The "missing heritability"-Problem in psychiatry: Is the interaction of genetics, epigenetics and transposable elements a potential solution?

Psychiatric disorders exhibit an enormous burden on the health care systems worldwide accounting for around one-third of years lost due to disability among adults. Their etiology is largely unknown and diagnostic classification is based on symptomatology and course of illness and not on objective biomarkers. Most psychiatric disorders are moderately to highly heritable.

Enhanced adenosine A receptor and Homer1a expression in hippocampus modulates the resilience to stress-induced depression-like behavior.

Resilience to stress is critical for the development of depression. Enhanced adenosine A receptor (AR) signaling mediates the antidepressant effects of acute sleep deprivation (SD). However, chronic SD causes long-lasting upregulation of brain AR and increases the risk of depression.

Enhanced mGlu5 Signaling in Excitatory Neurons Promotes Rapid Antidepressant Effects via AMPA Receptor Activation.

Conventional antidepressants have limited efficacy and many side effects, highlighting the need for fast-acting and specific medications. Induction of the synaptic protein Homer1a mediates the effects of different antidepressant treatments, including the rapid action of ketamine and sleep deprivation (SD). We show here that mimicking Homer1a upregulation via intravenous injection of cell-membrane-permeable TAT-Homer1a elicits rapid antidepressant effects in various tests.

The role of adenosine receptors in mood and anxiety disorders.

Adenosine receptor subtypes, first described 40 years ago, are known to regulate diverse biological functions and have a role in various conditions, such as cerebral and cardiac ischemia, immune and inflammatory disorders and cancer. In the brain, they limit potentially dangerous over excitation, but also regulate mechanisms essential in sleep and psychiatric disorders. In this review, we discuss the role of adenosine receptors in mood and anxiety disorders.

Recent insights into antidepressant therapy: Distinct pathways and potential common mechanisms in the treatment of depressive syndromes.

There is an urgent, unmet clinical need for faster and more efficient antidepressant drugs with higher response rates. In animal models of depression it was shown in the last few years that inhibition of three signaling molecules (BDNF, p11 and Homer1a) prevents efficacy of antidepressant therapy. These data not only show the crucial role of these factors for the treatment of depression, but may also point towards a better understanding of the molecular changes responsible for successful antidepressant therapy.