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Emmy Noether Junior Research Group - Circadian clocks as modulators of metabolic comorbidity in depression

  • Project Leader: Dr. Dominic Landgraf
  • Affiliation: Department of Psychiatry and Psychotherapy
  • Funding: since 2017

Our environment is characterized by the constant change between day and night. In the course of evolution, our body has adapted to these day rhythms with the result that all physiological processes take place differently during the day than at night. This process is controlled by so-called circadian clocks (body's own ~24 hour rhythms). A disturbance of the circadian system has far-reaching effects on our health. In particular, Dr. Landgraf's research group investigates the causal relationships between disturbed circadian clocks and the development of mental and metabolic diseases.

Depression is the second most common cause of disability worldwide. This can be attributed, among other things, to concomitant metabolic diseases such as obesity and metabolic syndrome. The risk of suffering from obesity or diabetes is significantly increased in depressive patients. In humans and animals, so-called circadian rhythms control both the mood and central metabolic processes such as energy consumption, glucose and fat metabolism. A disturbance of circadian rhythms is often associated with depression and metabolic diseases. Many depressed patients suffer from altered daily rhythms of sleep, wakefulness, appetite and endocrine functions. In addition, patients with disturbed circadian rhythms, such as shift workers, have a significantly higher risk of depression or obesity. For these reasons, Dr. Landgraf has developed the hypothesis that a circadian clock disorder can play a fundamental role in the simultaneous development of metabolic and mood disorders. Circadian rhythms in the brain and peripheral tissues are synchronized in time by the suprachiasmatic nucleus (SCN) of the hypothalamus. The neuropeptides orexin and melanin-concentrating hormone (ORX/MCH) form a system in the lateral hypothalamus which regulates mood, food intake and metabolism. This system is controlled by the circadian clock. Thus ORX/MCH neurons form a nodal point between metabolism, mood regulation and circadian rhythms. Together, the SCN and ORX/MCH neurons are an ideal starting point to investigate the role of disturbed circadian clocks in the development of metabolic and affective disorders. The characterization of causal relationships between disturbed circadian rhythms in SCN and the ORX/MCH system can provide new therapeutic targets for the simultaneous treatment of metabolic disorders and depression.

Source: GEPRIS