The Effect of Acute Minocycline Administration on Emotional Processing and Cognition in Healthy Volunteers
Condition: Mood; Cognitive Change
Study type: Interventional

Summary: 
      There is growing interest in the possibility of producing more effective antidepressant
      treatments that target a wider range of pathways involved in depression, including
      anti-inflammatory and anti-glutamatergic systems. Minocycline is a novel pharmacological
      agent; in addition to its antibiotic and anti-inflammatory properties, it also acts in the
      brain as an anti-glutamatergic and anti-oxidant agent. Since both excessive glutamate and
      oxidative stress are implicated in major depression, and appear to be connected to
      pro-inflammatory activity, this drug offers a unique tool with which the investigators can
      measure the effects of targeting these pathways on emotional processing. Participants will
      receive a single dose of either the drug (200 mg minocycline) or placebo, and will then
      undergo a well-validated computerised battery of emotional processing tasks that have
      previously been shown to be sensitive to standard antidepressant drugs. Tasks include
      presentation of positive and negative emotional words or pictures, to which participants'
      responses are measured. These tasks have been widely used previously without any adverse
      effects.
    

Detailed description: 
      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.
    

Intervention name(s): Minocycline; placebo
Intervention type(s): Drug; Other
Intervention description(s): Minocycline (200mg); Lactose (400mg)
Intervention MeSH terms: Minocycline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment