Serum proBDNF/BDNF and response to fluvoxamine in drug-naïve first-episode major depressive disorder patients.

BACKGROUND: We investigated the association between serum proBDNF, a precursor of brain-derived neurotrophic factor (BDNF), and response to fluvoxamine in patients with major depressive disorder (MDD) using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR): physically healthy and free of current alcohol or drug abuse, comorbid anxiety, or personality disorders. METHODS: Fifty-one patients with MDD (M/F, 19:32; age, 38 ± 19 years) and 51 healthy controls (M/F, 22:29; age, 34 ± 17 years) were studied using DSM-IV-TR: physically healthy and free of current alcohol or drug abuse, comorbid anxiety, or personality disorders. Serum levels of proBDNF and MDNF were measured by sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum mature BDNF levels in the MDD patients were significantly lower than those in the healthy controls (t = 3.046, p = 0.0018). On the other hand, no difference was found in serum proBDNF between the MDD patients and the healthy controls (t = -0.979, p = 0.833). A trend of negative correlation was found between baseline serum BDNF and baseline scores of the 17 items of the Hamilton Rating Scale for Depression (HAMD17) (r = -0.183, p = 0.071). No correlation was however found between HAMD17 scores and proBDNF at baseline (r = 0.092, p = 0.421). Furthermore, no correlation was observed between baseline HAMD17 scores and baseline proBDNF/BDNF (r = -0.130, p = 0.190). No changes were observed in serum levels of proBDNF and BDNF during the treatment periods. CONCLUSIONS: These results suggest that there is no association between serum proBDNF/BDNF and fluvoxamine response in MDD patients at least within 4 weeks of the treatment.

Stress at work alters serum brain-derived neurotrophic factor (BDNF) levels and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in healthy volunteers: BDNF and MHPG as possible biological markers of mental stress?

There is growing evidence that blood levels of brain-derived neurotrophic factor (BDNF) and catecholamine, and cytokines are related to not only to depressive, suicidal, and anxious states but also to depression-associated personality traits. Psychological job stress is well known to lead to symptoms of depression and anxiety. In the present study, we examined effects of psychological job stress on serum levels of BDNF and plasma levels of catecholamine metabolites, and cytokines in healthy volunteers (n=106, male/female=42/64, age=36+/-12 yr) working in a hospital setting. The values (mean+/-SD) of scores for stress items in the Stress and Arousal Check List (s-SACL), plasma MHPG levels, and, serum BDNF levels in all participants were 7.2+/-3.3, 5.2+/-3.4 ng/mL, and 23.3+/-14.7 ng/mL, respectively. A negative correlation was found between scores for s-SACL and serum BDNF levels (rho=-0.211, p=0.022). A positive correlation was also found between scores on the s-SACL and plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) (rho=0.416, p=0.01), but not homovanillic acid (HVA). No relationship was found between s-SACL scores and plasma levels of interleukin-6 (IL-6) or tumor necrosis factor alpha (TNFalpha). These results suggest that serum BDNF levels and plasma MHPG levels might be biological markers reflective of psychological job stress in hospital employees.

Two cases of burning mouth syndrome treated with olanzapine.

Two case reports of patients suffering from burning mouth syndrome (BMS), a type of somatoform disorder, who were treated with olanzapine are discussed. One case was a 54-year-old female with BMS who failed to respond to milnacipran treatment. Olanzapine (2.5 mg/day) brought about dramatic improvement in the patient's symptoms, and thereafter milnacipran withdrawal further eliminated her symptoms. The second case was a 51-year-old male with BMS who failed to respond to paroxetine treatment. Olanzapine (2.5 mg/day) was added to the treatment regimen and increased to 5.0 mg/day the following week. The patient noted a reduction in symptoms and continued to live normally thereafter without experiencing severe symptoms. These findings suggest that olanzapine may be useful in the treatment of BMS.

Effects of paroxetine or milnacipran on serum brain-derived neurotrophic factor in depressed patients.

Brain-derived neurotrophic factor (BDNF) is an important member of the neurotrophin family of growth factors, abundant in the brain and periphery. Researchers have reported that serum BDNF levels in drug-free depressed patients are lower than those of healthy controls, and have proposed that these low levels might reflect a failure of neuronal plasticity in depression. In the present study, we investigated the effects of paroxetine, an SSRI, and milnacipran, an SNRI, on serum BDNF levels in depressed patients. Serum levels of BDNF were measured by ELISA before, 4 weeks, and 8 weeks after the start of treatment with antidepressants. Forty-two patients were randomly administered paroxetine (21 cases) or milnacipran (21 cases). A negative correlation was found between serum BDNF levels and baseline Ham-D scores. The response and remission rates for each drug were not significantly different. Serum BDNF levels in responders were significantly increased 2.6- and 1.8-fold 8 weeks after treatment with paroxetine or milnacipran, respectively. These results suggest that both drugs improve the depressive state by increasing BDNF levels.

Treatment with risperidone for 4 weeks increased plasma 3-methoxy-4-hydroxypnenylglycol (MHPG) levels, but did not alter plasma brain-derived neurotrophic factor (BDNF) levels in schizophrenic patients.

In the present study, we investigated the effects of risperidone treatment for 4 weeks on plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and brain-derived neurotrophic factor (BDNF) in 89 schizophrenic patients. We also compared the plasma levels of BDNF and MHPG between the schizophrenic group and 103 sex-and age-matched normal controls. In addition, we investigated the effects of two SNPs of the noradrenaline transporter (NAT) gene on plasma levels of MHPG, BDNF, and clinical improvement. The mean dose of risperidone was 3.8+/-1.4 mg/day. We demonstrated that treatment with risperidone increased plasma MHPG levels, and this increase was associated with an improvement of the negative symptoms of schizophrenia. In contrast, plasma BDNF did not change after 4 weeks of risperidone treatment, and the two SNPs in NAT did not influence the response to risperidone treatment or plasma MHPG and BDNF levels. These results suggest that the enhancement of noradrenergic neurons by risperidone, which occurs independently of the two SNPs of NAT, plays a role in the clinical efficacy of the drug.

No alterations of brain GABA after 6 months of treatment with atypical antipsychotic drugs in early-stage first-episode schizophrenia.

We investigated the effects of atypical antipsychotic drugs on GABA concentrations in early-stage, first-episode schizophrenia patients. Sixteen (8 males, 8 females; age, 30±11 years old) patients were followed up for six months. We also included 18 sex- and age-matched healthy control subjects. All patients were treated with atypical antipsychotic drugs (5 patients with risperidone, 5 patients with olanzapine, 4 patients with aripiprazole, and 2 patients with quetiapine). In all three regions measured (frontal lobe, left basal ganglia, and parieto-occipital lobe), no differences in GABA concentrations were observed in a comparison of pre-treatment levels and those six months after treatment. These results suggest that relatively short-term treatment with atypical antipsychotic drugs may not affect GABAergic neurotransmission; however, it is also possible that such treatment prevents further reductions in brain GABA levels in people with early-stage, first-episode schizophrenia.

Blood levels of catecholamine metabolites and brain-derived neurotrophic factor in a case of Sydenham's chorea.

We report a case of Sydenham's chorea with neuropsychiatric symptoms who was successfully treated with low-dose risperidone. We also longitudinally investigated serum BDNF levels and plasma levels of catecholamine metabolite in the patient. Serum BDNF levels were increased and plasma levels of HVA and MHPG were decreased according to the recovery from the active phase of the disease. These results suggest that dysfunctions of catecholaminergic neurons and neurotrophic factors might exist in Sydenham's chorea, and the decreasing catecholamine activities in response to risperidone might be associated with the improvement of the disease.

Effects of acute paroxetine treatment on the consumption of cigarette smoking and caffeine in depressed patients.

In the present study, we examined the effects of acute treatment with paroxetine on the consumption of cigarette smoking and caffeine in 65 patients who met the DSM-IV criteria for major depressive disorder (M/F: 28/37, age: 48 +/- 15 years). Plasma levels of cotinine or caffeine were analysed using high-performance liquid chromatography (HPLC). The amount of cigarette smoking and plasma levels of cotinine, but not caffeine, decreased 4 weeks after paroxetine treatment. There was no difference between smokers and nonsmokers with respect to their response to paroxetine treatment. In addition, plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in responders to paroxetine treatment was higher than those in nonresponders, and there was a negative correlation between the changes in plasma MHPG levels and the changes in Hamilton rating scale for depression (Ham-D) scores before and 4 weeks after paroxetine administration. These results suggest that paroxetine has the potential to reduce the amount of cigarette smoking in depressed smokers, and we reconfirmed our previous results that depressed patients with higher plasma MHPG levels had better response to paroxetine treatment than those with lower plasma MHPG levels using larger depressed samples.