Increased, depression

• Depression usually manifests initially with physical symptoms, such as physical fatigue and sleep disturbances. A depressed mood may also be present. Therapy, in combination with pharmacological treatment, has positive effects when used together, more so than when they are used in isolation. (RE Rakel., 1999); Depression can affect not only one’s own health, but also relationships and cognitive performance, such as learning. As demonstrated, there is significant relevance surrounding depression, since data show a mortality risk higher than that associated with smoking. The lifetime incidence of a depressive episode is 17% in the United States and 13% in Europe. The analysis and interpretation of these data indicate that there is a need for, and relevance of, research addressing this disease (Bitsika et al., 2010; Mykletun et al., 2009; Alonso et al., 2004; Kessier et al., 1994)  Depression is common; however, it is serious. It is characterized by a depressed mood, loss of interest in activities previously performed by the individual, an abnormal reduction in energy, and a considerable increase in the risk of suicide. (Malhi e Mann, 2018). According to the DSM-5 classification, there are other types of depression, which include: persistent depressive disorder (previously called dysthymia); disruptive mood dysregulation disorder; premenstrual dysphoric disorder; substance/medication-induced depressive disorder; depressive disorder due to another medical condition; and unspecified depressive disorder (Bains et al., 2023). 

• The causes that lead to the development of depression are multifactorial, involving genetic factors as well as environmental factors that influence the onset of this mental disorder. First-degree relatives of individuals with depression have a threefold higher probability of developing the disorder compared to the general population. It is important to note that depression can also affect individuals without a family history of the disease. In addition to genetic factors, there are other factors that may trigger depression, particularly biological ones. These include neurodegenerative diseases, especially Alzheimer’s and Parkinson’s disease; stroke; multiple sclerosis; seizure disorders; cancer; macular degeneration; and chronic pain, all of which are also associated with depression (Chand et al., 2023; Pham et al., 2019; Namkung et al., 2019). 

• The pathophysiology related to depressive disorder is associated with evidence of a neurochemical imbalance among the neurotransmitters serotonin (5-HT), norepinephrine (NE), dopamine (DA), and glutamate, as well as Brain-Derived Neurotrophic Factor (BDNF) (Chand et al., 2023) 

Depression can be measured or detected through assessments conducted with standardized interviews and specific scoring, as well as through biological markers and brain imaging. Depression can be detected, classified, and also measured through specific questionnaires standardized by the DSM-5, such as the Hamilton Depression Rating Scale (HAM-D), Beck Depression Inventory (BDI), and Patient Health Questionnaire-9 (PHQ-9). Molecular biomarkers are also excellent tools that may assist in detecting depression, such as alterations in serotonin, dopamine, and norepinephrine levels; dysfunction of the HPA axis (cortisol measurement); and measurement of brain-derived neurotrophic factor (BDNF) (Stockings et al., 2015; Costa et al., 2016; Boby et al., 2025., Malik et al., 2021)

The increase in depression shows high applicability in mammals, particularly in humans and rodents. Its relevance to other vertebrates is also considerable and biologically plausible (Crawley et al., 2022; Houk et al., 2025). 

The increase in depression is associated with high suicide rates and a significant socioeconomic impact. 

• Kessler, R.C., McGonagle, K.A., Zhao, S., et al. (1994), Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: Results from the National Comorbidity Survey, Archives of General Psychiatry, 51(1): 8-19, http://dx.doi.org/10.1001/archpsyc.1994.03950010008002.

• Alonso, J., Angermeyer, M.C., Bernert, S., Bruffaerts, R., Brugha, T.S., Bryson, H. et al. (2004), Prevalence of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project, Acta Psychiatrica Scandinavica. Supplementum, 109(420): 21-27, http://dx.doi.org/10.1111/j.1600-0047.2004.00327.x.

• Mykletun, A., Bjerkeset, O., Øverland, S., Prince, M., Dewey, M., Stewart, R. (2009), Levels of anxiety and depression as predictors of mortality: the HUNT study, British Journal of Psychiatry, 195: 118-125, http://dx.doi.org/10.1192/bjp.bp.108.054866.

• Sharpley, C.F. & Bitsika, V. (2010), Joining the dots: neurobiological links in a functional analysis of depression, Behavioral and Brain Functions, 6: 73, http://dx.doi.org/10.1186/1744-9081-6-73

• Rakel, R.E. (1999), Depression, Primary Care: Clinics in Office Practice, 26(2): 211-224, http://dx.doi.org/10.1016/S0095-4543(08)70003-4 

• Malhi, G.S. & Mann, J.J. (2018), Depression, The Lancet, 392(10161): 2299-2312, http://dx.doi.org/10.1016/S0140-6736(18)31948-2 

• American Psychiatric Association (2013), Diagnostic and Statistical Manual of Mental Disorders: DSM-5, 5th ed., American Psychiatric Publishing, Washington, DC

• Bains, N. and S. Abdijadid (2023), Major Depressive Disorder, in StatPearls [Internet], StatPearls Publishing, Treasure Island (FL). Disponível em: https://www.ncbi.nlm.nih.gov/books/NBK559078/ 

• Chand, S.P. and H. Arif (2023), Depression, in StatPearls [Internet], StatPearls Publishing, Treasure Island (FL). Disponível em: https://www.ncbi.nlm.nih.gov/books/NBK430847/ 

• Kennis, M.; Gerritsen, L.; van Dalen, M.; Williams, A.; Cuijpers, P.; Bockting, C. (2015). Prospective biomarkers of major depressive disorder: A systematic review and meta-analysis. Molecular Psychiatry. Disponível em: https://pubmed.ncbi.nlm.nih.gov/25553406/ 

• Lopresti, A. L.; Hood, S. D.; Drummond, P. D. (2016). A review of peripheral biomarkers in major depression: The potential of inflammatory and neurotrophic markers. Progress in Neuro-Psychopharmacology & Biological Psychiatry. Disponível em: https://pubmed.ncbi.nlm.nih.gov/27304758/ 

• (Autores do artigo ScienceDirect). (2024). Depression diagnosis: EEG-based cognitive biomarkers and machine learning. Neuroscience & Biobehavioral Reviews. Disponível em: https://www.sciencedirect.com/science/article/abs/pii/S0166432824004819 

• Gadad, B. S.; Jha, M. K.; Czysz, A. H.; et al. (2021). Biomarkers of Major Depressive Disorder: Knowing is Half the Battle. International Journal of Molecular Sciences. Disponível em: https://pubmed.ncbi.nlm.nih.gov/33508785/ 

• Houk, J.; et al. From rodents to humans: conserved codistribution of dopaminergic with serotonergic neurons in the dorsal raphe nucleus. ScienceDirect, 2025. Disponível em: https://www.sciencedirect.com/science/article/pii/S0969996125003900 

• Crawley, J. N.; et al. Introducing a depression-like syndrome for translational neuropsychiatry: a plea for taxonomical validity and improved comparability between humans and mice. Molecular Psychiatry, 2022. Disponível em: https://www.nature.com/articles/s41380-022-01762-w