engleski

Sleep disturbances and serotonergic markers in psychiatric disorders

Sleep disorders include insomnia, narcolepsy, restless legs syndrome, sleep apnea, and circadian rhythm sleep disorders. Insomnia is characterized by difficulty in falling or staying asleep. A large proportion of general population, but also patients with schizophrenia, depression, alcoholism, posttraumatic stress disorder (PTSD), Alzheimer's disease, Parkinson's disease, suffer from insomnia. Insomnia elicits daytime fatigue, negatively impacts physical and social performances, and affects the quality of life. Various neurotransmitter pathways (orexin/hypocretin, adenosine, serotonin, noradrenaline, acetylcholine, histamine, dopamine), immune signaling molecules and hormones regulate sleep and wakefulness. Serotonin (5-hydroxytryptamine, 5-HT) controls many physiological and pathological functions and behaviors, including sleep, wakefulness, arousal states, vigilance behaviors, synchronization of the biological clock and circadian rhythmicity. Serotonin has a role in the etiology of depression, alcoholism and PTSD, which are frequently associated with sleep disturbances and insomnia. The activity of 5-HT is regulated by a 5-HT transporter (5-HTT), which is identical in neurons and platelets, and encoded by the same (SLC6A4) gene. A functional polymorphism (5-HTT gene-linked polymorphic region, 5-HTTLPR) in SLC6A4 has been widely studied in relation to antidepressant treatment response, vulnerability and/or resiliency to develop psychiatric disorders or addictions. Central 5-HT synaptosomes and platelets similarly store, release and metabolize 5-HT, and therefore blood platelets might be used as a limited peripheral model for the central 5-HT synaptosomes. Since platelet monoamine oxidase (MAO) activity and platelet 5-HT concentration have been altered in particular traits, behaviors and symptoms in different psychiatric disorders, and platelet 5-HT and 5-HTTLPR variants were reported to be changed in subjects with desynchronized circadian rhythm, we evaluated these biomarkers in patients with alcoholism, depression and PTSD, subdivided into those with or without insomnia. Clinical diagnosis of alcoholism, depression and PTSD was made according to the DSM-IV criteria, using Structured Clinical Interview. Insomnia was evaluated using psychiatric interview, Hamilton Rating Scale for Depression and Anxiety, as well as Clinician Administered PTSD Scale. Control group consisted of drug free healthy subjects with no personal or family history of psychiatric disorders or alcoholism. Biomarkers investigated were platelet 5-HT concentration, platelet MAO activity and 5-HTTLPR variants. Our results suggest that biomarkers are very important research tool in the assessment of insomnia in patients with PTSD, depression and alcoholism. Although sleep disturbances are common in these disorders, our data support the use of biomarkers, which may help to improve sleep quality and to target the therapeutic strategies, in order to achieve better physical and interpersonal functioning of these patients.

sleep disturbances, insomnia, alcoholism, depression and PTSD, platelet 5-HT concentration, platelet MAO activity, 5-HTTLPR

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