Sex-Specific Differences in the Biology of PTSD and Alcohol Abuse

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Post-Traumatic Stress Disorder (PTSD) is an anxiety disorder that is prevalent in some individuals who have experienced or witnessed a traumatic event. More often than not, these encompass serious accidents, physical/sexual abuse or combat exposure; for which reason, a large number of individuals affected by this disorder are veterans. In the United States, 7% to 8% of citizens experience symptoms of PTSD in their lifetime.

Posttraumatic Stress Disorder (PTSD) - Patrick Counseling
PTSD Symptoms. Image Source: Patrick Counselling

There is a high correlation between individuals that experience these levels of anxiety resorting to alcohol abuse, allowing us to ascertain that PTSD and Alcohol Use Disorder (AUD) go hand-in-hand. It has also been noted that those with anxiety disorders are also more at risk of relapse and of experiencing increased alcohol withdrawal symptoms.

Whilst the comorbidity of these disorders is well recognised, underlying biological factors was until recently, fairly misunderstood.

A recent study by the Scripps Research Institute looked at sex-specific differences in the brain chemistry of female and male rats. The researchers are hopeful that this might be valuable towards the development of more targeted treatments of PTSD and AUD. However, the complexity of these disorders has made it rather difficult to find effective treatments to tackle them.

In a study with rodents, researchers studying addiction and stress separately, united forces to investigate the neurological factors underlying these disorders, when experienced comorbidly. They assessed behavioural and sleeping patterns, inflammatory immune responses, and levels of the gamma-Aminobutyric acid (GABA) neurotransmitter to determine this relationship. GABA is a neurotransmitter often associated with fear and anxiety; its role is to lower anxiety and increases the feeling of relaxation. Alcohol is known to mimic the effects of GABA.

GABA receptor
Synapse (junction between two neurons) transmitting GABA neurotransmitters

The data showed that both male and female rats exhibited traumatic stress and alcohol dependence and other common symptoms of PTSD (e.g., social avoidance and defensive behaviour). Those identified as more vulnerable to drinking tendencies prior to the trauma, showed higher signs of avoidance of trauma-reminiscent places. 

However, the researchers were also able to observe that male and female rats differed in their behaviour post-trauma and in their patterns of GABA signalling. Whilst males showed increased GABA receptor function, females showed increased GABA release.

These findings are highly significant in improving medical interventions for such disorders, as we now understand that we must consider different levels of effectiveness for male and female patients. By understanding the biology, we can adapt the medicines accordingly.

Another important finding was that cytokines, proteins secreted by immune cells that determine vulnerability to AUD, were only seen in male rodents and not in females.

Further research is needed into the mechanisms behind the biological changes observed in this study. The researchers plan to test which brain systems can be targeted to treat both PTSD and AUD.

Original article: Steinman, M.Q., Kirson, D., Wolfe, S.A. et al. Importance of sex and trauma context on circulating cytokines and amygdalar GABAergic signaling in a comorbid model of posttraumatic stress and alcohol use disorders. Mol Psychiatry (2020).

Link: https://doi.org/10.1038/s41380-020-00920-2

Featured Image source: Phoenix Rising Recovery (2020)

Synapse Image source: University of Bristol. ‘GABA, A molecule of Relaxation’.

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