||Telomere, the ends of chromosomes, consists of simple hexameric repeats. In human, TTAGGG repeat is found at the ends of all chromosomes. Telomeres progressively shorten with age in somatic cells, because the insufficient telomerase activity fails to compensate the progressive telomeric erosion. Thus, the reduction of telomeric length in senescent cells is believed to result from active cell division that erodes chromosomal termini. The telomere length supposed to have been an evaluation tool for aging in human.|
Schizophrenia is a thought, perception disorder, generally regarded as an illness with onset in late adolescence or early adult life with a prevalence rate of 1%. Although the long-term course of schizophrenia shows great heterogeneity among patients, a significant number of patients experience very poor outcomes, shows severe cognitive impairment that is suggestive of a progressive neurodegenerative disorder. The aim of this study is to explore the relationship between neurodegenerative process and telomere length in schizophrenic patients. The latency of P300 event-related potentials is prolonged in disorders associated with neural damage and degeneration and also becomes prolonged in the course of aging process.
This study is separated as two parts: first part, using the event-related potentials P300 latency as a tool to evaluate the cognitive dysfunction and aging process in schizophrenics. One hundred and fifty three long-term hospitalization chronic schizophrenics were recruited as the experimental group of this research, including 44 male and 109 female patients with mean age of 38.4 years. These patients were divided into 2 groups according to the different responses to treatment, global assessment functional scale (GAF): 91 with good response to treatment; 62 with poor response to treatment. The normal control group included 101 normal people, male 37 and female 76, with mean age of 38.1 years. The event-related potentials was elicited by auditory oddball paradigm.
The P300 latency prolonged in these two schizophrenic patients. The longest P300 latency was found in the poor response schizophrenic group. The shortest P300 latency was found in the normal group. Linear regression coefficients were computed to determine the slope of component P300 latency on age and other factors. The slope of P300 latency on age in normal control group is 1.2 ms/y. In schizophrenic groups, not only the age, but the GAF as the most contributing factors in the neurodegenerative process.
Second part, the subjects were selected from part one, 48 chronic schizophrenia whose mean age was 37.9 years and 48 age-, handedness-, and gender-matched normal control subjects. The schizophrenic patients were divided into 2 groups according to the different responses to treatment: 34 with good response to treatment; 14 with poor response to treatment. The telomere length, measured by assay of terminal restriction fragments (TRFs), was determined in HinfI-digested DNA by Southern blot analysis using a (TTAGGG)4 probe. The shortest TRF length was found in the poor response schizophrenic group. There was no difference between the good response schizophrenic group and normal control group. TRF length in peripheral leukocytes obtained from normal control group decreased by approximately 89bP per year. In schizophrenic groups, the TRF length was found that not the age, but the age onset and GAF as the most contributing factors in linear regression model.
This study shows that the poor response schizophrenic patients have the most rapid neurodegenerative process in P300 latency and TRF length evaluation. It implicates the homogeneous group, and can be considered as the kraepelinian schizophrenics, very poor outcome group.