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The Power of Personalisation: The Role of Metabolic Profiling in Precision Medicine for Mental Illnesses

For centuries, mental health care has been primarily based on talk therapy and pharmaceuticals designed to correct perceived chemical imbalances in the brain. However, recent advances in biotechnology and neuroscience have resulted in the emergence of a new psychiatric research paradigm known as Metabolic Psychiatry. This interdisciplinary field combines principles from metabolomics, which is the large-scale analysis of small molecule metabolites in biological systems, with those from psychiatry, neurology, and other fields such as genetics and immunology. Metabolic researchers hope to gain insights into the underlying causes of various mental health disorders by analysing the chemical reactions that occur inside cells and how they relate to physiological functions. In this article, we will look at some of the key benefits of Metabolic Psychiatry, such as its role in understanding disease mechanisms, identifying new drug targets, providing personalised treatment options, and expanding our understanding of the relationships between nutrition, gut bacteria, and cognition.

Understanding Disease Mechanisms

Metabolic Psychiatry makes a significant contribution by shedding light on the molecular events that lead to mental health disorders. Traditionally, psychiatric research has concentrated on the activity of proteins, particularly those involved in neural communication like serotonin, dopamine, and norepinephrine. While this line of inquiry has yielded valuable discoveries, it falls short of capturing the full complexity of cellular physiology, which includes a wide range of other biochemical processes. Metabolic Psychiatry, on the other hand, emphasises the role of metabolism – the set of chemical transformations that cells use to convert nutrients into energy and building blocks needed for growth, maintenance, and reproduction – in shaping both normal and abnormal brain function.

Increasing evidence suggests that disruptions in metabolic homeostasis, whether inherited or acquired during life, can cause the emergence of psychiatric symptoms. For example, studies have found abnormalities in metabolic pathways involving lipid biosynthesis, mitochondrial respiration, and glucose utilisation in patients with depression, schizophrenia, and autism spectrum disorder. Some examples include reduced expression of genes encoding lipogenic enzymes, such as fatty acid synthase (FAS) and stearoyl-CoA desaturase (SCD), in postmortem brains from depressed people, impaired oxidative phosphorylation in lymphocytes isolated from schizophrenia patients, and elevated plasma levels of kynurenine, a tryptophan derivative linked to inflammation and stress responses, in children with autistic traits. By comprehensively characterising these metabolic perturbations, scientists can gain a better understanding of how they contribute to disease aetiology and progression, potentially guiding the development of effective interventions.

Furthermore, metabolic analyses may reveal previously unknown relationships between seemingly disparate phenotypes, thereby expanding our understanding of psychiatric disorders. For example, a 2019 systematic review found that people with bipolar disorder frequently experience hyperglycemia, hypoglycemia, and insulin resistance at the same time, implying a link between mood instability and carbohydrate metabolism. Similarly, a longitudinal study of adolescents with attention deficit/hyperactivity disorder (ADHD) discovered that higher urinary excretions of trimethylamine N-oxide (TMAO), a compound produced by bacterial carnitine degradation in the gut, predicted poorer academic performance later in life, regardless of ADHD symptoms. As these examples demonstrate, metabolic measures provide complementary perspectives on psychological disorders, allowing metabolic psychiatry clinicians to take a more comprehensive approach to managing patients’ overall health.

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