The CTMHR is comprised of five research projects and two cores that are designed to provide convergent tests of one central hypothesis. The figure below illustrates the type of study, level of analysis, principal technical approaches, species studied (M = monkey; H = human) and interactions with the cores for each of the projects. The bidirectional arrows indicate that each project tests aspects of the Central Hypothesis and is in turn informed and constrained by the findings of the other projects.
Project 1 — Molecular alterations of cortical layer 3 pyramidal cells in schizophrenia
This project will characterize at the cellular level the core molecular pathology in cortical layer 3 pyramidal cells in schizophrenia and determine how this pathology is moderated by factors that include regional specificity in the expression of mRNAs and miRNA regulatory elements. Project 1 will also provide insight into potential targets to restore functional balance along the visual cortical network.
Project 2 — Morphological alterations of cortical layer 3 pyramidal cells in schizophrenia
Individuals with schizophrenia have impairments in attention and working memory, the ability to retain information in mind, which are important determinants of day-to-day function. This project will determine if individuals with schizophrenia have impairments in the neuronal structures in three key brain regions that form the circuits responsible for attention and working memory.
Project 3 — Intrinsic properties of cortical layer 3 pyramidal cells in monkeys
This project will inform our understanding of the neural circuitry basis for attention and working memory impairments in schizophrenia through the use of a non-human primate model system to determine, with specificity at the levels of cell types, local circuits and inter-regional connections, the critical properties of the same neural circuitry studied at the functional and behavioral levels in human subjects.
Project 4 — Laminar organization of cortical functional connectivity in monkeys
This project will establish the role of layer 3 neurons in the cognitive deficits in schizophrenia.
Project 5 — Alterations of cortical connectivity and cognition in schizophrenia
Cognitive dysfunction is the main contributor to social and occupational problems in schizophrenia. This project will link knowledge about cellular pathology to cortical pathophysiology in medication naïve subjects in a first-episode of psychosis, providing the foundation for the development of pathophysiologically-informed biomarkers for new therapeutic approaches.
Statistics & Data Management Core
This Core will develop innovative statistical methodology when currently available statistical methods are not fully effective. New statistical methodology could provide advances beyond current statistical methods that can be utilized in other areas of translational mental health research, in addition to increasing the impact of studies conducted by Center investigators.
All five projects and the Statistics & Data Management Core are supported by the CTMHR Administrative Core.
Silvio O. Conte Center for Translational Mental Health Research
Funded by the National Institute of Mental Health (MH103204)