Need for education of psychiatric evaluation of offenders with mental disorders:A questionnaire survey for Japanese designated psychiatrists

BACKGROUND The management of offenders with mental disorders has been a significant concern in forensic psychiatry.In Japan,the introduction of the Medical Treatment and Supervision Act in 2005 addressed the issue.However,numerous psychiatric patients at risk of violence still find themselves subject to the administrative involuntary hospitalization(AIH)scheme,which lacks clarity and updated standards.AIM To explore current as well as optimized learning strategies for risk assessment in AIH decision making.METHODS We conducted a questionnaire survey among designated psychiatrists to explore their experiences and expectations regarding training methods for psychiatric assessments of offenders with mental disorders.RESULTS The findings of this study’s survey suggest a prevalent reliance on traditional learning approaches such as oral education and on-the-job training.CONCLUSION This underscores the pressing need for structured training protocols in AIH consultations.Moreover,feedback derived from inpatient treatment experiences is identified as a crucial element for enhancing risk assessment skills.

Novel insights into the mechanism of reactive oxygen species-mediated neurodegeneration

Neurite degeneration,a major component of many neurodegenerative diseases,such as Parkinson’s disease,Alzheimer’s disease,and amyotrophic lateral sclerosis,is not part of the typical apoptosis signaling mechanism,but rather it appears that a self-destructive process is in action.Oxidative stress is a well-known inducer of neurodegenerative pathways:neuronal cell death and neurite degeneration.Although oxidative stress exerts cytotoxic effects leading to neuronal loss,the pathogenic mechanisms and precise signaling pathways by which oxidative stress causes neurite degeneration have remained entirely unknown.We previously reported that reactive oxygen species generated by NADPH oxidases induce activation of the E3 ubiquitin ligase ZNRF1 in neurons,which promotes neurite degeneration.In this process,the phosphorylation of an NADPH oxidase subunit p47-phox at the 345serine residue serves as an important checkpoint to initiate the ZNRF1-dependent neurite degeneration.Evidence provides new insights into the mechanism of reactive oxygen species-mediated neurodegeneration.In this review,we focus specifically on reactive oxygen species-induced neurite degeneration by highlighting a phosphorylation-dependent regulation of the molecular interaction between ZNRF1 and the NADPH oxidase complex.

New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brainrelated diseases

Brain-derived neurotrophic factor(BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has beenreported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer's disease, Huntington's disease, depression and schizophrenia.

Impact of glucocorticoid on neurogenesis

Neurogenesis is currently an area of great interest in neuroscience.It is closely linked to brain diseases,including mental disorders and neurodevelopmental disease.Both embryonic and adult neurogeneses are influenced by glucocorticoids secreted from the adrenal glands in response to a variety of stressors.Moreover,proliferation/differentiation of the neural stem/progenitor cells（NSPCs）is affected by glucocorticoids through intracellular signaling pathways such as phosphoinositide 3-kinase（PI3K）/Akt,hedgehog,and Wnt.Our review presents recent evidence of the impact of glucocorticoids on NSPC behaviors and the underlying molecular mechanisms;this provides important information for understanding the pathological role of glucocorticoids on neurogenesis-associated brain diseases.

Prognostic value of post-treatment ^(18)F-FDG PET/CT for advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy

Objective：To clarify the prognostic value of post-treatment 18F-fluorodeoxyglucose （FDG） positron emission tomography （PET）/computed tomography （CT） in patients with advanced head and neck squamous cell carcinoma （HNSCC） after combined intra-arterial chemotherapy and radiotherapy （IACR）.Methods：Thirty-six patients with HNSCC who underwent IACR were recruited.The period from the end of IACR to the last post-treatment 18F-FDG PET/CT examination was 8-12 weeks.Both patient-based and lesion-based analyses were used to evaluate the PET/CT images.For lesion-based analysis,36 regions （12 lesions of recurrences and 24 scars at primary sites） were selected.The Kaplan-Meier method was used to assess the overall survival （OS） stratified by 18F-FDG uptake or visual interpretation results.Results：Twelve patients with recurrence were identified by six months after IACR.The sensitivity and specificity in the patient-based analysis were 67％ （8/12） and 88％ （21/24）,respectively.The mean OS was estimated to be 12.1 months （95％ CI,6.3-18.0 months） for the higher maximum standardized uptake value （SUVmax） group （n=7） and 44.6 months （95％ CI,39.9-49.3 months） for the lower SUVmax group （n=29）.OS in the higher SUVmax group （cut-off point,6.1） or positive visual interpretation group was significantly shorter than that in the lower SUVmax or negative visual interpretation group （P＜0.001 and P＜0.05,respectively）.Conclusions：The SUVmax and visual interpretation of HNSCC on post-IACR 18F-FDG PET/CT can provide prognostic survival estimates.

The <i>q</i>-Exponential Probability Discounting of Gain and Loss

Probability discounting is defined as the devaluation of outcomes as the probability of receiving or paying those decreases. A q-exponential probability discounting model based on Tsallis’ statistics has been proposed in econophysics (Takahashi, 2007, Physica A). We examined (a) fitness of the models to behavioral data of probability discounting of both gain and loss;and (b) relationships between parameters in the q-exponential probability discounting model across gain and loss. Our results demonstrated that, for both gain and loss, the q-exponential model better fits the behavioral data than exponential and hyperbolic functions, and there is the sign effect in q-exponential probability discounting. Relationships between Kahneman-Tversky’s prospect theory in behavioral economics and the q-exponential probability discounting are high-lightened.

Neurobehavioral and Hemodynamic Evaluation of Cognitive Shifting in Children with Autism Spectrum Disorder

The restrictive, stereotyped behavior in autism spectrum disorder (ASD) is considered to be related to deficits in execu- tive function. In particular, cognitive shifting in executive function is deeply related to stereotyped behavior in ASD. Previous investigations have clarified that the lateral prefrontal cortex is involved in cognitive shifting when flexible changes in attention were needed. However, a few studies have revealed a direct association between cognitive shifting tasks and lateral prefrontal cortex activity in children with ASD. We examined cognitive shifting in 7- to 12-year-old children with ASD and typically developing children using the dimensional change card sort task. In addition, using near-infrared spectroscopy, we examined prefrontal brain activity in conjunction with cognitive shifting. The autistic children provided fewer correct answers and slower reaction times in the task than typically developing children. Fur- thermore, the autistic children displayed a decline in right lateral prefrontal cortex activity during the task compared with typically developing children. In addition, a negative correlation was observed between the severity of autism and brain activity during the task. These results suggest that the activity and physiological indices used in this study may be useful for identifying the symptoms of ASD and discriminating ASD from other disabilities.

Novel aspects of extracellular adenosine dynamics revealed by adenosine sensor cells

Adenosine modulates diverse physiological and pathological processes in the brain, including neuronal activities, blood flow, and inflammation. However, the mechanisms underlying the dynamics of extracellular adenosine are not fully understood. We have recently developed a novel biosensor, called an adenosine sensor cell, and we have characterized the neuronal and astrocytic pathways for elevating extracellular adenosine. In this review, the physiological implications and therapeutic potential of the pathways revealed by the adenosine sensor cells are discussed. We propose that the multiple pathways regulating extracellular adenosine allow for the diverse functions of this neuromodulator, and their malfunctions cause various neurological and psychiatric disorders.

Possible protective action of neurotrophic factors and natural compounds against common neurodegenerative diseases

It has been suggested that altered levels/function of brain-derived neurotrophic factor （BDNF） play a role in the pathophysiology of neurodegenerative diseases including Alzheimer＇s disease. BDNF positively contributes to neural survival and synapse maintenance via stimulating its high affinity receptor TrkB, making upregulation of BDNF and/or activation of BDNF-related intracellnlar signaling an attractive approach to treating neurodegenerative diseases. In this short review, I briefly introduce small natural compounds such as flavonoids that successfully increase activation of the BDNF system and discuss their beneficial effects against neurodegeneration.

Spatiotemporal Neural Activity Changes in the Molluscan Olfactory Center Specifically Induced by Innately Aversive and <i>In Vitro</i>Aversively Conditioned Odors

In the procerebrum (PC), the olfactory center, of the land slug Limax, an oscillation of local field potential (LFP) with 0.5 - 1 Hz is observed by electrophysiological extracellular recording. The oscillation has a phase delay along the distal-proximal axis, resulting in the propagation of waves from the distal to proximal region. One important advantage of nervous systems of mollusks such as Limax is that their nervous systems in vitro retain several types of computational properties found in vivo (e.g. learning and memory). A previous study showed that the LFP frequency in the PC of Limax increased specifically in response to innately aversive and in vitro aversively conditioned odors. In the present study, we examined spatiotemporal neural activity changes induced in the PC by those odors using the fluorescent voltage imaging technique. The results showed that innately aversive (onion and hexanol) and in vitro aversively conditioned (carrot, which is innately attractive) odors specifically induced an increase in propagation speed of the neural activity in the PC, while innately attractive odors did not induce it. The results also suggested that the avoidance behavior by those odors might be induced by the increase of propagation speed and the following increases in the discharges of the partial nerve that transmits the motor output.

Antipsychotic Medication and Risk of QTc Prolongation: Focus on Multiple Medication and Role of Cytochrome P450 Isoforms

Objective: To identify the effects of antipsychotics on QTc prolongation in light of age, gender, antipsychotic combination pattern, antipsychotic doses and cytochrome P450 (CYP) mediation, using large database describing the antipsychotic treatment of patients with schizophrenia in Japan. Methods: Using database of 4176 patients with schizophrenia discharged between April 2004 and March 2005 and receiving outpatient treatment from 526 psychiatric hospitals in Japan. Of the patients, 1437 were included for the analysis. These patients were classified into three groups according to the antipsychotic CPZ-equivalent doses that they received (low, 1 - 299 mg;middle, 300 - 999 mg;and high, ≥1000 mg). QTc intervals ≥ 440 msec were considered prolonged. We reviewed all the package inserts of the antipsychotics used from the website of Pharmaceuticals and Medical Devices Agency. Results: The mean QTc interval of the total patient group was 410.4 ± 23.3 msec. The females had significantly higher QTc values than the males (414.5 ± 24.0 vs. 406.8 ± 22.2 msec, respectively;p 0.05). Logistic regression analysis revealed that female gender (odds ratio [OR] = 1.83;95% CI: 1.28 - 2.56), CYP3A4-metabolized drugs (OR 1.56;95% CI: 1.05 - 2.30) were associated with an increased risk of QTc prolongation. Conclusion: The co-prescription of CYP3A4-mediated antipsychotic drugs should be carefully considered in females due to potential risk of QTc prolongation. Further studies of the cardiovascular safety of antipsychotics are warranted in patients receiving multiple medications.

An Experimental Comparison of Quantum Decision Theoretical Models of Intertemporal Choice for Gain and Loss

In mathematical physics and psychology, “quantum decision theory” has been proposed to explain anomalies in human decision-making. One of such quantum models has been proposed to explain time inconsistency in human decision over time. In this study, we conducted a behavioral experiment to examine which quantum decision models best account for human intertemporal choice. We observed that a q-exponential model developed in Tsallis’ thermodynamics (based on Takahashi’s (2005) nonlinear time perception theory) best fit human behavioral data for both gain and loss, among other quantum decision models.

Improved Visualization of the Anterior Thalamic Radiation in Bipolar Disorder by Diffusion Tensor Tractography

Diffusion tensor imaging (DTI) is a method for noninvasively measuring and imaging the diffusion of water molecules using MRI. Diffusion tensor tractography (DTT) can be used to presume macroscopic nerve fascicle distribution by determining, based on information obtained by DTI, whether the diffusion anisotropy vectors of adjacent voxels are continuous or not. We prepared a DTT map of the cerebral white matter nerve fascicles and investigated its usefulness for differentiation between Alzheimer’s disease and bipolar disorder (BD), a major depressive disorder, based on the nerve fiber depiction, in addition to the fractional anisotropy and apparent diffusion coefficient values. We encountered two cases of BD in which the DTT image of the anterior thalamic radiation (ATR) improved following effective treatment with lamotrigine. Lamotrigine increases the synaptic strength due to its effect of promoting the traffic of the α-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor on the neuronal membrane. Downregulation of postsynaptic AMPA receptor expression can reportedly be observed during depressive episodes in BD. We consider that visualization of improvement of the ATR in response to treatment with lamotrigine (related to its pharmacological effect on the AMPA receptor) is valuable, as it suggests reversibility of the damage of the nerve fibers in this disease condition.

Association between the Consumption of Carbonated Beverages and Out-of-Hospital Cardiac Arrests of Cardiac Origin in Japan

Background: The consumption of carbonated beverages has been shown to increase the risk of developing metabolic syndrome. The associations between the consumption of carbonated beverages and left arterial dimension or left ventricular mass are believed to be likely related to the greater body weight of carbonated beverage drinkers relative to non-drinkers. Nonetheless, little is known about the association between the consumption of carbonated beverages and out-of-hospital cardiac arrests (OHCAs) in Japan. Methods: We compared the age-adjusted incidence of OHCAs to the expenditures on various beverages per person between 2005 and 2011 in the 47 prefectures of Japan. Patients who suffered from OHCAs of cardiac and non-cardiac origin were enrolled in All-Japan Utstein Registry of the Fire and Disaster Management Agency. The expenditures on various beverages per person in the 47 prefectures in Japan were obtained from data published by the Ministry of Health, Labour and Welfare of Japan. Results: There were 797,422 cases of OHCA in the All-Japan Utstein registry between 2005 and 2011, including 11,831 cases who did not receive resuscitation. Among these 785,591 cases of OHCA, 435,064 (55.4%) were classified as cardiac origin and 350,527 (44.6%) were non-cardiac origin. Non-cardiac origin included cerebrovascular disease, respiratory disease, malignant tumor, and exogenous disease (4.8%, 6.1%, 3.5%, and 18.9%, respectively). The expenditures on carbonated beverages were significantly associated with OHCAs of cardiac origin (r = 0.30, p = 0.04), but not non-cardiac origin (r = -0.03, p = 0.8). Expenditures on other beverages, including green tea, tea, coffee, cocoa, fruit or vegetable juice, fermented milk beverage, milk beverage, and mineral water, were not significantly associated with OHCAs of cardiac origin. Conclusion: Carbonated beverage consumption was significantly and positively associated with OHCAs of cardiac origin in Japan, indicating that beverage habits might play a role in OHCAs of cardiac origin.

Bipolar I disorder and expressed emotion of families: A cohort study in Japan

The relationships between expressed emotion (EE) of the families and the course of bipolar disorder have been examined only in a limited number of cohort studies. No study has yet been reported from Asia. The subjects were 12 patients that had been diagnosed with bipolar I disorder according to DSM-IV and their 12 key family members. The families of the patients were interviewed using the Camberwell Family Interview (CFI) within 2 weeks of the admission of the patients, and their EE were evaluated. The patients were then followed up for 9 months after their discharge from the hospital. The patients were divided into a high-EE group and a low-EE group using the cut-off based on the number of critical comments (CC) and emotional overinvolvement (EOI), and the 9-month relapse risk was compared. When the subjects with 3 or more CC or an EOI score of 3 or more were regarded as the high-EE group, and the others as the low-EE group, the 9-month relapse risk was 100% (3/3) for the high EE group and 0% (0/9) for the low EE group. (Fisher’s exact test p = 0.005) EE based on the CFI appear to be correlated with relapse in bipolar I disorder in Japan.

Investigating Neural Representation of Finger-Movement Directions Using Electroencephalography Independent Components

There are few EEG studies on finger movement directions because ocular artifacts also convey directional information, which makes it hard to separate the contribution of EEG from that of the ocular artifacts. To overcome this issue, we designed an experiment in which EEG’s temporal dynamics and spatial information are evaluated together to improve the performance of brain-computer interface (BCI) for classifying finger movement directions. Six volunteers participated in the study. We examined their EEG using decoding analyses. Independent components (ICs) that represented brain-source signals successfully classified the directions of the finger movements with higher rates than chance level. The weight analyses of the classifiers revealed that maximal performance of the classification was recorded at the latencies prior to the onset of finger movements. The weight analyses also revealed the relevant cortical areas including the right lingual, left posterior cingulate, left inferior temporal gyrus, and right precuneus, which indicated the involvement of the visuospatial processing. We concluded that combining spatial distribution and temporal dynamics of the scalp EEG may improve BCI performance.

The First Case of Human Herpesvirus 7-Related Epilepsy in the Republic of Belarus

Background:Human herpesvirus(HHV)-7 is usually associated with febrile seizures.Later onset and higher frequency of seizures are characteristic of pediatric HHV-7,compared with HHV-6 infection.The HHV-7-related severe neurological disorders are predominantly observed in immunocompromised individuals.Reports of healthy individuals with HHV-7 infection and diverse neurological disorders are limited.Patient Description:We present a case of HHV-7-related epilepsy in an immunocompetent 11-year old boy and extensive infectious and autoimmune testing positive only for HHV-7 in the cerebrospinal fluid.The patient made a good recovery after treatment with intravenous immunoglobulin and methylprednisolone.Discussion:This is the first reported case of epilepsy associated with HHV-7 in a previously healthy individual.It also demonstrates that intravenous immunoglobulin and steroids may be used in the course of this disorder and may be beneficial for recovery.

Behavioral and Neural Enhancing Effects of a Summer Treatment Program in Children with Attention Deficit Hyperactivity Disorder

Deficiency in executive functioning is a core symptom of attention deficit hyperactivity disorder (ADHD). The brain part responsible for executive functions is the prefrontal cortex (PFC). Although drug-based interventions can improve PFC activity, reports on PFC activity being improved by behavioral treatment are lacking. We evaluated whether a summer treatment program (STP) administering comprehensive behavioral treatment would increase PFC activity in children with ADHD. We examined behavioral and neural changes in 20 children before and after the STP, conducted over a 2-week period. We asked the parents/guardians to complete the Swanson, Nolan, and Pelham IV scale to assess severity of ADHD. The main task evaluating executive control was the reverse Stroop task. To examine changes in physiological indices, we used near-infrared spectroscopy to measure changes in PFC activity. Subjective assessments by parents/guardians indicated that ADHD symptoms improved significantly. There was also significant improvement in the number of correct responses and interference rates in the reverse Stroop task. Furthermore, post-intervention PFC activity was significantly higher. These results suggest that the STP improved inhibitory control in executive function, which is considered as a key symptom of ADHD. The increase in PFC activity further suggests that the STP improves cognition through neural function.

Alzheimer’s disease early diagnostic and staging biomarkers revealed by large-scale cerebrospinal fluid and serum proteomic profiling

Amyloid-b,tau pathology,and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease(AD).However,these proteins represent only a fraction of the complex biological processes underlying AD,and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic biomarkers.More ADspecific early diagnostic and disease staging biomarkers are needed.In this study,we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid(CSF)and serum samples in a discovery cohort comprising 98 participants.Candidate biomarkers were validated by parallel reaction monitoring–based targeted proteomic assays in an independent multicenter cohort comprising 288 participants.We quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort,identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers,respectively.In the validation cohort,58 and 21 CSF proteins,as well as 12 and 18 serum proteins,were verified as early diagnostic and staging biomarkers,respectively.Separate 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment(MCI)due to AD from normal cognition with areas under the curve of 0.984 and 0.881,respectively.The 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative diseases.Moreover,we identified 21 CSF and 18 serum stage-associated proteins re-flecting AD stages.Our findings provide a foundation for developing bloodbased tests for AD screening and staging in clinical practice.

Functional interactions between steroid hormones and neurotrophin BDNF

Brain-derived neurotrophic factor(BDNF),a critical neurotrophin,regulates many neuronal aspects including cell differentiation,cell survival,neurotransmission,and synaptic plasticity in the central nervous system(CNS) .Though BDNF has two types of receptors,high affinity tropomyosin-related kinase(Trk) B and low affinity p75 receptors,BDNF positively exerts its biological effects on neurons via activation of TrkB and of resultant intracellular signaling cascades including mitogenactivated protein kinase/extracellular signal-regulated protein kinase,phospholipase Cγ,and phosphoinositide 3-kinase pathways.Notably,it is possible that alteration in the expression and/or function of BDNF in the CNS is involved in the pathophysiology of various brain diseases such as stroke,Parkinson's disease,Alzheimer's disease,and mental disorders.On the other hand,glucocorticoids,stress-induced steroid hormones,also putatively contribute to the pathophysiology of depression.Interestingly,in addition to the reduction in BDNF levels due to increased glucocorticoid exposure,current reports demonstrate possible interactions between glucocorticoids and BDNF-mediated neuronal functions. Other steroid hormones,such as estrogen,are involved in not only sexual differentiation in the brain,but also numerous neuronal events including cell survival and synaptic plasticity.Furthermore,it is well known that estrogen plays a role in the pathophysiology of Parkinson's disease,Alzheimer's disease,and mental illness,while serving to regulate BDNF expression and/or function.Here,we present a broad overview of the current knowledge concerning the association between BDNF expression/function and steroid hormones(glucocorticoids and estrogen).