SIR – The clinical heterogeneity of schizophrenia has long been recognized as the signs and symptoms of the disease are so complex and diverse.1 To simplify the complexity of the clinical presentation of schizophrenia, a subdivision has been made into ‘positive’ and ‘negative’ symptoms.2, 3 The positive symptoms include hallucinations, delusions, disorganized speech, disorganized or catatonic behavior, and the negative symptoms include alogia, affective flattering and avolition.4, 5 On the other hand, genetic factors may predispose an individual to schizophrenia although the mode of transmission remains unknown. Schizophrenia may be a genetically heterogeneous disease. The catecholamine pathway is widely thought to be abnormal in schizophrenia. Dopaminergic overactivity has been postulated for more than three decades. However, investigators have been unable to find a faulty gene amongst those coding for dopamine receptors and the enzymes responsible for dopamine metabolism.6 Cholecystokinin (CCK) has been found to coexist with dopamine in the same neurons and to act as a mediator in modulating dopaminergic activity.7, 8 Since reduced CCK levels in the limbic lobe and reduced high affinity CCK binding in the hippocampus and frontal cortex have been observed in schizophrenia,9, 10 the genes coding for CCK receptors could be considered as candidate genes for schizophrenia. In a previous study, Wei and Hemmings reported that a Pst I polymorphic site in the boundary between intron 1 and exon 2 of the CCK-A receptor gene was significantly associated with auditory hallucinations in schizophrenia.11 It is uncertain whether or not such an association really reflects linkage between the CCK-A receptor gene and psychotic symptoms in schizophrenia. It was thought important to replicate the work with a different ethnic population to rule out a false-positive result from ethnic differences in the frequency distribution of the DNA marker or from the population structure. The present work was therefore undertaken to examine the association between the CCK-A receptor gene and psychotic symptoms of schizophrenia in a Chinese population.
Eighty-four unrelated male schizophrenic individuals and 70 unrelated male healthy subjects were recruited in this study. They were all Han Chinese and came from the area of Beijing or nearby, Northern China. The patients fulfilled the ICD-10 criteria for chronic schizophrenia. Their mean duration of illness was 20.4 ± 10.2 years. All the subjects gave informed consent to participate in the genetic research. The detailed clinical pictures, medical histories and family history regarding mental illness were taken. The psychotic symptoms under study included auditory hallucinations, hallucination-delusion syndrome (HDS), bizarre delusion, paranoid delusions, emotional and social withdrawal and thought disorders. The blood samples were drawn from the ante-cubital vein in the morning. Genomic DNA used for the polymerase chain reaction (PCR) was extracted from the whole blood sample. The sequence containing the Pst I polymorphic site in the boundary between intron 1 and exon 2 of the CCK-A receptor gene was amplified by a PCR-based process with a pair of primers, 5′-CTGTTCACTTGAG GAGCTTTG-3′ (sense strand) and 5′-TTAGA AACTGACCTCCAACATGG-3′ (antisense strand). Pst I digestion of the PCR products gave two individual alleles, A1 and A2. A1 allele was the undigested fragment and A2 allele was the digested one with two variant bands at 264 bp and 480 bp. Allelic frequencies were 0.25 (A1) and 0.75 (A2) in unrelated schizophrenic patients, and 0.2 (A1) and 0.8 (A2) in unrelated controls. The distribution of genotypic frequencies was in Hardy–Weinberg equilibrium in both unrelated patients and unrelated control subjects. The chi-square (χ2) test did not show a significant difference in either allelic or genotypic frequencies between schizophrenic patients and control subjects.
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