Neurochemical, Neuroinflammatory and Neurophysiological Dynamics in The Pathogenesis of Schizophrenia

Year 2025, Volume: 34 Issue: 2, 141 - 155, 30.06.2025

Cansu Sevinçli Bayram , Turker Erguzel

https://doi.org/10.17827/aktd.1614815

Abstract

Schizophrenia is a polygenetic and multifactorial neurodegenerative disease characterized by positive and negative symptoms and cognitive disorders. Considering its chronopathology, it is usually not diagnosed in the prodromal period due to the first psychosis occurring in adulthood. It is aimed to evaluate the relationship between genetic predisposition, epigenetic effects, inflammation, neurotrophic factors, oxidative stress, neurochemical and neurodevelopmental hypotheses and existing biomarkers from a holistic perspective. In this study, neuroimaging methods, blood and CSF values, animal experiments, genomic findings and epigenetic studies shaped by phenotype were analyzed. Hereditary factors, intrauterine developmental anomalies, congenital malformations, prenatal and postnatal stressor factors or exposure to infection are thought to play a role in the formation of the disease by affecting neurodevelopmental processes and brain plasticity. It is stated that cytokine irregularities and imbalances of neurotrophic factors, mitochondrial dysfunction, excessive synaptic pruning may cause dysregulation in oligodendrocytes, microglia and astrocytes. It is stated that oxidative stress factors and neuroinflammation affect neurochemical transmission. According to histological findings, abnormalities occurring in the premorbid period cause functional and structural changes in the brain. It is stated that it is important for candidate markers to reflect the pathological process rather than being epiphenomenal in determining the causal mechanisms related to the pathophysiology of the disease.

Keywords

Schizophrenia , Biomarker , Neurochemical , Neuroinflammation , Pathophysiology

Şizofreni Patogenezinde Nörokimyasal, Nöroenflamatuar ve Nörofizyolojik Dinamikler

Abstract

Şizofreni, pozitif ve negatif semptomlar ile bilişsel bozukluklarla karakterize olmuş poligenetik ve multifaktöriyel bir nörodejeneratif hastalıktır. Kronopatolojisi göz önüne alındığında genellikle ilk psikozun yetişkinlikte ortaya çıkması nedeniyle prodromal dönemde teşhis edilememektedir. Genetik yatkınlık, epigenetik etkiler, enflamasyon, nörotrofik faktörler, oksidatif stres, nörokimyasal ve nörogelişimsel hipotezler ile mevcut biyobelirteçler arasındaki ilişkiselliği holistik perspektiften değerlendirme hedeflenmektedir. Bu çalışmada nörogörüntüleme yöntemleri, kan ve BOS değerleri, hayvan deneyleri, genomik bulgular ve fenotip ile şekillenen epigenetik araştırmalar analiz edilmiştir. Kalıtımsal faktörler, intrauterin gelişim anomalileri, konjenital malformasyonlar, doğum öncesi ve sonrası stresör etkenler ya da enfeksiyona maruziyetin nörogelişimsel süreçleri, beyin plastisitesini etkileyerek hastalığın oluşumunda yer aldığı düşünülmektedir. Sitokin düzensizlikleri ve nörotrofik faktörlerin dengesizlikleri, mitokondriyal disfonksiyon, aşırı sinaptik budamanın oligodendrosit, mikroglia ve astrositlerde disregülasyona neden olabileceği belirtilmektedir. Oksidatif stres faktörleri ve nöroenflamasyonun, nörokimyasal transmisyonu etkilediğine yer verilmektedir. Histolojik bulgulara göre premorbid dönemde meydana gelen anormallikler, beyinde işlevsel ve yapısal değişimler oluşturmaktadır. Hastalığın patofizyolojisine ilişkin nedensel mekanizmaların belirlenmesinde aday belirteçlerin epifenomen olmasının ötesinde patolojik süreci yansıtmasının önemli olduğu ifade edilmektedir. Prodromal, tanısal, tedaviye yönelik belirteçlerin gelişmesi ve hastalığın patofizyolojisinin aydınlatılması için boylamsal çalışmalara ihtiyaç duyulmaktadır. Bu bağlamda, literatürdeki bulguların ve hipotezlerin bütüncül ve ilişkisel bir şekilde değerlendirilmesi amaçlanmaktadır.

Keywords

Şizofreni , Biyobelirteç , Nörokimyasal , Nöroenflamasyon , Patofizyoloji

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