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For women planning their pregnancy, adjusting their medications in advance for the impending future is desirable. Some psychotropic medications have been shown to have severe teratogenic effects during pregnancy. However, sudden discontinuation of such medication can worsen mental symptoms and have serious consequences. Therefore, it is necessary to carefully reduce or change medications while emphasizing two-way communication between patients and their families to carefully observe the mental symptoms.

The risk of developing or exacerbating psychiatric disorders increases in the perinatal period. However, there is a concern that psychotropic medications may be withheld from appropriate treatment by doctors, or patients or their families because of concerns about their effects on the fetus or infant. This article describes psychiatric disorders with risk of perinatal onset or exacerbation and presents the risks and benefits of standard pharmacotherapy to the fetus and infant. It is essential to consult with the patient and family before conception to make shared decisions based on correct information.

Systemic lupus erythematosus (SLE) is an autoimmune disease which causes damaging inflammation in multiple organs via the accumulation of immune complexes. SLE pathogenesis is associated with type I interferons (IFNs), which are central and reflective of disease activity in SLE. Even before clinical development of disease, genetic and environmental contributions to IFN production lead to abnormal innate and adaptive immune activation. Through the Janus kinase-signal transducer and activator of transcription signaling pathway, IFN play a central role in the immunopathogenicity of SLE. Thus, IFN-blocking therapy may be used to regulate inflammation in individuals with SLE. Food and Drug Administration (FDA)-approved anifrolumab (Saphnelo ® ), which is a human IgG1κ monoclonal antibody that binds to subunit 1 of the type I interferon receptor with high specificity and affinity, was also approved for the treatment of adult patients with moderate to severe SLE who are receiving standard therapy by Pharmaceuticals and Medical Device Agency (PMDA), in Japan in September 2021; anifrolumab is administered as an intravenous infusion, 300 mg over a 30-minute period, every 4 weeks. In this article, we reviewed the actions of type I IFN and anifrolumab as a treatment for SLE.

The pathophysiology of mental disorders remains unknown. This causes many gaps in pathophysiology, diagnosis, and treatment of mental disorders. To close these gaps, a new perspective, which is not bound by the existing diagnostic classifications or pathological hypotheses for mental disorders, is required. Recently, it has been reported that glial cells play active roles in normal brain function and circuit formation, and their disruption results in the onset of mental disorders. Here, we discuss mental disorders from the perspective of glial cell-related pathophysiology, along with our current efforts and research.

A 40-year-old man who had been surgically treated for the fracture of the right humerus with two Kirschner wires (K-wires) complained of chest pain and difficulty in breathing at fourth day after surgery and visited our hospital. Chest radiography revealed dislocation of the K-wire and right pneumothorax. Video-assisted thoracic surgery( VATS) was performed immediately, and the K-wire was removed safely.

We present a 76-year-old male patient on chronic dialysis for over 10 years with contained rupture of a mycotic abdominal aortic aneurysm, which was successfully treated by thoracic endovascular aortic repair(TEVAR) and computed tomography(CT) guided percutaneous drainage. Endovascular repair of mycotic aortic aneurysm is nowadays feasible and can be a suitable alternative especially in frail patients.

Autism spectrum disorder (ASD) is characterized by deficits in social interaction and social communication, along with restricted and repetitive sensory-motor behaviors. The diagnosis of ASD includes various phenotypes outlined in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM)-5. The comprehensive evaluation of each individual case with ASD is needed because many of them have comorbidity with number of neuropsychiatric disorders or somatic conditions. The growing number of genetic studies detected multiple rare variants with relatively large effect sizes. The results have revealed their common potential pathology including abnormal chromatin regulation, which induces epigenetic changes. More researches are expected to elucidate the pathogenesis of ASD and to develop therapeutic approaches.

An 81-year-old woman who had undergone laparoscopic distal gastrectomy complained of abdominal pain 21 days after the operation.Blood tests showed a strong inflammatory reaction.Abdominal CT revealed a perforation in the small intestinal diverticula.Partial jejunectomy including the diverticulum was performed.The diverticular perforation was attributed to the presence of undigested food in the diverticulum.The patient had an uneventful postoperative course, and she was discharged on postoperative day 32.

Psychiatric research is important to answer daily clinical questions, clarify the etiopathology, and develop diagnostic methods and treatments based on the etiopathology. Therefore, the goal of departments of psychiatry in universities is to train the next generation of leaders in psychiatry who can promote innovative and personalized care for patients. In terms of the development of research-oriented human resources, it is necessary to emphasize the importance of prioritizing patients' demands and education regarding the following points:1) After the critical appraisal of papers, we have to elucidate what we know and what we do not know to clearly determine the purpose of research (Social or scientific value). 2) We have to use accepted methods, including statistical techniques, to produce reliable and valid data (Scientific validity). In addition, we should introduce ethical considerations into clinical research, including informed consent. The development of research-oriented human resources is indispensable for future research focused on the needs of psychiatric patients and their families.

A 30-year-old man was admitted with anemia. Colonoscopy showed diffuse small polyps in the colon, 1 cancer in the sigmoid colon, and 2 cancers in the rectum. He was diagnosed with familial adenomatous polyposis (FAP). Total colectomy was conducted laparoscopically through 5 trocars, and a total proctocolectomy (TPC ) was performed. The operating time was 9 hours and 30 minutes, and intraoperative blood loss was 20 g. On the 1st postoperative day, he started oral intake. On the 14th postoperative day, he was discharged from our hospital. We thus consider laparoscopic resection to be a very useful technique for FAP.

In recent years there has been an increase in the number of laparoscopic surgeries for gastric cancer, with over 8,000 cases reported nationwide in 2012. To date, we have performed 420 total laparoscopic distal gastrectomy (TLDG) procedures. In all cases, the mean operative time was 304 minutes, intraoperative bleeding was at 52 g, 30 lymph nodes were dissected, and the length of postoperative hospital stay was 10.6 days, on average. We experienced 5 intraoperative complications and 13 postoperative complications. Of 4 patients, there were 2 cases of postoperative recurrence in liver metastases, 1 case of metastatic lung tumor, and 1 case of peritoneal metastasis. Based on surgical outcomes, TLDG is a safe and feasible procedure for gastric cancer.

We report a 17-year-old female with juvenile neuronal ceroid-lipofuscinosis (NCL) accompanied by hypertrophic cardiomyopathy (HCM) and left ventricular noncompaction (LVNC). Within our knowledge, this is the first reported case of juvenile NCL with LVNC, and the youngest case of HCM diagnosed by ultrasound. Juvenile NCL is a progressive hereditary disease involving multi-organ accumulation of ceroid-lipofuscin; its resulting complications require prompt attention. Due to its relative rarity, its cardiac involvement is not well known. Based on findings from this patient and related juvenile NCL cases, the risk of cardiac involvement tends to increase with age; a high frequency of ventricular hypertrophy has been reported in patients aged older than 20 years of age. Medical progress and comprehensive care have led to longer survival in patients with juvenile NCL, which likely increases the incidence of cardiac involvement. In relation to HCM in other metabolic disorders, attention should be paid to arrhythmias, including repolarization disturbances, sinus node dysfunction and ventricular tachycardia. LVNC is a cardiomyopathy characterized by prominent left ventricular trabeculae and deep intratrabecular recesses, which are associated with diastolic or systolic dysfunction, thromboembolic complications and arrhythmias. From ours and other case reports, we recommend regular follow-up of NCL patients as follows: echocardiography to estimate cardiomyopathy, Holter monitoring to identify arrhythmias, and computed tomography to detect thrombosis from both ventricles. The mechanism of the HCM and LVNC associated with juvenile NCL remains unclear. Our case requires careful follow-up. Prospective studies of the cardiac involvement in juvenile NCL are necessary to further elucidate its pathomechanism.

Treatment is comprised of three components, clinical expertise, clinical research evidence, and patients' preferences. Therefore, clinicians have to provide psychoeducation to enable patients to understand their treatment plan based on clinical expertise and research evidence, and play roles as an important partner. Psychoeducation should be conducted based on mutual participation and understanding between clinicians and patients, and not just as one-sided teaching. Moreover, the aim of pychoeducation is the development of the patient's true insight, composed of recognition of illness, treatment adherence, and relabeling of psychiatric symptoms. A structured group-psychoeducatinal program for bipolar disorders established by Colom et al. is composed of 21 sessions of 90 minutes, each aimed at improving 5 main issues: illness awareness, treatment compliance, substance abuse avoidance, early detection of prodromal symptoms and recurrence and lifestyle regularity. The program has been proven to have long-lasting prophylactic effects and good cost-effectiveness for individuals with bipolar disorders. Reconstruction of the diagnostic system for mental disorders based on elucidation of the pathogenesis and pathophysiology of these conditions is required to acquire a better mutual understanding between psychiatrists and patients.

The Japanese Society of Mood Disorders (JSMD) published the "Treatment Guideline II: Major Depressive Disorder, 2012 Ver. 1" on July 26, 2012. This guideline (GL) is the first one published by an academic society in Japan. Presently in Japan, many people have depressive symptoms, and the socioeconomic loss (suicide, absence from work, etc.) induced by this condition cannot be overlooked. Although the Japanese society, including mass media and psychiatrists, has attempted to solve this public problem, a solution has not been found. JSMD regarded diagnosis and psychiatric management of depression, among other factors, as the key to solving this problem. For example, patients who meet the DSM-IV major depressive disorder (MDD) criteria still have numerous subtypes, and they often have other psychiatric comorbidities that a diagnosis of MDD alone cannot detect. Although the process for differential diagnosis and treatment planning is indispensable, its methodology has not been necessarily shared even among psychiatrists until today. In this GL, considering the research evidence and its limitations, JSMD suggests necessary steps for appropriate information intake, diagnosis, therapeutic alliance formation, psychoeducation, and treatment modality choice in every phase (acute and continuation/maintenance). This GL also considers pharmaco-, psycho-, and electroconvulsive therapy for major depressive subtypes (mild, moderate/severe, and psychotic). Simultaneously, psychiatrists are required to be alert to the risk from diffuse and multiple prescription of benzodiazepine receptor agonists (dependence, deterioration of sleep apnea, cognitive decline, paradoxical reaction, etc.), especially barbiturates. This GL will be revised on the basis of public comments, including criticism. In the future, treatment GLs for comorbid patients, return-to-work cases, primary care physicians, psychiatric residents, and patients with depressions other than MDD (subthreshold depression, dysthymic disorder, and adaptation disorder) may be needed.

Although treatments for unresectable colorectal cancer have made great progress with new anticancer agents, they are still unsatisfactory. Development of anti-cancer therapy and its management are important in order to improve the treatment outcome of colorectal cancer. In the evaluation of treatment effect, obtaining a baseline image at the start of treatment is very important, and CT scan is generally performed for this purpose. In daily clinical practice, response evaluation criteria in solid tumors(RECIST)is usually adapted for the assessment of treatment outcomes. In addition, we should make decisions about continued therapy on the basis of both objective and symptomatic findings. Patients receiving palliative chemotherapy should be monitored with a CT scan every 2 to 3 months. It is important to make a treatment strategy individually in consideration of adverse events, purposes of the treatment, and tumor progression.

Developmental disorders, which are usually diagnosed in infancy, childhood, or adolescence, include mental retardation, learning disorders, motor skills disorder, communication disorders, pervasive developmental disorders (PDD), attention-deficit hyperactivity disorder (ADHD), and tic disorders. Epidemiological studies have indicated that these disorders are characterized not only by high heritability (e.g., 0.80 for PDD) but also by their shared genetic etiology. Furthermore, retrospective or prospective longitudinal studies have revealed that adult psychiatric disorders are often preceded either by their juvenile counterparts (homotypic continuity) or by different disorders (heterotypic continuity). Recent genetic studies have detected copy number variants (CNVs; e.g., deletions on 1q21.1, 3q29, and 22q.11.21 and duplications on 16p11.2) as shared genetic factors for PDD, mental retardation, and schizophrenia. While these CNVs are generally very rare (<1%), their effect size is much larger than that of single nucleotide polymorphisms. Although the mechanism by which CNVs cause these abnormalities remains unclear, pleiotropic effect of CNVs may provide insights into the high rate of comorbidity among developmental disorders and heterotypic continuity between developmental disorders and adult disorders. In addition, longitudinal neuroimaging studies have provided evidence for irregularities in the typical trajectories in developmental disorders. For instance, retarded cortical development is identified in ADHD in cortical trajectory, and early acceleration of brain growth is identified in PDD. Finally, we outlined several research topics as the future direction for investigation of developmental disorders: a longitudinal clinical study in subjects with specific disorder-related CNVs; detailed analysis of genetic factors relevant to developmental disorders, including smaller CNVs and INDELs; and functional analysis of genetic factors by using induced pluripotent stem cell technology or non-human primate animal models.

In 2010 Mr. Nagatsuma, the former Minister of the Ministry of Health, Labor and Welfare of Japan expressed his opinion that the health examination of work place should includes items to focus on mental disorders such as depression, just after the Japanese Society of Psychiatry and Neurology with related societies launched the Joint Declaration of Countermeasure for Depression. To carry out the examination the following requirement is necessary. 1) Keeping the results of the health examination in secret. 2) Enlightenment of mental disorders including depression, bipolar disorders, schizophrenia and pervasive developmental disorders. 3) Not only questionnaires for screening but also supportive and sympathetic interview methods that are reliable and valid. 4) Cooperation between work place and health professional In introduction of medical intervention and rehabilitation. The strategy to realize the above-mentioned requirements is as follows. 1) Education of the industrial mental health staff: public health nurses and psychologists. 2) Pilot study to examine the method of the health examination. 3) Research to establish the future preventive method of mental disrders. 4) Budgetary appropriation. As the health examination should be benefit for workers, hasty introduction of the examination should be avoided.

A 75-year-old woman was admitted to our department because of epigastric pain. Imagings revealed cancer of the head of the pancreas. She was an HBV carrier, although no liver dysfunction was observed. Her serum HBV-DNA level was lower than 2.6. We performed pancreaticoduodenectomy for pancreatic cancer. No postoperative complication was observed. The histopathological diagnosis was tubular adenocarcinoma of the pancreas. As a postoperative adjuvant chemotherapy, gemcitabine hydrochloride (GEM) was injected at a dose of 800mg/m2 once a week. Disorientation and jaundice were observed after six doses of GEM. Blood chemistry revealed that total bilirubin and ammonia were abnormally elevated, and that blood coagulant factors were diminished. Serum HBV-DNA level was lower than 2.6. It showed no reactivation of HBV. Abdominal CT showed no recurrence but fatty liver. Fresh frozen plasma was supplied and branched chain amino acids were injected after GEM was administration discontinued. Lactulose was also given orally. With these conservative treatments, she recovered completely. Careful monitoring of liver function during GEM administration is required in a HBV carrier.

Two episode of junctional ectopic tachycardia (JET) caused hemodynamic deterioration early after tetralogy of Fallot repair in an 8-month-old infant. Sinus rhythm resumed in each of the episodes immediately after intravenous administration of nifekalant hydrochloride (NIF), a newly developed Vaughan-Williams class III antiarrhythmic drug in Japan. Although QT interval was modestly prolonged with NIF, no life-threatening ventricular arrhythmia (i.e., torsades de pointes) occurred. NIF might be an effective alternative in the treatment of postoperative JET in congenital cardiac surgery.

Clinical interaction between primary care physicians and psychiatrists is important in the treatment of depression. Most depressive patients first visit to primary care physicians. In this paper, we explain early detection and initial treatment of depression to primary care physicians. They first should have a question about insomnia to their patients to detect depression. And we show seven principles in the initial treatment of depression to primary care physicians.

Schizophrenia is hypothesized as a neurodevelopmental and neurodegenerative disorder based on the following findings. 1. MRI studies have revealed brain structural abnormalities from the onset of schizophrenia and the progress of these structural abnormalities. 2. Histopathological studies have elucidated cytoarchitectural abnormalities in schizophrenic brains without gliosis. 3. Obstetric complications are one of the risk factors for schizophrenia. 4. Relapse of schizophrenia results in a deteriorating progress of the disorder. Furthermore, data from family, twin and adoption studies show evidence of a substantial genetic component in schizophrenia, Thus, a molecular genetic study combined with a neurodevelopmental and neurodegenerative hypothesis is required to elucidate the pathophysiology of schizophrenia. The positive association between neuregulin 1 and Icelandic schizophrenia that has been reproduced in Scottish and North European schizophrenia is one of the intriguing examples of this type of research. Neuregulin 1 regulates the cytoarchitecture of brain. Mice mutated for neuregulin 1 show a behavioral phenotype that overlaps with mouse models for schizophrenia. Furthermore, the behavioral phenotypes of the neuregulin 1 hypomorphs are reversible with clozapine. We also demonstrated a positive association between schizophrenia and a 5-HT5A receptor polymorphism, Pro15Ser, that may have role in cell differentiation in the brain.

We report 3 gastric cancer patients with peritoneal dissemination who failed to take TS-1 due to adverse effects and who were successfully treated with weekly paclitaxel administered intravenously. The patients were 2 men and 1 woman from 73 to 82 years in age. The histological types of gastric cancer were undifferentiated adenocarcinoma in all cases. Intravenous infusion of TXL (62-80 mg/m2) after short premedication was continued for 3 weeks followed by 1 week rest. Clinical symptoms, including ascites and intestinal obstruction, improved only after administration of 1 cycle in all patients. Except for 1 event with grade 3 neutropenia, no major adverse reactions were observed. Weekly administration of paclitaxel may be a promising chemotherapy for controlling peritoneal metastasis and improving the quality of life of patients with advanced or recurrent gastric cancer.

Spinal cord injury such as paraparesis and paraplegia remains one of the major concerns in surgery on the thoracoabdominal aortic aneurysm (TAAA). We utilize spinal cord protection including cerebrospinal fluid drainage (CSFD), adjuncts of aortic distal perfusion, reconstruction of the intercostal or lumbar arteries and deep hypothermia in TAAA repair. This report describes the results of surgical treatment for TAAA including postoperative neurological outcome. Between October 1999 and January 2004, 33 patients (mean age 66 years; range 26 to 81) underwent TAAA repair. Adamkiewicz artery could be detected using magnetic resonance angiography in 9 patients. CSFD was done in 20 patients. TAAA repair was achieved using adjuncts of aortic distal perfusion in 31 patients (partial cardiopulmonary bypass: 19, deep hypothermia: 9, left heart bypass: 3). We tried to reconstruct the intercostal or lumbar arteries which were located between Th8 and L2 as possible. Twenty-five patients underwent reconstruction of the intercostal or lumbar arteries. There were 6 hospital deaths. Postoperative spinal cord injury occurred in 4 patients (paraparesis: 1, paraplegia: 3). This clinical experience demonstrates that current technical strategies enable patients to undergo TAAA repair with acceptable early survival. However, despite aggressive spinal cord protection, few patients suffered from postoperative spinal cord injury. Future research should focus on spinal cord protection in patients with TAAA.

We report a case of advanced gastric cancer with metastasis to the paraaortic lymph nodes that showed a remarkable response to treatment with a combination of weekly paclitaxel and doxifluridine (5'-DFUR). The patient was a 72-year-old man. Oral chemotherapy of TS-1 was discontinued due to drug induced eruption. Alternatively, we administered weekly paclitaxel/5'-DFUR combination therapy. Paclitaxel was infused at a dose of 100-130 mg after short premedication and continued for 2-3 weeks with a 1 week rest. 5'-DFUR was administered orally at a dose of 800 mg/day for 14-21 consecutive days. After 4 courses of this therapy, the primary carcinoma and lymph nodes decreased in size (PR). Consequently, the patient underwent a total gastrectomy with paraaortic lymph node dissection, which resulted in a curative resection of the cancer cells macroscopically. Except for afebrile neutropenia (grade 4), no major adverse reactions were observed. Histological examination revealed that the cancer cells were degenerated to a moderate extent. Weekly paclitaxel/5'-DFUR combination may be a promising regimen for patients with advanced gastric cancer as preoperative chemotherapy.

Mood disorders are common diseases and cause a big burden on society, including suicide. Because there are many treatment resistant cases in mood disorders, it is very important to elucidate the pathophysiology of this condition to establish its prevention and its treatment. Genetic epidemiological studies have shown that genetic factors have an important role in the pathophysiology of mood disorders; therefore the molecular genetics studies of this condition have been extensively performed, such as positional approach (i.e., linkage study) and candidate gene approach (i.e., association study). Linkage studies have shown some candidate locations that have been reproduced in two or more studies, such as 1q21-42, 4p16, 10q21-26, 11p15, 12q23-24, 13q11-32, 18p11, 18q21-22, 22q11-13, Xp11, and Xq24-28. Most association studies have until now focused on the neurotransmitter system as a candidate molecule including serotonin transporter, serotonin receptors, dopamine receptors, tyrosine hydroxylase, MAO-A, COMT, and tryptophan hydroxylase. Moreover, phamacogenetic studies also have been carried out in this field to develop new drugs as well as personalized medicine. Future molecular genetic studies will find out the mood-disorder susceptible genes and open the gate to true treatment and prevention of this disorder as the Human Genome Project attains its goal.

A 71-year-old man with aortic stenosis due to calcification successfully underwent aortic valve replacement with a 21-mm CarboMedics "Top Hat" supraannular prosthesis. We were able to implant a "Top Hat" valve one size larger than would have been possible using a standard bileaflet valve. The postoperative recovery was uneventful, and echocardiography showed a peak gradient of 23 mmHg for this prosthesis. The CarboMedics supraannular valve allowed a gain in size over standard prostheses, resulting in favorable hemodynamics. This valve may be useful in difficult or unsuitable cases to enlarge the narrow aortic valve ring, such as patients with severe calcification of aortic root, elderly patients with less activity, or patients who can tolerate only short cardiopulmonary bypass time due to cardiac dysfunction.

Sexual problems are not specific for eating disorders. The etiology is complex and no one single causal facter has been identified. However, clinical as well as epidemiological studies have shown that eating disorders occur more commonly in females than males. The evidence that eating disorders are more common in females has resulted in the postulation that socio-cultural factors may be important. An important aspect of the socio-cultural position of women which may contribute to eating disorders is the conflict in roles. Clinical experience and research have shown the important role of sexual problems and traumas in the development of anorexia nervosa and bulimia. When compared to anorexics, bulimics reported greater sexual interest and activity.

Recently DDD pacemaker implantation for the children has undergone trials world wide; though regarding the approach, ways and positions of the epicardial lead, a few problems are still remained to be discussed. Now we report 9 cases (5 males, 4 females) of DDD pacemaker implantations by the left anterolateral thoracotomy approach. The 9 patients weighing 6.5 to 33 kg, were aged 11 months to 12 years (mean 6 years) of whom male 5, female 4 with degree of Block; 2 and 7. To all patients the stab-in type epicardial tips were implanted in the left atrium, the screw-in type ventricular epicardial tips were in the left ventricle by the 4th intercostal thoracotomy, and the pacemaker generators were beneath the fascia of the abdominal rectus muscle. We have no sensing and pacing failure, all pacemakers are working in the DDD mode well.

Approximately 80% of hepatocellular carcinoma (HCC) patients in Japan have associated liver cirrhosis, which increases the difficulty of surgical treatment. Liver dysfunction associated with liver cirrhosis is one of the most important predictive prognostic factors for HCC patients. Percutaneous ethanol injection therapy (PEIT) is useful for patients with small HCC or with poor hepatic functional reserve. Transcatheter arterial chemoembolization (TACE) is also useful both for patients with unresectable HCC and patients with multiple intrahepatic recurrence. Liver resection, however, lead to better outcome than other treatments when liver function is maintained after surgery. To determine operative procedures, it is important to evaluate the exact function of remnant liver, based on the preoperative liver function test and the evaluation of tumor character. For advanced HCC patients with vascular invasion, non-surgical treatments such as PEIT or TACE are not indicated, and surgical intervention can be an effective modality to improve their survival. Improvements of surgical technique and perioperative management have decreased fatal complications at a major liver resection and allowed us to carry out liver resection on patients with advanced HCC.

We evaluate the results of cardiac operation for 41 elderly patients (aged 75 years and over, mean, 77.5 years old). The overall hospital mortality was 12.2% (5/41) with mortality of 8.3% (2/24) in cases of elective operation and mortality of 17.6% (3/17) in cases of emergency operation. Causes of hospital death in emergency cases were congestive heart failure and left ventricular rupture (two cases) due to acute myocardial infarction. Patients who died in elective operation had been performed reoperation for bleeding and unstable sternum. These complications which need a reoperation seemed to be a potential risk for elderly patients. Because of poorer results of the emergency case, it is advocate to operate on these aged patients with an elective basis, if there is no absolute contraindications.

The influence of genetic factors in schizophrenia has been demonstrated by family, twin and adoption studies. The first-degree relatives of patients with schizophrenia have a risk of schizophrenia that is about 10 times greater than that of the general population. Concordance rate for schizophrenia is higher in monozygotic twins that in dizygotic twins. Biological relatives of individuals with schizophrenia have an increased risk of schizophrenia, although adoptive relatives have no increased risk. Many findings suggest the important role of serotonin (5-HT) in the pathophysiology of schizophrenia. Our direct analysis of 5-HT receptor genes in schizophrenia by single stranded conformational polymorphism revealed amino acid substitution in the 5-HT2A and 2C receptor genes. There is no association between the amino acid substitution in the 5-HT2A and 2C receptor genes and the antipsychotic response to clozapine, although both of the substitutions showed the functional influence of these receptors. So far linkage, affected sib pair and association studies have not been able to identify a susceptibility gene for schizophrenia. The molecular genetic approach to schizophrenia has been complicated by genetic heterogeneity, phenotypic heterogeneity and the small family size of this disorder.