engleski

Insomnia and serotonergic mechanisms in psychiatric disorders

Insomnia is an integral part of sleep disorders, frequently comorbid with different psychiatric disorders. Insomnia is a very common, characterized by difficulties in falling or staying asleep and non-restorative sleep. It is associated with daytime fatigue, reduced physical and social performances, and lower quality of life. It affects a large part of healthy population and patients with schizophrenia, depression, alcoholism, posttraumatic stress disorder (PTSD), Alzheimer's disease, Parkinson's disease. The neurobiological basis of insomnia includes the alterations in different neurotransmitter pathways, immune signaling molecules and hormones. Serotonin (5-hydroxytryptamine, 5-HT) controls sleep, wakefulness, arousal states, vigilance behaviors, synchronization of the biological clock and circadian rhythmicity. In addition, altered function of 5-HT is implicated in depression, alcoholism and PTSD, and these disturbances are frequently associated with insomnia. The main regulator of the 5-HT activity is a 5-HT transporter (5-HTT), identical in neurons and platelets, encoded by the same (SLC6A4) gene. A 5-HTT gene-linked polymorphic region (5-HTTLPR) in SLC6A4 is a functional polymorphism associated to vulnerability or resiliency to develop psychiatric disorders and addictions. Platelets might be used as a limited peripheral marker of the central 5-HT synaptosomes since they similarly store, release and metabolize 5-HT. Platelet markers (monoamine oxidase (MAO-B) activity and platelet 5-HT concentration) are altered in particular symptoms, traits, and behaviors in psychiatric disorders, while platelet 5-HT and 5-HTTLPR variants were reported to be changed in subjects with desynchronized circadian rhythm. Aim of this study was to evaluate these biomarkers in patients with alcoholism, depression and PTSD (diagnosed using Structured Clinical Interview based on DSM-IV criteria), subdivided into those with or without insomnia (evaluated using psychiatric interview, Hamilton Rating Scale for Depression and Anxiety, and Clinician Administered PTSD Scale). Biomarkers investigated were platelet 5-HT concentration, platelet MAO activity and 5-HTTLPR variants. Our results showed that platelet 5-HT concentration was significantly lower in male alcoholic patients with middle insomnia compared to male alcoholic patients without middle insomnia, and in male veterans with PTSD with insomnia or with flashbacks than in male veterans without insomnia or flashbacks. Platelet MAO activity was not affected by insomnia in alcoholism, PTSD and depression. The frequency of the 5HTTLPR genotypes (LL, LS or SS) or alleles (L or S) differed significantly in male veterans with PTSD subdivided into those with or without early insomnia. The data confirm that there is a bidirectional relationship between PTSD, depression, alcoholism and insomnia. Altered 5-HT biomarkers associated with insomnia stress the need to reveal the neurobiological mechanisms of insomnia and to develop targeted interventions for both insomnia, as well as PTSD, depression, and alcoholism.

insomnia; monoamine oxidase (MAO-B) activity; platelet 5-HT concentration; psychiatric disorders; 5HTTLPR

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