Investigation of chromosome Y loss in men with schizophrenia

Abstract

BackgroundLife expectancy is 10–20 years lower in patients with schizophrenia than in the general population. In addition, men with schizophrenia have an earlier age at onset, more pronounced deficit symptoms, poorer course, and poorer response to antipsychotic medications than women. Recent studies have indicated that loss of chromosome Y (LOY) in peripheral blood is associated with an increased risk of all-cause mortality. In order to elucidate the pathophysiology of male-specific features, we investigated the association between LOY and schizophrenia.Materials and methodsThe present study included 360 Japanese men (146 patients with schizophrenia vs 214 controls). The relative amount of Y chromosome was defined as the ratio of chromosome Y to chromosome X (Y/X ratio) based on the fluorescent signal of co-amplified short sequences from the Y-X homologous amelogenin genes (AMELY and AMELX).ResultsThere was no significant difference in the frequency of LOY between the schizophrenia and control groups. However, longer duration of illness was associated with LOY after controlling for age and smoking status in the schizophrenia group (P=0.007, OR =1.11 [95% CI =1.03–1.19]).ConclusionAccording to our results, schizophrenia may not have a remarkable effect on blood LOY; however, LOY may be associated with disease course in patients with schizophrenia.

Loss of Chromosome Y and Its Potential Applications as Biomarker in Health and Forensic Sciences

“…In this study, acute myeloid leukaemia patients exhibited Y chromosome hypoploidy in the bone marrow [Holmes et al, 1985]. Since then, several reports demonstrated an potential association between LOY and the development of diseases such as Alzheimer, cardiovascular events, autoimmune diseases, and a wide number of cancers [Holmes et al, 1985;Castedo et al, 1992;Hunter et al, 1993;Guttenbach et al, 1995;Sauter et al, 1995;Brunelli et al, 2003;Gilgenkrantz, 2008;Klatte et al, 2009;Persani et al, 2012;Lleo et al, 2013;Dumanski et al, 2016;Noveski et al, 2016;Forsberg, 2017;Forsberg et al, 2017;Haitjema et al, 2017;Hirata et al, 2018]. Furthermore, Arseneault et al…”

“…Alternative to the expensiveness of the previously mentioned methods, and the increased amount of data that need to be interpreted in SNP-arrays and WGS, PCRbased methods can be a better standardization option. For example, several studies have used a Y/X ratio to detect LOY [Noveski et al, 2016;Hirata et al, 2018;Kimura et al, 2018]. Multiplex quantitative fluorescent-PCR amplifies the 2 AMEL fragments that are on both the X and Y chromosomes.…”

“…Multiplex quantitative fluorescent-PCR amplifies the 2 AMEL fragments that are on both the X and Y chromosomes. The products are quantified by capillary electrophoresis, and the results are then compared with mixed samples for the assessment of LOY [Noveski et al, 2016;Hirata et al, 2018;Kimura et al, 2018]. The mixed samples have different proportions of a normal XY male and from an individual with Turner syndrome (45,X).…”

“…(TGCT) [Holmes et al, 1985;Castedo et al, 1992;Hunter et al, 1993;Guttenbach et al, 1995;Sauter et al, 1995;Brunelli et al, 2003;Gilgenkrantz, 2008;Klatte et al, 2009;Persani et al, 2012;Lleo et al, 2013;Dumanski et al, 2016;Noveski et al, 2016;Forsberg, 2017;Forsberg et al, 2017;Haitjema et al, 2017;Hirata et al, 2018]. Therefore, LOY can be seen as a biological age marker, and its presence has potential to be used as a predictor biomarker of male age-related diseases [Dumanski et al, 2016].…”

Intra-individual changes in the frequency of mosaic loss of chromosome Y over time estimated with a new method

“…For over 50 years it has been known that LOY is a frequent event in cells of the hematopoietic system(2) and LOY in leukocytes was long viewed as a neutral event related to normal aging without phenotypical consequences(3). However, recent studies suggest the opposite as LOY has been found to be associated with increased risk for all-cause mortality(4, 5) as well as a growing list of diverse diseases and outcomes such as various forms of cancer(4, 6-9), autoimmune conditions(10, 11), Alzheimer’s disease(12), major cardiovascular events(13, 14), suicide completion(15), schizophrenia(16), diabetes(14) as well as age-related macular degeneration (AMD)(17).…”