IMPORTANCEThe use of high-field magnetic resonance spectroscopy (MRS) in multiple brain regions of a large population of human participants facilitates in vivo study of localized or diffusely altered brain metabolites in patients with first-episode psychosis (FEP) compared to healthy participants. OBJECTIVE To compare metabolite levels in 5 brain regions between patients with FEP (evaluated within 2 years of onset) and healthy controls, and to explore possible associations between targeted metabolite levels and neuropsychological test performance.DESIGN, SETTING, AND PARTICIPANTS Cross-sectional design used 7-T MRS at a research MR imaging facility in participants recruited from clinics at the Johns Hopkins Schizophrenia Center and the local population. Eighty-one patients who had received a DSM-IV diagnosis of FEP within the last 2 years and 91 healthy age-matched (but not sex-matched) volunteers participated.MAIN OUTCOMES AND MEASURES Brain metabolite levels including glutamate, glutamine, γ-aminobutyric acid (GABA), N-acetylaspartate, N-acetylaspartyl glutamate, and glutathione, as well as performance on neuropsychological tests. RESULTSThe mean (SD) age of 81 patients with FEP was 22.3 (4.4) years and 57 were male, while the mean (SD) age of 91 healthy participants was 23.3 (3.9) years and 42 were male. Compared with healthy participants, patients with FEP had lower levels of glutamate (F 1,162 = 8.63, P = .02), N-acetylaspartate (F 1,161 = 5.93, P = .03), GABA (F 1,163 = 6.38, P = .03), and glutathione (F 1,162 = 4.79, P = .04) in the anterior cingulate (all P values are corrected for multiple comparisons); lower levels of N-acetylaspartate in the orbitofrontal region (F 1,136 = 7.23, P = .05) and thalamus (F 1,133 = 6.78, P = .03); and lower levels of glutathione in the thalamus (F 1,135 = 7.57, P = .03). Among patients with FEP, N-acetylaspartate levels in the centrum semiovale white matter were significantly correlated with performance on neuropsychological tests, including processing speed (r = 0.48; P < .001), visual (r = 0.33; P = .04) and working (r = 0.38; P = .01) memory, and overall cognitive performance (r = 0.38; P = .01).CONCLUSIONS AND RELEVANCE Seven-tesla MRS offers insights into biochemical changes associated with FEP and may be a useful tool for probing brain metabolism that ranges from neurotransmission to stress-associated pathways in participants with psychosis.

IMPORTANCE Prenatal maternal stress is increasingly associated with adverse outcomes in pregnant women and their offspring. However, the association between maternal stress and human fetal brain growth and metabolism is unknown. OBJECTIVE To identify the association between prenatal maternal psychological distress and fetal brain growth, cortical maturation, and biochemical development using advanced 3-dimensional volumetric magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS).

Various lines of evidence suggest that brain bioenergetics and mitochondrial function may be altered in schizophrenia. On the basis of prior phosphorus-31 (31P)-magnetic resonance spectroscopy (MRS), post-mortem and preclinical studies, this study was designed to test the hypothesis that abnormal glycolysis leads to elevated lactate concentrations in subjects with schizophrenia. The high sensitivity of 7 Tesla proton (1H)-MRS was used to measure brain lactate levels in vivo. Twenty-nine controls and 27 participants with schizophrenia completed the study. MRS scanning was conducted on a Philips ‘Achieva' 7T scanner, and spectra were acquired from a voxel in the anterior cingulate cortex. Patients were assessed for psychiatric symptom severity, and all participants completed the MATRICS Consensus Cognitive Battery (MCCB) and University of California, San Diego Performance-Based Skills Assessment (UPSA). The relationship between lactate, psychiatric symptom severity, MCCB and UPSA was examined. Lactate was significantly higher in patients compared with controls (P=0.013). Higher lactate was associated with lower MCCB (r=−0.36, P=0.01) and UPSA total scores (r=−0.43, P=0.001). We believe this is the first study to report elevated in vivo cerebral lactate levels in schizophrenia. Elevated lactate levels in schizophrenia may reflect increased anaerobic glycolysis possibly because of mitochondrial dysfunction. This study also suggests that altered cerebral bioenergetics contribute to cognitive and functional impairments in schizophrenia.

Purpose In proton MR spectra of the human brain, relatively broad macromolecule (MM) resonances underlie the narrower signals from metabolites. The purpose of this study was to quantify the MM profile in healthy human brain at 3T and 7T, both in gray matter (anterior cingulate cortex (ACC)) and white matter (centrum semiovale (CSO)). Methods A water-suppressed, inversion-recovery pulse sequence was used to null metabolite signals and acquire MM spectra in 20 healthy volunteers using very similar methodology at both field strengths (n=5 per region and field). The MM spectra were fitted with multiple Gaussian functions, and quantified relative to the unsuppressed water signal from the same volume. Results MM proton concentration values were in the range of 5 to 20 mmol/kg. No significant differences were found between the MM proton concentration measurements by region (p ≈ 0.8), nor by field strength (p ≈ 0.5). Linewidths of the well-resolved M1 peak were slightly more than double at 7T (43.0 ± 4.7 Hz in the ACC, 45.6 ± 4.1 Hz in the CSO) compared to 3T (19.8 ± 3.5 Hz in the ACC, 20.0 ± 4.3 Hz in the CSO). Conclusion The absence of differences in MM concentrations between white and gray matter implies that a single MM ‘baseline’ may be adequate for spectral fitting of multiple brain regions when determining metabolite concentrations. Visibility of MM signals is similar at 3 and 7T.

Purpose The purpose of this study was to compare magnetic resonance spectroscopy (MRS) of three different regions of the human brain between 3 and 7 Tesla, using the same subjects and closely matched methodology at both field strengths. Methods A semi-LASER (sLASER) pulse sequence with TE 32 ms was used to acquire metabolite spectrum along with the water reference at 3T and 7T using similar experimental parameters and hardware at both field strengths (n=4 per region and field). Spectra were analyzed in LCModel using a simulated basis set. Results Signal-to-noise ratio (SNR) at 7T was higher compared to 3T and linewidths (in ppm) at both field strengths were comparable in ppm scale. Of the 13 metabolites reported in the paper, most metabolites were measured with higher precision at 7T in all three regions. Conclusion The study confirms gains in SNR and measurement precision at 7T in all three representative brain regions using the sLASER pulse sequence coupled with a 32-channel phased-array head coil.

The extent of age-related changes in glutamate and other neurometabolites in the anterior cingulate cortex (ACC) in individuals with schizophrenia remain unclear. Magnetic resonance spectroscopy (MRS) at 7 Tesla, which yields precise measurements of various metabolites and can distinguish glutamate from glutamine, was used to determine levels of ACC glutamate and other metabolites in 24 individuals with schizophrenia and 24 matched controls. Multiple regression analysis revealed that ACC glutamate decreased with age in patients but not controls. No changes were detected in levels of glutamine, N-acetylaspartate, myo-inositol, GABA, glutathione or other metabolites. These results suggest that age may be an important modifier of ACC glutamate in schizophrenia.

Gamma-aminobutyric acid (GABA) and glutamate (Glu) levels, normalized to total creatine (tCr) were measured in the anterior cingulate and cerebellar vermis in healthy adults (n=19, age = 24.6 +/ 6.4 yrs) using 1H MRS at 3 Tesla and metabolite correlations across regions and subjects were determined. Mean anterior cingulate and cerebellar GABA:tCr ratios were 0.31 (0.08) and 0.23 (0.06), respectively, while corresponding Glu levels were 1.16 (0.10) and 0.70 (0.07), respectively. A correlation was observed for glutamate (r = 0.61, p = 0.01 and p = 0.06 when adjusted for multiple comparisons) between the anterior cingulate and the cerebellar vermis. It is unlikely that this correlation is driven by correlations in tCr, since inter-regional correlations were not observed for other metabolites referenced to tCr. Within both regions, correlations were observed between metabolites which were also weakly significant when correcting for multiple comparisons. N-acetyl-aspartate and glutamate (anterior cingulate: r = 0.66, p = 0.01 and p = 0.06 when adjusted for multiple comparisons; cerebellar vermis: r = 0.64, p = 0.01 and p = 0.06 when adjusted for multiple comparisons).

Key Points Question Is altered fetal brain development in the setting of maternal psychological distress associated with infant neurodevelopment? Findings In this cohort study of 97 mother-infant dyads who underwent 184 fetal magnetic resonance imaging studies (87 participants with 2 fetal studies each) and infant neurodevelopmental testing at 18 months, prenatal maternal stress was negatively associated with infant cognitive outcome, and this association was mediated by fetal left hippocampal volume. The study also found that increased fetal cortical local gyrification index and sulcal depth under elevated prenatal maternal distress were associated with decreased infant social-emotional scores measured by Bayley Scales of Infant and Toddler Development and competence scores measured by Infant-Toddler Social and Emotional Assessment. Meaning These findings suggest that altered in vivo fetal brain development in the setting of elevated prenatal maternal psychological distress may be associated with adverse neurodevelopment.