Dysbiosis in Bipolar Disorder (MOB)

Dysbiosis in Bipolar Disorder: MicrObiota Bipolar Study

The gut microbiota is a complex community comprising around 10^14 bacteria that live in the gut lumen. The imbalance of the normal structure and function of the microbiota, defined as dysbiosis, has been related to a wide diversity of pathologies, including mental health disorders. However, clinical evidence of the relationship between microbiota and mood disorders is lacking. The aim of this project is to examine the possible relationship of gut dysbiosis and the diagnosis of bipolar disorder (BD), of gut dysbiosis and mood relapses and of gut dysbiosis and cognitive impairment in bipolar patients.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder
• Intervention / Treatment: Other: Genome sequencing of fecal samples

Detailed Description

A prospective longitudinal study will be carried out with three groups of patients: a group of euthymic bipolar I or II patients without cognitive impairment (n=50), a second group of euthymic bipolar I or II patients with cognitive impairment (n=50) and a control group of healthy volunteers (n=50). Cognitive impairment will be defined as performance in any test of a domain below 2 standard deviations or more from the mean of normative data of each test assessed in the control group. Subjects will be recruited in the Hospital Clinic of Barcelona. At baseline clinical variables and diet patterns (ROME III) will be collected and neuropsychological performance (WCST, FAS, Stroop Colour-Word Interference test, TMT, WAIS-III, CVLT-II) and functionality (FAST) will be assessed. All subjects will be reassessed at 12 months follow-up. The mood state and possible affective relapses will be evaluated and treatments will be registered. All patients will receive standard psychiatric care according to international guidelines on bipolar disorders. Fecal samples will be collected and then frozen in the morning pre-prandial after having fasted overnight. DNA will be separated and stored at -80°C until assayed. Sequencing will be performed on an Illumina MiSeqTM platform. Statistical analysis will be performed with the latest existing version of the SPSS.

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic Barcelona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects with BD will be recruited in the Bipolar Unit outpatient clinic in the Hospital Clinic of Barcelona. Healthy volunteers will be selected from the community.

Description

Inclusion Criteria:

• Patients:

  • Diagnosis of bipolar disorder type I or II according to DSM-IV criteria (SCID);
  • Age between 18-55 years;
  • Euthymia (YMRS<6 and HMDRS<8) for at least 3 months;
  • Signed informed consent.

• Healthy controls:

  • No psychiatric diagnosis (SCID);
  • Age between 18-55 years; euthymia (YMRS<6 and HMDRS<8);
  • Signed informed consent.

Exclusion Criteria:

• Use of any type of antibiotics, antifungals or pro/prebiotics within at least one month prior to recruitment;
• IQ<85;
• Neurological illness;
• Stomach/gut problems;
• Current diagnosis of substance abuse or dependence according to DSM-IV criteria (SCID);
• Electroconvulsive therapy in the last year.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
BD with cognitive impairment; This group will include euthymic patients with bipolar disorder type I or II (YMRS<6 and HMDRS<8) and cognitive impairment. Intervention: Genome sequencing of fecal samples	Other: Genome sequencing of fecal samples; Fecal samples will be collected and then frozen in the morning pre-prandial after having fasted overnight. DNA will be separated and stored at -80°C in our center (Biobanc) until assayed. Sequencing will be performed with the most appropriate platform.
BD without cognitive impairment; This group will include euthymic patients with bipolar disorder type I or II (YMRS<6 and HMDRS<8) without cognitive impairment. Intervention: Genome sequencing of fecal samples	Other: Genome sequencing of fecal samples; Fecal samples will be collected and then frozen in the morning pre-prandial after having fasted overnight. DNA will be separated and stored at -80°C in our center (Biobanc) until assayed. Sequencing will be performed with the most appropriate platform.
Control group; This group will include healthy volunteers. Intervention: Genome sequencing of fecal samples	Other: Genome sequencing of fecal samples; Fecal samples will be collected and then frozen in the morning pre-prandial after having fasted overnight. DNA will be separated and stored at -80°C in our center (Biobanc) until assayed. Sequencing will be performed with the most appropriate platform.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composition of the gut microbiota.	To determine if patients diagnosed with BD present gut dysbiosis compared to controls through genome sequencing of fecal samples.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composition of the gut microbiota according to mood state.	Gut dysbiosis will be determined according to mood state, assessed using clinical evaluation.	12 months
Composition of the gut microbiota according to cognitive state.	Gut dysbiosis will be determined according to cognitive state, assessed using a pre-defined neuropsychological battery.	12 months

Collaborators and Investigators

• Sponsor: Hospital Clinic of Barcelona
• Collaborators: Instituto de Salud Carlos III; Institut d'Investigacions Biomèdiques August Pi i Sunyer
• Investigators: Principal Investigator: Iria Grande, MD, PhD, Bipolar Disorders Unit, Hospital Clinic, Institute of Neurosciences, University of Barcelona, IDIBAPS, CIBERSAM

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2019
• Primary Completion (ACTUAL): June 30, 2021
• Study Completion (ACTUAL): June 30, 2021

Study Registration Dates

• First Submitted: March 29, 2017
• First Submitted That Met QC Criteria: April 24, 2017
• First Posted (ACTUAL): April 25, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 26, 2021
• Last Update Submitted That Met QC Criteria: August 25, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Bipolar and Related Disorders; Bipolar Disorder; Dysbiosis
• Other Study ID Numbers: PI 16/00187

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED