Tomohiro Shirasaka

Effect of antidepressants on brain-derived neurotrophic factor (BDNF) release from platelets in the rats.

Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family, and enhances the growth and maintenance of several neuronal systems. In addition, BDNF may promote neurogenesis and protect against hippocampal volume loss in depressive disorders. Although first detected in brain, BDNF also exists in peripheral tissues and is mainly stored in platelets and circulates in blood. Recent reports indicate that serum BDNF levels in depressive patients are lower than in control subjects, and antidepressant treatment increases serum BDNF levels in responders. A single report suggests that decreased serum BDNF in major depression is related to mechanisms of platelet BDNF release; however, the mechanisms of changes in BDNF blood levels are still poorly understood. In the present study, we investigated the direct influence of antidepressants on BDNF release from platelets and their effects on serum levels. We used samples of washed platelets prepared from rat blood, and investigated the platelet BDNF release and serum BDNF concentration changes in response to adding antidepressants. We found that BDNF was dose-dependently released from platelets by direct treatment with various kinds of antidepressants in vitro, and serum BDNF concentration was also increased by intravenous antidepressant treatment. These results confirm that BDNF release from platelets is affected by antidepressants, which may relate to the circulating BDNF level change in peripheral blood. The response of BDNF release differs depending on the type and amount of antidepressants, making BDNF a serious candidate as a predictor of antidepressant treatment response.

Comparison of the Usefulness of Brain Perfusion SPECT and MIBG Myocardial Scintigraphy for the Diagnosis of Dementia with Lewy Bodies

Background: Supportive features in the diagnostic criteria for dementia with Lewy bodies (DLB) include occipital hypoperfusion and decreased cardiac uptake of 123I-metaiodobenzylguanidine (MIBG). In this study, we performed both brain perfusion single photon emission computed tomography (SPECT) and MIBG myocardial scintigraphy in the same subjects and evaluated their sensitivity to detect the characteristic features of DLB. Methods: Twenty-five patients with probable DLB (76.8 ± 5.1 years old, 10 male) underwent 99mTc-ethylcysteinate dimer brain perfusion SPECT and 123I-MIBG myocardial scintigraphy. The results of SPECT were analyzed using a qualitative analysis program, easy Z score imaging system (eZIS), and an automated quantitative analysis program, 3DSRT. Results: Qualitative analysis using eZIS demonstrated occipital hypoperfusion in 17 subjects (68%). The quantified mean blood perfusion in the occipital segment on the 3DSRT template was 40.7 ± 5.03 ml/100 g/min (right) and 40.5 ± 5.38 ml/100 g/min (left), and in 19 DLB patients these values were below the normal limit. Twenty-four of 25 subjects (96%) had decreased cardiac MIBG uptake in the delayed image. Conclusion: MIBG myocardial scintigraphy was superior to brain perfusion SPECT in detecting a characteristic feature of DLB. Our results suggest that combining SPECT and MIBG scintigraphy could increase the accuracy of clinical diagnosis of DLB.

An Update on Fetal Alcohol Syndrome-Pathogenesis, Risks, and Treatment.

Alcohol is a well-established teratogen that can cause variable physical and behavioral effects on the fetus. The most severe condition in this spectrum of diseases is known as fetal alcohol syndrome (FAS). The differences in maternal and fetal enzymes, in terms of abundance and efficiency, in addition to reduced elimination, allow for alcohol to have a prolonged effect on the fetus. This can act as a teratogen through numerous methods including reactive oxygen species (generated as by products of CYP2E1), decreased endogenous antioxidant levels, mitochondrial damage, lipid peroxidation, disrupted neuronal cell-cell adhesion, placental vasoconstriction, and inhibition of cofactors required for fetal growth and development. More recently, alcohol has also been shown to have epigenetic effects. Increased fetal exposure to alcohol and sustained alcohol intake during any trimester of pregnancy is associated with an increased risk of FAS. Other risk factors include genetic influences, maternal characteristics, for example, lower socioeconomic statuses and smoking, and paternal chronic alcohol use. The treatment options for FAS have recently started to be explored although none are currently approved clinically. These include prenatal antioxidant administration food supplements, folic acid, choline, neuroactive peptides, and neurotrophic growth factors. Tackling the wider impacts of FAS, such as comorbidities, and the family system have been shown to improve the quality of life of FAS patients. This review aimed to focus on the pathogenesis, especially mechanisms of alcohol teratogenicity, and risks of developing FAS. Recent developments in potential management strategies, including prenatal interventions, are discussed.

Stem cell therapy: social recognition recovery in a FASD model

To better understand the cellular pathogenetic mechanisms of fetal alcohol spectrum disorder (FASD) and the therapeutic benefit of stem cell treatment, we exposed pregnant rats to ethanol followed by intravenous administration of neural stem cells (NSCs) complexed with atelocollagen to the new born rats and studied recovery of GABAergic interneuron numbers and synaptic protein density in the anterior cingulate cortex, hippocampus and amygdala. Prenatal ethanol exposure reduced both parvalbumin-positive phenotype of GABAergic interneurons and postsynaptic density protein 95 levels in these areas. Intravenous NSC treatment reversed these reductions. Furthermore, treatment with NSCs reversed impaired memory/cognitive function and social interaction behavior. These experiments underscore an important role for synaptic remodeling and GABAergic interneuron genesis in the pathophysiology and treatment of FASD and highlight the therapeutic potential for intravenous NSC administration in FASD utilizing atelocollagen.

Internet addiction and self-evaluated attention-deficit hyperactivity disorder traits among Japanese college students.

Internet addiction (IA), also referred to as Internet use disorder, is a serious problem all over the world, especially in Asian countries. Severe IA in students may be linked to academic failure, attention‐deficit hyperactivity disorder (ADHD), and forms of social withdrawal, such as hikikomori. In this study, we performed a survey to investigate the relation between IA and ADHD symptoms among college students.

Internet addiction and self-evaluated ADHD traits among Japanese college students

Internet addiction (IA), also referred to as Internet use disorder, is a serious problem all over the world, especially in Asian countries. Severe IA in students may be linked to academic failure, attention‐deficit hyperactivity disorder (ADHD), and forms of social withdrawal, such as hikikomori. In this study, we performed a survey to investigate the relation between IA and ADHD symptoms among college students.

Stem cell therapy: a new approach to the treatment of refractory depression

To better understand the relationship of repeated exposure to adversity during early development as a risk factor for refractory depression, we exposed pregnant female rats to ethanol and the resulting pups to corticosterone during adolescence. A stressful forced swim test was then used to induce depression-like behavior. The adolescent rat brains were examined for the possible therapeutic benefit of a combination of sertraline, an antidepressant, and neural stem cells (NSCs) complexed with atelocollagen in relation to the level of GABAergic interneuron and synaptic protein density in different brain regions. The combined exposures of prenatal and adolescent stress resulted in a reduction in parvalbumin (PV)-positive phenotype of GABAergic interneurons and reduced postsynaptic density protein 95 (PSD-95) levels in the anterior cingulate cortex, amygdala, and hippocampus. Treatments with sertraline and NSCs reversed the reductions in PV-positive cells and PSD-95 levels. Furthermore, the combined treatment of sertraline and NSCs resulted in reduced depressive-like behaviors. These experiments underscore a potentially important role for synaptic remodeling and GABAergic interneuron genesis in the treatment of refractory depression and highlight the therapeutic potential of stem cell and pharmacological combination treatments for refractory depression.

Suicidal ideation and burnout among psychiatric trainees in Japan

Burnout is a psychological condition that may occur in all workers after being exposed to excessive work‐related stresses. We investigated suicidal ideation and burnout among Japanese psychiatric trainees as a part of the Burnout Syndrome Study (BoSS) International.