Hospital-presenting self-harm among older adults living in Ireland: a 13-year trend analysis from the National Self-Harm Registry Ireland.

OBJECTIVES: To examine trends in rates of self-harm among emergency department (ED) presenting older adults in Ireland over a 13-year period. DESIGN: Population-based study using data from the National Self-Harm Registry Ireland. SETTING: National hospital EDs. PARTICIPANTS: Older adults aged 60 years and over presenting with self-harm to hospital EDs in Ireland between January 1, 2007 and December 31, 2019. MEASUREMENTS: ED self-harm presentations. RESULTS: Between 2007 and 2019, there were 6931 presentations of self-harm in older adults. The average annual self-harm rate was 57.8 per 100,000 among older adults aged 60 years and over. Female rates were 1.1 times higher compared to their male counterparts (61.4 vs 53.9 per 100,000). Throughout the study time frame, females aged 60-69 years had the highest rates (88.1 per 100,000), while females aged 80 years and over had the lowest rates (18.7 per 100,000). Intentional drug overdose was the most commonly used method (75.5%), and alcohol was involved in 30.3% of presentations. Between the austerity and recession years (2007-2012), self-harm presentations were 7% higher compared to 2013-2019 (incidence rate ratio (IRR): 1.07 95% CI 1.02-1.13, p = 0.01). CONCLUSIONS: Findings indicate that self-harm in older adults remains a concern with approximately 533 presentations per year in Ireland. While in younger age groups, females report higher rates of self-harm, this gender difference was reversed in the oldest age group (80 years and over), with higher rates of self-harm among males. Austerity/recession years (2007-2012) had significantly higher rates of self-harm compared to subsequent years.

Physical and mental illness comorbidity among individuals with frequent self-harm episodes: A mixed-methods study.

Background: Research has indicated an increased risk of self-harm repetition and suicide among individuals with frequent self-harm episodes. Co-occurring physical and mental illness further increases the risk of self-harm and suicide. However, the association between this co-occurrence and frequent self-harm episodes is not well understood. The objectives of the study were (a) to examine the sociodemographic and clinical profile of individuals with frequent self-harm (regardless of suicidal intent) episodes and, (b) the association between physical and mental illness comorbidity, self-harm repetition, highly lethal self-harm methods, and suicide intent. Methods: The study included consecutive patients with five or more self-harm presentations to Emergency Departments across three general hospitals in the Republic of Ireland. The study included file reviews (n = 183) and semi-structured interviews (n = 36). Multivariate logistic regression models and independent samples t-tests were used to test the association between the sociodemographic and physical and mental disorders comorbidity on highly lethal self-harm methods and suicidal intent, respectively. Thematic analysis was applied to identify themes related to physical and mental illness comorbidity and frequent self-harm repetition. Findings: The majority of individuals with frequent self-harm episodes were female (59.6%), single (56.1%), and unemployed (57.4%). The predominant current self-harm method was drug overdose (60%). Almost 90% of the participants had history of a mental or behavioral disorder, and 56.8% had recent physical illness. The most common psychiatric diagnoses were alcohol use disorders (51.1%), borderline personality disorder (44.0%), and major depressive disorder (37.8%). Male gender (OR = 2.89) and alcohol abuse (OR = 2.64) predicted the risk of a highly lethal self-harm method. Suicide intent was significantly higher among those with a diagnosis of major depressive disorder (t = 2.43; p = 0.020). Major qualitative themes were (a) the functional meaning of self-harm (b) self-harm comorbidity (c) family psychiatric history and (d) contacts with mental health services. Participants described experiencing an uncontrollable self-harm urge, and self-harm was referred to as a way to get relief from emotional pain or self-punishment to cope with anger and stressors. Conclusion: Physical and mental illness comorbidity was high among individuals with frequent self-harm episodes. Male gender and alcohol abuse were associated with highly lethal self-harm methods. The mental and physical illness comorbidity of individuals with frequent self-harm episodes should be addressed via a biopsychosocial assessment and subsequent indicated treatment interventions.

Psychosocial and psychiatric factors preceding death by suicide: A case-control psychological autopsy study involving multiple data sources.

BACKGROUND: A range of factors including mental disorders and adverse life events can increase the risk of suicide. The objectives of this study were to examine psychosocial and psychiatric factors and service engagement among suicide decedents compared with living controls. METHODS: A case-control study using multiple sources was conducted. Information on 132 consecutive cases of suicide was drawn from coronial files, and interviews were carried out with 35 family informants and 53 living controls. GPs completed questionnaires for 60 suicide cases and 27 controls. RESULTS: The majority (83.3%) of suicide decedents had contacted a GP in the year prior to death, while 23.3% had 10 or more consultations during the year prior to death. Half of suicide decedents had a history of self-harm. Suicide cases were significantly more likely than controls to have a psychiatric diagnosis (60% vs. 18.5%) and a depressive illness (36.7% vs. 14.8%). Over one-quarter of suicide decedents had been treated as a psychiatric inpatient. DISCUSSION: Primary care providers should be supported to deliver multidisciplinary interventions to engage, assess, and treat patients at risk of suicide, targeting those who present very frequently, those with a history of self-harm or substance misuse, and those with psychological presentations.

Consultation-Liaison Psychiatry Services in Ireland: A National Cross-Sectional Study.

Objective: This study aimed to describe the provision of consultation-liaison psychiatry (CLP, also known as liaison psychiatry) services in acute hospitals in Ireland, and to measure it against recommended resourcing levels. Methods: This is a survey of all acute hospitals in Ireland with Emergency Departments, via an electronic survey sent by email and followed up by telephone calls for missing data. Data were collected on service configuration, activity, and resourcing. Data were collected from CLP or proxy services at all acute hospitals with an Emergency Department in Ireland (n = 29). This study measured staffing and activity levels where available. Results: None of the services met the minimum criteria set out by either national or international guidance per 500 bed general hospital. Conclusions: CLP is a relatively new specialty in Ireland, but there are clear international guidelines about the staffing levels required to run these services safely and effectively. In Ireland, despite clear national guidance on staffing levels, no services are staffed to the levels suggested as the minimum. It is likely that patients in Ireland's acute hospitals have worse outcomes, and hospitals have unnecessary costs, due to this lack. This is the first study of CLP provision in Ireland and demonstrates the resource constraints under which most services work and the heterogeneity of services nationally.

Factors associated with psychiatric admission and subsequent self-harm repetition: a cohort study of high-risk hospital-presenting self-harm.

BACKGROUND: Individuals presenting to hospital with self-harm of high lethality or high suicidal intent are at high risk of subsequent suicide. AIM: To examine factors associated with psychiatric admission and self-harm repetition following high-risk self-harm (HRSH). METHOD: A cohort study of 324 consecutive HRSH patients was conducted across three urban hospitals (December 2014-February 2018). Information on self-harm repetition was extracted from the National Self-harm Registry Ireland. Logistic regression models examined predictors of psychiatric admission and self-harm repetition. Propensity score (PS) methods were used to address confounding. RESULTS: Forty percent of the cohort were admitted to a psychiatric inpatient setting. Factors associated with admission were living alone, depression, previous psychiatric admission, suicide note and uncommon self-harm methods. History of emotional, physical or sexual abuse was associated with not being admitted. Twelve-month self-harm repetition occurred in 17.3% of cases. Following inverse probability weighting according to the PS, psychiatric admission following HRSH was not associated with repetition. Predictors of repetition were recent self-harm history, young age (18-24 years) and previous psychiatric admission. CONCLUSION(S): Findings indicate that psychiatric admission following HRSH is not associated with repeated self-harm and reaffirms the consistent finding that history of self-harm and psychiatric treatment are strong predictors of repetition.

Investigating the relationship between childhood sexual abuse, self-harm repetition and suicidal intent: mixed-methods study.

BACKGROUND: Research into the association between childhood sexual abuse (CSA) and self-harm repetition is limited. AIMS: We aimed to examine the association between self-harm repetition, mental health conditions, suicidal intent and CSA experiences among people who frequently self-harm. METHOD: A mixed-methods study was conducted including consecutive patients aged ≥18 years, with five or more self-harm presentations, in three Irish hospitals. Information was extracted from psychiatric records and patients were invited to participate in a semi-structured interview. Data was collected and analysed with a mixed-methods, convergent parallel design. In tandem, the association between CSA and self-harm repetition, suicidal intent and mental health conditions was examined with logistic regression models and independent sample t-test, with psychiatric records data. Thematic analysis was conducted with interview data, to explore CSA experiences and self-harm repetition. RESULTS: Between March 2016 and July 2019, information was obtained on 188 consecutive participants, with 36 participants completing an interview. CSA was recorded in 42% of the total sample and 72.2% of those interviewed. CSA was positively associated with self-harm repetition (odds ratio 6.26, 95% CI 3.94-9.94, P = 0.00). Three themes emerged when exploring participants' CSA experiences: CSA as a precipitating factor for self-harm, secrecy of CSA accentuating shame, and loss experiences linked to CSA and self-harm. CONCLUSIONS: CSA was frequently reported among people who frequently self-harm, and associated with self-harm repetition. Identification of patients at risk of repetition is key for suicide prevention. This is an at-risk group with particular characteristics that must be considered; comprehensive patient histories can help inform and tailor treatment pathways.

Study protocol for the implementation and evaluation of the Self-harm Assessment and Management for General Hospitals programme in Ireland (SAMAGH).

BACKGROUND: Previous self-harm is one of the strongest predictors of future self-harm and suicide. Increased risk of repeated self-harm and suicide exists amongst patients presenting to hospital with high-risk self-harm and major self-harm repeaters. However, so far evidence-based training in the management of self-harm for mental health professionals is limited. Within this context, we aim to develop, implement and evaluate a training programme, SAMAGH, Self-harm Assessment and Management Programme for General Hospitals in Ireland. SAMAGH aims to (a) reduce hospital-based self-harm repetition rates and (b) increase rates of mental health assessments being conducted with self-harm patients. We also aim to evaluate the training on self-harm knowledge, attitudes, and skills related outcomes of healthcare professionals involved in the training. METHODS/DESIGN: The study will be conducted in three phases. First, the SAMAGH Training Programme has been developed, which comprises two parts: 1) E-learning Programme and 2) Simulation Training. Second, SAMAGH will be delivered to healthcare professionals from general hospitals in Ireland. Third, an outcome and process evaluation will be conducted using a pre-post design. The outcome evaluation will be conducted using aggregated data from the National Self-Harm Registry Ireland (NSHRI) on self-harm repetition rates from all 27 public hospitals in Ireland. Aggregated data based on the 3-year average (2016, 2017, 2018) self-harm repetition rates prior to the implementation of the SAMAGH will be used as baseline data, and NSHRI data from 6 and 12 months after the implementation of SAMAGH will be used as follow-up. For the process evaluation, questionnaires and focus groups will be administered and conducted with healthcare professionals who completed the training. DISCUSSION: This study will contribute to the evidence base regarding the effectiveness of an evidence informed training programme that aims to reduce repeated hospital self-harm presentations and to improve compliance with self-harm assessment and management. This study is also expected to contribute to self-harm and suicide training with the possibility of being translated to other settings. Its feasibility will be evaluated through a process evaluation.

A population survey of prevalence rates of antenatal depression in the Irish obstetric services using the Edinburgh Postnatal Depression Scale (EPDS).

Ireland has the second-highest birth rate in Europe and poorly developed perinatal psychiatry services. There are no screening services for antenatal depression and no data available on prevalence rates of depression among women attending the Irish obstetric services. The aim of this study was to assess the prevalence rates of depression during pregnancy in a population sample in Ireland using the Edinburgh Postnatal Depression Scale (EPDS) as a screening tool. Pregnant women during all stages of pregnancy were recruited from five maternity hospitals throughout the Republic of Ireland. Approximately 5000 EPDS questionnaires were collected. Information on the participant's age, gestational week, gravidity, parity, and level of education attained was also collected. A score of > 12 was used as a measure of probable depression. Overall, 15.8% of pregnant women scored > 12 in the EPDS. There was a significant association between gestational week and rates of depression, with increasing rates occurring with advancing pregnancy (p < 0.001). Overall, higher socioeconomic groups were over-represented in the sample although we replicated the well-established findings of higher EPDS scores in women with lower educational attainment (p < 0.005). This study demonstrates that prevalence rates of probable antenatal depression are high among women attending the obstetric services in Ireland and highlight the importance of increasing awareness of antenatal depression. These high rates of antenatal depression may be related to certain conditions that are specific to an Irish setting: the absence of screening for depression in the context of grossly under-resourced perinatal psychiatry services. These findings provide indirect confirmatory evidence for the need for streamlined mental health services within reproductive health services.

Symptom-triggered therapy for assessment and management of alcohol withdrawal syndrome in the emergency department short-stay clinical decision unit.

INTRODUCTION: We previously reported that benzodiazepine detoxification for alcohol withdrawal using symptom-triggered therapy (STT) with oral diazepam reduced length of stay (LOS) and cumulative benzodiazepine dose by comparison with standard fixed-dose regimen. In this study, we aim to describe the feasibility of STT in an emergency department (ED) short-stay clinical decision unit (CDU) setting. METHODS: In this retrospective cohort study, we describe our experience with STT over a full calendar year (2014) in the CDU. A retrospective chart review was conducted and data collection included demographics, clinical details, total cumulative dose of diazepam, receipt of parenteral thiamine, LOS and disposition. RESULTS: 5% (n=174) of 3222 admissions to CDU required STT. Collapse or seizure (41%, n=71) and alcohol withdrawal (21%, n=37) were the most common reasons recorded for admission to CDU in those who required STT. Median Alcohol Use Disorders Identification Test score was 25 and 112 patients (64%) had at least one Clinical Institute Withdrawal Assessment for Alcohol revised measurement ≥10, triggering a dose of diazepam (20 mg). The median cumulative oral diazepam dose was 20 mg while 24 (15%) patients received a cumulative dose of 100 mg or more. Median time for STT was 12 hours (IQR=12, R=1-48). 3% (n=5) of patients required further general hospital admission and median LOS in CDU, was 22 hours (IQR=20, R=1-168). CONCLUSION: STT is potentially feasible as a rapid and effective approach to managing alcohol withdrawal syndrome in the ED/CDU short-stay inpatient setting where patient LOS is generally less than 24 hours.

Recommended next care following hospital-treated self-harm: Patterns and trends over time.

OBJECTIVE: The specific objectives of this study were to examine variation in the care of self-harm patients in hospital settings and to identify the factors that predict recommended next care following self-harm. METHODS: Data on consecutive presentations to Irish emergency departments (EDs) involving self-harm from the National Self-Harm Registry Ireland from 2004 to 2012 were utilised. Univariate and multivariate regression analyses were performed to assess the associations between patients' clinical and demographic characteristics, and recommended next care received. RESULTS: Across the study period a total 101,904 self-harm presentations were made to hospital EDs, involving 63,457 individuals. Over the course of the study there was a declining number of presentations resulting in patient admission following attendance with self-harm. Recommended next care varied according to hospital location, with general admission rates ranging from 11% to 61% across administrative health regions. Multinomial logistic regression identified that the factor which most strongly affected next care was the presenting hospital. Being male, older age, method, repeat self-harm, time of attendance and residence of the patient were all identified as influencing care received. Psychiatric admission was most common when highly lethal methods of self-harm were used (OR = 4.00, 95% CI, 3.63-4.41). A relatively large proportion of patients left the ED without being seen (15%) and the risk of doing so was highest for self-harm repeaters (1.64, 1.55-1.74 for those with 5+ presentations). CONCLUSIONS: The extensive hospital variation in recommended next care indicates that management of self-harm patients may be determined more by where they present than by the needs of the patient. The study outcomes underline the need to standardise the clinical management of self-harm patients in general hospital settings.

Steroid-induced mental disorders in cancer patients: a systematic review.

Corticosteroids are a central part of many cancer treatment regimens. Neuropsychiatric toxicity has complicated their use, including an association with a spectrum of symptoms, from insomnia, cognitive impairment and mood symptoms, to severe mental disorders, including mania, psychosis and severe depression. Although steroid-induced mental disorders were first reported in medicine more than 60 years ago, there is a dearth of evidence available to date on optimal treatment and prevention to guide cancer clinicians. We completed a systematic review of the current evidence for therapeutic and prophylactic interventions of steroid-induced mental disorders in cancer. We searched Medline, Embase and PsycINFO and selected studies related to steroid-induced mental disorder. The studies found were limited to case series and case reports only.

Urethral stricture secondary to self-instrumentation due to delusional parasitosis: a case report.

INTRODUCTION: Delusional parasitosis is a rare psychiatric disorder which often presents with dermatological problems. Delusional parasitosis, which involves urethral self-instrumentation and foreign body insertion, is exceptionally rare. This is the first case report to date that provides a detailed presentation of the urological manifestation of delusional parasitosis with complications associated with repeated self-instrumentation and foreign body insertion, resulting in stricture formation and requiring perineal urethrostomy. CASE PRESENTATION: A 45-year-old Irish man was electively admitted for perineal urethrostomy with chronic symptoms of dysuria, haematuria, urethral discharge, and intermittent urinary retention. He reported a 4-year history of intermittent pain, pin-prick biting sensations, and burrowing sensations, and held the belief that his urethra was infested with ticks. He also reported a 2-year history of daily self-instrumentation, mainly injecting an antiseptic using a syringe in an attempt to eliminate the ticks. He was found to have urethral strictures secondary to repeated self-instrumentation. A foreign body was found in his urethra and was removed via cystoscopy. On psychiatric assessment, he displayed a fixed delusion of tick infestation and threatened to surgically remove the tick himself if no intervention was performed. The surgery was postponed due his mental state and he was started on risperidone; he was later transferred to an acute in-patient psychiatric unit. Following a 3-week admission, he reported improvement in his thoughts and distress. CONCLUSIONS: Delusional parasitosis is a rare psychiatric disorder. Self-inflicted urethral foreign bodies in males are rare and have high comorbidity with psychiatric disorders; hence, these patients have a low threshold for referral for psychiatric assessment. The mainstay treatment for delusional parasitosis is second-generation antipsychotic drugs.

Psychiatric and neuropsychological profiles of people with psychogenic nonepileptic seizures.

OBJECTIVE: This study examined the psychiatric and neuropsychological profiles of people with psychogenic nonepileptic seizures (PNES). METHODS: Twenty-people who had been diagnosed with psychogenic nonepileptic seizures (PNES), but not epilepsy, were recruited into this study. A healthy control group was also recruited and was matched for age and gender. All participants underwent structured psychiatric assessment and psychometric assessment. Neuropsychological assessment was carried out using the Cambridge Neuropsychological Test Battery (CANTAB) after participants passed the Medical Symptom Validity Test (MSVT) of effort. RESULTS: One patient failed the MSVT and was excluded from the analysis. Therefore, data from 19 people with PNES and their matched healthy controls were analyzed. Compared with controls, people with PNES had significantly higher levels of depressive symptoms, anxiety symptoms, dissociative experiences, and alexithymic traits. In addition, people with PNES had impairments in spatial working memory and attention when compared with healthy controls. CONCLUSION: To our knowledge, this is the first study to report that, compared with controls, people with PNES have abnormal cognitive functioning after controlling for effects of effort and FSIQ. People with PNES also have high levels of anxiety, depressive, and dissociative symptoms. In addition, they appear to particularly focus on health problems and show evidence of chronic emotional dysregulation. Further studies are required to replicate our results and to help clarify the pathogenic mechanisms underlying PNES.

Anti-NMDA receptor encephalitis: a cause of acute psychosis and catatonia.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a newly described form of encephalitis associated with prominent psychiatric symptoms at onset. Recognition of the symptom complex is the key to diagnosis. Most patients with anti-NMDAR encephalitis develop a multistage illness that progresses from initial psychiatric symptoms to memory disturbance, seizures, dyskinesia, and catatonia. Psychiatric manifestations include anxiety, mania, social withdrawal, and psychosis (i.e., delusions, hallucinations, disorganized behavior). The disorder is more common in females (80%), in approximately half of whom it is associated with an underlying ovarian teratoma. Treatment involves immunosuppression, with steroids and intravenous immunoglobulin considered first line. The disorder is particularly relevant to psychiatrists, because most patients are initially seen by psychiatric services. Psychiatrists should consider anti-NMDAR encephalitis in patients presenting with psychosis as well as dyskinesia, seizures, and/or catatonia, especially if there is no history of a psychiatric disorder. We present the case of a 37-year-old woman who demonstrated many of the key clinical features of this potentially treatable disorder.

Symptom-triggered benzodiazepine therapy for alcohol withdrawal syndrome in the emergency department: a comparison with the standard fixed dose benzodiazepine regimen.

The aim of the study was to compare symptom-triggered and standard benzodiazepine regimens for the treatment of alcohol withdrawal syndrome in an emergency department clinical decision unit. The authors found that the symptom-triggered approach reduced cumulative benzodiazepine dose and length of stay.

Sensitivity and specificity of the Distress Thermometer and a two-item depression screen (Patient Health Questionnaire-2) with a 'help' question for psychological distress and psychiatric morbidity in patients with advanced cancer.

OBJECTIVES: Brief screening tools may help clinicians in busy settings detect patients who are experiencing severe psychological distress. This study examined the performance of the Distress Thermometer (DT) and a two-item depression screen [the Patient Health Questionnaire-2 (PHQ-2)] with a 'help' question in screening for distress and psychiatric morbidity among patients with advanced cancer. METHODS: Two hundred and five patients with advanced cancer completed the DT, the PHQ-2 and 'help' question and the Hospital Anxiety and Depression Scale and were interviewed using the Structured Clinical Interview for DSM-IV (SCID). The performance of the screening tools was examined against the Hospital Anxiety and Depression Scale and the SCID. RESULTS: Overall, discrimination levels were comparable for the DT [area under the curve (AUC) 0.80-0.81] and the PHQ-2 (AUC 0.73-0.85). The DT performed best in detecting cases of distress and mood, anxiety or adjustment disorders (sensitivity 100%), but it had poor specificity (49-60%). The best performance in terms of combined sensitivity and specificity was the PHQ depression item versus the SCID (sensitivity 88%, specificity 73%). The inclusion of the 'help' question with the PHQ-2 resulted in high levels of specificity (≥89%), but there was a significant drop in sensitivity (≤54%). CONCLUSION: Ultra-brief screening tools offer an efficient means of identifying patients with advanced cancer with severe distress or psychiatric morbidity but are less effective at identifying non-distressed individuals. Used in conjunction with a 'help' question, these tools can help clinicians identify patients who are both distressed and likely to accept professional support.

Methodological challenges in researching psychological distress and psychiatric morbidity among patients with advanced cancer: what does the literature (not) tell us?

Patients with advanced cancer experience multiple demands and losses that place them at risk for experiencing psychological distress. Researchers can face challenges in conducting research among this population because of their poor levels of physical and cognitive functioning. This paper aims to develop our understanding of these challenges. A systematic literature review was conducted of papers describing surveys in which a stated aim was to measure rates of psychological distress or psychiatric morbidity among patients with advanced cancer. We also included papers that focused on the development of assessment tools. Studies were identified through computerized (MEDLINE and PsycINFO) and manual searches for the years 1995-2009. Twenty-eight papers met the inclusion criteria. They describe findings in relation to a total of 3942 patients. The sample sizes ranged from 25 to 422 (median = 87). The main methodological challenge identified is the recruitment of large and representative samples. Significant portions of the advanced cancer population are excluded from distress studies or are refusing to take part. In conclusion, researchers can enhance the methodological knowledge base by presenting more detailed accounts of the participant recruitment and data collection processes. Future researchers should strive to develop more flexible methods of assessing distress among patients with advanced disease.

VGKC positive autoimmune encephalopathy mimicking dementia.

Voltage gated potassium channel antibodies (VGKC Abs) are known to cause three rare neurological syndromes- neuromyotonia, Morvan's syndrome and limbic encephalitis although an increasing array of other associated neurological symptoms are becoming recognised. The authors describe the case of a 60-year-old female who presented to the neurology clinic with an apparent early onset dementing process. She was noted to have both extrapyramidal and frontal release signs on examination and was admitted for further evaluation. Her dementia investigation including a neoplastic screen was negative except for VGKC antibody positivity. Her symptoms dramatically improved with commencement of immunosuppression. A non-paraneoplastic VGKC antibody associated dementia-like syndrome has rarely been described. The authors add to the few existing reports of what represents an important reversible cause of cognitive impairment.

Marked elevations in pro-inflammatory polyunsaturated fatty acid metabolites in females with irritable bowel syndrome.

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder referred to gastroenterologists. Although the pathophysiology remains unclear, accumulating evidence points to the presence of low-level immune activation both in the gut and systemically. Circulating polyunsaturated fatty acids (PUFA) have recently attracted attention as being altered in a variety of disease states. Arachidonic acid (AA), in particular, has been implicated in the development of a pro-inflammatory profile in a number of immune-related disorders. AA is the precursor of a number of important immunomodulatory eicosanoids, including prostaglandin E(2) (PGE(2)) and leukotriene B(4) (LTB(4)). We investigated the hypothesis that elevated plasma AA concentrations in plasma contribute to the proposed pro-inflammatory profile in IBS. Plasma AA and related PUFA were quantified by gas chromatography analysis in IBS patients and controls. Both PGE(2) and LTB(4) were measured in serum using commercially available ELISA assays. AA concentrations were elevated in our patient cohort compared with healthy controls. Moreover, we demonstrated that this disturbance in plasma AA concentrations leads to downstream elevations in eicosanoids. Together, our data identifies a novel proinflammatory mechanism in irritable bowel syndrome and also suggests that elevated arachidonic acid levels in plasma may serve as putative biological markers in this condition.

Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort.

BACKGROUND: Irritable bowel syndrome (IBS) is a common disorder that affects 10-15% of the population. Although characterised by a lack of reliable biological markers, the disease state is increasingly viewed as a disorder of the brain-gut axis. In particular, accumulating evidence points to the involvement of both the central and peripheral serotonergic systems in disease symptomatology. Furthermore, altered tryptophan metabolism and indoleamine 2,3-dioxygenase (IDO) activity are hallmarks of many stress-related disorders. The kynurenine pathway of tryptophan degradation may serve to link these findings to the low level immune activation recently described in IBS. In this study, we investigated tryptophan degradation in a male IBS cohort (n = 10) and control subjects (n = 26). METHODS: Plasma samples were obtained from patients and healthy controls. Tryptophan and its metabolites were measured by high performance liquid chromatography (HPLC) and neopterin, a sensitive marker of immune activation, was measured using a commercially available ELISA assay. RESULTS: Both kynurenine levels and the kynurenine:tryptophan ratio were significantly increased in the IBS cohort compared with healthy controls. Neopterin was also increased in the IBS subjects and the concentration of the neuroprotective metabolite kynurenic acid was decreased, as was the kynurenic acid:kynurenine ratio. CONCLUSION: These findings suggest that the activity of IDO, the immunoresponsive enzyme which is responsible for the degradation of tryptophan along this pathway, is enhanced in IBS patients relative to controls. This study provides novel evidence for an immune-mediated degradation of tryptophan in a male IBS population and identifies the kynurenine pathway as a potential source of biomarkers in this debilitating condition.