Understanding Anxiety Disorders
Understanding the Fundamental Physiology of Fear
The emotion for which the neuronal networks have been best expressed is fear. Documentation of the amygdala as a major contributor to anxiety developed when Kluver and Bucy in 1937 made lesions in the amygdala of primates. These monkeys displayed fearlessness in approaching objects that previously had alarmed them. Moreover, they were prone to orally explore previously feared stimuli (Phelps, 2006). Approximately 40 years later, LeDoux helped establish the recording of areas and networks of the amygdala. The amygdala plays a critical role in both fear in response to natural fear inducers and in fear conditioning. In the latter (fear conditioning), a natural fear stimulus is presented with a tone. Later, the presentation of the tone alone (called a conditioned stimulus) will elicit the fear response (conditioned response).
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​Different areas of the amygdala are activated in response to natural stimuli versus a conditioned stimulus. The medial amygdala initiates in reaction to the unconditioned stimulus. The lateral amygdala is involved in learning the association of the conditioned stimulus with the unconditioned stimulus. In terms of the output from the amygdala, the amygdala projects to the hypothalamus so that the appropriate autonomic responses (activation of the sympathetic nervous system) and hormonal responses (activation of the hypothalamic-pituitary-adrenal axis) ensue. The medial amygdala, which processes innate fear, also projects outward. Ultimately, for innate fears, the medial amygdala drives the output to the nucleus accumbens and the dorsal periaqueductal gray (for fight or flight).
The lateral amygdala, the association area for learning the connection between conditioned and unconditioned stimuli, projects to the central amygdala, which communicates to the ventral periaqueductal gray for ‘freezing’. Therefore, conditional on the signalling in the amygdala, the fear response can be fight or flight or freezing (Chen, Shemyakin and Wiedenmayer, 2006; Fogaca et al., 2012; Walker, Toufexis, and Davis, 2003). In relation to higher-order configurations, the dorsal anterior cingulate cortex is activated in response to observing a fearful expression (Milad, Wright, et al., 2007) and there are connections from the amygdala to the anterior cingulate cortex (Paus, 2001).
Studies on humans that explored fear or anxiety have also used the hypothesis of fear conditioning. For example, if a shock is paired with a light, the light will quickly stimulate the activation of the amygdala and sweaty palms ensue. Coherent with animal data, imaging work in human subjects with damage to the amygdala report that they fail to learn conditioned fear responses. Though individuals with a damaged amygdala can converse that the light means the shock is coming, their hands do not perspire in response to the light (Phelps, 2006). The amygdala will respond to insignificant cues signalling endangerment. For instance, Whalen and associates (2014) determined that the stimulus of “eyes which were opened wide” was enough to evoke a response in the amygdala. Furthermore, when fear-inducing stimuli are presented at subthreshold for awareness levels, the amygdala can be activated (Shin and Liberzon, 2010). Fear conditioning can transpire through observation of another individual receiving shock combined with a conditioned stimulus. Even when the observer has never been shocked but has witnessed the shock in the presence of the conditioned stimulus, the observer will present amygdala activation and increased palm perspiration in response to the conditioned stimulus (Phelps, 2006).
Different Types of Anxiety Disorders
At any given time point nearly 12% of the human population meets the criteria for an anxiety disorder (Pre COVID-19). Over the course of our life, almost 30% of the population will experience an anxiety disorder (Kessler et al., 2005). For some anxiety disorders, the stimulus that produces the anxiety is evident. For example, the anxiety-evoking stimuli are apparent for PTSD and for various phobias. Likewise, with OCD, the fear-eliciting stimuli that cause the anxiety-reducing routine behaviours are unmistakable. It is important to understand that there is considerable overlap between anxiety and depression. According to Murphy et al., (2014), about 33 to 50% of those individuals with depression also meet the criteria for anxiety disorder. Likewise, between 40 to 50% of those with anxiety will meet depression criteria at some point.
Generalised Anxiety Disorder
Generalised Anxiety Disorder (GAD) is categorised by discomfort and trepidation. Feeling “on edge,” being constantly fatigued, having sleeping difficulties, excessive muscle tension, irritability, and trouble concentrating contribute to the identification of GAD. Individuals who are high on trait anxiety have been reported to display greater amygdala activation when exposed to fear-provoking images, even when the exposure to these images is too fleeting to permit cognitive processing (Etkin et al., 2004; Ewbank et al., 2009).
There is also academic support for the view that anxious people do selectively attend to and dwell on dangers. For example, Doty et al., (2013) noted that individuals who are selected for extreme scores on measures of anxiety are faster in identifying angry faces and fearful faces in a crowd (Doty et al., 2013). When working on another task, those selected for high trait anxiety are more distracted by fearful faces or words that can evoke emotion. The results of a meta-analysis by Bar-Haim et al., (2007) suggested that the attention of anxious individuals is drawn to threat stimuli (Bar-Haim et al., 2007).
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The dorsolateral prefrontal cortex, a region connected in emotional regulation, is postulated to exercise some regulation over the brain’s fear structure, the amygdala. Bookheimer and Mazziotta, (2000) have reported that the dorsolateral prefrontal cortex, can downregulate the brain’s fear response. Although subjects in this study displayed activation of the amygdala in response to fearful faces when asked to catalogue the emotion in the faces, the dorsolateral prefrontal cortex is active and there is less activity in the amygdala.
Consequently, the dorsolateral prefrontal cortex offers a mechanism for restricting the amygdala's capacity for producing anxiety. Those individuals with anxiety disorders may be less efficient in restraining the amygdala. Research with young adults with high anxiety levels indicates a low level of association between the dorsolateral prefrontal cortex and the amygdala, as demonstrated by a weaker negative association between these two areas compared to healthy control subjects (Hardee et al., 2013; Monk et al., 2008). It has been suggested that shy (inhibited) children often display high anxiety levels as adults. An imaging study by Hardee et al., (2013) of young adults who had previously been identified as inhibited children confirmed lower levels of connectivity between the dorsolateral prefrontal cortex and the amygdala. In addition to using the dorsolateral prefrontal cortex to downregulate the amygdala, the parasympathetic nervous system (as measured by greater heart rate variability) is also involved in downregulating anxiety. Those with greater heart rate variability (high vagal tone) are better at controlling fear. However, those with anxiety disorders show lower levels of heart rate variability (Thayer, Friedman and Borkovec, 1996). Therefore, both emotional regulation through the dorsolateral prefrontal cortex regulation and regulation through the parasympathetic nervous system is suggested to be deficient in those with anxiety disorders.
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Several researchers suggest that GAD, panic disorders and PTSD have the same predisposes genic risk factors, however, phobias appear to be genetically independent (Chantarujikapong et al., 2001; Craske and Waters, 2005). Considerable attention has been given to the short serotonin transporter as a risk factor for depression and anxiety. The adjective short denotes the promoter region of the serotonin transporter. Because the promoter region is smaller, less of the serotonin transporter is made. Therefore, in those individuals who are anxious, serotonin remains in the synapse for a lengthier period. The short serotonin transporter allele has been suggested to be a risk factor for anxiety. Though, studies have reported that symptoms developing in an individual with the short transporter risk allele are highly dependent on environmental factors. For example, Petersen et al., (2012) performed research with genotyped children on their serotonin transporter allele as well as measuring the stressfulness of the subjects’ environments. The authors found that when subjects were paired with a stressful childhood environment, those with both the stress and the short transporter were more likely to exhibit symptoms of both depression and anxiety in adolescence. Conversely, those subjects with the long serotonin transporter were resistant in the stressful environment.
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Although some researchers have concentrated their studies on the interaction of alleles for the serotonin transporter and stressful environments others have focused on supportive environments. An example of this is the work of Way and Taylor (2010) who examined how individuals with the short serotonin transporter fare in supportive environments. The authors reported that subjects with the short serotonin transporter displayed superior mental health outcomes than others when raised in supportive environments. Consequently, the short allele for the serotonin transporter may be considered as presenting greater responsiveness to the environment rather than being a depression–anxiety risk aspect. The effect of the serotonin transporter alleles on momentary responses has also been evaluated. Hariri and associates (2008) genotyped subjects on the serotonin transporter and then imaged the subjects’ brains as they observed frightening images. Those subjects with the short transporter showed more activation in their amygdalae. Lonsdorf et al., (2009) reported that those with the short transporter presented stronger fear-potentiated startle, another indicator of anxiety.
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Key Points
Those individuals with GAD differ from others in specific ways. It appears that they focus and are drawn in by negative stimuli. In terms of the physiology for controlling distressing emotions, they show deficits. Evidence suggests that there are genetic variations that predispose to anxiety. However, genetic risk factors require specific environments before anxiety symptoms are exhibited. Research is consistent with regards to the possibility that anxiety indicators can be altered through environmental interventions.
Obsessive-Compulsive Disorder
Individuals with obsessive-compulsive disorder (OCD) frequently develop feelings of being anxious at specific periods and develop customs that reduce their anxiety. The “negative reinforcement” theory describes how this is applied. According to Christianson and colleagues (2012), OCD customs reduce individuals’ subjectivity, internal anxiety and therefore their behavioural routine becomes negatively reinforced. Deacon and Maack (2008) performed research in which subjects with OCD were encouraged to perform their escape or anxiety behaviours at an upper level each time escaping their preliminary anxiety, their fears of contamination were further enhanced. The authors noted the negative reinforcement effect and suggested that giving in to the impulses to perform OCD routines will increase their drive.
While OCD for most people is another type of anxiety disorder, previously it was stated that some individuals with OCD displayed problems in other brain circuits not normally connected with anxiety (Rapoport, 1989). There is academic evidence implying that the basal ganglia, structures linked with the control of movement, are involved in the expression of OCD behaviours in subsets of those with OCD. An array of studies led to the development of this evidence.
For example, specific individuals who are infected with group A beta-haemolytic streptococcus pharyngeal (throat) infection consequently develop rheumatic fever. Rheumatic fever affects the heart. Later, Sydenham’s chorea follows (Swedo et al., 1989). Sydenham’s chorea includes tics (involuntary, repetitive movements of the upper body and the face). Additionally, some individuals (17% in the Hounie et al., [2007] sample) acquire urges to circumvent germs and practices to avoid contamination (e.g., wiping doors, washing hands). Consequently, there appeared to be an association among infection with certain bacteria, an autoimmune response to the heart, movement difficulties, and distinctive OCD behaviours.
With improvements in immunology and a greater understanding of antibodies, it became possible to evaluate antibodies in the blood of individuals with Sydenham’s chorea. Moreover, it was established that those with Sydenham’s chorea had antibodies to proteins expressed in the basal ganglia (an area of the brain involved in controlling movements). The justification for the antibody increase is that proteins expressed by streptococcus bacteria are comparable in structure to proteins expressed in the basal ganglia. Therefore, the antibodies to the bacteria cross-react with proteins (lysoganglioside receptors) in the basal ganglia (Hounie et al., 2007). These outcomes suggested that the basal ganglia may be an important structure in the expression of OCD related behaviours. Consistent with this, some people displaying OCD behaviours have a reported history of scarlet fever followed by Sydenham’s chorea (Hounie et al., 2007; Mercadante et al., 2005).
Several people with OCD also meet the criteria for Tourette’s syndrome. Tourette’s syndrome is categorised by tics, which may include eye blinking; scowling; jaw, neck shoulder, or limb movements; sniffing; mumbling; chirping; throat clearing; compulsion to make offensive statements; biting; or hitting. In children with Tourette’s, 60 to 70% also display hyperactivity and 50% exhibit obsessive-compulsive behaviours (Swain et al., 2007). The occurrence of tics and ritualistic urges suggest that OCD behaviours of some individuals can be a form of movement disorder. Contemporary studies have confirmed that basal ganglia structures are central to the expression of OCD behaviours. Images from neurons in the basal ganglia suggest that this area of the brain is active during the expression of OCD behaviours, such as excessive checking (Burbaud et al., 2013).