Evidence of a role for the 5-HTTLPR genotype in the modulation of motor response to antidepressant treatment.

RATIONALE: Serotonergic mechanisms are thought to play an important role in the regulation of mood, motor activity and sleep patterns. Serotonin reuptake is controlled by the serotonin transporter (5-HTT) and by a common functional insertion/deletion polymorphism in the corresponding gene's promoter region (5-HTTLPR). Homozygosity for the long variant may confer a favourable response to treatment with serotonin reuptake inhibitors (SSRIs), and to sleep deprivation. OBJECTIVES: The study assessed the role of the 5-HTTLPR genotype in determining motor side effects of antidepressant medication. METHODS: Motor activity patterns of 62 patients with major depression who were being treated with either SSRIs or tricyclic antidepressants (TCAs) were monitored over a 24-h period using a wrist-actograph. Additionally, motor activity was rated in a semi-structured interview using the motor agitation and retardation scale (MARS). RESULTS: Night-time motor activity was significantly increased in homozygous carriers of the long 5-HTTLPR allele (LL-genotype) who were being treated with SSRIs in comparison to short allele carriers (LS-genotype and SS-genotype), regardless of the type of antidepressant treatment (P<0.001). It was also significantly increased in comparison to patients with the LL-genotype who were being treated with TCAs (P<0.01). Differences in actographic motor activity were most prominent between 11 p.m. and 4 a.m. Clinical ratings of motor activity also showed a trend toward higher agitation scores in patients with the LL-genotype who received SSRI treatment. CONCLUSIONS: Homozygosity for the long variant of the 5-HTTLPR may cause a predisposition to increased night-time motor activity in conjunction with SSRI treatment.

[No Association of the - 141C Ins/Del Polymorphism of the Dopamine D2 Receptor with Schizophrenia] / Keine Assoziation des - 141C-Ins/Del-Polymorphismus im Gen des Dopaminrezeptor D2 mit Schizophrenie.

Recently, a putative functional polymorphism (- 141C Ins/Del) in the 5'-flanking region of the dopamine D (2) receptor was found. An association of the Ins allele with schizophrenia has been described in a Japanese sample. In the present study this association was examined in a German schizophrenia patient population. In a family based approach 190 German family trios were analyzed for the - 141C Ins/Del genotype. Using the transmission disequilibrium test (TDT) we found no evidence for an association of the Ins allele with schizophrenia (TDT = 0.152, P = 0.696). In parallel, we performed an independent case control study with 268 schizophrenic patients and 244 controls. Again, we did not detect an overrepresentation of the Ins allele in patients (P = 0.124). Thus, our data do not support the hypothesis that the - 141C Ins variant plays a major role in predisposition to schizophrenia. To confirm our conclusion further preferentially family based studies are needed.

[No association of 141C-ins/del polymorphism in the D2 dopamine receptor gene in schizophrenia]. / Keine Assoziation des-141C-Ins/Del-Polymorphismus im Gen des Dopaminrezeptor D2 mit Schizophrenie.

Recently, a putative functional polymorphism (-141C Ins/Del) in the 5'-flanking region of the dopamine D2 receptor was found. An association of the Ins allele with schizophrenia has been described in a Japanese sample. In the present study this association was examined in a German schizophrenia patient population. In a family based approach 190 German family trios were analyzed for the -141C Ins/Del genotype. Using the transmission disequilibrium test (TDT) we found no evidence for an association of the Ins allele with schizophrenia (TDT = 0.152, P = 0.696). In parallel, we performed an independent case control study with 268 schizophrenic patients and 244 controls. Again, we did not detect an overrepresentation of the Ins allele in patients (P = 0.124). Thus, our data do not support the hypothesis that the -141C Ins variant plays a major role in predisposition to schizophrenia. To confirm our conclusion further preferentially family based studies are needed.

The auxin-induced maize gene ZmSAUR2 encodes a short-lived nuclear protein expressed in elongating tissues.

By differential screening of a cDNA library from auxin-induced maize coleoptiles we have isolated and characterized a SAUR gene, designated ZmSAUR2, belonging to a not yet characterized subtype of the SAUR family. ZmSAUR2 encodes a 15.3-kDa protein and is specifically induced by auxin in elongating coleoptile tissue but not in primary leaves or in roots. The transcript level rapidly increased within minutes and preceded auxin-stimulated elongation of coleoptile segments. Cycloheximide also induced ZmSAUR2 transcription, as has been shown for other early auxin-induced genes, whereas abscisic acid, brassinolide, ethylene, gibberellic acid, kinetin, and methyl jasmonate did not provoke an increase in ZmSAUR2 mRNA abundance. In pulse-chase experiments using auxin-induced coleoptiles and an anti-ZmSAUR2 antibody we were able to precipitate a protein of the expected molecular mass and to determine a half-life of about 7 min, which is among the shortest known in eukaryotes. In gel shift assays binding of calmodulin to ZmSAUR2 was demonstrated, suggesting the possibility of post-transcriptional regulation. Upon transformation of onion epidermal cells with a ZmSAUR2::GUS construct the corresponding chimeric protein was detected in the nucleus. The results suggest that ZmSAUR2 encodes a short-lived nuclear protein that might be involved in auxin-mediated cell elongation.