Kiyokazu Atake

Aripiprazole altered plasma levels of brain-derived neurotrophic factor and catecholamine metabolites in first-episode untreated Japanese schizophrenia patients.

We investigated the effects of aripiprazole on plasma levels of brain‐derived neurotrophic factor (BDNF) and catecholamine metabolites in first‐episode untreated schizophrenia patients.

Serum levels of brain-derived neurotrophic factor (BDNF), BDNF gene Val66Met polymorphism, or plasma catecholamine metabolites, and response to mirtazapine in Japanese patients with major depressive disorder (MDD)

OBJECT We investigated an association between the polymorphism of brain-derived neurotrophic factor (BDNF) gene Val66Met and the response to mirtazapine in Japanese patients with major depressive disorder (MDD). We also examined mirtazapines effects on the serum BDNF and plasma levels of catecholamine metabolites in these patients. METHODS Eighty-four patients who met the DSM-IV-TR criteria for MDD were treated with only mirtazapine for 4 weeks. The BDNF Val66Met polymorphism was detected by direct sequencing in the region, and serum BDNF levels and plasma levels of catecholamine metabolites were measured by ELISA and HPLC-ECD, respectively. RESULTS Mirtazapine treatment for 4 weeks significantly increased serum BDNF levels in the responders, whereas nonresponders showed significant decreases. No association was found between either of the two genotypes (Val/Val vs. Met-carriers) and the response to mirtazapine at T4 or the serum BDNF levels at T0. Mirtazapine did not alter the plasma levels of homovanillic acid (HVA) or 3-methoxy-4-hydroxyphenylglycol (MHPG). Discussion The dynamics of serum BDNF levels, but not plasma levels of HVA and MHPG, reflect the response to mirtazapine treatment; the BDNF Val66Met polymorphism in patients with depression is, however, associated with neither a particular response to mirtazapine treatment nor baseline serum BDNF levels. CONCLUSION Serum BDNF levels, but not plasma levels of HVA or MHPG, and BDNF Val66Met polymorphism are related to the mirtazapine response in MDD.

Plasma levels of brain-derived neurotrophic factor and interleukin-6 in patients with dysthymic disorder: comparison with age- and sex-matched major depressed patients and healthy controls

In the present study, we investigated the serum BDNF levels and plasma IL‐6 levels in patients with dysthymic disorder, major depressive disorder and control subjects. Eighteen patients who met the DSM‐IV criteria (American Psychiatric Association, 1994) for dysthymic disorder (male/female: 5/13; age: 36 ± 9 year) and 20 patients (male/female: 7/13; age: 38 ± 10 year) who met the criteria for major depressive disorder were enrolled. The serum BDNF levels in patients with dysthymic and major depressive disorder were significantly lower than those in the control subjects. However, no difference was found between the dysthymic group and major depression group. The plasma IL‐6 levels in the dysthymic group and major depression group were significantly higher than those in the control group. No difference was observed in the plasma IL‐6 levels between the dysthymic group and major depression group. These results suggest that the pathophysiology of dysthymic disorder and major depression might be similar in terms of the blood levels of BDNF and IL‐6. Copyright

Abnormal White Matter Integrity in the Corpus Callosum among Smokers: Tract-Based Spatial Statistics

In the present study, we aimed to investigate the difference in white matter between smokers and nonsmokers. In addition, we examined relationships between white matter integrity and nicotine dependence parameters in smoking subjects. Nineteen male smokers were enrolled in this study. Eighteen age-matched non-smokers with no current or past psychiatric history were included as controls. Diffusion tensor imaging scans were performed, and the analysis was conducted using a tract-based special statistics approach. Compared with nonsmokers, smokers exhibited a significant decrease in fractional anisotropy (FA) throughout the whole corpus callosum. There were no significant differences in radial diffusivity or axial diffusivity between the two groups. There was a significant negative correlation between FA in the whole corpus callosum and the amount of tobacco use (cigarettes/day; R = − 0.580, p = 0.023). These results suggest that the corpus callosum may be one of the key areas influenced by chronic smoking.

Plasma levels of interleukin-6 and selective serotonin reuptake inhibitor response in patients with major depressive disorder

We investigated the plasma levels of interleukin (IL)‐6 and 5‐HTT polymorphisms in patients with major depressive disorder (MDD). This is the first report, to our knowledge, of an investigation into the association between 5‐HTT gene polymorphism, plasma IL‐6 levels, and responses to selective serotonin reuptake inhibitors (SSRIs) in Japanese patients with MDD.

Switching to antipsychotic monotherapy can improve attention and processing speed, and social activity in chronic schizophrenia patients

OBJECTIVE This study sought to examine whether switching polypharmacy therapy to monotherapy would improve the cognitive function and social function of patients with schizophrenia. METHODS Thirty-nine patients with schizophrenia who were receiving therapy with two antipsychotics were randomly divided into a switch to monotherapy group (switching group) and a polypharmacy continued group (continuing group). For the patients allocated to the switching group, the dose level of one of the two antipsychotic drugs was gradually reduced to zero. Psychotic symptoms, cognitive function and social function scale scores were assessed immediately before and 24 weeks after switching, and the time courses of these scores were compared between the two groups. RESULTS Compared with the continuing group, the switching group demonstrated significantly greater improvement in attention after switching (p = 0.02). Furthermore, the improvement in daily living (p = 0.038) and work skills (p = 0.04) was significantly greater in the switching group. In an analysis of the correlation among sub-items with respect to the degrees of improvement, a significant correlation was noted between improvement in executive function and improvement in daily living (r = -0.64, p = 0.005) and between improvement in work skills and improvement in attention (r = -0.51, p = 0.038). CONCLUSION In patients with schizophrenia receiving polypharmacy, switching to monotherapy resulted in improvements in attention. Furthermore, improvements in executive function led to improvements in daily living, and improvements in attention led to improvements in work skills. Thus, switching to monotherapy is a useful option.

Relationships between serum brain-derived neurotrophic factor, plasma catecholamine metabolites, cytokines, cognitive function and clinical symptoms in Japanese patients with chronic schizophrenia treated with atypical antipsychotic monotherapy

Abstract Objectives: Catecholamines, brain-derived neurotrophic factor (BDNF) and cytokines may be involved in the pathophysiology of schizophrenia. The aim of this study was to examine the associations between serum BDNF levels, plasma catecholamine metablolites, cytokines and the cognitive functions of patients with schizophrenia treated with atypical antipsychotic monotherapy. Methods: One hundred and forty-six patients with schizophrenia and 51 age- and sex-matched healthy controls were examined for peripheral biological markers and neurocognitive test. Results: There were positive correlations between serum BDNF levels and scores for verbal memory and attention and processing speed as well as between serum BDNF levels and negative symptoms. Furthermore, there was a negative correlation between the plasma homovanillic acid (HVA) level and motor function and a positive correlation between the plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) level and attention and processing speed. There were no significant correlations between interleukin-6 or tumour necrosis factor alpha and cognitive function. Moreover, there were no significant correlations between the plasma levels of HVA, MHPG, cytokines and clinical symptoms. Conclusions: Serum BDNF levels are positively related to the impairment of verbal memory and attention, plasma HVA levels are positively related to motor function, and plasma MHPG levels are positively related to attention in patients with schizophrenia.

Serum Levels of Brain-Derived Neurotrophic Factor at 4 Weeks and Response to Treatment with SSRIs

Objective It is important to predict a response to an antidepressant in early time after starting the antidepressant. We previously reported that serum brain-derived neurotrophic factor (BDNF) levels in responders to treatment with antidepressants were increased, whereas, those in nonresponders were not. Therefore, we hypothesized that the changes in serum levels of BDNF from baseline (T0) to 4 weeks (T4) after treatment with selective serotonin reuptake inhibitors (SSRIs) predict the response to the treatment at 8 weeks (T8) in depressed patients. To confirm the hypothesis, we measured serum BDNF at T0, T4, and T8 during the treatment with SSRIs (paroxetine, sertraline, and fluvoxamine). Methods One hundred fifty patients (M/F; 51/99, age; 50.4±15.1 years) met major depressive disorder (MDD) using by DSM-IV-TR enrolled in the present study. We measured serum BDNF concentrations at T0, T4, and T8 in patients with MDD treated with SSRIs. Results The changes in serum BDNF, age, sex, dose of SSRIs, and HAMD-17 score did not predict the response to SSRIs at T8. Conclusion These results suggest that the changes in serum BDNF levels from T0 to T4 could not predict the subsequent responses to SSRIs at T8.

Relationships between brain-derived neurotrophic factor, clinical symptoms, and decision-making in chronic schizophrenia: data from the Iowa Gambling Task.

The levels of brain-derived neurotrophic factor (BDNF) are significantly decreased in patients with schizophrenia and correlate with impairments in cognitive function. However, no study has investigated the relationship between the serum BDNF levels and decision-making. We compared patients with schizophrenia to healthy controls with respect to their decision-making ability and serum BDNF levels. Eighty-six chronic schizophrenia patients and 51 healthy controls participated in this study. We controlled for gender, age, and estimated intelligence quotient (IQ), and we investigated the differences in decision-making performance on the Iowa Gambling Task (IGT) between the schizophrenia patient and control groups. We also compared the IGT scores, the serum BDNF levels, and the clinical symptoms between the groups. The IGT scores of the schizophrenia patients were lower than those of the controls. A negative correlation was detected between the mean net scores on the trials in the final two blocks and the serum BDNF levels (p < 0.05). Multiple regression analysis revealed that depressive symptoms and the serum BDNF levels were significantly associated with the mean net scores on the trials in the final two blocks. Based on these results, impaired sensitivity to both reward and punishment is associated with depressive symptoms and reduced serum BDNF levels in chronic schizophrenia patients and may be related to their poor performance on the IGT.

Catechol-O-methyltransferase Val158Met genotype and the clinical responses to duloxetine treatment or plasma levels of 3-methoxy-4-hydroxyphenylglycol and homovanillic acid in Japanese patients with major depressive disorder.

Purpose This study investigated the relationships among the plasma levels of catecholamine metabolites, the clinical response to duloxetine treatment, and Val158Met polymorphism of the catechol-O-methyltransferase (COMT) gene. Subjects and methods Sixty-four patients and 30 healthy control subjects were recruited. Major depressive episodes were diagnosed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. The severity of depression was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD17). Patients whose HAMD17 scores were 15 or greater were enrolled in the study. Blood sampling and clinical evaluation were performed at week 0 and week 8. The levels of plasma catecholamine metabolites were measured using high-performance liquid chromatography with electrochemical detection. Genotyping was performed using direct sequencing. Results Thirty of 45 patients (67%) responded to duloxetine treatment during the 8 weeks of treatment. The baseline plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG), but not homovanillic acid (HVA), were lower in patients with major depressive disorder (MDD) who had the Val/Val genotype than in patients who were Met-carriers. Patients with MDD and the Val/Val genotype, but not Met carriers, had increased plasma levels of MHPG after 8 weeks of duloxetine treatment. The baseline plasma MHPG levels in healthy control subjects with the Val/Val genotype were significantly higher than those in patients with MDD. Among the subjects in the MDD group with the Val/Val genotype, the plasma MHPG levels increased to the same degree as in the healthy control subjects with the Val/Val genotype after 8 weeks of duloxetine treatment. Conclusion The relationship among the COMT Val158Met polymorphism, plasma levels of catecholamine metabolites, and responses to duloxetine is complex. Nevertheless, our results suggest that patients with MDD and the Val/Val genotype are more sensitive to the influence of noradrenergic neurons by duloxetine treatment.