Week 4: Biological Impact Of Major Depressive Disorder

Hi everyone! Welcome back to this week’s blog.

This week, I’ve been reading research papers on the biological impacts of major depressive disorders. Since depression is a complex and multifaceted disease, there isn’t any one factor that impacts the brain. The chemical imbalance theory that states depression is caused by the imbalance of neurotransmitters such as serotonin, promoted by pharmaceutical companies since the early 2000s was denied by the recent meta-analysis essay by University College London (Moncrieff et al., 2022). The study found no correlation between the level of serotonin associated with depression. Furthermore, some cohort groups showed reduced serotonin levels caused by the use of antidepressants.

I found it extremely interesting that research shows major depressive disorder increases activities in the cortical midline structure (CMS). CMS are a group of brain regions that are located along the midline of the cerebral cortex, which is the outer layer of the brain. These regions include the medial prefrontal cortex, anterior cingulate cortex, and posterior cingulate cortex. CMS are involved in various functions, such as self-referential processing, social cognition, emotional regulation, and attentional control. Dysfunction of CMS has been implicated in various neurological and psychiatric disorders, including major depressive disorder. Keskin et al. (2023) utilized advanced brain scan techniques and a complex statistical model, multinomial regression, to discover that heightened global infra-slow brain activity (very slow brain waves that are present across the entire brain) specifically related to the exteroceptive (perception and processing of sensory information that comes from outside the body) and mental self is linked to emotion dysregulation, resulting in greater severity of negative emotions. These findings suggest that targeting the abnormal global signal topography of self could potentially be a promising approach for treating emotion dysregulation in major depressive disorder.

Another meta-analysis essay investigates the kynurenine pathway in major depressive disorders. The kynurenine pathway is a metabolic pathway that breaks down the amino acid tryptophan, which is an essential amino acid that the body cannot produce on its own and must be obtained through diet. The kynurenine pathway is involved in many important biological functions, including the regulation of the immune system and the synthesis of neurotransmitters, which are chemical messengers in the brain. In this pathway, tryptophan is converted into a number of metabolites, including kynurenine, which can then be further metabolized into other compounds. Marx et al. (2021) explore the relationship between the kynurenine pathway and mental disorders. A meta-analysis was conducted on 101 studies that investigated kynurenine metabolites in people with major depressive disorder (MDD), bipolar disorder (BD), or schizophrenia (SZ) compared to controls. The results revealed that tryptophan and kynurenine were decreased in all three disorders. Overall, the findings suggest that there is a shift in tryptophan metabolism from serotonin to the kynurenine pathway in these psychiatric disorders. Furthermore, there is a different pattern between mood disorders and SZ, with a preference for the potentially neurotoxic quinolinic acid over the neuroprotective kynurenic acid in mood disorders, but not in SZ. The results indicate that focusing on the kynurenine pathway may be a hopeful strategy for creating novel therapies for these conditions.I believe this shows the complexity of major depressive disorder by revealing how biological mechanisms may be involved in the progression of the disease.

Next week, I will work on lining up interviews to attempt to talk to experts and researchers in the field. I will also continue research on the correlation between major depressive disorders, epidemiology, and epigenetics.

References: Marx, W., McGuinness, A. J., Rocks, T., Ruusunen, A., Cleminson, J., Walker, A. K., Gomes-Da-Costa, S., Lane, M., Sanches, M., Diaz, A. P., Tseng, P., Lin, P., Berk, M., Clarke, G., O’Neil, A., Jacka, F. N., Stubbs, B., Carvalho, A. F., Quevedo, J., . . . Fernandes, B. S. (2021). The kynurenine pathway in major depressive disorder, bipolar disorder, and schizophrenia: a meta-analysis of 101 studies. Molecular Psychiatry, 26(8), 4158–4178. https://doi.org/10.1038/s41380-020-00951-9

Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. (2022). The serotonin theory of depression: a systematic umbrella review of the evidence. Molecular Psychiatry. https://doi.org/10.1038/s41380-022-01661-0

Keskin, K., Eker, M.Ç., Gönül, A.S. et al. Abnormal global signal topography of self modulates emotion dysregulation in major depressive disorder. Transl Psychiatry 13, 107 (2023). https://doi.org/10.1038/s41398-023-02398-2