HTTLPR functional polymorphism in schizophrenia: executive functions vs. sustained attention dissociation.
BACKGROUND
Recently attention has been addressed to the role of 5-HT in cognition and several experimental studies revealed that manipulations of the central 5-HT system can produce quite specific changes in cognitive functioning. These results may suggest new treatment strategies to improve cognition in psychiatric conditions characterized by neuropsychological impairments, such as schizophrenia. It is possible to investigate the involvement of 5-HT in cognition by examining the impact of genetic variation in key regulators of serotoninergic neurotransmission. Among these, the serotonin transporter (5-HTT) presents a functional polymorphism in the transcriptional control region of the gene (5-HTTLPR) affecting transcriptional efficiency. In the present study, we aimed to analyze the effect of 5-HTTLPR polymorphism on specific cognitive functions, known to be affected by 5-HT manipulation and altered in schizophrenia.


METHODS
223 schizophrenia patients were tested with Wisconsin Card Sorting Test (WCST), for the evaluation of cognitive flexibility, Continuous Performance Test (CPT), for the evaluation of attention, and genotyped for the 5-HTTLPR.


RESULTS
We found a significant association between HTT polymorphism and executive functions and inversely with sustained attention. The presence of the high-activity long (L) allele in homozygosis was a predictor of better executive performances and poorer performances of attention.


CONCLUSIONS
Our findings suggest that factors affecting serotonin availability may play a specific role in cognitive processes, probably through complex modulation of the different performance components.
Bosia
Marta
M
Department of Clinical Neurosciences, San Raffaele Universitary Scientific Institute Hospital, Via Stamira d'Ancona 20, 20127 Milano, Italy. bosia.marta@hsr.it
Anselmetti
Simona
S
Pirovano
Adele
A
Ermoli
Elena
E
Marino
Elena
E
Bramanti
Placido
P
Smeraldi
Enrico
E
Cavallaro
Roberto
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D056344:Executive Function / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D055815:Young Adult
D014150:Antipsychotic Agents; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins