Lower distress intolerance is associated with higher glutathione levels in adolescent cannabis users.

Cannabis (CB) use and psychological stressors increase oxidative stress in the brain. Glutathione (GSH), the most abundant antioxidant in the brain, protects against oxidative stress. Furthermore, distress intolerance, the inability to tolerate psychological or physiological stress is a risk factor for CB use.

Glutamate measurements using edited MRS.

Purpose: To demonstrate J-difference coediting of glutamate using Hadamard encoding and reconstruction of Mescher-Garwood-edited spectroscopy (HERMES).

Methods: Density-matrix simulations of HERMES (TE 80 ms) and 1D J-resolved (TE 31-229 ms) of glutamate (Glu), glutamine (Gln), γ-aminobutyric acid (GABA), and glutathione (GSH) were performed. HERMES comprised four sub-experiments with editing pulses applied as follows: (A) 1.

Examination of gamma-aminobutyric acid and glutamate-glutamine levels in association with impulsive behavior in adolescent marijuana users.

Background: Adolescent marijuana (MJ) use has been associated with alterations in brain structure and function as well as behavior. Examination of neurochemical correlates such as GABA (gamma-aminobutyric acid) and Glx (glutamate + glutamine) in MJ users remains limited. Impulsivity, identified as a risk factor and consequence of MJ use, has been associated with GABA and Glx levels in healthy and clinical populations.

Supplementation with a putative calorie restriction mimetic micronutrient blend increases glutathione concentrations and improves neuroenergetics in brain of healthy middle-aged men and women.

Background: Caloric restriction (CR) without micronutrient deficiency has been shown to increase both lifespan and healthspan. In animals, CR has been demonstrated to increase glutathione (GSH), a neuroprotective antioxidant, in the brain and preserve brain mitochondrial function by altering neuroenergetics. In humans it has been associated with improvements in mood states and cognitive function.

Increased myoinositol in the anterior cingulate cortex of veterans with a history of traumatic brain injury: a proton magnetic resonance spectroscopy study.

Traumatic brain injury (TBI) is one of the most prevalent forms of morbidity in veterans and service members, with mild traumatic brain injury (mTBI) being the most common. The diagnosis of mTBI in veterans is difficult because of mixed etiologies and high comorbidity with other disorders such as posttraumatic stress disorder (PTSD), depression, and substance use. Advanced neuroimaging techniques such as magnetic resonance spectroscopy (MRS) may be useful in identifying neurochemical alterations in TBI, which may aid the development of new targets for therapeutic intervention.

An exploratory proton MRS examination of gamma-aminobutyric acid, glutamate, and glutamine and their relationship to affective aspects of chronic pain.

Veterans experience chronic pain more frequently than civilians. Identification of neurobiological mechanisms underlying the pathophysiology of chronic pain in a veteran population may aid in the development of novel treatment targets. In this pilot proof-of-concept study, veterans with chronic pain (N = 61) and no chronic pain (N = 19) completed clinical interviews, self-report questionnaires inquiring about pain history, interference of pain with daily life, and pain catastrophizing, as well as measures of depressive and anxious symptoms.

Image processing and analysis methods for the Adolescent Brain Cognitive Development Study.

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning.

Intraindividual changes in brain GABA, glutamate, and glutamine during monitored abstinence from alcohol in treatment-naive individuals with alcohol use disorder.

Proton magnetic resonance spectroscopy ( H-MRS) studies have demonstrated abnormal levels of a variety of neurometabolites in treatment-seeking individuals with moderate-severe alcohol use disorder (AUD) following acute withdrawal. In contrast, few studies have investigated neurochemical changes across early abstinence in less severe, treatment-naïve AUD. The present study, which represents the primary report of a research grant from ABMRF/The Alcohol Research Fund, measured dorsal anterior cingulate cortex (dACC) GABA, glutamate, and glutamine levels in treatment-naïve AUD (n = 23) via three H-MRS scans spaced across a planned week of abstinence from alcohol.

Evidence for a unique association between fronto-cortical glycine levels and recent heavy drinking in treatment naïve individuals with alcohol use disorder.

Although the neurotransmitters/modulators glutamate and, more recently, glycine have been implicated in the development and maintenance of Alcohol Use Disorder (AUD) in preclinical research, human proton magnetic resonance spectroscopy (H-MRS) studies have focused solely on the measurement of glutamate. The purpose of the present analysis was to examine the relative associations of brain glutamate and glycine levels with recent heavy drinking in 41 treatment naïve individuals with AUD using H-MRS. The present study is the first that we are aware of to report in vivo brain glycine levels from an investigation of addiction.

Reduced gamma-amino butyric acid (GABA) and glutamine in the anterior cingulate cortex (ACC) of veterans exposed to trauma.

Background: Trauma-related diagnoses such as posttraumatic stress disorder (PTSD) are prevalent in veterans. The identification of mechanisms related to stress vulnerability and development of PTSD specifically in a veteran population may aid in the prevention of PTSD and identification of novel treatment targets.

Methods: Veterans with PTSD (n = 27), trauma-exposed veterans with no PTSD (TEC, n = 18) and non-trauma-exposed controls (NTEC, n = 28) underwent single-voxel proton (H) magnetic resonance spectroscopy (MRS) at 3 Tesla in the dorsal anterior cingulate cortex (dACC) using a two-dimensional (2D) J-resolved point spectroscopy sequence in addition to completing a clinical battery.

Brain Glutamate, GABA, and Glutamine Levels and Associations with Recent Drinking in Treatment-Naïve Individuals with Alcohol Use Disorder Versus Light Drinkers.

Background: Proton magnetic resonance spectroscopy ( H-MRS) studies have demonstrated abnormal levels of a variety of neurometabolites in inpatients/outpatients with alcohol use disorder (AUD) following acute alcohol withdrawal relative to healthy controls. In contrast, few studies have compared neurometabolite levels between less severe, treatment-naïve AUD individuals and light drinkers (LD) or related them to recent alcohol consumption. The present study compared neurometabolite levels between treatment-naïve AUD and LD individuals.

Two-Dimensional Proton Magnetic Resonance Spectroscopy versus J-Editing for GABA Quantification in Human Brain: Insights from a GABA-Aminotransferase Inhibitor Study.

Metabolite-specific, scalar spin-spin coupling constant (J)-editing H MRS methods have become gold-standard for measuring brain γ-amino butyric acid (GABA) levels in human brain. Localized, two-dimensional (2D) H MRS technology offers an attractive alternative as it significantly alleviates the problem of severe metabolite signal overlap associated with standard 1D MRS and retains spectroscopic information for all MRS-detectable species. However, for metabolites found at low concentration, a direct, in vivo, comprehensive methods comparison is challenging and has not been reported to date.

Hippocampal GABA enables inhibitory control over unwanted thoughts.

Intrusive memories, images, and hallucinations are hallmark symptoms of psychiatric disorders. Although often attributed to deficient inhibitory control by the prefrontal cortex, difficulty in controlling intrusive thoughts is also associated with hippocampal hyperactivity, arising from dysfunctional GABAergic interneurons. How hippocampal GABA contributes to stopping unwanted thoughts is unknown.

Relationship of executive functioning deficits to N-acetyl aspartate (NAA) and gamma-aminobutyric acid (GABA) in youth with bipolar disorder.

Background: Although cognitive deficits in bipolar disorder (BD) have been repeatedly observed, our understanding of these impairments at a mechanistic level remains limited. Few studies that investigated cognitive impairments in bipolar illness have examined the association with brain biochemistry. This pilot study utilized proton magnetic resonance spectroscopy (H-MRS) to evaluate the relationship between neurocognitive performance and brain metabolites in youth with BD.

In Vivo Detection of CPP-115 Target Engagement in Human Brain.

CPP-115, a next-generation γ-amino butyric acid (GABA)-aminotransferase (AT) inhibitor, shows comparable pharmacokinetics, improved safety and tolerability, and a more favorable toxicity profile when compared with vigabatrin. The pharmacodynamic characteristics of CPP-115 remain to be evaluated. The present study employed state-of-the-art proton magnetic resonance spectroscopy techniques to measure changes in brain GABA+ (the composite resonance of GABA, homocarnosine, and macromolecules) concentrations in healthy subjects receiving oral daily doses of CPP-115 or placebo.

Associations Between Recent Heavy Drinking and Dorsal Anterior Cingulate N-Acetylaspartate and Glutamate Concentrations in Non-Treatment-Seeking Individuals with Alcohol Dependence.

Background: Proton magnetic resonance spectroscopy ((1) H-MRS) studies have consistently found abnormal brain concentrations of N-acetylaspartate (NAA) and glutamate in individuals with alcohol use disorders (AUD) relative to light drinkers. However, most such studies have focused on individuals in treatment for severe alcohol dependence (AD), and few studies have investigated associations between neurochemical concentrations and recent alcohol consumption. This study focused on associations between recent drinking and prefrontal neurometabolite concentrations in nonsevere, non-treatment-seeking individuals with AUD.

Molecular features assisting in diagnosis, surgery, and treatment decision making in low-grade gliomas.

The preferred management of suspected low-grade gliomas (LGGs) has been disputed, and the implications of molecular changes for medical and surgical management of LGGs are important to consider. Current strategies that make use of molecular markers and imaging techniques and therapeutic considerations offer additional options for management of LGGs. Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes suggest a role for this abnormal metabolic pathway in the pathogenesis and progression of these primary brain tumors.

Anterior cingulate cortex choline levels in female adolescents with unipolar versus bipolar depression: a potential new tool for diagnosis.

Background: Delayed diagnosis in bipolar disorder (BD) due to misdiagnosis as major depressive disorder (MDD) is a significant public health concern. Thus, identification of relevant diagnostic biomarkers is a critical unmet need, particularly early in the course of illness. The anterior cingulate cortex (ACC) is thought to play an important role in mood disorder pathophysiology.

In vivo T(2) relaxation time measurement with echo-time averaging.

The accuracy of metabolite concentrations measured using in vivo proton ((1) H) MRS is enhanced following correction for spin-spin (T2 ) relaxation effects. In addition, metabolite proton T2 relaxation times provide unique information regarding cellular environment and molecular mobility. Echo-time (TE) averaging (1) H MRS involves the collection and averaging of multiple TE steps, which greatly simplifies resulting spectra due to the attenuation of spin-coupled and macromolecule resonances.

Brain gamma-aminobutyric acid (GABA) abnormalities in bipolar disorder.

Objectives: Gamma-aminobutyric acid (GABA) abnormalities have been implicated in bipolar disorder. However, due to discrepant studies measuring postmortem, cerebrospinal fluid, plasma, and in vivo brain levels of GABA, the nature of these abnormalities is unclear. Using proton magnetic resonance spectroscopy, we investigated tissue levels of GABA in the anterior cingulate cortex and parieto-occipital cortex of participants with bipolar disorder and healthy controls.

γ-Amino butyric acid and glutamate abnormalities in adolescent chronic marijuana smokers.

Background: An increasing body of evidence from neuropsychological and neuroimaging studies suggests that exposure to marijuana throughout adolescence disrupts key cortical maturation processes occurring during this developmental phase. GABA-modulating pharmacologic treatments that elevate brain GABA concentration recently have been shown to decrease withdrawal symptoms and improve executive functioning in marijuana-dependent adult subjects. The goal of this study was to investigate whether the lower ACC glutamate previously reported in adolescent chronic marijuana smokers is associated with lower ACC GABA levels.