Characterizing the gut microbiota in adults with bipolar disorder: a pilot study.

Background: Convergent evidence implicates gut microbiota in human health and disease. Hitherto, relatively few studies have evaluated the gut microbiota profile in individuals with bipolar disorder (BD) relative to healthy controls (HC). Methods: Fecal samples were collected from subjects (aged 18-65) meeting DSM-5-defined criteria for BD and age- and sex-matched HC without current or past history of mental or major medical disorders. Samples were sequenced using Illumina sequencing and association of specific taxa and co-occurrence of taxa with sample groups including the effect of diet was assessed using cluster analysis and analysis of communities of microorganisms (ANCOM). Nutritional composition was evaluated using the Dietary Questionnaire for Epidemiological Studies (DQES v2) Food Frequency Questionnaire. Results: Forty-six subjects were enrolled (n=23 BD, n=23 HC). Cluster analyses did not identify any significant differences between BD and HC (p=0.38). Lower microbiota diversity was observed among BD subjects relative to HC (p=0.04). A greater abundance of a Clostridiaceae OTU was observed among BD subjects when compared to HC and of Collinsella among BD-II subjects relative to BD-I. Cluster analysis revealed that neither diagnosis (p=0.38) nor diet (p=0.43) had a significant effect on overall gut microbiota composition. Limitations: This study has a small sample size and insufficient control for some potential moderating factors (e.g. psychotropic medication and smoking). Conclusion: This study suggests that individuals with BD may have a distinct gut microbiota profile compared to healthy controls, with a greater abundance of Clostridiaceae and Collinsella. These findings need to be replicated in future studies with larger sample sizes.

A qualitative investigation of optimal perinatal health: the perspectives of south Asian grandmothers living in southern Ontario, Canada.

BACKGROUND: Perinatal health-seeking behaviours are influenced by various factors, including personal beliefs. South Asian women, who often live within a wide kinship system, can be influenced by the advice and guidance of their mothers and/or mothers-in-law. METHODS: To explore the cultural health perceptions of South Asian grandmothers within this context, we used constructivist grounded theory to sample and interview 17 South Asian grandmothers who reside in Southern Ontario, Canada. Interviews were audio-recorded, transcribed verbatim, and coded/analyzed by three independent coders. RESULTS: Many grandmothers emphasized that the preconception phase should focus on building healthy habits around nutrition, physical activity, and mental wellness; the pregnancy period should encompass an enriched environment (positive relationships, healthy routines, nutritional enhancement); and the postpartum phase should emphasize healing and restoration for both the mother and newborn (self-care, bonding, rebuilding healthy habits). Many of the grandmothers conceptualized these stages as a cyclical relationship where healing and restoration transitions gradually to re-establishing healthy habits before having a subsequent child. They also expressed responsibility in supporting their daughters and/or daughters-in-law with their family units and encouraging the transfer of perinatal health information. CONCLUSIONS: South Asian grandmothers are involved in supporting the family units of their children and involving them in perinatal health programming can be an effective way to translate health knowledge to South Asian women. Video abstract. In order to impact a broad, diverse audience of community members, we collaborated with a South Asian film-maker to distil the research findings, write an impactful script, and produce a short digital story based on the research findings. Currently available on social media (https://www.youtube.com/watch?v=tjcNUVOwatU), the film was celebrated with a CIHR Institute for Human Development, Child and Youth Health Video Talks Prize in 2016.

The gut microbiome in psychiatry: A primer for clinicians.

Research in the past decade has shown that variations in the gut microbiome may influence behavior, and vice versa. As such, interest in the role of the gut microbiome in psychiatric conditions has drawn immense interest. This is evidenced by the recent surge in published studies examining microbial dysbiosis in clinical psychiatric populations, particularly autism spectrum disorder and depression. However, critical examination of these studies reveals methodological flaws in design and execution, suggesting that they may not be held to the same standards as other bodies of clinical research. Given the complex nature of the gut microbiome, this narrative review attempts to clarify concepts critical to effectively examine its potential role in psychopathology to appropriately inform mental health researchers. More specifically, the numerous variables known to affect the gut microbiome are discussed, including inflammation, diet, weight, and medications. A comprehensive review of the extant microbiome literature in clinical psychiatric populations is also provided, in addition to clinical implications and suggestions for future directions of research. Although there is a clear need for additional studies to elucidate the gut microbiome's role in psychiatric disorders, there is an even greater need for well-designed, appropriately controlled studies to truly impact the field.

Impact of High-Dose Vitamin D3 Supplementation in Patients with Crohn's Disease in Remission: A Pilot Randomized Double-Blind Controlled Study.

AIM: To assess the tolerability and efficacy of high-dose vitamin D3 in patients with Crohn's disease (CD). METHODS: This was a randomized, double-blind placebo-controlled trial of high-dose vitamin D3 at 10,000 IU daily (n = 18) compared to 1000 IU daily (n = 16) for 12 months in patients with CD in remission. The primary outcome was change in serum 25-hydroxy-vitamin D levels. Secondary outcomes included clinical relapse rates and changes in mood scores. RESULTS: High-dose vitamin D3 at 10,000 IU daily significantly improved 25-hydroxy-vitamin D levels from a mean of 73.5 nmol/L [standard deviation (SD) 11.7 nmol/L] to 160.8 nmol/L (SD 43.2 nmol/L) (p = 0.02). On an intention-to-treat basis, the rate of relapse was not significantly different between patients receiving low- and high-dose vitamin D3 (68.8 vs 33.3%, p = 0.0844). In per-protocol analysis, clinical relapse of Crohn's disease was less frequently observed in patients receiving a high dose (0/12 or 0%) compared to those receiving a low dose of 1000 IU daily (3/8 or 37.5%) (p = 0.049). Improvement in anxiety and depression scores and a good safety profile were observed in both groups treated with vitamin D3. CONCLUSIONS: Oral supplementation with high-dose vitamin D3 at 10,000 IU daily significantly improved serum 25-hydroxy-vitamin D levels. Rates of clinical relapse were similar between both groups. Larger studies using high-dose vitamin D3 for treatment of inflammatory bowel diseases are warranted. CLINICALTRIALS. GOV REGISTRATION NO: NCT02615288.

"WHAT'S BUGGING THE GUT IN OCD?" A REVIEW OF THE GUT MICROBIOME IN OBSESSIVE-COMPULSIVE DISORDER.

The gut microbiome has become a topic of major interest as of late, with a new focus specifically on psychiatric disorders. Recent studies have revealed that variations in the composition of the gut microbiota may influence anxiety and mood and vice versa. Keeping the concept of this bidirectional "microbiota-gut-brain" axis in mind, this review aims to shed light on how these findings may also be implicated in obsessive-compulsive disorder (OCD); potentially outlining a novel etiological pathway of interest for future research in the field.

Risk of upper gastrointestinal bleeding with selective serotonin reuptake inhibitors with or without concurrent nonsteroidal anti-inflammatory use: a systematic review and meta-analysis.

OBJECTIVES: There is emerging concern that selective serotonin reuptake inhibitors (SSRIs) may be associated with an increased risk of upper gastrointestinal (GI) bleeding, and that this risk may be further increased by concurrent use of nonsteroidal anti-inflammatory (NSAID) medications. Previous reviews of a relatively small number of studies have reported a substantial risk of upper GI bleeding with SSRIs; however, more recent studies have produced variable results. The objective of this study was to obtain a more precise estimate of the risk of upper GI bleeding with SSRIs, with or without concurrent NSAID use. METHODS: MEDLINE, EMBASE, PsycINFO, the Cochrane central register of controlled trials (through April 2013), and US and European conference proceedings were searched. Controlled trials, cohort, case-control, and cross-sectional studies that reported the incidence of upper GI bleeding in adults on SSRIs with or without concurrent NSAID use, compared with placebo or no treatment were included. Data were extracted independently by two authors. Dichotomous data were pooled to obtain odds ratio (OR) of the risk of upper GI bleeding with SSRIs +/- NSAID, with a 95% confidence interval (CI). The main outcome and measure of the study was the risk of upper GI bleeding with SSRIs compared with placebo or no treatment. RESULTS: Fifteen case-control studies (including 393,268 participants) and four cohort studies were included in the analysis. There was an increased risk of upper GI bleeding with SSRI medications in the case-control studies (OR=1.66, 95% CI=1.44,1.92) and cohort studies (OR=1.68, 95% CI=1.13,2.50). The number needed to harm for upper GI bleeding with SSRI treatment in a low-risk population was 3,177, and in a high-risk population it was 881. The risk of upper GI bleeding was further increased with the use of both SSRI and NSAID medications (OR=4.25, 95% CI=2.82,6.42). CONCLUSIONS: SSRI medications are associated with a modest increase in the risk of upper GI bleeding, which is lower than has previously been estimated. This risk is significantly elevated when SSRI medications are used in combination with NSAIDs, and physicians prescribing these medications together should exercise caution and discuss this risk with patients.

Vitamin D deficiency and depression in adults: systematic review and meta-analysis.

BACKGROUND: There is conflicting evidence about the relationship between vitamin D deficiency and depression, and a systematic assessment of the literature has not been available. AIMS: To determine the relationship, if any, between vitamin D deficiency and depression. METHOD: A systematic review and meta-analysis of observational studies and randomised controlled trials was conducted. RESULTS: One case-control study, ten cross-sectional studies and three cohort studies with a total of 31 424 participants were analysed. Lower vitamin D levels were found in people with depression compared with controls (SMD = 0.60, 95% CI 0.23-0.97) and there was an increased odds ratio of depression for the lowest v. highest vitamin D categories in the cross-sectional studies (OR = 1.31, 95% CI 1.0-1.71). The cohort studies showed a significantly increased hazard ratio of depression for the lowest v. highest vitamin D categories (HR = 2.21, 95% CI 1.40-3.49). CONCLUSIONS: Our analyses are consistent with the hypothesis that low vitamin D concentration is associated with depression, and highlight the need for randomised controlled trials of vitamin D for the prevention and treatment of depression to determine whether this association is causal.

Aboriginal birth cohort (ABC): a prospective cohort study of early life determinants of adiposity and associated risk factors among Aboriginal people in Canada.

BACKGROUND: Aboriginal people living in Canada have a high prevalence of obesity, type 2 diabetes, and cardiovascular disease (CVD). To better understand the pre and postnatal influences on the development of adiposity and related cardio-metabolic factors in adult Aboriginal people, we will recruit and follow prospectively Aboriginal pregnant mothers and their children - the Aboriginal Birth Cohort (ABC) study. METHODS/DESIGN: We aim to recruit 300 Aboriginal pregnant mothers and their newborns from the Six Nations Reserve, and follow them prospectively to age 3 years. Key details of environment and health including maternal nutrition, glucose tolerance, physical activity, and weight gain will be collected. At birth, cord blood and placenta samples will be collected, as well as newborn anthropometric measurements. Mothers and offspring will be followed annually with serial measurements of diet and physical activity, growth trajectory, and adiposity. DISCUSSION: There is an urgent need to understand maternal and child factors that underlie the early development of adiposity and type 2 diabetes in Aboriginal people. The information generated from this cohort will assist the Six Nations community in developing interventions to prevent early adiposity in Aboriginal children.

The psychiatric presentation of mitochondrial disorders in adults.

Although comorbid psychiatric illness is increasingly being recognized in patients with mitochondrial disorders, there has been relatively little attention to psychiatric symptomatology as the primary clinical presentation. The authors report detailed clinical, biochemical, neuroradiological, and genetic findings in a series of 12 patients with mitochondrial disorders in whom psychiatric symptoms were a prominent aspect of the clinical presentation. The psychiatric presentations included depression, anorexia nervosa, bipolar disorder, and obsessive-compulsive disorder. A review of the literature, in conjunction with the present series, indicates that psychiatric symptoms can be the presenting feature of mitochondrial disorders and highlights the importance of considering this diagnosis.

The mitochondrial genome and psychiatric illness.

Psychiatric disorders are a leading cause of morbidity and mortality, yet their underlying pathophysiology remains unclear. Searches for a genetic cause of bipolar disorder, schizophrenia, and major depressive disorder have yielded inconclusive results. There is increasing interest in the possibility that defects in the mitochondrial genome may play an important role in psychiatric illness. We undertook a review of the literature investigating mitochondria and adult psychiatric disorders. MEDLINE, PsycINFO, and EMBASE were searched from their inception through September 2011, and the reference lists of identified articles were reviewed for additional studies. While multiple lines of evidence, including clinical, genetic, ultrastructural, and biochemical studies, support the involvement of mitochondria in the pathophysiology of psychiatric illness, many studies have methodological limitations and their findings have not been replicated. Clinical studies suggest that psychiatric features can be prominent, and the presenting features of mitochondrial disorders. There is limited but inconsistent evidence for the involvement of mitochondrial DNA haplogroups and mitochondria-related nuclear gene polymorphisms, and for mitochondrial ultrastructural and biochemical abnormalities in psychiatric illness. The current literature suggests that mitochondrial dysfunction and mitochondrial genetic variations may play an important role in psychiatric disorders, but additional methodologically rigorous and adequately powered studies are needed before definitive conclusions can be drawn.

Maternal diet, depression and antidepressant treatment in pregnancy and across the first 12 months postpartum in the MPEWS pregnancy cohort study: Perinatal diet, depression and antidepressant use.

BACKGROUND: There is increasing interest in the association between perinatal depression and diet including whether diet may have an impact on depressive symptoms and equally whether depression influences diet. Furthermore, whether pharmacological treatment of depression with antidepressant medication also may influence diet. METHODS: We examine diet, perinatal depression, and antidepressant use in 442 women recruited in early pregnancy and followed until 12 months postpartum as part of the Mercy Pregnancy Emotional Wellbeing Study. Measures included Structured Clinical Interview for the DSM at recruitment in early pregnancy and comprehensive dietary intake questions, Edinburgh Postnatal Depression Scale, and self-report and recorded antidepressant use at third trimester and 6 and 12 months postpartum. RESULTS: This study found that those women with untreated, current depression in pregnancy had higher unhealthy takeaway food intake across the perinatal period compared to those taking antidepressant medication or healthy control women, albeit the overall effects were small and the clinical significance unknown. Higher depressive symptoms in the postpartum were also associated with higher takeaway intake. There was no difference in fruit and vegetable intake between the three groups and intake was highest for all women late in pregnancy and declined in the postpartum period. In all, women's takeaway food intake increased from pregnancy across the postpartum. LIMITATIONS: Lack of information on pre-pregnancy diet. CONCLUSIONS: Unhealthy takeaway intake was found to be associated with depression; however, for those women who took antidepressant treatment, their diet patterns were similar to healthy controls. Future research should examine the relationship of treatments for depression in addition to depression and associated dietary behaviours.

Psychological interventions for reducing anxiety in patients undergoing first-time colonoscopy: a pilot and feasibility study.

OBJECTIVES: To assess the feasibility of a randomized controlled trial (RCT), evaluating the efficacy and patients' perceptions of a psychological intervention aimed at reducing anxiety levels in adults undergoing first-time colonoscopy. METHODS: Adults undergoing first-time colonoscopy were randomized to a psychological intervention vs. sham intervention. The primary outcome was feasibility, defined as a recruitment rate of >50%. Patients' state anxiety was assessed before and after the intervention using the state-trait inventory for cognitive and somatic anxiety (STICSA) score. Follow-up interviews were performed within 1 week with a sample of patients and focus groups with clinical staff. RESULTS: A total of 130 patients were recruited from 180 eligible patients (72%). Eighty were randomized and completed the study (n = 39) in the psychological intervention group and (n = 41) in the sham. In the psychological intervention group, pre- and postmedian STICSA scores were 29 and 24 (P < 0.001), respectively. In the sham group, pre- and postmedian scores were 31 and 25 (P < 0.001), respectively. Follow-up interviews with patients (n = 13) suggested that 100% of patients perceived the psychological intervention as beneficial and would recommend it to others. CONCLUSION: The study was feasible. Patients in both groups improved their anxiety scores, but there were no significant differences between arms. Despite this, patients receiving psychological intervention perceived a benefit from the relaxation exercises.

Does this patient with diabetes have large-fiber peripheral neuropathy?

CONTEXT: Diabetic peripheral neuropathy predisposes patients to foot ulceration that heals poorly and too often leads to amputation. Large-fiber peripheral neuropathy (LFPN), one common form of diabetic neuropathy, when detected early prompts aggressive measures to prevent progression to foot ulceration and its associated morbidity and mortality. OBJECTIVE: To systematically review the literature to determine the clinical examination findings predictive of asymptomatic LFPN before foot ulceration develops. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: MEDLINE (January 1966-November 2009) and EMBASE (1980-2009 [week 50]) databases were searched for articles on bedside diagnosis of diabetic peripheral neuropathy. Included studies compared elements of history or physical examination with nerve conduction testing as the reference standard. DATA SYNTHESIS: Of 1388 articles, 9 on diagnostic accuracy and 3 on precision met inclusion criteria. The prevalence of diabetic LFPN ranged from 23% to 79%. A score greater than 4 on a symptom questionnaire developed by the Italian Society of Diabetology increases the likelihood of LFPN (likelihood ratio [LR], 4.0; 95% confidence interval [CI], 2.9-5.6; negative LR, 0.19; 95% CI, 0.10-0.38). The most useful examination findings were vibration perception with a 128-Hz tuning fork (LR range, 16-35) and pressure sensation with a 5.07 Semmes-Weinstein monofilament (LR range, 11-16). Normal results on vibration testing (LR range, 0.33-0.51) or monofilament (LR range, 0.09-0.54) make LFPN less likely. Combinations of signs did not perform better than these 2 individual findings. CONCLUSIONS: Physical examination is most useful in evaluating for LFPN in patients with diabetes. Abnormal results on monofilament testing and vibratory perception (alone or in combination with the appearance of the feet, ulceration, and ankle reflexes) are the most helpful signs.

In which sequence? Does it matter?

This article was migrated. The article was marked as recommended. A distinctive feature between the delivery of traditional preclinical and clinical curricula is that discipline-based clinical curriculum is delivered in a series of parallel clinical rotations for different groups of students, whereas the curriculum is synchronized across the cohort in preclinical years. Therefore, the sequence of learning themes or topics is more relevant to the preclinical years compared to clinical years in which the beginning and end points of the curriculum are different from one student to another. Many factors, both pedagogical and logistic, influence the optimal sequence of themes for the preclinical curriculum. During the process of reorganizing the sequence of themes for the preclinical curriculum at the University of Notre Dame Australia Fremantle, we identified a relative gap in literature on this topic. Given the importance of the sequence of themes for learning in the preclinical years, we were surprised to learn that publications on this topic are sparse. While sharing the challenges that we came across in our decision making process, we invite the scholars in this area to share their experience. This will undoubtedly benefit curriculum developers and educators in creating or reviewing the preclinical curriculum at their respective institutions.

Higher prevalence of irritable bowel syndrome and greater gastrointestinal symptoms in obsessive-compulsive disorder.

BACKGROUND: Anxiety and mood symptoms often co-occur with gastrointestinal problems, such as irritable bowel syndrome (IBS). The extent to which these relate to Obsessive-Compulsive Disorder (OCD) is unclear, despite anxiety being a prominent symptom of this disorder. The purpose of this analysis was to examine gastrointestinal symptoms in unmedicated, non-depressed adult OCD patients compared to age- and sex-matched community controls. METHODS: Twenty-one OCD patients and 22 controls were recruited from the community (Hamilton, ON, Canada) and enrolled in this cross-sectional study. In addition to a standardized psychiatric assessment, participants completed clinician- and self-rated psychiatric and gastrointestinal symptom severity measures. Presence of IBS was assessed using Rome III criteria. RESULTS: Gastrointestinal symptom severity (GSRS total; OCD = 8.67 ±â€¯6.72 vs. controls = 2.32 ±â€¯2.12) and prevalence of IBS (OCD = 47.6%; Controls = 4.5%) was higher in OCD patients than in controls. A comparison of OCD patients based on IBS status revealed greater depressive symptom severity (total MADRS: 12.60 ±â€¯1.89 vs 6.91 ±â€¯2.77), p < 0.001) among those with IBS. CONCLUSIONS: High prevalence and severity of gastrointestinal symptoms may be an important clinical consideration when treating OCD patients. More specifically, assessment of IBS and gastrointestinal symptoms may be useful when considering pharmacotherapeutic treatments options for patients. Given the high comorbidity noted with IBS, a disorder of the "gut-brain axis", results may suggest a shared pathophysiological mechanism between psychiatric and gastrointestinal disorders which should be explored in future research.