Radial glia are elongated bipolar cells present in the CNS during development. Our understanding of the unique roles these cells play has significantly expanded in the last decade. Historically, radial glial cells were primarily thought to provide an architectural framework for neuronal migration. Recent research reveals that radial glia play a more dynamic and integrated role in the development of the brain and spinal cord. They represent a major progenitor pool during early development and can give rise to a small population of multipotent cells in neurogenic niches of the adult CNS. Radial glial cells are a heterogeneous population, with divergent and often poorly understood roles across different brain and spinal cord regions during development; this heterogeneity extends to specialised adult subtypes, such as tanycytes, Müller glial cells and Bergman glial cells which possess morphological similarities to radial glial but play distinct functional roles in the CNS.

Magnetic resonance spectroscopy (MRS) is a non-invasive analytical technique that investigates the presence and concentrations of brain metabolites. In the context of major depressive disorder (MDD), MRS has revealed regional biochemical changes in GABA, glutamate, and choline across different brain compartments. Technical and methodological advances in MRS data acquisition, in particular proton-based 1H-MRS, have resulted in a significant increase in the incidence of reports utilizing the technique for psychiatric disorder research and diagnosis. The most recent comprehensive meta-analysis reviewing MRS in MDD stems from 2006. Using contemporary systemic reviews and meta-analysis, the aim is to first test a neurochemical circuit-based theory of depression and then to determine if clinical scores relate to metabolite concentrations before and during treatment. Region-specific metabolite changes in MDD will be assessed by systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Inclusion criteria will include participant age (18 to 65), English language studies, known regions of interest, and detailed documentation of 1H-MRS procedures. Reported brain regions will be standardized according neuroanatomical expertise allowing increased power of the meta-analysis. Regions of interest will initially include the hippocampus, thalamus, prefrontal cortex, anterior and posterior cingulate gyri, parietal lobe, and basal ganglia. Exclusion criteria will include comorbid psychiatric illness and drug use. Two independent reviewers will undertake all data extraction, while a third reviewer will check for reviewer discrepancies. Statistical analysis will be performed using STATA supplemented by Metan software and SPSS. This data will shed new light on the biochemical basis of depression in different brain regions, thereby highlighting the potential of MRS in identifying biomarkers and generating models of MDD and treatment response. PROSPERO CRD42018091494