Department of Psychiatry

Penn Behavioral Health

Siegel Lab Research

Current Research Programs

Animal Models of Brain Abnormalities in Schizophrenia
Translational Neuroscience Program is also dedicated to understanding the neural basis for brain abnormalities in schizophrenia in an effort to improve future treatments. One approach to achieve this goal is through the use of animal models. People with schizophrenia are thought to have abnormal brain responses following auditory stimuli (sound). Although it is not known how this abnormal brain activity is related to symptoms, it provides a method to study neuronal abnormalities in people with the illness. Although the complex symptoms of schizophrenia cannot be modeled in animals, abnormal neural activity following auditory stimuli can be recreated in mice in order to study the underlying biology of this phenomenon. These patterns of neural activity in response to noise are called sensory processing. In order to examine the neural basis of abnormal sensory processing in schizophrenia, we are studying the genetics and cellular biology of sensory processing in mice that share schizophrenia-like patterns of neural activity following auditory stimuli.

Development of long-term delivery systems to increase medication adherence
The Translational Neuroscience Program is a national leader in creating and advocating for the use of long-term delivery systems to help people with schizophrenia remain on medication. Noncompliance with medication is the major reason for poor clinical outcome in schizophrenia today and up to 80% of people with schizophrenia are not able to take their medication as prescribed. There are many reasons for poor compliance, including difficulties with access to medication, side effects and poor insight into the illness and the consequences of not taking medicine. Most people can achieve periods of remission on medicine. However, difficulties arise when periods off medicine lead to relapse, poor judgment and further decline. During these periods of relapse, patients' decisions are clouded by psychosis and often do not reflect their own best interests. Long-term delivery systems are designed to increase patient autonomy by allowing people to make their own treatment choices while they are well, rather than during periods of relapse.

Publications

Click Here for the Most Recent Lab Publications

Electrophysiological and behavioral responses to ketamine in mice with reduced Akt1 expression. Featherstone RE, M Tatard-Leitman V, Suh JD, Lin R, Lucki I, Siegel SJ.Psychopharmacology (Berl). 2013 Feb 8. [Epub ahead of print] PMID: 23392353

Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice. Wang IT, Allen M, Goffin D, Zhu X, Fairless AH, Brodkin ES,Siegel SJ, Marsh ED, Blendy JA, Zhou Z. Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21516-21.

Electroencephalographic changes following direct current deep brain stimulation of auditory cortex: a new model for investigating neuromodulation. De Rojas JO, Saunders JA, Luminais C, Hamilton RH, Siegel SJ. Neurosurgery. 2013 Feb;72(2):267-75

Delivery systems and dosing for antipsychotics. Rabin CR, Siegel SJ. Handb Exp Pharmacol. 2012;(212):267-98.

Nicotine receptor subtype-specific effects on auditory evoked oscillations and potentials. Featherstone RE, Phillips JM, Thieu T, Ehrlichman RS, Halene TB, Leiser SC, Christian E, Johnson E, Lerman C, Siegel SJ. PLoS One. 2012;7(7):e39775.

The electrophysiological signature of motivational salience in mice and implications for schizophrenia. Moessnang C, Habel U, Schneider F, Siegel SJ.Neuropsychopharmacology. 2012 Dec;37(13):2846-54.

GABAB-mediated rescue of altered excitatory-inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction. Gandal MJ, Sisti J, Klook K, Ortinski PI, Leitman V, Liang Y, Thieu T, Anderson R, Pierce RC, Jonak G, Gur RE, Carlson G, Siegel SJ. Transl Psychiatry. 2012 Jul 17;2:e142.

NMDA antagonist MK801 recreates auditory electrophysiology disruption present in autism and other neurodevelopmental disorders. Saunders JA, Gandal MJ, Roberts TP,Siegel SJ. Behav Brain Res. 2012 Oct 1;234(2):233-7.

Mice with reduced NMDA receptor expression: more consistent with autism than schizophrenia? Gandal MJ, Anderson RL, Billingslea EN, Carlson GC, Roberts TP,Siegel SJ. Genes Brain Behav. 2012 Aug;11(6):740-50.

Subchronic ketamine treatment leads to permanent changes in EEG, cognition and the astrocytic glutamate transporter EAAT2 in mice. Featherstone RE, Liang Y, Saunders JA, Tatard-Leitman VM, Ehrlichman RS, Siegel SJ. Neurobiol Dis. 2012 Sep;47(3):338-46.

Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Makadia HK, Siegel SJ. Polymers (Basel). 2011 Sep 1;3(3):1377-1397.

Nicotine normalizes event related potentials in COMT-Val-tg mice and increases gamma and theta spectral density. Cao YA, Featherstone RE, Gandal MJ, Liang Y, Jutzeler C, Saunders J, Tatard-Leitman V, Chen J, Weinberger DR, Lerman C, Siegel SJ. Behav Neurosci. 2012 Apr;126(2):332-43

MeCP2+/- mouse model of RTT reproduces auditory phenotypes associated with Rett syndrome and replicate select EEG endophenotypes of autism spectrum disorder. Liao W, Gandal MJ, Ehrlichman RS, Siegel SJ, Carlson GC. Neurobiol Dis. 2012 Apr;46(1):88-92.

NMDA antagonists recreate signal-to-noise ratio and timing perturbations present in schizophrenia. Saunders JA, Gandal MJ, Siegel SJ. Neurobiol Dis. 2012 Apr;46(1):93-100..

Rett syndrome mutation MeCP2 T158A disrupts DNA binding, protein stability and ERP responses. Goffin D, Allen M, Zhang L, Amorim M, Wang IT, Reyes AR, Mercado-Berton A, Ong C, Cohen S, Hu L, Blendy JA, Carlson GC, Siegel SJ, Greenberg ME, Zhou Z. Nat Neurosci. 2011 Nov 27;15(2):274-83.

mGluR5-antagonist mediated reversal of elevated stereotyped, repetitive behaviors in the VPA model of autism. Mehta MV, Gandal MJ, Siegel SJ. PLoS One. 2011;6(10):e26077.

Dysbindin-1 mutant mice implicate reduced fast-phasic inhibition as a final common disease mechanism in schizophrenia. Carlson GC, Talbot K, Halene TB, Gandal MJ, Kazi HA, Schlosser L, Phung QH, Gur RE, Arnold SE, Siegel SJ. Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):E962-70..

What can we expect from long-acting formulations for schizophrenia? Siegel SJ. Curr Psychiatry Rep. 2011 Aug;13(4):243-4.

Gamma synchrony: towards a translational biomarker for the treatment-resistant symptoms of schizophrenia. Gandal MJ, Edgar JC, Klook K, Siegel SJ.Neuropharmacology. 2012 Mar;62(3):1504-18.


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