Analytical Value of Cell-Free DNA Based on Alu in Psychiatric Disorders

Abstract

Psychiatric disorders impose a huge burden on individuals, families, and society. The Alu repeat sequence is a member of the short interspersed nuclear element (SINE) family of mammalian genomes, however, its expression pattern and role in psychiatric disorders is unclear. The current paper aimed at determining the concentrations of Alu in patients with schizophrenia (SZ), major depressive disorder (MDD), and alcohol-induced psychotic disorder (AIPD), and to further define the role and value of Alu as a potential biomarker in psychiatric disorders. In this work, we found that the concentration of Alu was considerably incremented in patients with SZ, and a significant difference existed between patients diagnosed with SZ and MDD or AIPD. ROC analysis also indicated that Alu was effective in the complementary diagnosis of SZ, and differentially diagnosed between SZ patients and patients with MDD or AIPD. In addition, we found a positive relationship between the Alu concentrations and interleukin-1b (IL-1b) in patients with SZ, MDD, and AIPD, and between the concentrations of Alu and interleukin-18 (IL-18) in patients with SZ. Overall, the present work indicates that Alu might be an innovative biomarker for diagnosing psychiatric disorders, and provides the basis for hypotheses about the pathophysiology of psychiatric disorders.

Circulating Cell-Free DNA Levels in Psychiatric Diseases: A Systematic Review and Meta-Analysis

“…However, they were also excluded because two reports were not enough to conduct a meta-analysis for this type of cfDNA (see further). For the same reason, one report on cf-gDNA was excluded from the DDs group [ 36 ], as the remaining studies analyzed cf-mtDNA. Ultimately, the following numbers of reports were included in the meta-analysis: schizophrenia, 8 [ 24 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]; BD, 4 [ 25 , 35 , 43 , 44 ]; DDs, 5 [ 35 , 45 , 46 , 47 , 48 ].…”

“…For the same reason, one report on cf-gDNA was excluded from the DDs group [ 36 ], as the remaining studies analyzed cf-mtDNA. Ultimately, the following numbers of reports were included in the meta-analysis: schizophrenia, 8 [ 24 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]; BD, 4 [ 25 , 35 , 43 , 44 ]; DDs, 5 [ 35 , 45 , 46 , 47 , 48 ]. The total number of individual studies included in the meta-analysis was sixteen because some reports considered several diseases simultaneously.…”

In Vitro Analysis of Biological Activity of Circulating Cell-Free DNA Isolated from Blood Plasma of Schizophrenic Patients and Healthy Controls

“…All the studies reported a two- to three-fold c-cfDNA increase in SZ patients. The concentrations of mtDNA [ 38 ], rDNA [ 7 ], GC-rich Alu repeats [ 50 ], and oxy-DNA [ 6 ] in the blood plasma of SZ patients exceeded the concentrations in the blood plasma of healthy controls (hc-cfDNA).…”

“…The increased plasma levels of gc-DNA and oxy-DNA suggest that sz-cfDNA is a biologically active molecule. For example, the authors [ 50 ] found a positive relationship between the contents of Alu and interleukin-1β and interleukin-18 in SZ patients. However, a priori, we cannot determine what could be responsible for the potential biological activity of sz-cfDNA: a high concentration of c-cfDNA fragments or an altered composition of sz-cfDNA compared to hc-cfDNA fragments.…”

Concentration of Circulating Cell-Free DNA in the Peripheral Blood Plasma of Patients with Acute Endogenous and Exogenous Etiology Psychoses

“…Однако в литературе мало сведений об изменении концентраций вкДНК у больных с психозами. Было показано, что концентрации вкДНК возрастают в плазме крови китайских больных шизофренией [13,14]. Авторы этого исследования ранее на небольшой выборке также обнаружили, что концентрации вкДНК возрастают в плазме крови нелеченых больных шизофренией [15,16].…”