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Concurrent Symposia Presentations S3that surround PV cells. Second, we analyzed the transcriptome of PV cells captured by laser microdissection. Third, we evaluated the number of excitatory inputs to PV cells and the integrity of the ErbB4 signaling system that regulates the localization of PSD95 to excitatory synapses in PV neurons. Results: In the prefrontal cortex, the normal complements of PV cells and PNNs are preserved in schizophrenia, but the levels of PV protein and of individual PNN components, especially the carbohydrate moieties, are lower. Transcriptome profiling of laser-captured layer 3 PV neurons identified over 1000 genes that are differentially expressed in schizophrenia, most of which are not altered in layer 3 pyramidal neurons. Some of the alterations in PV neurons suggest a state of heightened plasticity, consistent with the alterations in PNNs, another plasticity regulator of PV cells. Finally, quantitative confocal immunocytochemical studies revealed that PV neurons receive fewer excitatory inputs in schizophrenia. This reduction appears to be attributable to altered splicing of ErbB4, which could disrupt the localization of PSD95 to excitatory synapses, selectively in PV neurons. Conclusion:In concert, these findings provide new insights into the nature of PV neuron alterations in schizophrenia. Which of these findings represent a primary pathology of PV neurons and which are secondary in the disease process remain critical questions. Answers to these questions will inform which findings represent potential new targets for therapeutic interventions as well as how those targets should be attacked. CAN NEUROBIOLOGICAL SUBGROUPS IN PSYCHOTIC ILLNESS ADVANTAGE DRUG DISCOVERY?Carol Background: Are there neurobiological subgroups in schizophrenia or across psychotic illnesses that will select individuals who will respond to drugs that enhance parvalbumin (PV)-positive inhibitory interneuron function? The question requires not only clarification and validation of biomarker-based schizophrenia subgrouping options but also specific models around how to fit these with the pathology of PV-positive inhibitory neuronal dysfunction. Methods: Recent studies have proposed approaches for defining neurobiologically distinct psychosis groups. The Bipolar Schizophrenia Network for Intermediate Phenotypes study collected a large group of probands with psychosis, their relatives, and healthy controls for precise diagnosis, clinical characterization, and a deep phenotyping study in 5 sites across the United States. Using the resultant biomarkers (including cognitive, electrophysiological [EEG], motor, and imaging biomarkers), hypothesis-free statistical clustering analyses were carried out, using only biomarker data to cluster the probands on biologically based characteristics rather than by clinical symptoms. Results: These analyses resulted in outcomes showing neurobiologically compelling, biomarker-based clusters of psychotic probands called Biotypes. The psychosis Biotypes were distinguished by several cha...

Objective: The dual-specificity phosphatase 6 (DUSP6) gene resides at chromosome location 12q22-23, which is one of the candidate loci for susceptibility to bipolar disorder and which encodes a phosphatase selective for extracellular signal-regulated kinase (ERK). In this study, we investigated the genetic association between DUSP6 gene and BD, and also investigated the functions of the Leu114Val and Ser144Ala mutations in DUSP6 proteins, which were raised by T/G polymorphisms in exon 1 and exon 2, respectively.Methods: This study investigated the genetic association of DUSP6 with BD and schizophrenia (SPR) in the Korean population. Based on the evidence of the sexdimorphic effect of DUSP6 on BD, we performed two independent analyses in homogeneous samples of female and male patients. Moreover, the effects of missense mutations in the Leu114Val and Ser144Ala of DUSP6 proteins associated with T/G polymorphisms in exons 1 and 2, which showed positive associations with BD in this study, were also investigated in terms of their activation of ERK1/2 in response to lithium treatment. A. Diez-Revuelta, C. Tobon, J.M. Porto, M.V. Perea, V. Molina, R. Hornero and M. Franco-Martin Objective: Several lines of research currently support the existence of disorganized activity patterns in schizophrenia. Electroencephalogram (EEG) studies can help understand the possible implication of such disruption for cognitive deficits shown by patients with schizophrenia.

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