ABSTRACT
Patients with schizophrenia (SCZ) exhibit higher suicide rates than the general population. However, the molecular mechanism responsible for the high rate of suicidal behavior in SCZ remains poorly understood. MTHFR Ala222Val (C677T; rs 1801133) polymorphism has repeatedly demonstrated to play a pathological role in numerous mental disorders, but none of these studies focused on the susceptibility of suicidal behavior in SCZ. In the present cross-sectional study, we recruited 957 chronic inpatients with SCZ and 576 healthy controls to assess the psychopathological symptoms of SCZ and compare the frequency of the MTHFR Ala222Val genotype in both suicide attempters and non-attempters. Our results demonstrated no significant differences in MTHFR Ala222Val genotype and allele distributions between the SCZ patients and controls (p > 0.05), but showed a statistical significance in the distribution of Ala/Val genotype between suicide attempters and non-attempters (p < 0.05). Further logistic regression analysis showed that MTHFR Ala222Val genotype, psychopathological symptoms, number of cigarettes smoked per day and drinking status were related to suicide attempts in SCZ (p < 0.05). Our study demonstrated that MTHFR Ala222Val polymorphism and some clinical characteristics might confer susceptibility to suicide in patients with SCZ.
Subject(s)
Genetic Predisposition to Disease/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Genetic , Schizophrenia/genetics , Schizophrenic Psychology , Suicide, Attempted , Adult , Alcohol Drinking/adverse effects , Chronic Disease , Cigarette Smoking/adverse effects , Cross-Sectional Studies , Female , Humans , Male , Middle AgedABSTRACT
Patients with schizophrenia (SCZ) exhibit higher suicide rates than the general population. However, the molecular mechanism remains poorly understood. Tumor necrosis factor (TNF)-alpha polymorphisms have been repeatedly indicated to play a pathogenetic role in various mental disorders, but none of these studies focused on the susceptibility to suicidal behavior in SCZ. We recruited 1087 chronic inpatients with SCZ and 576 controls to assess the psychopathological symptoms of SCZ using the Positive and Negative Syndrome Scale scales. We selected 2 polymorphisms (-308G>A and -1031C>T) in the TNF-alpha gene and analyzed their associations with SCZ and suicide. Our results showed that TNF-alpha -308G>A and -1031C>T were not related to SCZ and suicide. However, we found that suicide attempters with the C allele carriers exhibited suicidal behaviors significantly later than those with TT genotype in the SCZ patients. The haplotype containing the T allele of the -1031 was significantly associated with the age of suicide initiation. Further logistic regression analysis showed that -1031C>T interacted with psychopathological symptoms and drinking, age of smoking, and related to the initiation age of suicide attempts. Our study demonstrated that the TNF-alpha variants may affect the age at which suicide attempts started among SCZ suicide attempters.
Subject(s)
Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Schizophrenia/etiology , Schizophrenic Psychology , Suicide, Attempted/psychology , Tumor Necrosis Factor-alpha/genetics , Adult , Age of Onset , Alleles , Case-Control Studies , Female , Genetic Association Studies , Genotype , Haplotypes , Humans , Male , Middle Aged , Phenotype , Risk Factors , Schizophrenia/epidemiologyABSTRACT
OBJECTIVE: Cognitive impairment is a core symptom of schizophrenia (SCZ); however, its pathophysiological mechanisms remain unclear. The sensory gating (SG) deficits reflected by P50 inhibition are recurring in SCZ, and this inhibition may be related to the cognitive deficits seen in these individuals. This study aimed to investigate the relationship between P50 inhibition and cognitive dysfunction in SCZ, which has not been fully investigated up to this point. METHODS: A total of 270 individuals with chronic SCZ and 116 healthy controls were enrolled in the study. Psychopathology of SCZ was rated by the positive and negative syndrome scale (PANSS), while cognitive function and P50 inhibition of subjects were assessed by the MATRICS Consensus Cognitive Battery (MCCB) and the electroencephalography system. RESULTS: The MCCB total and its 10 index scores were significantly lower in patients than those in healthy controls (all pâ¯<â¯0.001). SCZ patients had a lower amplitude of S1, and higher P50 ratio than healthy controls (both pâ¯<â¯0.01). However, there were no significant correlations between the P50 ratio and any of the PANSS total and its subscale scores in SCZ patients (all pâ¯>â¯0.05). Moreover, no correlation was found between the P50 components and the MCCB scores (all pâ¯>â¯0.05). CONCLUSIONS: Our findings suggest that the P50 inhibition deficits occur in Chinese individuals with SCZ, which may not be associated with their clinical symptoms and cognitive impairment.
