Sleep and depression

Sleep and depression are intimately connected: almost all depressed patients have sleep problems. On the other hand, insufficient sleep is an independent risk factor for developing depression. We have been particularly interested in the early phases of depression and the development/assessment of sleep problems in that phase.

We have combined studies using animal models to epidemiological studies and studies with patients. We have tried to identify molecules that are involved both in development of depression and sleep regulation, and developed and used animal models to clarify this question. Most of the studies have been performed in collaboration with Professor Tiina Paunio.

A commonly accepted hypothesis on causes of depression links depression with unsuccessful neural plasticity, either during the early period of life, or during stressful life events. One of the key molecules of activity-dependent neural plasticity is BDNF, which has also been identified as a sleep regulatory molecule. We have performed several studies measuring BDNF-related variables in both humans and animal models.

We have used two animal models of depression: one pharmacological (clomipramine treatment=CLI) and one behavioral (change of pups between mothers). We have measured behavior, sleep and levels of adenosine, nitric oxide and BDNF in young, adolescent and adult rats.

The results show that sleep, particularly REM sleep, is a sensitive indicator of early life events (either pharmacological or behavioral trauma). Both treatments during early life induced increase in REM sleep in adulthood. Also adenosine and BDNF levels were affected. We conclude that early life negative events can leave a permanent marking in the brain, which often takes a form of disturbed sleep. The trauma, or trauma-induced sleep disturbance, may act as a vulnerability factor in later life.

Savelyev, S.A., Rantamäki,T., Rytkönen, K-M., Castren, E., Porkka-Heiskanen, T., Sleep homeostasis and depression: studies with the rat clomipramine model of depression. Neuroscience 212:149-58, 2012

Santangeli O, Lehtikuja H, Palomäki E, Wigren H-K, Paunio T, Porkka-Heiskanen T, Sleep and behavior in cross fostering rats: developmental and sex aspects. Sleep 39(12): 2211-2221, 2017

Prompted by the finding of the animal models - that adenosine levels change in depression - we conducted an epidemiological survey on the adenosine metabolism-related gene variants in a human population with depression symptoms. We observed that the adenosine transporter gene, SLC29A3, variants correlated with depression.

Gass N, Ollila HM, Utge S, Partonen T, Kronholm E, Pirkola S, Suhonen J, Silander K, Porkka-Heiskanen T, Paunio T. Contribution of adenosine related genes to the risk of depression with disturbed sleep. Journal of Affective Disorders 126 (1-2): 134-139, 2010

Moreover, we have studied sleep in adolescent depression patients, in collaboration with Dr. Anna-Sofia Urrila. These studies also evidence that changes in sleep associate with depression: the dissipation of sleep pressure was disturbed in patients compared to  healthy controls.

Santangeli et. al. Sleep and slow-wave activity in depressed adolescent boys: a preliminary study. Sleep; in press 2017