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Panels, Mini-Panels and Study Groupsdecember 4 Neuropsychopharmacology (2016) 41, S1–S115 © 2016 American College of Neuropsychopharmacology. All rights reserved 0893-133X/16 www.neuropsychopharmacology.org Panels, Mini-Panels and Study Groups Microbial communities were evaluated by DNA sequencing December 4–8, 2016 of the V4 region of the 16S gene. Behavioral changes were measured by weekly determinations of sucrose drinking and preference scores, as a measure of anhedonic-like behavior, Sponsorship Statement: Publication of this supplement is as well as changes in despair-like behavior in the forced sponsored by the ACNP. swim test. Individual contributor disclosures may be found within the Results: Exposure to chronic mild stress leads to a decrease abstracts. Part 1: All Financial Involvement with a pharma- in bacterial species diversity as compared with non-stressed ceutical or biotechnology company, a company providing controls and these changes precede decreases in sucrose clinical assessment, scientific, or medical products or preference. Further, we identified specific bacterial popula- companies doing business with or proposing to do business tions that were associated with the stressed and non-stressed with ACNP over past 2 years (Calendar Years 2014–Present); behavioral phenotypes. In addition, exposure to feces from Part 2: Income Sources & Equity of $10,000 per year or stressed rats rapidly (within 5 days) altered behavioral greater (Calendar Years 2014 - Present): List those financial outcomes in naïve rats. However, exposure to feces from relationships which are listed in part one and have a value non-stressed rats did not rapidly improve depressive-like greater than $10,000 per year, OR financial holdings that are phenotypes, but there is a tendency to accelerate recovery. listed in part one and have a value of $10,000 or greater as of Conclusions: Overall, these findings suggest that gut the date of disclosure; Part 3: Financial Involvement with microbiome-brain interactions play an important role in a pharmaceutical or biotechnology company, a company modulating brain function and behavioral outcomes and providing clinical assessment, scientific, or medical products may be more likely to exacerbate stress-induced behavioral or companies doing business with or proposing to do disruptions than to serve as an intervention. business with ACNP which constitutes more than 5% of Disclosure: Nothing to Disclose. personal income (Calendar Years 2014 - Present); Part 4: Grants from pharmaceutical or biotechnology company, a company providing clinical assessment, scientific, or medical 1.2 The Gut Microbiome Composition Varies in Bipolar products directly, or indirectly through a foundation, Disorder and Associates With Self-Reported Severity of university, or any other organization (Calendar Years 2014 Illness - Present); Part 5: My primary employer is a pharmaceutical/ biotech/medical device company. Simon Evans Asterisks in the author lists indicate presenter of the abstract University of Michigan, Ann Arbor, Michigan, at the annual meeting. United States Background: The gut microbiome is emerging as an Panel important factor in regulating mental health yet it remains 1. Gut Feelings: How the Microbiome May Affect Mental unclear what the target should be for psychiatric treatment. Illness and Interact With Treatment We aimed to elucidate the complement of the gut- microbiome community and its relationship with burden of disease measures in a population of individuals with 1.1 Gut Microbial Community and Behavioral Changes bipolar disorder. in a Chronic Mild Stress Model of Depression in Rats Methods: We compared the stool microbiome from individuals with bipolar disorder (n = 115) and control Emily Jutkiewicz subjects (n = 64) using 16S ribosomal RNA (rRNA) gene University of Michigan, Ann Arbor, Michigan, United sequence analysis to assess case-control differences. We States further tested for relationships between expression of Operational Taxonomic Units (OTUs) and self-reported Background: Recent evidence demonstrates that the gut burden of disease measures. microbiome affects brain function and emotional behavior, Results: Analysis of Molecular Variance (AMOVA) revealed suggesting that the microbiome-gut-brain axis may play a global community case-control differences (AMOVA pathophysiological role in psychiatric diseases such as p = 0.047). OTU level analysis revealed lower levels depression. At this time, there are limited studies investigat- (po0.001) of Firmicutes Faecalibacterium after adjustment ing whether gut microbiome and brain interactions have for age, sex, BMI and False Discovery Rate (FDR) correction directional causality. To this end, the current study evaluated at the po0.05 level. Within individuals with bipolar disorder, time-dependent changes in gut microbial communities in Faecalibacterium levels positively associated with better self- male Sprague-Dawley rats during exposure to 7 weeks of reported health outcomes based on the Short Form Health chronic, variable mild stress and evaluated the effects of Survey (SF12); the Patient Health Questionnaire (PHQ9); the microbial exposures on mood-related behaviors. Pittsburg Sleep Quality Index (PSQI); the Generalized Methods: Behavioral measures and fresh fecal samples were Anxiety Disorder Scale (GAD7); and the Altman Mania collected weekly prior to, during, and after stress exposure. Rating Scale (ASRM). ACNP 55th Annual Meeting Abstracts S2 Conclusions: This study provides the first analysis of underpinnings of this medication-related risk are not associations between the gut microbiome and multiple understood. A recent study in adolescent males determined psychiatric domains from a bipolar population. The data that new-onset risperidone treatment resulted in a gradual supports the hypothesis that targeting the microbiome may change in gut microbiota in association with body-mass be an effective treatment paradigm for bipolar disorder. index (BMI) gain. Our primary hypothesis is that AAP- Disclosure: Nothing to Disclose. treatment in adults results in gut dysbiosis that potentiates metabolic disease criteria such as increased BMI. Methods: In a cross sectional design, 117 subjects (49 Bipolar 1.3 Effects of Major Depression and SSRIs on the Gut Disorder (BD)-diagnosis and 68 Controls) from the Prechter Microbiota Longitudinal Study of Bipolar Disorder were analyzed to assess the effects of AAP-treatment on the gut microbiome. Chadi Calarge Fifty-two of the BD subjects were treated with an AAP. Age, Baylor College of Medicine, Houston, Texas, United States gender and BMI metadata were also collected for each subject. The V4 sequences of 16S rRNA were analyzed using Background: Human studies suggest that manipulation of the mothur v1.36. Analysis of molecular variance was used to gut microbiome can alter emotions. In rodents, such manipu- detect significant clustering of treatment groups and the lations are associated with a variety of changes in emotion- inverse Simpson index was used to calculate alpha diversity. relevant brain areas. Alterations in the gut microbiota (i.e., Detection of deferentially abundant OTUs between treat- dysbiosis) in mood disorders have not been well investigated, ment groups was performed using metastats. neither have mechanisms that mediate such associations. Results: Regression analysis of AAP-treated BP-subjects Methods: Stool samples (n = 200) were collected from revealed higher BMI values that remained significant after participants (n = 162, 57% females, age: 19.8 ± 1.8 years) correcting for age (p = 0.016). There were statistically enrolled in a longitudinal study examining the skeletal effects of significant differences in overall gut microbial profiles selective serotonin reuptake inhibitors (SSRIs). As a result, between AAP-treated and non-AAP treated BD subjects repeated samples were available when participants were in a (p = 0.04). There were three abundant organisms that were depressive episode (n = 79), in remission (n = 66), or never important in this separation. OTU #2, Bacteroides (Phylum : depressed (n = 55), while medicated with SSRIs (n = 62) and Bacteroidetes; p = 2E-05) and OTU #7, Roseburia (Phylum: not (n = 138). Microbiome composition is analyzed by culture- Firmicutes; p = 8E-06) and OTU #11, Alstipes (Phylum: independent methods using Illumina sequencing. Further, the Bacteroidetes; p = 0.0002). Species diversity between medica- production of indole/oxindoles was measured. Analyses include tion groups did not differ until stratified by gender. AAP- alpha and beta-diversity measures and multivariate statistics are treated females showed a significant decrease in species used to identify differences in microbiome profiles and indole/ diversity when compared to non-AAP treated females oxindolesproductionacrossdifferentstates. (p = 0.02). Males did not show a difference in diversity Results: The extant literature relating changes in the gut between groups (p = 0.38). microbiota to emotion regulation in rodents and humans Conclusions: These data suggest that AAP-treatment is will be briefly reviewed. Findings from our study, 31% associated with specific representation of gut bacterial during SSRI use, Between and within individual analyses will families and decreased species richness in females, which is show differences in gut bacterial composition in depressive a measure of gut health. disorders, particularly in relation to the presence of Disclosure: Nothing to Disclose. neurovegetative symptoms, and comorbid generalized anxi- ety
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