The Effect of Acute Minocycline Administration on Emotional Processing and Cognition in Healthy Volunteers
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|ClinicalTrials.gov Identifier: NCT03768557|
Recruitment Status : Completed
First Posted : December 7, 2018
Last Update Posted : April 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Mood Cognitive Change||Drug: Minocycline Other: placebo||Not Applicable|
Current antidepressant treatments, which largely target monoamine pathways, are efficacious in treating many aspects of major depression, however it is estimated that more than 30% of depressed patients fail to respond to standard antidepressant medications. Thus, there is a strong clinical need to identify and investigate novel treatment strategies that target different pathways involved in the pathophysiology of mood disorders. Mounting evidence indicates a potentially important role of inflammation in major depression; both clinical and animal studies have shown that pro-inflammatory cytokines can induce a behavioural repertoire of symptoms collectively referred to as 'sickness behaviours,' which include cognitive and mood symptoms, such as depression, anxiety, memory impairment, fatigue and anhedonia. Furthermore, elevated levels of peripheral pro-inflammatory cytokines, such as tumour necrosis factor (TNF)-α and interleukin (IL)-6, have been consistently reported in clinical mood disorders, including major depression. Evidence also points to the ability of pro-inflammatory cytokines to cause excitotoxicity (due to increased release of glutamate) and oxidative stress that are strongly implicated in the pathophysiology of major depression. Such evidence has therefore led to growing interest in testing effects of anti-inflammatory treatments on mood and emotional function to investigate whether the inflammatory-mood pathway could represent a novel drug target for new antidepressant therapies.
Minocycline has been selected for use in the present study as it is a pharmacologically interesting agent with an unusual combination of anti-inflammatory activity, in addition to anti-glutamatergic, anti-oxidant and neuro-protective actions. Thus, owing to its central action on systems that are thought to be involved in major depression, minocycline provides an interesting tool to investigate effects on cognition and emotional processing, particularly negative affective biases.
Negative affective biases in emotional processing are highly relevant to clinical mood disorders and they are well-recognised in the aetiology and maintenance of depression, such that depressed individuals are more likely to interpret, focus on and remember negative compared to positive emotional cues in self-relevant neuropsychological tasks. Antidepressant treatments have been shown to cause early, subconscious positive changes in emotional processing biases, which are evident in computerised tasks after one single dose of antidepressant. Recent theory suggests that over time this positive change in emotional bias contributes to improved mood.
Since elevated inflammatory markers appear to negatively affect mood and neuropsychological function, the investigators believe there is a need to expand our understanding of the psychological effects of reducing inflammatory markers. To do so, subjects will be administered either a single dose of 200 mg minocycline or placebo, after which they will complete a well-validated computerized battery of psychological tasks, which includes paradigms such as facial expression recognition, emotional categorization and emotional memory tasks that have previously been shown to be sensitive to conventional antidepressant treatments in healthy volunteers.
The results of this study will be compared to effects of common antidepressant treatments found using this same model within the investigators' lab and others. If effects are found to be comparable, this could not only provide further support for the emotional processing theory of antidepressant action, but it could also help to identify novel therapeutic targets for new treatments that could benefit depressed patients who do not respond successfully to current antidepressants.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||The Effect of Acute Minocycline Administration on Emotional Processing and Cognition in Healthy Volunteers|
|Actual Study Start Date :||April 26, 2017|
|Actual Primary Completion Date :||October 25, 2018|
|Actual Study Completion Date :||October 25, 2018|
single dose of minocycline (200mg)
Placebo Comparator: Placebo
lactose pills (400mg)
- Facial Expression Recognition Task [ Time Frame: 2 hours ]
- Emotional Categorization Task [ Time Frame: 2 hours ]
- Emotional Recall Task [ Time Frame: 2 hours ]
- Emotional Recognition Memory Task [ Time Frame: 2 hours ]
- Attentional Dot-Probe [ Time Frame: 2 hours ]
- N-back Task [ Time Frame: 2 hours ]
- Contextual Cueing Task [ Time Frame: 2 hours ]
- Priming Task [ Time Frame: 2 hours ]
- Concentration of the inflammatory marker TNF-alpha in serum Serum inflammatory cytokines and metabolites [ Time Frame: 0 and 4 hours ]
- Concentration of the inflammatory marker IL-6 in serum [ Time Frame: 0 and 4 hours ]
- Concentration of the inflammatory marker C-reactive protein in serum [ Time Frame: 0 and 4 hours ]
- Concentration of the stress hormone cortisol in serum [ Time Frame: 0 and 4hours ]
- Concentration of metabolites (amino acids and lipids) in serum [ Time Frame: 0 and 4 hours ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03768557
|Oxford, Oxfordshire, United Kingdom, OX3 7JX|