[Forensic Analysis of 133 Cases of Knee Injuries].

ABSTRACT: Objective To discuss the types, characteristics, and the evaluation of disability of knee injuries. Methods The data of 133 cases of knee injury from 2017 to 2019 were collected and statistically analyzed according to the region of injury, the degree of disability, etc. Results One hundred and twenty-five cases of injury were compound, and 8 cases were simple. The incidences of ligament injury, meniscus injury and fracture were 88.72%, 75.19% and 57.89%, respectively. Of the cruciate ligament injuries, 12 cases were posterior cruciate ligament injury while 51 cases were anterior cruciate ligament injury, and the differences between the two kinds of injury had statistical significance （P<0.05）; 32 cases were secondary traumatic arthritis. The rates of disability of knee injuries were 38.35% （Grade Ⅸ and Ⅹ）. Conclusion Compound knee injuries are common, and traumatic arthritis has a relatively high rate. Multiple injuries can affect the stability and weight-bearing of the knee joint. It is suggested that in addition to evaluating the range of motion of knee joint, multiple factors should be considered to assess disability.

Polymorphisms of the oxytocin receptor gene and overeating: the intermediary role of endophenotypic risk factors.

BACKGROUND/OBJECTIVES: Oxytocin (OXT) is an evolutionarily ancient neuropeptide with strong links to affiliative and prosocial behaviors, and the management of stress. Increases in OXT also tend to decrease food intake, especially of sweet carbohydrates. The social correlates of low OXT levels mesh with the social deficits and stress proneness identified in interpersonal models of overeating, as well as the increased appetite for highly palatable foods typically seen in chronic overeaters. The objectives of this study were to investigate links between polymorphisms of the oxytocin receptor (OXTR) gene and overeating, and to examine OXTR links with relevant endophenotypes of overeating related to reward and stress sensitivity, and to food preferences. SUBJECT/METHODS: The sample comprised 460 adults between the ages of 25 and 50 years recruited from the community, and representing a broad range of body weights. Overeating, reward and punishment sensitivity, and food preferences, were quantified as composite variables using well-validated questionnaires. In addition, seven single-nucleotide polymorphisms (rs237878, rs237885, rs2268493, rs2268494, rs2254298, rs53576, rs2268498) of the OXTR gene were genotyped. RESULTS: Analyses identified a four-marker haplotype that was significantly related to food preferences. Individual genotype analyses also found that at least one of the markers was related to each of the phenotypic variables. In addition, an empirically derived structural equation model linking genetic and phenotype variables produced a good fit to the data. CONCLUSIONS: The results of this preliminary study have demonstrated that OXTR variation is associated with overeating, and with endophenotypic traits such as sweet and fatty food preferences, and reward and punishment sensitivity. In general, the genetic findings also favor the view that overeating may be associated with relatively low basal OXT levels.

Genome-wide association study on antipsychotic-induced weight gain in the CATIE sample.

Antipsychotic-induced weight gain (AIWG) is a common side effect with a high genetic contribution. We reanalyzed genome-wide association study (GWAS) data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) selecting a refined subset of patients most suitable for AIWG studies. The final GWAS was conducted in N=189 individuals. The top polymorphisms were analyzed in a second cohort of N=86 patients. None of the single-nucleotide polymorphisms was significant at the genome-wide threshold of 5x10(-8). We observed interesting trends for rs9346455 (P=6.49x10(-6)) upstream of OGFRL1, the intergenic variants rs7336345 (P=1.31 × 10(-5)) and rs1012650 (P=1.47 × 10(-5)), and rs1059778 (P=1.49x10(-5)) in IBA57. In the second cohort, rs9346455 showed significant association with AIWG (P=0.005). The combined meta-analysis P-value for rs9346455 was 1.09 × 10(-7). Our reanalysis of the CATIE GWAS data revealed interesting new variants associated with AIWG. As the functional relevance of these polymorphisms is yet to be determined, further studies are needed.The Pharmacogenomics Journal advance online publication, 1 September 2015; doi:10.1038/tpj.2015.59.

Methylenetetrahydrofolate reductase gene variants and antipsychotic-induced weight gain and metabolic disturbances.

Weight gain and metabolic disturbances represent serious side-effects in antipsychotic (AP) treatment, particularly with clozapine and olanzapine. The methylenetetrahydrofolate reductase (MTHFR) gene is a key determinant in the folate metabolism and previous studies reported a significant effect on AP-induced weight gain and related metabolic abnormalities. Thus, we investigated MTHFR gene variants and changes in several important metabolic parameters in AP-treated patients. In this study, two functional MTHFR polymorphisms, rs1801133 (C677T) and rs1801131 (A1298C), were investigated for changes in weight and metabolic parameters. Genotypic associations were evaluated in a large population (n = 347 including 66 first episode psychosis, FEP patients) treated mostly with clozapine and olanzapine. We did not detect any genotypic association with weight changes (p > 0.05) in our total sample and in the sample refined for ancestry and medication. In our allelic analyses, we observed a trend for the 677-C allele to be associated with weight gain in the total sample (p = 0.03). This effect appeared to be driven by the FEP patients where those carrying the C-allele gained, on average, twice as much weight. Exploratory analyses revealed a significant association between the C677T and the A1298C polymorphism with HDL cholesterol serum levels in patients (p = 0.031). Overall we did not detect a major effect of two functional MTHFR gene variants and AP-induced weight gain. However, our findings suggest an effect of the C677T polymorphism in FEP patients and changes in weight and cholesterol levels. Further investigations in a larger sample are required.

Genetic association study between antipsychotic-induced weight gain and the melanocortin-4 receptor gene.

Antipsychotic-induced weight gain (AIWG) may result in the metabolic syndrome in schizophrenia (SCZ) patients. Downstream variants of the melanocortin-4 receptor (MC4R) gene have been associated with obesity in various populations. Thus, we examined single-nucleotide polymorphisms (SNPs) in the MC4R region for association with AIWG in SCZ patients. Four SNPs (rs2229616, rs17782313, rs11872992 and rs8087522) were genotyped in 224 patients who underwent treatment for SCZ and were evaluated for AIWG for up to 14 weeks. We compared weight change (%) across genotypic groups using analysis of covariance for three SNPs (r²≤0.8). European-ancestry patients who were rs8087522 A-allele carriers (AG+AA) on clozapine gained significantly more weight than non-carriers (P=0.027, n=69). These observations were marginal after correction for multiple testing. We performed in vitro electrophoretic mobility-shift assay that suggested that the presence of the A-allele may create a transcription factor-binding site. Further investigation is warranted for both these exploratory findings.

The role of oxytocin and oxytocin receptor gene variants in childhood-onset aggression.

Aggressive antisocial behaviours are the most common reasons why adolescents are referred to mental health clinics. Antisocial behaviours are costly in social and financial terms. The aetiology of aggressive behaviours is unknown but growing evidence suggests it is heritable, and certain genetic variants have been implicated as contributing factors. The purpose of this study was to determine whether genes regulating the hormone oxytocin (OXT) were associated with aggressive antisocial behaviour. The case-control study sample consisted of 160 cases of children displaying extreme, persistent and pervasive aggressive behaviour. This case sample was compared with 160 adult controls. We used polymerase chain reaction (PCR) to determine the genotype for three oxytocin gene (OXT) single nucleotide polymorphisms (SNPs): rs3761248, rs4813625 and rs877172; and five oxytocin receptor gene (OXTR) SNPs: rs6770632, rs11476, rs1042778, rs237902 and rs53576. Genotypic analyses were performed using stata, while differences in haplotypic and allelic frequencies were analysed using Unphased. We also performed within-case analyses (n = 236 aggressive cases) examining genotypic and allelic associations with callous-unemotional (CU) scores (as measured by the psychopathic screening device). OXTR SNPs rs6770632 and rs1042778 may be associated with extreme, persistent and pervasive aggressive behaviours in females and males, respectively. These and haplotype results suggest gender-specific effects of SNPs. No significant differences were detected with respect to CU behaviours. These results may help to elucidate the biochemical pathways associated with aggressive behaviours, which may aid in the development of novel medications.

Systematic analysis of dopamine receptor genes (DRD1-DRD5) in antipsychotic-induced weight gain.

Antipsychotic-induced weight gain has emerged as a serious complication in the treatment of patients with most antipsychotics. We have conducted the first in-depth examination of dopamine receptor genes in antipsychotic-induced weight gain. A total of 206 patients (139 of European descent and 56 African Americans) who underwent treatment for chronic schizophrenia or schizoaffective disorder were evaluated after on average over 6 weeks of treatment. Thirty-six tag single nucleotide polymorphisms (SNPs) and one variable-number tandem repeat, spanning the five dopamine receptor genes (DRD1-DRD5) were analyzed. In the total sample, we found a nominally significant association between the DRD2 rs1079598 marker and weight change using a cutoff of 7% gain (P=0.03). When stratifying the sample according to ethnicity and antipsychotics with highest risk for weight gain, we found significant associations in three DRD2 SNPs: rs6277 (C957T), rs1079598 and rs1800497 (TaqIA). The other genes were primarily negative. We provide evidence that dopamine receptor DRD2 gene variants might be associated with antipsychotic-induced weight gain in chronic schizophrenia patients.

Association study of cannabinoid receptor 1 (CNR1) gene in tardive dyskinesia.

Tardive dyskinesia (TD) is a severe, debilitating movement disorder observed in 25-30% of the patients treated with typical antipsychotics. Cannabinoid receptor 1 (CNR1) activators tend to inhibit movement, an effect prevented by rimonabant and other selective CNR1 antagonists. Furthermore, CNR1 receptor is downregulated in Huntington's disease and upregulated in Parkinson's disease. Twenty tagSNPs spanning the CNR1 gene were analyzed in schizophrenia patients of European ancestry (n=191; 74 with TD). Significant genotypic (P=0.012) and allelic (P=0.012) association was observed with rs806374 (T>C). Carriers of the CC genotype were more likely to be TD positive (CC vs TT+TC, odds ratio=3.4 (1.5-7.8), P=0.003) and had more severe TD (CC vs TT+TC; 9.52±9.2 vs 5.62±6.9, P=0.046). These results indicate a possible role of CNR1 in the development of TD in our patient population. However, these observations are marginal after correcting for multiple testing and need to be replicated in a larger patient population.

Opiates, overeating and obesity: a psychogenetic analysis.

OBJECTIVE: This study provides an original perspective on the associations among endogenous opiates, overeating and obesity. The aim was to assess whether variability in the OPRM1 gene, as assessed by seven single-nucleotide polymorphisms, relates to individual differences in the preference for sweet and fatty foods. We also anticipated that these food preferences would be positively associated with binge eating, hedonic eating and emotionally driven eating-patterns of overeating that would, in turn, predict higher body mass index (BMI). DESIGN: Analysis of variance procedures examined genotype differences in food preferences; bivariate correlation coefficients examined the relationships among food preferences and the overeating variables; and a regression analysis tested the combined influences of the overeating variables on BMI. DNA was extracted from whole blood for the genotyping, and measures of food preferences and eating behaviours were obtained from well-validated self-report questionnaires. SUBJECTS: Participants were 300 healthy adult men and women recruited from the community. RESULTS: All the predicted associations were supported by statistically significant results. In particular, the G/G genotype group of the functional A118G marker of the OPRM1 gene reported higher preferences for sweet and fatty foods compared with the other two groups. Food preferences were also related to all overeating measures, which in turn accounted for a substantial proportion of the variance in BMI. CONCLUSIONS: Our findings suggest that some of the diversity in the preference for highly palatable foods can be explained by genotypic differences in the regulation of mu opioid receptors. The associations reported in this paper are important from a public-health perspective because of the abuse potential of sweet-fat foods and their strong relationship with obesity.

Replicated association of the NR4A3 gene with smoking behaviour in schizophrenia and in bipolar disorder.

Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analysed the association of six single nucleotide polymorphisms (SNPs) within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (P = 0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (P = 0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction.

Effect of dopamine D3 receptor gene polymorphisms and clozapine treatment response: exploratory analysis of nine polymorphisms and meta-analysis of the Ser9Gly variant.

D2 blockade has been implicated in having a central role in antipsychotic response. However, treatment refractoriness, in spite of complete D2 blockade, as well as the efficacy of clozapine (CLZ) in a portion of this patient population, indicates the involvement of other factors as well. Several lines of evidence suggest a role for D3. Furthermore, an earlier meta-analysis by Jönsson et al. (2003) (n=233) suggested a role for genetic variation in the D3 gene. Relevant to this study, Jönsson et al. found the Ser allele of the D3 serine-to-glycine substitution at amino acid position 9 (Ser9Gly) polymorphism to be associated with worse CLZ response compared with the Gly allele. In this study, we attempt to validate these findings by performing a meta-analysis in a much larger sample (n=758). Eight other variants were also tested in our own sample to explore the possible effect of other regions of the gene. We report a negative but consistent trend across individual studies in our meta-analysis for the DRD3 Ser allele and poor CLZ response. A possible minor role for this single-nucleotide polymorphism cannot be disregarded, as our sample size may have been insufficient. Other DRD3 variants and haplotypes of possible interest were also identified for replication in future studies.

Association of HPA axis genes with suicidal behaviour in schizophrenia.

Family, adoption and twin studies show that genetics influences suicidal behaviour, but do not indicate specific susceptibility variants. Stress response is thought to be mediated by the corticotrophin-releasing hormone (CRH), which is known to be a regulator of the hypothalamic-pituitary-adrenal pathway (HPA). Alterations in HPA system have been related to impulsivity, aggression and suicidal behaviour, common feature in schizophrenia. CRH is the hypothalamic factor that stimulates the pituitary gland. To search for markers conferring genetic susceptibility to suicide, we typed six HPA axis genes (CRH, CRHR1, CRHR2, CRHBP, MC2R, NC3R1) in a cohort of 231 subjects with schizophrenia in which 81 attempted suicide. The genotype analyses yielded significant association between CRH binding protein (CRHBP) and suicide attempt (P = 0.035). The genotype analysis for quantitative measures of suicidal behaviour showed no association. The interaction analysis showed a significant interaction between CRH receptor type 1 (CRHR1) and CRH binding protein (CRHBP) in influencing suicide attempt and the severity of suicidal behaviour. Current results show that genetic variation in HPA axis genes could be associated with suicidal behaviour in schizophrenia. This is to our knowledge the first study on suicidal behaviour investigating the interaction among the HPA axis genes.

Association study of tardive dyskinesia and five DRD4 polymorphisms in schizophrenia patients.

Tardive dyskinesia (TD) is a side effect of chronic antipsychotic medication exposure. Abnormalities in dopaminergic activity in the nigro-striatal system have been most often suggested to be involved because the agents that cause TD share in common potent antagonism of dopamine D(2) receptors (DRD2). Thus, a number of studies have focused on the association of dopamine system gene polymorphisms and TD, with the most consistent findings being an association between TD and the Ser9Gly polymorphism of the DRD3 gene and the TaqIA site 3' of the DRD2 gene. The DRD4 gene codes for the third member of the D(2)-like dopamine receptor family, and the variable number tandem-repeat polymorphism in exon 3 of DRD4 has been associated with TD. However, other polymorphisms have not been thoroughly examined. In this study, we investigated five polymorphisms spanning the DRD4 gene and their association with TD in our European Caucasian sample (N=171). Although the exon 3 variable number tandem repeat was not associated with TD, haplotypes consisting of four tag polymorphisms were associated with TD in males. This study suggests that DRD4 may be involved in TD in the Caucasian population, although further replication studies are needed.

Genetics and sleep disorders.

This review describes the recent growth of our knowledge in the genetics of these sleep disorders and reports some of our preliminary molecular studies in restless legs syndrome.

Linkage study of two polymorphisms at the dopamine D3 receptor gene and attention-deficit hyperactivity disorder.

Data from animal studies suggest that the dopamine D3 receptor gene may have a role in locomotion and behavioral regulation. Therefore, this gene has been suggested as a candidate for attention-deficit hyperactivity disorder (ADHD). The dopamine D3 receptor gene (DRD3) has two common polymorphisms, one in exon I that changes a Serine to Glycine (Ser9Gly) and alters the recognition site for the restriction enzyme MscI [Lannfelt et al., 1992]. The other common polymorphism is located in intron 5 and results in the change of a restriction site for MspI [Griffon et al., 1996]. We investigated the possibility of linkage of the dopamine D3 receptor gene in 100 small, nuclear families consisting of a proband with ADHD, their parents, and affected siblings. We examined the transmission of the alleles of each of these polymorphisms and the haplotypes of both polymorphisms using the transmission disequilibrium test [Spielman et al., 1993]. We did not observe biased transmission of the alleles at either polymorphism or any haplotype. Our findings using this particular sample do not support the role of the dopamine D3 gene in ADHD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:114-117, 2000.

[The RFLP of LDR152/PstI in the Chinese and its application to linkage analysis in a myotonic dystrophy family].

Myotonic dystrophy (DM) is inherited as an autosomal dominant trait and is characterized by variable expressivity and late age-of-onset. In the present paper, the DNA from 61 normal individuals and a DM family with 15 members of 4 generations were collected and digested with PstI, then hybridized with the LDR152 (D19S19). The results showed that the alleles for the PstI polymorphism were 19 and 11kb in size (gene frequencies were 0.4344 and 0.5656 respectively, which are obviously different from the previous data reported). In this DM family, the carriers who had lived most of their life without knowing that they had been infected with the disease were detected by the LDR152 and the estimation of DM risk on at-risk-individuals was also calculated.

[Diagnostic value of magnetic resonance imaging for syringomyelia].

Ten cases of syringomyelia confirmed by magnetic resonance imaging (MRI) were presented. The cavities in the spinal cord were of low signal on T1 weighted image (T1WI) and high signal on T2 weighted image (T2WI). The segments of the spinal cord with involved lesion resembled "bamboo joints" or were of "beaded" shape on sagittal section image and of "necklace" shape on cross section image. Size of the lesions in the spinal cord shown by MRI was larger than that judged by clinical symptoms. MRI can clearly show the position, size and shape of the cavities and other abnormal conditions. Results of this study show that MRI is the most useful diagnostic tool for syringomyelia. It should be emphasized that there was no dissociated impairment of pain and temperature and touch sensation in 40% of the patients and chronic spontaneous segmental pain was one of the important clinical characteristics of syringomyelia.