Neurobiology of Depression and Irritable Bowel Syndrome Comorbidity

Yıl 2009, Cilt: 1 Sayı: 2, 120 - 131, 01.06.2009

M. Çağdaş Eker Özlem Donat Eker

Öz

Irritable bowel syndrome is a disabling functional disorder with a frequent comorbidity of depression though underlying mechanisms remain yet little understood. Various signs and symptoms have been determined as diagnostic criteria in recent years and standardized as Rome-III criteria. Irritable bowel syndrome can have constipation-dominant, diarrhea-dominant or mixed clinical presentations. Main features can be summarized as continuous and recurrent abdominal pain or discomfort associated with a change of stool frequency or consistency and usually relief of symptoms with defe-cation in the absence of physical or laboratory abnormalities indicative of an organic etiology. The frequency of major depressive disorder diagnosis reaches up to two thirds of irritable bowel syndrome patients. Moreover, the comorbidity of irritable bowel syndrome among patients with major depression is highly frequent (30%). The mechanism underlying irritable bowel syndrome which have been considered as a kind of a somatization disorder for a long time and now as a functional bowel disease is in the brain-gut axis. Low grade mucosal inflammation and cytokines originating from mucosal inflammation have important functions in the pathophysiology of irritable bowel syndrome and its comorbidity with major depression. Besides the inflammatory factors lumbosacral visceral hyperexcitability which is an individual variation is proposed as the main underlying cause of irritable bowel syndrome. Visceral hyper-excitability is mediated by cytokines and neuro-mediators and stress is known to increase the effect of this mechanism. Furthermore, molecules participating in this mechanism (e.g. cytokines, corticotrophin releasing factor, neurokinins and monoamines) play important roles in the pathophysiology of depression. Increased activation in the pain matrix (thalamus – insula – prefrontal cortex) and insufficiency of endogenous pain inhibitory system are regarded as possible casuses of excessive feeling of irritable bowel syndrome symptoms leading to the dysfunction in the cortical representation of bodily states and negative emotional experiences. Individual variations in the interaction of cytokines, corticotrophin releasing factor, neurokinins (substance P, neurokinin A and neurokinin B) and monoamines (serotonin and norepinephrine), and neuroanatomic functions may answer the question of "why do some irritable bowel syndrome patients experience depression and some do not?". Moreover, irritable bowel syndrome patients with comorbid depression and anxiety disorders are reported to be complaining more about their irritable bowel syndrome symptoms. Although several treatment strategies are considered by clinicians in the management of irritable bowel syndrome, it is suggested that antidepressant medications to have the priority in the treatment of irritable bowel syndrome with the comorbidity of depression. Selective serotonin re-uptake inhibitors are the drug of choice regarding thei

Anahtar Kelimeler

Major depressive disorder, irritable bowel syndrome, comorbidity, neurobiology, treatment

Depresyon ve İrritabl Barsak Sendromu Birlikteliğinin Nörobiyolojisi

Öz

İrritabl barsak sendromu (İBS) yaşamı güçleştiren ve depresyonla birlikteliği çok sık karşılaşılan işlevsel bir barsak hastalığı olmasına karşın altında yatan düzenek tam olarak aydınlatılamamıştır. Tanı ölçütleri olarak değişik zamanlarda güncellenen belirti ve bulgular tanımlanmış, son olarak Roma-III olarak belirlenen ölçütlerde karar kılınmıştır. Konstipasyon-baskın, diare-baskın ya da karma irritabl barsak sendromu şeklinde görülen, irritabl barsak sendromu sürekli veya yineleyici karın ağrısı ya da karında rahatsızlık hissi ile barsak alışkanlığındaki değişkenlik, hastanın defekasyon ile rahatlaması ve yakınmaları organik yönden açıklayacak fiziksel veya laboratuar bulgularının olmayışı ile karakterizedir. İrritabl barsak sendromu olan hastalarda major depresif bozukluk sıklığı hastaların üçte ikisini kapsayacak düzeylere kadar çıkmıştır. Ayrıca, major depresif bozukluk tanısı almış olan hastalarda da irritabl barsak sendromu ek tanısının sıkça (%30) görüldüğü bilinmektedir. Uzunca bir süre bir çeşit somatizasyon bozukluğu olduğu düşünülen ve günümüzde işlevsel gastrointestinal hastalıklar içinde yer alan irritabl barsak sendromunun altında yatan düzenek beyin-barsak eksenindedir. Düşük düzeydeki mukozal yangı ile bu yangıdan kaynaklanan sitokinler irritabl barsak sendromunun patofizyolojisine ve depresyonla olan ilişkisinde önemli yer tutmaktadır. Yangısal elemanların yanısıra bireysel yatkınlıkla geliştiği düşünülen lumbosakral viseral aşırı-uyarılabilirliğin irritabl barsak sendromunun altında yatan esas patoloji olduğu öne sürülmüştür. Viseral aşırı-uyarılabilirlik gerek sitokinler, gerekse nöromediatörler aracılığı ile gelişmekte ve stres bu düzeneğin etkisini artırmaktadır. Ayrıca, bu düzenekte görevli moleküller (sitokinler, kortikotropin salgılatıcı faktör, nörokininler, monoaminler) depresyon patofizyolojisinde de rol oynamaktadır. Ağrı matriksindeki (talamus – insula - prefrontal korteks) artmış etkinlik ve endojen ağrı-kesici sistemin yetersizliğinin irritabl barsak sendromu belirtilerinin abartılı hissedilmesine neden olduğu ileri sürülmüştür. Bu durum bedenin kortikal temsilinde aksamalara ve olumsuz emosyonel yaşantılara neden olmaktadır. Sitokinler, kortikotropin salgılatıcı faktör, nörokininler (substans P, nörokinin A ve nörokinin B) ile monoaminlerin (serotonin ve norepinefrin) etkileşimindeki ve nöroanatomik işlevlerdeki bireysel farklılıklar, bazı irritabl barsak sendromu hastalarında major depresyon görülürken bazılarında görülmemesini açıklayabilir. Dahası, depresyon ve anksiyete bozukluklarının eşlik ettiği irritabl barsak sendromu hastalarının belirtilerden daha çok yakındığı da bilinmektedir. Tedavi konusunda klinisyenlerin pek çok seçeneği değerlendirdiği irritabl barsak sendromuna depresyonun eşlik etmesi durumunda sağaltımda öncelikle antidepresanlara yer verilmesi önerilmektedir. Antidepresan ilaçlar arasında birinci sırada güvenlik ve yan etki profili açısından seçici serotonin geri-alım inhibitörleri yer almak

Anahtar Kelimeler

major depresif bozukluk, irritabl barsak sendromu, komorbidite, nörobiyoloji, sağaltım

Kaynakça

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