Stress changes neural connections, decreases brain volume, and contributes to Alzheimer’s disease
Researchers from Zurich, Switzerland were surprised and excited by what they discovered about how stress changes the brain in a 2019 study published in Neuron.
When we perceive a threat, the neurotransmitter noradrenaline (aka norepinephrine) is released. Previous research has suggested that noradrenaline probably facilitates connections between parts of the brain. The research team from Zurich manipulated the brains of mice so that they could control when noradrenaline was released. They found that noradrenaline instantly “rewired” the mouse brains, making actual structural changes to neural connections. This finding suggests that the long-term effects of stress on the brain may be more profound than previously thought.
In the study, the most significant structural changes occurred in areas of the brain that process sensory information (like what we see and hear) and in the amygdala. The amygdala is a cluster of nuclei in the limbic system that plays an important role in the emotional responses of fear, anxiety, and aggression, as well as in memory and decision-making. The amygdala is typically overactive in people with stress-related conditions, including anxiety and depression.
Chronic stress affects the amygdala by another means as well. Prolonged high levels of glucocorticoids stimulate neuron growth in the amygdala and make synapses more active and sensitive.
Stress and the release of glucocorticoids have also been shown to hardwire neural connections between the hippocampus and the amygdala, potentially creating a cycle in which the brain becomes stuck in a constant state of stress.
Of equal concern is the fact that effect that chronic stress has on decreasing brain volume and connectivity. Data from 2,231 participants in the Framingham Heart Study shows that people with increased levels of cortisol (one of the glucocorticoids) experience brain shrinkage and memory loss.
And a study of 103 healthy subjects showed decreased brain volume in the medial prefrontal cortex and the insula in people who had experienced repeated exposure to stress as well as those who had only experienced a recent stressful event. The affected areas of the brain regulate emotions, stress, reward regulation, memory, decision-making, and impulse control. The study authors suggest that this decrease in brain matter may help to explain the connection between stressful life events and an increased risk of depression, addiction, and other stress-related disorders.
Glucocorticoids have also been shown to decrease volume of the hippocampus, a part of the brain involved in memory, learning, attention, and ironically, regulating glucocorticoid secretion. So the more stress you experience and the more damage is done to your hippocampus, the less effective it is at regulating glucocorticoid levels, and the more glucocorticoids build up in your system. This is a vicious cycle that can make it difficult to reduce your level of stress.
There is a growing body of research on how stress contributes to Alzheimer’s disease. Based on current research, stress increases the expression of Amyloid Precursor Protein (APP) and the production of Aβ peptide, which then gets deposited into amyloid plaques. Amyloid plaques trigger an inflammatory response in the brain, and it’s believed that neurotoxic inflammatory substances contribute to the neurodegeneration that occurs in Alzheimer’s. Stress also elevates levels of the Tau protein, which leads to neurofibrillary tangle formation and neurodegeneration.