Mood disorders are among the most challenging health problems for both clinicians and patients, and they are not a respecter of age, sex, societal class or economic status. Major depression is now considered the most common mental disorder in the United States. In 2016, 16.2 million adults (6.7% of all U.S. adults) and 3.1 million adolescents (12.8% of the U.S. population aged 12 to 17 years) experienced at least one major depressive episode. In an average of 67% of these individuals, depression caused severe impairment to their quality of life. Medication, psychotherapy, or combined treatment remains the treatment of choice. In fact, from 1999 to 2014, antidepressant use increased by 65 percent and the CDC reported that 1 in every 8 Americans over the age of 12 was taking an antidepressant medication. Concern lies in the fact that common antidepressant medications still come with severe side effects, including suicide.

Many experts believe we could point the finger to the rise in chronic stress as an underlying cause in our epidemic of mood disorders. “Stressed and depressed” is a tagline often used to describe current trends. Certainly, neurotransmitter imbalances lie at the root of depression and other mood disorders, but could it be possible that these roots are feeding in the soil of cortisol, the primary stress hormone?

The Basics of Neurotransmitters and Mood

Depression and other mood disorders have most often been explained as imbalances in three key neurotransmitters: dopamine, norepinephrine, and serotonin. Most medications, therefore, target these. Tricyclics and MAO inhibitors increase levels of all three neurotransmitters by either blocking their reuptake into the axon terminals or by inhibiting enzymatic degradation of these chemicals. Selective serotonin reuptake inhibitors (SSRIs) focus on increasing the “happy neurotransmitter” serotonin by blocking its reuptake into axon terminals. Unlike serotonin, epinephrine and dopamine are responsible for providing drive, motivation, and pleasure, rather than happy feelings. Experts still argue about whether depression actually stems from too little of the neurotransmitters or too much (leading to down-regulation of the receptors). Both sides of the argument present complications.

Cortisol and Neurotransmitters

Chronic stress predisposes its victim to an onslaught of mood disorders, including depression. The sustained secretion and circulation of glucocorticoids such as cortisol eventually alters the balance of neurotransmitters. They deplete dopamine, which decreases activity in the pleasure pathways of the brain; reduce norepinephrine, leading to a lack of motivation and alertness; and lower serotonin, reducing feelings of happiness and well-being.

Studies show that older adults with mood-related mental disorders such as depression and anxiety have significantly higher salivary cortisol levels which begs the question of which condition (stress or depression) is the chicken and which is the egg.

Cortisol and the Hippocampus

Depression and other mood disorders almost always involve impaired memory. Memory is a function of the hippocampus, a region of the brain that is rich in glucocorticoid receptors. Chronically elevated levels of cortisol, due to chronic stress, have been shown to decrease hippocampus volume and induce loss of neurons, which will inevitably impair memory. As expected, reduced hippocampal volume is observed in individuals with long-term depression and it is certainly possible that elevated cortisol could be a contributing factor.

Cortisol and Brain-Derived Neurotropic Factor

Chronic stress decreases the expression of brain-derived neurotrophic factor (BDNF) in the limbic structures of the brain that control memory and mood, and may offer one explanation for how chronic stress decreases hippocampal volume. BDNF is a protein that supports the growth and differentiation of new neurons in the central and peripheral nervous system. It is most active in the hippocampus and frontal cortex regions of the brain, which control memory and mood. In a study seeking to determine the relationship between chronic stress, BDNF and depression, sows were recurrently tethered for 1.5 to 4.5 years to establish a stressful situation. The frontal cortex and hippocampus were analyzed following slaughter and revealed decreased BDNF protein levels, and increased cortisol levels and adrenal weight. These effects were more pronounced in the sows that experienced tethering for a longer duration, indicating that chronic stress progressively depletes BDNF protein levels, resulting in neuron degeneration in areas of the brain responsible for memory and mood.

Chronic stress and mood disorders most certainly run their race together, and as the prevalence of mood disorders such as depression rise, it becomes vital that we tackle the beast of chronic stress. Supporting a healthy balance of neurotransmitters can be helpful and, truthfully, essential, but focusing on adrenal support, cortisol balance, and long-term stress-management is important for addressing root causes of one of our most epidemic health conditions.

By Nicole Spear, MS, CNS