Catechol-O-methyltransferase gene expression in stress-induced and non-stress induced schizophrenia.

INTRODUCTION: As schizophrenia is a complex mental disorder and the outcome of gene-gene-environmental interactions, there are different possible pathophysiological mechanisms in different schizophrenia subtypes corresponding to various risk factors. This study was aimed at examining the impact of one of the most likely interactions, that is, 'dopamine and stress', in schizophrenia pathogenesis. METHODS: Here, we investigated the interaction between 'war-related psychological trauma' without brain trauma and catechol-O-methyltransferase gene. Using real-time PCR analysis we measured catechol-O-methyltransferase gene expression level in the blood cells of 66 male subjects in four groups, namely veteran schizophrenia patients as 'stress-exposed schizophrenia' (S-schizophrenia), their healthy brothers as 'their genetically closest relatives' (S-siblings), schizophrenia patients without any history of significant stress as 'non-stress-exposed schizophrenia' (NoS-schizophrenia), and the control group. The results were analyzed by Relative Expression Software Tool 2009 software. RESULTS: The catechol-O-methyltransferase gene expression was not significantly different between the S-schizophrenia and NoS-schizophrenia groups. However, compared to the control group, the catechol-O-methyltransferase expression was significantly decreased in three groups of S-schizophrenia, their healthy siblings, and NoS-schizophrenia patients. CONCLUSION: This data supports that reduced blood catechol-O-methyltransferase expression, which may be associated with higher dopamine level, is involved both in stress-induced and non-stress-induced schizophrenia.

Citicoline Combination Therapy for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: Residual symptoms of major depressive disorder are a source of long-term morbidity. New therapeutic strategies are required to alleviate this morbidity and enhance patient quality of life. Citicoline has been used for vascular accidents and has been effective in cognitive rehabilitation. It has been used successfully to reduce craving in patients with substance abuse disorder and for mood management of bipolar disorder. Here, we test citicoline effectiveness as an adjuvant therapy in major depression. METHOD: A double-blind randomized trial was designed on 50 patients with major depressive disorder who were under treatment with citalopram. Patients were allocated to 2 groups and received citicoline (100 mg twice a day) or placebo as an adjuvant treatment for 6 weeks. Depressive symptoms were assessed by the Hamilton Depression Rating Scale (HDRS) at baseline and at weeks 2, 4, and 6. RESULTS: Significantly greater improvement was observed in the HDRS scores of the citicoline group compared with the placebo group from baseline to weeks 2, 4, and 6 (Ps = 0.030, 0.032, and 0.021, respectively). Repeated-measures general linear model demonstrated a significant effect for time × treatment interaction on the HDRS score (F2.10,101.22 = 3.12, P = 0.04). Remission rate was significantly higher in the citicoline group compared with the placebo group (P = 0.045). CONCLUSIONS: Citicoline was an effective adjuvant to citalopram in the therapy of major depressive disorder.

Effect of creatine supplementation on cognitive performance and apoptosis in a rat model of amyloid-beta-induced Alzheimer's disease.

OBJECTIVES: Neuroprotective effect of creatine (Cr) against ß-amyloid (Aß) is reported in an in vitro study. This study investigated the effect of Cr supplementation on ß-amyloid toxicity in vivo. MATERIALS AND METHODS: Thirty two, male Wistar rats were divided into 4 groups. During ten weeks of study, control group went through no surgical or dietary intervention. At the 4th week of study Sham group had a hippocampal normal saline injection, while Aß and AßCr groups had an ß-amyloid injection in the hippocampus. AßCr group were fed by Cr diet during the study. After 10 weeks, Morris water maze (MWM) test was administered to measure learning ability and memory retrieval. Animals were sacrificed for TUNEL anti apoptotic assay and staining of amyloid plaques by Thioflavin-T. RESULTS: There was a significant retention deficit among AßCr and Aß group while the escape latency and the distance traveled to the platform were significantly higher in AßCr group compared to Aß group. AßCr group had same percent of TUNEL positive neurons compared to Aß group. CONCLUSION: Cr supplementation before and after ß-amyloid injection into the CA1 area of hippocampus deteriorates the learning and memory impairment of rats and it does not protect neuronal apoptosis caused by ß-amyloid.

Effects of creatine supplementation on learning, memory retrieval, and apoptosis in an experimental animal model of Alzheimer disease.

BACKGROUND: Alzheimer disease is the main cause of dementia in middle-aged and elderly people. Considering the improving effects of creatine supplementation on cognitive performance, this study aimed to determine the effects of creatine supplementation on learning, memory, and apoptosis in an experimental model of Alzheimer's disease. METHODS: Thirty-two male Wistar rats each weighing 250±50 grams were divided into four groups. The AdCr+ (Aß injection, creatine supplementation) and AdCr- groups (Aß injection, no creatine supplementation) were injected bilaterally with amyloid beta (Aß) (0.2µg in each CA1 area), and the sham group was injected with normal saline in the same area. After the injection, the AdCr+ group received a diet of 2% creatine for six weeks. The control group underwent no surgical or dietary intervention. After six weeks the Morris Water Maze (MWM) test was administered, to measure learning and memory retrieval. After sacrificing the animals, TUNEL staining for an anti-apoptosis assay was performed for the sham, AdCr+, and AdCr- groups. All groups were compared by independent ttest using SPSS software. RESULTS: RESULTS of MWM show that rats in sham and control groups performed better than those in the AdCr- and AdCr+ groups. Compared to sham group, AdCr+ and AdCr- groups had more TUNEL positive neurons count. RESULTS indicated no differences between the AdCr+ and AdCrgroups in learning, memory retrieval, and percentage of TUNEL positive neurons. CONCLUSION: After Aß injection, creatine supplementation had no effect on learning, memory retrieval, or neuron apoptosis in male Wistar rats.

Comparative assessment of neuro-cognitive impairments among patients with brain tumor and healthy adults.

AIM: Most brain tumor patients encounter cognitive impairments. Coping with such challenges is intolerable for them. OBJECTIVE: This study tries to determine the diagnostic role of cognitive tests, CPT, Stroop and TOL, in assessing neuro-cognitive impairments among patients with brain tumor and healthy participants. MATERIAL AND METHODS: A cross-sectional study was done on a sample of 15 to 65 years old of 84 brain tumor patients and 84 healthy Iranians. Participants of both groups were physically and mentally examined and approved by neurosurgeons, neurologists and psychiatrists. By completing the questionnaires, they all entered the study and were referred to the neuroscientist for performing the tests. RESULTS: According to CPT, Stroop and TOL tests, the performance of both groups was significantly regarding about age, sex and education variables (P < 0.05). CONCLUSION: Brain tumor patients in comparison to healthy participants met more cognitive changes on sustained, selective attention and planning. Therefore, diagnosis and assessment of these cognitive changes before and after the surgery can help rehabilitating patients' brains and improve their lives quality.

Alpha- and beta-synucleins mRNA expression in lymphocytes of schizophrenia patients.

Alpha-synuclein is largely, but not entirely, expressed in the central nervous system. A high concentration of alpha-synuclein in presynaptic terminals can mimic the normal function of endogenous alpha-synuclein in regulating synaptic vesicle mobilization at nerve terminals. Beta-synuclein protein is seen primarily in brain tissue and it is suggested that beta-synuclein acts as an inhibitor of alpha-synuclein aggregation, which occurs in neurodegenerative diseases. With respect to the role of synucleins in neurologic diseases such as Parkinson's disease, we decided to study the changes of alpha- and beta-synucleins in schizophrenia patients in relation to a control group. For this purpose, total RNA was extracted from the lymphocytes of patients and controls and then cDNA was synthesized and used for real-time polymerase chain reaction. Calculation of the relative expression of alpha- and beta-synucleins showed downregulation in patients in comparison to the control group. Independent two-tailed t-test showed that beta-synuclein mRNA expression in the control group was significantly higher than that in the patient group (p < 0.01), but downregulation of alpha-synuclein gene was not significant. Therefore, a significant downregulation of beta-synuclein mRNA expression appears to be a suitable biomarker for the diagnosis of schizophrenia.

Interaction between gamma-aminobutyric acid GABAB and cannabinoid CB1 receptors in spinal pain pathways in rat.

Antinociceptive effects of cannabinoids are mediated, in part, at the spinal level. Cannabinoid CB1 receptors are co-localized with dorsal horn interneurons containing gamma-aminobutyric acid (GABA). In this study, we investigated the interaction between intrathecally administered cannabinoid and GABA(B) receptor agonists and antagonists in the modulation of formalin-induced pain at the spinal level. Intrathecal pretreatment of rats with a cannabinoid receptor antagonist [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1-H-pyrazole-3-carboxamide] (SR141716A, 30 microg) decreased the analgesic effect of the intrathecal administration of the GABA(B) receptor agonist, baclofen (0.125 microg and 0.25 microg). Intrathecal administration of the GABA(B) receptor antagonist, saclofen (30 microg), 10 min before administration of the cannabinoid receptor agonist (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)-phenyl]-trans-4-(3-hydroxy-propyl)-cyclohexano (CP55940), did not affect the analgesia produced by the cannabinoid receptor agonist. Our results confirm that intrathecal administration of cannabinoid and GABA(B) receptor agonists have analgesic effects and that spinal antinociceptive effects of GABA(B) receptor agonists are likely through endocannabinoid modulation.