Acute and subsequent continuation electroconvulsive therapy elevates serum BDNF levels in patients with major depression

IntroductionThe induction of brain-derived neurotrophic factor (BDNF) release and subsequent restoration of neuroplastic homeostasis may underlie the effects of electroconvulsive therapy (ECT).ObjectivesWe aimed to assess serum and plasma BDNF levels during the course of acute ECT, as well as before and after subsequent continuation ECT, in patients with depression.MethodsWe included 24 patients with major depressive disorder (mean age ± SD: 54.5 ± 13.7; f/m: 17/7; baseline 17-item Hamilton Depression Rating Scale score of 26.79 ± 4.01). Serum and plasma BDNF (sBDNF, pBDNF) levels were assessed at nine time-points before, during, and after acute ECT series. Data were analysed using linear regression and linear mixed models, which were adjusted for multiple comparisons via Bonferroni correction. Five patients received continuation ECT subsequent to the acute ECT series. In these patients, BDNF levels were assessed before and after each two continuation ECT sessions using Wilcoxon signed-rank tests.ResultsRelative to baseline (mean ng/ml ±SD: 24.68 ± 14.40), sBDNF levels were significantly higher 1 day (33.04 ± 14.11, p = 0.013, corrected), 1 week (37.03 ± 10.29, p < 0.001, corrected), and 1 month (41.05 ± 10.67, p = 0.008, corrected) after the final ECT session, while pBDNF levels did not significantly differ (p > 0.1). Furthermore, our results indicated that sBDNF levels increased after each continuation ECT session. There was no significant association between sBDNF levels and clinical parameters or treatment response.ConclusionThe absence of an association between changes in sBDNF levels and depressive symptoms challenges the proposed concept of sBDNF/pBDNF as key markers of the effects of ECT.     

No change between the serum brain-derived neurotrophic factor in female patients with anorexia nervosa before and after partial weight recovery

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family. Several lines of evidence indicate that BDNF plays a role in the pathophysiology of eating disorders (ED). We found that serum BDNF levels in patients with ED were significantly lower than in normal controls. The aim of this longitudinal study was to compare serum BDNF levels in patients with anorexia nervosa (AN) before (n=13, initial mean body mass index (BMI)=14.2 kg/m(2)+/-0.7) and after partial recovery (mean BMI=16.2 kg/m(2)+/-1.7, mean weight gain 5.0 kg+/-2.0), with age-matched normal control subjects (n=17, mean BMI=20.4 kg/m(2)+/-1.5). METHODS: Eating related psychopathology and depressive symptoms were evaluated before and after partial weight recovery, using the Eating Disorder Inventory-2 (EDI-2) and the 17-item Hamilton Depression Rating Scale (HDRS). Serum BDNF levels were measured using a sandwich enzyme-linked immunosorbent assay. RESULTS: Serum BDNF levels with the AN patients (14.5+/-4.4 ng/ml) were significantly (p<0.01) lower than in control subjects (22.1+/-8.9 ng/ml). There were no significant differences in serum BDNF levels between the patients with AN before (14.5+/-4.4 ng/ml) and after (17.2+/-6.9 ng/ml) partial weight recovery. In all subjects, there was a positive correlation (r=0.5, p<0.01) between the baseline BDNF levels and the EDI-2 scores (n=30). Furthermore, in all subjects there was a positive correlation (r=0.4, p<0.05) between the BDNF levels and the BMI. CONCLUSIONS: Serum BDNF levels did not change after partial weight recovery in AN patients. Our results suggest that an alteration of the serum BDNF in AN patients is not due to changes in body weight. Thus, other possible mechanisms that could be related to low serum BDNF levels in AN patients should be evaluated.     

The effect of chronic antidepressant treatment on serum brain-derived neurotrophic factor levels in depressed patients: a preliminary study

Recent studies suggested a role of brain-derived neurotrophic factor (BDNF) in depression. While BDNF levels are lower in depressed patients, antidepressant treatment increases serum BDNF levels of depressed patients. Our study aims to test the effect of chronic venlafaxine treatment on serum BDNF levels in patients with a major depressive disorder. Ten patients diagnosed as major depressive disorder according to DSM-IV are included in the study. Two of the patients had their first episode and were drug-naive, the other eight patients were drug-free for at least 4 weeks. The severity of depression was assessed with Hamilton Depression Rating Scale (HDRS). The control group consisted of ten age- and sex-matched subjects without any psychiatric disorder. Blood samples were collected at the baseline and after 12 weeks of antidepressant treatment (during remission). At the baseline the mean serum BDNF level was 17.9+/-9.1 ng/ml and the mean HDRS score was 23.2+/-4.6. Serum BDNF levels of the study group were significantly lower than in the control group (31.6+/-8.6 ng/ml). At the end of the study, the mean serum BDNF level was 34.6+/-7.1 ng/ml whereas the mean HDRS score was 8.2+/-3.9. From the baseline to the remission after 12 weeks of treatment, the increase in serum BDNF level and the decrease in HDRS score were statistically significant, respectively. When we compared the serum BDNF level of depressed patients at remission to that of the controls, there was no statistically significant difference. This study shows that venlafaxine treatment of depression improves serum BDNF level which may be considered as a nonspecific peripheral marker of depression.     

广泛性焦虑障碍治疗前后血清脑源性神经营养因子水平的变化

目的研究广泛性焦虑障碍(generalized anxiety disorder,GAD)患者血清脑源性神经营养因子(brain derived neurotrophic factor,BDNF)水平的特点及其治疗变化。方法收集GAD患者及正常对照者各40名,采用帕罗西汀片有效治疗量治疗12周,治疗前后采用汉密尔顿焦虑量表(Hamilton Anxiety Scale,HAMA)进行疗效评估,采用ELISA法测定血清BDNF的浓度并与对照组比较。结果治疗前GAD患者的血清BDNF水平[(26.03±10.52)ng/mL]低于对照组[(43.27±10.28)ng/mL],治疗后GAD患者血清BDNF水平[(35.85±11.96)ng/mL]较治疗前升高,但仍低于正常对照组,其差异均有统计学意义(P均<0.05);治疗后GAD显效患者[(39.43±12.35)ng/mL]与对照组血清BDNF水平的差异无统计学意义(P>0.05);基线时,GAD患者血清BDNF水平与HAMA量表总分、精神性焦虑因子分呈负相关(P<0.05),与躯体性焦虑因子分的相关没有统计学意义(P>0.05);治疗后,GAD患者血清BDNF水平的变化与HAMA总分、躯体性焦虑因子分、精神性焦虑因子分变化均呈负相关(P均<0.05)。结论血清BDNF水平可能是GAD的状态性指标之一。     

Reduced serum levels of brain-derived neurotrophic factor in adult male patients with autism

BACKGROUND: The precise mechanisms underlying the pathophysiology of autism are currently unknown. Given the key role of brain-derived neurotrophic factor (BDNF) in brain development, we hypothesized that BDNF may play a role in the pathophysiology of autism. In this study, we studied whether serum levels of BDNF are altered in patients with autism. METHODS: We measured serum levels of BDNF in 18 adult male patients with autism and 18 age-matched healthy male control subjects. RESULTS: The serum levels of BDNF in patients with autism (25.6+/-2.15 ng/ml (mean+/-S.D.)) were significantly (z = -4.42, p < 0.001) lower than those of normal controls (61.6+/-10.9 ng/ml (mean+/-S.D.)). Nevertheless, we found no correlations between BDNF levels and clinical variables in autistic patients. CONCLUSIONS: This study suggests that reduced BDNF levels may play a role in the pathophysiology of autism.     

Serum brain-derived neurotrophic factor levels in conversion disorder: Comparative study with depression

The aim of the present study was to compare serum brain-derived neurotrophic factor (BDNF) levels of patients with major depressive disorder (MDD) and conversion disorder (CD). Serum BDNF levels were measured in the following three groups: 15 CD patients without any comorbid diagnosis of psychiatric disorder, 24 patients with MDD, and 26 healthy subjects without any psychiatric diagnosis or psychiatric treatment. The serum BDNF level of the healthy control group (31.4 +/- 8.8 ng/mL) was statistically higher than the level of the MDD group (21.2 +/- 11.3 ng/mL) and the CD group (24.3 +/- 9.0 ng/mL; P = 0.008). This suggests that BDNF level may play a similar role in the pathophysiology of MDD and CD.     

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.     

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.     

Elevation of plasma concentration of adhesion molecules in late-life depression

OBJECTIVES: Late-life depression may be associated with vascular disease. The purpose of the study was to investigate this association by determining the levels of soluble adhesion molecules (sICAM-1 and sVCAM-1) which represent markers of ischemia-induced inflammation in elderly individuals with depression. METHODS: Blood samples were obtained from 33 subjects with depression selected from a community-dwelling population after screening with the Geriatric Depression Scale, and 33 matched controls. Serum concentrations of sICAM-1 (ng/mL) and sVCAM-1 (ng/mL) were measured in both groups. RESULTS: Depressed patients (Group A) possessed significantly higher sICAM-1 levels compared to healthy controls (Group B) (674.94 +/- 166.90 ng/ml vs 467.05 +/- 231.26 ng/ml, respectively, p < 0.01). Similarly the same groups demonstrated elevated sVCAM-1 levels compared to controls (572.14 +/- 182.20 ng/ml vs 449.04 +/- 285.27 ng/ml, p < 0.05); a difference that in both cases remained significant after adjustment for potential confounders (gender, smoking, presence of metabolic syndrome). CONCLUSION: These findings indicate an association between high serum levels of VCAM-1, and ICAM-1 and depression in the elderly and further support the vascular depression hypothesis, which has important implications for the understanding and management of late-life depression.     

Decreased serum brain-derived neurotrophic factor levels in major depressed patients

Recent findings with animal models have suggested a possible role for brain-derived neurotrophic factor (BDNF) in depression. We have therefore hypothesized that depression could be characterized by low levels of serum BDNF. Major depressed patients (15F + 15M) diagnosed according to DSM-IV criteria and healthy controls (15F + 15M) participated in the study. Serum BDNF was assayed with the ELISA method and the severity of depression was evaluated with Montgomery-Asberg-Depression Rating Scale (MADRS). BDNF levels were significantly lower in patients than in controls: 22.6 +/- 3 and 26.5 +/- 7 ng/ml (t-test = 2.7; d.f. = 58; P < 0.01). They were negatively correlated to the MADRS scores (r = -0.55; P < 0.02). Female patients were more depressed and released less BDNF than men. Analysis of covariance (MADRS and gender as independent variable vs. BDNF as dependent variable) indicated that depression severity mainly accounted for the negative correlation. These results suggest that major depression is characterized by low serum BDNF levels and support the hypothesis of neurotrophic factor involvement in affective disorders.     

Plasma brain-derived neurotrophic factor as a peripheral marker for the action mechanism of antidepressants

Numerous studies have demonstrated that depression is associated with a decreased expression of brain-derived neurotrophic factor (BDNF). BDNF shows antidepressant-like effects in animal models. Therefore, we tested the hypothesis that BDNF might be a peripheral marker for the mechanism of action of antidepressant agents in humans. Thirty-two patients meeting the DSM-IV criteria for major depressive disorder and 50 normal control subjects were recruited for this study. Plasma BDNF levels and Hamilton Depression Rating Scales were measured at baseline and 6 weeks after antidepressant administration. At baseline, the mean plasma BDNF level was lower in the depressive patients (698.1 +/- 537.7 pg/ml) than in the control subjects (830.7 +/- 624.8 pg/ml), although the difference was not statistically significant (p = 0.33). The plasma BDNF levels in depressive patients significantly increased from 698.1 +/- 537.7 to 1,028.9 +/- 744.5 after 6 weeks of antidepressant treatment (p = 0.01). Moreover, plasma BDNF levels were significantly increased after 6 weeks of treatment in the responder group, while there was no statistically significant change in the unresponsive group. These results suggest that the therapeutic response after antidepressant administration might be attributable to the increase in BDNF levels. BDNF may play a critical role in the action mechanism of antidepressant drugs. Further studies with a larger number of subjects are needed to verify these findings.     

Serum BDNF levels in suicide attempters related to psychosocial stressors: a comparative study with depression

Although many studies have examined the neurobiological aspects of suicide, the molecular mechanisms and pathophysiologic mechanisms associated with suicide remain unclear. In this study, it is aimed to investigate whether there is a difference in serum brain-derived neurotrophic factor (BDNF) levels among suicide attempters without a major psychiatric disorder, compared to major depressive disorder patients and healthy subjects. It was undertaken with the hypothesis that suicide per se lowers serum BDNF levels, since it is a source of stress. The study was carried out in Celal Bayar University Hospital, Manisa, Turkey. Ten suicide attempters, 24 patients with major depressive disorder and 26 subjects without any psychiatric diagnosis and any psychiatric treatment were included in the study. All subjects were asked to give their written consent. Blood samples were collected at the baseline. Serum BDNF was kept at -70 degrees C before testing, and assayed with an ELISA kit (Promega; Madison, Wisc., USA) after dilution with the block and sample solution provided with the kit. The data were subjected to the Kruskal-Wallis test for nonparametric analysis of variance. Mean serum BDNF levels were significantly lower in the suicide group (21.2 +/- 12.4 ng/ml) and the major depressive disorder group (21.2 +/- 11.3 ng/ml) than the control group (31.4 +/- 8.8 ng/ml; p = 0.004). These results suggest that BDNF may play an important role in the neurobiology of suicidal behavior. BDNF levels may be a biological marker for suicidal behavior. To investigate the role of BDNF in suicide, further studies with a wider sample size and a variety of psychiatric diagnoses accompanying suicide attempt are needed.     

Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants.

BACKGROUND: Because researchers have reported that antidepressants increase the expression of brain-derived neurotrophic factor (BDNF) in the rat hippocampus, we investigated whether serum BDNF levels may be used as a putative biological marker for major depressive disorders (MDD). METHODS: We measured serum BDNF in the following three groups: antidepressant-naive patients with MDD (n = 16), antidepressant-treated patients with MDD (n = 17), and normal control subjects (n = 50). Patients were evaluated using the Hamilton Rating Scale for Depression (HAM-D). Serum BDNF was assayed with the sandwich ELISA method. RESULTS: We found that serum BDNF was significantly lower in the antidepressant-naive group (mean, 17.6 ng/mL; SD, 9.6) than in the treated (mean, 30.6 ng/mL; SD, 12.3; p =.001) or in the control group (mean, 27.7 ng/mL; SD, 11.4; p =.002). There was a significant negative correlation (r = -.350, z = -2.003, p =.045) between serum BDNF and HAM-D scores in all patients. In a preliminary examination, reduced BDNF values of three drug-naive patients recovered to basal levels after antidepressant treatment. CONCLUSIONS: Our study suggests that low BDNF levels may play a pivotal role in the pathophysiology of MDD and that antidepressants may increase BDNF in depressed patients.     

Low plasma BDNF is associated with suicidal behavior in major depression

Brain-derived neurotrophic factor (BDNF), the most abundant neurotrophin in the brain, has a known association with the pathophysiology of anxiety and depression. However, the role of BDNF in suicide has not been well investigated to date. This study examined plasma BDNF levels in 32 major depressive disorder (MDD) patients who had recently attempted suicide, 32 non-suicidal MDD patients, and 30 normal controls. The lethality of the suicide attempt was measured using the Risk-Rescue Rating (RRR) and Lethality Suicide Attempt Rating Scale (LSARS). The severity of depression was measured with the Hamilton Depression Rating Scale (HDRS). Plasma BDNF levels were measured by enzyme linked immunosorbent assay. BDNF levels were significantly lower in suicidal MDD patients (430.5+/-397.0 pg/ml) than non-suicidal MDD patients (875.80+/-663.02 pg/ml) or normal controls (889.4+/-611.3 pg/ml) (F=6.682, p=0.002). The most suitable cut-off point of BDNF level between suicidal depression and non-suicidal depression groups was 444.58 pg/ml. At this cut-off point, the sensitivity=68.7%, specificity=78.1%, positive predictive value=75.9%, and negative predictive value=71.4%. However, there was no significant difference in BDNF levels between the depressive control and normal control groups (p=0.996). LSARS and RRR did not reveal any significant correlations with BDNF levels in suicidal patients. In addition, BDNF levels were not different between fatal and non-fatal suicide attempts. These results suggest that reduction of plasma BDNF level is related to suicidal behavior in major depression and that BDNF level may be a biological marker of suicidal depression.     

Effects of fluoxetine and venlafaxine on serum brain derived neurotrophic factor levels in depressed patients

Background

Several studies demonstrated that depressed patients had low serum BDNF levels which correlated with the severity of their depression, and antidepressant treatment increases levels of serum BDNF in depressed patients. It was speculated that agents acting on both noradrenergic and serotonergic transporters might have a greater influence on BDNF levels. The aim of our study was to determine effects of venlafaxine vs. fluoxetine on serum BDNF levels in depressive patients.

Methods

Forty-three patients diagnosed as major depressive disorder according to DSM-IV are included in the study. Forty-three patients were randomized to take fluoxetine (22 cases) or venlafaxine (21 cases). Serum levels of BDNF were measured by ELISA at baseline and 6 weeks after the start of treatment.

Results

Baseline levels of BDNF were not significantly different between the patient group and the controls. But male patients and the male controls showed statistical differences with respect to baseline BDNF levels. BDNF levels of the patient group did not change with treatment. Yet, the increase of BDNF levels was close to statistically significant in the fluoxetine group, whereas not significant in the venlafaxine group. There were no significant differences in baseline and 6th week BDNF levels between the responders and the non-responders.

Conclusion

Further studies controlling for a wide variety of confounding variables are needed, which may help to reach a clear conclusion about the potential of BDNF as a biomarker for depression or as a predictor of antidepressant efficacy.     

Serum brain-derived neurotrophic factor level in dysthymia: a comparative study with major depressive disorder

In this present work, it is aimed to demonstrate BDNF serum concentrations in patients with dysthymia and to compare them with BDNF serum concentrations in patients with major depressive disorder and healthy subjects. The study was carried out in Celal Bayar University Hospital, Manisa, Turkey. Seventeen patients with dysthymia, 24 patients with major depressive disorder and 26 subjects without any psychiatric diagnosis and any psychiatric treatment were included in the study. The severity of depression was assessed with 17-item HAM-D. All subjects were asked to give their written consent. Blood samples were collected at baseline. Serum BDNF was kept at -70 degrees C before testing, and assayed with an ELISA Kit (Promega; Madison, WI, USA), after dilution with the Block and Sample solution provided with the kit. The data were subjected to the analysis of variance. The BDNF serum concentrations of the dysthymia group (mean=28.9+/-9.2 ng/ml) were significantly higher than that of the major depressive disorder group (21.2+/-11.3 ng/ml) (p=0.002), and it was not different from the level of the control group (31.4+/-8.8 ng/ml). BDNF serum concentrations and HAM-D score did not have any significant correlation in the dysthymia and major depression groups (r=-0.276, p=0.086). The low level of BDNF in patients with dysthymic disorder seems to point out that BDNF changes in mood disorders are state-dependent and vary according to the severity of depressive episodes.     

Proxy validation of patient self-reports of ADL and IADL function before and after electroconvulsive therapy

OBJECTIVE: To determine whether electroconvulsive therapy (ECT) patients' self-reported functional status is similar to that reported by a proxy. BACKGROUND: Increasing levels of depression are associated with deteriorating functional status as reflected in the Instrumental Activities of Daily Living (IADL) scale. Depressed patients referred for ECT have poorer IADL status compared with depressed patients receiving medications, suggesting that IADL status may shape physicians' decision to recommend ECT ( 1). Further, IADL status improves with treatment of depression, both in ECT-and medication-treated patients. Given the potential importance of IADL status for ECT patients, we examined whether IADL status as reported by patients prior to ECT was comparable to IADL status as described by a proxy. DESIGN/METHODS: Forty depressed patients (23 men and 17 women, mean age 58.1 +/- 17.5) were each interviewed alone with the 21-item Hamilton Depression Rating Scale (HDRS), Mini-Mental State Exam (MMSE), an Activities of Daily Living (ADL) scale, and an IADL scale. We then privately interviewed a first-degree relative who lived with each patient and recorded their impression of the patient's ADL and IADL function before ECT, and at 2 and 4 weeks after ECT. RESULTS: baseline scores for HDRS and MMSE were consistent with a severe level of depressive symptoms and intact global cognitive function. Patients' and proxies' IADL scores were highly correlated before ECT, 2 weeks after ECT, and 4 weeks after ECT. Significant, but slightly weaker correlations were seen for ADL scores. CONCLUSIONS: Ideally, ADL and IADL function would be measured by direct observation rather than either patient or proxy report. At this time it is unknown whether the patient or the proxy report should be considered the "gold standard." In this study, the patients' self-reported functional scores were highly correlated with the proxies' scores. We conclude that patients' reports of their function are roughly comparable to proxies' impressions before and after ECT.     

High-frequency repetitive transcranial magnetic stimulation improves refractory depression by influencing catecholamine and brain-derived neurotrophic factors

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive and easily tolerated method of altering cortical physiology. To date, numerous open and sham controlled clinical trials have explored the antidepressant potential of rTMS. In the present study, we investigated clinical trials of high-frequency rTMS (20 Hz) for treatment of refractory depression, and also examined the effect of rTMS on plasma levels of catecholamine metabolites and brain-derived neurotropic factor (BDNF). METHODS: Twenty-six depressed inpatients who met the DSM-IV criteria for major depressive disorder and had failed to respond to treatment with at least two antidepressant drugs given at adequate doses (above 150 mg/day in an equivalent dose of imipramine) and durations (at least 4 weeks for each drug) were enrolled in this study. Eleven were males, 15 females. The ages of the subjects ranged from 19 to 78 years old (mean +/- SD = 52.9 +/- 17.8). All patients were administered left prefrontal 20 Hz rTMS at 80 % MT (total 800 pulses a day) over ten daily sessions. The plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were analyzed by high-performance liquid chromatography. The plasma levels of BDNF were also measured with the sandwich ELISA method. RESULTS: The mean 17-item Hamilton Rating Scale for Depression (Ham-D) score of 20.5 +/- 5.2 before rTMS was significantly decreased to 15.6 +/- 7.3 after rTMS. Nine of 26 patients (35 %) demonstrated some improvement (Ham-D > or = 25 %) by rTMS. The levels of plasma MHPG, but not those of HVA, were significantly reduced after rTMS treatment, and a negative correlation was observed between the change in plasma MHPG levels and the change in scores of agitation. In addition, the plasma levels of BDNF were significantly increased by 23 % in responders and partial responders, but not in nonresponders, after rTMS treatment, and a trend for association was found between the changes in Ham-D scores and changes in plasma BDNF levels in all patients after rTMS treatment. CONCLUSION: These results suggest that rTMS treatment brings about some improvement in refractory depression, especially for symptoms such as agitation, by influencing MHPG and BDNF, which is in accordance with previous reports showing that BDNF was increased by various antidepressants treatments.     

Investigation of serum BDNF levels in drug-naive patients with schizophrenia

The role of brain-derived neurotrophic factor (BDNF) is to promote and modulate the neuronal responses across neurotransmitter systems in the brain. Therefore, abnormal BDNF signaling may be associated with the pathophysiology of schizophrenia. Decreased BDNF levels in the brain and the serum of patients with psychotic disorders have been reported. In the present study, we assessed serum BDNF levels in a group of 14 drug-naive first-episode patients with schizophrenia (FEP), compared to 15 healthy controls. The serum BDNF levels in the sample of FEP patients was significantly reduced compared to normal controls (23.92+/-5.99 ng/ml vs. 30.0+/-8.43 ng/ml, F=5.01, df=1, p=.034). Negative correlations were shown between serum BDNF levels of the patients and the PANSS Positive and Negative subscale scores. Our findings indicate that BDNF levels at the onset of schizophrenia may reflect associated pathophysiological processes as well as the severity of positive and negative psychotic symptoms.     

Concurrent administration of clozapine and electroconvulsive therapy in clozapine-resistant schizophrenia

OBJECTIVE: The aim of this article is to critically review all published studies regarding the efficacy and safety of the concurrent administration of clozapine (CLZ) and electroconvulsive therapy (ECT) in CLZ-resistant schizophrenic or schizoaffective patients. METHOD: A MEDLINE search from January 1980 to July 2005 was conducted. RESULTS: One open-label trial and 6 case studies were located, comprising 21 schizophrenic and 1 schizo affective patients (12 men and 10 women) with a mean age of 41.9 years. The duration and dosage of CLZ monotherapy before ECT were reported at least 12 weeks and 300 mg/d, respectively, in 10 patients (45.4%). Plasma CLZ levels before ECT were assessed in 12 patients (54.5%), in which only 7 (31.8%) were reported to be higher than 350 ng/mL. The CLZ dosage during ECT ranged from 200 to 900 mg/d (mean, 518.2 +/- 203.3 mg/d). The number of ECT sessions ranged from 2 to 20 (mean, 11.5 +/- 5.4). Application of electrodes was unilateral in 7 patients, bilateral in 10 patients, and mixed in 2 patients. Sixteen patients (72.7%) showed marked improvement whereas 6 patients (27.3%) had moderate, minimal, or no improvement. No predictors of outcome could be isolated. Side effects reported by 5 patients (22.7%) were nausea, tachycardia, hypertension, memory problems, and confusion. Ten patients (45.4%) relapsed during follow-up. Substantial improvement persisted beyond 4 months in only 5 patients (22.7%). CONCLUSION: Preliminary evidence exists for the safety and short-term efficacy of the concurrent administration of CLZ and ECT in CLZ-resistant schizophrenic or schizoaffective patients.