Depression in Children with Inflammatory Bowel Disease

January 5, 2015 · Posted in Current Treatments, Risk Factors · Comment 

boy with stomach painThe incidence of irritable bowel disease has been increasing in recent years as obesity has increased. At a symposium at the 2014 meeting of the American Academy of Child and Adolescent Psychiatry, researcher Eva Szigethy discussed depression in inflammatory bowel disease, which most often involves Crohn’s disease or ulcerative colitis. These conditions are associated with increased levels of inflammatory markers such as interleukin 1 (IL-1), interleukin 6 (IL-6), and TNF alpha, and these in turn induce the acute phase reactive protein called c-reactive protein (CRP). The interleukins peak in the first 12 hours after an inflammatory challenge and CRP peaks at 48 hours and returns to normal at 120 hours. Il-6 is most closely associated with the somatic symptoms of inflammation, including depression, fatigue, loss of appetite, and decreased sleep, while TNF alpha is associated with non-somatic symptoms, such as irritability.

Szigethy found that in a randomized trial of cognitive behavior therapy versus supportive therapy in children with inflammatory bowel disease, inflammatory activity decreased significantly with cognitive behavioral therapy, and the therapy particularly helped the somatic symptoms of fatigue, sleep disorder, anhedonia (loss of interest in activities once enjoyed), appetite suppression, and mood dysregulation. In contrast, when antidepressants are given to those with inflammatory bowel disease, the drugs are not particularly helpful for these somatic symptoms. Inflammatory bowel diseases are treated with steroids in 21% of patients and with a genetically engineered drug called infliximab in 30%. Adding cognitive behavioral therapy to the regimen decreases CRP and red cell sedimentation rate, an associated measure of inflammation.

The discussant of the symposium on inflammation, Frank Lotrich, described how inflammation alters sleep, and this appeared to interact with genetic risk of illness. For example, those with certain genetic variations (the short SS allele of the serotonin transporter and the val-66-met allele of proBDNF) were most likely to experience sleep disturbance following treatment with interferon gamma, a treatment that fights the virus that causes Hepatitis C, creating inflammation in the process. Interferon gamma causes depression in about one-third of the patients who take it.

Lotrich pointed out that low levels of omega-3 fatty acids are associated with increased irritability and anger, and this is related to the presence of the A allele of TNF alpha. TNF alpha is also closely linked with irritability and anger, suggesting the possible benefits of omega-3 fatty acid supplementation to target irritability and anger more selectively. This would be consistent with the data of researcher Mary A. Fristad.

Il-6 is closely associated with the somatic symptoms of depression, particularly poor sleep, which is itself associated with increases in depression. This is consistent with inflammation being a marker of poor response to antidepressants; Lotrich noted that the selective serotonin reuptake inhibitors (SSRIs), which help depression, are far more effective against the non-somatic aspects of depression and less effective against low energy, decreased interest, and fatigue. However, extrapolating from the data on inflammatory bowel disease, cognitive behavioral therapy may be most helpful on these somatic symptoms.

 

 

Cognitive Behavioral Therapy Helps Depression And Inflammation In Inflammatory Bowel Disease

December 6, 2013 · Posted in Potential Treatments · Comment 

Teen girl with bellyacheCognitive behavioral therapy may improve both depression symptoms and inflammatory bowel disease. At a symposium on early-onset depression at the 2013 meeting of the American Academy of Child and Adolescent Psychiatry, Eva Szigethy of the University of Pittsburg discussed depression in inflammatory bowel disease (IBD), i.e. Crohn’s disease or ulcerative colitis. Depression and bipolar disorder are often associated with elevated inflammatory markers, such as IL-1b, IL-2, IL-6, INF gamma, TNF alpha, and CRP (C-reactive protein). This kind of inflammation can cause symptoms like decreased appetite, fatigue, anhedonia (loss of pleasure in activities one once enjoyed), and motor slowing.

In children with IBD randomized to cognitive behavioral therapy or just routine supportive care, the somatic symptoms of those receiving cognitive behavioral therapy improved, as did their IBD.

Other treatments may also target both depression and inflammation. Szigethy noted that there is some evidence that the TNF alpha–inhibiting anti-inflammatory drug infliximab has some antidepressant effects in those with high CRP and in patients with the autoimmune condition psoriasis. She indicated that the antidepressant bupropion decreases depression and inflammation in IBD and that bupropion has anti–TNF alpha effects (at least in animals).

Currently levels of inflammation are measured with blood drawn from a vein, but new techniques may be more child-friendly.  These include measuring inflammatory markers in hair (which reflects levels over the previous two weeks), saliva, or with a drop of blood from a pinprick (as used by researcher Ben Goldstein).

In Veterans, PTSD Is Associated With Autoimmune Illnesses

July 2, 2013 · Posted in Comorbidities, Risk Factors · Comment 

US soldier

At a recent scientific meeting, Thomas Neylan and colleagues reported that post-traumatic stress disorder (PTSD) may be connected to autoimmune illnesses. In this study, 673,277 veterans of the US military who had served in Iraq and Afghanistan were screened for the development of PTSD. The illness was diagnosed in 31% of the veterans, and those individuals had a higher incidence of autoimmune-related disorders including thyroiditis, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and systemic lupus erythematosus. Neylan’s research group specifically examined those whose disorders developed after the onset of the PTSD, and found that the statistical relationship between their illnesses and PTSD was strong. However, the researchers also found that there was evidence of a similarly strong relationship in the other direction: veterans who were first diagnosed with some of these same autoimmune difficulties also went on to develop PTSD.

Many previous clinical and preclinical studies have linked altered immune and autoimmune mechanisms to severe stressors such as those that are involved in PTSD. This is the first study to unequivocally demonstrate the relationship in an extraordinarily large number of patients.

Editor’s Note:  These findings resemble those that suggest that among the general population, childhood adversity is associated with an increased incidence of a variety of medical disorders in adulthood. Similarly, in the Bipolar Collaborative Network in which this editor (Post) is an investigator, we found that a history of childhood adversity in patients with bipolar disorder was associated with an increased incidence of a variety of medical illnesses in adulthood, including some related to immune and autoimmune function.

More research that would measure inflammatory markers in PTSD and mood disorders is needed. It would also be important to ascertain whether treatment of mood disorders and PTSD reduces the risk of autoimmune disorders.