The role of the retinoids in schizophrenia: genomic and clinical perspectives

Abstract

Signalling by retinoid compounds is vital for embryonic development, with particular importance for neurogenesis in the human brain. Retinoids, metabolites of vitamin A, exert influence over the expression of thousands of transcripts genome wide, and thus, act as master regulators of many important biological processes. A significant body of evidence in the literature now supports dysregulation of the retinoid system as being involved in the aetiology of schizophrenia. This includes mechanistic insights from large-scale genomic, transcriptomic and, proteomic studies, which implicate disruption of disparate aspects of retinoid biology such as transport, metabolism, and signalling. As a result, retinoids may present a valuable clinical opportunity in schizophrenia via novel pharmacotherapies and dietary intervention. Further work, however, is required to expand on the largely observational data collected thus far and confirm causality. This review will highlight the fundamentals of retinoid biology and examine the evidence for retinoid dysregulation in schizophrenia.

Clozapine modulates retinoid homeostasis in human brain and normalizes serum retinoic acid deficit in patients with schizophrenia

“…demonstrated, did not differ between groups [74,75]. While the expression of RA-inducible RARB, for which associations with schizophrenia have been demonstrated [21,25] did not differ significantly between groups (Fig. 5b), the tendency toward reduced expression in SCZ-CZP is similar to the pattern observed for CYP26A and STRA6 (Fig.…”

“…These processes are regulated by paracrine retinoid signaling [16][17][18]. Several lines of evidence directly point toward disturbed retinoid signaling in schizophrenia [19][20][21][22][23][24][25]. All-trans retinoic acid (at-RA), the most active metabolite of vitamin A is locally produced and tightly regulated in brain tissue through cytochrome P450-(CYP450) mediated degradation into polar metabolites [26].…”

StableDNMT3LOverexpression in SH-SY5Y Neurons Recreates a Facet of the Genome-Wide Down Syndrome DNA Methylation Signature

“…However, there were also phase-specific GO terms, including the glucuronidation hierarchy of GO terms in the phase 1 comparison. While represented by xenobiotic glucuronidation, the glucuronidation hierarchy appears to represent retinoic acid, which is added to the media in phase 1, since the glucuronidation of retinoic acid is involved in neurodevelopment (38).…”

Advances in schizophrenia research: first special issue, 2020

“…Proteasome dysfunction in postmortem cortex in schizophrenia was examined by Scott and Meador-Woodruff [13]. Reay and colleagues have two interesting articles that shed new light on the role of retinoids in schizophrenia [14,15].…”