[Advances in Imaging Genetics of Suicidal Behavior].

Suicide,a major public health problem,is the death caused by injuring oneself with the intent to die.In this paper,we reviewed the genes encoding serotonin system,calcium voltage-gated channel subunit alpha1 C,γ-aminobutyric acid,and spindle and kinetochore associated complex subunit 2,as well as their related brain regions,from the perspective of imaging genetics,aiming to provide new ideas for the research and intervention on suicidal behavior.

[Proton magnetic resonance spectroscopy and diffusion tensor imaging study of first-episode patients with positive symptoms of schizophrenia].

OBJECTIVE: To study the changes in the frontal white matter, the head of the hippocampus, and the anterior cingulate fasciculus metabolites in first-episode patients with positive symptoms of schizophrenia. METHODS: Twenty first-episode patients with positive symptoms of schizophrenia underwent diffusion tensor imaging (DTI) and proton multi-voxel spectroscopy (1H-MRS) examination. 1H-MRS images were obtained from two sides of the frontal white matter, the head of the hippocampus and the anterior cingulate fasciculus regions. The metabolites detected included N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine and phosphocreatine (Cr), and the ratios of NAA/Cr, Cho/Cr and NAA/Cho were determined. The fractional anisotropy (FA) values were measured in the frontal white matter, the head of the hippocampus, and the anterior cingulate fasciculus. RESULTS: The Cho/Cr ratio was significantly reduced in the left frontal white matter (1.18 ± 0.21) of the patients as compared to the right side (1.44 ± 0.34, P<0.05). In the left head of the hippocampus, NAA/Cr (1.34 ± 0.45) and Cho/Cr (1.41 ± 0.39) were significantly reduced compared to those of the right side (1.75 ± 0.15 and 1.76 ± 0.36, respectively, P<0.05). No significant differences in the metabolite levels were found between the left and right anterior cingulate fasciculus (P>0.05). DTI showed similar FA values between the left and right sides of the frontal white matter, the head of the hippocampus, and the anterior cingulate fasciculus (P>0.05). CONCLUSIONS: Patients with positive symptoms of schizophrenia have diminished neuronal integrity and/or function in the left frontal white matter and head of the hippocampus, but not in the anterior cingulate fasciculus.

Novel oxoisoaporphine-based inhibitors of acetyl- and butyrylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation.

A series of novel oxoisoaporphine-based inhibitors (10-aminoalkylamino-1-azabenzanthrone Ar-NH(CH(2))(n)NR(1)R(2)) of acetylcholinesterase (AChE) has been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE) and AChE-induced ß-amyloid (Aß) aggregation. The synthetic compounds exhibited high AChE inhibitory activity with IC(50) values in the submicromolar range in most cases. Non-competitive binding mode was found for these derivatives by the graphical analysis of steady-state inhibition data. Moreover, all compounds exhibit significant inhibitory activity on AChE-induced Aß aggregation with inhibitory potency from 54.5% to 93.5%. Finally, six out of twelve synthetic compounds were predicted to be able to cross the blood-brain barrier (BBB) to reach their targets in the central nervous system (CNS) according to a parallel artificial membrane permeation assay for BBB. The result encourages us to study this class of compounds thoroughly and systematically.

Hybrids of oxoisoaporphine-tacrine congeners: novel acetylcholinesterase and acetylcholinesterase-induced ß-amyloid aggregation inhibitors.

A series of dual binding site acetylcholinesterase (AChE) inhibitors have been designed, synthesized, and tested for their ability to inhibit AChE, butyrylcholinesterase (BChE), AChE-induced and self-induced ß-amyloid (Aß) aggregation. The new hybrids consist of a unit of 1-azabenzanthrone and a tacrine or its congener, connected through an oligomethylene linker containing an amine group at variable position. These hybrids exhibit high AChE inhibitory activity with IC(50) values in the nanomolar range in most cases. Moreover, five out of the 12 hybrids of this series, particularly those bearing a tetrahydroacridine moiety, exhibit a significant in vitro inhibitory activity toward the AChE-induced and self-induced Aß aggregation, which makes them promising anti-Alzheimer drug candidates.