History of diagnostic criteria[edit]
The American Psychiatric Association introduced GAD as a diagnosis in the DSM-III in 1980, when anxiety neurosis was split into GAD and panic disorder.[29] The definition in the DSM-III required uncontrollable and diffuse anxiety or worry that is excessive and unrealistic and persists for 1 month or longer. High rates in comorbidity of GAD and major depression led many commentators to suggest that GAD would be better conceptualized as an aspect of major depression instead of an independent disorder.[30] Many critics stated that the diagnostic features of this disorder were not well established until the DSM-III-R.[31] Since comorbidity of GAD and other disorders decreased with time, the DSM-III-R changed the time requirement for a GAD diagnosis to 6 months or longer.[32] The DSM-IV changed the definition of excessive worry and the number of associated psychophysiological symptoms required for a diagnosis.[30] Another aspect of the diagnosis the DSM-IV clarified was what constitutes a symptom as occurring "often".[33] The DSM-IV also required difficulty controlling the worry to be diagnosed with GAD. The DSM-5 emphasized that excessive worrying had to occur more days than not and on a number of different topics.[31] It has been stated that the constant changes in the diagnostic features of the disorder have made assessing epidemiological statistics such as prevalence and incidence difficult, as well as increasing the difficulty for researchers in identifying the biological and psychological underpinnings of the disorder. Consequently, making specialized medications for the disorder is more difficult as well. This has led to the continuation of GAD being medicated heavily with SSRIs.[31]
Risk factors[edit]
Genetics, family and environment[edit]
The relationship between genetics and anxiety disorders is an ongoing area of research.[14] It is broadly understood that there exists a hereditary basis for GAD, but the exact nature of this hereditary basis is not fully understood.[9] While investigators have identified several genetic loci that are regions of interest for further study, there is no singular gene or set of genes that have been identified as causing GAD.[14] Nevertheless, genetic factors may play a role in determining whether an individual is at greater risk for developing GAD,[34] structural changes in the brain related to GAD,[35] or whether an individual is more or less likely to respond to a particular treatment modality.[34] Genetic factors that may play a role in development of GAD are usually discussed in view of environmental factors (e.g., life experience or ongoing stress) that might also play a role in development of GAD.[12] The traditional methods of investigating the possible hereditary basis of GAD include using family studies and twin studies (there are no known adoption studies of individuals who have anxiety disorders, including GAD).[9][12] Meta-analysis of family and twin studies suggests that there is strong evidence of a hereditary basis for GAD in that GAD is more likely to occur in first-degree relatives of individuals who have GAD than in non-related individuals in the same population.[12] Twin studies also suggest that there may be a genetic linkage between GAD and major depressive disorder (MDD), which may explain the common occurrence of MDD in individuals who have GAD (e.g., comorbidity of MDD in individuals with GAD has been estimated at 60%[36]).[9][37] When GAD is considered among all anxiety disorders (e.g., panic disorder, social anxiety disorder), genetic studies suggest that hereditary contribution to the development of anxiety disorders amounts to only approximately 30–40%, which suggests that environmental factors are likely more important to determining whether an individual may develop GAD.[9][12] In regard to environmental influences in the development of GAD, it has been suggested that parenting behaviour may be an important influence since parents potentially model anxiety-related behaviours.[9] It has also been suggested that individuals with GAD have experienced a greater number of minor stress-related events in life and that the number of stress-related events may be important in development of GAD (irrespective of other individual characteristics).[9]
Studies of possible genetic contributions to the development of GAD have examined relationships between genes implicated in brain structures involved in identifying potential threats (e.g., in the amygdala) and also implicated in neurotransmitters and neurotransmitter receptors known to be involved in anxiety disorders.[35] More specifically, genes studied for their relationship to development of GAD or demonstrated to have had a relationship to treatment response include:
PACAP (A54G polymorphism): remission after 6-month treatment with Venlafaxine suggested to have a significant relationship with the A54G polymorphism (Cooper et al. (2013))[35]
HTR2A gene (rs7997012 SNP G allele): HTR2A allele suggested to be implicated in a significant decrease in anxiety symptoms associated with response to 6 months of Venlafaxine treatment (Lohoff et al. (2013))[35]
SLC6A4 promoter region (5-HTTLPR): Serotonin transporter gene suggested to be implicated in significant reduction in anxiety symptoms in response to 6 months of Venlafaxine treatment (Lohoff et al. (2013))[35]
Problematic digital media use[edit]
See also: Screen time, Binge-watching, Fear of missing out, Internet addiction disorder, Nomophobia, Problematic smartphone use, Problematic social media use, Television addiction, and Video game addiction
This section is an excerpt from Digital media use and mental health § Anxiety.[edit]
In April 2018, the International Journal of Environmental Research and Public Health published a systematic review of 24 studies researching associations between internet gaming disorder (IGD) and various psychopathologies that found a 92% correlation between IGD and anxiety and a 75% correlation between IGD and social anxiety.[38] In August 2018, Wiley Stress & Health published a meta-analysis of 39 studies comprising 21,736 subjects that found a small-to-medium association between smartphone use and anxiety.[39]
In December 2018, Frontiers in Psychiatry published a systematic review of 9 studies published after 2014 investigating associations between problematic social networking sites (SNS) use and comorbid psychiatric disorders that found a positive association between problematic SNS use and anxiety.[40] In March 2019, the International Journal of Adolescence and Youth published a systematic review of 13 studies comprising 21,231 adolescent subjects aged 13 to 18 years that found that social media screen time, both active and passive social media use, the amount of personal information uploaded, and social media addictive behaviors all correlated with anxiety.[41] In February 2020, Psychiatry Research published a systematic review and meta-analysis of 14 studies that found positive associations between problematic smartphone use and anxiety and positive associations between higher levels of problematic smartphone use and elevated risk of anxiety,[42] while Frontiers in Psychology published a systematic review of 10 studies of adolescent or young adult subjects in China that concluded that the research reviewed mostly established an association between social networks use disorder and anxiety among Chinese adolescents and young adults.[43]
In April 2020, BMC Public Health published a systematic review of 70 cross-sectional and longitudinal studies investigating moderating factors for associations for screen-based sedentary behaviors and anxiety symptoms among youth that found that while screen types was the most consistent factor, the body of evidence for anxiety symptoms was more limited than for depression symptoms.[44] In October 2020, the Journal of Behavioral Addictions published a systematic review and meta-analysis of 40 studies with 33,650 post-secondary student subjects that found a weak-to-moderate positive association between mobile phone addiction and anxiety.[45] In November 2020, Child and Adolescent Mental Health published a systematic review of research published between January 2005 and March 2019 on associations between SNS use and anxiety symptoms in subjects between ages of 5 to 18 years that found that increased SNS screen time or frequency of SNS use and higher levels of investment (i.e. personal information added to SNS accounts) were significantly associated with higher levels of anxiety symptoms.[46]
In January 2021, Frontiers in Psychiatry published a systematic review of 44 studies investigating social media use and development of psychiatric disorders in childhood and adolescence that concluded that the research reviewed established a direct association between levels of anxiety, social media addiction behaviors, and nomophobia, longitudinal associations between social media use and increased anxiety, that fear of missing out and nomophobia are associated with severity of Facebook usage, and suggested that fear of missing out may trigger social media addiction and that nomophobia appears to mediate social media addiction.[47] In March 2021, Computers in Human Behavior Reports published a systematic review of 52 studies published before May 2020 that found that social anxiety was associated with problematic social media use and that socially anxious persons used social media to seek social support possibly to compensate for a lack of offline social support.[48] In June 2021, Clinical Psychology Review published a systematic review of 35 longitudinal studies published before August 2020 that found that evidence for longitudinal associations between screen time and anxiety among young people was lacking.[49] In August 2021, a meta-analysis was presented at the 2021 International Conference on Intelligent Medicine and Health of articles published before January 2011 that found evidence for a negative impact of social media on anxiety.[50]
In January 2022, The European Journal of Psychology Applied to Legal Context published a meta-analysis of 13 cross-sectional studies comprising 7,348 subjects that found a statistically significant correlation between cybervictimization and anxiety with a moderate-to-large effect size.[51] In March 2022, JAMA Psychiatry published a systematic review and meta-analysis of 87 studies with 159,425 subjects 12 years of age or younger that found a small but statistically significant correlation between screen time and anxiety in children,[52] while Adolescent Psychiatry published a systematic review of research published from June 2010 through June 2020 studying associations between social media use and anxiety among adolescent subjects aged 13 to 18 years that established that 78.3% of studies reviewed reported positive associations between social media use and anxiety.[53] In April 2022, researchers in the Department of Communication at Stanford University performed a meta-analysis of 226 studies comprising 275,728 subjects that found a small but positive association between social media use and anxiety,[54] while JMIR Mental Health published a systematic review and meta-analysis of 18 studies comprising 9,269 adolescent and young adult subjects that found a moderate but statistically significant association between problematic social media use and anxiety.[55]
In May 2022, Computers in Human Behavior published a meta-analysis of 82 studies comprising 48,880 subjects that found a significant positive association between social anxiety and mobile phone addiction.[56] In August 2022, the International Journal of Environmental Research and Public Health published a systematic review and meta-analysis of 16 studies comprising 8,077 subjects that established a significant association between binge-watching and anxiety.[57] In November 2022, Cyberpsychology, Behavior, and Social Networking published a systematic review of 1,747 articles on problematic social media use that found a strong bidirectional relationship between social media use and anxiety.[58] In March 2023, the Journal of Public Health published a meta-analysis of 27 studies published after 2014 comprising 120,895 subjects that found a moderate and robust association between problematic smartphone use and anxiety.[59] In July 2023, Healthcare published a systematic review and meta-analysis of 16 studies that established correlation coefficients of 0.31 and 0.39 between nomophobia and anxiety and nomophobia and smartphone addiction respectively.[60]
In September 2023, Frontiers in Public Health published a systematic review and meta-analysis of 37 studies comprising 36,013 subjects aged 14 to 24 years that found a positive and statistically significant association between problematic internet use and social anxiety,[61] while BJPsych Open published a systematic review of 140 studies published from 2000 through 2020 found that social media use for more than 3 hours per day and passive browsing was associated with increased anxiety.[62] In January 2024, the Journal of Computer-Mediated Communication published a meta-analysis of 141 studies comprising 145,394 subjects that found that active social media use was associated with greater symptoms of anxiety and passive social media use was associated with greater symptoms of social anxiety.[63] In February 2024, Addictive Behaviors published a systematic review and meta-analysis of 53 studies comprising 59,928 subjects that found that problematic social media use and social anxiety are highly and positively correlated,[64] while The Egyptian Journal of Neurology, Psychiatry and Neurosurgery published a systematic review of 15 studies researching associations between problematic social media use and anxiety in subjects from the Middle East and North Africa (including 4 studies with subjects exclusively between the ages of 12 and 19 years) that established that most studies found a significant association.[65]
Pathophysiology[edit]
Amygdala (in red) brain structures linked to anxiety disorders
The pathophysiology of GAD is an active and ongoing area of research often involving the intersection of genetics and neurological structures.[9] Generalized anxiety disorder has been linked to changes in functional connectivity of the amygdala and its processing of fear and anxiety.[16] Sensory information enters the amygdala through the nuclei of the basolateral complex (consisting of lateral, basal and accessory basal nuclei).[16] The basolateral complex processes the sensory-related fear memories and communicates information regarding threat importance to memory and sensory processing elsewhere in the brain, such as the medial prefrontal cortex and sensory cortices.[16] Neurological structures traditionally appreciated for their roles in anxiety include the amygdala, insula and orbitofrontal cortex (OFC).[9] It is broadly postulated that changes in one or more of these neurological structures are believed to allow greater amygdala response to emotional stimuli in individuals who have GAD as compared to individuals who do not have GAD.[9]
Individuals with GAD have been suggested to have greater amygdala and medial prefrontal cortex (mPFC) activation in response to stimuli than individuals who do not have GAD.[9] However, the exact relationship between the amygdala and the frontal cortex (e.g., prefrontal cortex or the orbitofrontal cortex [OFC]) is not fully understood because there are studies that suggest increased or decreased activity in the frontal cortex in individuals who have GAD.[9] Consequently, because of the tenuous understanding of the frontal cortex as it relates to the amygdala in individuals who have GAD, it's an open question as to whether individuals who have GAD bear an amygdala that is more sensitive than an amygdala in an individual without GAD or whether frontal cortex hyperactivity is responsible for changes in amygdala responsiveness to various stimuli.[9] Recent studies have attempted to identify specific regions of the frontal cortex (e.g., dorsomedial prefrontal cortex [dmPFC]) that may be more or less reactive in individuals who have GAD[9] or specific networks that may be differentially implicated in individuals who have GAD.[16] Other lines of study investigate whether activation patterns vary in individuals who have GAD at different ages with respect to individuals who do not have GAD at the same age (e.g., amygdala activation in adolescents with GAD).[9]
Treatment[edit]
Traditional treatment modalities broadly fall into two categories, i.e., psychotherapeutic and pharmacological intervention.[19] In addition to these two conventional therapeutic approaches, areas of active investigation include complementary and alternative medications (CAMs), brain stimulation, exercise, therapeutic massage and other interventions that have been proposed for further study.[66] Treatment modalities can, and often are, utilized concurrently so that an individual may pursue psychological therapy (i.e., psychotherapy) and pharmacological therapy.[67] Both cognitive behavioral therapy (CBT) and medications (such as SSRIs) have been shown to be effective in reducing anxiety.[68] A combination of both CBT and medication is generally seen as the most desirable approach to treatment.[69] Use of medication to lower extreme anxiety levels can be important in enabling patients to engage effectively in CBT.[citation needed]
Psychotherapy[edit]
Psychotherapeutic interventions[13] include a plurality of therapy types that vary based upon their specific methodologies for enabling individuals to gain insight into the working of the conscious and subconscious mind and which sometimes focus on the relationship between cognition and behavior.[70][67] Cognitive behavioral therapy (CBT) is widely regarded as the first-line psychological therapy for treating GAD.[67] Additionally, many of these psychological interventions may be delivered in an individual or group therapy setting.[67] While individual and group settings are broadly both considered effective for treating GAD, individual therapy tends to promote longer-lasting engagement in therapy (i.e., lower attrition over time).[67]
Psychodynamic therapy[edit]
Psychodynamic therapy is a type of therapy premised upon Freudian psychology in which a psychologist enables an individual explore various elements in their subconscious mind to resolve conflicts that may exist between the conscious and subconscious elements of the mind.[71][67] In the context of GAD, the psychodynamic theory of anxiety suggests that the unconscious mind engages in worry as a defense mechanism to avoid feelings of anger or hostility because such feelings might cause social isolation or other negative attribution toward oneself.[70] Accordingly, the various psychodynamic therapies attempt to explore the nature of worry as it functions in GAD in order to enable individuals to alter the subconscious practice of using worry as a defense mechanism[70] and to thereby diminish GAD symptoms.[67] Variations of psychotherapy include a near-term version of therapy, "short-term anxiety-provoking psychotherapy (STAPP).[67]
Behavioral therapy[edit]
Behavioral therapy is therapeutic intervention premised upon the concept that anxiety is learned through classical conditioning (e.g., in view of one or more negative experiences) and maintained through operant conditioning (e.g., one finds that by avoiding a feared experience that one avoids anxiety). Thus, behavioral therapy enables an individual to re-learn conditioned responses (behaviors) and to thereby challenge behaviors that have become conditioned responses to fear and anxiety, and which have previously given rise to further maladaptive behaviors.[70]
Cognitive therapy[edit]
Cognitive therapy (CT) is premised upon the idea that anxiety is the result of maladaptive beliefs and methods of thinking.[70] Thus, CT involves assisting individuals to identify more rational ways of thinking and to replace maladaptive thinking patterns (i.e., cognitive distortions) with healthier thinking patterns (e.g., replacing the cognitive distortion of catastrophizing with a more productive pattern of thinking).[70] Individuals in CT learn how to identify objective evidence, test hypotheses, and ultimately identify maladaptive thinking patterns so that these patterns can be challenged and replaced.[70]
Acceptance and commitment therapy[edit]
Acceptance and commitment therapy (ACT) is a behavioral treatment based on acceptance-based models. ACT is designed with the purpose to target three therapeutic goals: (1) reduce the use of avoiding strategies intended to avoid feelings, thoughts, memories, and sensations; (2) decreasing a person's literal response to their thoughts (e.g., understanding that thinking "I'm hopeless" does not mean that the person's life is truly hopeless), and (3) increasing the person's ability to keep commitments to changing their behaviors. These goals are attained by switching the person's attempt to control events to working towards changing their behavior and focusing on valued directions and goals in their lives as well as committing to behaviors that help the individual accomplish those personal goals.[72] This psychological therapy teaches mindfulness (paying attention on purpose, in the present, and in a nonjudgmental manner) and acceptance (openness and willingness to sustain contact) skills for responding to uncontrollable events and therefore manifesting behaviors that enact personal values.[73]
Intolerance of uncertainty therapy[edit]
Intolerance of uncertainty (IU) refers to a consistent negative reaction to uncertain and ambiguous events regardless of their likelihood of occurrence. Intolerance of uncertainty therapy (IUT) is used as a stand-alone treatment for GAD patients. Thus, IUT focuses on helping patients in developing the ability to tolerate, cope with and accept uncertainty in their life in order to reduce anxiety. IUT is based on the psychological components of psychoeducation, awareness of worry, problem-solving training, re-evaluation of the usefulness of worry, imagining virtual exposure, recognition of uncertainty, and behavioral exposure. Studies have shown support for the efficacy of this therapy with GAD patients with continued improvements in follow-up periods.[74]
Motivational interviewing[edit]
A promising innovative approach to improving recovery rates for the treatment of GAD is to combine CBT with motivational interviewing (MI). Motivational interviewing is a strategy centered on the patient that aims to increase intrinsic motivation and decrease ambivalence about change due to the treatment. MI contains four key elements: (1) express empathy, (2) heighten dissonance between behaviors that are not desired and values that are not consistent with those behaviors, (3) move with resistance rather than direct confrontation, and (4) encourage self-efficacy. It is based on asking open-ended questions and listening carefully and reflectively to patients' answers, eliciting "change talk", and talking with patients about the pros and cons of change. Some studies have shown the combination of CBT with MI to be more effective than CBT alone.[74]
Cognitive behavioral therapy[edit]
Cognitive behavioral therapy (CBT) is an evidence-based type of psychotherapy that demonstrates efficacy in treating GAD and which integrates the cognitive and behavioral therapeutic approaches.[67] The objective of CBT is to enable individuals to identify irrational thoughts that cause anxiety and to challenge dysfunctional thinking patterns by engaging in awareness techniques such as hypothesis testing and journaling.[67] Because CBT involves the practice of worry and anxiety management, CBT includes a plurality of intervention techniques that enable individuals to explore worry, anxiety and automatic negative thinking patterns.[67] These interventions include anxiety management training, cognitive restructuring,[75] progressive relaxation,[75] situational exposure and self-controlled desensitization.[67] Several modes of delivery are effective in treating GAD, including internet-delivered CBT, or iCBT.[76]
Emotion-focused therapy[edit]
Emotion-focused therapy (EFT) is a short-term psychotherapy that is focused on humanistic needs of emotions when treating individuals with GAD. EFT can incorporate numerous practices such as experimental therapy, systemic therapy, and elements of CBT to allow individuals to work through difficult emotional states.[77] The primary goal of EFT is assisting individuals in living with their vulnerable emotions and overcoming avoidance so that adaptive experiences such as compassion and protective anger can be generated in response to the emotional needs that are embedded in core emotional vulnerability.
Sandplay therapy[edit]
Sandplay therapy (SPT) is an intervention based on nonverbal therapeutic practices. The main objective of SPT is to allow the individual the ability to work through their emotional problems from childhood traumas (CT) through play using sand and toy figures.[78] Although the therapy is mainly focused on nonverbal cues, verbal cues are also observed and documented during the rehabilitation process of the individual.[79] SPT allows a multisensory experience through a safe and protected space allowing the individual the opportunity to regulate their mind and emotions. This therapeutic practice is offered in both adults and children.
Exposure therapy[edit]
There is empirical evidence that exposure therapy can be an effective treatment for people with GAD, citing specifically in vivo exposure therapy (exposure through a real-life situation),[80] which has greater effectiveness than imaginal exposure in regards to generalized anxiety disorder. The aim of in vivo exposure treatment is to promote emotional regulation using systematic and controlled therapeutic exposure to traumatic stimuli.[81] Exposure is used to promote fear tolerance.[82]
Exposure therapy is also a preferred method for children who struggle with anxiety.[83]
Other forms of psychological therapy[edit]
Relaxation techniques (e.g., relaxing imagery, meditational relaxation)[67]
Metacognitive therapy (MCT): The objective of MCT is to alter thinking patterns regarding worry so that worry is no longer used as a coping strategy. It has promising results in treatment of GAD as well as other mental issues.[84]
Mindfulness based cognitive therapy (MBCT):[70] The goal of MBCT is to be used as an alternative or adjunctive to Cognitive Behavior Therapy (CBT).[85]
Supportive therapy: This is a Rogerian method of therapy in which subjects experience empathy and acceptance from their therapist to facilitate increasing awareness.[67] Variations of active supportive therapy include Gestalt therapy, Transactional analysis and Counseling.[67]
Internet-delivered interpretation training: The focus of this training is to reduce worry and anxiety while promoting positive outcomes and positive interpretations.[86]
Pharmacotherapy[edit]
Medications that have been studied were reviewed in a recent network meta-analysis that compared all studied medications with placebo and also with each other [87] and another compared the rates of remission between different medications.[88] Benzodiazepines (BZs) have been used to treat anxiety starting in the 1960s.[89] There is a risk of dependence and tolerance to benzodiazepines.[67][90] BZs have a number of effects that make them a good option for treating anxiety including anxiolytic, hypnotic (induce sleep), myorelaxant (relax muscles), anticonvulsant, and amnestic (impair short-term memory) properties.[90] While BZs work well to alleviate anxiety shortly after administration, they are also known for their ability to promote dependence and are frequently used recreationally or non-medically.[13][90] Antidepressants (e.g., SSRIs / SNRIs) have become a mainstay in treating GAD in adults.[67][68] First-line medications from any drug category often include those that have been approved by the Food and Drug Administration (FDA) or other similar regulatory body such as the EMA or TGA for treating GAD because these drugs have been shown to be safe and effective.[13]