Possible association between DBH 19 bp insertion/deletion polymorphism and clinical symptoms in schizophrenia with tardive dyskinesia.

Overactivity of dopaminergic neurotransmission is a putative mechanism of tardive dyskinesia (TD). Previous studies have found dysfunction in plasma dopamine beta-hydoxylase (DBH) in schizophrenia with TD. Moreover, DBH, whose activity and levels are strongly controlled by the DBH gene, is a key enzyme in the conversion of dopamine (DA) to norepinephrine (NE) associated with excited behavior. This study examined whether the DBH5'-insertion/deletion (Ins/Del) polymorphism was associated with excited behavior in schizophrenia with TD. The presence of the DBH5'-Ins/Del polymorphism was determined in 741 schizophrenia with TD (n = 345) and without TD (n = 396). The Abnormal Involuntary Movement Scale and Positive and Negative Syndrome Scale were used to assess the severity of TD and psychopathology of schizophrenia. There was no significant difference in the allelic and genotypic frequencies of the DBH5'-Ins/Del polymorphism between schizophrenia with and without TD (both p > 0.05). However, the excited symptoms score was significantly different to the DBH5'-Ins/Del genotypic groups in schizophrenia with TD (p < 0.05) but not in the two groups of non-TD and total patients (both p > 0.05). The excited symptoms score was higher in TD patients with the Del/Del genotype than those with Ins alleles (p = 0.015). Our findings suggest that the DBH5'-Ins/Del polymorphism may not contribute directly to the development of TD in schizophrenia, but it may be involved in the excited behavior of TD patients.

Association of angiotensin-converting enzyme gene polymorphism with schizophrenia and depressive symptom severity in a Chinese population.

BACKGROUND: Depressive symptoms are frequently observed in schizophrenia patients. Angiotensin-converting enzyme (ACE), a key enzyme of renin-angiotensin system, can catalyze the degradation of neuropeptides and modulate dopaminergic and serotonergic neurotransmission. Previous studies have revealed the association of the ACE gene insertion/deletion polymorphism with depressive disorder and its treatment response but not with the depressive symptoms in schizophrenia. OBJECTIVE: The aim of this study is to examine whether this polymorphism was associated with susceptibility to schizophrenia and with its psychopathological symptoms, especially depressive symptoms in a Han Chinese population. METHODS: This polymorphism was genotyped in 382 chronic patients and 538 healthy controls. Psychopathology was characterised using the positive and negative syndrome scale. RESULTS: The allelic and genotypic frequencies of this polymorphism significantly differed between patients and controls (both p < 0.001). A significant difference in the positive and negative syndrome scale depressive symptom score was observed among the three genotypes (p < 0.03), with higher score in patients with insertion/insertion (I/I) than with deletion/deletion (D/D) genotypes (p < 0.05). Furthermore, there was a significant linear correlation between the number of I alleles and the depressive symptom score (p < 0.05). CONCLUSIONS: The ACE gene insertion/deletion polymorphism may play a role in susceptibility to schizophrenia and also in its depressive symptom severity in a Han Chinese population.

Effects of astigmatic keratotomy combined with scleral tunnel incisions for the treatment of high astigmatism after penetrating keratoplasty.

The present study aimed to evaluate the efficacy, predictability and safety of astigmatic keratotomy (AK) combined with scleral tunnel incisions in the treatment of high astigmatism after penetrating keratoplasty (PKP). Paired AK combined with scleral tunnel incisions was performed at the steep astigmatic meridian in 8 eyes of 8 patients with high keratometric astigmatism [>5.0 diopters (D)] after PKP. Pre- and post-operative parameters, including uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), refraction and keratometric astigmatism were evaluated. The Alpins method for vector analysis was used to evaluate the changes in keratometric astigmatism. The results indicated a statistically significant reduction in the mean keratometric astigmatism from 8.16±3.02 D pre-operatively to 2.28±1.07 D at 3 months postoperatively. The mean UCVA improved from 0.95±0.24 logarithm of the minimum angle of resolution (logMAR) pre-operatively to 0.61±0.17 logMAR at 3 months postoperatively (P<0.05). The mean BCVA improved from 0.41±0.18 logMAR pre-operatively to 0.26±0.12 logMAR at 3 months postoperatively (P>0.05). Between 3 and 6 months after the surgery, the keratometric astigmatism remained stable. Alpins vector analysis demonstrated the relative predictability of this combined surgical treatment. The surgically induced astigmatism was significantly correlated with the target induced astigmatism (r=0.76, P<0.05). None of the patients had any severe complications. The present study indicated that AK combined with scleral tunnel incisions is an effective, relatively predictable and safe treatment for high astigmatism after PKP.

Association of different susceptibilities to morphine with the expression of 5-HTT and 5-HT1AR mRNA in brain regions of SD rats.

OBJECTIVE: To investigate the possible mechanism for the different CPP susceptibilities. METHODS: Using a conditioned place preference (CPP) model, rats were selected into high and low preference groups. Using in situ hybridization, we examined the mRNA expression of 5-hydroxytryptamine transporter (5-HTT) and 5-hydroxytryptamine 1A receptor (5-HT1AR) in 3 crucial regions in addiction, namely the ventral tegmental area (VTA), the nucleus accumbens (NAc), and the medial prefrontal cortex (mPFC), during the dependence and withdrawal. RESULTS: During dependence state, the expression of 5-HTT mRNA in each of the regions in the high preference group was significantly lower than that of the low preference group, while higher expression of 5-HT1AR mRNA in each of the regions in the high preference group than that of the low preference group was found (P < 0.05). During withdrawal state, the expression of 5-HTT mRNA in each of the regions in high preference group was significantly higher than that of the low preference group, while lower expression of 5-HT1AR mRNA in each of the regions in the high preference group than that of the low preference group was found (P < 0.05). CONCLUSION: 5-HTT and 5-HT1AR may play a role in differences in susceptibility to morphine.

[Dopamine D2 receptor and transportor [corrected] in the medial prefrontal contex of morphine-induced conditioned place preference in Sprague-Dawley rats].

OBJECTIVE: To investigate the expression of dopamine D2 receptors (D2R) and dopamine transportors (DAT) located in the medial prefrontal contex (mPFC) in high and low conditioned place preference (CPP) rats, and to unveil the possible mechanism leading to different CPP susceptibilities. METHODS: One hundred and sixty male Sprague-Dawley rats were randomly assigned into an experiment group (n = 130) and a control group (n = 30). The experiment group was re-classified into 2 groups according to CPP values:high preference group (HP group) and low preference group (LP group). According to the execution time-points after the last administration, the HP and LP group was classified into a 3-hour group (3 h), a 72-hour group (J3d), and a 14-day group (J14d), respectively. At 3 hours, 72 hours, and 14 days after the final injection, rats were killed and cardio-perfused, and the brains were removed and sliced up coronarily. The mRNA levels of D2R and DAT in mPFC were determined with in situ hybridization. RESULTS: There were no significant differences of pretest scores staying at the non-preference chamber among the groups(P = 0.470). However, the test scores of the CPP time stayed at pretest natural preference in the HP group were significantly higher than those of the LP group(P = 0.000). In 3h, J3d, and J14d groups,the expressions of D2R mRNA in the HP group (125.43 +/- 2.90 approximately 142.92 +/- 3.32) were lower than those of LP group (122.25 +/- 2.20 approximately 136.67 +/-5.39) (P = 0.000). In 3h and J3d,the expressions of DAT mRNA in the HP group (157.00 +/- 3.55 approximately 145.15 +/- 3.69) were significantly lower than those of the LP group (150.69 +/- 3.12 approximately 138.84 +/- 3.99) (P = 0.000). In J14d, there were no differences among 3 groups in mPFC (P = 0.458). CONCLUSION: D2R and DAT may be correlated closely and underlie the different susceptibilities to morphine induced CPP.

Correlations of PTEN genetic polymorphisms with the risk of depression and depressive symptoms in a Chinese population.

OBJECTIVE: This study aimed to investigate the correlations of three common single nucleotide polymorphisms (SNPs) in the PTEN gene (rs701848 T>C, rs2735343 G>C and rs112025902 A>T) with the risk of depression and depressive symptoms in a Chinese population. METHODS: From July 2011 to June 2013, a total of 384 patients with depression and 400 healthy individuals were included in this study. These SNPs in the PTEN gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing. The Hamilton Depression Rating Scale (HAMD) was used to evaluate the severity of depression. RESULTS: The C allele of rs701848, the C allele of rs2735343 and the T allele of rs112025902 were associated with an increased risk of depression (odds ratio [OR]=3.814, 95% CI: 3.093-4.703, P<0.001; OR=2.642, 95% CI: 2.152-3.242, P<0.001; OR=2.882, 95% CI: 2.347-3.539, P<0.001; respectively). Depression patients carrying C allele (TC+CC) of rs701848 and carrying T allele (AT+TT) of rs112025902 had higher HAMD total scores and HAMD anxiety factor scores than those carrying TT genotype of rs701848 and carrying AA genotype of rs112025902 (all P<0.05). Furthermore, depression patients carrying C allele (GC+CC) of rs2735343 had lower HAMD total scores and HAMD factors associated with depression scores than those carrying GG genotype (both P<0.05). Logistic regression analysis revealed that rs701848, rs2735343 and rs112025902 polymorphisms in the PTEN gene may be independent risk factors of depression (relative risk [RR]=1.807, 95% CI=1.023-3.193, P=0.042; RR=1.759, 95% CI=1.033-2.995, P=0.038; RR=1.646, 95% CI=1.018-2.663, P=0.042; respectively). CONCLUSION: Our findings provide evidence that rs701848, rs2735343 and rs112025902 polymorphisms in the PTEN gene may be correlated with the risk of depression and depressive symptoms in the Chinese population.

Protective Effect of Rutin Against H2O2-Induced Oxidative Stress and Apoptosis in Human Lens Epithelial Cells.

PURPOSE: The aim of this study was to evaluate the effect of rutin on oxidative stress and apoptosis induced by H2O2 in human lens epithelial (HLE) cells and the associated mechanisms involved. METHODS: Cell viability was assessed by 4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay and cell apoptosis was determined by flow cytometry, TUNEL assay and DNA fragmentation assay after 24 h treatment of 100 µM H2O2 with or without rutin pretreatment at various concentrations. The level of reactive oxygen species (ROS) was examined using 2',7'-dichlorodihydrofluorescein diacetate by flow cytometry. The activity of superoxide dismutase (SOD) was measured by xanthinoxidase method and the contents of glutathione (GSH) and malondialdehyde (MDA) were quantified by enzyme-linked immunosorbent assay. The expression change of Bcl-2, Bax and caspase-3 at mRNA and protein levels were detected by real-time polymerized chain reaction (RT-PCR) and Western-blot analysis, respectively. Activation and translocation of nuclear factor-kappaB (NF-кB/p65) were examined by Western blot and immunocytochemistry. RESULTS: Rutin pretreatment protected HLE cells from H2O2-induced cell viability decrease and apoptosis. In addition, in the presence of rutin, H2O2-induced intracellular excessive ROS and MDA were attenuated, whereas intracellular SOD and GSH depletion were prevented. Moreover, rutin also inhibited the up-regulation of caspase-3 and Bax expression and rescued down-regulation of Bcl-2 expression. Lastly, rutin blocked the activation and translocation of NF-кB/p65 induced by H2O2. CONCLUSIONS: Our results demonstrated that rutin effectively protects HLE cells from H2O2-induced oxidative stress and apoptosis in a dose-dependent manner. The involved mechanisms may be related to the regulation of ROS production, the inhabitation of lipid peroxidation, the protection of intracellular antioxidant system and its modulation of Bcl-2/Bax family and NF-кB/p65 signaling pathway.

SMILE and Wavefront-Guided LASIK Out-Compete Other Refractive Surgeries in Ameliorating the Induction of High-Order Aberrations in Anterior Corneal Surface.

Purpose. To compare the change of anterior corneal higher-order aberrations (HOAs) after laser in situ keratomileusis (LASIK), wavefront-guided LASIK with iris registration (WF-LASIK), femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK), and small incision lenticule extraction (SMILE). Methods. In a prospective study, 82 eyes underwent LASIK, 119 eyes underwent WF-LASIK, 88 eyes underwent FS-LASIK, and 170 eyes underwent SMILE surgery. HOAs were measured with Pentacam device preoperatively and 6 months after surgery. The aberrations were described as Zernike polynomials, and analysis focused on total HOAs, spherical aberration (SA), horizontal coma, and vertical coma over 6 mm diameter central corneal zone. Results. Six months postoperatively, all procedures result in increase of anterior corneal total HOAs and SA. There were no significant differences in the induced HOAs between LASIK and FS-LASIK, while SMILE induced fewer total HOAs and SA compared with LASIK and FS-LASIK. Similarly, WF-LASIK also induced less total HOAs than LASIK and FS-LASIK, but only fewer SA than FS-LASIK (P < 0.05). No significant difference could be detected in the induced total HOAs and SA between SMILE and WF-LASIK, whereas SMILE induced more horizontal coma and vertical coma compared with WF-LASIK (P < 0.05). Conclusion. FS-LASIK and LASIK induced comparable anterior corneal HOAs. Compared to LASIK and FS-LASIK, both SMILE and WF-LASIK showed advantages in inducing less total HOAs. In addition, SMILE also possesses better ability to reduce the induction of SA in comparison with LASIK and FS-LASIK. However, SMILE induced more horizontal coma and vertical coma compared with WF-LASIK, indicating that the centration of SMILE procedure is probably less precise than WF-LASIK.

Serotonin regulates brain-derived neurotrophic factor expression in select brain regions during acute psychological stress.

Previous studies suggest that serotonin (5-HT) might interact with brain-derived neurotrophic factor (BDNF) during the stress response. However, the relationship between 5-HT and BDNF expression under purely psychological stress is unclear. In this study, one hour before psychological stress exposure, the 5-HT1A receptor agonist 8-OH-DPAT or antagonist MDL73005, or the 5-HT2A receptor agonist DOI or antagonist ketanserin were administered to rats exposed to psychological stress. Immunohistochemistry and in situ hybridization revealed that after psychological stress, with the exception of the ventral tegmental area, BDNF protein and mRNA expression levels were higher in the 5-HT1A and the 5-HT2A receptor agonist groups compared with the solvent control no-stress or psychological stress group in the CA1 and CA3 of the hippocampus, prefrontal cortex, central amygdaloid nucleus, dorsomedial hypothalamic nucleus, dentate gyrus, shell of the nucleus accumbens and the midbrain periaqueductal gray. There was no significant difference between the two agonist groups. In contrast, after stress exposure, BDNF protein and mRNA expression levels were lower in the 5-HT1A and 5-HT2A receptor antagonist groups than in the solvent control non-stress group, with the exception of the ventral tegmental area. Our findings suggest that 5-HT regulates BDNF expression in a rat model of acute psychological stress.

Association between DßH 5'-insertion/deletion polymorphism and cognition in patients with chronic schizophrenia.

BACKGROUND: Cognitive deficits have been identified as a core feature of patients with schizophrenia. Many genes associated with the dopamine and norepinephrine systems are related to the cognitive deficits of patients with schizophrenia. Dopamine ß-hydroxylase (DßH) is a key enzyme that converts dopamine to norepinephrine and for which activity and levels are under strong genetic control. OBJECTIVE: To examine whether the DßH 5'-insertion/deletion (Ins/Del) polymorphism influences cognitive function in patients with chronic schizophrenia. METHOD: The presence of the DßH 5'-Ins/Del polymorphism was determined in 733 patients with chronic schizophrenia (diagnosed according to DSM-IV) and 544 healthy controls using a case-control design. We assessed all of the patients' psychopathology using the Positive and Negative Syndrome Scale (PANSS) and cognition in 540 patients with chronic schizophrenia and 297 healthy controls using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). This study was conducted between 2008 and 2011. RESULTS: The allelic and genotypic frequencies of the DßH 5'-Ins/Del polymorphism were not significantly different between patients with schizophrenia and healthy controls (both P values > .05). However, the cognitive test scores were significantly lower in patients than in the healthy controls for all scales (all P values < .05), except visuospatial/constructional (P > .05). The attention score significantly differed according to the genotypic group (P < .05) in patients but not in the healthy controls (P > .05). In patients with chronic schizophrenia, the mean ± SD attention score was lower in the DßH 5'-Del/Del genotype (65.7 ± 16.8) than in the DßH 5'-Ins/Del genotype (71.4 ± 18.0; P = .007) and the DßH 5'-Ins/Ins genotype (70.8 ± 17.1; P = .02). CONCLUSIONS: This study found that patients with chronic schizophrenia had poorer cognitive function than the healthy controls in all examined cognitive domains except for visuospatial/constructional. No significant association was found between the DßH 5'-Ins/Del polymorphism and patients with chronic schizophrenia. However, the DßH 5'-Del/Del genotype may be specific to attentional decrements in patients with chronic schizophrenia.

Identification of Mutations in Myocilin and Beta-1,4-galactosyltransferase 3 Genes in a Chinese Family with Primary Open-angle Glaucoma.

BACKGROUND: Glaucoma is a major cause of irreversible blindness worldwide. There is evidence showing that a subset of the disease is genetically determined. In this study, we screened for mutations in chromosome 1q-linked open-angle glaucoma (GLC1A) in a Chinese family with primary open-angle glaucoma (POAG). METHODS: A total of 23 members from five generations of a family were enrolled and underwent thorough ophthalmologic examinations. In addition, 200 unrelated healthy Chinese controls were also recruited as normal control. GLC1A gene was amplified by polymerase chain reaction, and DNA sequencing was performed to screen for mutations. RESULTS: Six members were diagnosed as POAG, with severe clinical manifestations, and history of high intraocular pressures. The mean age of disease onset was 26.3 years. However, the others were asymptomatic. In six affected and three asymptomatic members, gene sequencing revealed a mutation c.C1456T in exon 3 of myocilin gene (MYOC). Furthermore, we also identified a novel mutation c.G322A in beta-1,4-galactosyltransferase 3 (B4GALT3) gene in all six affected and three asymptomatic members, which was not reported previously in POAG patients. The two newly identified variants were absent in other family members as well as controls. CONCLUSION: The mutations c.1456C < T (p.L486F) in MYOC and c.322G < A (p.V108I) in B4GALT3 are likely responsible for the pathogenesis of POAG in this family.

An Updated Meta-Analysis: Risk Conferred by Glutathione S-Transferases (GSTM1 and GSTT1) Polymorphisms to Age-Related Cataract.

Purpose. To study the effects of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms on age-related cataract (ARC). Methods. After a systematic literature search, all relevant studies evaluating the association between GSTs polymorphisms and ARC were included. Results. Fifteen studies on GSTM1 and nine studies on GSTT1 were included in this meta-analysis. In the pooled analysis, a significant association between null genotype of GSTT1 and ARC was found (OR = 1.229, 95% CI = 1.057-1.429, and P = 0.007). In subgroup analysis, the association between cortical cataract (CC) and GSTM1 null genotype was statistically significant (OR = 0.713, 95% CI = 0.598-0.850, and P < 0.001). In addition, GSTM1 null genotype was significantly associated with ARC causing risk to individuals working indoors and not individuals working outdoors. The association between GSTT1 null genotype and risk of ARC was statistically significant in Asians (OR = 1.442, 95% CI = 1.137-1.830, and P = 0.003) but not in Caucasians. Conclusions. GSTM1 positive genotype is associated with increased risk of CC and loses the protective role in persons who work outdoors. Considering the ethnic variation, GSTT1 null genotype is found to be associated with increased risk of ARC in Asians but not in Caucasians.

TCF4 gene polymorphism is associated with cognition in patients with schizophrenia and healthy controls.

BACKGROUND: Cognitive deficits have been identified as an important core feature of schizophrenia. Single nucleotide polymorphisms in the transcription factor 4 (TCF4) gene have been reported to be involved in the susceptibility to schizophrenia and be significantly related to cognitive deficits of schizophrenia and controls. This study examines whether the TCF4 rs2958182 polymorphism influences cognitive functions in chronic schizophrenia and controls. METHODS: The presence of the TCF4 rs2958182 was determined in 976 patients and 420 controls using a case-control design. We assessed all the patients' psychopathology using the Positive and Negative Syndrome Scale (PANSS). Cognition was assessed in 777 patients and 399 controls by using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RESULTS: There were marginally significant differences in the TCF4 rs2958182 allelic and genotypic distributions between patients and controls (χ2 = 3.48, p = 0.062 and χ2 = 0.036, p = 0.036, respectively). Cognitive test scores were significantly lower in patients than in controls on all scales (all p < 0.001) except for the visuospatial/constructional index (p > 0.05). There were significant genotype effects on delayed memory score (p = 0.013), the RBANS total score (p = 0.028) and language score (p = 0.034). Further analysis showed that the language score significantly differed according to the genotypic groups (A/A+T/A group versus T/T group) (p = 0.007) in patients but not in controls (p > 0.05), and the delayed memory score also significantly differed according to the genotypic groups (A/A+T/A group versus T/T group) (p = 0.021) in controls but not in patients (p > 0.05). CONCLUSIONS: This study found that the A allele of the TCF4 rs2958182 polymorphism was the risk allele of schizophrenia, and was associated with lower cognitive performance in language in schizophrenia and delayed memory in controls. In contrast, the T allele of this polymorphism was found to be the schizophrenia risk allele in another study in Han Chinese people.