Electronic Theses and Dissertation

ABSTRAK

Latar Belakang: Skizofrenia merupakan gangguan psikiatri kronis yang dipengaruhi faktor genetik, salah satunya polimorfisme Val66Met Gen Brain-Derived Neurotrophic Factor (BDNF) yang berperan dalam regulasi neuroplastisitas. Variasi ini diduga mempengaruhi gejala klinis, fungsi kognitif, dan respons terapi anti psikotik, namun bukti pada populasi Aceh masih terbatas. Penelitian ini bertujuan menilai hubungan polimorfisme Val66Met Gen BDNF dengan gejala klinis, Fungsi kognitif, dan respons terapi anti psikotik pada orang dengan skizofrenia (ODS) suku Aceh.
Metode: Studi observasional komparatif dengan kohort prospektif dilakukan pada 207 ODS berusia 18–45 tahun. Genotipe ditentukan menggunakan PCR–RFLP. Gejala klinis dinilai dengan PANSS dan fungsi kognitif dengan MoCA-INA pada hari ke-0, 14, dan 42 terapi risperidon. Analisis dilakukan untuk membandingkan perbedaan antar genotipe Val/Val, Val/Met, dan Met/Met serta pola perbaikan dari waktu ke waktu.
Hasil: Distribusi genotipe didominasi Val/Met (52,17%), disusul Val/Val (28,01%) dan Met/Met (19,8%). Pada hari ke-0, Val/Val menunjukkan gejala awal paling ringan dibanding dua kelompok lainnya. Setelah terapi, Val/Val konsisten memberikan respons klinis terbaik, dengan penurunan skor PANSS paling besar pada hari ke-14 dan mencapai −110,31 poin pada hari ke-42, jauh lebih tinggi dibandingkan Met/Met (−51,57 poin) dan Val/Met. Selain itu, Val/Val menunjukkan peningkatan kognitif paling cepat pada hari ke-14 (+9,27 poin), sedangkan Met/Met paling rendah (+5,34 poin). Pada hari ke-42, ketiga genotipe mengalami perbaikan kognitif yang relatif serupa (sekitar +10–11 poin), meskipun perbedaan statistik tetap signifikan. Pola ini menunjukkan adanya mekanisme delayed compensation pada pembawa alel Met.
Kesimpulan: Polimorfisme Val66Met gen BDNF berhubungan dengan gejala klinis, fungsi kognitif, dan respons terapi antipsikotik. Genotipe Val/Val menunjukkan luaran awal yang lebih baik, sedangkan alel Met berkaitan dengan pemulihan awal yang lebih lambat tetapi tetap menunjukkan perbaikan jangka menengah.

Kata Kunci: Polimorfisme Val66Met gen BDNF, skizofrenia, fungsi kognitif, respons terapi anti psikotik.

ABSTRACT Background: Schizophrenia is a chronic psychiatric disorder influenced by genetic factors, including Val66Met Polymorphism of the Brain-Derived Neurotrophic Factor (BDNF) Gene, which plays a key role in neuroplasticity regulation. This genetic variation has been associated with differences in clinical symptoms, cognitive function, and antipsychotic treatment response, although evidence among the Acehnese population remains limited. This study aimed to examine the association of the Val66Met Polymorphism of the Brain-Derived Neurotrophic Factor (BDNF) Gene with clinical symptoms, cognitive function, and antipsychotic treatment response in Acehnese individuals with schizophrenia. Methods: This observational comparative study with a prospective cohort design included 207 subjects aged 18–45 years. Genotyping was performed using PCR–RFLP. Clinical symptoms were assessed using the PANSS, and cognitive function was evaluated using the MoCA-INA on days 0, 14, and 42 of risperidone treatment. Analyses compared differences among Val/Val, Val/Met, and Met/Met genotypes and examined patterns of improvement over time. Results: Genotype distribution was dominated by Val/Met (52.17%), followed by Val/Val (28.01%) and Met/Met (19.8%). At baseline, Val/Val subjects displayed the mildest clinical symptoms. After treatment, Val/Val consistently showed the strongest therapeutic response, with the greatest PANSS reduction at day 14 and reaching −110.31 points by day 42—substantially greater than Met/Met (−51.57 points) and Val/Met. Val/Val also demonstrated the most rapid early cognitive improvement on day 14 (+9.27 points), while Met/Met showed the smallest gain (+5.34 points). By day 42, all genotypes showed relatively similar cognitive improvement (approximately +10–11 points), although statistically significant differences remained. This pattern suggests a delayed compensation mechanism among Met-allele carriers. Conclusion: Val66Met Polymorphism of the Brain-Derived Neurotrophic Factor (BDNF) Gene influences symptom severity, cognitive function, and antipsychotic treatment response. Val/Val represents the most favorable clinical and cognitive outcome, whereas the Met allele is associated with slower early recovery but comparable medium-term improvement. Keywords: Val66Met Polymorphism of the (BDNF) Gene, schizophrenia, cognitive function, antipsychotic treatment response.