Personality Traits of Schizophrenic Patients in Remission and Their First-Degree Relatives: A Dopaminergic and Glutamatergic Gene Polymorphism Study

摘要

Objective: The dopaminergic and glutamatergic systems are of major interest in the etiology of schizophrenia and supposed endophenotypes such as personality traits. In the present study, we investigated the association between the catechol-O-methyltransferase (COMT) gene P2 promoter rs2075507, Val/ Met (rs4680), the dopamine transporter gene (DAT1) VNTR and the glutamate transporter gene (SLC1A2) promoter -181A/C polymorphisms, and personality traits as well as symptomatic features in schizophrenia.Methods: There were 112 healthy subjects, 51 schizophrenic patients in remission for at least six months and 45 first-degree relatives of the patients enrolled in the study. The samples were genotyped for the COMT P2 promoter rs2075507, Val/Met, DAT1 VNTR and SLC1A2 promoter -181A/C polymorphisms and assessed with the Temperament and Character Inventory (TCI). Schizophrenia patients were also evaluated using the Operational Criteria Checklist for Psychotic Illness (OPCRIT) for each of the five factor-derived scales (negative symptoms, delusions, hallucinations, mania, and depression) and The Positive and Negative Symptom Scale.Results: Our findings demonstrate that schizophrenic patients, even after remission, had a different personality pattern from controls, showing higher scores in harm avoidance and self-transcendence and lower scores in novelty seeking, persistence, self-directedness and cooperativeness. First-degree relatives of patients also had profiles distinguishable from those of the patients only by intermediate levels of harm-avoidance and higher levels of cooperativeness. In the association of genotypes and personality, COMT Val/Met polymorphism was not associated with personality in patients or in healthy subjects. Another functional polymorphism in the COMT gene the P2 promoter rs2075507 G allele was associated with significantly higher novelty seeking scores in patients than was the A allele. DAT1 VNTR long alleles (10 or 11 repeats) were demonstrated to show a non-significant trend to association with higher self-transcendence scores than in those with the short alleles (3, 7, 8 or 9 repeats) in control samples and patients. In SLC1A2 promoter -181A/C polymorphism, the C allele was significantly associated with higher self-transcendence scores than in those with the A allele in healthy subjects. We did not find any associations between the psychotic symptom dimensions of patients and DAT1 VNTR, SLC1A2 promoter -181A/C and COMT Val/Met polymorphism; however, COMT P2 promoter rs2075507 polymorphism showed an association with the delusion and mania factor scores.Conclusions: Schizophrenia may be associated with different personality patterns from controls and some personality dimensions may be associated with the appearance of psychotic symptoms. The same genes may be responsible for the development of the disease, with personality patterns seen in at least one group of patients.?ZETAma?: Dopaminerjik ve glutamaterjik sistem, ?izofreninin ve ?izofreni ile ili?kili oldu?u ?ng?rülen ki?ilik ?zellikleri gibi endofe-notiplerin etyolojisinde ?nemli ilgi alanlar? aras?nda yer almaktad?r. Bu ?al??mada katekol-o-metil transferaz (COMT) geni P2 promoter rs2075507 ve Va l/Met (rs4680) polimorfizmleri, dopamin transporter geni (DAT1) VNTR ve glutamat transporter geni (SLC1A2) promoter 181 A/C polimorfizmlerinin ki?ilik ?zelliklerinin yan? s?ra ?izofreninin semptomatik ?zellikleri ile ili?kisinin ara?t?r?lmas? ama?lanm??t?r.Y?ntem: ?al??maya 112 sa?l?kl? kontrol, en az 6 ayd?r remisyonda olan 51 ?izofreni hastas? ve 45 birinci derece hasta yak?n? al?nm??t?r. Denekler COMT P2 promoter rs2075507, val/met, DAT1 VNTR ve SLC1A2 promoter -181A/C polimorfizmleri y?nünden genotiplendirilmi? ve Karakter ve Miza? Envanteri ile de?erlendirilmi?tir. ?izofreni hastalar? ayr?ca PANSS ve Psikotik Hastal?k i?in Operasyonel Kriterler Kontrol Listesi'nden (Operational Criteria Checklist for Psychotic Illness/OPCRIT) elde edilen be? fakt?r skalas? (negatif semptomlar, delüzyonlar, halusinasyonlar, mani ve depresyon) ile de?erlendirilmi?tirBulgular: ?al??mam?z ?izofreni hastalar?n?n remisyon sonras?nda bile sa?l?kl? kontrollerden farkl? bir ki?ilik paternine; zarardan ka??nmada ve kendini a?mada daha yüksek skorlara; yenilik aray???, sebatkarl?k, kendini y?netme ve i?birli?i yapmada daha dü?ük skorlara sahip olduklar?n? g?stermi?tir. ?izofreni hastalar?n?n birinci derece yak?nlar? ise hastalardan orta düzeyde zarardan ka??nma ve daha yüksek i?birli?i yapma skorlar? ile ayr??m??lard?r. Genotipler ve ki?ili?in ili?kisi incelendi?inde, COMT val/met polimorfizminin hastalarda veya sa?l?kl? kontrollerde ki?ilikle ili?kisi saptanmam??t?r. COMT geninde di?er bir foksiyonel polimorfizm olan P2 promoter rs2075507 G aleli, ?izofreni hastalar?nda istatistiksel anlaml? olarak A alelinden daha yüksek yenilik aray??? skorlar?yla ili?kiliydi. DAT1VNTR polimorfizmi uzun alelleri (10 ve 11 tekrar) hastalarda ve sa?l?kl? kontrollerde k?sa allerde