Early Senescence and Leukocyte Telomere Shortening in SCHIZOPHRENIA: A Role for Cytomegalovirus Infection?

Abstract

Schizophrenia is a severe, chronic mental disorder characterized by delusions and hallucinations. Several evidences support the link of schizophrenia with accelerated telomeres shortening and accelerated aging. Thus, schizophrenia patients show higher mortality compared to age-matched healthy donors. The etiology of schizophrenia is multifactorial, involving genetic and environmental factors. Telomere erosion has been shown to be accelerated by different factors including environmental factors such as cigarette smoking and chronic alcohol consumption or by psychosocial stress such as childhood maltreatment. In humans, telomere studies have mainly relied on measurements of leukocyte telomere length and it is generally accepted that individuals with short leukocyte telomere length are considered biologically older than those with longer ones. A dysregulation of both innate and adaptive immune systems has been described in schizophrenia patients and other mental diseases supporting the contribution of the immune system to disease symptoms. Thus, it has been suggested that abnormal immune activation with high pro-inflammatory cytokine production in response to still undefined environmental agents such as herpesviruses infections can be involved in the pathogenesis and pathophysiology of schizophrenia. It has been proposed that chronic inflammation and oxidative stress are involved in the course of schizophrenia illness, early onset of cardiovascular disease, accelerated aging, and premature mortality in schizophrenia. Prenatal or neonatal exposures to neurotropic pathogens such as Cytomegalovirus or Toxoplasma gondii have been proposed as environmental risk factors for schizophrenia in individuals with a risk genetic background. Thus, pro-inflammatory cytokines and microglia activation, together with genetic vulnerability, are considered etiological factors for schizophrenia, and support that inflammation status is involved in the course of illness in schizophrenia.

The Psychoemotional Stress-Induced Changes in the Abundance of SatIII (1q12) and Telomere Repeats, but Not Ribosomal DNA, in Human Leukocytes

“…The length of telomeres (TR content) is known to diminish with aging [ 28 , 29 , 30 ]. The TR count was reduced in the DNA of SZ patients compared to healthy controls [ 31 , 32 ] ( Figure 2 ). Oxidative stress may also reduce the telomere length in human cells [ 34 ].…”

“…The nature and functional significance of this variability are still not clear [ 28 , 29 , 30 ]. The literature presents ambiguous data on the TR content in the genomes of SZ patients [ 31 , 32 ]. The TR content in the human body is determined by many factors.…”

Proline Metabolism in Neurological and Psychiatric Disorders

“…Accelerated senescence has been detected in patients with schizophrenia, AD and PD ( Martinez-Cue and Rueda, 2020 ; Solana et al, 2018 ). It is plausible that proline metabolism-associated senescence may play a role in schizophrenia, AD and PD.…”

Telomere Biology in Mood Disorders: An Updated, Comprehensive Review of the Literature

“…Major psychiatric disorders like mood disorders and schizophrenia show biological abnormalities that cut across diagnostic categories, and importantly, include increased inflammation, oxidative stress, serum cortisol aberrations and autonomic system anomalies 44). These biochemical irregularities likely cause telomere attrition, so that the latter may be related to specific biological processes or endophenotypes rather than psychiatric diagnoses per se 45).…”