We have investigated the gene for dystrobrevin-binding protein 1 (DTNBP1), or dysbindin, which has been strongly suggested as a positional candidate gene for schizophrenia, in three samples of subjects with schizophrenia and unaffected control subjects of German (418 cases, 285 controls), Polish (294 cases, 113 controls), and Swedish (142 cases, 272 controls) descent. We analyzed five single-nucleotide polymorphisms (P1635, P1325, P1320, P1757, and P1578) and identified significant evidence of association in the Swedish sample but not in those from Germany or Poland. The results in the Swedish sample became even more significant after a separate analysis of those cases with a positive family history of schizophrenia, in whom the five-marker haplotype A-C-A-T-T showed a P value of.00009 (3.1% in controls, 17.8% in cases; OR 6.75; P=.00153 after Bonferroni correction). Our results suggest that genetic variation in the dysbindin gene is particularly involved in the development of schizophrenia in cases with a familial loading of the disease. This would also explain the difficulty of replicating this association in consecutively ascertained case-control samples, which usually comprise only a small proportion of subjects with a family history of disease.
Whereas the present Swedish case-control analysis did not yield any evidence for association with the diagnosis, the present meta-analysis suggests that the DRD3 gene confer susceptibility to schizophrenia. Reasons for the discrepancies between prior studies are discussed.
Human family and twin studies have established considerable heritable components influencing individual differences in personality traits as assessed by self-report questionnaires. We have investigated a trinucleotide repeat polymorphism in the androgen receptor gene and personality traits. Healthy Swedish subjects (n = 335) were assessed with the Karolinska Scales of Personality inventory. There were tendencies (P > or = 0.006) in some scales indicating possible relationships between the androgen receptor allele length and personality traits related to dominance and aggression. However, after correction for multiple testing, no significant differences were found. We conclude that no significant association could be found between the androgen receptor polymorphism investigated and any personality trait, although the tendencies found are worthwhile subjects for replication attempts.
To investigate in more detail concordance between the recently developed Comprehensive Psychopathological Rating Scale (CPRS) and the recently developed Self-Rating Scale for Affective Syndromes (CPRS-S-A), a total of 101 psychiatric out-patients were assessed using these procedures and a diagnostic interview according to DSM-III-R. Depressive and anxiety syndromes were the most common diagnoses on Axis I. Approximately one-third of the patients had a diagnosis of clinical personality disorder on Axis II. The majority of the patients were assessed as predominantly manifesting either Cluster B or Cluster C traits. In general, the correlation between self- and expert-ratings was strong (0.83 for the Montgomery-Asberg Rating Scale (MADRS) depression subscale and 0.76 for the Brief Scale for Anxiety (BSA) anxiety subscale), but it tended to be weaker in the group of patients with clinical personality disorders. The correlation between the two ratings was also weaker in the group with predominantly Cluster B character traits than in the group with predominantly Cluster C traits or the group with no predominant traits, and weaker in the depressive group than in the anxiety group. However, personality disorder diagnoses were over-represented in the depressive group. The weaker correlations in the groups mentioned above may have been attributable to psychological factors and qualitative differences in cognitive and communicative style. The CPRS-S-A is considered to be a useful and reliable instrument for quantitative rating of symptoms in out-patients. Our results highlight the potential value of using appropriate self-assessment forms as complementary tools in clinical practice and research.
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