Objective To observe non-displaceable binding potential (BPND) changes of striatal dopamine D2 receptors(SDDR) in patients with first-episode major depressive disorder (MDD) using 11C-Raclopride PET/CT,and to analyze the relationship between BPND and Hamilton rating scale for depression (HAM-D).Methods From December 2014 to December 2015,patients with first-episode MDD and age/gender-matched healthy controls underwent brain MRI and 11C-Raclopride PET/CT in this prospective study.BPND of bilateral SDDR was calculated by molecular imaging and kinetic analysis toolbox (MIAKAT).BPND changes of bilateral SDDR and their relationship with HAM-D score were analyzed.Paired t test,two-sample t test and Pearson correlation analysis were used.Results A total of 20 MDD patients (8 males,12 females,average age: (32.80±9.76) years) and 20 healthy controls (9 males,11 females,average age:(29.25±6.93) years) were enrolled in this study.The 11C-Raclopride uptake in brain tissue of the MDD group and control group were mainly distributed in bilateral striatum,and very few 11C-Raclopride was distributed in bilateral cerebral cortex and cerebellum.In MDD group,the BPND level of bilateral SDDR had no statistical differences(t values: 0.69,0.35,both P>0.05),and similar results were found in the control group(t values: 0.28,0.24,both P>0.05).Compared with the control group,however,the MDD group had lower BPND level of bilateral SDDR(t values: 3.13-4.41,all P<0.05).The BPND of bilateral caudate nucleus and/or putamen D2 receptors was correlated with HAM-D total score,anxiety/somatization factor score,cognitive impairment factor score,retardation factor score and sleep disturbance factor score(r values: from-0.688 to-0.453,all P<0.05).Conclusions The binding potential of SDDR in patients with first-episode MDD is declined,and the BPND level of SDDR is correlated with symptoms of depression.The abnormality of SDDR may be an important molecular mechanism of the abnormality of midbrain-striatal dopamine reward circuits in MDD patients.

The aim of this study was to establish a high performance liquid chromatography-mass spectrometry method for the determination of 5-(4′-(bromomethyl)-［1, 1′-biphenyl］-2-yl)- 1H-tetrazole(BBT1)and 5-(4′-(dibromomethyl)-［1, 1′-biphenyl］-2-yl)-1H-tetrazole(BBT2), which are two genotoxic impurities in olmesartan medoxomil. Chromatographic separation was based on an Agilent Zorbax Eclipse Plus C18(250 mm × 4. 6 mm, 5 μm)column using water(containing 0. 1% formic acid)- acetonitrile as mobile phase in gradient elution mode. Mass spectrometry was operated in positive ion mode. Selective ion monitors were set at m/z 315 for BBT1 and at m/z 395 for BBT2. Good linear correlations were observed in the range of 0. 009 4- 0. 561 0 μg/mL(r=0. 998)with the quantification limit at 9. 35 ng/mL and the detection limit at 3. 12 ng/mL for BBT1, and in the range of 0. 018 2- 0. 547 5 μg/mL(r=0. 999)with the quantification limit at 18. 25 ng/mL and the detection limit at 6. 08 ng/mL for BBT2. Furthermore, the average recoveries of the three spiked concentration level were 96. 5%(n=9, RSD=4. 8%)and 98. 0%(n=9, RSD=5. 1%)for BBT1 and BBT2, respectively. The proposed method is simple, specific and accurate, and quite suitable for the determination of BBT1 and BBT2 in olmesartan medoxomil.

Objective To explore the correlation between changes of striatal dopamine D2receptors non-displaceable binding potential (BPND) in 11C-Raclopride PET-CT and brain regional homogeneity (ReHo) derived from resting state functional MRI (fMRI) in patients with first-episode major depressive disorder (MDD) . Methods Patients with first-episode MDD and age and sex matched healthy volunteers accepted brain 11C-Raclopride PET-CT and resting state fMRI. MIAKAT based on MATLAB and Rest 1.8 were used to calculate BPNDof brain dopamine D2receptors and brain ReHo, respectively. Changes of striatal dopamine D2receptors BPNDand brain ReHo values were analyzed by paired-sample t test and two independent sample t-test, and Pearson correlation analysis was used to analyze the correlation between BPNDand ReHo. Results Twenty patients with first-episode MDD were enrolled as MDD group, and 20 healthy volunteers as the control group. The two groups were all right-handed, and there were no statistical differences for age (t =1.33,P=0.19)and gender(χ2=0.10,P=0.75). Compared with the control group, the ReHo in MDD patients increased in the bilateral striatum (caudate nucleus and putamen), bilateral medial prefrontal lobes, and right thalamic (27 to 56 voxels, P＜0.05) and decreased in the left middle frontal gyrus, the left anterior cingulate, the left hippocampal and the right amygdala (21 to 35 voxels, P＜0.05). In addition, compared with the control group, BPNDof bilateral caudate nucleus and putamen dopamine D2receptors in the MDD group were decreased (t=－4.41 to －3.13, P＜0.05). Furthermore, there was a negative correlation between D2 receptors BPNDand ReHo of bilateral caudate nucleus and putamen (r=－0.81 to－0.62, P＜0.05). And there was a negative correlation between ReHo of the bilateral medial prefrontal lobes and BPNDof the same lateral caudate nucleus and putamen D2receptors in the MDD group (r=－0.86 to－0.52, P＜0.05). Besides, ReHo of the left middle frontal gyrus, right thalamic, left anterior cingulate, left hippocampal and right amygdala had no correlation with the D2receptors BPNDof the striatum in the MDD group (－0.27 to 0.39, P＞0.05). Conclusion There were abnormal levels of dopamine neurotransmitter in the cerebral striatum regions and abnormal brain activities in the brain region associated with dopamine reward circuit in the first-episode MDD patients, and there was a correlation between the two abnormalities.

Objective To explore the changes of dopamine D2 receptor in dopamine pathway in in-somnia patients and discuss its clinical significance. Methods From January 2016 to December 2016, 15 patients with insomnia (1 male, 14 females, age:(44.3±8.6) years) and 15 gender-/age-matched-healthy volunteers (control group;3 males, 12 females, age:(40.5±9.0) years) were included to undergo resting brain 11C-Raclopride PET/CT imaging. The D2 receptor binding potential (BPND) of the dopamine pathway was calculated by molecular imaging and kinetic analysis toolbox ( MIAKAT) software. The BP ND , Hamilton depression scale ( HAMD) , transient and graphics memory scale results were compared with two-sample t test and Mann-Whitney u test between the two groups. Pearson correlation analysis was used to evaluate the correlation between BPND(nucleus accumbens, caudate nucleus, putamen) and Pittsburgh sleep quality in-dex ( PSQI) , HAMD, course of disease, transient memory and graphical memory scale scores in the patient group. Results The BP ND in bilateral putamen, nucleus accumbens and left caudate nucleus of patients was lower than that of controls( left putamen:z=-2.717, right putamen:z=-2.883, both P<0.01;left nu-cleus accumbens:t=-2.269, right nucleus accumbens:t=-2.410, both P<0.05;left caudate nucleus:t=-2.632,P<0. 05), but the BPND level of right caudate nucleus was not significantly different(z=-0.850, P>0.05) . The scores of HAMD in the patient group were higher than those in control group ( t=10. 273, P<0. 01), while the scores of instantaneous memory (t=-4.888, P<0.01) and graphical memory scale (t=-2.624, P<0.05) were lower. There were significant negative correlations between the BP ND of bilateral nucleus ac-cumbens, caudate nucleus and putamen and the course of insomnia in the patient group ( r range:-0.761 to-0.682, all P<0.01) . Conclusion Patients with insomnia have abnormal neurotransmitter system of dopa-mine D2 and it may play a role in the pathogenesis of insomnia.

Objective:To study the correlation between changes of cerebral striatal dopamine D 2 receptors non-displaceable binding potential (BP ND), functional connectivity (FC) and clinical symptoms in patients with first-episode major depressive disorder (MDD), by 11C-Raclopride PET/CT and resting state fMRI (rs-fMRI). Methods:Thirty-eight first-episode depression patients (MDD group) and forty healthy volunteers (control group) matched with age, gender and years of education were selected. All subjects were scored with Hamilton depression scale (24 versions) before enrollment.All the subjects underwent cerebral 11C-Raclopride PET/CT and rs-fMRI in resting state. MIAKAT and DPARSF were used to analyze BP ND of cerebral striatal dopamine D 2 receptors and FC of striatum and the whole brain in subjects, respectively. Changes of striatal dopamine D 2 receptors BP ND and striatum and the whole brain FC of MDD were analyzed, and correlations among BP ND, FC and Hamilton depression rating scale were calculated by Rest 1.8 and SPSS 20.0. Results:Compared with the control group, BP ND of bilateral caudate nucleus and putamen dopamine D 2 receptors in the MDD group were decreased(left caudate nucleus: 1.16±0.37 vs 1.48±0.39, right caudate nucleus: 1.21±0.31 vs 1.62±0.48, left putamen: 1.73±0.47 vs 2.21±0.66, right putamen: 1.79±0.46 vs 2.17±0.65, t=3.66, -4.42, -3.68, -2.91, all P<0.001). Besides, FC of left caudate nucleus and left medial prefrontal lobes(4.38±1.31, 2.35±0.48), left caudate nucleus and left middle frontal gyrus(3.36±1.11, 1.64±0.56), left caudate nucleus and left superior frontal gyrus(3.14±0.78, 1.64±0.53), left putamen and left medial prefrontal lobes(4.10±1.42, 2.42±0.64, t=6.82, P<0.05), right caudate nucleus and right medial prefrontal lobes (4.32±1.30, 2.33±0.63, t=8.51, P<0.05), right putamen and right medial prefrontal lobes(3.77±1.25, 2.31±0.63, t=6.49, P<0.05)in the MDD group were increased.FC of left putamen and left anterior cingulate(1.60±0.55, 2.68±0.84, t=-6.76, P<0.05), right caudate nucleus and right amygdala (1.67±0.57, 3.46±0.64, t=-8.27, P<0.05) in the MDD group were decreased. Furthermore, there were significant negative correlations between D 2 receptors BP ND of bilateral striatum and FC of the same lateral striatum and medial prefrontal lobes ( r=-0.66, -0.50, -0.67, -0.47, all P<0.05). In MDD group, FC in left caudate nucleus and left medial prefrontal lobe were positively correlated with total score of Hamilton depression scale and anxiety somatization( r=0.55, 0.68, P<0.001). FC in left putamen and left medial prefrontal cortex were positively correlated with cognitive impairment and retardation ( r=0.37, 0.40, P=0.021, 0.001). FC of right caudate nucleus and right medial prefrontal lobe were positively correlated with Hamilton depression scale total score and anxiety somatization ( r=0.52, 0.67, all P<0.001). FC in right putamen and right medial prefrontal cortex was positively correlated with cognitive impairment ( r=0.50, P=0.002). Conclusion:The abnormal BP ND of cerebral striatal dopamine D 2 receptor of patients with first-episode depression is related to the abnormal activity of dopamine reward circuit related neurons in patients with MDD, which was related to clinical symptoms of depression. It may be involved in the pathogenesis of depression.