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.

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

OBJECTIVE: 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. METHOD: One-hundred and eighteen patients (51 male, 67 female) who met the DSM-IV criteria for MDD were enrolled. Their ages ranged from 24 to 78 (mean ± SD = 44 ± 12) years. The patients were treated with SSRIs (paroxetine in 66 cases, sertraline in 42 cases) for 8 weeks. RESULTS: The plasma levels of IL-6 were significantly higher in the SSRI responders than in the nonresponders (p = 0.0328), and the changes in plasma IL-6 levels correlated significantly with the changes in severity of depressive state (p = .0.007). No difference was found in baseline and the changes in plasma IL-6 levels between the patients with a 5-HTT gene (5-HTTLPR) L-carrier and those with S/S. CONCLUSION: These results suggest that the plasma levels of IL-6 reflect the severity of MDD and that plasma IL-6 levels might be another biological-state marker for the depressive state. In addition, the 5-HTTLPR polymorphism might be independent of plasma IL-6 levels.

Plasma catecholamine metabolite levels and the activities of psychiatric symptoms in systemic lupus erythematosus.

OBJECTIVES: Neuropsychiatric systemic lupus erythematosus (NPSLE) is accompanied by neurological or psychiatric symptoms that can be severe. We hypothesized plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) levels were the biological marker that reflected the severity of the NPSLE psychiatric symptoms, and we examined MHPG and HVA levels in systemic lupus erythematosus (SLE) patients. METHODS: The participants were 42 healthy volunteers and 41 SLE patients. SLE patients were divided into the three groups: NPSLE with psychiatric symptoms (NP group), NPSLE without psychiatric symptoms (NN group), and SLE without neuropsychiatric symptoms (S group). All blood samples were drawn before (T0) and after 4 weeks of treatment (T4) in all SLE patients, and once in the healthy volunteers. Plasma levels of MHPG and HVA were analyzed using high-performance liquid chromatography. RESULTS: Plasma MHPG levels at T0 were significantly increased in the SLE compared to those in healthy volunteers. The NN group had the greatest increase compared with other SLE patient groups. There were no significant differences in plasma HVA levels at T0 between the four groups, and there was also no difference in MHPG and HVA plasma levels between T0 and T4. CONCLUSION: Hyperactivity of noradrenergic neurons and/or sympathetic nerves might be involved in SLE pathophysiology.

The effects of a walking intervention on depressive feelings and social adaptation in healthy workers.

The effects of walking on mental health problems among healthy Japanese workers are not fully understood. In the present study, we investigated the effects of a four-week walking program on the psychological functioning of a nonclinical sample of healthy workers in Japan.A total of 606 healthy subjects were enrolled in the study and were evaluated by the Zung Self-rating Depression Scale (SDS) and the Social Adaptation Self-evaluation Scale (SASS) both before and after the walking program.The subjects were divided into an exercising group and a non-exercising group.There were significant differences in the SDS and SASS scores between the exercising and the non-exercising groups.Following the walking program, the non-exercising group's SDS scores decreased and their SASS scores increased compared to before the walking program.In contrast, the SDS and SASS scores of the exercising group did not change.These results suggest that subjects who exercise regularly experience fewer depressive feelings and exhibit better social adaptation in the workplace than those who do not exercise.The walking program improved depressive feelings and social adaptation in the non-exercising group.

Plasma levels of metabolites of catecholamine in nicotine-dependent patients treated with varenicline.

INTRODUCTION: Our hypothesis is that varenicline decreases the plasma levels of catecholamine metabolites; such a decrease is associated with the main mechanisms of smoking cessation and leads to a depressive state. To confirm the hypothesis, we investigated the association of plasma homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in patients with nicotine dependence in comparison with nonsmokers. METHODS: To confirm the hypothesis, we investigated the association of plasma HVA and MHPG levels in patients with nicotine dependence in comparison with nonsmokers. In addition, we also examined the plasma HVA and MHPG levels before (T0) and 8 weeks after the varenicline treatment (T8). RESULTS: Seventeen of 20 smokers (85.0%) stopped smoking during the 12 weeks of treatment. Plasma HVA levels and MHPG levels in the patients at T0 (HVA 5.1 ± 2.1 ng/ml, MHPG 2.2 ± 0.6 ng/ml) were significantly higher than those of the control group (HVA 3.0 ± 1.0 ng/ml, MHPG 1.6 ± 1.4 ng/ml; HVA p = .0012, MHPG p = .0069). In this study, the plasma HVA and MHPG levels were not changed after treatment with varenicline, although the smokers had already quit. CONCLUSIONS: These results suggest that varenicline sustains higher catecholamine levels. The findings that the treatment with varenicline did not decrease the plasma levels of catecholamine metabolites can explain why none of the smokers had become depressed after the varenicline treatment.

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 mirtazapine's 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.

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

OBJECTIVE: We investigated the effects of aripiprazole on plasma levels of brain-derived neurotrophic factor (BDNF) and catecholamine metabolites in first-episode untreated schizophrenia patients. METHODS: The subjects were 50 Japanese first-episode untreated schizophrenia patients who met the Diagnostic and Statistical Manual of Mental Disorders Text Revision criteria and were treated with aripiprazole monotherapy. Twenty-nine were males, and 21 were females. The age ranged from 21 to 42 years (mean ± SD; 30.8 ± 5.3 years). Plasma BDNF and catecholamine metabolites were measured by ELISA and HPLC, respectively. Psychiatric symptoms were evaluated using by Positive and Negative Syndrome Scale. RESULTS: Treatment with aripiprazole for 8 weeks significantly increased plasma BDNF levels. It also changed plasma levels of homovanillic acid and 3-methoxy-4-hydroxyphenylglycol. A negative correlation was also observed between duration of psychosis and plasma BDNF levels. No correlation was observed however between plasma BDNF levels and the dose of aripiprazole. CONCLUSIONS: To the best of our knowledge, this is the first report showing that aripiprazole increases plasma BDNF levels in first-episode untreated schizophrenia patients. Furthermore, the BDNF Val66Met polymorphism was independent of the response to aripiprazole.

Several prescription patterns of antipsychotic drugs influence cognitive functions in Japanese chronic schizophrenia patients.

OBJECTIVE: We hypothesized that an excessive dose of antipsychotic drug and/or a larger number of antipsychotic drug worsens cognitive functions in schizophrenia patients. To confirm the hypothesis, we compared several cognitive functions in the patients taking a second-generation antipsychotic drug (SGA) only (SGA monotherapy group) with those in patients taking more than two kinds of antipsychotic drugs (polypharmacy group). METHODS: The cognitive functions of 136 chronic schizophrenia patients were evaluated using the Brief Assessment of Cognition in Schizophrenia, Japanese-language version (BACS-J). RESULTS: A significantly negative correlation was found between the composite score in the BACS-J and the chlorpromazine equivalence of doses of antipsychotic drugs in whole patients (r = -0.43, P < 0.001). Schizophrenia patients in the polypharmacy group had lower composite scores than those in the SGA monotherapy group in the BACS-J. No difference was observed in the composite score and the primary score in each item in the BACS-J between patients with first- plus second-generation antipsychotic drug (FGA + SGA group) and those with two kinds of SGA (SGA + SGA group). CONCLUSION: These results suggest that an excessive dose of antipsychotic drugs regardless of FGA and SGA might cause the deterioration of cognitive functions in chronic Japanese schizophrenia patients.

Erythema annulare centrifugum associated with herpes zoster.

Erythema annulare centrifugum (EAC) presents as erythematous or urticarial papules, each with an annular shape, that exhibit peripheral extension. Internal malignancies are occasionally associated with EAC, and infectious diseases, including fungal, bacterial or viral infections, have also been regarded as possible causes of EAC. A 35-year-old man had a 1-week history of a painful vesicular eruption over the trunk corresponding to dermatomes Th8-10. Concomitantly, he developed several annular eruptions over the trunk. We diagnosed the former lesions as herpes zoster and the latter as EAC associated with herpes zoster. Although DNA was extracted from the EAC region, no varicella-zoster virus DNA was detected. We consider that this is Wolf's isotopic response, which is caused by an alteration of the local immunity due to viral infection. An etiologic relationship between EAC and herpes zoster is strongly suggested by the present case and by our review.

Relationships between stress, social adaptation, personality traits, brain-derived neurotrophic factor and 3-methoxy-4-hydroxyphenylglycol plasma concentrations in employees at a publishing company in Japan.

There is growing evidence that blood levels of brain-derived neurotrophic factor (BDNF) and 3-methoxy-4-hydroxyphenylglycol (MHPG), a major metabolite of noradrenaline, are related to depression-associated personality traits as well as to depressive, suicidal and anxious states. Psychological job stress is well known to lead to symptoms of depression, anxiety and suicide. We have recently reported that psychological job stress among hospital employees altered blood levels of BDNF and MHPG (Mitoma et al., 2008). In the present study, we re-examined the effects of social adaptation and personality traits, as well as those of psychological job stress, on plasma levels of BDNF and MHPG in healthy employees (n=269, male/female=210/59, age=49 ± 10years) working in a publishing company in Japan. The values (mean ± SD) of scores on the Stress and Arousal Check Lists (s-SACL and a-SACL), Social Adaptation Self-evaluation Scale (SASS), plasma MHPG levels and plasma BDNF levels were 6.0 ± 3.4, 5.7 ± 2.3, 33.7 ± 6.8, 5.8 ± 4.3 and 4.6 ± 3.1ngml(-1), respectively. A positive correlation was found between plasma MHPG levels and scores on the s-SACL, but not the a-SACL. A positive correlation was also found between SASS scores and plasma MHPG levels and between SASS scores and plasma BDNF levels. A negative correlation was found between plasma BDNF levels and s-SACL scores. Furthermore, a positive correlation between NEO-Five factor Inventory (Openness) scores and plasma MHPG levels was observed, as well as between NEO-Five factor Inventory (Extroversion) scores and plasma BDNF levels. These results suggest that levels of plasma BDNF and plasma MHPG might be associated with psychological job stress and certain personality traits among employees in the publishing industry in Japan.

No association between BDNF Val66Met polymorphism and emergence of psychiatric symptoms in systemic lupus erythematosus patients.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays an important role in the regulation of synaptic plasticity and neurotransmitter release across multiple neurotransmitter systems. Recent studies have suggested that BDNF plays a role in the pathogenesis of psychiatric symptoms in patients with systemic lupus erythematosus (SLE). OBJECTIVES: We hypothesized that the polymorphism of BDNF Val66Met is associated with the emergence of psychiatric symptoms (PS) and serum BDNF levels in SLE patients. To examine the hypothesis, we compared the BDNF Val66Met polymorphism and serum BDNF levels in patients with SLE with or without PS. METHODS: Psychiatric symptoms were assessed in 54 patients with SLE. PS were evaluated using the Brief Psychiatric Rating Scale. Genotyping was carried out using a 54-nuclease assay. Serum BDNF levels were measured by using enzyme-linked immunosorbent assay. RESULTS: The presence of the Met allele was not significantly associated with the presence of PS or with serum BDNF levels in patients with SLE. CONCLUSION: Our data do not support the common variant Val66Met of the BDNF gene as an etiologic factor in the various forms of PS and serum BDNF levels in SLE.

Three polymorphisms of the eNOS gene and plasma levels of metabolites of nitric oxide in depressed Japanese patients: a preliminary report.

BACKGROUND: Depression is a risk factor for coronary heart disease. Nitric oxide (NO) plays an important role in both coronary heart disease and depression. METHODS: Fifty-one inpatients and outpatients who met the Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition criteria for major depressive disorder (MDD) in the university hospital of the University of Occupational and Environmental Health and 58 age-matched and sex-matched healthy controls enrolled in this study. We investigated the association between the three polymorphisms of the endothelial nitric oxide synthase (eNOS) gene (single-nucleotide polymorphism (SNP); rs2070744, rs1799983, variable number tandem repeat (VNTR) in intron 4) and scores on the Hamilton Rating Scale for Depression, plasma metabolites of NO (NO(x) ) or ankle brachial index in patients with MDD and healthy controls. RESULTS: We did not find significant differences in the genotype distributions between patients with MDD and healthy volunteers. No associations were observed between any of the polymorphisms of the eNOS gene and the Hamilton Rating Scale for Depression or ankle brachial index in patients with MDD. However, plasma NO(x) level was significantly associated with a polymorphism of the eNOS gene (rs207044 and variable number tandem repeat in intron 4). CONCLUSION: These results suggest that the direct association was not observed between the polymorphisms of the eNOS gene and the pathogenesis of depression.

Reliability, validity and clinical utility of a Japanese version of the Social Adaptation Self-evaluation Scale as calibrated using the Beck Depression Inventory.

AIM: The Social Adaptation Self-evaluation Scale (SASS) was developed to assess the social impairment caused by depression. The purposes of this study were to develop a Japanese version of the SASS (SASS-J) and to evaluate its reliability and validity. METHODS: The SASS-J and the 21-item Beck Depression Inventory (BDI) were administered to 322 participants (95 working patients who were working while under treatment for depression, 99 non-working patients who were absent from their work due to depression, and 128 healthy controls). The healthy controls underwent both questionnaires twice, at baseline and 2 weeks later, in order to assess test-retest reliability. RESULTS: Cronbach's alpha was 0.81. Significance correlations were found between SASS-J scores at baseline and 2 weeks later in healthy controls (R = 0.845, P < 0.001). There were negative correlations between the SASS-J and BDI scores (ρ = -0.683, P < 0.001). Mean SASS-J scores differed significantly among the three groups (working patients: 33.7 ± 7.9; non-working patients: 25.2 ± 7.8; healthy controls: 36.1 ± 6.0 [mean ± SD]). The best compromise between the true positive and the false negative rate in this study was at a cut-off point of 25/26. CONCLUSION: SASS-J showed sufficient reliability and validity, and could be considered a suitable instrument to evaluate social functioning in depressive patients.

Critical examination of a correlation between brain gamma-aminobutyric acid (GABA) concentrations and a personality trait of extroversion in healthy volunteers as measured by a 3 Tesla proton magnetic resonance spectroscopy study.

We hypothesized that brain gamma-aminobutyric acid (GABA) levels are associated with neuroticism, a trait associated with depression and anxiety disorders. We examined the correlation between brain GABA concentrations and the five factors included in the NEO Five-Factor Inventory (NEO-FFI) in healthy volunteers using magnetic resonance spectroscopy (MRS) at 3 T. Forty-one healthy subjects (21 males, 20 females; age: 35+/-7 years) were enrolled in this study. Each subject underwent a 3T 1H-MRS study with a MEGA-PRESS sequence. Spectroscopy voxels (3 cm x 3 cm x 3 cm) were placed in the frontal lobe and the parieto-occipital lobe. A negative correlation was found between the GABA/creatine ratios in the frontal lobe and scores of extroversion on the NEO-FFI. These results suggest that GABAergic neurons are related to personality traits of healthy subjects.

Association between plasma nitric oxide metabolites levels and negative symptoms of schizophrenia: a pilot study.

Nitric oxide (NO) is involved in pathophysiology of psychiatric disorders such as depression and schizophrenia. We hypothesize that plasma levels of NO and its metabolites (NO(x)) are decreased in patients with schizophrenia. To examine the hypothesis, we compared plasma NO(x) levels between 30 schizophrenic patients (M/F: 18/12, age: 38 +/- 15 years) and age- and sex-matched 30 healthy controls (M/F: 18/12, age: 41 +/- 19 years), and we also examined the effects of risperidone on plasma NO(x) levels in schizophrenic patients. The baseline plasma NO(x) levels were significantly lower in the schizophrenia group (1.85 +/- 0.70 microM) than those in control group (3.37 +/- 2.27 microM). A significantly negative correlation was found between plasma NO(x) levels and PANSS-N scores before risperidone administration (rho = -0.385, p = 0.0416). Treatment with risperidone significantly increased the plasma NO(x) levels by 8 weeks (before; 1.85 +/- 0.70 microM, after; 2.25 +/- 1.00 microM, p = 0.0491). These results suggest that NO might be one of the candidates factors which are associated with the pathophysiology of negative symptoms of schizophrenia.

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.

Varenicline does not increase serum BDNF levels in patients with nicotine dependence.

Varenicline, alpha4beta2 nicotinic acetylcholine receptor (nAChR) partial agonist, is a new class of medications for treating nicotine dependence. As an alpha4beta2 nAChR partial agonist, varenicline serves to reduce nicotine withdrawal symptoms, while high-affinity binding of the agonist mitigates the reinforcing effects of smoking. In the present study, we compared serum brain-derived neurotrophic factor (BDNF) levels of nicotine dependence and nonsmokers, and we investigated changes in serum BDNF levels after 8 weeks of treatment with varenicline. Patients met the DSM-IV criteria for nicotine dependence. Both the Fagerström test for nicotine dependence (FTND) and the Tobacco Dependence Screener (TDS) were used. Serum BDNF levels and breath carbon monoxide (CO) levels were measured before and 8 weeks after varenicline treatment. Fourteen of 16 subjects (87.5%) stopped smoking within 12 weeks of varenicline treatment. Thirteen healthy nonsmokers who never had previously smoked were randomly selected as a control group. Serum BDNF levels of patients before treatment (4.8 +/- 3.8 ng/ml) were significantly lower than those in the control group (12.4 +/- 6.13 ng/ml). Serum BDNF levels had not increased from baseline (4.8 +/- 3.8 ng/ml) to 8 weeks after varenicline treatment (3.0 +/- 1.1 ng/ml) of patients. These results suggest that smoking might decrease serum BDNF levels and that treatment with varenicline for 8 weeks, combined with 12 weeks of not smoking, does not increase serum BDNF levels in smokers.

No difference in adherence to paroxetine between depressed patients with early remission and those with late remission based on monitoring of plasma paroxetine concentrations.

Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat both anxiety disorders and depressive disorders. However, nonadherence to SSRIs is a major issue in recurrence. In the present study, we investigated paroxetine adherence in depressed patients by monitoring the plasma paroxetine concentrations between patients with rapid and those with a late response to paroxetine treatment. Twenty inpatients in our university hospital, who met the DSM-IV-TR diagnosis of major depressive disorder in a single episode, were enrolled in the study. Twelve patients (M/F: 7/13, age: 37.4 +/- 10.4 years) were treated with paroxetine (40 mg/day), and all achieved remission (HAMD < or = 7) within at least 12 weeks. We divided the patients into two groups, an early-remission group (HAMD < or = 7 within 4 weeks) and a late-remission group (HAMD < or = 7 within 8-12 weeks). Their dosages of paroxetine were constant because of no emerging adverse effects. Blood samples were obtained on the day the subjects were discharged (B) and 12 weeks after discharge. The paroxetine concentrations in the early-remission group were significantly decreased 12 weeks after discharge, and no difference was found between the early- and late-remission groups. These results suggest that adherence to paroxetine was independent of the duration of the depressive state suffered by the patients. Clinicians always take their cautions for the adherence to paroxetine regardless of the clinical time courses the patients recovering from their depressive symptoms.

[Brain-derived neurotrophic factor (BDNF) and mood disorder].

Brain-derived neurotrophic factor (BDNF) is the most abundant and widely expressed neurotrophin in the brain. BDNF is believed to play an important role in depressive disorder. Chronic stress decreases the synthesis of hippocampal BDNF, which leads to atrophy of the hippocampus in the depressed patients. Blood BDNF levels also decreased in depressed patients and a correlation is observed between severities of depressive state and blood BDNF levels. Selective serotonin reuptake inhibitors and serotonin noradrenalin reuptake inhibitors both recover the decreased blood BDNF levels. These findings indicate that the blood BDNF level is one of the candidate biomarkers for depression.

[Blood levels of brain-derived neurotrophic factor (BDNF) in major depressive disorder].

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that has been linked to the viability of neurons in brain circuits that regulate emotion, memory, learning, sleep, and appetite. BDNF has been most extensively studied in relation to depression. Depressed patients show reduced levels of hippocampal and cortical BDNF in postmortem studies. Recently, to the best of our knowledge, there are at least three meta-analyses regarding blood BDNF levels in depressed patients, suggesting that blood BDNF levels are decreased in depressive state, and those are recovered after treatment with biological treatments such as antidepressants, ECT, and rTMS. From these findings into account, it is possible that blood (plasma and serum) BDNF level is a biological marker for depressive state. We have recently demonstrated that a significantly negative correlation was observed between the HAMD scores and serum BDNF levels. In addition, responders to fluvoxamine, paroxetine, milnacipran, and sertraline all increased serum BDNF levels. Blood BDNF levels did not distinguish between responders and remitters to the treatment. In conclusion, blood BDNF levels partially reflect those in the brain, and there is also strong and consistent evidence indicating that these levels normalize following the biological intervention for depression.