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What we have learned from stress and addiction research

January 2, 2020

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Stress, dopamine, and the risks of mental illness.

Experts and professionals have become increasingly aware of the health effects of trauma and stress. Trauma, sexual, physical, or emotional, can change the brain and increase risks for many psychiatric conditions and diseases. Adverse Childhood Experiences (ACEs), for example, which refer to traumatic events in the lives of people under the age of 18, can negatively affect the brain and lead to addiction, academic problems, heart disease, and depression. A recent study found that ACEs and lifetime adversity exposure were significantly associated with increased risk of substance-related hospitalization, overdose, witnessing overdose, and having a friend and family member who overdosed.1 Similar data have been reported recently for suicide.2 Discussing trauma and stress can be difficult and evoke feelings of depression or shame: they are heavily stigmatized, compounding many of these potential problems and sapping individual reserves of resilience. Science shows us that stress and adversity aren’t just generally irritating aspects of everyone’s lives. In severe forms, they’re also major threats to our health and ability to think clearly and logically.3 

Not all traumatic experiences cause Post-traumatic stress disorder (PTSD) or substance use disorder (SUD). Recent research findings from the Yale group suggest that trauma in the absence of a PTSD diagnosis does not lead to a stronger craving for alcohol.4 Yet researchers know that the risk of developing mental illness rises because of psychosocial adversity.5 “These adverse factors,” write the authors of one recent study, “include developmental psychological trauma and adult life events (situations or occurrences that bring about a negative change in personal circumstances and involve threat).” These factors can also increase the risk of developing SUD. Researchers are investigating how various therapies, including mindfulness, modify triggers and traumatic memories.6 But experts have not clearly identified the ways in which stress and trauma dispose people to later problems. In this recent study, researchers wondered whether stress affects dopamine levels, impairing them over a longer term. They exposed participants to stress and gauged their reactions through state-of-the art PET scans.

What does this study find about adversity and dopamine?

This study found that long-term experiences of adversity decrease dopamine function, making it harder to not only experience pleasure, but to handle stressful situations. Earlier research on animals suggests that dopamine levels might be the link between mental health challenges and adversity. This study wanted to explore that link by testing people. Researchers found one group of 17 participants who said that they dealt with a lot of stress as adults and children, and another group of 17 who reported fewer experiences of adversity. Stressors included parental loss, bullying and abuse, life-threatening medical conditions, bereavement, job change, relationship breakdown, unemployment, and minority ethnic status, among other factors.

This study had participants take a test while exposing them to “scripted verbal negative feedback.” After the test and negative feedback, researchers used position emission tomography (PET) to measure dopamine output in participants. They found limited dopamine production in the group with more stressful life experiences and elevated threat perception relative to the group with less exposure to stress. This study also gauged blood pressure and cortisol levels to determine threat perception and stress in participants. This study’s authors write, “Although the case-control design of this study is not able to confirm a causative relationship between psychosocial stress and dopamine dysfunction, these findings warrant further research into potential causative mechanisms.”

Why is this important?

Limitations of this study include the possibility that recall bias interferes with self-reported experiences of stress and adversity, and the possibility that genetics explain the results. Dr. Michael Bloomfield, this study’s lead, said that while this research doesn’t prove that experiences of long-term adversity reducing dopamine are the primary cause of SUD and other mental health conditions, “We have provided a plausible mechanism for how chronic stress may increase the risk of mental illnesses by altering the brain’s dopamine system.”7 This is an important view of the link between trauma and the development of serious medical conditions like addiction, and additional research could help practitioners approach prevention and treatment in new ways. The authors of this study also call for more research on how dopamine changes increase risks for the development of health problems.

This research also emphasizes the importance of studying the dangers of stress and experiences of adversity, and of searching for ways to limit stress. And, as is the case for addiction, stress is not confined to any single population or socioeconomic group. A Washington Post report in September, for example, observed that poverty and discrimination are risk factors for adolescents, but increasingly, high-pressure schools are, too: “Even activities that once were stress-reducers, like playing a musical instrument or a sport, have become a means to an end, that end being a spot at one of the country’s most competitive colleges and then on to a prestigious, high-paying career.” 

These findings point to the significance of PTSD, which is sadly very common in the U.S., affecting about 8 percent of the population and around 30 percent of combat veterans and 80 percent of refugees and victims of torture. PTSD is associated with higher rates of depression, suicidal thinking, and SUD. Disruption in the default mode network (DMN) has been implicated in PTSD. Substance use only makes things worse. PTSD and alcohol use disorder (AUD) together are more severe than either condition on its own, making veterans with both conditions 3 times likelier to attempt suicide.8 It’s also important, and dispiriting, to consider these findings in the context of rising SUDs, overdoses, and suicide rates among the young. 

Reinforcing resilience, intervening to help with stress, and providing tools to learn stress management and trauma responses are important strategies. We can not diagnose PTSD through brain scans, but it is pretty clear that PTSD, while classified as an anxiety disorder, changes the brain. Ariana Grande recently shared her own PTSD experiences after the suicide bombing that killed 22 people at her concert in the U.K., and shared brain images that she said show PTSD. PTSD-related brain changes may be studied by looking at dopamine systems and related systems involved in reward. In early studies, PTSD patients may have an enhanced response to traumatic triggers, with alarm bells going off in the amygdala and memory changes visible in the hippocampus, but might also have dopamine deficiencies and associated dysfunctional reward circuitry.9

Early life stress and cumulative adversity are critical to understand and prevent as they play a major role in the development of SUD, relapse, and recovery. Again, it is complicated. Unlike other drugs of abuse, opioids appear to have different effects on stress biology in rodents as compared to humans. In rats, morphine increases ACTH and corticosterone. In human studies, opioid agonists, including methadone and buprenorphine, acutely suppress cortisol levels. PET research demonstrates drug-related and now stress-related loss of dopamine transmission. Whether these blunted dopamine changes are just related to stress effects on the glucocorticoids is not known. Still, these data clearly suggest that we should be paying close attention to stress. Alcohol or drug-induced activation of stress and dopaminergic pathways is highly interactive. And even the “high” or relief reported after substance use, or absolute reinforcing drug effects, may depend on this interaction. We should take a closer look at trauma, stress, and anxiety but also pay attention to gender. Estrogen and progesterone play an important role in substance experience, reinforcement, metabolism, and the effects of administration. More recently, researchers have found that relatively severe exposure to childhood maltreatment is associated with preference for increased interpersonal distance and less pleasurable responses to touch, pleasure and even tactile discrimination.10

Research also shows that “Effective modulation of the stress response is an essential component of resilience and is dependent on a complex interplay of neurobiological and behavioral factors.”11 We may come to find that reducing significant stress among vulnerable groups is one of the most important behavioral, prevention, and public health goals. Stress is certainly a major cause of drug and alcohol craving.12 It also causes a drive for relief, which is often seen as the proximal event in relapse. Prevention efforts focused on high-stress system risk individuals (e.g., trauma, early life adversity, psychiatric co-morbidity, PTSD, genetic, family history) may be a way to make these otherwise arcane dopamine-pleasure system data useful to people today. 

References:

  1. El-Bassel, N., Marotta, P.L., Goddard-Eckrich, D., Chang, M., Hunt, T., Wu, E., Gilbert, L. (2019) Drug overdose among women in intimate relationships: The role of partner violence, adversity and relationship dependencies. PLoS One
  2. Koyama, E., Zai, C.C., Bryushkova, L., Kennedy, J.L., Beitchman, J.H. (2019) Predicting risk of suicidal ideation in youth using a multigene panel for impulsive aggression. Psychiatry Res
  3. Homan, P., Levy, I., Feltham, E., Gordon, C., Hu, J., Li, J., Pietrzak, R.H., Southwick, S., Krystal, J.H., Harpaz-Rotem, I., Schiller, D. (2019) Neural computations of threat in the aftermath of combat trauma. Nat Neurosci
  4. Ralevski, E., Southwick, S., Petrakis, I. (2019) Trauma- and Stress-Induced Craving for Alcohol in Individuals Without PTSD. Alcohol Alcohol
  5. Van Os, J., Kenis, G., Rutten, B.P.F. (2010) The environment and schizophrenia. Nature
  6. Goldfarb, E.V., Sinha, R. (2019) Fighting the Return of Fear: Roles of Mindfulness-Based Stress Reduction and the Hippocampus. Biol Psychiatry
  7. Press Pack. (2019) Chronic adversity dampens dopamine production. eLife. Retrieved from https://elifesciences.org/for-the-press/49f3ac1d/chronic-adversity-dampens-dopamine-production
  8. Norman, S.B., Haller, M., Hamblen, J.L., Southwick, S.M., Pietrzak, R.H. (2018) The burden of co-occurring alcohol use disorder and PTSD in U.S. Military veterans: Comorbidities, functioning, and suicidality. Psychol Addict Behav
  9. Boukezzi, S., Baunez, C., Rousseau, P.F., Warrot, D., Silva, C., Guyon, V., Zendjidjian, X., Nicolas, F., Guedj, E., Nazarian, B., Trousselard, M., Chaminade, T., Khalfa, S. (2019) Posttraumatic Stress Disorder is associated with altered reward mechanisms during the anticipation and the outcome of monetary incentive cues. Neuroimage Clin
  10. Maier, A., Gieling, C., Heinen-Ludwig, L., et al. (2020) Association of childhood maltreatment with interpersonal distance and social touch preferences in adulthood. Am J Psychiatry
  11. Akiki, T.J., et al. (2018).Topology of brain functional connectivity networks in posttraumatic stress disorder. Data Brief
  12. Wemm, S.E., Larkin, C., Hermes, G., Tennen, H., Sinha, R. (2019) A day-by-day prospective analysis of stress, craving and risk of next day alcohol intake during alcohol use disorder treatment. Drug Alcohol Depend

 

Citation:

1. Bloomfield, M.A.P., McCutcheon, R.A., Kempton, M., Freeman, T.P., Howes, O. (2019) The effects of psychosocial stress on dopaminergic function and the acute stress response. eLife

 

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Mark Gold, MD

Dr. Mark S. Gold is a teacher of the year, translational researcher, author, mentor and inventor best known for his work on the brain systems underlying the effects of opiate drugs, cocaine and food. Read more by Dr. Gold here.