Differences by Sex and Genotype in the Effects of Stress on Executive Functions
NCT ID: NCT04273880
Last Updated: 2024-05-08
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
146 participants
INTERVENTIONAL
2018-04-28
2024-12-31
Brief Summary
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Detailed Description
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At low doses the mode of action of MPH increases DA efflux specifically in PFC and preferentially enhances signal processing in PFC. Low dosages of MPH are often effective in improving EFs and specifically because of their effect on PFC. This slight increase of DA in the PFC is similar to the effects of mild stress on the brain, which is why the study uses a low dose of MPH as the pharmacological model of mild stress. Even mild stress markedly increases DA levels in PFC, impairing PFC function and EFs. The use of MPH is meant to mimic the effect of mild stress on the PFC and executive functions.
Purpose/objective: This double-blind study aims to compare performance on tasks of executive function between males, females when their estrogen levels are high, and females when their estrogen levels are low when they have undergone a pharmacological model of mild stress (low dosage of MPH) and when they have not undergone this stress. It also aims to compare the same across the three variants of the catechol-O-methyltransferase (COMT) genotype (methionine-methionine, methionine-valine, and valine-valine).
Hypotheses: MPH, like mild-stress, should raise PFC DA levels in COMT-Vals to optimal, but raise PFC DA levels in COMT-Mets past optimal (since low dose of MPH increases DA levels in PFC). While COMT-Mets generally show better EFs than COMT-Vals without MPH, on MPH that should be reversed with COMT-Vals performing better. An increase in PFC DA levels pharmacologically should mimic the sex difference in the effect of mild stress on EFs, harming females with high estrogen level's performance while enhancing males' performance on tasks of executive functions.
Conditions
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Study Design
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RANDOMIZED
CROSSOVER
BASIC_SCIENCE
TRIPLE
Study Groups
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10 mg Psychostimulant
Drug: Methylphenidate (MPH) Participants will be tested twice, approximately one month apart. In one of the sessions, they will be given 10mg of MPH an hour and a half before the testing session is set to begin, to account for the time taken for the effects of the drug to start.
Methylphenidate
10mg of MPH taken an hour and a half before one of the testing sessions.
90 mg Vitamin C
Placebo: Vitamin C Participants will be tested twice, approximately one month apart. In one of the sessions, they will be given 90mg of Vitamin an hour and a half before the testing session is set to begin, to follow the exact protocol that is used for MPH.
Vitamin C
90 mg of Vitamin C taken an hour and a half before the other testing session
Interventions
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Methylphenidate
10mg of MPH taken an hour and a half before one of the testing sessions.
Vitamin C
90 mg of Vitamin C taken an hour and a half before the other testing session
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
* inability to understand the task instructions (which are in English), or difficulty hearing the instructions, seeing the stimuli, or executing a manual response.
* a serious adverse event during pregnancy or birth.
* an injury (such as a head injury with loss of consciousness) that might affect EF performance.
* a major trauma that might affect current EFs and stress responsivity
* undue current life stress level
* taking any medication that affects thinking, memory, mental clarity, or any other EF ability.
* taking any medication that influences circulating gonadal hormone levels (such as oral contraceptives \[birth control pill\]).
* having taken such medications within the preceding four months.
* smokers
* use of recreational drugs or consumption of alcohol 24 hours prior to the testing sessions
* women without a period that occurs roughly every month (predicting the onset of the next menses in women who don't have their period monthly is difficult)
* women who are pregnant or who are nursing.
* having the eye problem glaucoma
* having a heart condition
* being anxious, tense or agitated
* taking or have taken within the past 14 days an anti-depression medicine called a monoamine oxidase inhibitor or MAOI.
* taking pressor agents (for hypotension treatment)
* taking coumarin anticoagulants
* taking anticonvulsants (phenobarbital, diphenylhydantoin, primidone)
* taking phenylbutazone (nonsteroidal anti-inflammatory drug)
* taking tricyclic antidepressants (imipramine, desipramine)
* taking cold or allergy medicine that contain decongestants
* being allergic to anything in either the MPH or Vitamin C capsules (methylphenidate HCL, ascorbic acid, lactose, gelatin, Titanium dioxide, D\&C Red #28, FD\&C Blue #1, FD\&C Red #40)
20 Years
35 Years
ALL
Yes
Sponsors
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National Institute on Drug Abuse (NIDA)
NIH
University of British Columbia
OTHER
Responsible Party
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Adele Diamond
Professor and Tier 1 Canada Research Chair
Principal Investigators
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Adele Diamond, PhD
Role: PRINCIPAL_INVESTIGATOR
University of British Columbia
Locations
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Developmental Cognitive Neuroscience Lab, Department of Psychiatry, University of British Columbia
Vancouver, British Columbia, Canada
Countries
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Central Contacts
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Facility Contacts
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References
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Arnsten AF, Goldman-Rakic PS. Noise stress impairs prefrontal cortical cognitive function in monkeys: evidence for a hyperdopaminergic mechanism. Arch Gen Psychiatry. 1998 Apr;55(4):362-8. doi: 10.1001/archpsyc.55.4.362.
Barkley, R. A. (2001). The inattentive type of ADHD as a distinct disorder: What remains to be done. Clinical Psychology: Science and Practice, 8, 489-493.
Barkley RA, DuPaul GJ, McMurray MB. Attention deficit disorder with and without hyperactivity: clinical response to three dose levels of methylphenidate. Pediatrics. 1991 Apr;87(4):519-31.
Berridge CW, Devilbiss DM, Andrzejewski ME, Arnsten AF, Kelley AE, Schmeichel B, Hamilton C, Spencer RC. Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biol Psychiatry. 2006 Nov 15;60(10):1111-20. doi: 10.1016/j.biopsych.2006.04.022. Epub 2006 Jun 23.
Cerqueira JJ, Mailliet F, Almeida OF, Jay TM, Sousa N. The prefrontal cortex as a key target of the maladaptive response to stress. J Neurosci. 2007 Mar 14;27(11):2781-7. doi: 10.1523/JNEUROSCI.4372-06.2007.
Devilbiss DM, Berridge CW. Cognition-enhancing doses of methylphenidate preferentially increase prefrontal cortex neuronal responsiveness. Biol Psychiatry. 2008 Oct 1;64(7):626-35. doi: 10.1016/j.biopsych.2008.04.037. Epub 2008 Jun 30.
Dickerson SS, Kemeny ME. Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychol Bull. 2004 May;130(3):355-91. doi: 10.1037/0033-2909.130.3.355.
Elliott R, Sahakian BJ, Matthews K, Bannerjea A, Rimmer J, Robbins TW. Effects of methylphenidate on spatial working memory and planning in healthy young adults. Psychopharmacology (Berl). 1997 May;131(2):196-206. doi: 10.1007/s002130050284.
Lataster J, Collip D, Ceccarini J, Haas D, Booij L, van Os J, Pruessner J, Van Laere K, Myin-Germeys I. Psychosocial stress is associated with in vivo dopamine release in human ventromedial prefrontal cortex: a positron emission tomography study using [(1)(8)F]fallypride. Neuroimage. 2011 Oct 15;58(4):1081-9. doi: 10.1016/j.neuroimage.2011.07.030. Epub 2011 Jul 23.
Milich, R., Balentine, A. C., & Lynam, D. R. (2001). ADHD combined type and ADHD predominantly inattentive type are distinct and unrelated disorders. Clinical Psychology: Science and Practice, 8, 463-488.
Morrow BA, Roth RH, Elsworth JD. TMT, a predator odor, elevates mesoprefrontal dopamine metabolic activity and disrupts short-term working memory in the rat. Brain Res Bull. 2000 Aug;52(6):519-23. doi: 10.1016/s0361-9230(00)00290-2.
Roth RH, Tam SY, Ida Y, Yang JX, Deutch AY. Stress and the mesocorticolimbic dopamine systems. Ann N Y Acad Sci. 1988;537:138-47. doi: 10.1111/j.1749-6632.1988.tb42102.x. No abstract available.
Schmeichel BE, Zemlan FP, Berridge CW. A selective dopamine reuptake inhibitor improves prefrontal cortex-dependent cognitive function: potential relevance to attention deficit hyperactivity disorder. Neuropharmacology. 2013 Jan;64(1):321-8. doi: 10.1016/j.neuropharm.2012.07.005. Epub 2012 Jul 11.
Spencer RC, Klein RM, Berridge CW. Psychostimulants act within the prefrontal cortex to improve cognitive function. Biol Psychiatry. 2012 Aug 1;72(3):221-7. doi: 10.1016/j.biopsych.2011.12.002. Epub 2011 Dec 29.
Weiss M, Worling D, Wasdell M. A chart review study of the inattentive and combined types of ADHD. J Atten Disord. 2003 Sep;7(1):1-9. doi: 10.1177/108705470300700101.
Other Identifiers
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H13-00286
Identifier Type: -
Identifier Source: org_study_id
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