Generalized anxiety disorder

Generalized anxiety disorder
Other names	Generalised anxiety disorder
Specialty	Psychiatry, psychology
Symptoms	Excessive worry, restlessness, trouble sleeping, feeling tired, irritability, difficulty concentrating, muscle tension,[1] sweating, trembling[2]
Complications	Depression, heart disease, suicide[3]
Differential diagnosis	Panic disorder, post-traumatic stress disorder, social anxiety disorder, borderline personality disorder, antisocial personality disorder, obsessive-compulsive disorder, a phobia
Treatment	Behavioral therapy, metacognitive therapy, medications
Frequency	3–5% (lifetime prevalence)[4]

Generalized anxiety disorder (GAD) is a mental and behavioral disorder,^[5] specifically an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities.^[6] Worry often interferes with daily functioning, and individuals with GAD are often overly concerned about everyday matters such as health, finances, death, family, relationship concerns, or work difficulties.^[7][8] Symptoms may include excessive worry, restlessness, trouble sleeping, exhaustion, irritability, sweating, and trembling.^[2]

Symptoms must be consistent and ongoing, persisting at least six months, for a formal diagnosis of GAD.^[6][7] Individuals with GAD often have other disorders including other psychiatric disorders (e.g., major depressive disorder), substance use disorder, obesity, and may have a history of trauma or family with GAD.^[9] Clinicians use screening tools such as the GAD-7 and GAD-2 questionnaires to determine if individuals may have GAD and warrant formal evaluation for the disorder. Additionally, sometimes screening tools may enable clinicians to evaluate the severity of GAD symptoms.^[10][11]

GAD is believed to have a hereditary or genetic basis (e.g., first-degree relatives of an individual who has GAD are themselves more likely to have GAD),^[12] but the exact nature of this relationship is not fully appreciated.^[9][13][14] Genetic studies of individuals who have anxiety disorders (including GAD) suggest that the hereditary contribution to developing anxiety disorders is only approximately 30–40%, which suggests that environmental factors may be more important to determining whether an individual develops GAD.^[9][12] There is a strong overlapping relationship between GAD and major depressive disorder (MDD), with 72% of those with a lifelong diagnosis of GAD also being diagnosed with MDD at some point in their lives.^[15]

The pathophysiology of GAD implicates several regions of the brain that mediate the processing of stimuli associated with fear, anxiety, memory, and emotion (i.e., the amygdala, insula and the frontal cortex).^[16][9] The amygdala is part of the brain that is associated with experiencing emotions. In the amygdala, the basolateral amygdala complex recognizes sensory information and activates GABAergic neurons which can cause somatic symptoms of anxiety. GABAergic neurons control the nervous system by reducing feelings of stress, anxiety, and fear. When there is an inadequate number of GABAergic neurons, those negative feelings become apparent and can release somatic responses of stress.^[17] It has been suggested that individuals with GAD have greater amygdala and medial prefrontal cortex (mPFC) activity in response to stimuli than individuals who do not have GAD.^[9] However, the relationship between GAD and activity levels in other parts of the frontal cortex is the subject of ongoing research with some literature suggesting greater activation in specific regions for individuals who have GAD but where other research suggests decreased activation levels in individuals who have GAD as compared to individuals who do not have GAD.^[9][16]

Treatment includes psychotherapy (e.g., cognitive behavioral therapy [CBT] or metacognitive therapy) and pharmacological intervention (e.g., cannabis,^[18] citalopram, escitalopram, sertraline, duloxetine, and venlafaxine).^[19][9] CBT and selective serotonin reuptake inhibitors (SSRIs) are first-line psychological and pharmacological treatments; other options include selective norepinephrine reuptake inhibitors (SNRIs). In Europe, pregabalin is also used.^[20] The positive effects (if any) of complementary and alternative medications (CAMs), exercise, therapeutic massage and other interventions have been studied.^[21]

Estimates regarding prevalence of GAD or lifetime risk (i.e., lifetime morbid risk [LMR])^[22] for GAD vary depending upon which criteria are used for diagnosing GAD (e.g., DSM-5 versus ICD-10) although estimates do not vary widely between diagnostic criteria.^[9] In general, ICD-10 is more inclusive than DSM-5, so estimates regarding prevalence and lifetime risk tend to be greater using ICD-10.^[9] In regard to prevalence, in a given year, about two (2%) percent of adults in the United States^[22] and Europe have been suggested to have GAD.^[23][24] However, the risk of developing GAD at any point in life has been estimated at 9.0%.^[22] Although it is possible to experience a single episode of GAD during one's life, most people who experience GAD experience it repeatedly over the course of their lives as a chronic or ongoing condition.^[9] GAD is diagnosed twice as frequently in women as in men.^[25][9]