Impulsive aggressive behavior can complicate severe forms of many different neuropsychiatric disorders across the lifespan, resulting in impaired function and institutionalization. Current treatments for impulsive aggression include behavioral and pharmacological approaches, though for some patients these are ineffective or confer substantial side effects. My research uses mouse models to identify brain regions and neural circuits that are important regulators of aggressive behavior, as well as mechanisms to selectively modulate the activity of these regions and circuits. To this end, we are studying how nicotinic acetylcholine receptors govern aggression-related neurocircuitry, with a focus on the hippocampal formation. Concurrent with our basic scientific studies, we are studying the effects of transdermal nicotine on aggression and related behaviors in adults with autism spectrum disorder who have persistent aggression that interferes with their lives. The goal of this translational study is to determine the tolerability and potential efficacy of a nicotinic receptor therapy for an aggression indication and support future studies using more specific nicotinic pharmacotherapies.
- Lewis AS, van Schalkwyk GI, Bloch MH (2017) Alpha-7 nicotinic agonists for cognitive deficits in neuropsychiatric disorders: A translational meta-analysis of rodent and human studies. Progress in Neuropsychopharmacology and Biological Psychiatry. In press.
- Lewis AS, Mineur YS, Smith PH, Cahuzac EL, Picciotto MR (2015) Modulation of aggressive behavior in mice by nicotinic receptor subtypes. Biochemical Pharmacology 97:488-97.
- Van Schalkwyk GI, Lewis AS, Qayyum Z, Koslosky K, Picciotto MR, Volkmar FR (2015) Reduction of Aggressive Episodes After Repeated Transdermal Nicotine Administration in a Hospitalized Adolescent with Autism Spectrum Disorder. J Autism Dev Disord. 45:3061-6.
- Picciotto MR, Lewis AS, van Schalkwyk GI, Mineur YS (2015) Mood and anxiety regulation by nicotinic acetylcholine receptors: a potential pathway to modulate aggression and related behavioral states. Neuropharmacology. 96(Pt B):235-43.
- Lewis AS, Picciotto MR (2013) High-affinity nicotinic acetylcholine receptor expression and trafficking abnormalities in psychiatric illness. Psychopharmacology (Berl) 229:477-485.
- Lewis AS, Schwartz E, Chan CS, Noam Y, Shin M, Wadman WJ, Surmeier DJ, Baram TZ, Macdonald RL, Chetkovich DM (2009) Alternatively spliced isoforms of TRIP8b differentially control h channel trafficking and function. Journal of Neuroscience 29:6250-6265.
- Lewis AS, Vaidya SP, Blais CA, Liu Z, Stoub TR, Brager DH, Chen X, Bender RA, Estep CM, Popov AB, Kang CE, van Veldhoven PP, Bayliss DA, Nicholson DA, Powell CM, Johnston D, Chetkovich DM (2011) Deletion of the HCN channel auxiliary subunit TRIP8b impairs hippocampal Ih localization and function and promotes antidepressant behavior in mice. Journal of Neuroscience 31:7424-7440.
Full List of PubMed Publications
- van Schalkwyk GI, Lewis AS, Beyer C, Johnson J, van Rensburg S, Bloch MH: Efficacy of antipsychotics for irritability and aggression in children: a meta-analysis. Expert Rev Neurother. 2017 Oct; 2017 Sep 11. PMID: 28847182
- Lewis AS, van Schalkwyk GI, Bloch MH: Alpha-7 nicotinic agonists for cognitive deficits in neuropsychiatric disorders: A translational meta-analysis of rodent and human studies. Prog Neuropsychopharmacol Biol Psychiatry. 2017 Apr 3; 2017 Jan 5. PMID: 28065843
- Lewis AS, Oberleitner LM, Morgan PT, Picciotto MR, McKee SA: Association of Cigarette Smoking With Interpersonal and Self-Directed Violence in a Large Community-Based Sample. Nicotine Tob Res. 2016 Jun; 2015 Dec 30. PMID: 26718905
- Heuermann RJ, Jaramillo TC, Ying SW, Suter BA, Lyman KA, Han Y, Lewis AS, Hampton TG, Shepherd GMG, Goldstein PA, Chetkovich DM: Reduction of thalamic and cortical Ih by deletion of TRIP8b produces a mouse model of human absence epilepsy. Neurobiol Dis. 2016 Jan; 2015 Oct 14. PMID: 26459112
- Lewis AS, Mineur YS, Smith PH, Cahuzac ELM, Picciotto MR: Modulation of aggressive behavior in mice by nicotinic receptor subtypes. Biochem Pharmacol. 2015 Oct 15; 2015 Jul 23. PMID: 26212554
- Van Schalkwyk GI, Lewis AS, Qayyum Z, Koslosky K, Picciotto MR, Volkmar FR: Reduction of Aggressive Episodes After Repeated Transdermal Nicotine Administration in a Hospitalized Adolescent with Autism Spectrum Disorder. J Autism Dev Disord. 2015 Sep. PMID: 25982311
- Picciotto MR, Lewis AS, van Schalkwyk GI, Mineur YS: Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states. Neuropharmacology. 2015 Sep; 2015 Jan 9. PMID: 25582289
- Lewis AS, Oldham MA: Delusional Infestation With Black Mold Presenting to the General Hospital. Prim Care Companion CNS Disord. 2015; 2015 Apr 9. PMID: 26443034
- Brager DH, Lewis AS, Chetkovich DM, Johnston D: Short- and long-term plasticity in CA1 neurons from mice lacking h-channel auxiliary subunit TRIP8b. J Neurophysiol. 2013 Nov; 2013 Aug 21. PMID: 23966674
- Lewis AS, Picciotto MR: High-affinity nicotinic acetylcholine receptor expression and trafficking abnormalities in psychiatric illness. Psychopharmacology (Berl). 2013 Oct; 2013 Apr 28. PMID: 23624811
- Huang Z, Lujan R, Martinez-Hernandez J, Lewis AS, Chetkovich DM, Shah MM: TRIP8b-independent trafficking and plasticity of adult cortical presynaptic HCN1 channels. J Neurosci. 2012 Oct 17. PMID: 23077068
- Marcelin B, Lugo JN, Brewster AL, Liu Z, Lewis AS, McClelland S, Chetkovich DM, Baram TZ, Anderson AE, Becker A, Esclapez M, Bernard C: Differential dorso-ventral distributions of Kv4.2 and HCN proteins confer distinct integrative properties to hippocampal CA1 pyramidal cell distal dendrites. J Biol Chem. 2012 May 18; 2012 Apr 16. PMID: 22511771
- Bankston JR, Camp SS, DiMaio F, Lewis AS, Chetkovich DM, Zagotta WN: Structure and stoichiometry of an accessory subunit TRIP8b interaction with hyperpolarization-activated cyclic nucleotide-gated channels. Proc Natl Acad Sci U S A. 2012 May 15; 2012 May 1. PMID: 22550182
- Marcelin B, Liu Z, Chen Y, Lewis AS, Becker A, McClelland S, Chetkovich DM, Migliore M, Baram TZ, Esclapez M, Bernard C: Dorsoventral differences in intrinsic properties in developing CA1 pyramidal cells. J Neurosci. 2012 Mar 14. PMID: 22423094
- Khurana S, Liu Z, Lewis AS, Rosa K, Chetkovich D, Golding NL: An essential role for modulation of hyperpolarization-activated current in the development of binaural temporal precision. J Neurosci. 2012 Feb 22. PMID: 22357864
- Wilkars W, Liu Z, Lewis AS, Stoub TR, Ramos EM, Brandt N, Nicholson DA, Chetkovich DM, Bender RA: Regulation of axonal HCN1 trafficking in perforant path involves expression of specific TRIP8b isoforms. PLoS One. 2012; 2012 Feb 21. PMID: 22363812
- Han Y, Noam Y, Lewis AS, Gallagher JJ, Wadman WJ, Baram TZ, Chetkovich DM: Trafficking and gating of hyperpolarization-activated cyclic nucleotide-gated channels are regulated by interaction with tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) and cyclic AMP at distinct sites. J Biol Chem. 2011 Jun 10; 2011 Apr 19. PMID: 21504900
- Lewis AS, Vaidya SP, Blaiss CA, Liu Z, Stoub TR, Brager DH, Chen X, Bender RA, Estep CM, Popov AB, Kang CE, Van Veldhoven PP, Bayliss DA, Nicholson DA, Powell CM, Johnston D, Chetkovich DM: Deletion of the hyperpolarization-activated cyclic nucleotide-gated channel auxiliary subunit TRIP8b impairs hippocampal Ih localization and function and promotes antidepressant behavior in mice. J Neurosci. 2011 May 18. PMID: 21593326
- Lewis AS, Chetkovich DM: HCN channels in behavior and neurological disease: too hyper or not active enough? Mol Cell Neurosci. 2011 Feb; 2010 Dec 3. PMID: 21130878
- Chan CS, Glajch KE, Gertler TS, Guzman JN, Mercer JN, Lewis AS, Goldberg AB, Tkatch T, Shigemoto R, Fleming SM, Chetkovich DM, Osten P, Kita H, Surmeier DJ: HCN channelopathy in external globus pallidus neurons in models of Parkinson's disease. Nat Neurosci. 2011 Jan; 2010 Nov 14. PMID: 21076425
- Lewis AS, Estep CM, Chetkovich DM: The fast and slow ups and downs of HCN channel regulation. Channels (Austin). 2010 May-Jun. PMID: 20305382
- Lewis AS, Schwartz E, Chan CS, Noam Y, Shin M, Wadman WJ, Surmeier DJ, Baram TZ, Macdonald RL, Chetkovich DM: Alternatively spliced isoforms of TRIP8b differentially control h channel trafficking and function. J Neurosci. 2009 May 13. PMID: 19439603
- Chung WK, Shin M, Jaramillo TC, Leibel RL, LeDuc CA, Fischer SG, Tzilianos E, Gheith AA, Lewis AS, Chetkovich DM: Absence epilepsy in apathetic, a spontaneous mutant mouse lacking the h channel subunit, HCN2. Neurobiol Dis. 2009 Mar; 2008 Dec 25. PMID: 19150498