Biomarkers in Major Depressive Disorder – 1

Majör Depresif Bozuklukta Biyobelirteçler - 1

Major Depressive Disorder is a psychiatric disorder in which the depressive effects are observed the most. In depression, deteriorations are seen in brain functions such as, cognition, concentration, attention, motivation, mood regulation. Following the deteriorations in the cognition, a general decline is observed in the quality of life of the individuals, including their living, physical, psychological and social spaces.

Considering the time elapsed in the treatment administered, as well as the side effects, risk of suicide, and the financial burden on the patient and health system, the clinical and research field bears the ethical responsibility for researching the pathophysiology of major depressive disorder in terms of brain functions. Biological markers are being researched both for measuring the effectiveness of the treatments administered in major depressive disorder (pharmacotherapy, psychotherapy, brain stimulation treatments), and for predicting the responses to be given to the treatments administered.

What are Biological Markers (Biomarkers)?

“Biomarker” is defined as a trait, which can be an indicator of the pharmacologic answer for biological processes, pathological processes, or for a therapeutic process, and which can be objectively measured and evaluated (2001).

How are Biomarkers Obtained in Major Depressive Disorder?

Being utilized in many studies which are challenging to conduct on humans in many fields, animal models have an important position in the detection and testing of new treatment instruments (Başar, 2005). Depression models, which include various brain regions, are set forth by using various neuroimaging techniques (fMRI, EEG, PET, SPECT, NIRS, MEG), with the help of biomarkers that are effective in diagnosing depression and in predicting the response to treatment in advance.

For instance, in the animal depression model created in the field of Major Depressive Disorder, it was shown that the participation of the mood-regulating circuit, such as the frontal regions of the brain and limbic regions in particular, can be extremely important for synaptic plasticity, antidepressant effect, memory function, and resistance to treatment (the Fronto-Limbic model). In this model, the mood-regulating circuit of the brain consists of dorsolateral-prefrontal cortex (DLPFC) which is activated in the executive functions of the brain (attention, concentration, etc.); anterior cingulate cortex (ACC) which takes part in the reactions against negative stimulants, as well as amygdala and hippocampus which play a part in emotional memory. Besides the fronto-limbic model, thanks to the fMRI imaging technique, a neural network model was created which works in the brain’s resting state (Default Mode Network), and this model was found to be correlated with recurring negative thoughts about the self, which create the psychodynamic of depression. Parietal regions were also seen to be playing an active part, in addition to the fronto-limbic model, along with the brain regions that are effective in the Default Mode Network.

There are advantages and disadvantages that each neuroimaging technique offers for the research (temporal analysis, spatial analysis, time of measurement, cost, effects of radiation, etc.) Even though the research made regarding the biomarkers of depression could yield different results due to the differences in the imaging techniques and methodological diversity, some compilations of studies in this field offer corresponding results in the diagnosis of depression and the prediction of the response to treatment, based on some brain regions and brain activities. You may have a look at those findings in the next installment of the article.

Başar, K., & Ertuğrul, A. (2005). Depresyon araştırmalarında kullanılan hayvan modelleri. Klinik Psikiyatri Dergisi, 8(3), 123-134.
– Biomarkers Definitions Working Group, Atkinson Jr, A. J., Colburn, W. A., DeGruttola, V. G., DeMets, D. L., Downing, G. J., … & Zeger, S. L. (2001). Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clinical pharmacology & therapeutics, 69(3), 89-95.
– Lai, C. H. (2021). Fronto-limbic neuroimaging biomarkers for diagnosis and prediction of treatment responses in major depressive disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 107, 110234.