Depression is a disease that affects millions of people around the world. It has long been understood that depression is complicated, with many factors coming into play, such as genetics, environment, stress, and lifestyle. Despite the effort and resources dedicated to treating depression, it can still be difficult to find a successful treatment. In order to understand why this is, we must examine the possible causes behind why depression treatments sometimes fail.
Depression has been understood for some time as being driven by an imbalance in the neurotransmitter serotonin, leading to the development of SSRI-based antidepressant medications which act to increase levels of this neurotransmitter in the brain. However, recent research has shown that the serotonin theory of depression may be too simplistic to account for the complexities surrounding this disorder. Rather, Major Depressive Disorder (MDD) should be viewed as having multiple causes, and effective treatments should be tailored to the individual person’s unique etiology.
One likely cause of unsuccessful depression treatment is neuroinflammation, which has been linked to MDD in several studies. Neuroinflammation is caused by an excessive amount of inflammatory cytokines being produced in response to psychological stress. These cytokines can modify pathways related to memory, emotion processing, and can disrupt the neural circuitry that regulates mood. Thus, if inflammation is present in the brain, then the current standard treatments, which only focus on increasing serotonin levels, may not be enough to provide relief and depth of clinical response necessary for symptom remission in some cases.
Another potential cause of unsuccessful depression treatment is poor adherence to treatment regimens. Even with the best treatments available, outcomes are often limited when individuals do not follow instructions or complete the course of treatment. This can be due to a variety of reasons, from the stigma associated with mental health disorders, to fear of side effects from the medications, to simply forgetting to take needed (or prescribed) medications.
Finally, there may also be biological explanations for why depression treatments don’t work for some people. DNA sequencing studies have heightened our understanding of the genetic architecture of depression, and recent studies support the notion that certain genetic factors, such as the serotonin transporter gene, may impede the effectiveness of antidepressant treatments. Additionally, the major depressive disorder of certain individuals may be a result of epigenetic influences, meaning that their environment interacts with a person's genes and is impacting the way his/her body functions in regards to depression.
Depression is a complex, multi-factorial disorder, and the explanations for why depression treatments fail are similarly varied. The serotonin theory of depression should no longer be accepted as the sole etiology of MDD, and treatments should be customized to address different factors such as neuroinflammation, non-adherence, genetic and epigenetics. To reach this goal, further research needs to be conducted to uncover additional underlying causes for why depression treatments don’t work for some people.
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