Are GRIK3 (T928G) gene variants in schizophrenia patients different from those in their first-degree relatives?

We examined whether the GRIK3 (T928G) polymorphic variants in patients with schizophrenia are different from those of their first-degree relatives and healthy controls. The study population was composed of 256 patients with schizophrenia, 305 first-degree relatives of schizophrenia patients and 242 healthy control subjects. The GRIK3 (T928G) polymorphism was determined by restriction fragment length polymorphism. The frequency of the TT genotype was predominant, whereas the GG genotype was rare among all groups. The frequencies of GRIK3 (T928G) genotype distributions in the patients with schizophrenia were similar to those of their relatives. The frequency of the GG genotype was significantly higher in patients than in healthy controls. Similarly, GG genotype distribution in relatives was elevated compared with that in controls, but this value did not reach statistical significance. On the other hand, the subgroups of schizophrenia patients did not show a significant association with the GRIK3 (T928G) gene. It appears that the patients share the same (GRIK3) T928G gene variants with their relatives. One interpretation of our findings is that the relatives are at risk for the development of schizophrenia in the future.

Scopolamine-induced convulsions in fasted mice after food intake: the effect of duration of food deprivation.

It has been shown that mice and rats treated with antimuscarinic drugs, scopolamine or atropine, after fasting for 48 h develop convulsions soon after refeeding. The present study was performed to evaluate whether mice also develop convulsions after being deprived of food for 1-24 h. The effect of day-night fasting on the development of convulsions was also determined in 12-h deprived animals. Mice were deprived of food for periods of 1, 2, 3, 6, 9, 12, 18, 24, and 48 h. Animals fasted for 12 h during the day or night were deprived of food at 08:00 or 20:00 h, respectively. At the time of testing, animals were treated with intraperitoneal (i.p.) saline or 3 mg/kg scopolamine. Twenty minutes later, they were given food and allowed to eat ad lib. All animals were observed for 30 min for the incidence and onset of convulsions. Fasted animals treated with scopolamine developed clonic convulsions after food intake. Incidence of convulsions was significant in 2-, 3-, 12-, 18-, 24-, and 48-h deprived animals. Convulsions observed after deprivation of food for 12 h during the day or at night were almost similar in both regimens. Our results indicate that food deprivation itself, rather than its duration, seems to be the principal factor in the development of these convulsions.

Do schizophrenia and bipolar disorders share a common disease susceptibility variant at the MMP3 gene?

There is growing evidence of partial etiological overlap between schizophrenia (SZ) and bipolar I disorder (BD-I) from linkage analysis, genetic epidemiology and molecular genetics studies. SZ and BD-I are neurodevelopmental disorders with genetic and environmental etiologies. Recent studies have demonstrated that matrix metalloproteinase 3 (MMP3) is a key event in associative memory formation, learning and synaptic plasticity, which are important in psychiatric disorders. In the light of these findings, we analyzed the genetic variations in the MMP3-1171 5A/6A in patients with SZ, patients with BD-I and healthy controls. To the best of our knowledge, this is the first study to report an association of variation in gene encoding MMP3 with SZ. Our study group consisted of 111 unrelated patients with SZ, 141 unrelated patients with BD-I, and 121 unrelated healthy controls. The frequencies of 6A6A genotype and 6A allele distributions of MMP3 in patients with SZ were significantly decreased when compared with controls. In contrast, in patients with SZ, the distributions of 5A5A genotype and 5A allele of MMP3 gene were significantly increased as compared with healthy controls. When the frequencies of genotypes or alleles in schizophrenic patients and bipolar patients were compared, 6A6A genotype and 6A allele in patients with BD-I were significantly higher than patients with SZ. In contrast, 5A5A genotype and 5A allele distributions of MMP3 gene were significantly frequent in patients with SZ. On the other hand, no significant differences were found in the allele or genotype distribution in patients with BD-I compared with controls. In conclusion, our data have supported the hypothesis that there is a possible relationship between -1171 5A/6A polymorphism of MMP3 gene and SZ. A larger sample group is needed to confirm the potential role of this gene in the pathophysiology of psychiatric disorders.

Effects of insulin-like growth factor-I and platelet-rich plasma on sciatic nerve crush injury in a rat model.

OBJECT: Local administration of insulin-like growth factor-I (IGF-I) has been shown to increase the rate of axon regeneration in crush-injured and freeze-injured rat sciatic nerves. Local administration of platelet-rich plasma (PRP) has been also shown to have a measurable effect on facial nerve regeneration after transection in a rat model. The objective of the study was to compare the effects of locally administered IGF-I and PRP on the parameters of the Sciatic Function Index (SFI), sensory function (SF), axon count, and myelin thickness/axon diameter ratio (G-ratio) in a rat model of crush-injured sciatic nerves. METHODS: The right sciatic nerve of Wistar albino rats (24 animals) was crushed using a Yasargil-Phynox aneurysm clip for 45 minutes. All animals were randomly divided into 3 groups: Group 1 (control group) was treated with saline, Group 2 was treated with IGF-I, and Group 3 was treated with PRP. Injections were performed using the tissue expander's injection port with a connecting tube directed at the crush-injured site. Functional recovery was assessed with improvement in the SFI. Recovery of sensory function was using the pinch test. Histopathological examination was performed 3 months after the injury. RESULTS: The SFI showed an improved functional recovery in the IGF-I-treated animals (Group 2) compared with the saline-treated animals (Group 1) 30 days after the injury. In IGF-I-treated rats, sensory function returned to the baseline level significantly faster than in saline-treated and PRP-treated rats as shown in values between SF-2 and SF-7. The G-ratios were found to be significantly higher in both experimental groups than in the control group. CONCLUSIONS: This study suggests that the application of IGF-I to the crush-injured site may expedite the functional recovery of paralyzed muscle by increasing the rate of axon regeneration.

Scopolamine-induced convulsions in fasted mice after food intake: evaluation of the sedative effect in the suppression of convulsions.

Food intake triggers convulsions in fasted mice and rats treated with antimuscarinic drugs, scopolamine or atropine. Most of the drugs produced anticonvulsant efficacy in these convulsions have sedative effects. Thus, the present study was performed to evaluate the contribution of sedation in the suppression of convulsions by using sedative drugs chlorpromazine, morphine, amitriptyline and diphenhydramine. Mice fasted for 24h and treated with 3mg/kg scopolamine developed convulsions soon after refeeding. Treatment of chlorpromazine and morphine during food deprivation did not provide a preventive effect in the development of convulsions observed after food intake in fasted animals. Pretreatment of amitriptyline, but not diphenhydramine, before scopolamine treatment suppressed the incidence of convulsions. Present results could not clearly demonstrate the role played by sedative effect in suppression of convulsions in fasted animals.

Angiotensin-converting enzyme polymorphism in schizophrenia, bipolar disorders, and their first-degree relatives.

BACKGROUND: Family, twin and adoption studies have provided major evidence for the role of genetics in numerous psychiatric disorders including schizophrenia (SZ) and bipolar disorders (BDs). As SZ and BD have some susceptibility genes in common and since unaffected first-degree relatives of these patients carry a high likelihood of these susceptibility genes, we aimed to elucidate the role of angiotensin-converting enzyme (ACE) genetic variants in patients with SZ, BD and their first-degree relatives. METHODS: The study sample comprised 239 patients with SZ, 184 patients with BD, 284 unaffected first-degree biological relatives of patients with SZ and 301 unaffected first-degree biological relatives of patients with BD and 210 healthy controls. The ACE genotypes were determined by polymerase chain reaction. RESULTS: ACE insertion/deletion polymorphism was associated with SZ and BD. DD genotype and D allele distributions in bipolar patients and their first-degree relatives were significantly higher than those of SZ patients, their relatives, and controls. In contrast, II genotype and I allele were reduced in both the patient groups and their relatives as compared with controls. CONCLUSION: In this study, the D allele might be responsible for clustering of psychotic symptoms and results in the psychotic manifestations of BD, whereas I allele seems to be protective against development of SZ and BD. SZ and BD characterized by similar or different gene variant in ACE could be a useful marker for these psychiatric disorders, if this polymorphism is replicated in the future studies.