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.