Association of SAPAP3 allelic variants with symptom dimensions and pharmacological treatment response in obsessive–compulsive disorder.

Abstract

doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

SAPAP3, SPRED2, and obsessive-compulsive disorder: the search for fundamental phenotypes

“…While no studies of SPRED2 in patients with OCD have been published to date, a cautious affirmative answer can be offered in the case of SAPAP3 . A specific four-locus haplotype of SAPAP3 has been associated with an earlier age of onset in OCD, again pointing to a possible effect on neurodevelopment (Boardman et al, 2011 ); an allelic variant in a specific single nucleotide polymorphism ( rs 6662980) of SAPAP3 has been specifically associated with the Contamination/Washing dimension of OCD, as well as with a poor response to serotonin reuptake inhibitors (Naaz et al, 2020 ); and two single-nucleotide polymorphisms in SAPAP3 have been associated with symptom severity in early-onset OCD (Mas et al, 2016 ). In addition, a genome-wide association study has found that variations in SAPAP1 (also known as DLGAP1 ), coding for a protein related to SAPAP3 which is also involved in synaptic connectivity, were significantly associated with clinical OCD (Stewart et al, 2013 ).…”

Spinophilin limits metabotropic glutamate receptor 5 scaffolding to the postsynaptic density and cell type-specifically mediates excessive grooming

“…Dysfunction in metabotropic glutamate receptor 5 (mGluR5) signaling and/or its interaction with postsynaptic density (PSD) scaffolding proteins is associated with repetitive motor dysfunction in numerous preclinical models for understanding psychiatric disorders [19,[37][38][39][40][41][42]. Of these, mutations in the striatal-enriched mGluR5 scaffold protein, disks large-associated protein 3 (SAPAP3), are associated with repetitive grooming and washing symptoms in OCSDs [43][44][45]. Genetic deletion of SAPAP3 in rodent results in striatal circuit abnormalities and increased mGluR5 function that promotes excessive grooming [13,[46][47][48][49][50][51][52], a complex sequential motor program that becomes excessively initiated and sustained despite negative consequences [53].…”