authors Smita Sahay
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date 12/2/2024
title The power struggle in our brain: Energy imbalance in mental health

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# The power struggle in our brain: Energy imbalance in mental health

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Imagine your brain as a city, powered by a fuel called ATP, which keeps its systems active and balanced.

ATP is mainly created through the breakdown of food, supplying energy to all cells in the body. When this energy is not made or managed correctly in the brain, cells fail to function properly, much like a city losing power and slowing down.

The goal of my research is to investigate how ATP disruptions contribute to mental health disorders such as schizophrenia, major depressive disorder, and suicide risk.

A central player in keeping the brain powered is the purinergic system, which oversees ATP formation, movement, and breakdown. This system is efficient, using special proteins to move ATP smoothly through the brain’s cells to where it’s needed. In mental health conditions like schizophrenia, major depressive disorder, and suicide, however, this carefully controlled flow is not the same. We now know that certain parts of the purinergic system have glitches in these mental health disorders, causing energy imbalances.

Our research focuses on the brain’s frontal lobe — much like a city’s central district, responsible for regulating emotions and complex decision-making. In schizophrenia, major depressive disorder, and in those who have died by suicide, the purinergic system’s usual patterns in this central district break down, leading to a loss of usual ATP movement. Normally, proteins within this system make sure ATP does its job in maintaining stability. But in the case of mental illnesses, it’s as though some city workers are skipping tasks, leaving cells without proper energy and resulting in assorted problems in this area of the brain. This compromised activity partly explains why people with these conditions may experience delusions, persistent sadness, and, in severe cases, suicidal thoughts.

An important part of our research is studying purinergic receptors, which are proteins that direct how ATP and its breakdown products interact with cells during stress responses. In schizophrenia, these receptors in the brain act like faulty signal lights in a city, becoming either unresponsive or overactive, leading to impulsive behaviors, hallucinations, or mood swings. For people with major depressive disorder and those who die by suicide, we noticed similar receptor disruptions but with slightly different effects. These broken signals influence feelings of hopelessness or a loss of joy.

Problems with these purinergic receptors over time change the way the brain responds to stress.

Another discovery shows that when ATP is not broken down correctly, the frontal lobe of the brain may become overwhelmed. This imbalance may worsen emotional instability or the feeling of being trapped in negative thought cycles. This is akin to a city-wide traffic jam in which one area’s overload slows down the entire system. These findings suggest that an out-of-balance purinergic system does not just contribute to mental illnesses but may amplify them, creating feedback loops of low energy and high stress that affect the entire brain.

Adding to these discoveries, we found important differences in how the purinergic system functions in females versus males. While these differences in brain function are often understudied in mental health research, our work reveals distinct variations in the presence of purinergic proteins and receptors between females and males. Biological differences shape how each brain responds to stress, processes emotions, and makes decisions. These patterns in the purinergic system help explain why females and males may exhibit different symptoms despite having the same mental health disorder. This discovery brings us closer to developing more targeted treatments tailored to each sex.

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- J.D. Watson
- F. H. C. Crick

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Medical Research Council Unit for the Study of the Molecular Structure of Biological Systems, Cavendish Laboratory, Cambridge.

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