A cross-sectional study of gastrointestinal symptoms, depressive symptoms and trait anxiety in young adults.

BACKGROUND: >Patients with functional gastrointestinal disorders have a high psychiatric co-morbidity. This study aimed to investigate and characterise gastrointestinal symptoms in relation to depressive symptoms and trait anxiety in a well-defined population of young adult psychiatric outpatients and healthy controls. METHODS: Gastrointestinal symptoms were assessed with the Gastrointestinal Symptom Rating Scale for Irritable Bowel Syndrome (GSRS-IBS). Depressive symptoms were assessed with the Montgomery-Åsberg Depression Rating Scale- Self assessment (MADRS-S). Trait anxiety was estimated with three of the Swedish universities of Personality (SSP) scales: Somatic trait anxiety, Psychic trait anxiety and Stress susceptibility. Self-ratings were collected from 491 young adult psychiatric outpatients and 85 healthy controls. Gastrointestinal symptom severity was compared between patients with and without current psychotropic medication and controls. Associations between gastrointestinal symptoms, depressive symptoms and trait anxiety were assessed using Spearman's coefficients and generalized linear models adjusting for possible confounders (sex, body mass index, bulimia nervosa). RESULTS: Patients, with and without current psychotropic medication, reported significantly more gastrointestinal symptoms than controls. In the generalized linear models, total MADRS-S score (p < 0.001), Somatic trait anxiety (p < 0.001), Psychic trait anxiety (p = 0.002) and Stress susceptibility (p = 0.002) were independent predictors of the total GSRS-IBS score. Further exploratory analysis using unsupervised learning revealed a diverse spectrum of symptoms that clustered into six groups. CONCLUSION: Gastrointestinal symptoms are both highly prevalent and diverse in young adult psychiatric outpatients, regardless of current psychotropic medication. Depressive symptom severity and degree of trait anxiety are independently related to the total gastrointestinal symptom burden.

The Relationship Between Daytime Salivary Melatonin and Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care.

OBJECTIVE: The pathophysiology of irritable bowel syndrome (IBS) is not completely understood, although we do know that patients with IBS have a high prevalence of psychiatric comorbidity (mainly depression and anxiety disorders). Melatonin, produced in the gastrointestinal tract, influences gut motility. Psychiatric conditions are associated with circadian disturbances in peripheral melatonin levels. This study aimed to investigate associations between daytime salivary melatonin and gastrointestinal symptoms in young adult psychiatric patients. METHODS: Ninety-six patients (86% women), aged 18-25 years (M (SD) = 21 (2)), seeking psychiatric care with primarily anxiety disorders, affective disorders, or both were included in the study. Total scores from the Gastrointestinal Symptoms Rating Scale - IBS were compared with salivary melatonin measured at three time points (30 minutes after waking up, at 11:00 hours and 30 minutes after lunch) during the waking hours of 1 day. RESULTS: After adjustment for potential confounders, melatonin levels in saliva 30 minutes after lunch remained significantly correlated to the total Gastrointestinal Symptoms Rating Scale - IBS score after correction for multiple testing (B = 0.016, SE = 0.006, p = .015, q = 0.045). In a post hoc analysis, symptoms of gastrointestinal pain and bloating contributed most to this association. CONCLUSIONS: In young adult psychiatric patients, salivary melatonin levels after lunch are associated with gastrointestinal symptoms, which is consistent with the proposed effect of elevated levels of gastrointestinal melatonin on gut motility. This result suggests a link between IBS symptoms and regulation of melatonin in patients with psychiatric disorders.

Melatonin Immunoreactivity in Malignant Small Intestinal Neuroendocrine Tumours.

BACKGROUND/AIMS: Small intestinal neuroendocrine tumours (SI-NETs) are derived from enterochromaffin cells. After demonstrating melatonin in enterochromaffin cells, we hypothesized that SI-NETs may express and secrete melatonin, which may have an impact on clinical factors and treatment response. METHODS: Tumour tissue from 26 patients with SI-NETs, representing paired sections of primary tumour and metastasis, were immunohistochemically stained for melatonin and its receptors, MT1 and MT2. Plasma melatonin and immunoreactivity (IR) for melatonin, MT1 and MT2 in tumour cells were compared to other tumour markers and clinical parameters. Melatonin was measured at two time points in fasting morning plasma from 43 patients with SI-NETs. RESULTS: Melatonin IR was found in all SI-NETS. Melatonin IR intensity in primary tumours correlated inversely to proliferation index (p = 0.022) and patients reported less diarrhoea when melatonin IR was high (p = 0.012). MT1 IR was low or absent in tumours. MT2 expression was medium to high in primary tumours and generally reduced in metastases (p = 0.007). Plasma-melatonin ranged from 4.5 to 220.0 pg/L. Higher levels were associated with nausea at both time points (p = 0.027 and p = 0.006) and flush at the second sampling. In cases with disease stabilization or remission (n = 34), circulating melatonin levels were reduced in the second sample (p = 0.038). CONCLUSION: Immunoreactive melatonin is present in SI-NETs. Circulating levels of melatonin in patients with SI-NETs are reduced after treatment. Our results are congruent with recent understanding of melatonin's endocrine and paracrine functions and SI-NETs may provide a model for further studies of melatonin function.

Human gastroenteropancreatic expression of melatonin and its receptors MT1 and MT2.

BACKGROUND AND AIM: The largest source of melatonin, according to animal studies, is the gastrointestinal (GI) tract but this is not yet thoroughly characterized in humans. This study aims to map the expression of melatonin and its two receptors in human GI tract and pancreas using microarray analysis and immunohistochemistry. METHOD: Gene expression data from normal intestine and pancreas and inflamed colon tissue due to ulcerative colitis were analyzed for expression of enzymes relevant for serotonin and melatonin production and their receptors. Sections from paraffin-embedded normal tissue from 42 individuals, representing the different parts of the GI tract (n=39) and pancreas (n=3) were studied with immunohistochemistry using antibodies with specificity for melatonin, MT1 and MT2 receptors and serotonin. RESULTS: Enzymes needed for production of melatonin are expressed in both GI tract and pancreas tissue. Strong melatonin immunoreactivity (IR) was seen in enterochromaffin (EC) cells partially co-localized with serotonin IR. Melatonin IR was also seen in pancreas islets. MT1 and MT2 IR were both found in the intestinal epithelium, in the submucosal and myenteric plexus, and in vessels in the GI tract as well as in pancreatic islets. MT1 and MT2 IR was strongest in the epithelium of the large intestine. In the other cell types, both MT2 gene expression and IR were generally elevated compared to MT1. Strong MT2, IR was noted in EC cells but not MT1 IR. Changes in gene expression that may result in reduced levels of melatonin were seen in relation to inflammation. CONCLUSION: Widespread gastroenteropancreatic expression of melatonin and its receptors in the GI tract and pancreas is in agreement with the multiple roles ascribed to melatonin, which include regulation of gastrointestinal motility, epithelial permeability as well as enteropancreatic cross-talk with plausible impact on metabolic control.