Anxiety and Anxiety Related Disorders

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Anxiety. Anxiety is an evolutionarily adaptive response to danger that helps facilitate avoidance behavior, but it becomes maladaptive when it interferes with daily life[1]. Maladaptive anxiety is characterized by excessive and enduring fear and avoidance of threats (out of proportion to the threat or to nonexistent threats) [2].

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Current scientific evidence indicates that anxiety arises from disruptions in the neural circuits used to process sensory stimuli and determine threat from those stimuli, leading to a state of high arousal and negative valence [3]. There are noticeable differences between fear and anxiety; fear responses are due to clear and perceived threats, with an immediate fight or flight response, and it subsides as the threat is removed. In comparison, anxiety responses are due to unknown threats, and they last longer than fear responses [4, 5].

Epidemiology. Anxiety related disorders are the most prevalent form of psychiatric illness in the world, and one of the leading causes of disability [6, 7]. One in four individuals is likely to have or be diagnosed with an anxiety disorder in their lifetime [8], and the 12 month prevalence of anxiety disorders in Europe is 14% [6]. Disability is exacerbated by a relatively early age of onset in comparison to other psychiatric disorders [1, 9], along with a high likelihood symptom recurrence [1, 9, 10]. Anxiety is highly comorbid with other mental disorders which can complicate treatment and diagnosis [9, 11]. Anxiety disorders can disrupt cognitive development and social rules, and can reduce quality of life by causing problems including school failure, underachievement, unemployment or underemployment, and social problems [2, 12].

Diagnosis of Anxiety. The diagnostic criteria for individual anxiety disorders varies across disorder and diagnostic manual used, either the DSM-5 or ICD-10. Genetic markers, blood tests, and psychophysiological testing lack the sensitivity or specificity to be used for the diagnosis of these disorders, so a trained physician must rely on the clinical interview, screening questionnaire, and subjective judgement [2, 4]. Distinguishing anxiety from other medical conditions is a major challenge to the proper diagnosis of anxiety, as presence of other mental or physical conditions are commonly associated with anxiety[13, 14].

Treatment of anxiety. Behavioral therapies are the first line treatment, but pharmacological treatment can be used as an alternative or adjunctive therapy[2, 15, 16]. Some of the pharmacological targets in anxiety include serotonergic, adrenergic, glutamatergic, neuropeptide, and endocannabinoid systems [15, 16]. Antidepressants, such as SSRIs or SNRIs, are the first line treatment for anxiety because of their efficacy, but they are associated with some adverse effects, including common side effects similar to symptoms of anxiety, discontinuation syndrome, and risk of increased suicidal ideation in youth [17].

Brain Regions Associated with Anxiety. Many regions, including amygdala (BLA and CeA), ventral hippocampus (vHPC),

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