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Journals / Psikiyatride Güncel Yaklaşımlar / 2026 / Cilt: 18 Sayı: 2

Molecular Evidence Underlying the Dopamine Hypothesis of Schizophrenia

Şizofrenide Dopamin Hipotezinin Moleküler Temelleri

Burcu Çaykara Peran(SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0001-7063-2140
Pages
452–465
Publication Date
2026-04-04
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

This study discusses the validity of the dopamine hypothesis by reviewing molecular evidence and relevant findings from the literature.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Schizophrenia is a chronic psychiatric disorder characterized by positive symptoms such as delusions and hallucinations, and negative symptoms like alogia and avolition.
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Key Findings & Data:Affecting approximately 1% of the population, its etiology remains unclear, but it is believed to arise from the interaction of genetic and environmental factors, primarily impacting the frontal and temporal lobes.
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Conclusion & Impact:This study discusses the validity of the dopamine hypothesis by reviewing molecular evidence and relevant findings from the literature.
🔬Design:Review & Systematic Survey
📍Scope:Comprehensive Sample
⚙️Variables:Şizofreni · dopamin · dopamin reseptörleri

Abstract

Schizophrenia is a chronic psychiatric disorder characterized by positive symptoms such as delusions and hallucinations, and negative symptoms like alogia and avolition. Affecting approximately 1% of the population, its etiology remains unclear, but it is believed to arise from the interaction of genetic and environmental factors, primarily impacting the frontal and temporal lobes. The dopamine hypothesis, a leading theory in explaining schizophrenia’s pathophysiology, is based on observations that dopamine-enhancing substances like amphetamines can induce psychotic symptoms. Postmortem brain studies showing increased dopamine levels and D2 receptor density further support this hypothesis. Changes in D2R expression and dimerization are significant in schizophrenia’s molecular basis. However, the dopamine hypothesis faces criticism due to inconsistencies between dopamine levels and symptoms, and the limited efficacy of antipsychotics in addressing negative and cognitive symptoms. Other neurotransmitter systems, including glutamate, GABA, and serotonin, also contribute to schizophrenia. Notably, NMDA receptor hypofunction is linked to neurodevelopmental and neurodegenerative processes. Genetic studies highlight variations in genes like ZNF804A, BDNF, and HLA as risk factors. Epigenetic mechanisms further influence gene expression, contributing to the disorder’s pathophysiology. Schizophrenia requires a multifactorial model beyond dopamine dysfunction, with promising new treatments targeting glutamatergic, serotonergic, and immune pathways. This study discusses the validity of the dopamine hypothesis by reviewing molecular evidence and relevant findings from the literature.

Özet

Şizofreni, sanrılar, varsanılar gibi pozitif semptomlar ile aloji, avolüsyon gibi negatif semptomları içeren kronik bir psikiyatrik bozukluktur. Toplumda yaklaşık %1 oranında görülen hastalığın etiyolojisi tam bilinmemekle birlikte, genetik ve çevresel faktörlerin etkileşimiyle frontal ve temporal lobları etkilediği düşünülmektedir. Dopamin hipotezi, şizofreninin patofizyolojisini açıklayan temel teorilerden biridir ve amfetamin gibi dopamin artırıcı maddelerin psikotik semptomları tetiklediği gözlemlerine dayanır. Postmortem beyin örneklerinde dopamin yoğunluğu ve D2 reseptörlerindeki artışlar bu hipotezi destekler. Şizofrenide D2R ekspresyonundaki değişiklikler ve dimerizasyon, hastalığın moleküler temelinde önemli rol oynar. Ancak, dopamin hipotezi, semptomlarla dopamin düzeyleri arasındaki tutarsızlıklar ve negatif/bilişsel semptomlarda antipsikotiklerin sınırlı etkisi nedeniyle eleştirilmektedir. Glutamat, GABA ve serotonin gibi diğer nörotransmitter sistemleri de şizofrenide rol oynar. Özellikle NMDA reseptör hipofonksiyonu, nörogelişimsel ve nörodejeneratif süreçlerle ilişkilendirilir. Genetik çalışmalar, ZNF804A, BDNF ve HLA gibi genlerdeki varyasyonların hastalık riskini artırdığını gösterir. Epigenetik mekanizmalar da gen ekspresyonunu etkileyerek patofizyolojiye katkıda bulunur. Şizofreni, dopamin disfonksiyonunun ötesinde, çok faktörlü bir modelle açıklanmalı; glutamaterjik, serotoninergik ve immün yolları hedefleyen yeni tedaviler umut vadetmektedir. Bu çalışma, dopamin hipotezinin geçerliliğini moleküler kanıtlara ve literatürdeki ilgili bulgulara dayandırarak tartışmaktadır.

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Cite This Article

Peran, B. Ç. (2026). Molecular Evidence Underlying the Dopamine Hypothesis of Schizophrenia. Psikiyatride Güncel Yaklaşımlar, Cilt: 18 Sayı: 2, 452–465. https://doi.org/10.18863/pgy.1646228

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