Negative Symptoms, Cognitive Function, Platelet Serotonin Concentration And Polymorphisms Of 5-HT_2A\2C Receptors In The First Degree Relatives Of Schizophrenia

【Background】Genetic factor is one of the most important risk factors of schizophrenia. The morbidity rate of the first-degree relatives of schizophrenic patients is ten times as high as normal population. Some studies and clinical practice showed that the first-degree relatives of schizophenic patients manifested neurobiologic defects, neuropsychologic dysfunction and some negative symptoms. On this basis, "schizotaxia"was proposed to describe the genetic trait of schizophrena. Schizotaxia is a syndrome characterized by negative symptoms, neuropsychologic dysfunction and social psychologic defects. Nonpsychotic first-degree relatives of schizophrenic patients are at high risk for schizotaxia. Dopamine (DA) and 5-HT are two most important neurotransmitters in the pathogenesis of schizophrenia. Furthermore, 5-HT is closely associated with negative symptomes and cognitive dysfunction. 【Objective】(1)To assess negative symptoms and cognitive impairment in the first degree relatives of schizophrenic patients, and study their relationship. (2)To explore platelet serotonin concentration and polymorphisms of 5-HT 2a\2c receptors in the first degree relatives of schizophrenic patients, and analyse the relationship between these polymorphisms and negative symptomes and cognitive dysfunction. 【Subjects and methods】In this study, 22 probands and 62 first-degree ralatives of 27 simplex families, 15 probands, 10 comorbid relatives and 29 first-relatives of 15 complex families, 15 normal controls and 35 first-relatives of 15 normal control families were enrolled. To evaluate their neuropsychologic function (attention/working memory, long-term verbal memory, or executive function) and negative symptoms, all subjects were assesed by Wisconsin Card Sorting Test (WCST), Continuous Performance Task (CPT), Verbal Explanation Subscale of Wechsler Adult Intelligence Scale (WAIS) and negative symptoms subscale of Positive and Negative Symptom Scale (PANSS). Platelet serotonin concentration was measured by HPLC-fluorometric method. Polymorphisms of 5-HT 2a\2c receptors were assessed by PCR and restricted length polymorphism (RELP). 【Results】The first-degree relatives of schizophrenic patients show moderate higher negative symptoms and poorer cognitive function in WCST and Continuous Performance Task(CPT) than those of the control group. The relatives of the complex families show severer negative symptoms and neuropsychologic defects than those of the simplex families. The scores of neuropsychological tests of the simplex families are situated between that of the complex families and control group. Moreover, those negative symptoms are more associated with deficits in cognition in the first degree relatives of schizophrenia. The serotonin concentration in platelet in the first degree relatives is lower than that of schizophrenia patients and control group. The T-allelotype genotypic frequency of 5-HT 2a receptor T102C polymorphism of first-degree relatives is higher than those of control group, but no difference of 5-HT2c recepor polymorphisms have been found between the relatives and control group, only the –759 mutant and –697 mutant of schizophrenic patients are higher than relative group. 【Conclusions】Part of the first-degree relatives of schizophrenic patients manifested cognitive dysfunctions and negative symptoms in different levels. Moreover, those negative symptoms are more associated with deficits in cognition of the first degree relatives of schizophrenia. These data demonstrate that they may have some heredity traits and may be athigher risk for schizophrenia. Their platelet serotonin concentration may have potential changes and T-allelotype genotypic frequency of 5-HT 2a receptor T102C polymorphism is statistically significant higher than that of control group, which may indicate the genetic traits of first degree relativs of schizophrenia. but no difference has been found between the relatives and control group, only the –759 mutant and –697 mutant of schizophrenic patients are higher than relative group.