Increased Plasma Ceruloplasmin Levels in Schizophrenia

OZET: fiizofrenide artm›fl plazma seruloplazmin duzeyleri Amac: Seruloplazmin hepatositler taraf›ndan sentezlenen insan serumunda bulunan bir proteindir. Ayr›ca karacier d›fl›nda beyin, akcier, dalak ve testis gibi organlarda da gen ekspresyonlar› gosterilmifltir. Seruloplazmin serum ba- k›r›n›n yaklafl›k %95'ini icerir ve bak›r› dier bircok dokuya tafl›r. Seruloplazmin buyuk oranda bak›r younluunu yans›t›r. Seruloplazmin ayn› zamanda antiok- sidan etkiye sahiptir ve bir akut faz reaktan›d›r. Ayr›ca, seruloplazmin serotonin, epinefrin ve norepinefrinin oksidasyonunda da rol almaktad›r. Seruloplazmin anormallii bircok norodejeneratif hastal›kla iliflkilendirilmifltir. Seruloplazminin flizofreni ve hastan›n akut veya kronik fazda olmas›, hastal›k suresi, hastan›n te- davide olup olmamas› gibi flizofreninin baz› klinik ozellikleriyle de balant›l› ol- duu bildirilmifltir. Bununla beraber, seruloplazmin ve flizofreni iliflkisi hakk›nda hala celiflkiler vard›r, cunku flizofrenide seruloplazmin duzeyinin artt›¤›, azald›¤› ve normal s›n›rlarda kald›¤› ile ilgili yay›nlar da bulunmaktad›r. Bu celiflki, kulla- n›lan olcum yonteminin farkl›l›¤›ndan, hastalar›n klinik durumunun farkl› olma- s›ndan ve etnobiyolojik farkl›l›klardan kaynaklanabilir. Biz bu cal›flmada Turk hastalarda plazma seruloplazmin duzeyi ile flizofreni iliflkisini araflt›rmay› amaclad›k. Yontem: Cal›flmaya Gaziantep Universitesi, T›p Fakultesi, Psikiyatri Anabilim Da- l›, Psikotik Bozukluklar Birimi'nde ayaktan takip edilen 116 hasta icinden DSM- IV'e gore flizofreni tan›s› konulmufl ve d›fllama olcutlerini karfl›lamayan 60 has- ta (24 erkek, 36 kad›n, yafl ortalamas› 31.93±9.37 y›l, yafl aral›¤› 19-55 y›l) al›n- d›. Yafl ve cinsiyet olarak benzer 40 sal›kl› kifliden (17 erkek, 23 kad›n, yafl orta- lamas› 35.53±9.86 y›l, yafl aral›¤› 20-58) kontrol grubu oluflturuldu. Heparinize tuplere sol on koldan venoz kan ornekleri al›nd›. Kan ornekleri santrifuj edilerek plazma ayr›ld›. Ferroz iyonun ferik iyona enzimatik oksidasyonu temeline daya- nan Erel'in seruloplazmin olcum yontemi ile seruloplazmin olcumu yap›ld›. Bulgular: Seruloplazmin duzeyi flizofreni hastalar›nda sal›kl› kontrollere gore anlaml› olarak yuksekti (p<0.001). Ayr›ca kad›n hastalar erkek hastalara gore daha yuksek plazma seruloplazmin duzeyine sahipti (p<0.001), oysa kontroller- de kad›n ve erkekler aras›nda fark yoktu. Seruloplazmin ile yafl, hastal›k suresi, sigara kullan›m›, flizofreni alt tipleri, belirti fliddeti ve antipsikotik tedavi aras›nda iliflki yoktu. Tart›flma: Bu cal›flma seruloplazminin flizofreni fizyopatolojisinde rolu olabilece- ¤ini ortaya koymufltur. Ayr›ca, bildiimize gore literaturde ilk defa olarak, plaz- ma seruloplazmin duzeyi kad›n hastalarda erkek hastalara gore daha yuksek olarak bulunmufltur. Artm›fl seuloplazminin duzeyinin flizofrenideki rolunun ve cinsiyet fark›n›n oneminin ac›kl›¤a kavuflturulmas› icin ileri cal›flmalar gerek- mektedir. ABSTRACT: Increased plasma ceruloplasmin levels in schizophrenia Objective: Ceruloplasmin is a protein in the human serum that is synthesized by hepatocytes, but extrahepatic gene expression in the brain, lung, spleen, and testis has also been reported. Ceruloplasmin contains approximately 95% of serum copper and it carries copper from liver to numerous tissues. Ceruloplasmin level reflects largely the copper concentration of the serum. However, ceruloplasmin has also an antioxidant function that is known as the acute phase reactant. Additionally, ceruloplasmin has a role in the oxidation of serotonin, epinephrine, and norepinephrine. Abnormalities in ceruloplasmin levels have been associated with several neurodegenerative diseases. Moreover, the alteration of plasma ceruloplasmin levels has been linked to schizophrenia and its some clinical characteristics including acute or chronic phase, the length of the disease or whether the patients on treatment or not. However, there exists a controversy on relationship between the plasma level of ceruloplasmin and schizophrenia. There are number of reports on the increased or decreased and/or normal level of plasma ceruloplasmin in association with schizophrenia. These differences may have been originated from the usage of different measurement methods, clinical situations, and ethnobiological differences. In the present study, we aimed to investigate the association between plasma ceruloplasmin level and schizophrenia in Turkish patients. Methods: 60 patients (36 women and 24 men, mean of age 31.93±9.37 years, range 19-55) that were diagnosed as schizophrenia according to DSM-IV were included for this study at the Psychotic Disorders Unit, Department of Psychiatry, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey. The control group consisted of 40 healthy subjects in similar age and gender (23 women, 17 men). Venous blood samples were collected from the left forearm into heparinized tubes. The blood samples were centrifuged and the plasma was removed. Erel's ceruloplasmin measurement method that is based on the enzymatic oxidation of ferrous ions to ferric ions was used. SPSS Windows program 13.0 was applied for statistical analysis. Results: Plasma ceruloplasmin levels of schizophrenic patients were significantly higher than the healthy controls (p<0.001). In addition, female patients had higher ceruloplasmin levels than male patients (p<0.001), while there was no statistically significant difference between women and men in the control group. There was no association between the ceruloplasmin levels and the age, the duration of illness, smoking, schizophrenia subtypes, symptom severity, and antipsychotic therapy. Conclusions: The study suggests that ceruloplasmin may play a role in pathophysiology of schizophrenia. Moreover, female patients having a higher level of ceruloplasmin than those of male patients that is first time reported in the literature. However, further studies are needed to clarify the higher level of ceruloplasmin in schizophrenia and to reveal the importance of the gender differences in ceruloplasmin levels in schizophrenia.