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What Causes Depression? Is it Genetic?

Depression, a complex illness, is influenced by various factors. While scientists have long suspected a genetic component in depression, uncovering the specific links has proven challenging. However, a groundbreaking study published in the journal Nature Genetics in 2018 shed light on this matter. The research revealed 44 genetic risk factors for depression, with approximately 30 of them being previously unknown. This discovery opens up possibilities for understanding how these genetic variants impact the prevention and treatment of depression in the future. New research linking genes and depression


In this study, a global consortium of over 200 scientists conducted a meta-analysis. They meticulously examined the DNA of more than 135,000 individuals suffering from depression and compared it to the DNA of nearly 350,000 individuals in good mental health. Through this extensive analysis, the researchers identified 44 gene variants that appear to contribute to an increased susceptibility to depression. Prior to this study, only around twelve genetic variants had been associated with the risk of developing depression. These genetic variants, known as SNPs, play a significant role in our understanding of depression and its underlying genetic mechanisms.


The difficulty of treating depression


Depression poses a significant challenge in terms of treatment, often arising from a combination of socioeconomic factors, trauma, relationship dynamics, family history, physical illness, and biochemistry. The recent study carries substantial importance as it has the potential to shed light on why approximately 50% of individuals with depression do not respond to standard treatment approaches. By delving into the genetic foundations of depression, we can gain insights into the varying responses people exhibit towards commonly prescribed antidepressant medications like selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs).

Notably, the study uncovered several genetic variants that are closely associated with the mechanisms by which current antidepressants operate. For example, certain gene variants impact neurotransmitters such as dopamine (DRD2), the excitatory neurotransmitter glutamate (GRIK5 and GRM5), and adrenaline. Interestingly, some of these genetic variants have no apparent connection to neurotransmitters, which may help elucidate the reasons behind the ineffectiveness of existing depression treatments for numerous individuals. With around 30 additional genetic avenues to explore, thanks to this research, scientists now have the potential to develop personalized medications tailored to an individual's specific genome, offering unique treatment options for patients.


Depression and genetics


In the study, various genes linked to depression were found to be associated with specific functions. For instance, the gene LRFN5 was identified as being involved in neuron development and brain inflammation, while OLFM4 and NEGR1 were associated with weight and body size. Additionally, genes responsible for regulating the immune system were found to play a role in the risk of developing depression.

These functional genes have a notable impact on the prefrontal and anterior cingulate cortex, regions of the brain that contribute to executive function, emotional regulation, and decision-making processes. Moreover, the study also explored the involvement of DNA methylation, a crucial process for regulating gene expression. Several of the identified genes were found to influence this fundamental process, highlighting its significance in understanding the genetic mechanisms underlying depression.


What’s next for genetics and depression?


Although it would have been convenient to discover a single genetic variant with a significant impact on the risk of depression, the research revealed that each genetic mutation contributes only marginally to an individual's susceptibility. This implies that while many of us may carry one or more of the genetic variants identified in this study, these variations do not inherently create the same level of risk for developing depression. Instead, the occurrence of depression is largely influenced by our phenotype, which is shaped by environmental, lifestyle, and dietary factors.

The positive aspect of identifying genetic risk factors for depression lies in the potential to develop targeted nutrigenomic strategies. These strategies can aim to decrease or increase the expression of specific genes based on their perceived role in the condition. By doing so, we can enhance our resilience and mitigate the impact of life experiences that might otherwise collaborate with our genetic predispositions to trigger depressive symptoms. This offers promising avenues for interventions that can empower individuals in navigating potential challenges related to depression.


Can nutrition be used as a therapy for depression?


In the near future, the approach to treating and preventing depression could involve an assessment of an individual's genome alongside considering the influences of lifestyle, diet, and environment on their phenotype. By combining these factors, physicians can recommend personalized interventions that target specific aspects related to depression, such as abnormal protein synthesis, inflammation, immune dysfunction, impaired synaptic signaling, and neuronal underdevelopment.

Natural products like curcumin have exhibited the ability to modulate the expression of specific genes associated with cognitive function and mood, offering potential benefits in alleviating depression symptoms. Additionally, omega-3 fatty acids, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have shown promise in reducing brain tissue inflammation and supporting proper brain development. Some studies have even found them to be beneficial in managing depression symptoms.

It's worth noting that while there may be claims about 5-HTP being a good supplement for depression, there are differing opinions on its efficacy. For more information, refer to John's post on natural methods to enhance serotonin, where this topic is further explored.


Conclusion

The field of nutrigenomics holds great potential in addressing abnormal inflammatory pathways, immune activity, cell signaling, and neuronal development and proliferation in individuals who possess genetic variants that heighten their susceptibility to depression. Although the practical application of this approach is yet to be fully explored, there is already evidence linking our dietary choices and activity levels to our mood and the risk of depression. It is crucial for individuals experiencing depression symptoms to seek proper medical advice and treatment. While natural interventions can be beneficial, they should complement, rather than replace, appropriate medical care, and be utilized under the guidance of qualified healthcare professionals.



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