NKCC1 to KCC2 mRNA Ratio in Schizophrenia and Its Psychopathology: a Case–Control Study

• Published in: Journal of molecular neuroscience 2022-08, Vol.72 (8), p.1670-1681
• Main Authors: Mohaghghegh, Hoorie, Ananloo, Esmaeil Shahsavand, Hadjighasem, Mahmoudreza, Karimipour, Morteza, Hashemizadeh, Shiva, Abhari, Seyyed Ali Ahmadi
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Blood; Case-Control Studies; Cell Biology; Chloride transport; Diagnosis; Female; Gene expression; Genes; Human populations; Humans; Male; Males; Mental disorders; mRNA; Neurochemistry; Neurology; Neurosciences; Patients; Peripheral blood; Phenotypes; Potassium-chloride cotransporter; Proteomics; Psychiatry; Psychopathology; Ribonucleic acid; RNA; RNA, Messenger - genetics; Scale (ratio); Schizophrenia; Schizophrenia - genetics; Solute Carrier Family 12, Member 2 - genetics; Solute Carrier Family 12, Member 2 - metabolism; Statistical analysis; Symporters - genetics; Symporters - metabolism; γ-Aminobutyric acid
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-021-01879-7

Schizophrenia (SCZ) is a debilitating, destructive, and chronic mental disorder and affects approximately one percent of the human population. Diagnosis in psychiatry is based on the patient’s descriptions of his/her symptoms, interviewer’s observations, history of disorder over time, and response to treatment. All of these data measure phenotype-based functions. But it appears that accurate diagnosis of such a complex disorder must be based on valid and reliable factors. In the present study, gene selection was based on the possible role of γ-aminobutyric acid (GABA) in psychopathology of SCZ and expression in blood. We evaluated the association of Na + -K + -Cl − co-transporter 1 ( NKCC1) and K + -Cl − co-transporter 2 ( KCC2 ) genes’ messenger ribonucleic acid (mRNA) levels, and also the NKCC1/KCC2 ratio with positive and negative syndrome scale (PANSS) and brief psychiatric rating scale (BPRS) scores in an SCZ group. By using real-time PCR (RT-PCR), the present study is the first attempt to explore levels of NKCC1 and KCC2 expression at mRNA level and their relative expression in human peripheral blood of patients with SCZ. Our results showed that the NKCC1 to KCC2 mRNA ratio is significantly increased (but based on the delta cycle of threshold [ ∆ Ct] is significantly lower) in the total sample of cases rather than controls ( p  = 0 . 045) and also higher in male sample cases rather than male controls ( p  = 0 . 016). In female samples, we found a trend toward a significant effect between the case and control participants ( p  = 0 . 075). We also found statistically significant association between mRNA of NKCC1 and KCC2 genes and NKCC1 / KCC2 mRNA ratio with the positive and negative syndrome scale (PANSS) and brief psychiatric rating scale (BPRS) scores.