Involvement of dysregulated hippocampal histone H3K9 methylation at the promoter of the BDNF gene in impaired memory extinction.

Rationale: Since the precise mechanisms of posttraumatic stress disorder (PTSD) remain unknown, effective treatment interventions have not yet been established. Impaired extinction of fear memory (EFM) is one of the core symptoms of PTSD and is associated with stress-induced epigenetic change in gene expression.

Objectives: In this study, we examined whether the involvement of histone H3 lysine 9 dimethylation (H3K9me2) in EFM is mediated through brain-derived neurotrophic factor (BDNF) expression in the hippocampus, and whether BIX01294, a selective G9a and GLP histone methyltransferase inhibitor, could be treatment for impaired EFM in an animal model of PTSD.

Neonatal Isolation Increases the Susceptibility to Learned Helplessness through the Aberrant Neuronal Activity in the Ventral Pallidum of Rats.

Objective: : Environmental deprivation, a type of childhood maltreatment, has been reported to constrain the cognitive developmental processes such as associative learning and implicit learning, which may lead to functional and morphological changes in the ventral pallidum (VP) and pessimism, a well-known cognitive feature of major depression. We examined whether neonatal isolation (NI) could influence the incidence of learned helplessness (LH) in a rat model mimicking the pessimism, and the number of vesicular glutamate transporter 2 (VGLUT2)-expressing VP cells and Penk-expressing VP cells.

Methods: : The number of escape failures from foot-shocks in the LH test was measured to examine stress-induced depression-like behavior in rats.

Long-term mental health and resilience of the first responders in Japanese ground self-defense forces engaging body recovery after the great east Japan earthquake.

Handling human remains is extremely difficult and stressful task, and it can contribute to the development of stress-related mental health problems. To prevent disaster from the development of mental disorders in first responders, it will be important to elucidate factors sustaining psychological well-being following the events requiring handling of human remains. Japanese Ground Self-Defense Forces (JGSDF) first responders (n = 146), involved in human remains recovery after the Great East Japan Earthquake (GEJE) participated.

Chondroitin sulfate expression around spinal motoneurons during postnatal development in rats.

Perineuronal nets are extracellular matrix structures that surround neuronal cell bodies and their proximal dendrites in the central nervous system. Chondroitin sulfate proteoglycans, which contain chondroitin sulfates (CSs) are major components of perineuronal nets. CSs are considered to have inhibitory roles in neural plasticity, although the effects differ according to their sulfation pattern.

Chemogenetic activation of the mPFC alleviates impaired fear memory extinction in an animal model of PTSD.

Background And Aim: Although impaired extinction of fear memory (EFM) is a hallmark symptom of posttraumatic stress disorder (PTSD), the mechanisms underlying the impairment are unknown. Activation of the infralimbic cortex (IL) in the medial prefrontal cortex (mPFC) has been reported to predict successful fear extinction, whereas functionally disrupting this region impairs extinction. We examined whether chemogenetic activation of the IL could alleviate impaired EFM in a single prolonged stress (SPS) rat model of PTSD.

The role of glucocorticoid receptors in the induction and prevention of hippocampal abnormalities in an animal model of posttraumatic stress disorder.

Rationale: Since the precise mechanisms of posttraumatic stress disorder (PTSD) remain unknown, effective treatment interventions have not yet been established. Numerous clinical studies have led to the hypothesis that elevated glucocorticoid levels in response to extreme stress might trigger a pathophysiological cascade which consequently leads to functional and morphological changes in the hippocampus.

Objectives: To elucidate the pathophysiology of PTSD, we examined the alteration of hippocampal gene expression through the glucocorticoid receptor (GR) in the single prolonged stress (SPS) paradigm, a rat model of PTSD.

Structural variation in the glycogen synthase kinase 3β and brain-derived neurotrophic factor genes in Japanese patients with bipolar disorders.

Background: Lithium is the first-line drug for the treatment of bipolar disorders (BDs); however, not all patients responded. Glycogen synthase kinase (GSK) 3β and brain-derived neurotrophic factor (BDNF) play a role in the therapeutic action of lithium. Since structural variations were reported in these genes, it is possible that these genomic variations may be involved in the therapeutic responses to lithium.

Combined brain-derived neurotrophic factor with extinction training alleviate impaired fear extinction in an animal model of post-traumatic stress disorder.

Impaired fear memory extinction (Ext) is one of the hallmark symptoms of post-traumatic stress disorder (PTSD). However, since the precise mechanism of impaired Ext remains unknown, effective interventions have not yet been established. Recently, hippocampal-prefrontal brain-derived neurotrophic factor (BDNF) activity was shown to be crucial for Ext in naïve rats.

Musical disability in children with autism spectrum disorder.

Although enhanced musical ability is reported in individuals with autism spectrum disorders (ASD), this observation may be uncommon, and reports of auditory processing deficits suggest musical ability may be impaired. We hypothesized that musical ability would be impaired in children with ASD, that the severity of impairment would correlate with cognitive dysfunction, and with clinical features of illness. We evaluated 26 children with ASD and 27 typically developing (TD) children using the Montreal Battery of Evaluation of Amusia short version (MBEA-s) as well as cognitive tests and clinical evaluations of ASD symptomatology.

The influence of aging on the methylation status of brain-derived neurotrophic factor gene in blood.

Objective: Brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of psychiatric disorders in adults and elderly individuals, and as a result, the DNA methylation (DNAm) of the BDNF gene in peripheral tissues including blood has been extensively examined to develop a useful biomarker for psychiatric disorders. However, studies to date have not previously investigated the effect of age on DNAm of the BDNF gene in blood. In this context, we measured DNAm of 39 CpG units in the CpG island at the promoter of exon I of the BDNF gene.

Musical deficits and cortical thickness in people with schizophrenia.

Investigation of acquired amusia caused by brain damage suggested that cortical lesions of the right hemisphere contributed to musical deficits. We previously reported reduced musical ability in schizophrenia; these deficits were correlated with clinical manifestations such as cognitive dysfunction and negative symptoms. However, the neural substrate underlying the musical disability in schizophrenia remains unclear.

Sex differences in auditory verbal hallucinations in early, middle and late adolescence: results from a survey of 17 451 Japanese students aged 12-18 years.

Objectives: Women have higher rates of auditory verbal hallucinations (AVH) than men; however, less is known about sex differences in the prevalence of AVH in early, middle and late adolescence. We sought to elucidate the differences in the prevalence of AVH and to examine the degree to which these differences could be explained by differences in levels of depressive symptoms.

Design: We used a cross-sectional design and a self-reported questionnaire.

Schizophrenia as a prodromal symptom in a patient harboring SNCA duplication.

We present the case of a patient who developed delusions and auditory hallucinations and was clinically diagnosed as having schizophrenia. Ten years after the onset of schizophrenia, the disease progressed to mild parkinsonism. SNCA duplication was confirmed.

Cortical activation changes and sub-threshold affective symptoms are associated with social functioning in a non-clinical population: A multi-channel near-infrared spectroscopy study.

Few studies have examined the relationship between social function and brain activation in non-clinical populations. The aim of the present study was to assess this relationship and examine the underlying cortical mechanisms in a non-clinical population. Eighty healthy volunteers performed a serial arithmetic task according to the Uchida-Kraepelin performance test while hemoglobin concentration changes were assessed on the surface of the prefrontal cortex (PFC) using 32-channel near-infrared spectroscopy.

The potential use of histone deacetylase inhibitors in the treatment of depression.

Numerous preclinical studies demonstrate that changes in gene expression in the brain occur in animal models of depression using exposure to stress, such as social defeat and leaned helplessness, and that repeated administration of antidepressants ameliorates these stress-induced changes in gene expression. These findings suggest that alteration in gene transcription in the central nervous system in response to stress plays an important role in the pathophysiology of depression. Recent advances in epigenetics have led to the realization that chromatin remodeling mediated by histone deacetylase (HDAC) is closely involved in the regulation of gene transcription.

Comparing the driving behaviours of individuals with frontotemporal lobar degeneration and those with Alzheimer's disease.

Background: Assessing driving aptitude in dementia patients is critically important for both patient and public safety. However, there have been only a few reports on the driving behaviours and accident risk of patients with dementia, especially frontotemporal lobar degeneration (FTLD). Therefore, we compared the characteristics of driving behaviours in patients with FTLD and those with Alzheimer's disease (AD).

Blood diagnostic biomarkers for major depressive disorder using multiplex DNA methylation profiles: discovery and validation.

Aberrant DNA methylation in the blood of patients with major depressive disorder (MDD) has been reported in several previous studies. However, no comprehensive studies using medication-free subjects with MDD have been conducted. Furthermore, the majority of these previous studies has been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions.

The potential of SLC6A4 gene methylation analysis for the diagnosis and treatment of major depression.

We examined the utility of DNA methylation profiles at the CpG island of SLC6A4 (DMS) as a diagnostic biomarker for major depression (MD). In addition, the relationship between DMS and the serotonin transporter gene-linked polymorphic region (5-HTTLPR) allele, the severity of symptoms, number of early adversities, and therapeutic responses to antidepressants were examined. Genomic DNA was extracted from peripheral blood of Japanese healthy controls and patients with MD before and after treatment.

Studies of extraction and transport system for highly charged ion beam of 18 GHz superconducting electron cyclotron resonance ion source at Research Center for Nuclear Physics.

An 18 GHz superconducting electron cyclotron resonance ion source is installed to increase beam currents and to extend the variety of ions especially for highly charged heavy ions which can be accelerated by cyclotrons of Research Center for Nuclear Physics (RCNP), Osaka University. The beam production developments of several ions from B to Xe have been already done [T. Yorita, K.

[Epigenetic mechanism of major depression].

A recent genome-wide association mega analyses of major depression suggests that major depression is a polygenic and multifactorial disease and that a gene-environmental interaction plays a pivotal role in its pathophysiology. Recent advances in epigenetics, such as improved methods for the measurement of DNA methylation, and covalent histone modifications, have shed light on the molecular mechanisms by which environmental stimuli affect gene expression in the brain and subsequently alter the cognitive function. Herein, we summarize how recent progress in epigenetics has advanced our understanding of the pathophysiology of major depression, particularly the role of glucocorticoid receptors and brain-derived neurotrophic factor, including the development of stress vulnerability and resilience, and we discuss the possibility of using epigenetic drugs, such as histone deacetylase inhibitors, for the treatment of major depression.

Resting state low-frequency fluctuations in prefrontal cortex reflect degrees of harm avoidance and novelty seeking: an exploratory NIRS study.

Harm avoidance (HA) and novelty seeking (NS) are temperament dimensions defined by Temperament and Character Inventory (TCI), respectively, reflecting a heritable bias for intense response to aversive stimuli or for excitement in response to novel stimuli. High HA is regarded as a risk factor for major depressive disorder and anxiety disorder. In contrast, higher NS is linked to increased risk for substance abuse and pathological gambling disorder.

Electroconvulsive seizure induces thrombospondin-1 in the adult rat hippocampus.

Synaptic dysfunction has recently gained attention for its involvement in mood disorders. Electroconvulsive therapy (ECT) possibly plays a role in synaptic repair. However, the underlying mechanisms remain uncertain.