Bun Hee Lee

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.

Differences in cytokines between non-suicidal patients and suicidal patients in major depression.

Several studies have shown that there is an imbalance between pro-inflammatory and anti-inflammatory cytokines in major depressive disorder (MDD). However, little is known about the role of cytokines in suicide. In the present study, amounts of IL-6, IL-2, IFN-gamma, IL-4, and TGF-beta1 produced by mitogen-stimulated whole blood were measured in 36 MDD patients who had recently attempted suicide, 33 non-suicidal MDD patients, and 40 normal controls. The severity of depression symptoms and suicidal behaviors was evaluated using Hamiltons depression rating scale (HDRS), the Lethality Suicide Attempt Rating Scale (LSARS), and the Risk-Rescue Rating (RRR). Non-suicidal MDD patients had significantly higher IL-6 production than suicidal MDD patients and normal controls (p<0.001). Suicidal MDD patients had significantly lower IL-2 compared with non-suicidal patients and normal controls (p<0.001). Both MDD groups, with or without attempted suicide, had significantly lower IFN-gamma and IL-4 and higher TGF-beta1 production. HDRS scores had significant positive correlations with IL-6, IFN-gamma, and the Th1/Th2 ratio and significant negative correlations with IL-4 in non-suicidal depression patients (p<0.005); however, these correlations did not hold true for suicidal patients. Suicidal MDD patients had no significant correlations between the LSARS or RRR scores and cytokine release. Our findings suggest that the immune response has distinct differences between non-suicidal patients and suicidal patients. Non-suicidal MDD may be associated with increased IL-6 production and a Th1/Th2 imbalance with a shift to Th1, while suicidal MDD may be associated with decreased IL-2.

T-helper types 1, 2, and 3 cytokine interactions in symptomatic manic patients.

It has been reported that the balance between T-helper type 1 (Th1) cytokines and T-helper type 2 (Th2) cytokines plays a role in psychiatric disorders such as bipolar disorder. The T-helper type 3 (Th3) cytokine, which transforming growth factor beta-1 (TGF-beta1), has been shown to modulate the production of Th1 and Th2 cytokines. However, the role of TGF-beta1 in bipolar disorder has not yet been explored. A total of 70 manic patients with bipolar disorder and 96 normal controls was recruited. The plasma levels of IFN-gamma, IL-4, and TGF-beta1 were studied at the time of admission and 8 weeks after mood stabilizer treatment. The detection rate and plasma concentrations of IFN-gamma and IL-4 and the IFN-gamma/TGF-beta1 and IL-4/TGF-beta1 ratios were significantly higher in patients than in controls, while the TGF-beta1 level was significantly lower. The TGF-beta1 level increased significantly after treatment and the IFN-gamma/TGF-beta1 and IL-4/TGF-beta1 ratios returned to control values. TGF-beta1 may play a role in the pathophysiology of bipolar disorder through the action of TGF-beta1 in modulating the IL-4/TGF-beta1 ratio.

Increased levels of plasma brain-derived neurotrophic factor (BDNF) in children with attention deficit-hyperactivity disorder (ADHD)

BACKGROUND Recent reports have suggested a pathophysiological role of brain-derived neurotrophic factor (BDNF) in attention deficit-hyperactivity disorder (ADHD). We evaluated the plasma levels of BDNF in patients with ADHD. METHODS Plasma BDNF levels were measured in 41 drug naive ADHD patients and 107 normal controls. The severity of ADHD symptoms was determined by patient scores on the ADHD rating scale (ARS) and the computerized ADHD diagnostic system (ADS). RESULTS ANCOVA with age and gender as covariates showed that the mean plasma BDNF levels were significantly higher in ADHD patients than in normal controls (F=16.968, p<0.001). There were also significant differences in plasma BDNF levels of ADHD patients and those of normal controls for males and females (Mann-Whitney U-test, p=0.001 and 0.041, respectively). We also found a significant correlation between plasma BDNF levels and omission errors in ADS outcome-variable T-scores (p<0.001). CONCLUSIONS Our study suggests that there is an increase of plasma BDNF levels in untreated ADHD patients, and that plasma BDNF levels had a significant positive correlation with the severity of inattention symptoms. Further studies are required to elucidate the source and role of circulating BDNF in ADHD.

Using aripiprazole to resolve antipsychotic-induced symptomatic hyperprolactinemia: a pilot study.

OBJECTIVE To assess the effectiveness of substituting aripiprazole for other antipsychotic drugs taken by stable schizophrenic patients suffering from antipsychotic agent-induced symptomatic hyperprolactinemia. METHODS Seven female schizophrenic patients with symptomatic hyperprolactinemia (167.6+/-58.0 microg/L) were recruited to take part in an 8-week open label trial of aripiprazole (10-20 mg/day) as a replacement for amisulpride or risperidone. Efficacy was assessed via PANSS and CGI-I scores. Serum prolactin levels were measured at baseline, week 4, and week 8. Data were collected from November, 2004 to May, 2005. RESULTS At the end of weeks 4, serum prolactin levels were normalized (8.8+/-5.5 microg/L) and hyperprolactinemic symptoms were resolved in all patients. However, aripiprazole treatment was discontinued within 6 weeks for 2 of the 7 subjects due to aggravated auditory hallucinations. CONCLUSION Results from this admittedly small-scale open-label study indicate that switching to aripiprazole may be useful for resolving antipsychotic-induced hyperprolactinemia and associated symptoms.

Increased Plasma Brain-Derived Neurotropic Factor, Not Nerve Growth Factor-Beta, in Schizophrenia Patients with Better Response to Risperidone Treatment

Background: Some neurotropins, including brain-derived neurotropic factor (BDNF) or nerve growth factor-β (β-NGF), play important roles in neurodevelopment and neuroprotection. We examined the plasma levels of these 2 factors in schizophrenia patients at the time of admission and after 6 weeks of treatment with risperidone. Methods: Plasma BDNF and β-NGF levels were measured in 36 schizophrenia patients and 36 healthy controls. All the patients underwent 6 weeks of treatment with risperidone. The severity of schizophrenia and response to treatment were assessed with the positive and negative syndrome scale (PANSS). We compared plasma BDNF and β-NGF levels among much-improved (n = 13, 36.1%, ≥50% PANSS score reduction), minimal-improved (n = 15, 41.7%, ≥25% and <50% PANSS score reduction) and nonresponse patients (n = 8, 22.2%, <25% PANSS score reduction). Results: At baseline, plasma BDNF had no significant difference between schizophrenia patients and controls, but β-NGF levels were significantly lower in schizophrenia patients than controls (p = 0.037). Plasma BDNF and β-NGF in all schizophrenia patients had no significant changes between pre- and posttreatment. Baseline BDNF levels were significantly lower in nonresponse patients than others (p = 0.038). After treatment, much-improved patients had significantly higher plasma BDNF than nonresponse patients (p = 0.023). However, β-NGF levels had no significant differences between them. Conclusions: Our data suggest that higher plasma BDNF levels might be associated with better response to risperidone treatment, while plasma β-NGF levels might have no effect on the clinical response in schizophrenia patients.

Increased plasma nitric oxide metabolites in suicide attempters.

Objective: To evaluate any correlation between plasma levels of nitric oxide metabolites (NOx) and suicide attempt. Method: Plasma NOx levels were measured in 53 patients who had recently attempted suicide, 58 nonsuicidal psychiatric patients, and 75 normal controls. The severity of suicidal behaviors was evaluated using Weisman and Worden’s Risk-Rescue Rating Scale. Results: Plasma NOx levels were significantly higher in suicidal patients than nonsuicidal psychiatric patients or normal control subjects (F = 11.029, d.f. = 2, 183, p < 0.001). Among the patients with a diagnosis of major depression, suicidal depressive patients had significantly higher plasma NOx levels than nonsuicidal depressive patients (t = –3.090, d.f. = 84, p = 0.003). Conclusion: Our study suggests that increased NO production in plasma is associated with suicide attempt, especially in depressive patients.

Reduced plasma nitric oxide metabolites before and after antipsychotic treatment in patients with schizophrenia compared to controls

BACKGROUND Nitric oxide (NO) is believed to have a role in the pathophysiology of schizophrenia. We examined plasma levels of NO metabolites in patients with schizophrenia and normal controls. We also determined the impact of 6-week risperidone treatment on circulating NO metabolites in patients with schizophrenia. METHOD Plasma NO metabolite (NO(x)) levels were measured in 55 schizophrenia patients before and after 6-week treatment with risperidone and in 55 normal controls. Severity of schizophrenia and response to treatment were assessed with the positive and negative syndrome scale (PANSS) for schizophrenia. NO(x) levels were estimated by the Griess method. RESULTS Pre-treatment plasma NO(x) levels in schizophrenia patients (8.97+/-6.74 micromol/L) were lower than those of normal controls (14.51+/-6.30 micromol/L) (p<0.01). Schizophrenia patients had lower post-treatment NO(x) levels (10.99+/-8.31 micromol/L) than those of normal controls (p<0.01). There was marginal significant change between plasma NO(x) levels before and after 6-week treatment (p=0.056). Moreover, in 37 treatment responders (> or = 30% improvement in PANSS score), post-treatment plasma NO(x) significantly increased in comparison to pre-treatment NO(x) (p=0.028). CONCLUSIONS Plasma levels of NO(x) in patients with schizophrenia were significantly lower than normal controls both before and after the treatment. Our findings suggest that the improvement of psychiatric symptoms can lead to partially normalize a deficiency of NO after treatment in schizophrenia patients. Our findings support the hypothesis that the NO system is dampened in schizophrenia.

Potential peripheral biological predictors of suicidal behavior in major depressive disorder

Previous studies have shown that dysfunctions in the serotonin system and hypothalamic-pituitary-adrenal axis (HPA) are associated strongly with suicidal behavior and suicide, especially among individuals with major depressive disorder. Suicidal behavior has been explained using both the stress-diathesis model and the state-trait interaction model. Specifically, diatheses, or trait-dependent risk factors, are associated with dysfunctions in the serotonin system; however, stress responses, or state-dependent factors, are associated with HPA hyperactivity. Decreases in cholesterol and brain-derived neurotrophic factor (BDNF) levels have been associated with impaired brain plasticity among individuals with suicidal behavior. Decreased serotonin functioning has been measured using cerebral spinal fluid (CSF) 5-HIAA, fenfluramine challenge studies, and platelet 5-HT2A receptors. HPA axis dysfunction has been evaluated with the dexamethasone suppression test. Cholesterol and BDNF levels have been measured in blood serum or plasma. Nevertheless, challenges to finding promising and accessible neurobiological predictors of suicide and suicidal behavior remain. As suicide behavior is a complex phenomenon, a combined or multidimensional approach, including each of the aforementioned methods, may be required to predict suicide risk among individuals with major depressive disorder.

Antipsychotics and dopamine transporter gene polymorphisms in delirium patients

Abstract  The main objective of the present study was to determine the relationship between treatment responses of delirium and genetic polymorphisms in the dopamine transporter. The optimal dosages of haloperidol and risperidone in the treatment of delirium were also investigated. Either haloperidol or risperidone was administered to delirium patients, and delirium symptoms were measured daily until remission. Variable number of tandem repeat (VNTR) polymorphisms of the dopamine transporter were determined using the polymerase chain reaction. Among 42 subjects, symptoms of delirium appeared a mean of 9.68 days after hospitalization. A majority of the subjects (83.3%) had the type 10/10 polymorphism. Dosages of haloperidol and risperidone at the day of recovery were 1.67 mg/day (SD = 1.32; range 0.5–2.5 mg/day) and 1.19 mg/day (SD = 1.14; range 0.5–5.0 mg/day), respectively. The mean drug response time was 8.5 days in the haloperidol group and 4.8 days in the risperidone group (no significant difference). The response rates at the 3rd and 7th days after medication did not differ with either the drug group or the dopamine transporter polymorphism. Relatively low doses of risperidone and haloperidol exhibited similar efficacies, and dopamine transporter polymorphisms do not appear to play a major role in the action of antipsychotics on delirium.