Association study in three different populations between the GPR88 gene and major psychoses

Abstract

GPR88, coding for a G protein-coupled orphan receptor that is highly represented in the striatum, is a strong functional candidate gene for neuropsychiatric disorders and is located at 1p22-p21, a chromosomal region that we have previously linked to bipolar disorder (BD) in the Sardinian population. In order to ascertain the relevance of GPR88 as a risk factor for psychiatric diseases, we performed a genetic association analysis between GPR88 and BD in a sample of triads (patient and both parents) recruited in the Sardinian and the Palestinian population as well as between GPR88 and schizophrenia (SZ) in triads from the Xhosa population in South Africa. We found a positive association between GPR88 and BD in the Sardinian and Palestinian triads. Moreover, we found a positive association between GPR88 and SZ in triads from the Xhosa population in South Africa. When these results were corrected for multiple testing, the association between GPR88 and BD was maintained in the Palestinian population. Thus, these results suggest that GPR88 deserves consideration as a candidate gene for psychiatric diseases and requires to be further investigated in other populations.

Developmental and adult expression patterns of the G‐protein‐coupled receptor GPR88 in the rat: Establishment of a dual nuclear–cytoplasmic localization

“…In animals, psychostimulant, antidepressant, mood stabilizer, or opiate treatments upregulate GPR88 expression (Ogden et al, ; Brandish et al, ; Bohm et al, ; Conti et al, ; Befort et al, ); on the other hand, chronic stress paradigms and anxiety‐ and depression‐like behaviors are associated with a downregulation of GPR88 expression (Kim and Han, ). In humans, genetic associations were found between GPR88 and major psychoses (Le‐Niculescu et al, ; Del Zompo et al, ). All these previous studies indirectly linked GPR88 to depression, mood disorders, schizophrenia, stress, and addiction.…”

GPR88 in A2A receptor‐expressing neurons modulates locomotor response to dopamine agonists but not sensorimotor gating

“…These findings complement our previous work showing that GPR88 in striatal A 2A R/D2R‐expressing MSNs acts as an important modulator of risk taking behaviours and social behaviour (Meirsman et al ., ). Recent human genetic studies have implicated GPR88 in both schizophrenia and bipolar disorder (Ogden et al ., ; Del Zompo et al ., ). Our work corroborates these studies and further suggests that alterations of GPR88 signalling in A 2A R‐expressing neurons may contribute to some aspect of psychomotor agitation associated with these psychiatric diseases.…”

“…The distinctive pattern of GPR88 expression has generated considerable excitement regarding the physiological role of this orphan receptor and its implication in brain diseases associated with striatal dysfunction. Human genetic studies revealed a positive association between GPR88 and schizophrenia as well as bipolar disorder (Ogden et al, 2004;Del Zompo et al, 2014). Deleterious mutation in GPR88 was also linked to a familial developmental disorder characterized by a childhood chorea (hyperkinetic movement disorder), learning disabilities and speech retardation (Alkufri et al, 2016).…”

G-protein coupled receptor 88knock-down in the associative striatum reduces the psychiatric symptoms in a translational model of Parkinson’s disease

“…Animal studies were authorized by an ethical committee reporting to the French Ministry of Agriculture (APAFIS reference #3669-2016011817516297) and were conducted in the in-house SPF animal facility, which was approved by the Veterinary Inspection Office (agreement reference B75- [13][14][15][16][17][18][19]. The animals were handled throughout the study in compliance with the European Union 2010 Animal Welfare Act, and the 2010/63 French directive.…”

“…In this context, the orphan G-protein Coupled Receptor 88 (GPR88) is emerging as a particularly suited target. GPR88 has been associated with Bipolar Disorder and Schizophrenia (13,14), and deleterious mutations were found to induce profound learning deficits and a hyperkinetic movement disorder in humans (15). GPR88 is mainly expressed in striatal Medium Spiny Neurons (MSN) at the level of the corticostriatal synapse (16), where it exerts an inhibitory control over monoamine and neuropeptide neurotransmission through G i/o coupling (17).…”