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Key Points Question Are clinical and demographic factors associated with brain glutamate or glutamate plus glutamine (Glx) levels in schizophrenia? Findings In this mega-analysis of 1251 patients with schizophrenia and 1197 healthy volunteers, medial frontal cortex glutamatergic metabolite levels were lower in patients and negatively associated with the dose of antipsychotic medication, although a reduction in glutamate levels with age was not accelerated in patients with schizophrenia compared with healthy individuals. Higher medial frontal cortex and medial temporal lobe glutamate levels were associated with more severe symptoms in patients with schizophrenia. Meaning Lower brain glutamate levels may be associated with antipsychotic exposure rather than with greater age-related decline, whereas higher glutamate levels may serve as a biomarker of illness severity in patients with schizophrenia., Importance Proton magnetic resonance spectroscopy (1H-MRS) studies indicate that altered brain glutamatergic function may be associated with the pathophysiology of schizophrenia and the response to antipsychotic treatment. However, the association of altered glutamatergic function with clinical and demographic factors is unclear. Objective To assess the associations of age, symptom severity, level of functioning, and antipsychotic treatment with brain glutamatergic metabolites. Data Sources The MEDLINE database was searched to identify journal articles published between January 1, 1980, and June 3, 2020, using the following search terms: MRS or magnetic resonance spectroscopy and (1) schizophrenia or (2) psychosis or (3) UHR or (4) ARMS or (5) ultra-high risk or (6) clinical high risk or (7) genetic high risk or (8) prodrome* or (9) schizoaffective. Authors of 114 1H-MRS studies measuring glutamate (Glu) levels in patients with schizophrenia were contacted between January 2014 and June 2020 and asked to provide individual participant data. Study Selection In total, 45 1H-MRS studies contributed data. Data Extraction and Synthesis Associations of Glu, Glu plus glutamine (Glx), or total creatine plus phosphocreatine levels with age, antipsychotic medication dose, symptom severity, and functioning were assessed using linear mixed models, with study as a random factor. Main Outcomes and Measures Glu, Glx, and Cr values in the medial frontal cortex (MFC) and medial temporal lobe (MTL). Results In total, 42 studies were included, with data for 1251 patients with schizophrenia (mean [SD] age, 30.3 [10.4] years) and 1197 healthy volunteers (mean [SD] age, 27.5 [8.8] years). The MFC Glu (F1,1211.9 = 4.311, P = .04) and Glx (F1,1079.2 = 5.287, P = .02) levels were lower in patients than in healthy volunteers, and although creatine levels appeared lower in patients, the difference was not significant (F1,1395.9 = 3.622, P = .06). In both patients and volunteers, the MFC Glu level was negatively associated with age (Glu to Cr ratio, F1,1522.4 = 47.533, P, This mega-analysis assesses whether age, symptom severity, level of functioning, and antipsychotic treatment are associated with glutamate or glutamatergic metabolite levels measured with proton magnetic resonance spectroscopy in the medial frontal cortex or medial temporal lobe of patients with schizophrenia.

Purpose: Optical coherence tomography (OCT) is useful in diagnosing and monitoring retinal pathology such as age-related macular degeneration, diabetic macular edema (DME), central serous chorioretinopathy, and epiretinal membrane, among others. This study compared the ability of horizontal (H) 25-, 13-, and 7-cut macular OCT vs 24-, 12-, and 6-cut radial (R) macular OCT in identifying various macular pathology. Methods: This was a prospective study of 161 established patients evaluated at Wilford Hall Eye Center Retina Clinic between September and October of 2019. Pathology included age-related macular degeneration, central serous chorioretinopathy, DME, and epiretinal membrane, among others. Patients obtained 25-, 13-, and 7-cut H raster OCT as well as 24-, 12-, and 6-cut R OCT. Primary outcomes were sensitivity in detecting macular fluid and each macular abnormality. Results: The 24-cut radial (R24) OCT equally or out-performed the H25 (horizontal 25-cut OCT) in detecting macular fluid across all pathological groups. Generally, a higher number of cuts correlated with better detection of fluid. In detecting any macular abnormalities, H25, R24, and R12 had 100% sensitivity. R6 OCT had near 100% sensitivity across all groups, except for DME (95%). Overall, R OCT had better sensitivity (0.960) than H OCT (0.907) in detecting macular pathology. Conclusions: R outperformed H macular OCT in detecting fluid and other abnormalities. Clinically, both scanning patterns can be used by ophthalmologists in diagnosis and management of commonly encountered macular diseases. Technicians may be able to use a variety of these scans to screen for pathology prior to physician evaluation.

An ongoing prospective study is acquiring preoperative imaging data for men with prostate cancer (PCa) using the molecular imaging agent [ F]-DCFPyL targeted against prostate-specific membrane antigen (PSMA). To date, six men (of a planned accrual of 24) with clinically localized, biopsy-proven PCa have undergone preoperative [ F]-DCFPyL positron emission tomography (PET) imaging and multiparametric magnetic resonance imaging acquired using a hybrid PET/MRI system. Lesions identified by [ F]-DCFPyL uptake on PET/MRI were characterized in terms of maximum standardized uptake value (SUV ) and volume using a boundary threshold of 40% SUV . Following surgery, all prostatectomy specimens were processed using a whole-mount technique for accurate deformable co-registration and correlation with PCa foci defined on digitized pathology images. Well-defined intraprostatic dominant lesions were identified by [ F]-DCFPyL PET/MRI (mean SUV 11.4 ± 8.25; mean volume 2.2 ± 2.4 cm ) in all six men. Co-registered digitized whole-mount pathology for the first case revealed that intense [ F]-DCFPyL uptake (SUV 27 ± 1.1 cm ) and multiparametric MRI changes (Prostate Imaging Reporting and Data System score of 4) were highly correlated with a 0.5-cm dominant (largest) lesion with Gleason pattern 4 PCa in the right mid peripheral zone. A smaller focus (0.01 cm ) of lower-grade PCa (Gleason pattern 3) had much lower uptake (SUV 2.7). These early prospective data show that dominant intraprostatic lesions could be identified in all six men using [ F]-DCFPyL as an imaging probe. Trial accrual will continue to quantify in terms of spatial concordance the ability of [ F]-DCFPyL to identify the location and characterize the grade of intraprostatic cancer foci in clinically localized PCa. Patient summary: Positron emission tomography using a novel probe called [ F]-DCFPyL directed against the prostate-specific membrane antigen protein was able to identify locations of prostate cancer in the prostate glands of men undergoing imaging before surgery. In the future, such imaging may allow better targeting of treatment to the portion of the prostate containing the most aggressive components of cancer rather than treating the whole prostate in a uniform fashion. [ F]-DCFPyL positron emission tomography/magnetic resonance imaging shows promise for identifying high-grade intraprostatic foci of prostate cancer in a spatially accurate fashion to facilitate targeted biopsy and treatment. 18 18 18 18 3 18 3 3 3 18 18 18 18 max max max max

We modeled Stroop performance among schizophrenia participants undertaken during functional neuroimaging using Systems Factorial Technology (SFT) and related methods. Results indicated that schizophrenia participants' encoding of Stroop stimuli entailed an additional number of constituent encoding-process operations, or subprocesses. However, cognitive-workload capacity in terms of rate of subprocess completion was normal. Psychiatric controls with major depressive disorder were characterized by a similar model of performance but with a smaller increase in the number of subprocess. SFT measures revealed spared and disorder-affected intratrial dynamics of task performance. This work illustrates in part the potential value of SFT in elucidating the functional side of functional neuro-imaging.

Glutamate abnormalities have been suggested to be associated with symptoms of schizophrenia. Using functional magnetic resonance spectroscopy (1H-fMRS), it is possible to monitor glutamate dynamically in the activated brain areas, which has yet to be reported in schizophrenia. It was hypothesized that subjects with schizophrenia would have weaker glutamatergic responses in the anterior cingulate to a color-word Stroop Task. The aim of this study was to gain insight into the health of GLU neurotransmission and the GLU-GLN cycle in SZ using a 1H-fMRS protocol. Spectra were acquired from the anterior cingulate of 16 participants with schizophrenia, 16 healthy controls and 16 participants with major depressive disorder (MDD) while performing the Stroop task in a 7T magnetic resonance imaging scanner. 1H-fMRS spectra were acquired for 20 min in which there were three 4-min blocks of cross fixation interleaved with two 4-min blocks of the Stroop paradigm. A repeated-measures analysis of variance revealed a main effect of time for glutamate concentrations of all groups (P

Glutamatergic dysfunction is implicated in the pathoaetiology of schizophrenia, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls, using the log coefficient of variation ratio (CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data using Hartigan’s unimodality dip test. MEDLINE and EMBASE databases were searched from inception to October 2021 for proton magnetic resonance spectroscopy (1H-MRS) studies reporting glutamate, glutamine or Glx in schizophrenia patients compared to controls. 116 studies reporting on 7,844 patients and 7,305 controls were included. Compared with controls, patients demonstrated greater variability in glutamatergic metabolites in the medial frontal cortex (MFC, glutamate: CVR = 0.15, p