engleski

Serotonergic markers of insomnia in PTSD

Introduction: Post-Traumatic Stress Disorder (PTSD) is a complex psychiatric disorder that develops after traumatic experience(s). Sleep disorders, including nightmares and insomnia, are one of the main features of PTSD. Although the neurobiological basis of PTSD is unclear, it involves complex interactions of genetic and environmental factors. Due to its role in controlling mood, arousal, and sleep, serotonin system is important for development of PTSD symptoms. The aim of the study was to determine the possible association of serotonin transporter (5-HTT) gene polymorphism and platelet serotonin concentration with sleep disorders in patients with PTSD. Methods: The study enrolled 393 Croatian male war veterans with PTSD from the University Psychiatric Hospital Vrapce, Zagreb, Croatia. The diagnoses of PTSD, comorbid psychiatric disorders and various sleep disorders have been made using Structured Clinical Interview (SCID) based on DSM-IV criteria, the Hamilton Rating Scale for Anxiety (HAMA), the Hamilton Depression Scale (HDRS) and the Clinician Administered PTSD Scale (CAPS). Veterans with PTSD were divided into those with or without insomnia and other sleep disorders (nightmares, interrupted sleep). After isolation of DNA from blood using salting out method, the genotyping of 5-HTTLPR polymorphism in the serotonin transporter gene was performed using polymerase chain reaction and specific primers. The DNA fragments were separated on a 2% agarose gel and visualized. The serotonin concentration in platelets isolated from the blood by a series of centrifugation was determined spectrophotometrically. Statistical analyses were performed with GraphPad Prism version 4.00. This work was supported by Croatian Science Foundation grant IP-2014-09-4289. Results: 5-HTTLPR polymorphism genotypes were similarly distributed in veterans with PTSD and control subjects. The distribution of 5-HTTLPR polymorphism genotypes was also similar in veterans with PTSD with and without comorbid depression, while platelet serotonin concentrations were lower in veterans with PTSD and comorbid depression in comparison to veterans without comorbid depression. Higher platelet serotonin concentration and higher incidence of LL 5-HTTLPR polymorphism genotypes compared to S alleles was found in veterans with PTSD with symptoms of early insomnia compared to veterans without early insomnia. In veterans with PTSD and comorbid depression, various sleep disorders were not associated with 5-HTTLPR polymorphism genotypes or with altered platelet serotonin concentration. Conclusion: Early insomnia was the sleep disturbance significantly associated with the 5-HTTLPR polymorphism in the serotonin transporter gene (over-representation of the LL genotype) and higher platelet 5-HT concentration in veterans with PTSD without comorbid depression. Other sleep disturbances were not associated with 5-HTTLPR polymorphism genotypes or platelet 5-HT concentration in veterans with PTSD with or without comorbid depression. Further studies with larger groups should clarify the role of serotonergic system in sleep disturbances in PTSD.

PTSD ; sleep disorders ; platelet serotonin ; serotonin transporter ; 5-HTTLPR polymorphism

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