Depression is a mood disorder that involves a sad mood or loss of pleasure in normal activities (NIH). It can have impacts on cognition, motivation, and emotional reactions. It’s important to find treatment to improve the quality of life and functional abilities of those who suffer from depressive disorders. When focusing on biological risks for depression, most research focuses on neurotransmitters. Specifically, low levels of serotonin may be contributing factors to depressive disorders (Healthline). However, new research has demonstrated the role of neuroinflammation in depression. This discovery may impact the types of treatments patients are given in the future.
Serotonin is circulated around the brain. Its pathway originates in the raphe nuclei (in the brainstem), and serotonergic neurons will spread throughout the brain from this origin (ScienceDirect). The regions of the brain with serotonergic neurons are important for brain balance. Serotonin affects mood, emotions, appetite, and digestion. It also helps to regulate the sleep-wake cycles (Medical News Today). Basically, it helps the brain achieve homeostasis. When serotonin is low in depressive disorders, the brain is not at balance. Depression treatments focus on increasing serotonin to bring the brain back to a balanced state.
While there are many types of antidepressants, the most common are SSRIs. SSRIs (selective serotonin reuptake inhibitors) increase the level of serotonin in the brain (MedlinePlus). After a neuron releases serotonin into the synapse, this serotonin binds to the dendrite of the next neuron, allowing it to send a signal to that neuron. This is how our brain communicates. Typically, after a neurotransmitter binds, it will go back into the synapse and the process of reuptake brings the neurotransmitter back into the presynaptic neuron (or the neuron that released it in the first place). When an SSRI is used, the transporter that brings serotonin back into the presynaptic neuron is blocked. Therefore, serotonin will stay in the synapse, and then it will keep binding to the dendrites of the next neuron. Effectively, the serotonin will keep sending its signal as long as it stays in the synapse. Therefore, SSRIs increase serotonin in the synapses of the brain and allow it to send signals regulating mood. Most antidepressants focus on adjusting the levels of neurotransmitters, such as serotonin, in the synapse to improve mood.
While it is true that serotonin may play a role in depression, another theory has to do with neuroinflammation and its effect on homeostasis of the brain. Inflammation is the body’s response to tissue injury caused by pathogens or trauma (NIH1). Some signs of inflammation are redness, swelling, immobility, pain, and heat. During inflammation, macrophages phagocytose (consume) bacteria and release inflammatory cytokines (chemical messengers) to recruit other immune cells to fight the infection (NIH2).The swelling and other signs of inflammation are caused by the influx of immune cells to that area to fight the infection. Neuroinflammation is the same thing as inflammation, but it happens in the brain. The macrophages in the brain are called microglia. They phagocytose harmful materials and release inflammatory cytokines to recruit immune cells to the brain. When PAMPs (pathogen associated molecular patterns – only found on bacteria) interact with PRRs (pathogen recognition receptors – on microglia) called toll-like receptors, this leads to the activation of the microglia and subsequent inflammation. This process helps support the survival of neurons. While normal brain inflammation can improve brain plasticity and function, high amounts of inflammation and chronic inflammation can lead to cognitive impairment, neuronal damage, as well as depression and anxiety (NIH3). Neuroinflammation has been implicated in both brain degenerative disorders as well as psychological disorders.
It’s interesting how the focus of the research community has been on serotonin, but brain inflammation can also play a role in depression. In general, both inflammation and serotonin are important to maintain homeostasis in the brain. When there is too much inflammation, the brain is not able to function properly. When serotonin is too low, the brain cannot maintain a state of “normal.” While these two possible causes for depression would entail different types of treatments (e.g., in one trying to reduce inflammation, in the other trying to increase serotonin), they both are focused on brain balance.
My next blog will focus on how inflammation is implicated in depression, and possible ways to treat brain inflammation.
Leave a Reply