Selective serotonin reuptake inhibitors (SSRI) are widely used antidepressants characterized by less-frequent adverse effects compared with classical anti-depressive agents. On the other hand, SSRI can cause hemorrhagic events more due to impaired platelet aggregation induced by a depletion of serotonin in the peripheral platelet. Epidemiological studies have indicated that patients taking SSRI are predisposed to gastrointestinal hemorrhage, especially in case that nonsteroidal anti-inflammatory drugs are prescribed concomitantly. Here we describe a risk of the gastrointestinal hemorrhage in patients taking SSRI.

Nicotinic acetylcholine receptor (nAChR) mediates pleiotropic actions in brain not only for nicotinic neurotransmission but also glutamatergic, dopaminergic, norepinephrinergic, GABAergic, and serotonergic transmissions, especially through allosteric potentiating ligand (APL) action. Because nAChR is rich in thalamus, the direct stimulation of nAChR through APL action is expected to show increasing function of cerebral cortex and limbic system through thalamic activation. In fact, a choline esterase inhibitor with this APL action such as galantamine exerts both cognitive and affective improvements which is called dual benefit for Alzheimer's disease patients.

Blau syndrome (BS) and early-onset sarcoidosis (EOS) are both systemic granulomatous disease evoked by the mutated NOD2. It occurs in children younger than 4 years of age and is characterized by a distinct triad of skin, joint, and eye disorders without apparent pulmonary involvement. NOD2 encodes an intracellular receptor for muramyl dipeptide (MDP), the common component of bacterial cell wall peptidoglycan, and is expressed in cytoplasm of monocytic cells and epithelial cells. While its loss-of-function mutations are recognized in Crohn's disease, the mutations observed in BS/EOS are gain-of-function, and induced MDP-independent basal NF-kappaB activation. But we still do not know the precious molecular mechanism how the activation of NOD2 induces granuloma formation in the skin, joints and eyes.

To date, antipsychotic drugs have been developed mainly by targeting dopamine D2 receptors. No significant changes have occurred in this trend despite mental disorders being treated more frequently with so-called "atypical" antipsychotic drugs. The action of antipsychotic drugs on dopamine D2 receptors can play an important role in the development of future antipsychotic drugs. However, there is a growing trend of developing new antipsychotic drugs by targeting new pathways. In this article, we discuss the vision for future antipsychotic drugs through an increase in the number of new antipsychotic drugs that are currently being developed or are already on international markets.

Bleuler has said that we have to provide community care for people with schizophrenia. In Japan, the process of modernization already ended by the miraculously swift growth of the economy in the postwar era. So it will be difficult to maintain facilities such as psychiatric hospital because the maintenance costs are too high. The core of mental health system should be community care in the future. The deinstitutionalization is essential to realize community care. Assertive community treatment (ACT) is the effective support system for people with severe mental illness (SMI). A characteristic of ACT is multidisciplinary team consisting of specialists in welfare and in medical service (ex. nurse, psychiatric social worker, occupational therapist, doctor, etc.) providing care for people with SMI. The following are detailed explanations of ACT.

Outreach services are very important in community mental health care. There are two types for outreach services. One is mental health activities, such as early intervention and consultation, and the other is intended to prevent recurrence and readmission by supporting the daily living activities of a patient in a community. We have 2.73 psychiatric care beds in hospitals per 1,000 population. So, it is just the beginning in changing from hospital centered psychiatry to community mental health care. Outreach services are being tried in several places in our country. In this essay, we describe mental health outreach services in Japan and we have illustrated vocational rehabilitation and outreach job support in our day treatment program.

In Japan, multiple antipsychotic drugs are administered at a high dose to schizophrenia patients. Many patients suffer from side effects, among which extrapyramidal and autonomic side effects frequently occur. We suggest a method in which antipsychotic drugs are slowly reduced as follows: for low potency drugs, the dose is decreased with 25 mg or lower of a chlorpromazine-equivalent dose per week, and, for high potency drugs, the dose is decreased with 50mg or lower of a chlorpromazine-equivalent dose per week. A randomized controlled trial involving 10 hospitals demonstrated that antipsychotic drugs can be reduced with relative safety according to our method. Our method is also expected to be useful to switch between antipsychotics to avoid polypharmacy.

We conducted clinical research at Jichi Medical University Hospital psychiatric ward on 38 patients over the age of 40 with late-onset schizophrenia and on 278 patients under the age of 40 with early-onset schizophrenia. Cases with onset after age 40 reported in 12% of the total population. Female cases were 20.4%, and the result was significantly higher than the male cases of 4.3%. Paranoid type was 55.3% of the total population of the late-onset cases, and it was significantly higher than the early-onset cases of younger than 40 years old. 55.3% of late-onset cases were combined with depressive symptoms, and they rated significantly higher than early-onset cases.

Childhood-onset schizophrenia has been clinically studied and is believed to be on a continuum with adult-onset schizophrenia. However, childhood-onset schizophrenia is more difficult to diagnose than it is in adults, since children are in a developmental state. This article reviewed the literature regarding childhood-onset schizophrenia. This article discusses the clinical features, development until manifestation, possibility of early diagnosis, and treatment. Early intervention may improve the prognosis of psychotic disorders such as schizophrenia. However, early intervention of childhood-onset schizophrenia requires case histories with accurate descriptions of the development of the disease until its onset.

Electroconvulsive therapy (ECT) was initially developed as a treatment for schizophrenia. Currently, the application of ECT for schizophrenia is controversial because of several international guidelines; however, catatonia is acceptable for the indications by all guidelines. Schizophrenic patients with affective, catatonic, and positive symptoms of recent onset may respond favorably to ECT. Additionally, ECT may improve responsivity to pharmacotherapy for some indications. Therefore, a combination of ECT with pharmacotherapy including clozapine may be effective for the pharmacotherapy -resistant schizophrenia. Another argument is that the relapse rate after ECT response is very high compared to that of mood disorders; development of maintenance therapy(pharmacotherapy or ECT) is anticipated for the prevention of relapse. Because maintenance ECT seems to be a burden on remitted patients, to study both maintenance pharmacotherapy and the novel application of non-invasive treatment, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), for maintenance therapy instead of ECT could be fruitful.