Latar Belakang: Skizofrenia merupakan gangguan jiwa berat yang kompleksdengan angka harapan hidup yang rendah karena penyakit kardiovaskular. Orangdengan skizofrenia rentan mengalami sindroma metabolik meskipun tidakmendapat pengobatan antipsikotika. Sebuah penelitian di RSUPN CiptoMangunkusumo menunjukkan prevalensi sindroma metabolik sebanyak 3,3%sampai 68% yang berhubungan dengan stress oksidatif dan berpotensi menurunkanproduksi ATP. Penelitian ini berusaha menjelaskan patofisiologi sindromametabolik pada skizofrenia dan hubungannya terhadap polimorfisme gen GCLCGAG TNR, stres oksidatif dan aktivitas metabolisme seluler.Metode: Penelitian merupakan penelitian observasional analitik. Subjek sebanyak25 pasien skizofrenia dan 25 pasien kontrol sehat dilakukan pengambilan fibroblasdan PBMC kemudian dilakukan pengamatan polimorfisme gen GCLC GAG TNR,stres oksidatif (kadar MDA, MnSOD, GSH, GSSG, dan rasio GSH/GSSG),aktivitas metabolisme seluler (kadar ATP), dan parameter sindroma metabolik(lingkar pinggang, Indeks Massa Tubuh (IMT), LDL-c, HDL-c, TG, HbA1C, dantekanan darah). Hubungan dianalisis dengan uji komparasi atau uji korelasi.Hasil: Terdapat korelasi pada sel fibroblas dengan PBMC yaitu korelasi kuat padaMnSOD (r=0.797) dan korelasi sedang pada GSSG (r=0.581). Didapatkanperbedaan yang bermakna pada kadar stres oksidatif yaitu MDA (p=0.013), GSH(p≤0.001), GSSG (p≤0.001), dan rasio GSH/GSSG (p≤0.001) pada kelompokskizofrenia dan kontrol serta didapatkan hubungan polimorfisme gen GCLC GAGTNR terhadap MDA (p=0.054) dan GSSG (p=0.010) pada kelompok skizofreniatetapi tidak ditemukan perbedaan kadar ATP dan hubungan antara polimorfismeGCLC GAG TNR terhadap kadar ATP. Pada orang dengan skizofrenia didapatkanlingkar pinggang, IMT, LDL-c, dan HDL-c yang lebih rendah(p=0.025;p=0.003;p=0.022;p=0.010) dan TG yang lebih tinggi (p=0.038)dibandingkan kelompok kontrol.Simpulan: Polimorfisme gen GCLC GAG TNR memiliki hubungan terhadap stresoksidatif tetapi tidak ada hubungan terhadap aktivitas metabolisme seluler. Tidakterdapat perbedaan aktivitas metabolisme seluler pada orang dengan skizofreniadan tidak ditemukan hubungan antara metabolisme seluler dengan sindromametabolik. Terjadi perubahan kadar penanda stres oksidatif yang memilikihubungan terhadap sindroma metabolik pada orang dengan skizofrenia

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Background: Schizophrenia is a complex severe mental disorder with low life

expectancy due to cardiovascular disease. People with schizophrenia is prone to

metabolic syndrome even if they do not receive antipsychotic. One study in Cipto

Mangunkusumo General Hospital showed the prevalence of metabolic syndrome

as much as 3.3% to 68% which correlate with oxidative stress and has the potential

to reduce ATP production. This study aims to explain the pathophysiology of the

metabolic syndrome in schizophrenia and its relationship to the GCLC GAG TNR

gene polymorphism, oxidative stress and metabolic activity.

Methods: This research is an observational analytic study. Twenty five

schizophrenic patients and 25 healthy control patients were admitted to study.

Fibroblast and PBMC (peripheral blood mononuclear cell) were taken to measure

GCLC GAG TNR gene polymorphism, oxidative stress (levels of MDA, MnSOD,

GSH, GSSG, and GSH/GSSG ratio), cellular metabolic activity (ATP levels), and

metabolic syndrome parameters (waist circumference, body mass index (BMI),

LDL-c, HDL-c, TG, HbA1C, and blood pressure). Relationship between variables

were analyzed by comparison test or correlation test.

Results: There is a correlation in fibroblast cells with PBMC with a strong

correlation in MnSOD (r=0.797) and a moderate correlation in GSSG (r=0.581).

There were significant differences in the levels of oxidative stress, namely MDA

(p=0.013), GSH (p≤0.001), GSSG (p≤0.001), and GSH/GSSG ratio (p≤0.001) in

the schizophrenia and control groups. There was correlation found for the

polymorphism of the GCLC GAG TNR gene towards MDA (p=0.054) and GSSG

(p=0.010) in the schizophrenia group but found no difference in ATP levels in the

schizophrenia and control groups alongside with GCLC GAG TNR polymorphism

and ATP levels. In people with schizophrenia, waist circumference, BMI, LDL-c,

and HDL-c were lower (p=0.025;p=0.003;p=0.022;p=0.010) and higher TG

(p=0.038) than the control group.

Conclusion: GCLC GAG TNR gene polymorphism has correlation to oxidative

stress but not to cellular metabolic activity. There is no difference in metabolic

activity in people with schizophrenia and no relationship between cellular

metabolism and the metabolic syndrome. There is alteration of oxidative stress

markers which have an association with metabolic syndrome in people with

schizophrenia.