No abstract available.
Brain-Derived Neurotrophic Factor

OBJECTIVE: The aim of the present study was to examine the impact of personality traits on emotional responses to interpersonal stress. METHODS: Thirty-two healthy college students (18 men, 14 women; age 25.2+/-2.7 years) participated in the study. Mood and anxiety were assessed with the Beck Depression Inventory and the State Trait Anxiety Inventory. Personality traits were assessed with the Interpersonal Sensitivity Measure (IPSM). The subjective emotional responses of participants to different (i.e., negative, neutral, and positive) interpersonal feedback were measured. RESULTS: Subject responses were positive to positive interpersonal feedback and negative to negative interpersonal feedback. The IPSM fragile inner self subscore was negatively correlated with the subjective emotional ratings in response to interpersonal feedback. No correlation was found between validation measures (i.e., the degree of attention in the task and task difficulty) and subjective emotional responses. CONCLUSIONS: Taken together, emotional responses to interpersonal stress may be modulated by personality traits and may impact health and psychological outcomes. Therefore, proper screening and stress management programs that focus on personality traits may improve the mental health of college students.
Anxiety ; Depression ; Humans ; Interpersonal Relations ; Male ; Mass Screening ; Mental Health ; Stress, Psychological

OBJECTIVE: This study examined the association between the brain-derived neurotrophic factor (BDNF) (Val66Met) polymorphism and the response to the addition of an atypical antipsychotic drug to a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) in treatment-refractory depression. METHODS: The study enrolled 64 patients meeting the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for major depressive disorder who were treated with at least two courses of a single antidepressant, but who had Hamilton Depression Rating Scale (HAMD-17) scores > or =15 points that were reduced less than 50% over at least a 4-week treatment period. There were 24 males and 40 females (age range 27-68 years; mean+/-SD, 48+/-13 years). The patients' clinical improvement was evaluated using the HAMD-17. Patients with at least a 50% decrease in the HAMD-17 score were defined as responders. Serum BDNF levels were assayed using enzyme-linked immunosorbent assays and the presence of the BDNF (Val66Met) polymorphism was determined using the TaqMan genotyping assay. RESULTS: No correlation was found between the BDNF (Val66Met) polymorphism and a positive response to adding an atypical antipsychotic drug. No differences were observed in the changes in the serum BDNF levels and HAMD-17 scores between Val66Val and Met-carriers. In addition, in patients who experienced remission, the atypical antipsychotic drug was discontinued after at least 3 months of treatment and the patients were then followed for 1 year; 14 of 27 patients (52%) relapsed within 1 year. CONCLUSION: These results suggest that the BDNF (Val66Met) polymorphism is not associated with the response to the augmentation of a SSRI or SNRI with an atypical antipsychotic drug, and that the combination of an atypical antipsychotic drug and a SSRI or SNRI should be continued for 3 months or more in refractory depressed patients in the Japanese population.
Asian Continental Ancestry Group ; Brain-Derived Neurotrophic Factor ; Depression ; Depressive Disorder, Major ; Depressive Disorder, Treatment-Resistant ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Norepinephrine ; Serotonin

OBJECTIVE: Panic disorder is characterized by recurrent panic attacks, persistent concerns about additional attacks, and worry about the implications of the attack or significant changes in behavior related to the attacks. We examined the efficacy of 24-week naturalistic, open-label escitalopram treatment in terms of the response and remission rates and functional disability in 119 adult Korean patients with panic disorder from 6 clinical centers in South Korea. METHODS: Clinical severity and functional impairment were assessed at baseline and at 4, 12, and 24 weeks after the treatment using the Panic Disorder Severity Scale and Sheehan Disability Scale. Ninety-six patients (80.7%) showed a treatment response, and 87 patients (73.1%) had attained remission after 24 weeks of escitalopram treatment. RESULTS: Continuous improvement in the Panic Disorder Severity Scale and Sheehan Disability Scale scores was found over the 24 weeks of treatment. CONCLUSION: These findings suggest that escitalopram treatment is very effective for panic disorder in terms of both response and remission rates and that long-term pharmacotherapy with escitalopram continuously improved panic symptoms and functional disability in Korean patients with panic disorder.
Adult ; Antidepressive Agents ; Citalopram ; Humans ; Panic ; Panic Disorder ; Prospective Studies

OBJECTIVE: Glycine transporter 1 (GlyT-1) is one of the most attractive therapeutic targets for schizophrenia. There is great interest in developing radioligands for in vivo imaging of GlyT-1 in the brain using positron emission tomography. Here, we report the properties of three novel non-sarcosine-based radioligands [11C]CHIBA-3007, [11C]CHIBA-3009, and [11C]CHIBA-3011, for GlyT-1 imaging in the mouse brain in vivo. METHODS: The three radioligands were synthesized by N-[11C] methylation of the corresponding desmethyl precursor. A pharmacological characterization of these radioligands for in vivo imaging of GlyT-1 in the brain was conducted using male ddY mice. RESULTS: [11C]CHIBA-3009 and [11C]CHIBA-3011 were scarcely incorporated into the brain, whereas [11C]CHIBA-3007 showed slight but considerable brain uptake. Regional brain uptake of [11C]CHIBA-3007 (medulla oblongata>cerebellum>cortex) was similar to the distribution of the GlyT-1 protein. However, pretreatment with CHIBA-3007 (1 mg/kg) or the GlyT-1 selective inhibitor ALX5407 (N-[(3R)-3-([1,1'-Biphenyl]-4-yloxy)-3-(4-fluorophenyl)propyl]-N-methylglycine) (30 mg/kg) did not significantly decrease brain uptake of [11C]CHIBA-3007, suggesting low specific binding to GlyT-1. Pretreatment with cyclosporin A significantly increased brain uptake of [11C]CHIBA-3009 and [11C]CHIBA-3011, suggesting a role for P-glycoprotein in the brain uptake of these ligands. All three radioligands were rapidly degraded intact forms were 3-18% in plasma and 15-74% in the brain at 15 min after injection. CONCLUSION: The results suggest that these three radioligands are not suitable for in vivo imaging of GlyT-1 in the brain because of low brain uptake and rapid metabolism. Further structural refinement is necessary to enhance brain uptake.
Animals ; Brain ; Cyclosporine ; Glycine ; Glycine Plasma Membrane Transport Proteins ; Humans ; Ligands ; Male ; Methylation ; Mice ; Niacinamide ; P-Glycoprotein ; Plasma ; Positron-Emission Tomography ; Schizophrenia ; Thiophenes

OBJECTIVE: Given the ability of mood stabilizers and antipsychotics to promote cell proliferation, we wanted to determine the effects of these drugs on neuronal markers previously reported to be altered in subjects with psychiatric disorders. METHODS: Male Sprauge-Dawley rats were treated with vehicle (ethanol), lithium (25.5 mg per day), haloperidol (0.1 mg/kg), olanzapine (1.0 mg/kg) or a combination of lithium and either of the antipsychotic drugs for 28 days. Levels of cortical synaptic (synaptosomal associated protein-25, synaptophysin, vesicle associated protein and syntaxin) and structural (neural cell adhesion molecule and alpha-synuclein) proteins were determined in each treatment group using Western blots. RESULTS: Compared to the vehicle treated group; animals treated with haloperidol had greater levels of synaptosomal associated protein-25 (p<0.01) and neural cell adhesion molecule (p<0.05), those treated with olanzapine had greater levels of synaptophysin (p<0.01) and syntaxin (p<0.01). Treatment with lithium alone did not affect the levels of any of the proteins. Combining lithium and haloperidol resulted in greater levels of synaptophysin (p<0.01), synaptosomal associated protein-25 (p<0.01) and neural cell adhesion molecule (p<0.01). The combination of lithium and olanzapine produced greater levels of synaptophysin (p<0.01) and alpha-synuclein (p<0.05). CONCLUSION: Lithium alone had no effect on the neuronal markers. However, haloperidol and olanzapine affected different presynaptic markers. Combining lithium with olanzapine additionally increased alpha-synuclein. These drug effects need to be taken into account by future studies examining presynaptic and neuronal markers in tissue from subjects with psychiatric disorders.
alpha-Synuclein ; Animals ; Antipsychotic Agents ; Benzodiazepines ; Cell Adhesion ; Cell Proliferation ; Haloperidol ; Humans ; Lithium ; Male ; Nerve Tissue Proteins ; Neural Cell Adhesion Molecules ; Neurons ; Neurotransmitter Agents ; Proteins ; Qa-SNARE Proteins ; Rats ; SNARE Proteins ; Synaptophysin

Earlier structural magnetic resonance imaging in schizophrenia have noted smaller white matter volumes in diverse brain regions and recent diffusion tensor imaging (DTI) studies have allowed better elucidation of changes in brain white matter integrity within the illness. As white matter abnormalities have been reported to occur early in the course of schizophrenia, we systematically review extant DTI studies of anomalies of white matter integrity in first episode schizophrenia (FES) up till October 2011. Overall, disruptions of white matter integrity were found in the cortical, subcortical brain regions and white matter associative and commissural tracts, suggesting that changes of cortical-subcortical white matter integrity were found at an early stage of the disorder. These changes in white matter integrity were correlated with specific cognitive deficits (verbal and spatial working memory) as well as psychopathology (positive more than negative symptoms) in patients with FES. The correlation of these white matter integrity changes with cognitive and phenomenological factors may shed light on neurobiological substrates underlying these clinical manifestations. Future studies need to validate these findings in larger samples of subjects and in different populations as well as chart the progress of these cerebral white matter changes over time so as to better appreciate their trajectory with illness course, treatment and chronicity.
Anisotropy ; Brain ; Diffusion ; Diffusion Tensor Imaging ; Humans ; Light ; Magnetic Resonance Imaging ; Psychopathology ; Schizophrenia

Schizophrenia is a psychiatric disorder that includes symptoms such as hallucinations, disordered thoughts, disorganized or catatonic behaviour, cognitive dysfunction and sleep-wake disturbance. In addition to these symptoms, cardiometabolic dysfunction is common in patients with schizophrenia. While previously it has been thought that cardiometabolic symptoms in patients with schizophrenia were associated with medications used to manage this disorder, more recently it has been demonstrated that these symptoms are present in drug naive and unmedicated patients. Sleep-wake disturbance, resulting in chronic sleep loss has also been demonstrated to induce changes in cardiometabolic function. Chronic sleep loss has been associated with an increased risk for weight gain, obesity and cardiac and metabolic disorders, independent of other potentially contributing factors, such as smoking and body mass index. We hypothesise that the sleep-wake disturbance comorbid with schizophrenia may play a significant role in the high prevalence of cardiometabolic dysfunction observed in this patient population. Here we present a critical review of the evidence that supports this hypothesis.
Body Mass Index ; Hallucinations ; Humans ; Obesity ; Prevalence ; Schizophrenia ; Smoke ; Smoking ; Weight Gain

Clozapine use is associated with various adverse events, some of which have received little attention, including eosinophilia, pleural effusion, and hepatitis. Because of the fatality of jaundice with hepatitis, it is necessary to understand the course and management of clozapine-induced eosinophilia and hepatitis. We report on a case in which the eosinophil count began to increase shortly after clozapine use, and pleural effusion and fever then developed at the time eosinophilia was at its peak level. Jaundice with hepatitis consecutively developed when all the above symptoms subsided. The liver function recovered rapidly after clozapine was discontinued. We recommend that patients who develop rapid eosinophilia at the beginning of clozapine treatment should be monitored with LFTs, chest X-rays, and urine analysis tests.
Clozapine ; Eosinophilia ; Eosinophils ; Fever ; Hepatitis ; Humans ; Jaundice ; Liver ; Pleural Effusion ; Thorax

OBJECTIVE: Several studies have suggested that repetitive transcranial magnetic stimulation (rTMS) of the right prefrontal cortex may be useful in the treatment of posttraumatic stress disorder (PTSD). The aim of this study was to compare the effect of rTMS on the right prefrontal cortex with that of sham stimulation among patients with PTSD. METHODS: In total, 18 patients with PTSD were randomly assigned to the 1-Hz low-frequency rTMS group or the sham group for 3 weeks. Primary efficacy measures were the Clinician-Administered PTSD Scale (CAPS) and its subscales, assessed at baseline and at 2, 4, and 8 weeks. RESULTS: All CAPS scores improved significantly over the study period. We found significant differences in the re-experiencing scores (F=7.47, p=0.004) and total scores (F=6.45, p=0.008) on the CAPS. The CAPS avoidance scores showed a trend toward significance (F=2.74, p=0.055), but no significant differences in the CAPS hyperarousal scores were observed. CONCLUSION: The present study showed low-frequency rTMS to be an effective and tolerable option for the treatment of PTSD. Trials using variable indices of rTMS to the right prefrontal cortex and explorations of the differences in the effects on specific symptom clusters may be promising avenues of research regarding the use of rTMS for PTSD.
Humans ; Prefrontal Cortex ; Salicylamides ; Stress Disorders, Post-Traumatic ; Transcranial Magnetic Stimulation