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Mental Health

Anxiety disorders

Introduction

Overestimation of perceived threat or an erroneous danger appraisal of a situation which leads to excessive and inappropriate responses

Aetiology

Fear is an automatic neurophysiological state of alarm characterized by a fight or flight response to a cognitive appraisal of present or imminent danger (real or perceived). Anxiety is linked to fear and manifests as a future-oriented mood state that consists of a complex cognitive, affective, physiological, and behavioral response system associated with preparation for the anticipated events or circumstances perceived as threatening.

Symptom progression model of anxiety disorders. | Craske, M., Stein, M., Eley, T. et al. Anxiety disorders. Nat Rev Dis Primers 3, 17024 (2017). https://doi.org/10.1038/nrdp.2017.24

Pathophysiology

Limbic system;

Emotional-processing brain structures historically are referred to as the “limbic system”. The limbic cortex is part of the phylogenetically ancient cortex. It includes the insular cortex and cingulate cortex. The limbic cortex integrates the sensory, affective, and cognitive components of pain and processes information regarding the internal bodily state.
The limbic system. (A) Lateral view of cortex. (B) Sagittal view of slice through midline. | NAc, nucleus accumbens; OFC, orbital frontal cortex; PAG, periaqueductal gray, VTA, ventral tegmental area. | Martin, E. I., Ressler, K. J., Binder, E., & Nemeroff, C. B. (2009). The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. The Psychiatric clinics of North America, 32(3), 549–575. https://doi.org/10.1016/j.psc.2009.05.004

Hippocampus:

Limbic system structure with tonic inhibitory control over the hypothalamic stress-response system and plays a role in negative feedback for the hypothalamic–pituitary–adrenal (HPA) axis. Hippocampal volume and neurogenesis (growth of new cells) in this structure have been implicated in stress sensitivity and resiliency in relationship to mood and anxiety disorders

Amygdala:

An evolutionarily ancient limbic system structure, the amygdala, processes emotionally salient external stimuli and initiates the appropriate behavioral response. The amygdala is responsible for the expression of fear and aggression as well as species-specific defensive behavior, and it plays a role in the formation and retrieval of emotional and fear-related memories. The central nucleus of the amygdala (CeA) is heavily interconnected with cortical regions including the limbic cortex. It also receives input from the hippocampus, thalamus, and hypothalamus.
Fear circuitry: Fear response is a hardwired process involving the amygdala. | Davis M. The role of the amygdala in fear and anxiety. Ann Rev Neurosci 1992;15:356; with permission.)

The significant mediators of anxiety in the central nervous system are thought to be norepinephrine, serotonin, dopamine, and gamma-aminobutyric acid (GABA). The autonomic nervous system, especially the sympathetic nervous system, mediates most of the symptoms.

Clinical features

Diagnostic and statistical manual of mental disorders, 5th ed (DSM–5) criteria:

Anxiety disorders | Craske, M., Stein, M., Eley, T. et al. Anxiety disorders. Nat Rev Dis Primers 3, 17024 (2017). https://doi.org/10.1038/nrdp.2017.24
  • Separation anxiety disorder: Anxiety and fear atypical for his/her age and development level of separation from attachment figures.
    • Symptoms include nightmares and physical symptoms
  • Selective mutism: Consistent failure to speak in social situations where there is an expectation to speak even though the individual speaks in other circumstances, can speak, and comprehends the spoken language.
  • Specific phobia: Fearful/anxious about specific objects/situations which they avoid or endure with intense fear or anxiety.
  • Social anxiety disorder: Marked/intense fear/anxiety of social situations in which one could be the subject of scrutiny.
  • Panic disorder: Recurrent, unexpected panic attacks and experience persistent concern and worry about having another panic attack.
    • Panic attacks are abrupt surges of intense fear or extreme discomfort that reach a peak within minutes, accompanied by physical and cognitive symptoms such as palpitations, sweating, shortness of breath, fear of going crazy, or fear of dying.
  • Agoraphobia: Fearful and anxious in ≥ 2 of the following circumstances:
    • Using public transportation
    • Being in open spaces
    • Being in enclosed spaces like shops and theaters
    • Standing in line or being in a crowd
    • Being outside of the home alone
  • Generalized anxiety disorder: Persistent and excessive worry about various domains, including work and school performance, that the individual finds hard to control.
  • Substance/medication-induced anxiety disorder: Anxiety symptoms due to substance intoxication or withdrawal or to medical treatment.
  • Anxiety disorder due to other medical conditions:
    • Endocrine disease: Hypothyroidism, hypoglycemia, and hypercortisolism
    • Cardiovascular disorders: Congestive heart failure, arrhythmia, and pulmonary embolism
    • Respiratory illness: Asthma and pneumonia; metabolic disturbances: B12 or porphyria
    • Neurological illnesses: Neoplasms, encephalitis, and seizure disorder.

Management

Stepped-care treatment algorithm. | AD = antidepressant therapy; CBT = cognitive–behavioral therapy; MED = medication; rTMS = repetitive transcranial magnetic stimulation; SSRI = selective serotonin reuptake inhibitor. | Roy-Byrne PP, Craske MG, Stein MB, et al. A randomized effectiveness trial of cognitive–behavioral therapy and medication for primary care panic disorder. Arch Gen Psychiatry. 2005;62(3):290–298. | Roy-Byrne P, Craske MG, Sullivan G, et al. Delivery of evidence-based treatment for multiple anxiety disorders in primary care: A randomized controlled trial. JAMA. 2010;303(19):1921–1928.

Pharmacotherapy:

  • SSRIs (first-line treatment): Fluoxetine, sertraline, paroxetine, escitalopram, and citalopram) are an effective treatment for all anxiety disorders and considered
  • SNRIs (as effective as SSRIs and also first-line treatment, particularly for generalized anxiety disorder): Venlafaxine and duloxetine
  • Tricyclic antidepressants (TCAs): Amitriptyline, imipramine, and nortriptyline
  • Benzodiazepines (for short-term treatment and in panic attacks): Alprazolam, clonazepam, diazepam, and lorazepam
  • Buspirone (atypical anxiolytic): Mild slow acting tranquilizer similar to benzodiazepines and takes about 2 weeks to start working
  • Beta-blockers (control physical symptoms such as rapid heart rate, a trembling voice, sweating, dizziness, and shaky hands): Propranolol and atenolol

Psychotherapy:

  • Cognitive-behavioral therapy (CBT): Structured, goal-oriented, and didactic form of therapy that focuses on helping individuals identify and modify characteristic maladaptive thinking patterns and beliefs that trigger and maintain symptoms.
  • Exposure therapy: Utilized to move individuals towards facing the anxiety-provoking situations and stimuli which they typically avoid which results in a reduction in anxiety symptoms as they learn that their anxiety is causing them to experience false alarms and they do not need to fear the situation or stimuli and can cope effectively with such a situation.

Summary:

Anxiety disorders comprise several different disorders that are characterized by excessive fear and anxiety. | Anxiety disorders. Nat Rev Dis Primers 3, 17025 (2017). https://doi.org/10.1038/nrdp.2017.25

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