Differences by Sex and Genotype in the Effects of Stress on Executive Functions

Summary

The aim of this project is to test the effects of an environmental factor (mild stress) on prefrontal cortex (PFC) and the cognitive functions that depend on PFC (collectively called executive functions \[EFs\]), and to test our predictions concerning how those effects differ by biological factors (hormones and genotype). To test our hypotheses concerning mechanism, the investigators will model the effects of mild stress on EFs pharmacologically. The purpose is to pharmacologically model the effects of mild stress on the cognitive functions (collectively called "executive functions" \[EFs\]) dependent on the frontal lobe. The investigators would also like to investigate how gender differences and genotype mediate the effect of methylphenidate (MPH) on EFs.

Timeline

Start

2018-04-28

Primary completion

2024-12

Completion

2024-12

Publications

• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.

Drugs

Indications

No indication recorded.