Generalized Anxiety Disorder (GAD)
overview
Anxiety is a general term that describes a range of subjective mental states which generally arise in response to both internal and external stressors. Worries, doubts, and sometimes even anxiety, are a part of a healthy life. It is natural and essential to our well-being to occasionally feel nervous about upcoming uncertainty or danger. However, when these worries start to feel uncontrollable, persistent and are causing significant distress or impairment to your everyday life, it may be time to reach out for help.
GAD is characterized by persistent, uncontrollable, excessive, and often irrational worry about everything, but also nothing in particular. This is slightly different from other anxiety disorders, as it is a diffuse sense of anxiousness that covers most aspects of a person’s life. While someone with a spider phobia may be consistently worried about a future interaction with a spider, or a person with social anxiety disorder might be afraid to engage in social situations, a person with GAD may experience a general sense of anxiety when thinking about both those things, as well as multiple of other parts of their life. People with GAD are preoccupied with a range of concerns, which could include issues such as health, death, disasters, money, family, friends, or work. The idea of a terrible event happening can cause endless worrying while experiencing a minor adverse event can be viewed as a catastrophe. The excessive worrying and catastrophizing are accompanied by other nonspecific psychological and physical symptoms.
According to the DSM-5, the general sense of persistent anxiety is present for more than 6 months, causes significant impairment or distress, and associated with three or more of the following symptoms: restlessness, being easily fatigued, difficulty concentrating, irritability, muscle tension, and/or sleep disturbance. These symptoms must not be better explained by another disorder or the effects of a substance[1].
GAD can present itself in very different ways from person to person. Some other symptoms may include:
Persistent worrying that is out of proportion to the impact of the events
Perceiving situations and events as threatening
Feeling anxious for no apparent reason
Difficulty handling uncertainty
Unable to relax
Unable to concentrate
Fatigue
Inability to sleep
Trembling
Sweating
Muscle tension
Irritability
Being easily startled
Nausea
Diarrhea
Irritable bowel syndrome
Imagine a day where you’ve spent almost the whole day feeling anxious. If you have GAD, then this is a pretty typical day for you, you’re anxious more days than not for at least the past six months. If you don’t have GAD, this could still happen, but this is pretty unlike you and only happens once in a while. Maybe you drank too much coffee or are stressed about an upcoming deadline.
Now, let’s image that your partner usually comes home around 6pm. It is now 6:30 and they haven’t answered your text. What do you think? If you have GAD, you might normally find yourself worrying that they have been in a terrible car accident. Or maybe they are breaking up with you. You call them excessively while checking the traffic report. For people without GAD, it’s more normal to think that maybe they got caught in traffic or stayed a little later at work. They are probably just being a responsible driver and not looking at their phone.
One patient described her GAD as a feeling of always being on edge and afraid as if something awful might happen. She explained how she interpreted perfectly normal situations in her everyday life as catastrophic. Despite being logical in other areas of her life, she is unable to reason with herself as to why the catastrophization may not be accurate. For example, if her boyfriend left for work in a rush and did not text her throughout the day, she thought she was doing something wrong, he was angry, and he was most-definitely going to break up with her. However, while this happened every day, she was unable to prove the negative thoughts and worries wrong. She also explained that she works very hard to make sure the worst-case scenario is less-likely to happen. This meant that small inconveniences or inconsistencies would cause her to lash out at the people in her life. For example: implementing a rigorous daily 10-hour study schedule to maintain her university grades. If anything came up in the day where she was unable to follow that schedule, it was viewed as 'the worst thing ever,' and she would lash out at the people who 'ruined' her day.
GAD has also been explained in numerous different ways by the people who live with it daily:
It is like living with a boulder sitting on your chest, you are unable to catch a deep breath.
You are never able to turn off your brain from thinking.
You are too busy over-analyzing every small detail that you can never enjoy the situation.
There is a siren going off in your head, you feel as if a disaster is about to happen, but it never does.
The feeling when you are driving and the wheels of the car slip on a patch of ice. Panic ensues, and there is nothing you can really do to prevent crashing. This feeling, but all the time.
Every minor inconvenience is a significant and overwhelming problem. Even if you find a solution or it doesn't go so terribly, you can find flaws or focus on another issue.
It feels like you are cramming for an exam the night before. But it never ends, and there is always a new exam.
Prevalence
Data from the World Health Organization’s (WHO) Mental Health Survey collected general population surveys from 150 000 adults across 26 countries[3]. Results indicate that GAD has a global lifetime prevalence of 3.7%, a 12-month prevalence of 1.8%, and a 30-day prevalence of 0.8%. (Time period prevalence rates simply indicate the number of people we could expect to report having the disorder in a given time period.) Lifetime prevalence was highest among high-income countries and lowest among low-income countries. This is despite having a negative association between GAD and socioeconomic status within countries. GAD has an earlier average age of onset and is associated with more severe impairment across common life domains for people in higher income countries. Treatment is sought by approximately half of affected individuals (49.2%) especially those with severe role impairment (59.4%), comorbid disorders (55.8%), and those living in high-income countries (59%)[3].
Prevalence rates within the United States vary widely, even when looking at reputable sources. On the low-end, the Anxiety and Depression Association of America reports that GAD effects 6.8 million adults (3.1% of the population)[4], while the National Comorbidity Survey Replication (NCS-R) reports that GAD affects almost double that amount (5.7%)[5]. Regardless of the source, common themes related to prevalence emerge:
Under half of people with clinically significant GAD will seek treatment[6]
GAD is twice as likely to occur in women than in men[5,6].
GAD has the oldest average age of onset of all the anxiety disorders, typically beginning in a person’s 30s[6].
GAD is the most common anxiety disorder diagnosed in older adults[5,6]
Severity
In the previously mentioned NCS-R study, 77% of GAD cases were classified as being moderate or severe, with impairment in occupation or role function being a requirement for both of these classifications5. All classifications of GAD are associated with significant decreases in self-report measures of overall wellbeing and quality of life[7]. However, a meta-analytic report found that while people with anxiety disorders had a significantly lower quality of life than non-clinical controls, specific anxiety disorders did not differ in terms of quality life. Individuals, no matter the anxiety disorder, who had higher levels of impairment and symptom severity, experienced the lowest quality of life[7].
Brain Basis
Similar to other anxiety disorders, there are specific and distinct areas of the brain, which contribute to the onset and maintenance of GAD. The amygdala is an ancient evolutionary structure that is responsible for processing emotion and is activated when we feel scared or aggressive[8]. Most notably, it is responsible for our distinctive fight or flight response to danger. The amygdala reacts faster than the more rational, executive areas of our brain and can even operate unconsciously[9]. In people with anxiety disorders, these reactions occur more frequently as the amygdala becomes sensitive and more greatly overreacts to situations than people without an anxiety disorder would[10]. For instance, people with anxiety are more-likely to view neutral faces as negative or aggressive[11]. Over time, the amygdala learns that such faces are dangerous (or at least perceived as hazardous) and reacts accordingly10. A recent Functional Magnetic Resonance (fMRI) study suggests that these types of maladaptive learning processes are possibly due to lower connectivity between the right amygdala and the right superior frontal gyrus, right paracingulate/anterior cingulate cortex, and right supramarginal gyrus. Furthermore, this pathway is thought to be underlying the uncontrollable worry and rumination experienced by people with GAD[12].
The amygdala is profoundly connected to other limbic structures in our brain such as the hypothalamus and hippocampus[13]. In a dangerous situation, the amygdala will signal the hypothalamus to release hormones quickly to kickstart our heart rate, blood pressure, and activate our muscles. These are the kind of reactions we would need if we were gearing up to fight or flee a dangerous situation; this is done through something called our hypothalamus-pituitary-adrenal (HPA) axis[14]. The initial release of corticotropin-releasing hormone by the hypothalamus stimulates the release of adrenocorticotropic hormone from the anterior pituitary, which causes the release of cortisol from the adrenal gland. Feedback inhibition mechanisms should modulate the activity of the HPA axis, however, these mechanisms are less efficient in people who have anxiety disorders[15]. Over the past decade, researchers have begun to understand how this occurs. One study identified that people with anxiety disorders have genetic markers which indicate they are oversensitive to cortisol[16], may have experienced prenatal stress which kickstarted HPA reactivity[17] or have experienced childhood trauma[18]. However, not all GAD is related to childhood trauma or prenatal stress. Individuals with GAD have decreased hypothalamus volumes when compared to both healthy control groups and those with other anxiety disorders, due to the damage caused by higher cumulative doses of cortisol in the long-term[19].
While your hypothalamus is gearing your body up for “fight or flight”, the hippocampus is working to store the event as an essential emotional memory[20]. Excessive avoidance is a learned behavior and a core feature of all anxiety disorders1. The hippocampus plays an essential role in storing memories and helping us learn which situations are dangerous, and which ones are not. Due to interferences from the hypothalamus, the brain begins to learn that many regular events are evoking a stress response, making us want to avoid those situations in the future. Recent evidence suggests that maladaptive circuit changes in the lateral habenula (located within the hippocampus) modulate dopamine and serotonin systems during an emotional event to affect mood regulation and learned aversion20. Similar to the hypothalamus, there is reduced hippocampal volume in people with GAD [21]. It was previously believed that cell death in the hippocampus occurred as the result of a traumatic response[22]. However, other evidence suggests that reduced hippocampal volume pre-exists trauma exposure and acts as a predisposing factor in anxiety disorders[23]. Evidence on this topic continues to vary as longitudinal brain imaging studies are expensive and restricted to small sample sizes. Whether it comes before or after trauma, when the hippocampus is directly damaged in rodent studies, we can increase avoidance learning and interfere with how we interpret threats[24].
Environmental Factors
Various biological and ecological factors have been associated with the onset of GAD. However, it is important to note that not all people with GAD have experienced the before-mentioned environmental risk factors, and not all people who experience these risk factors will go on to develop GAD.
Life events such as divorce, separation, becoming widowed, unemployment, low levels of education, and being a homemaker were significantly associated with GAD across multiple sources[25]. Long-term abuse of specific substances, such as alcohol[26], and disrupted childhood experiences are frequently associated with the onset of an anxiety disorder[27].
Many researchers have speculated on the mechanisms of the association between adverse life events and the onset of GAD or another anxiety disorder. The scar hypothesis suggests that exposure to adverse events and the induced negative emotional states that occur afterwards, eventually cause people to be vigilant and sensitive to negative events that may cause these negative emotional states[27]. This individual then begins to interpret many small events as harmful and is after that vulnerable to the development of an anxiety disorder[28]. The stress generation model speculates that people are active contributors to their environment[29]. The exposure to adverse events can cause the development of maladaptive characteristics, traits, attachment styles, or expectations. Because of this, these maladaptive stressors make it more difficult for the person to operate in the world, be socially adjusted, have successful interpersonal relationships, etc. The causal pathway theory suggests that because there are very few specific and replicable interrelationships between childhood trauma and psychopathology support the hypothesis of a general vulnerability to psychopathology as a result of trauma[29].
There is some evidence for specific childhood events and the manifestation of particular disorders and symptoms. For example, a 2005 study explored different types of trauma and the symptom presentation of people with GAD. Results indicated that people with GAD who had experienced sexual abuse before the age of 18 presented with fewer physical symptoms, such as muscle tension, trembling, and sweating[30]. However, most theorists agree that early neglect has broader cognitive and behavioral implications which influence future thoughts, emotions, interpretations, and actions.
Popular websites, such as the Mayo Clinic[31] and National Institute of Mental Health[32], suggest that certain personality traits, such as being shy, timid, or reserved are risk factors for GAD. The literature presents mixed evidence on this, with some studies suggesting correlation of GAD with anti-social personality traits[33], while others found that people with GAD had average levels of extraversion[34]. Other evidence points to people with GAD being high in neuroticism, a trait where a person is inflexible and ridged, as well as high in avoidance and dependence traits[35]. A 2010 meta-analysis found that people with anxiety and/or depression disorders exhibited similar personality traits regardless of the disorder[36]. There were moderate associations between internalizing disorders and neuroticism, low extraversion, and low conscientiousness. As of right now, it is difficult to determine if these personality traits emerged before the disorder or because of the disorder. Personality traits have shown some fluctuation, the results are moderate, and longitudinal studies have yet to be conducted, making it difficult to determine if these personality traits existed before the disorder, possibly contributed to the disorder, or were exacerbated as a result of the disorder[36].
Genetic Factors
Many studies have found genetic contributors to the personality traits associated with anxiety disorders. For example, behavioral inhibition (BI) is a trait that explains the tendency to withdrawal from unfamiliar situations. This is a relatively stable trait and has been shown through longitudinal studies to predict anxiety disorders when observed in children[37]. Variants in RGs2 have been related to anxiety disorders and are related to over-activity of the amygdala and increased negative interpretation of faces[38]. Neuroticism and harm-avoidance are also stable personality traits observed within anxiety disorders, but large-scale studies and meta-analysis have not yet found a genetic relationship between these traits and genetic variations[39].
Apart from personality, researchers are continually looking for genetic markers of different mental disorders. As far as we know, there are no specific genetic markers for GAD or any anxiety disorder for that matter. However, there are multiple genes which have been identified to predispose an individual to develop some type of anxiety disorder or trait levels of anxiety[40,41]. Shared genetic components have much stronger associations with anxiety disorders than when individual genetic components are analyzed[42]. A 2016 review[43] suggests that the development of an anxiety disorder is strongly related to variations and modifications of the following genes:
COMT: inactivates neurotransmitters such as dopamine and epinephrine.
BDNF: implemented in the survival and growth of neurons.
GAD1: contributes to the production of GABA, an inhibitory neurotransmitter responsible for stress reduction and relaxation.
PPARGC1A: related to higher-order and advanced cognition, one of the genes that differentiate humans from apes.
It should be noted that this research is often limited by small sample sizes and difficulty differentiating anxiety disorders or establishing clinical boundaries for anxiety. While someone may have a genetic predisposition, their environmental factors always have an essential role in if these genes will be expressed or not. In general, there are modest effect sizes when we try to relate anxiety personality traits and genetics, suggesting that environment still plays a huge role in these gene expressions and variations[43].
Today, the existing evidence points to interacting factors that lead to the development of psychopathology. A person may have a genetic vulnerability to develop psychopathology, and circumstantial life events interfere with components of the stress response to further increase the vulnerability for a particular disorder.
Cognitive Contributors
Multiple theoretical models for the cognitive structure of GAD have been proposed over the past two decades. While each of them serves a significant role in developing an understanding of GAD, each theory continues to undergo scrutiny and modification with time.
The Avoidance Model of Worry and GAD: Worry is a linguistic, thought-based activity that inhibits the vivid mental imagery that would be distressing to the individual. Mostly, worry is seen as a way of avoiding complete processing of a painful event or thought. The inhibition of mental, emotional experiences interrupts the emotional processing of fear that is theoretically needed to successfully move past a distressing idea or something that the person is afraid of[44,45]. Verbal worry is negatively reinforced as it removes the fearful and aversive images by giving the person something else to focus on[46].
Intolerance and Uncertainty Model: People with GAD find the idea of uncertainty more stressful and upsetting than what could typically be expected for the given situation. Because of this, worry serves as an adaptive feature to avoid and plan for uncertainty. However, this causes the individual to believe that they cannot handle a situation, they do not develop strong problem-solving skills, and as a result, they do not do well in these uncertain situations. This causes unpredictable situations not to go so well, and perpetuate the cycle of worry and avoidance[46].
The Meta-Cognitive Model: A common feature of GAD is that the person genuinely believes that worrying will help alleviate the situation. A situation must be continuously checked, analyzed, and worried about the outcome to be successful. Because this is done every time a situation is faced, when it goes well, the positive result is attributed to the amount of worrying and planning that occurred. If a situation does not go well, it is because there was not enough worrying or planning. In this model, there are two types of worry. Type one is worrying about external events, and type two is worrying about one's own thinking. Type two is the distinct feature of GAD, where worrying is seen by the individual as an adaptive way of dealing with situations but also evidence that the person is unable to handle the situation because if it were easy, then they wouldn't need to worry about it[47].
Emotion Dysregulation Model: People with GAD experience more intense emotions than what we would expect from the general population. They are hyperaware of their situations and are more likely to interpret situations as harmful or dangerous. They feel negative about their emotions and engage in maladaptive emotion regulation strategies, such as avoidance and excessive worrying[46].
Cognitive Model: In most people, events generate automatic thoughts, feelings, or physiological responses. If these automatic responses are negative, the person implements strategies to avoid these responses in the future. People with GAD use maladaptive strategies like avoidance or worrying about dealing with these situations in the future and decreasing their subjective feelings of distress. Because there is an increased negative focus on the situation, the person may interpret the situation as even more distressing than they had previously, thus generating more negative interpretations of their experience and the implementation of even more maladaptive strategies to decrease this distress. It is a continuous cycle between the situation, automatic thoughts, and emotional, behavioral, or physiological responses determine how the situation should be dealt with in the future[48].
Prevention
There is no guaranteed way to predict what will cause someone to develop GAD, and thus, prevention is sometimes tricky. No recent evidence has been able to create a significant or consistent method of GAD prevention. However, if some of the symptoms (as listed above) of GAD start to arise, interventions are always more effective and result in less impairment when started early[49].
Treatment
Cognitive behavior therapy is often regarded as the gold standard in the treatment of Generalized Anxiety Disorder[50], as well as other anxiety disorders. A 2008 meta-analysis of randomized placebo-controlled trials for adult anxiety disorders, showed that CBT shows strong efficacy for adult anxiety disorders[51]. A 2014 review of psychological treatments of generalized anxiety disorder, finding that CBT was more effective than placebo, wait-list control conditions, applied relaxation therapy, acceptance and commitment therapy, spiritual therapy, subconscious training, relaxation therapy, and pharmacotherapy at reducing maladaptive cognitions and behaviors related to anxiety[52]. More recent studies have explored the effects of CBT for multiple types of anxiety disorders across adolescents, adults, and older adults, finding that CBT is still the best treatment option[53]. While CBT is the most effective treatment for reducing immediate maladaptive cognitions and beliefs, strong evidence has emerged for the use of psychodynamic therapies for reducing the underlying causes of anxiety, such as trauma or harmful core beliefs[54].
Contributed by: Molly Rooyakkers
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