Schizophrenia is a severe mental illness with a prevalence of approximately 1%. Its core features are delusions, hallucinations, affective flattening and disorganized behaviors. Although schizophrenia is severe psychiatric disorder, it is classified in the category of common diseases. Many studies have shown a strong genetic component for the development of schizophrenia. Heritability of schizophrenia is estimated to be approximately 80%. The mode of inheritance is multifactorial. Schizophrenia is a common and genetically complex disease. Schizophrenia research has developed rapidly in recent years. This is based on developments in the technology for molecular genetics. The advanced technologies can be used to perform genome-wide association study (GWAS) and copy number variant/variation (CNV) study. GWAS has revealed associations between schizophrenia and ZNF804A, NOTCH4 (major histocompatibility complex region: MHC), NRGN, TCF4, LSM1, BRP44, NFKB, NKAPL and TSPAN18 genes. The CNV study has found associations between schizophrenia and duplications/deletions of 1q21.1, 3q29, 16p11.2, 15q11.2, 15q13.3, 17q12 and 22q11.2 regions. The 22q11.2 deletion is the most interesting region in the genetic etiology of schizophrenia. A patient with 22q11.2 deletion is referred to as having 22q11.2 deletion syndrome (22q11.2DS). This syndrome is also called DiGeorge/Velocardiofacial syndrome. Patients with 22q11.2DS have a high incidence of schizophrenia (~23%). Schizophrenia may exhibit etiological heterogeneity. On the basis of the GWAS and CNV study findings, we consider that there are two subtypes that are caused by many genes with low power for development (multifactorial disease) and few genes with high power (i.e., a Mendelian disease) in schizophrenia.

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In the 5th century BC, people believed that depression was caused by an excess of black bile in the gall bladder. In the 1960s, the “monoamine hypothesis”, the first major theory about the biological etiology of depression, was formulated based on the antidepressant efficacy of iproniazid and imipramine. This hypothesis has dominated our understanding of depression for over 40 years and it has led the development of new classes of drugs, such as selective serotonin reuptake inhibitors. However, the monoamine hypothesis does not fully explain the mechanisms of depression, due to the 2-3 week delay between the rapid increase in the monoamine levels until the therapeutic effect. Although the pathophysiology of depression remains unknown, recent advances in neuroscience have provided new insights into the mechanisms of depression. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the most consistent biological findings in depression. Elevated cortisol as a consequence of HPA axis overactivity leads to structural changes and neuronal damage in the hippocampus, which may be associated with symptoms of depression. Neurochemical studies have revealed that antidepressants promote hippocampal neurogenesis by increasing expression of brain-derived neurotrophic factor (BDNF). In the field of neuroimmunology, alterations in serum and cerebrospinal fluid concentrations of a number of inflammatory markers have been found in patients with depression. The most replicated findings are raised levels of C reactive protein, tumor necrosis factor a and interleukin-6. Neuroimaging studies of depression have provided evidence of abnormalities in brain areas associated with emotion regulation. The identification of a single candidate gene associated with depression is difficult because this disorder is likely a polygenic disease. However, the most recent meta-analysis of genetic association studies has found statistical evidence supporting roles for at least five genes (MTHFR, SLC6A3, DRD4, GNB3 and SLC6A4) in the propensity to depression.

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Dementia is a serious global impairment of cognitive ability that goes beyond what might be expected from normal aging in a previously unimpaired person. Dementia is not a single disease, but rather a non-specific illness syndrome. Cognitive impairment frequently emerges together with various emotional and behavioral symptoms. Some of the most common forms of dementia are: Alzheimer´s disease (AD), vascular dementia, dementia with Lewy bodies, and frontotemporal dementia. Precise history taking, cognitive testing, laboratory tests, and imaging are necessary for the proper differential diagnosis of dementia. Although numerous research studies have indicated that the disease is associated with plaques and tangles in the brain, the causes and progression of AD are not well understood. Current approved drug treatment for patients with AD includes cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the NMDA receptor antagonist, memantine. These drugs are relatively simple to use, although they only help alleviate the symptoms of the disease. Over the last 20 years, drug development has been directed towards ‘disease modifying drugs´ that could modify the pathological steps leading to AD and counteract the progression of the disease. Disease modifying drugs developed so far include drugs to reduce b amyloid (A b) production, prevent A b aggregation, promote A b clearance, drugs targeting tau phosphorylation and assembly and other approaches. Unfortunately none of these drugs has demonstrated efficacy in phase 3 studies. The failure of clinical trials with disease modifying drugs raises a number of questions, spanning from methodological flaws to our fundamental understanding of AD pathophysiology and biology. The use of complementary and alternative medicine (CAM) appears to be on the rise to delay cognitive symptoms. However, there is no conclusive evidence to support their benefit.

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Patients with mild cognitive impairment (MCI) have memory impairment beyond that expected for their age and education, and yet they are not demented. While objective evidence of impairment in one or more cognitive domains, typically including memory, is generally observed, they also show preservation of independence in functional abilities. The estimated prevalence of MCI in population based studies ranges from 10-20% in persons older than 65 years of age. The number of persons with MCI is about 1.5-2 times that for Alzheimer's disease (AD). MCI is subdivided into the major subdivisions of amnestic and nonamnestic MCI, followed by further subclassification into single- or multiple-domain categories. The etiology of MCI includes neurodegenerative disease, cerebrovascular disease, endocranial disease, mental disorder, systemic internal disease, and drug intoxication. Most MCI progresses to AD. Finally, more than 90% of patients with amnestic MCI progress to AD. Recently, MCI criteria incorporating biomarkers were proposed. If patients meet the Core Clinical Criteria for MCI and have positive biomarkers for both Aβ and neuronal injury, there is the highest level of certainty that they have “MCI due to AD”. At present, there are no radical treatments to prevent the progression of MCI to AD. However, adequate exercise and a balanced diet are effective to some extent.

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Recently there have been reports of an increase in the prevalence of developmental disorders. Developmental disorders include psychological and physical disorders, autism spectrum disorders (ASD), attention-defect/hyperactivity disorder (AD/HD), and learning disorders (LD), as a consequence of impairment of the normal development of motor or cognitive skills. Although the increase in developmental disorders may arguably be due to a change in the diagnostic criteria, improved screening and early detection, especially of ASD, remains a concern for health and educational professionals who provide intervention programs for these increasing numbers. The diagnosis of developmental disorder is made by recognizing patterns of behavior that are present early in life. All systems for diagnosis that have been suggested, including the international classification of diseases (ICD) and diagnostic and statistical manual (DSM), agree that childhood ASD, for example, is a pervasive developmental disorder that is characterized by abnormal functioning in 3 main areas of development before the age of 3 years: (1) reciprocal social interaction, (2) communication, and (3) stereotypical repetitive behavior. In this paper, I propose the importance of appropriate behavior intervention programs for preschool children with developmental disorders to support their cognitive, adaptive behavior, and language development.

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Recent epidemiol ogic studies have clearly shown that sleep problems are common in industrial countries, as well as developing ones. A survey conducted in Japan reported that 21.4% of adults had complaints of insomnia, which were frequently associated with other psychological and somatic symptoms. Insomnia is clinically defined as sleep difficulty despite adequate opportunity and circumstance for sleep associated with daytime impairment in quality of life, and requires appropriate therapeutic interventions because it is likely to cause several serious mental and physical disorders including hypertension, diabetes, heart diseases and depression. Here I reviewed recent articles on epidemiology, pathogenesis, diagnosis and treatment of insomnia, and found the following documented facts. Pathophysiologic mechanism of insomnia seems to be multifactorial and needs further study. Diagnosis of insomnia in clinical settings is carried out mainly by excluding mental or physical diseases that are possibly cause symptoms of insomnia, as well as other primary sleep disorders. Current progress in sleep medicine has proposed that pharmacological and non-pharmacological interventions should be combined in the treatment of insomnia. New generation hypnotics that act through mechanisms other than central GABAnergic ones, i.e., melatonin receptor agonists, orexin receptor antagonists, are expected to play an important roll in future sleep medicine practice.

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Electroconvulsive therapy (ECT), in which brain seizure discharges are therapeutically induced by transcranial electric stimulation, has been recognized as a treatment for psychiatric disorders including depression, mania and schizophrenia for over 70 years. Many clinical studies have proved its efficacy and safety relative to psychotropic drug therapies. Recent advance in clinical psychiatry has proposed a modification of the ECT procedure, a modified ECT (mECT), in which peripheral muscle relaxant is used to suppress motor manifestations due to the brain seizure discharge. In this article the author carried out a comprehensive review on ECT in respect with its history, clinical indication and practice together with mechanism of action. First, literature review has revealed that indication of ECT is widely described in a variety of disorders. Successful outcome has been reported in the treatment of not only psychiatric disorders but also neurological disorders such as Parkinson´s disease, neuroleptic malignant syndrome or drug resistant chronic pain. Second, the author documented a detailed mECT procedure that has recently been conducted in the department of psychiatry Nihon University School of Medicine. Lastly, clinical considerations on the mechanism of action were made based on recent therapeutic ECT studies using positron emission tomography. Finally the author concluded that the therapeutic effects of ECT involve multiple neurotransmitter systems.

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Deep brain stimulation (DBS) has been recognized as an effective therapy for involuntary movements. As DBS has become more widely used, it has sometimes been observed that psychiatric symptoms and personality changes are induced by DBS. Such phenomena are associated with the close cooperative function of motor, associative and limbic circuits in the cortico-basal ganglia-thalamic-cortical (CBTC) circuit, which is often selected as a target for DBS. On the other hand, clinical studies of DBS by stimulating the CBTC circuit for depression and obsessive compulsive disorder are being conducted in Western countries. The reversibility of DBS allows it to be used as a new therapeutic method for psychiatric disorders, epilepsy, aggressiveness, obesity, and cluster headache, among others. However, apprehension due to the history of abuse of psychosurgery delays the development of this field. The neurologist Egas Moniz is regarded as the founder of psychosurgery. He performed the first prefrontal leukotomy in 1935. His interventions on the brain substance caught great attention worldwide and led to the Nobel Prize in 1949; an award that remains highly controversial today. However, DBS for psychiatric diseases differs greatly from previous psychosurgery because of the reversibility of the process. The prospects and ethical and social issues of DBS for psychiatric diseases should be discussed.

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We report the efficacy of BioGlue^®, (CryoLife Inc, Kennesaw, GA, USA) in emergency surgery for acute type A aortic dissection. Between August 2011 and April 2012, seven patients underwent ascending aorta replacement for type A aortic dissection in our institution. At the time of surgery, the aortic stumps were reinforced with BioGlue^®. The average durations of the operation, cardiopulmonary bypass, and circulatory arrest were 217 ± 32.7, 129 ± 17.5 and 25.4 ± 3.4 min, respectively. There were no incidents of operative death or postoperative complications. Postoperative enhanced computed tomography revealed that there was no patent false lumen in the aortic root or aortic pseudoaneurysm at the anastomotic site in any of the patients. Furthermore, thrombosed false lumen was found in the descending aorta in 5 patients. It was considered that BioGlue^® might be effective in providing very quick adhesion of the false lumen during emergency surgery for acute type A aortic dissection.

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Purpose: Meckel´s diverticulum (MD) is the most common congenital anomaly of the small intestine. Its main importance lies in the possibility of complications that may manifest themselves as acute abdomen. We analyzed the clinical features of children with complicated MD. Material and Methods: A series of seven consecutive patients with complicated MD were included in this study. These were six males and one female, between 3 months and 15 years of age, with a mean age of 6.1 years. Patients with complicated MD were operated upon in our hospital during the past 10 years. We performed a retrospective analysis of the clinical findings in these patients. Results: The kinds of complicated MD were strangulated intestinal ileus (3 cases), diverticulitis (2 cases), perforation (1 case) and melena due to ulcer of an ectopic gastric mucosa (1 case). The preoperative diagnosis was ileus (3 cases), acute appendicitis (2 cases), panperitonitis (1 case) and acute enteritis (1 case). The preoperative diagnosis of MD was difficult. Their main chief complaints were abdominal pain (right-side lower abdominal pain: 2 cases, lower abdominal pain: 1 case). These symptoms generally persisted for more than 3 days (range: 3 days to 3 years) except for one case (5 hours after onset). The types of operation were 4 diverticulectomy (wedge resection) and 3 partial resection of ileum with MD. The mean distance of the MD from the ileocecal junction was 76.3 cm (range: 50 to 150 cm). The size of the MD varied from 1cm to 10 cm (mean: 4.0 cm). All cases were located on the antimesenteric border of the ileum. Ectopic tissue (gastric mucosa) was observed in 1 case. Conclusion: The preoperative diagnosis of MD was difficult. However, surgical treatment of the complicated MD could be performed safely without postoperative complications.

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Background: The mismatch negativity (MMN) component is an event-related potential (ERP) that can be elicited by any changes, particularly in the acoustic environment. Recently, several studies have obtained visual MMN. MMN is said to reflect the process by which stimuli are detected automatically. We have reported the developmental changes of visual MMN in children. In this study, we present the clinical utility of MMN in children with mental retardation. Methods: The subjects were 29 mentally retarded patients. Electroencephalograms were recorded from Fz, Cz, Pz and Oz electrode locations (international 10-20 method) with reference to the earlobe. MMNs were measured by using different waveforms by subtracting the ERP to the frequent stimuli from that to rare stimuli. We compared the latencies of visual MMN between normal and mental retarded subjects. Results: In this study, the visual MMN latency of mentally retarded patients was longer than that of normal subjects. In particular, there was a significant difference in the visual MMN latency between normal and mentally retarded children above six years of age. Conclusion: Clinically, age-related changes of visual MMN in normal subjects are very important in the assessment of the maturation of pre-attentional processing. Our results suggest that some mentally retarded patients exhibit impairment of pre-attentional processing in the visual cognitive function.

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We assessed the safety of combination chemotherapy with carboplatin and paclitaxel (TJ therapy) by comparing the occurrence of adverse events and treatment completion before and after switching from brand-name to generic drugs. Thirty-four respiratory surgical patients underwent TJ therapy as preoperative chemotherapy (n = 1), for cancer recurrence (n = 13), and as postoperative adjuvant chemotherapy (n = 20) at the outpatient chemotherapy unit of our hospital between April 2006 and August 2010. Twelve of these 34 patients underwent treatment using generic products. Intergroup comparison of the incidence of adverse events revealed that grade 3 or more severe adverse events occurred in 2 of the 22 patients treated with the brand-name drugs, and 4 of the 12 patients treated with the generic drugs. As for treatment course, treatment withdrawal and dose reduction were necessary in 3 and 2 patients, respectively, in the groups of patients treated with the brand-name or generic drugs. No statistically significant differences were observed in the incidence of adverse events or the treatment course between the two groups. The results indicate that the brand-name drugs and generic drugs are equivalent in terms of safety; however, long-term outcomes need to be carefully followed up.

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In this study, we examined the relationship between smoking and insomnia by analyzing the results of an epidemiological study of approximately 100,000 adolescents in Japan. The survey design was a cross-sectional sampling survey. The targets of the survey were junior and senior high schools throughout Japan. Self-reported anonymous questionnaires were sent to sample schools for all students to complete. A total of 103,650 adolescents responded and 102,451 questionnaires were subjected to analysis. We found that the prevalences of difficulty in initiating sleep (DIS), difficulty in maintaining sleep (DMS), and early morning awaking (EMA) generally increased with the increases in the number of smoking days, the average number of cigarettes smoked per day and the degree of nicotine dependence. Multiple logistic regression analysis showed that the odds ratios (ORs) for all three sleep problems were significantly higher in daily smokers, smokers consuming 21 cigarettes or more per day, and smokers who always felt like smoking immediately after waking up. The present findings suggest that the close relationship between smoking status and insomnia may be explained by the association between the quantity of nicotine taken into the body and sleep. Therefore, health education to prevent both smoking as well as sleeping problems may be necessary in junior and senior high school.

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We report a case of a 65-year-old patient with obstructive jaundice after administration of ceftriaxone. He was treated with ceftriaxone for 5 days because of acute colitis. Laboratory examination showed elevated hepatic and biliary enzymes, and we found sludge in the common bile duct and gall bladder by CT scan. We diagnosed him with obstructive jaundice by sludge due to ceftriaxone. We treated the patient with ursodeoxycholic acid after endoscopic sphincterotomy. This case is rare but clinicians need to be aware of the potential for obstructive jaundice by sludge due to ceftriaxone treatment.

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Subglottic hemangioma is a rare airway disease that usually presents as severe air way obstruction during the first year of life. We report the clinical usefulness of contrast-enhanced CT in the evaluation of suspected subglottic hemangioma in an infants. A 2-month-old male infant was referred to our hospital with inspiratory stridor and retraction. Although subglottic hemangioma could not be established on laryngoscopy, we were able to recognize a 9 X 6 mm tumor by contrast-enhanced CT. He was treated with systemic corticosteroid, and his respiratory symptoms improved after treatment. In this case, it is considered that contrast-enhanced CT is a valuable noninvasive method for the evaluation of subglottic hemangioma in a restless infant with respiratory distress.

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An 83-year-old male was admitted to our hospital for cardiac rehabilitation. Two drug-eluting stents (DES) had been implanted into the diffuse and severe stenosis of his left anterior descending artery (LAD) when he was admitted to another hospital because of acute coronary syndrome. After five days, stent thrombosis occurred and emergent percutaneous coronary intervension (PCI) was performed. After the PCI, he had congestive heart failure (CHF) and ischemic cardiomyopathy with low left ventricular ejection fraction (LVEF) (20-30%) caused by broad anterior myocardial infarction. Although cardiac rehabilitation was attempted in our hospital, he was forced to stay on bed rest for one month, because of uncontrollable congestive heart failure and ventricular arrhythmia. Thereafter, he underwent cardiac rehabilitation using a cycle ergometer. Cardiopulmonary exercise testing (CPX) was performed to evaluate the patientÅfs exercise capacity. He was also educated about heart failure. He continued aerobic exercise on a cycle ergometer based on the prescription of exercise at home after discharge, which was impaired by medical treatment, and was recorded in a notebook and managed by the medical staff. We reported that re-admission of this case was prevented due to a successful supervised and non-supervised cardiac rehabilitation program at home.

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A 70-year-old man was admitted to our hospital with the complaint of right hypochondralgia. Abdominal X-ray showed gas in the right upper quadrant. Abdominal CT showed gas in the gallbladder and an approximately 55 mm hepatic tumor in S7 of the liver. We report a case that underwent cholecystectomy and hepatectomy for emphysematous cholecystitis with hepatocellular carcinoma.

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Acute interstitial pneumonia is a subset of idiopathic interstitial pneumonia, and has a poor prognosis due to the lack of effective treatments. A 51 year-old woman was admitted to our hospital because of long-lasting (18 days) non-productive cough and dyspnea. Radiographic findings were compatible with cryptogenic organizing pneumonia, whereas her condition continued to rapidly and progressively deteriorate. The increase in neutrophils in the bronchoalveolar lavage fluid was compatible with acute interstitial pneumonia. We therefore initiated pulse methylprednisolone therapy and endotoxin absorption therapy using polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP). Although the PaO2/FiO2 ratio improved, her radiographic findings persisted. Therefore, we added further immunosuppressive treatment with cyclosporine A with success. This case suggests that combination therapy with corticosteroid, cyclosporine A, and PMX-DHP could be a new therapeutic strategy for acute interstitial pneumonia.

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[in Japanese]

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