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


OBJECTIVE
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.
Department of Psychiatry, University of Regensburg, 93042 Regensburg, Germany. albert.putzhammer@medbo.de
Albert
A
Putzhammer
Anja
A
Schoeler
Thomas
T
Rohrmeier
Philipp
P
Sand
Goeran
G
Hajak
Peter
P
Eichhammer
D017109:Akathisia, Drug-Induced / Q000235:genetics*; D000483:Alleles; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects* / Q000627:therapeutic use; D002872:Chromosome Deletion; D002940:Circadian Rhythm / Q000187:drug effects; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D009043:Motor Activity / Q000187:drug effects*; D016254:Mutagenesis, Insertional / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use
D000929:Antidepressive Agents, Tricyclic; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human