Molecular Mechanisms and Pathophysiology of Anxiety and Depression

Dear Colleagues, 

Depression and anxiety are highly prevalent disorders and are considered a major public health concern worldwide. The social cost of the physical, mental, and broader personal difficulties associated with these disorders is substantial.

Since the 1960s, the serotonin hypothesis has ruled over as the main explanation for the manifestation of depression. According to the hypothesis, depression is the result of low levels of the serotonin neurotransmitter in the brain. Based on this assumption, researchers developed numerous anti-depressive and anti-anxiolytic drugs that raise the levels of the serotonin neurotransmitter. Unfortunately, despite the availability of a wide range of drugs for treating depression and anxiety, most patients fail to achieve complete and sustained remission of symptoms. The current treatments for depression and anxiety have some pronounced limitations. Notably, they are characterized by low success rates, a variety of side effects, and delayed onset. The delayed onset is particularly interesting: if the serotonin hypothesis is indeed correct, one would expect that once serotonin levels are upregulated, there would be a clinical benefit. However, although SSRIs rapidly increase serotonin levels soon upon treatment initiation, the clinical benefit can take 3–4 weeks to manifest. This calls for a shift from the well-studied ‘serotonin hypothesis’ to a thorough investigation into the mechanisms underlying depression and anxiety.

These mechanisms can arise from various directions—from exploring peripheral mechanisms, such as the connection between the immune system and depression, to studying different central neurocircuitry than monoaminergic or focusing on receptors rather than on neurotransmitters.

The aim of the current research topic is to progress the understanding of the underlying causes  of depression and anxiety as well as the biological mechanisms of the major drawbacks and side-effects of current antidepressant treatments.

This research topic calls for all types of articles (Original Research, Methods, Reviews, Protocols, etc.) that cover, but are not restricted to, the following points:

• Novel receptor and/or brain region that may be relevant for depression and anxiety
• The involvement of mitochondrial dysfunction on depression and anxiety
• The role of glial cells in the development of depression and anxiety
• Molecular differences between anxiety and depression
• Molecular mechanisms for side-effects, such as weight gain and loss of sexual interest
• Genetic variance in the susceptibility to side-effects
• Placebo effect in anti-depressant and anxiolytic treatments
• Diagnostical biomarkers for depression
• Long-term biochemical and structural changes in the brain in response to depression and anxiety
• Long-term effects of chronic stress and depression on individual behaviour
• Gender differences in the Pathophysiology of Anxiety and Depression.

Dr. Ravid Doron
Dr. Alon Shamir
Prof. Dr. Gal Yadid
Guest Editors

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