Human brain imaging highlights a relationship between excitatory and antioxidant neurochemicals and psychosis
Valerie Sydnor was the lead author on this study. Valerie is a PhD candidate in Ted Satterthwaite’s lab studying how brain plasticity changes throughout neurodevelopment. Valerie aims to uncover how developmental programs contribute to the emergence of youth psychiatric disorders.
or technically,
A meta-analysis of ultra-high field glutamate, glutamine, GABA and glutathione 1HMRS in psychosis: Implications for studies of psychosis risk
[See Original Abstract on Pubmed]
Authors of the study: Valerie Sydnor & David Roalf
PsychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. is a complex and neurodevelopmental brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. disorder that typically presents in adolescence or early adulthood. Characterized by disorganized thought and behavior, low motivation, and the presence of hallucinations or delusions, psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. can have a devastating impact on social, occupational, and daily functioning. It’s also more common than you may think. According to the National Alliance on Mental Illness, approximately 100,000 young people experience psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. each year in the U.S. alone. In addition to affecting basic day-to-day life, episodes of psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. are associated with changes in both brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. structure and brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. function. For example, psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. has been linked with changes in the way neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. are both connected to (structural change) and communicate with (functional change) one another. Interestingly, these structural and functional changes have been found not only in patients with psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning., but also in youth at genetic or clinical risk for developing psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. This finding means that it may be possible to use information about the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. to predict and diagnose psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. as well as to inform psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. treatment strategies, which represents a huge step forward for psychiatry.
So, what exactly are these psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.-related brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. changes? Well, Neuroscience Graduate Group (NGG) student Valerie Sydnor, her co-author Dr. David Roalf, and many others in the field, think that a neurochemical called glutamatethe most abundant excitatory neurotransmitter plays a critical role in psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. Glutamatethe most abundant excitatory neurotransmitter is the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.’s main excitatory neurotransmitterchemicals released by neurons; can have an excitatory or inhibitory effect, meaning it plays a large role in neuronal communication. (It’s present at approximately 80% of synapsesthe site of transmission of electric nerve impulses between two nerve cells (neurons) that form the basis for neuronal communication, which serve as the point of communication between neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles!) Recently, the receptorsReceives an input some stimulus and transmits a the information to other cells or neurons. that bind glutamatethe most abundant excitatory neurotransmitter to enable this neuronal communication have also been shown to bind drugs, like ketamine, that induce a mental state similar to that of acute psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. It is this functional link between glutamatethe most abundant excitatory neurotransmitter receptorsReceives an input some stimulus and transmits a the information to other cells or neurons. and a psychotic-like state that clued Valerie and others into a potential role for glutamatethe most abundant excitatory neurotransmitter in this perplexing disorder. Importantly, in addition to its role in communication throughout the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals., glutamatethe most abundant excitatory neurotransmitter can also influence other neurochemicals, including glutamine (a glutamatethe most abundant excitatory neurotransmitter metabolite), gamma aminobutyric acid (GABA; the main inhibitory neurotransmitterchemicals released by neurons; can have an excitatory or inhibitory effect), and glutathione (an antioxidant that protects the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. from oxidative stressdamage done to the body due to a build-up of unstable oxygen-containing molecules). This means that alterations in brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. glutamatethe most abundant excitatory neurotransmitter levels, which are thought to occur in psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning., may result in changes in any (or all) of these other three neurochemicals. So, in order to get a complete picture of the relationship between glutamatethe most abundant excitatory neurotransmitter and psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning., it’s necessary to systematically investigate an entire group of neurochemicals.
However, if we want to use these neurochemicals to help predict, diagnose, and treat psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning., we need a way to measure them in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. Fortunately, with the development of new technology, we can do just that! Recent advances in ultra-high field MRI technology (think: more than two times stronger than the magnetic field of your average MRI scanner) and proton magnetic resonance spectroscopy (1HMRS) techniques (which enable non-invasive assessment of regional brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. chemistry) allow researchers to more accurately and reliably quantify neurochemical levels in the brainsThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. of humans. With this promising leap in neurochemical-based brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. imaging, there has been an emergence of research applying the technology to psychiatric disorders like psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. To date, nine studies have used ultra-high field 1HRMS to investigate neurochemical concentrations in psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. With the goal of synthesizing results across these studies, Valerie and David conducted a meta-analysis. By leveraging available data and quantitatively summarizing the findings, their work provides insight into whether concentrations of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.'s main neurotransmitterschemicals released by neurons; can have an excitatory or inhibitory effect -- glutamatethe most abundant excitatory neurotransmitter and GABA -- and their associated metabolites are altered in psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning..
So, what did Valerie’s meta-analysis find? After combining data from all individuals who participated in the nine available 1HMRS imaging studies, there were a total of 255 individuals with psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. and 293 healthy participants without psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. Comparing metabolite levels for glutamatethe most abundant excitatory neurotransmitter, GABA, glutathione, and glutamine between these two groups, Valerie found that the concentration of both glutamatethe most abundant excitatory neurotransmitter and glutathione was reliably lower in patients with psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. This finding adds to a growing body of evidence from animal models, post-mortem brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. tissue, and genetic studies suggesting that glutamatethe most abundant excitatory neurotransmitter system dysfunction contributes to psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. It also provides insight into why psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. may emerge during late stages of neurodevelopment, given that these maturational stages are characterized by extensive changes in neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles that communicate using glutamatethe most abundant excitatory neurotransmitter. Valerie’s work paves the way for future research, which could leverage this non-invasive technique to collect longitudinal samples of brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. chemistry in order to better understand the developmental time course of these neurochemical alterations. With these kinds of efforts, it won’t be long until concentrations of neurochemicals, like glutamatethe most abundant excitatory neurotransmitter, can be incorporated into individualized psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. risk calculators, serve as biological predictors of the transition from at-risk for developing psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. to a formal psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. diagnosis, and function as druggable targets for decreasing psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. risk.
So, what exactly are these psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.-related brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. changes? Well, Neuroscience Graduate Group (NGG) student Valerie Sydnor, her co-author Dr. David Roalf, and many others in the field, think that a neurochemical called glutamatethe most abundant excitatory neurotransmitter plays a critical role in psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. Glutamatethe most abundant excitatory neurotransmitter is the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.’s main excitatory neurotransmitterchemicals released by neurons; can have an excitatory or inhibitory effect, meaning it plays a large role in neuronal communication. (It’s present at approximately 80% of synapsesthe site of transmission of electric nerve impulses between two nerve cells (neurons) that form the basis for neuronal communication, which serve as the point of communication between neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles!) Recently, the receptorsReceives an input some stimulus and transmits a the information to other cells or neurons. that bind glutamatethe most abundant excitatory neurotransmitter to enable this neuronal communication have also been shown to bind drugs, like ketamine, that induce a mental state similar to that of acute psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. It is this functional link between glutamatethe most abundant excitatory neurotransmitter receptorsReceives an input some stimulus and transmits a the information to other cells or neurons. and a psychotic-like state that clued Valerie and others into a potential role for glutamatethe most abundant excitatory neurotransmitter in this perplexing disorder. Importantly, in addition to its role in communication throughout the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals., glutamatethe most abundant excitatory neurotransmitter can also influence other neurochemicals, including glutamine (a glutamatethe most abundant excitatory neurotransmitter metabolite), gamma aminobutyric acid (GABA; the main inhibitory neurotransmitterchemicals released by neurons; can have an excitatory or inhibitory effect), and glutathione (an antioxidant that protects the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. from oxidative stressdamage done to the body due to a build-up of unstable oxygen-containing molecules). This means that alterations in brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. glutamatethe most abundant excitatory neurotransmitter levels, which are thought to occur in psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning., may result in changes in any (or all) of these other three neurochemicals. So, in order to get a complete picture of the relationship between glutamatethe most abundant excitatory neurotransmitter and psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning., it’s necessary to systematically investigate an entire group of neurochemicals.
However, if we want to use these neurochemicals to help predict, diagnose, and treat psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning., we need a way to measure them in the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.. Fortunately, with the development of new technology, we can do just that! Recent advances in ultra-high field MRI technology (think: more than two times stronger than the magnetic field of your average MRI scanner) and proton magnetic resonance spectroscopy (1HMRS) techniques (which enable non-invasive assessment of regional brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. chemistry) allow researchers to more accurately and reliably quantify neurochemical levels in the brainsThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. of humans. With this promising leap in neurochemical-based brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. imaging, there has been an emergence of research applying the technology to psychiatric disorders like psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. To date, nine studies have used ultra-high field 1HRMS to investigate neurochemical concentrations in psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. With the goal of synthesizing results across these studies, Valerie and David conducted a meta-analysis. By leveraging available data and quantitatively summarizing the findings, their work provides insight into whether concentrations of the brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals.'s main neurotransmitterschemicals released by neurons; can have an excitatory or inhibitory effect -- glutamatethe most abundant excitatory neurotransmitter and GABA -- and their associated metabolites are altered in psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning..
So, what did Valerie’s meta-analysis find? After combining data from all individuals who participated in the nine available 1HMRS imaging studies, there were a total of 255 individuals with psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. and 293 healthy participants without psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. Comparing metabolite levels for glutamatethe most abundant excitatory neurotransmitter, GABA, glutathione, and glutamine between these two groups, Valerie found that the concentration of both glutamatethe most abundant excitatory neurotransmitter and glutathione was reliably lower in patients with psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. This finding adds to a growing body of evidence from animal models, post-mortem brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. tissue, and genetic studies suggesting that glutamatethe most abundant excitatory neurotransmitter system dysfunction contributes to psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning.. It also provides insight into why psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. may emerge during late stages of neurodevelopment, given that these maturational stages are characterized by extensive changes in neuronsA nerve cell that uses electrical and chemical signals to send information to other cells including other neurons and muscles that communicate using glutamatethe most abundant excitatory neurotransmitter. Valerie’s work paves the way for future research, which could leverage this non-invasive technique to collect longitudinal samples of brainThe brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. chemistry in order to better understand the developmental time course of these neurochemical alterations. With these kinds of efforts, it won’t be long until concentrations of neurochemicals, like glutamatethe most abundant excitatory neurotransmitter, can be incorporated into individualized psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. risk calculators, serve as biological predictors of the transition from at-risk for developing psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. to a formal psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. diagnosis, and function as druggable targets for decreasing psychosisA symptom of mental illness in which the person loses touch with reality and thinks or behaves in bizarre ways. Psychosis is a complex brain disorder that typically presents in adolescence or early adulthood with devastating impacts on social, occupational, and daily functioning. risk.
About the brief writer: Kara McGaughey
Kara is a PhD candidate in Josh Gold’s lab studying how we make decisions in the face of uncertainty and instability. Combining electrophysiology and computational modeling, she’s investigating the neural mechanisms that may underlie this adaptive behavior.