More Than a Feeling: The Living Neurobiology for a Depressed Brain

Written By: Vanessa Rosario

Edited By: Evelyn Castro

Introduction

Going into my undergraduate studies as a Neuroscience major, I was intrigued by brain chemistry and shifts in mental disorders. Learning about what’s going on in my head became a major catalyst in studying mental illness from a biological perspective. My aspirations in pursuing a neuroscience career with specializations in mental health motivated me to research this topic. Depression and depressive disorders are usually viewed purely as a psychological concept, yet neurobiology plays a role in depression via its physical brain alterations. This paper explores the complex neurobiological landscapes in Major Depressive Disorder (MDD), Depression, and other depressive disorders.

Macro-Level Shifts in Brain Activity

Analyzing neural networks from contemporary research shows that depression is a profound failure of context-dependent adaptation. In their meta-analysis, Palmert et al. (2015) show that macro-level neurofunctional alterations in MDD depend on the specific task at hand. In simpler terms, Depression changes how the brain responds depending on what a person is doing. Interestingly, the researchers discovered that the brain has a split between thinking and emotional tasks. When the brain processes thinking tasks, such as trying to focus or remember things, its executive control networks conflict and fail to activate properly. Executive control networks are a large-scale system of brain regions that work in unison to manage complex thinking. In detail, the brain goes through a systematic failure to recruit executive control networks. The brain essentially functions beyond its limits to process basic cognitive tasks. Conversely, when the brain processes emotional tasks, such as processing feelings and stress, the amygdala and other emotional centers become dysregulated. Depression causes a whole networking problem as the brain loses its ability to function and switch gears between thinking and feeling. The neurobiology of depression can be described as a dynamic inability to modulate macro-level networks.

The Evolution of Depression Neuroscience

For decades, the mainstream belief about depression was simply reduced to a “chemical imbalance, " with those arguing that depression was a lack of essential neurotransmitters in the brain. To counter this thinking, Alexander Kaltenboeck and Catherine Harmer (2018) discuss in their review that our biological understanding and definition of the disorder have evolved from this streamlined view. We now recognize depression as a complex network disease and a sort of failure in synaptic plasticity. Synaptic plasticity plays a role in allowing us to think, feel, and move by passing chemical and electrical signals through synapses. In the modern day, the traditional pills that alter brain chemistry have been assisted by various interventions such as neurostimulation and other novel therapies. These new interventions are aimed at reducing neuroinflammation, which lessens the immune response in the brain and spinal cord. Neuroinflammation is simply the inflammation and swelling of the brain and spinal cord. Minimizing neuroinflammation can stop chemical attacks that alter an individual’s mood and energy and, in this context, affect depression’s emotional, reward, and memory centers. The evolution of depression neuroscience has completely transformed from the mainstream definition of chemical imbalances to a complex, network-based, explicit understanding. We are now using this new network of inflammatory science to spot severe depression in individuals. 

Molecular Biomarkers and Clinical Severity

The network-based model is actively changing how we can identify severe depression in patients. The 2023 study by Li et al. (2023) researched how patients with Major Depressive Disorder had elevated levels of the protein called mature Brain-Derived Neurotrophic Factor (mBDNF). The mBDNF is a protein responsible for synaptic plasticity, fostering brain cell survival, growth, and adaptation. Research found that patients with the highest levels of suicidal ideation had elevated plasma levels of mBDNF and increasingly high inflammatory levels. This evidence suggests that psychological and inflammatory strain triggers the brain to a compensatory distress signal, which overwhelms the system with mBDNF as a physical attempt to protect and repair its failing networks. Depression through the biological lens uncovers physical pain inside.

Conclusion

Depression is a far more complex subject than a shortage of neurotransmitters like serotonin; it’s a dynamic network failure in the brain. The brain essentially struggles to switch between thinking and emotional regulation due to its aggravated neuroinflammation. A chronically hyperactive immune response in the central nervous system floods the brain with inflammatory chemicals that disrupt communication throughout the brain. The constant inflammatory stress forces the brain into an uphill battle to maintain baseline mood and cognitive function. Fortunately, there is hope and alternative methods to help manage depressive symptoms. When we reflect on how the brain floods itself with mBNDF counterparts to counteract inflammatory damage, we can recognize from a biological perspective that our brain is trying to fight back to heal itself. Depression is a psychological battle, but our brains are structurally made to adapt and rewire. By introducing tools to calm neuroinflammation and fix network communications, science is actively figuring out how to alleviate the brain’s broken circuits from depression.

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References

Kaltenboeck, A., & Harmer, C. (2018). The neuroscience of depressive disorders: A brief review of the past and some considerations about the future. Brain and Neuroscience Advances, 2, 1–12. doi.org [1]

Li, H., Zhao, M., Jiang, C., Zhao, H., Wu, C., Li, Y., Zhang, S., Xu, P., Mou, T., Xu, Y., & Huang, M. (2023). Elevated plasma levels of mature brain-derived neurotrophic factor in major depressive disorder patients with higher suicidal ideation. Journal of Clinical Medicine, 12(17), 5462. doi.org

Palmer, S. M., Crewther, S. G., & Carey, L. M. (2015). A meta-analysis of changes in brain activity in clinical depression. Frontiers in Human Neuroscience, 8, 1045. doi.org [1]