Dysbindin-1, a Schizophrenia-Related Protein, Functionally Interacts with the DNA- Dependent Protein Kinase Complex in an Isoform-Dependent Manner

DTNBP1 has been recognized as a schizophrenia susceptible gene, and its protein product, dysbindin-1, is down-regulated in the brains of schizophrenic patients. However, little is known about the physiological role of dysbindin-1 in the central nervous system. We hypothesized that disruption of dysbindin-1 with unidentified proteins could contribute to pathogenesis and the symptoms of schizophrenia. GST pull-down from human neuroblastoma lysates showed an association of dysbindin-1 with the DNA-dependent protein kinase (DNA-PK) complex. The DNA-PK complex interacts only with splice isoforms A and B, but not with C. We found that isoforms A and B localized in nucleus, where the kinase complex exist, whereas the isoform C was found exclusively in cytosol. Furthermore, results of phosphorylation assay suggest that the DNA-PK complex phosphorylated dysbindin-1 isoforms A and B in cells. These observations suggest that DNA-PK regulates the dysbindin-1 isoforms A and B by phosphorylation in nucleus. Isoform C does not contain exons from 1 to 6. Since schizophrenia-related single nucleotide polymorphisms (SNPs) occur in these introns between exon 1 and exon 6, we suggest that these SNPs might affect splicing of DTNBP1, which leads to impairment of the functional interaction between dysbindin-1 and DNA-PK in schizophrenic patients

Psychometric properties of the Alabama Parenting Questionnaire.

We examined the psychometric properties of a German translation of the Child Global Report version of the Alabama Parenting Questionnaire (AP

Relationship between social anxiety symptoms and behavioral impairment in adolescents: The moderating role of perfectionism and learning motivation.

Numerous studies have found that adolescents with social anxiety disorder experience greater difficulty in school adjustment and show higher dropout rates. Perfectionism and learning motivation are known to be significant predictors of academic achievement; these factors may enhance or diminish behavioral impairment within the school setting. The purpose of the present study was to examine the relationship between social anxiety, learning motivation, perfectionism, and behavioral impairment within a community sample of adolescents. Five hundred ninety-four German middle school students aged 12-17 years (mean age = 14.60, SD=1.64; 59.4% female) were recruited through their schools to respond to a questionnaire package consisting of Spence Children’s Anxiety Scale, the Child and Adolescent Perfectionism Scale, impact supplement of the Strengths and Difficulties Questionnaire, and intrinsic values subscale of Motivational Strategies for Learning Questionnaire. Results of correlational and multiple regression analysis showed that social anxiety symptoms were a significant predictor of distress and behavioral impairment, especially in friendship and classroom learning domains. It was shown that intrinsic learning motivation promotes classroom learning in students with high levels of social anxiety, whereas perfectionism interferes with domains outside the classroom, such as friendships and leisure activities. Limitations and implications for future research were discussed