**6. Conclusions**

The immune response could function to generate the networked synaptic connections in the brain during development and throughout life. Soon after an ischemic insult, increased levels of cytokines and chemokines enhance the expression of adhesion molecules on cerebral endothelial cells. This causes the adhesion and transendothelial migration of circulating neutrophils and monocytes [36]. These immune cells may accumulate in the capillaries, decreasing cerebral blood flow. They can further extravasate into the brain parenchyma, thus impacting

Besides this, the infiltrating leukocytes, as well as resident brain cells, (neurons and macrophage-like microglia) may release pro-inflammatory agents like cytokines, chemokines, and oxygen/nitrogen radicals that result in tissue damage [38]. Moreover, recent studies have highlighted the involvement of matrix metalloproteinases in the propagation and regulation of neuroinflammatory responses to ischemic brain injury. These enzymes cleave protein components of the extracellular matrix such as collagen, proteoglycan, and laminin, but also process a number of cell-surface and soluble proteins, including receptors and cytokines such as interleukin-1β, thus promoting CNS inflammation and the potential for anxiety dis-

The innate immune cells, macrophages, are classified into inflammatory or anti-inflammatory. Inflammatory macrophages differentiate in response to microbial and tumor antigens and interferon γ by producing pro-inflammatory cytokines at the site of nascent infection and

Anti-inflammatory macrophages differentiate via signaling by glucocorticoids or anti-inflammatory (type II) cytokines like IL-4, IL-13, and IL-10 where they promote TH2 immunity and mediate tissue remodeling, wound healing, and immune modulation.IL-4 and IL-13 drive anti-inflammatory macrophage polarization through the IL-4 receptor alpha chain (IL-4Rα), and anti-inflammatory polarization is also promoted by activation of several master regulators, including signal transducer and activator of transcription 6 (STAT6), Krüppel-like factor 4 (KLF4), and interferon regulatory factor 4 (IRF4), thus implicating all of these proteins in control

Macrophage polarity and activation are linked to neuropsychiatric conditions including GAD

Acute respiratory distress syndrome (ARDS) is associated with an imbalance in the level of

ological states and GAD. ARDS can be fatal if not treated appropriately. In adults, it is associated with stiffness of the respiratory system evident in the pulmonary oxygenation step. This results in both chronic and acute hypoxemia. ARDS pathology is characterized by injury to the capillary endothelia and subsequent damage to alveoli, severe arterial vasoconstriction, and pulmonary hypertension [42]. Subsequent to lung injury, ARDS patients are typically treated with granulocyte/macrophage colony stimulating factor (GM-CSF) as a component of

release and thus is linked to known potential pathophysi-

and MDD. A case in point is acute respiratory distress syndrome (ARDS) [41].

neuropsychiatric states [37].

26 Anxiety Disorders - From Childhood to Adulthood

orders [39].

cancerous lesions [40].

over the generation of anxiety [40].

respiratory oxygen intake and CO2

their pharmacotherapy [41].

The pre-programming of the neuroimmuno epigenome may be one of the pillars of longitudinal psychiatric disease development. A diaeventological paradigm is thus developing to explain the biological patterning of anxiety disorders. **Figure 2** below provides a developmental time course for the molecular and cellular GAD patterning described in the text.

head and neck cancer: A 6-month follow-up study. Neuropsychiatric Disease and

The Diaeventology of Anxiety Disorders http://dx.doi.org/10.5772/intechopen.82176 29

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**Figure 2.** The diaeventomic development of anxiety disorders.
