Bipolar Disorder; Depressive Disorder; Schizophrenia
Converging evidence implicates abnormalities of white matter connections and function within specific neural circuitry in schizophrenia, bipolar disorder and major depressive disorder. New brain scanning techniques (diffusion tensor imaging which provides measures of structural connectivity and functional connectivity which is a new way to analyze functional magnetic resonance image data and provides measures of functional connectivity) are used to investigate neural circuitry abnormalities in these disorders. Recently, findings suggest genetic variations influence neural circuitry to produce the clinical phenotypes of mental disorders. We aim to investigate neural circuitry abnormalities using multiple brain scanning techniques with a combined molecular genetic study to determine which genes might contribute to these abnormalities. Our work will enhance our understanding of the causes of these disorders, our ability to detect the disorders early and to develop novel and more effective treatments.
Extensive Research Description
My longstanding interest is identification of neural circuitry abnormalities using multimodal neuroimaging techniques and investigation of how genetic variations influence neural circuitry to produce the clinical phenotypes of mental disorders, such as schizophrenia, bipolar disorder and major depressive disorder. My primary research interests lie in developing novel multimodal magnetic resonance imaging techniques to characterize the critical neural circuitry abnormalities underlying these disorders and identifying the specific genetic variations that contribute to them. Our work in translational research will contribute to elucidating the neuropathophysiological mechanisms underlying the disorders, aid in the development of new methods for early detection, and importantly, improve treatment of debilitating psychiatric illnesses.
1. Methods of multimodal neuroimaging:
This project aims to use multimodal neuroimaging techniques to identify abnormalities of important neural circuitry in mental disorders. I developed diffusion tensor imaging (DTI) methods to study the cingulum, a white matter structure important in cortico-limbic circuitry. My work demonstrated abnormalities in the anterior cingulum in schizophrenia and bipolar disorder; however, findings demonstrate a different distribution of white matter abnormalities in the two disorders. I have also developed functional magnetic resonance imaging methods to study cortico-limbic functional connectivity to be integrated with DTI methods. Using these methodologies, I have obtained exciting findings that demonstrate altered structural and functional connectivity in cortico-limbic neural circuitry in mood disorders. Moreover, I have identified an association between structural and functional connectivity within this circuitry in bipolar disorder, providing some of the first evidence that these structural abnormalities may contribute to disruptions in the ability of the cortical region to modulate the functioning of limbic structure in mood disorders.
2. Integration of multimodal neuroimaging and molecular genetics:
This project aims to develop translational research approaches of integrating molecular genetics with multimodal neuroimaging to identify novel effects of genetic variations on cortico-limbic circuitry in mental disorders. I have reported an important finding of the influence of genetic variation in neuregulin 1 on dorsal frontotemporal white matter connection abnormalities in schizophrenia. I have also recently authored psychiatric genetic papers in mood disorders including a paper that reports a novel finding of an association between variation in the vascular endothelial growth factor gene and cortico-limbic structure and on two papers on the association between the brain-derived neurotrophic growth factor gene/serotonin transporter protein gene and cortico-limbic structure/function in bipolar disorder.
- Frontotemporal Neural Systems in Bipolar Disorder and Schizophrenia: This project aims to investigate differences in the distribution of brain abnormalities in bipolar disorder and schizophrenia and to determine which genes may contribute to the distinct distributions.
- Structural and Functional Connectivity of the Perigenual Anterior Cingulate in Adolescents with Bipolar Disorder: This project proposes to integrate multimodal magnetic resonance imaging techniques in order to investigate the different developmental trajectories of structural and functional connections between the amygdala and anterior cingulate cortex in adolescents with and without bipolar disorder.
- The Neural Circuitry of Adolescent Major Depressive Disorder: A Multi-modality Magnetic Resonance Imaging Study: This project proposes to integrate multimodal magnetic resonance imaging techniques in order to investigate the structural and functional connections between the ventral prefrontal cortex and the amygdala in adolescents with and without major depressive disorder.
- Wang F, Kalmar JH, He Y, et al. Functional and structural connectivity between the perigenual anterior cingulate and amygdala in bipolar disorder. Biol. Psychiatry 2009;66:516-21
- Wang F, Kalmar JH, Edmiston E, et al. Abnormal corpus callosum integrity in bipolar disorder. Biol. Psychiatry 2008; 64: 730-733.
- Wang F, Jiang T, Sun Z, et al. Neuregulin 1 genetic variation and anterior cingulum integrity in schizophrenia and in health. J. Psychiatry Neuroscience 2009; 34:181-6.
- Wang F, Jackowski M, Karlmar JH, et al. Abnormal anterior cingulum integrity in bipolar disorder determined through diffusion tensor imaging. Brit. J. Psychiatry 2008; 193:126-129.
- Blumberg HP*, Wang F*, Chepenik LG, et al. Influence of vascular endothelial growth factor variation on human hippocampus morphology. Biol. Psychiatry 2008; 64: 901-903. * Co-first authors.
- Wang F, Sun Z, Cui L, et al. Anterior cingulum abnormalities in male schizophrenia with diffusion tensor imaging. Am. J. Psychiatry 2004; 161:573-575.