Journal Article Annotations
2021, 1st Quarter

GI Psychiatry

Annotations by Ashwini Nadkarni, MD
March, 2021

Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis.
Association between inflammatory bowel disease and psychiatric morbidity and suicide: A Swedish nationwide population-based cohort study with sibling comparisons.
The Brain-Gut Axis: Psychological Functioning and Inflammatory Bowel Diseases.

- Gut microbiota in psychiatric disorders: Better understanding or more complexity to be resolved?
- Impact of Recreational Cannabis Legalization on Hospitalizations for Hyperemesis.

PUBLICATION #1 — GI Psychiatry

Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis.

Brigida Barberio, Mohammad Zamani, Christopher J Black, Edoardo V Savarino, Alexander C Ford

Abstract: Lancet Gastroenterol Hepatol. 2021 Mar 12;S2468-1253(21)00014-5. doi: 10.1016/S2468-1253(21)00014-5. Online ahead of print.

Background
Inflammatory bowel disease (IBD) is a lifelong condition with no cure. Patients with IBD might experience symptoms of common mental disorders such as anxiety and depression because of bidirectional communication via the gut–brain axis and chronicity of symptoms, and because of impaired quality of life and reduced social functioning. However, uncertainties remain about the magnitude of this problem. We aimed to assess prevalence of symptoms of anxiety or depression in adult patients with IBD.

Methods
In this systematic review and meta-analysis, we searched MEDLINE, Embase, Embase Classic, and PsycINFO for papers published from inception to Sept 30, 2020, reporting observational studies that recruited at least 100 adult patients with IBD and that reported prevalence of symptoms of anxiety or depression according to validated screening instruments. We excluded studies that only used a structured interview to assess for these symptoms and studies that did not provide extractable data. We extracted data from published study reports and calculated pooled prevalences of symptoms of anxiety and depression, odds ratios (OR), and 95% CIs.

Findings
Of 5544 studies identified, 77 fulfilled the eligibility criteria, including 30 118 patients in total. Overall, pooled prevalence of anxiety symptoms was 32·1% (95% CI 28·3–36·0) in 58 studies (I²=96·9%) and pooled prevalence of depression symptoms was 25·2% (22·0–28·5) in 75 studies (I²=97·6%). In studies that reported prevalence of anxiety or depression in patients with Crohn’s disease and ulcerative colitis within the same study population, patients with Crohn’s disease had higher odds of anxiety symptoms (OR 1·2, 95% CI 1·1–1·4) and depression symptoms (1·2, 1·1–1·4) than patients with ulcerative colitis. Overall, women with IBD were more likely to have symptoms of anxiety than were men with IBD (pooled prevalence 33·8% [95% CI 26·5–41·5] for women vs 22·8% [18·7–27·2] for men; OR 1·7 [95% CI 1·2–2·3]). They were also more likely to have symptoms of depression than men were (pooled prevalence 21·2% [95% CI 15·4–27·6] for women vs 16·2% [12·6–20·3] for men; OR 1·3 [95% CI 1·0–1·8]). The prevalence of symptoms of anxiety (57·6% [95% CI 38·6–75·4]) or depression (38·9% [26·2–52·3]) was higher in patients with active IBD than in patients with inactive disease (38·1% [30·9–45·7] for anxiety symptoms and 24·2% [14·7–35·3] for depression symptoms; ORs 2·5 [95% CI 1·5–4·1] for anxiety and 3·1 [1·9–4·9] for depression).

Interpretation
There is a high prevalence of symptoms of anxiety and depression in patients with IBD, with up to a third of patients affected by anxiety symptoms and a quarter affected by depression symptoms. Prevalence was also increased in patients with active disease: half of these patients met criteria for anxiety symptoms and a third met criteria for depression symptoms. Encouraging gastroenterologists to screen for and treat these disorders might improve outcomes for patients with IBD.

Annotation

The finding:
Pooled prevalence of anxiety symptoms in IBD patients was 32% and pooled prevalence of depression sx was 25%. Women with IBD—particularly women with Crohn’s disease— were more likely to experience anxiety than men with IBD. Patients with active disease had a higher probability of experiencing both anxiety and depressive symptoms than did patients with inactive disease.

Strength and weaknesses:
Although this meta-analysis was rigorous in its inclusion and exclusion criteria of relevant studies, the lack of DSM-5 nomenclature makes this report less useful in sharing new insights for psychiatrists (as opposed to gastroenterologists who often need more coaching to implement consistent screening).

Relevance:
This article provides an overview of the frequency and types of mood disorders observed in patients with IBD, a major autoimmune illness with a bidirectional relationship with psychiatric co-morbidity and likely a large source of referrals for C-L psychiatrists

Type of study (EBM guide):
Systematic review or meta-analysis

PUBLICATION #2 — GI Psychiatry

Association between inflammatory bowel disease and psychiatric morbidity and suicide: A Swedish nationwide population-based cohort study with sibling comparisons.

Jonas F Ludvigsson, Ola Olén, Henrik Larsson, Jonas Halfvarson, Catarina Almqvist, Paul Lichtenstein, Agnieszka Butwicka

Abstract: J Crohns Colitis. 2021 Feb 26;jjab039. doi: 10.1093/ecco-jcc/jjab039. Online ahead of print.

Background and Aims
Inflammatory bowel disease (IBD) is linked to psychiatric morbidity, but few studies have assessed general population comparators. We aimed to investigate the risk of psychiatric morbidity and suicide in adult-onset IBD patients.

Methods
Nationwide population-based cohort study in Sweden (1973-2013). We studied the risk of psychiatric disorders and suicide in 69,865 adult-onset IBD patients (ulcerative colitis, UC: n=43,557; Crohn’s disease, CD: n=21,245; and IBD-unclassified: n=5063) compared to 3,472,913 general population references and 66,292 siblings.

Results
During a median follow-up of 11 years, we found 7,465 (10.7%) first psychiatric disorders in IBD (incidence rate, IR/1000 person-years 8.4) and 306,911 (9.9%) in the general population (IR 6.6), resulting in 1.8 extra psychiatric morbidity per 100 patients followed-up for 10 years and a hazard ratio (HR) of 1.3 (95% confidence interval, 95%CI=1.2-1.3). The highest risk of overall psychiatric morbidity was seen in the first year after IBD diagnosis (HR=1.4, 95%CI=1.2-1.6) and in patients with extraintestinal manifestations (HR=1.6, 95%CI=1.5-1.7). Psychiatric morbidity was more common in all IBD subtypes (HRs 1.3 to 1.5). An increased risk of suicide attempts was observed among all IBD types (HRs=1.2 to 1.4), whereas completed suicide was explicitly associated with CD (HR=1.5) and elderly-onset (diagnosed at the age of >60 years) IBD (HR=1.7).

Conclusion
Adult-onset IBD was associated with an increased risk of psychiatric disorders and suicide attempts. Psychological follow-up should be provided to patients with IBD, especially those with extraintestinal manifestations and elderly-onset IBD. This follow-up should transpire within the first year after IBD diagnosis.

Annotation

The finding:
There is an increased risk of psychiatric disorders and suicide attempts among patients with IBD and an increased risk of completed suicide seen in patients with Crohn’s disease and elderly onset of IBD (age 60 or greater).

Strength and weaknesses:
This study provides useful information to psychiatrists making risk assessments of patients with IBD. While it evaluates psychiatric co-morbidity and completed suicide, the study does not assess these together in patients with IBD. It does describe which psychiatric disorders pose increased risk among IBD patients for suicide (eg, bipolar disorder).

Relevance:
As a chronic medical illness with strong psychiatric co-morbidity, IBD poses a higher risk of suicide, but the data guiding us on this question remains uncertain. The study adds to the growing body of evidence of increased risk.

Type of study (EBM guide):
Cohort study

PUBLICATION #3 — GI Psychiatry

The Brain-Gut Axis: Psychological Functioning and Inflammatory Bowel Diseases.

Spyros Peppas, Claudia Pansieri, Daniele Piovani, Silvio Danese, Laurent Peyrin-Biroulet, Andreas G Tsantes, Enrico Brunetta, Argirios E Tsantes, Stefanos Bonovas

Abstract: J Clin Med. 2021 Jan 20;10(3):377. doi: 10.3390/jcm10030377.

The brain-gut axis represents a complex bi-directional system comprising multiple interconnections between the neuroendocrine pathways, the autonomous nervous system and the gastrointestinal tract. Inflammatory bowel disease (IBD), comprising Crohn’s disease and ulcerative colitis, is a chronic, relapsing-remitting inflammatory disorder of the gastrointestinal tract with a multifactorial etiology. Depression and anxiety are prevalent among patients with chronic disorders characterized by a strong immune component, such as diabetes mellitus, cancer, multiple sclerosis, rheumatoid arthritis and IBD. Although psychological problems are an important aspect of morbidity and of impaired quality of life in patients with IBD, depression and anxiety continue to be under-diagnosed. There is lack of evidence regarding the exact mechanisms by which depression, anxiety and cognitive dysfunction may occur in these patients, and whether psychological disorders are the result of disease activity or determinants of the IBD occurrence. In this comprehensive review, we summarize the role of the brain-gut axis in the psychological functioning of patients with IBD, and discuss current preclinical and clinical data on the topic and therapeutic strategies potentially useful for the clinical management of these patients. Personalized pathways of psychological supports are needed to improve the quality of life in patients with IBD.

Annotation

The finding:
This article explains the complex relationship between the brain-gut-microbiome axis and the impact on resulting psychiatric conditions in IBD. The review is based on a MEDLINE and EMBASE literature search.

Strength and weaknesses:
This article provides the most up-to-date summary of the existing data of the bidirectional relationship between psychiatric disorders and IBD and also assesses data for treatment strategies. For many psychiatrists, no new information is presented that would aid in managing IBD patients with psychiatric disorders. However, an explanation of the relevance of diet and fecal microbiota transplantation may be interesting to psychiatrists interested in the most cutting-edge treatments for IBD. The question of whether such treatments and their impact on the intestinal microbiome proves relevant to psychiatric illnesses remains to be uncovered.

Relevance:
The brain-gut-microbiome is the pathophysiological basis for the relationship between IBD and psychiatric disorders; this article details the relationship and the impact on psychiatric disorders. The article also identifies relevant management strategies for psychiatric disorders

Type of study (EBM guide):
Systematic review or meta-analysis

Also of interest – PUBLICATION #4 — GI Psychiatry

Gut microbiota in psychiatric disorders: Better understanding or more complexity to be resolved?

Błażej Misiak, Jerzy Samochowiec, Wojciech Marlicz, Igor Łoniewski

Abstract: Prog Neuropsychopharmacol Biol Psychiatry. 2021 Mar 10;110:110302. doi: 10.1016/j.pnpbp.2021.110302. Online ahead of print.

The ongoing progress in molecular biology has led to the development of new technologies that provide grounds for better understanding of the mechanisms underlying the pathophysiology of psychiatric disorders (PDs). Thereby, our understanding of PDs has largely shifted from the perception of them as disorders with psychopathological processes limited to the brain to those with multisystemic pathophysiology. Indeed, several PDs, especially psychotic and mood disorders, have been associated with a number of peripheral blood alterations related to subclinical inflammation, oxidative stress or metabolic disturbances (Kucukgoncu et al., 2019; Misiak et al., 2019; Pillinger et al., 2019; Salim, 2014). Some of them have also been found to correlate with neurostructural and neurofunctional abnormalities (Najjar and Pearlman, 2015). In addition, certain peripheral blood markers might predict clinical and functional outcomes of PDs (García-Gutiérrez et al., 2020). However, the origins of peripheral blood alterations in PDs still need to be established. With the recognition of the mechanisms linking gut microbiota to the activity of the central nervous system, it has been proposed that multisystemic pathophysiology of psychiatric disorders might originate from the alterations of gut microbiota. In this special issue, we provide a forum of articles summarizing current evidence in this field, proposing novel insights and mechanisms behind the association of gut microbiota with PDs as well as reporting novel findings.

Annotation (unstructured)

This article provides a summary of the evidence for the role of the intestinal microbiome in the pathophysiology of neurodevelopmental disorders, mood disorders, and dementia. Its value is in providing a clear, well-written synthesis of the available data and describing the use of psychobiotics (eg, psychotropics which impact the gut microbiome and consequently treat psychiatric disorders) and probiotics in treating psychiatric disorders.

Type of study (EBM guide):
Systematic review or meta-analysis

Also of interest – PUBLICATION #5 — GI Psychiatry

Impact of Recreational Cannabis Legalization on Hospitalizations for Hyperemesis.

Laura Nemer, Luis F Lara, Alice Hinton, Darwin L Conwell, Somashekar G Krishna, Gokulakrishnan Balasubramanian

Abstract: Am J Gastroenterol. 2021 Mar 1;116(3):609-612. doi: 10.14309/ajg.0000000000001182.

Chronic cannabis use had been associated with hyperemesis. We sought to determine whether cannabis liberalization contributed to increased hospitalizations for hyperemesis. Cannabis use and admissions for hyperemesis in legalized states were compared with those of nonlegalized states, before and after cannabis legalization, using state inpatient databases. From 2011 to 2015, cannabis use increased 2.2 times in legalized states and 1.8 times in nonlegalized states. The odds of presentation with hyperemesis were higher in 2015 compared with those of 2011 in all states. Recreational legalization may be contributing to rising cannabis use. Hospitalizations for hyperemesis have also increased but did not seem to be solely due to cannabis legalization.

Annotation (unstructured)

Cannabinoid hyperemesis syndrome may be a common reason for consult for C/L psychiatrists. This study examines the relationship between increased access to marijuana, and consequently, increased usage and incidents of hyperemesis resulting in hospitalization. This study examines the relationship between cannabis access, increased usage and resulting increase in hospitalizations. Unfortunately, the value of the study is limited in that it does not adequately address confounding factors.

Type of study (EBM guide):
Cohort study