Anksiyete Bozukluklarında Hipotalamus Hipofiz Adrenal (HPA) Ekseni Düzensizliğinin İki Fazlı Modeli: Sistematik Bir İnceleme

Öz

Anksiyete bozuklukları, önemli morbidite ve sakatlık ile ilişkilidir. Hipotalamus-hipofiz-adrenal (HPA) ekseninin düzensizliği, önemli bir biyolojik hipotez olmaya devam etmektedir, ancak bozukluklar ve yöntemler arasındaki bulgular heterojendir. 2014 yılında yayınlanan yapılandırılmış incelemeyi, aynı metodolojik yaklaşımı kullanarak Nisan 2014'ten Kasım 2025'e kadar yapılan çalışmaları da içerecek şekilde güncelledik. Altmış iki kayıt taranmış, yirmi dört tam metin değerlendirilmiş ve on beş çalışma nitel sentez için dahil edilme kriterlerini karşılamıştır. 2014 sonrası literatür, önceki gözden geçirmenin temel sonucunu, yani çalışmalar arasında önemli heterojenliği korurken, bozukluğa özgü gelişmeleri de eklemektedir: (a) maruz kalma öncesi glukokortikoid uygulamasının belirli (basit) fobilerde maruz kalma terapisini kolaylaştırabileceğine dair randomize ve deneysel kanıtlar; (b) yaygın anksiyete bozukluğunda (GAD) saç kortizol konsantrasyonu (HCC) ve uzunlamasına HCC değerlendirmelerinin kullanımının artması, geçici olarak dinamik HPA modellerine dair kanıtlar üretmektedir; ve (c) sosyal anksiyete bozukluğunda (SAD) seans sırasında akut kortizol artışlarının daha kötü maruz kalma sonuçlarını öngörebileceğine dair artan veriler. Genel olarak, güncellenen kanıtlar, akut anksiyete durumlarının genellikle geçici HPA hiperaktivasyonu ve yüksek kortizol ile birlikte görüldüğü, kronik veya tekrarlayan hastalıkların ise HPA aşağı regülasyonu veya kortizol üretiminin azalmasına veya HCC'nin normalleşmesine yol açan körelmiş tepkilerle karakterize olabileceği iki fazlı bir modeli desteklemektedir.

Anahtar Kelimeler

• Anksiyete bozuklukları
• kortizol
• sistematik inceleme
• hipotalamus-hipofiz-adrenal eksen

A Dual-Stage Model of Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation in Anxiety Disorders: A Systematic Review

Öz

Anxiety disorders are associated with substantial morbidity and disability. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis remains a prominent biological hypothesis, but findings across disorders and methods are heterogeneous. We updated the structured review published in 2014 to include studies from April 2014 to November 2025 using the same methodological approach. Sixty-two records were screened; twenty-four full texts were assessed and fifteen studies met inclusion criteria for qualitative synthesis. The post-2014 literature preserves the principal conclusion of the earlier review, substantial inter-study heterogeneity, while adding disorder-specific advances: (a) randomised and experimental evidence that pre-exposure glucocorticoid administration can facilitate exposure therapy in specific (simple) phobia; (b) increasing use of hair cortisol concentration (HCC) and longitudinal HCC assessments in generalised anxiety disorder (GAD) producing evidence for temporally dynamic HPA patterns; and (c) growing data that acute in-session cortisol elevations in social anxiety disorder (SAD) may predict poorer exposure outcomes. Overall, the updated evidence provides convergent support for a dual-phase model in which acute anxiety states are commonly accompanied by transient HPA hyperactivation and elevated cortisol, while chronic or recurrent illness may be characterised by HPA down-regulation or blunted responses leading to reduced cortisol output or normalised HCC.

Anahtar Kelimeler

• anxiety disorders
• HPA axis
• cortisol
• systematic review
• hypothalamic-pituitary-adrenal axis

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