Neuroligins, proteins of the ␣/␤-hydrolase fold family, are found as postsynaptic transmembrane proteins whose extracellular domain associates with presynaptic partners, proteins of the neurexin family. To characterize the molecular basis of neuroligin interaction with neurexin-␤, we expressed five soluble and exportable forms of neuroligin-1 from recombinant DNA sources, by truncating the protein before the transmembrane span near its carboxyl terminus. The extracellular domain of functional neuroligin-1 associates as a dimer when analyzed by sedimentation equilibrium. By surface plasmon resonance, we established that soluble neuroligins-1 bind neurexin-1␤, but the homologous ␣/␤-hydrolase fold protein, acetylcholinesterase, failed to associate with the neurexins. Neuroligin-1 has a unique N-linked glycosylation pattern in the neuroligin family, and glycosylation and its processing modify neuroligin activity. Incomplete processing of the protein and enzymatic removal of the oligosaccharides chain or the terminal sialic acids from neuroligin-1 enhance its activity, whereas deglycosylation of neurexin-1␤ did not alter its association capacity. In particular, the N-linked glycosylation at position 303 appears to be a major determinant in modifying the association with neurexin-1␤. We show here that glycosylation processing of neuroligin, in addition to mRNA splicing and gene selection, contributes to the specificity of the neurexin-␤/neuroligin-1 association.Appropriate differentiation and maturation of neurons are essential requirements for synapse formation and achieving patterns of fidelity for cell signaling. Because of the multiplicity of potential targets for any given axon and because of the asymmetric nature of the synapse, partner recognition is critical for developing and maintaining functional synapses (1, 2). Neurexin and neuroligin appear to form heterologous cell contacts at synaptic connections and are suitable candidates for controlling synaptic recognition patterns. 1 is a member of a large family of neuronal proteins, composed of at least three genes (neurexins 1 through 3) driven by two promoters (␣ and ␤), resulting in the expression of at least six neurexin forms. Alternative mRNA splicing confers additional complexity to the possible gene products (3). The neuroligins form a family of cell adhesion proteins encoded by at least four genes that are widely expressed in brain as well as in selected locations outside the central nervous system (4 -7). Neuroligin-1 (NL1) has been localized at postsynaptic densities of glutamatergic synapses (8). Association between the neurexin-␤ and neuroligins appears to be Ca 2ϩ -dependent and selectively blocked by insertion of an alternatively spliced region in NX1␤ (4, 9, 10). Recently, mutations in neuroligin-3 and -4 were shown to be linked to autistic spectrum disorders in man (11). Consistent with the hypothesis that NX1␤ and NL1 can mediate the assembly of the pre-and postsynaptic terminals, a recent investigation delineates some of the cellular process...

Background: Some reports have suggested the involvement of the D₂ dopaminergic function in the expression of suicidal behavior. Here, we examined associations between suicide attempts and two kinds of functional polymorphisms in the dopamine D₂ receptor (DRD2) gene, namely, TaqIA and –141C Ins/Del. Methods: Subjects included 120 suicide attempters and 123 unrelated volunteers. Those who attempted suicide were severely injured and were transferred to the emergency unit in our university hospital. To determine each genotype, we performed polymerase chain reaction and restriction fragment length polymorphism analyses. Results: We found significant differences in genotypic and allelic frequencies of –141C Ins/Del and TaqIA polymorphisms between suicide attempters and healthy controls (–141C Ins/Del, p = 0.01; TaqIA,p = 0.036). The Ins allele of –141C Ins/Del was significantly more frequent in suicide attempters (p = 0.011), as well as the A2 allele of TaqIA (p = 0.017). Haplotype analysis revealed no significant linkage disequilibrium between –141C Ins/Del and TaqIA polymorphisms (D′ = 0.226, r² = 0.016, p = 0.10). Conclusions: These findings suggest that DRD2 gene polymorphisms may be involved in the biological susceptibility to suicide.

BackgroundThe feasibility of shared decision making (SDM) for patients with schizophrenia remains controversial due to the assumed inability of patients to cooperate in treatment decision making. This study evaluated the feasibility and efficacy of SDM in patients upon first admission for schizophrenia.MethodsThis was a randomized, parallel-group, two-arm, open-label, single-center study conducted in an acute psychiatric ward of Numazu Chuo Hospital, Japan. Patients with the diagnosis of schizophrenia upon their first admission were randomized into a SDM intervention group or a usual treatment group in a 1:1 ratio. The primary outcome was patient satisfaction at discharge. The secondary outcomes were attitudes toward medication at discharge and treatment continuation at 6 months after discharge.ResultsTwenty-four patients were randomly assigned. The trial was prematurely terminated due to slow enrollment. At discharge, the mean score on satisfaction was 23.7 in the SDM group and 22.1 in the usual care group (unadjusted mean difference: 1.6; 95% CI: −5.2 to 2.0). Group differences were not observed in attitude toward medication and treatment continuation. There was no statistically significant difference between the groups for the mean Global Assessment of Functioning score at discharge or length of stay as safety endpoint.ConclusionsNo statistical differences were found between the SDM group and usual care group in the efficacy outcomes and safety endpoints. Large trials are needed to confirm the efficacy of the SDM program upon first admission for schizophrenia.Trial registrationThe study has been registered with ClinicalTrials.gov as NCT01869660 (registered 27 May, 2013).

Background: Family history of suicide attempt is one of the risks of suicide. We aimed at exploring the characteristics of Japanese suicide attempters with and without a family history of suicide attempt.

Suicide attempt is a potent risk factor of subsequent suicide. Understanding the characteristics of suicide attempters is important for preventing suicide. The authors investigated aggression in medically serious suicide attempters at an emergency department. Trait aggression was evaluated in 55 suicide attempters and 71 healthy individuals as a control group using the Japanese version of the Buss-Perry Aggression Questionnaire (BAQ). Total BAQ scores (t = 2.782, P = 0.006) and the hostility scores (t = 3.735, P < 0.001) were significantly higher in the suicide attempters than the controls. It suggested that to focus on aggression and its management is one of the key components for preventing suicide.