About this Research Topic

Background

Psychological processes include two equally important aspects of mental function, cognition and emotion. However, emotional disorders may account for more than 90% of all mental disorders. Major depression is an emotional disorder that affects more than 1 in 5 people worldwide, making it one of the most prevalent health-related causes of human suffering, as well as being a leading risk factor for the estimated 1 million deaths by suicide per year world-wide. Despite emotion regulation being critically important to healthy brain function, it is one of the least understood biological phenomenon of the brain, meaning that the mechanisms underpinning emotional disorders are not clearly elucidated. In addition, current treatments for these disorders are not always effective either, often acting very slowly and only showing improvements in a subset of patients. Stress is an evolutionary adaptive response that evolved to deal with situations that impose a threat to an organism and require a rapid “flight or fight” response, and is thus an essential process for increasing an organisms chances of survival. However, overwhelming stress is one of the main risk factors for the development of emotional disorders such as anxiety and depression. For example, the onset of major depression is often correlated with recent stressful life events. Additionally, early life stress also correlates with depression in adult life, highlighting how stress is capable of inducing long term changes in the brain that increase the risk for developing emotionality-related mental disorders.

The mechanisms underpinning how external stressors induce the onset of emotional disorders have been the subject of extensive research over the past 60 years, and remain an active field of experimental and theoretical research. As a result, there is now compelling evidence of a causal link between chronic stress, the sympathetic system and dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis and emotional disorders. Stress also causes the elevation of corticosteroids and other stress hormones, such as CRF (corticotropic-releasing factor). Beyond the hypothalamus, the locus coeruleus plays an important role in the response to chronic inescapable or unpredictable stress. When animals are faced with stress, a major function of the norepinephrine (NE) system is to facilitate “fight or flight” responses in an attempt to remove the stressor. If the stress is inescapable, the long term failure of dealing with the stressor results in changes to the NE system that result in “learned helplessness,” a state in which animals display emotionality-related behavioral changes resembling the depressive state. The exact mechanisms behind this behavioral change remain unclear, but chronic unpredictable stress is often used to produce animal models of depression that are extensively studied in preclinical research. Furthermore, the central NE system innervates many vital parts of the immune system including the lymph organs, spleen and the thymus. It has been reported that lymphocyte activity is dramatically reduced in depressed patients and that lymphocytes, mast cells and other immune system cells contain adrenoreceptors that respond to the peripheral release of NE. Finally, stress can induce long term changes in the endocrine systems, thus cytokines are also regarded as a candidate mechanism driving the onset of depression.

Moreover, some epigenetic changes or neural circuit changes induced by early life stress might be involved in the etiology of emotional disorders. The expression of receptors for the previously mentioned neuromodulators, neurotransmitters, and cytokines can be affected by epigenetic processes and evidence is accumulating that this epigenetic regulation is crucially involved in the development of emotional disorders. Therefore, as this is a rapidly progressing field, the goal of this Research Topic is to collect recent cutting edge research elucidating the mechanisms of how stress induces emotional disorders, such as depression and anxiety disorders (including phobias). We welcome the following types of studies: original quantitative or qualitative research articles, review articles, and mini-review articles. Specific themes we strongly suggest addressing may include (but are not limited to) the following:

1. Molecular and cellular neuronal changes induced by early life stress, or traumatic stress in adulthood
2. Molecular mechanisms that activate neuronal changes underlying stress induced changes, especially those
involving NE, dysregulation of the HPA axis, and cytokine production
3. Epigenetic or protein expression changes for astrocytes and microglia, such as Kir4.1
4. Functional studies of neurons or astrocytes in response to inescapable or unpredictable chronic stress
4. Most advanced studies about emotional theory that helps understanding the emotional disorders
5. ERP or fMRI studies with patients suffering from emotional disorders
6. Potential novel drugs that affect neuronal function in animal models of depression or anxiety

Keywords: emotion, mental health, depression, stress, neurotransmitters, epigenetics

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