Emotional Processing and Cognitive Function in Perimenopausal Women Experiencing Cognitive Perturbations, Perimenopause, Perimenopause-Related Depression, Perimenopausal Women
Conditions
Keywords
perimenopause, menopause, gut microbiome and perimenopause, cognition and perimenopause, emotional processing and perimenopause, mood and perimenopause, gut microbiome and cognition, probiotics, probiotic, gut microbiome
Brief summary
Recent evidence suggests multi-strain probiotics containing Lactobacillus rhamnosus and Bifidobacterium longum have been found to enhance emotional processing and reduce salience to negative cues in studies involving people with mood disorders, as well as improve cognitive functions, such as memory and concentration, in healthy participants. By administering computer-based tasks, questionnaires and checking biological measures (cortisol, immune markers, blood metabolites, gut microbiota) using blood and faecal samples, this experimental medicine study aims to investigate whether a probiotic supplement has an effect on emotional processing and cognition in perimenopausal women. We also aim to study changes in gut bacteria from stool samples before and after taking the supplement to see if any microbiome changes are associated with any effects in emotional processing, cognitive function, and biological markers.
Detailed description
Perimenopause, the transition period leading up to menopause, involves fluctuating levels of oestrogen and other hormones, contributing to a variety of physical and metabolic changes. It is also a period associated with an increased risk of depression and a decline in cognitive functioning. When compared to the pre-perimenopausal period, perimenopausal women are two to five times more susceptible to experiencing depressive episodes. Cognitive decline, including memory and concentration issues, is also prevalent, with an estimated 44-62% of individuals reporting challenges with memory. Research often highlights the role of the gut-brain axis, where the gut microbiota influences cognitive function and emotional processing via neurotransmitters, inflammatory markers, and stress response pathways. Recent evidence suggests that multi-strain probiotics containing Lactobacillus rhamnosus and Bifidobacterium longum enhance emotional processing and reduce salience to negative cues in studies involving people with mood disorders, as well as improving cognitive functions, such as memory and concentration, in healthy participants. One 8-week study also found preliminary evidence supporting the potential of probiotics as a safe and effective adjunctive treatment for major depressive disorder in individuals with incomplete responses to antidepressant medication. Given these observed benefits, the investigation into the effects of multi-strain probiotics to address emotional processing and cognitive disturbances and perturbations in a perimenopausal population is lacking. With the increasing demand for natural, non-pharmacological therapeutic interventions to manage perimenopausal symptoms, this project could provide valuable evidence supporting the use of probiotics as a beneficial adjunct therapy in perimenopausal health management. The current proposal will assess the effects of a commercial probiotic on emotional processing and cognitive function in perimenopausal women, alongside changes in gut microbial composition that may mediate any observed metabolic changes and effects on inflammatory markers and metabolites. This is an important next step in elucidating the role probiotics may play in perimenopause and in generating data to guide future clinical applications of probiotics in managing perimenopausal symptoms.
Interventions
DIETARY_SUPPLEMENTMulti-strain probiotic
A commercially available probiotic known to support gut health and is generally well-tolerated.
DIETARY_SUPPLEMENTPlacebo
A microcrystalline cellulose-based capsule.
Sponsors
University of Oxford
ADM Protexin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
A researcher, not involved in the study, will generate the randomisation code using an online tool (https://www.sealedenvelope.com/simple-randomiser/v1/lists). Participants will be stratified by BMI, and participants will receive identical daily capsules, either probiotic or placebo. Treatment allocation will be documented on a Randomisation List, updated for each participant, and stored securely. Participants will remain unaware of their group allocation to ensure blinding.
Intervention model description
Participants are randomized into one of two groups, each undergoing 60 days of either 1) Placebo or 2) Probiotic.
Eligibility
Sex/Gender
FEMALE
Age
45 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Female at birth * You are aged 45-60 years and in perimenopause (determined by changes in menstrual bleeding patterns (such as changes in cycle length of 7 days or longer in either direction from what is normal for you), AND vasomotor symptoms (e.g., hot flushes and sweats) AND mild to moderate mood or cognitive disturbances, or joint and muscle pain over the previous 12 months) * You are willing and able to give informed consent for participation in the study * You are sufficiently fluent in English to understand and complete tasks * You are at least 12 months post-natal * Willing to withhold from having grapefruit juice
Exclusion criteria
* Currently receive or seek treatment for any mental health condition * Have a BMI \>=30 OR \<=18.5 * Have lost or gained more than 10% of body weight in a short period (e.g., 6 months), as this can affect mood and cognition * Currently using hormonal contraception or have used hormonal contraception in the last 6 months * Have had gender reassignment surgery or gender-affirming hormone therapy * Had a head injury causing concussion or unconsciousness in the past 6 months * Participated in other studies that may influence mood, cognition, or gut health in the last three months * Are currently diagnosed with and/or treated for psychiatric or neurological disorders * Are on perimenopausal hormone replacement therapy (HRT) (e.g., estrogen, progesterone, testosterone) or other hormone-modulating medications (e.g., GLP-1 agonists, thyroxine replacement), as these can impact mood and cognitive functions * Currently use statins or have used statins in the last 6 months, as these may impact mood and cognitive functions * Participated in any other study with the same tasks in the last year * Currently use medications that influence cognition or mood, such as antidepressants, anxiolytics, antipsychotics, stimulants, mood-stabilizers, or cognitive-enhancing drugs * Have chronic or severe gastrointestinal diseases (e.g., inflammatory bowel disease, Crohn's disease, celiac disease, or severe acid reflux; treatment with e.g., corticosteroids, antacids), as these conditions and treatments can affect the gut microbiota and immune responses differently from healthy individuals * Have a compromised immune system * Currently smoke, vape, or use any other nicotine products * Have a current diagnosis of cognitive impairment or neurodegenerative disorders (e.g., mild cognitive impairment, dementia), as these conditions could confound cognitive assessments. * Have severe medical conditions requiring ongoing medication that may independently affect cognition or mood (e.g., diabetes) * Currently or recently used antibiotics (last 3 months), as antibiotics may alter gut microbiota and interfere with probiotic effects * Currently or recently used probiotics or prebiotics or consumed fermented products (e.g., kimchi, kombucha, sauerkraut, kefir, etc.) on a regular basis (last 3 months), which might interfere with the study intervention * Have known allergies or intolerances to probiotics or components in the probiotic supplement. * Have substance abuse or dependence (e.g., alcohol, recreational drugs) that may affect mood and cognition. * Have Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (Long COVID) * Have had a hysterectomy * Are pregnant or lactating, as hormonal changes associated with these states could confound results. * Score of 20 or above on PHQ-9 depression questionnaire, indicating severe depression * Score of \>1 on PHQ-9 suicidality item, indicating significant suicidality (as assessed by medical on-site professionals
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Facial Expression Recognition Task (FERT) | End of the 60-day intervention | Accuracy, reaction time and misclassifications on the FERT compared between probiotic and placebo groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Emotional Go/No-Go (EGNG) | Post-intervention (end of 60-day intervention) | Cognitive control and inhibitory control assessed using the EGNG task, including commission errors, omission errors, and reaction time to emotionally valenced stimuli. Performance will be compared between probiotic and placebo groups at post-intervention. |
| Probabilistic Reversal Learning (PRL) Task | Post-intervention (end of 60-day intervention) | Cognitive flexibility and reward-based learning assessed using the PRL task, including measures such as response accuracy, reversal errors, and sensitivity to reward and punishment. Performance will be compared between probiotic and placebo groups at post-intervention. |
| N-back Task | Post-intervention (end of 60-day intervention) | Working memory performance assessed using the n-back task, including accuracy and reaction time across task conditions. Performance will be compared between probiotic and placebo groups at post-intervention. |
| Auditory Verbal Learning Test (AVLT) | Post-intervention (end of 60-day intervention) | Verbal learning and memory assessed using the AVLT, including measures of immediate recall, delayed recall, and recognition memory. Performance will be compared between probiotic and placebo groups at post-intervention. |
| Serum cortisol | Baseline and end of 60-day intervention | Serum cortisol concentration assessed using ELISA compared between the placebo and probiotic groups |
| Inflammatory markers | Baseline and end of 60-day intervention | Inflammatory marker concentrations (CRP, IL-1b, TNF-alpha, IL-6) assessed using ELISA compared between placebo and probiotic groups |
| Serum metabolites | Baseline and end of 60-day intervention | Serum metabolite profiles assessed using ELISA compared between placebo and probiotic groups |
| Gut microbiome composition | Baseline and end of 60-day intervention | Gut microbiome composition assessed using stool samples, including measures of alpha diversity, beta diversity, and relative abundance of microbial taxa, compared between placebo and probiotic groups. |
| Emotional Categorisation Task | End of the 60-day intervention | Accuracy and reaction time performance on emotional word categorization task compared between probiotic and placebo groups. |
| Digit Span Task | End of the 60-day intervention | Maximum span length compared between probiotic and placebo groups |
| Emotional word recall/recognition task | End of the 60-day intervention | Performance on emotional word recall (hits and false alarms) and recogntion (hits, false alarms and reaction time) compared between probiotic and placebo groups |
Countries
United Kingdom
Contacts
CONTACTPhil Burnet, Professor
CONTACTSusannah Murphy, Professor
PRINCIPAL_INVESTIGATORPhil Burnet, Professor
University of Oxford
Outcome results
None listed