Cognitive Behavioral Therapy for Social Anxiety Linked with Improved Cellular Protection from Aging
By: Josie Chen
Telomere shortening is a defining characteristic of cellular aging associated with senescence, apoptosis, and the oncogenic transformation of somatic cells (Shammas, 2011). Although researchers have yet to acquire a complete understanding of the complex mechanisms behind aging, shorter telomeres have been frequently reported in individuals with mood and social anxiety disorders (SAD), demonstrating their relation to health and longevity. Telomeres are repeating sequences of nucleotide cytosine and guanine base pairs located at the ends of linear eukaryotic chromosomes to concur genomic stability and protection (Baird 2007). Specifically, a process involves a guanine-rich sequence called the G-overhang forming secondary protein structures to protect chromosomes from being targeted as damaged DNA (Chow et al., 2013). An end replication problem arises from the mechanisms behind incomplete DNA replication; an enzyme within the body known as telomerase counteracts this. Without telomerase, a gradual shortening of the telomere ends occurs (Figure 1), leading to senescence or apoptosis (Maestroni et al., 2017). Interestingly, research has shown that telomere length not only dictates the degradation of cellular viability but also coupled with the rate of DNA damage, plays a critical role in determining species lifespan (Whittermore et al., 2019). Oxidative stress serves as another contributor to increased cellular aging, stemming from an imbalance of oxygen reactive species within organismal tissues and the subsequent damage that ensues from a lack of proper detoxification. Over time, accumulation of oxidative stress may induce a surge in the body’s aging and chronic and degenerative diseases (Pizzino et al., 2017). Just as telomerase counteracts telomere shortening, the antioxidant enzyme glutathione peroxidase (GPx) provides antioxidant abilities for oxidative stress, and consequently, cellular aging.
Figure 1. Telomere shortening results from an end-replication problem, in which the ends of eukaryotic DNA are left uncopied as a single strand during each replication cycle. Over time, the continuous shortening of telomeres leads to senescence and genome instability (Doksani et al. 2019).
A popular treatment for SAD is cognitive behavior therapy (CBT), aimed at targeting a variety of psychological problems such as depression, eating disorders, anger and aggression, psychotic disorders, and social anxiety (Goldin et al., 2013). There are three core principles of CBT: thoughts, behaviors, and emotions. Based on the idea that all mental disorders involving psychological distress contain a cognitive component, this method of treatment has become mainstream in both research and clinical settings (Hoffman, 2012). By reconciling thinking with emotional and behavioral patterns, the goal of CBT is to reduce symptoms of mental illness and allow patients to generate useful coping mechanisms (Society of Clinical Psychology, 2017).
While more replicates and studies are needed, this novel data provides a starting point for the idea that the biological mechanisms behind cellular protection are linked to responses from psychosocial interventions for anxiety.
In a recent study by Mansson et al., the relationship between the length and activity of telomeres as well as GPx activity was measured among SAD patients undergoing cognitive behavioral therapy (CBT) (Mansson et al., 2019). The novel study treated a cohort of 46 participants who met the criteria for SAD based on results from the full Mini-International Neuropsychiatric Interview and social phobia section of the Structured Clinical Interview for DSM-IV—Axis I Disorders. Over the course of nine weeks, patients were administered standardized Internet-delivered CBT in the form of guided self-help and feedback from a clinical psychologist on a weekly basis. To track telomerase activity, researchers used modified real-time telomeric repeat amplification protocols to collect assays with an efficiency rate of 95-101%. They then used real-time quantitative PCR to determine relative telomere to single-copy gene ratios for telomere lengths. As for GPx activity, researchers utilized a BioVision Glutathione Peroxidase Activity Colorimetric Assay Kit to calculate values based on an NADPH curve.
Figure 2. This graph demonstrates a negative association between telomerase activity and LSAR-SR values; as telomerase activity increases, social anxiety decreases. Similarly, there is a negative association between GPx levels and LSAR-SR values, indicating that reduced social anxiety is correlated with increased GPx activity (Månsson et. al 2019).
Ultimately, CBT was proven to be an effective treatment for the patients’ social anxiety given a substantial decrease in LSAS-SR scores. Not only did the researchers demonstrate a negative association between telomerase activity and LSAR-SR values, showing that there was a significant increase (p=0.001) in telomerase activity (Figure 2) as CBT was applied, but GPx activity also followed a similar pattern of a significantly negative association (p=0.029). The findings demonstrated substantial increases in telomerase and GPx activity in patients, along with significant SAD symptom improvement; therefore, the results of the study provided strong evidence that cellular protection through telomere preservation and antioxidation corresponds to reduced social anxiety. Additionally, while not all subjects saw increases in enzyme activity, those with the greatest clinical improvements also had a greater chance of increasing telomerase and GPx activity throughout treatment. Nonetheless, it is important to note that changes in telomerase and GPx in relation to anxiety were not statistically related, pointing to cellular mechanisms that are independent to some degree. While more replicates and studies are needed, this novel data provides a starting point for the idea that the biological mechanisms behind cellular protection are linked to responses from psychosocial interventions for anxiety. By grasping a full understanding of the minuscule, yet complex processes behind remission, we may be able to advance the potential for novel treatments against cellular aging in the future.
References
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Applied Behavior Analysis Edu. (2023). 5 cognitive behavioral therapy techniques professionals use to change lives: Applied behavioral analysis. Applied Behavioral Analysis | How to Become an Applied Behavior Analyst. https://www.appliedbehavioranalysisedu.org/2022/08/5-cognitive-behavioral-therapy-techniques-professionals-use-to-change-lives/
Doksani, Y. (2019). Figure 4. Telomere loss due to replication problems [Digital image]. Retrieved 2021, from https://www.mdpi.com/2073-4425/10/4/318/xml
Månsson, K. N., Lindqvist, D., Yang, L. L., Svanborg, C., Isung, J., Nilsonne, G., . . . Furmark, T. (2019). Fig. 3: Telomerase and glutathione peroxidases changes associated with treatment response. [Digital image]. Retrieved 2021, from https://www.nature.com/articles/s41398-019-0668-2#citeas
