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2010 Schizophrenia International Research Society Conference

Click on this image to view the SIRS Welcome Video

John Kane, president of the Schizophrenia International Research Society, welcomes researchers and clinicians to make plans to attend the 2nd Schizophrenia International Research Society Conference, 10–14 April 2010, in Florence, Italy. As Kane mentions in his Welcome Video, among the highlights will be plenary sessions on the latest research on genetics, neuropsychopharmacology, and neuroimaging.

A special keynote address will be given by Elyn Saks, professor of law at the University of Southern California, who detailed her struggle with schizophrenia in the best-selling The Center Cannot Hold, and who was a 2009 recipient of a MacArthur "genius" award. And to whet your appetite, check out the photos from the 2008 Venice meeting.


Select SIRS 2010 Lecture Slidecasts Online

Thanks to SIRS, we are able to bring you slides and audio of some of the plenary talks and sessions at the SIRS 2010 meeting. You can either watch the slides here at SRF, or navigate over to the SIRS website to watch them.


The 2010 SIRS/SRF Essay Contest

Rajiv Radhakrishnan

Congratulations are in order for the winner of the 2010 SIRS/SRF Essay Contest—Rajiv Radhakrishnan, a postdoctoral fellow at Yale University School of Medicine, who receives free registration and hotel stay at the Florence SIRS meeting. We recognize Anna Docherty of the University of Missouri-Columbia and Thomas Whitford, Melbourne Neuropsychiatry Centre, University of Melbourne; Psychiatry Neuroimaging Laboratory, Harvard Medical School, with honorable mentions.

Finally, we also thank the judges—Dan Javitt of the Nathan Kline Institute, John McGrath of the University of Queensland, and Jim van Os of Maastricht University—who evaluated the entries on the criteria of originality, argument, and implementation in response to this challenge:

Help Break the Logjam!
The field of schizophrenia research does not lack for data: neuroscience, epidemiology, and technology, among others, have produced piles of data. What we lack are unifying hypotheses. SIRS and SRF ask that you wade out into the river of data and help break the logjam.

Choose five compelling facts from various fields and describe a unifying hypothesis for schizophrenia based upon these. And don't forget the predictions—what do you propose that your colleagues should do to test your hypothesis?

Read all 12 of the top-scoring essays!


Rajiv Radhakrishnan
Yale University School of Medicine
New Haven, Connecticut

Fact 1: Exposure to amphetamine can result in schizophrenia-like symptoms in some individuals. This effect is observed in chronic, but not acute, amphetamine use (Segal et al., 1997).

Fact 2: The electrophysiological characteristics of prefrontal cortex neurons begin to change after just a few doses of the drug, and amphetamine exposure has opposite effects in two subregions of prefrontal cortex—a progressive hyperactivation of orbitofrontal cortex and hypoactivation of medial prefrontal cortex (mPFC) (Homayoun et al., 2006).

Fact 3: mPFC abnormalities are present in schizophrenia on multimodal imaging (Pomarol-Clotet et al., 2010). In first-episode antipsychotic-naïve patients with schizophrenia, the mPFC is smaller compared to controls (Venkatasubramanian et al., 2008).

Fact 4: The mPFC is an important hub of the default mode network (DMN). An aberrant functional connectivity of the DMN is seen in schizophrenia (Garrity et al., 2007) involving the mPFC, in particular (Camchong et al., 2009).

Fact 5: The endocannabinoid system is abnormal in schizophrenia (Fernandez-Espejo et al., 2009). Inhibition of interneuron firing extends the spread of endocannabinoid signaling (as has been shown in the cerebellum) (Kreitzer et al., 2002). The rate of firing can determine if the endocannabinoid system causes a net inhibitory long-term depression (LTD) or disinhibitory LTD (Adermark et al., 2009).

Hypothesis
Conversion from ultra high risk to schizophrenia is characterized by spread of activation of the mPFC to the dorsolateral prefrontal cortex (DLPFC), resulting in a disruption of the normal feedback regulation of the mPFC. This leads to progressive denervation of the mPFC. This process is mediated by the endocannabinoid system. It is predicted that: 1) There would be a decrease in activation of mPFC and increase in activation of DLPFC in both a working memory paradigm and a DMN paradigm as ultra high-risk patients progress to schizophrenia; 2) Cannabinoid receptor number and density will increase in the mPFC during progression from ultra high risk to schizophrenia and subsequently decrease with denervation.

Testing the Hypothesis
1. Characterization of the activity and volume of mPFC and DLPFC in DMN and working memory task paradigms in prodromal, ultra high-risk subjects over time to conversion to schizophrenia. The hypothesis suggests that the current discrepancy with regard to working memory tasks (with some studies showing hyperactivity and others showing hypoactivity in DLPFC) can be explained by the functional integrity of the mPFC; with progressive denervation of mPFC, DLPFC activity will decrease.

2. Characterization of temporal pattern of cannabinoid receptor (CB1, CB2) number and density in prodromal, ultra high-risk subjects until conversion to schizophrenia.

3. Demonstration of inhibitory LTD and disinhibitory LTD in the medial PFC in an animal model mediated by endocannabinoid signaling.

4. Demonstration of spread of activation from mPFC to DLPFC in an animal model by modulating endocannabinoid signaling.

References:
Segal DS, Kuczenski R. An escalating dose ‘‘binge’’model of amphetamine psychosis: behavioral and neurochemical characteristics. J Neurosci. 1997;17:2551–2566. Abstract

Homayoun H, Moghaddam B. Progression of cellular adaptations in medial prefrontal and orbitofrontal cortex in response to repeated amphetamine.J Neurosci. 2006 Aug 2;26(31):8025-39. Abstract

Pomarol-Clotet E, Canales-Rodríguez EJ, Salvador R, Sarró S, Gomar JJ, Vila F, Ortiz-Gil J, Iturria-Medina Y, Capdevila A, McKenna PJ. Medial prefrontal cortex pathology in schizophrenia as revealed by convergent findings from multimodal imaging. Mol Psychiatry. 2010 Jan 12. Abstract

Venkatasubramanian G, Jayakumar PN, Gangadhar BN, Keshavan MS. Automated MRI parcellation study of regional volume and thickness of prefrontal cortex (PFC) in antipsychotic-naïve schizophrenia. Acta Psychiatr Scand. 2008 Jun;117(6):420-31. Abstract

Garrity AG, Pearlson GD, McKiernan K, Lloyd D, Kiehl KA, Calhoun VD. Aberrant "default mode" functional connectivity in schizophrenia.Am J Psychiatry. 2007 Mar;164(3):450-7. Abstract

Camchong J, Macdonald AW 3rd, Bell C, Mueller BA, Lim KO. Altered Functional and Anatomical Connectivity in Schizophrenia. Schizophr Bull. 2009 Nov 17. Abstract

Fernandez-Espejo E, Viveros MP, Núñez L, Ellenbroek BA, Rodriguez de Fonseca F. Role of cannabis and endocannabinoids in the genesis of schizophrenia. Psychopharmacology (Berl). 2009 Nov;206(4):531-49. Abstract

Kreitzer AC, Carter AG, Regehr WG. Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum. Neuron. 2002 May 30;34(5):787-96. Abstract

Adermark L, Lovinger DM. Frequency-dependent inversion of net striatal output by endocannabinoid-dependent plasticity at different synaptic inputs. J Neurosci. 2009 Feb 4;29(5):1375-80. Abstract


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