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From human to cell: New approaches and methods in studies of circadian rhythms in patients with affective disorders and schizophrenia

Publication at Faculty of Science, Central Library of Charles University |
2016

Abstract

Recently, the role of the central circadian clock has been widely discussed in connection with the pathology of various psychiatric disorders. It has been observed to be primarily associated with diseases that include changes in mood and sleep rhythms, which are linked to changes in the functional state of the circadian system.

These changes are typically observed in patients with affective disorders or schizophrenia. In most of these diseases, regular sleep onset is compromised or unstable; changes in sleep architecture occur and the ability to synchronize the rhythm of sleep and wakefulness with external conditions is reduced.

Since the discovery of the circadian molecular mechanism, a series of studies dealing with molecular markers have affirmed the association of these conditions with the functional state of the circadian clock. With advanced molecular techniques, we can obtain accurate information about the state of the endogenous circadian system that responds dynamically to changes in the external environment.

It is particularly sensitive to changes in lighting conditions but also responds to stress or food intake. It appears that these factors may also affect the long-term changes and operation of the biological clock.

Taking these facts into account, it can be deduced that these long-term changes can be caused by epigenetic modifications of DNA and histones in the protein-coding region that conditions the clockwork mechanism. Apart from the genetic studies, we are witnessing an increase in the importance of epigenetic modification studies of the molecular mechanism of the circadian system.

The development of psychiatric disorders is not necessarily determined by genetic factors only - it is often connected with aspects such as stress or nutrition. Neuroanatomical studies have demonstrated that circadian clock in the suprachiasmatic nucleus of the hypothalamus directly affects many areas of the brain, including the amygdala, the prefrontal cortex and the hypothalamus regions, regulating sleep.

The role of the circadian system in the aetiology and progress of psychiatric disorders is not yet fully understood. Behavioural output rhythms indicate that it does play a role, but lacks evidence on the level of molecular markers, genetic variability and epigenetic modifications.