended for all patients.