Depresyon ve ?rritabl Barsak Sendromu Birlikteli?inin N?robiyolojisi Neurobiology of Depression and Irritable Bowel Syndrome Comorbidity

摘要

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 their safety and side effects profile. Nevertheless, tricyclic antidepressants may also have beneficial effects in lower doses than needed to treat clinical depression. Hypnosis, supportive or cognitive behavioral therapies, dietary and defecation habits management are also suggested as beneficial. The recognition of irritable bowel syndrome by psychiatrists may enhance the success of treatment of depression with the comorbidity of irritable bowel syndrome, which disables the patient and frequently accompanies to major depression. In this review, evidence for depression and irritable bowel syndrome comorbidity, the possible underlying mechanisms of this comorbidity and current treatment approaches regarding proposed mechanisms will be discussed.