Stress and Brain Function

Types of Stress

The term “stress” covers a wide range of experience and each has an effect on the functioning of the brain.

  • Good stress makes us more adaptive and resilient in the face of daily challenges. Sometimes good stress can actually improve memory or enable us to take quick action.1
  • Tolerable stress occurs when things go wrong but we are able to cope, re-evaluate, and grow.
  • Toxic stress happens when things go wrong and we don't have good support to get through it. With toxic stress, the inability to cope is likely to have adverse effects on behavior and physiology, and this will result in excess wear and tear on the body, known as allostatic overload.2 Our body naturally attempts to maintain stability by changing involuntary physical functions such as heart rate, blood pressure, body temperature, or levels of stress hormones to attempt to bring homeostatis. But continued functions modified in this way result in allostatic overload..

Chronic Stress

Negative or toxic stress leaves us chronically in the “fight and flight” mode where we are not able to relax after we deal with the daily life challenges. This form of stress overtime affects one’s health and even changes the brain architecture.

  • Chronic stress results in immune suppression,3, 4 as well as many other health conditions including high blood pressure and digestive disorders.
  • Chronic stress can result in reduced brain plasticity. With persistence of this condition, involving excessive activation of excitatory amino acids, potentiated by glucocorticoids, irreversible damage occurs; this is postulated to be a key step in the irreversible activation of the cascade leading to Alzheimer’s disease involving inactivation of the adaptive insulin receptor mechanism.5
  • Chronic stress effects on the brain varies on different parts of the brain. For example, the medial amygdala shows a chronic stress-induced loss of spines6 and shrinkage of dendrites.7
  • These alterations are implicated in increased anxiety, post traumatic stress disorder (PTSD)-like behaviors,8 as well as social avoidance.9, 10

In contrast, normal brain aging involves potentially reversible loss of resilience, which, for example, can often be counteracted by regular physical activity, as well as regular forms of meditation, stress management, a healthy diet, and targeted supplementation, particularly related to deficiencies in certain nutrients.

Environmental Toxins

Along with emotion-based stress factors, environmental stressors contribute to cognitive damage and decline.

Recreational drugs accelerate aging Basically, all illegal substances abused accelerate aging. For example, methamphetamine damages the blood-brain barrier, the tight junctions in the vasculature that prevent damaging molecules from entering the brain. Structural and functional differences in the brain have been linked to early and heavy cannabis use.11 Cocaine induces alterations in neurotransmitters, neurotrophins, glucocorticoids, and promote inflammatory agents that affect neurogenesis in the hippocampus.12

Smoking and brain cell loss.

Nicotine can kill brain cells, stop new neurons forming in the hippocampus, and significantly impact the ability to promote new neurons.13 Nicotine may also lead to higher levels of dependence by exerting neurotoxic effects in the prefrontal cortex (PFC) interfering with cognitive development, executive functioning, and inhibitory control. These effects are particularly evident under stressful or emotionally intense states and are most pronounced when smoking begins during early adolescence.14 Once nicotine has entered the body, it is distributed quickly through the bloodstream and crosses the blood–brain barrier reaching the brain within ten to twenty seconds after inhalation.15 Smoking may affect plasticity and refinement of cortical connections,16 and may it may have functional implications for maturation and function of the prefrontal network.17

Air pollution. Researchers are now linking increased exposure to air pollution with a higher risk of developing neurodegenerative conditions like Alzheimer's disease. Air pollution effectively accelerates many aging conditions linked to reduced cognitive capacity.18 In a long-term study of over 5,300 older participants, an increase in NO2 and fine particulate matter in the air was linked to higher rates of cognitive impairment at the outset of the study, and more rapid rates of decline over time.19

Next: Prevention


1. McEwen B, Lupien S. Stress: hormonal and neural aspects. In: Ramachandran VS, editor. Encyclopedia of the human brain. Amsterdam: Elsevier; 2002. pp. 463–474. Memory formation under stress: quantity and quality. Schwabe L, Wolf OT, Oitzl MS Neurosci Biobehav Rev. 2010 Mar; 34(4):584-91.
2. McEwen BS. (2015). "Chapter 34 – Stress". In Neurobiology of Brain Disorders. Pp 558-569.
3. Dhabhar FS. (2009). Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. Neuroimmunomodulation. 16(5):300-17.
4. Dhabhar FS, Malarkey WB, Neri E, McEwen BS. (2012). Stress-induced redistribution of immune cells--from barracks to boulevards to battlefields: a tale of three hormones--Curt Richter Award winner. Psychoneuroendocrinology. Sep; 37(9):1345-68.
5. De Felice FG, Lourenco MV, Ferreira ST. (2014). How does brain insulin resistance develop in Alzheimer's disease? Alzheimers Dement. Feb; 10(1 Suppl):S26-32.
6. Bennur S, Shankaranarayana Rao BS, Pawlak R, Strickland S, McEwen BS, Chattarji S. (2007). Stress-induced spine loss in the medial amygdala is mediated by tissue-plasminogen activator. Neuroscience. Jan 5; 144(1):8-16.
7. Lau T, Bigio B, Zelli D, McEwen BS, Nasca C. (2017). Stress-induced structural plasticity of medial amygdala stellate neurons and rapid prevention by a candidate antidepressant. Mol Psychiatry. Feb; 22(2):227-234.
8. Vyas A, Mitra R, Shankaranarayana Rao BS, Chattarji S. (2002). Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J Neurosci. Aug 1; 22(15):6810-8.
9. Ibid. Lau. (2017).
10. Krishnan V, Han MH, Graham DL, Berton O, Renthal W, Russo SJ, Laplant Q, et al. (2007). Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions., Nestler EJ Cell. 2007 Oct 19; 131(2):391-404.
11. Burggren AC, Shirazi A, Ginder N, London ED. (2019). Cannabis effects on brain structure, function, and cognition: considerations for medical uses of cannabis and its derivatives. Am J Drug Alcohol Abuse. Jul 31:1-17.
12. Castilla-Ortega E, Ladron de Guevara-Miranda D, Serrano A, Pavon FJ, Suarez J, et al. (2017). The impact of cocaine on adult hippocampal neurogenesis: Potential neurobiological mechanisms and contributions to maladaptive cognition in cocaine addiction disorder. Biochem Pharmacol. Oct 1;141:100-117.
13. Abrous DN, Adriani W, Montaron MF, Aurousseau A, Rougon G, Le Moal M, et al. (2002). Nicotine Self-Administration Impairs Hippocampal Plasticity. J Neurosci. May 22 (9) 3656-3662.
14. DeBry SC, Tiffany ST. (2008). Tobacco-induced neurotoxicity of adolescent cognitive development (TINACD): a proposed model for the development of impulsivity in nicotine dependence. Nicotine Tob Res. Jan; 10(1):11-25.
15. Le Houezec J. (2003). Role of nicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: a review. IntJ Tuberc Lung Dis. Sep; 7(9):811-9.
16. Couey JJ, Meredith RM, Spijker S, Poorthuis RB, Smit AB, Brussaard AB, et al. (2007). Distributed network actions by nicotine increase the threshold for spike-timing-dependent plasticity in prefrontal cortex. Neuron. Apr 5; 54(1):73-87.
17. Guillem K, Bloem B, Poorthuis RB, Loos M, Smit AB, Maskos U, et al. (2011). Nicotinic acetylcholine receptor B2 subunits in the medial prefrontal cortex control attention. Science. Aug 12; 333(6044):888-91.
18. Haghani A., Morgan TE, Forman HJ, Finch CE. (2020). Pollution Neurotoxicity in the Adult Brain: Emerging Concepts from Experimental Findings. J Alzheimers Dis. 2020;76(3):773-797.
19. Kulick ER, Wellenius GA, Boehm AM, Joyce NR, Schupf N, et al. (2020). Long term exposure to air pollution and trajectories of cognitive decline among older adults. Neurology. Apr 28;94(17):31782.