Beyond Chemical Imbalances: Rethinking the Root Causes of Mental Health Disorders
For decades, psychiatrists have been taught that the majority of mental illnesses stem from a chemical imbalance in the brain. During my early years of training, much was still unknown. While certain medications seemed to alleviate symptoms, the reasons behind their effectiveness weren’t fully understood. One of the largest clinical trials for depression, the STAR*D study, revealed that only 27% of patients achieved full remission after 14 weeks of antidepressant treatment. Over time, however, it has become clear that the causes of mental illness are far more complex than a simple chemical imbalance. Growing evidence now points to a variety of factors contributing to the rising prevalence of mental health disorders. Among these, nutrition plays a significant role, as does the state of inflammation in the body. The saying, "You are what you eat," has never been more relevant. As America increasingly embraces a fast-food culture, we are losing essential nutrients, making people more vulnerable to mental health issues. We have highlighted some of these nutrients in previous posts and will continue to explore them further as the year unfolds.
A 2020 article in Brain, Behavior, and Immunity by Chang highlights several important nutritional interventions that support mental well-being. For example, blueberries, rich in antioxidants, show promise in improving cognitive function, particularly in neurodegenerative conditions like alcohol-induced dementia. Additionally, CBD (cannabidiol without THC) has been noted for its anxiolytic effects, helping to reduce anxiety symptoms. Omega-3 fatty acids, known for their anti-inflammatory properties, have demonstrated benefits in treating various mental health conditions, including depression, bipolar disorder, and schizophrenia. The article also emphasizes the importance of the gut-brain axis, showing how a lack of beneficial gut bacteria can increase the risk of mental health problems.
A systematic review by Pouranayatihosseinabad et al. suggests that antibiotic exposure may increase the risk of developing depression by up to 20%, with this risk potentially lasting for decades after treatment. In addition, a study by Lee et al. in a Korean population found that cumulative antibiotic exposure was linked to a higher risk of depression. As we enter cold and flu season, this evidence encourages us to reconsider the widespread use of antibiotics. While antibiotics are undeniably essential and life-saving in many cases, they are often overprescribed. We frequently overlook the potential long-term mental health effects of even one or two courses of antibiotics over the course of a year.
Antibiotics can alter the diversity of the gut microbiota, which affects the production of short-chain fatty acids (SCFAs) and neurotransmitters like serotonin. This disruption leads to dysbiosis, an imbalance in gut bacteria, and increases gut permeability. As a result, bacterial toxins can enter the bloodstream, triggering inflammation. This inflammation raises stress levels and cortisol production, both of which are associated with an increased risk of depression and anxiety. Inflammation plays a more significant role in depression than previously understood. Katherine and Timothy Dinan discuss this phenomenon in their article Antibiotics and Mental Health: The Good, the Bad, and the Ugly, published in the Journal of Internal Medicine. While not all antibiotics have a negative impact—such as Isoniazid, the first antibiotic, which has been shown to improve depression—some antibiotics significantly reduce gut diversity, and this loss of diversity has been identified as a key risk factor for worsening depression.
Our understanding of mental health has evolved beyond the simple notion that there is a chemical imbalance in the brain. Increasing evidence underscores the complex interplay of various factors, such as nutrition, inflammation, and the gut microbiota, in shaping mental well-being. As we deepen our understanding of these connections, it is clear that preserving gut health and using antibiotics thoughtfully play a crucial role in supporting mental well-being. While antibiotics have undeniably saved countless lives, their overuse and effect on gut diversity can contribute to mental health problems such as depression and anxiety. When antibiotics are necessary, it is important to focus on replenishing the gut microbiome by consuming foods and utilizing pre/probiotics that enhance microbial diversity. Moving forward, adopting a more holistic approach to mental health—one that incorporates these broader factors—will be essential in developing more effective prevention and treatment strategies for mental health disorders.
“Our understanding of mental health has evolved beyond the simple notion that there is a chemical imbalance in the brain”
References:Chang, J. P., & Su, K. P. (2020). Nutrition and immunology in mental health: Precision medicine and integrative approaches to address unmet clinical needs in psychiatric treatments. Brain, behavior, and immunity, 85, 1–3. https://doi.org/10.1016/j.bbi.2019.09.022Dinan, K., & Dinan, T. (2022). Antibiotics and mental health: The good, the bad and the ugly. Journal of Internal Medicine, 292(6), 858-869. https://doi.org/10.1111/joim.13543Hao, W. Z., Li, X. J., Zhang, P. W., & Chen, J. X. (2020). A review of antibiotics, depression, and the gut microbiome. Psychiatry Research, 284, 112691. https://doi.org/10.1016/j.psychres.2019.112691Lee, J., Park, S. J., Choi, S., et al. (2024). Cumulative antibiotic exposure and the risk of depression: A cohort study. Psychiatry Research, 339, 115992. https://doi.org/10.1016/j.psychres.2024.115992Pouranayatihosseinabad, M., Bezabih, Y., Hawrelak, J., et al. (2023). Antibiotic exposure and the risk of depression: A systematic review. Journal of Psychosomatic Research, 164, 111113. https://doi.org/10.1016/j.jpsychores.2022.111113