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Biomarkers for Psychiatric Disorders

1.1 Introduction

In general, psychiatric disorders are health illnesses characterised by changes in behaviour, emotion, or thinking that are associated with difficult social functioning. DSM-5 sets criteria for diagnosing distinct types of Psychiatric Disorders. However, each ailment is a heterogeneous entity, making proper diagnosis difficult, especially when symptoms overlap. For example, 30% of bipolar disorder (BD) patients may be originally diagnosed with major depression disorder (MDD) in depressive phases or schizophrenia (SCZ) in manic episodes. Furthermore, substantial concern remains about false positive diagnoses due to the subjective nature of clinical criteria previously utilised by physicians. As a result, identifying disease-specific biomarkers is critical and would provide a far more reliable and accurate technique in disease detection, facilitating patient management.

Biomarkers are one field of biological psychiatry research that could address and potentially solve these issues. Central biomarkers in the brain, as well as peripheral biomarkers such as proteins in blood, plasma, and tissue, are biological signatures that have helped us understand the causes and pathophysiology of psychiatric diseases. Identifying biomarkers not only in the CNS but also in other physiological systems with which it interacts may lead to more precise diagnosis and more effective treatments that target faulty pathways in these disorders. It also has the ability to forecast and prevent them in a patient-specific manner. 

However, it would rely on how biological, psychological, and social factors interact to impact biomarker effects on the brain and mind. Biomarkers bring ethical and social concerns, which must be addressed alongside their therapeutic and preventive potential.


1.2 What are Biomarkers?

In order to standardise the word "biomarker," the Food and Drug Administration (FDA) and the NIH Joint Leadership Council formed the FDA-NIH Biomarker Working Group in 2016. This group shortened the concept of a biomarker to "a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention". Furthermore, to assure its clinical utility, a suitable biomarker should be assessed with high reproducibility, exhibit a significant signal-to-noise ratio, and, most crucially, meet the criterion of being modified in a dynamic and reliable manner as the clinical condition progresses. In addition, a biomarker should be accessible for its detection and measurement, as would be the case of a plasmatic parameter or a genetic marker, or being detected by histological or image/neuroimaging techniques 


2.1 Types of Biomarkers in Clinical Practice


Fig 1: Types of Biomarkers





  1. Diagnostic Biomarker

It includes a range of biomarkers that are employed in the detection or confirmation of a disease or other medical condition. It is possible to identify illness subgroups using this kind of biomarker. The dawn of the precision medicine era highlights the value of diagnostic biomarkers in both redefining disease classification and helping to identify people who have a given condition. Therefore, diagnostic biomarkers would enhance personalised treatment by raising the therapeutic response's efficacy. 


  1. Monitoring Biomarker

This category covers biomarkers that are examined periodically to track the progression of a disease or other medical condition as well as biomarkers of an intervention's effect, such as exposure to a drug or environmental toxin. Variations in the values of biomarkers are regarded as assessments of the pharmaceutical response and other forms of clinical interventions, as well as signs of how the clinical state is progressing. 

  1. Pharmacodynamic or Response Biomarker

A pharmacodynamic biomarker is modified in response to a medical condition or clinical intervention, including drug treatments. It is often regarded as a monitoring biomarker due to the serial nature of its measurement. Its primary use is to direct clinical care by offering vital information for making treatment continuation decisions. Furthermore, it is particularly valuable in the early stages of therapeutic drug development, as it can help direct dose-response studies and provide evidence that a medicine causes pharmacodynamic changes in humans that are associated with its clinical benefit. 

  1. Predictive Biomarker

When a marker's existence or alteration makes it possible to identify the patient or group of patients who are most likely to have a particular outcome after being exposed to a medical product or environmental contaminant, the marker is referred to as a predictive biomarker. This outcome could be a beneficial symptom, a rise in survival rates, or a negative incident. Randomised controlled clinical trials of novel medicines often employ these biomarkers. 

  1. Prognostic Biomarker

This biomarker is frequently used to determine the likelihood that a patient with an illness or other medical condition would experience a clinical event. These occurrences include passing away, a sickness developing or returning, or a new medical issue emerging. Prognostic biomarkers are used in clinical trials to identify groups at higher risk by identifying people who are more likely to experience a clinical event or the progression of their condition.

  1. Susceptibility or Risk Biomarker

It is employed as a risk assessment tool for illnesses or medical conditions. In order to construct preventative strategies in clinical practice, susceptibility/risk biomarkers are crucial for the development of epidemiological studies intended to evaluate the risk of getting a disease.


2.2 Biomarkers in Diagnosis and Treatment


Fig 2: Biomarkers in different psychiatric disorders




Neuroimaging techniques, such as structural and functional scans, can identify important biomarkers for psychiatric disorders, aiding in accurate diagnosis and personalised treatment. For example, diffusion tensor imaging (DTI) can distinguish Bipolar I disorder from major depression by highlighting different abnormalities in white matter tracts. This distinction is crucial since antidepressants can worsen bipolar disorder, which is better treated with lithium.

Neuroimaging can also differentiate anxiety from depression by showing varying metabolic activity in brain regions like the amygdala and ventral tegmental area. This helps tailor treatments more effectively. Additionally, biomarkers can guide therapy for major depressive disorder (MDD), indicating whether a patient will respond better to cognitive behavioural therapy (CBT) or medication.

Studies show that hypometabolism in the insula suggests a good response to CBT but a poor response to SSRIs, while hypermetabolism predicts the opposite. These insights help address treatment resistance in depression. For schizophrenia, imaging can reveal different activity patterns in brain circuits, aiding in the selection of appropriate antipsychotic treatments. Overall, biomarker-guided therapies can improve symptom management and reduce harmful side effects.


2.3 Social Issues

Screening adolescents for major depressive disorder (MDD) using genetic and other biomarkers in primary care settings can help prevent or lessen its impact. However, implementing such programs worldwide may face challenges due to cost and sustainability, especially in lower-income countries. Unequal access to preventive interventions could lead to disparities in mental health care. Biomarker information may also impact how individuals, including parents and educators, perceive and interact with children, potentially affecting their development and opportunities. Additionally, biomarkers could contribute to stigma and discrimination if not managed ethically, highlighting the need for legal protections and ethical considerations in using such information.


3.1 Conclusion

The development of biomarkers for psychiatric disorders holds promise for improving diagnosis, treatment, and prevention strategies. However, challenges such as heterogeneity and ethical considerations must be addressed for their effective and equitable use in clinical practice.


References:

  1. Glannon, W. (2022, October). Biomarkers in psychiatric disorders. Cambridge quarterly of healthcare ethics : CQ : the international journal of healthcare ethics committees. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9672933/ 

  2. García-Gutiérrez, M. S., Navarrete, F., Sala, F., Gasparyan, A., Austrich-Olivares, A., & Manzanares, J. (2020, May 15). Biomarkers in psychiatry: Concept, definition, types and relevance to the clinical reality. Frontiers in psychiatry. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243207/ 

  3. Author links open overlay panelJemmyson Romário de Jesus a, a, b, c, AbstractPsychiatric disorders represent a significant socioeconomic and healthcare burden worldwide. Of these, Jesus, J. R. de, Rook, L., Scassellati, C., Enokida, T., Leucht, S., Miller, B. J., Wang, W. Y., Johnson, S. L., Ali, M., Scaini, G., Isgren, A., Gama, C. S., Huang, T. L., Fulton, S., … Du, Y. (2023, September 26). Biomarkers in psychiatric disorders. Advances in Clinical Chemistry. https://www.sciencedirect.com/science/article/abs/pii/S0065242323000501?via%3Dihub 

  4. Candidate biomarkers in psychiatric disorders: State of the ... Candidate biomarkers in psychiatric disorders: state of the field. (2023, May 9). https://onlinelibrary.wiley.com/doi/full/10.1002/wps.21078 

  5. Waszkiewicz, N. (2020, July 25). Mentally sick or not-(bio)markers of psychiatric disorders needed. MDPI. https://www.mdpi.com/2077-0383/9/8/2375 



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