A/ Clocks are found in many different cerebral structures, including those involved in the neuropsychiatric disorders. These are called peripheral clocks (orange), and contrast with the master circadian clock (yellow) located in the suprachiasmatic nucleus (SCN) of the hypothalamus.
B/ As a master clock, the SCN generates and synchronizes many biological rhythms such as hormones, neuronal connections, body temperature, metabolites and paracrine signals. These circadian signals in turn entrain the molecular clockwork within peripheral clocks, so that their biological and physiological functions are optimal at the most appropriate times of day (plain, thick arrow). The SCN is, in contrast, resistant to most rhythmic signals it synchronizes (dashed, thin arrow).
The molecular clockwork in humans relies on transcriptional feedback loops in which the transcriptions factors BMAL1, CLK and NPAS2 rhythmically activate the expression of their transcriptional repressors Per and Cry genes, as well as many other “clock-controlled genes”. Clock-controlled genes are the output of the clocks and contribute to their rhythmic physiology.
External factors that desynchronize rhythmic signals within peripheral oscillators, as well as genetic mutation of clock genes, provoke improper clock function, which impacts on overall gene expression. Such a clock malfunction within brain oscillators accounts for some of the symptoms observed in patients suffering from neuropsychiatric disorders.