Although current nosology defines schizophrenia (SCZ) and bipolar disorder as unique constructs with distinctive clinical characteristics, there exist significant symptomatic and familial overlap. Epidemiologic and genetic studies suggest that SCZ shares common susceptibility genes with psychotic bipolar disorder (PBD), as opposed to nonpsychotic bipolar disorder (NPBD), suggesting that they may also share similar structural abnormalities in gray and white matter in the brain. We hypothesize that: 1) PBD and NPBD will differ in measures of subcortical gray matter and white matter integrity, 2) abnormalities in PBD will be intermediate between SCZ and NPBD, and 3) there will be a significant relationship between lifetime psychosis severity and structural measures.
The Aims of this proposal are to: 1) collect MRI scans from 40 PBD and 40 NPBD subjects and generate volume and shape metrics for the hippocampus, thalamus and basal ganglia, and measures of corpus callosum integrity, 2) compare these measures between PBD, NPBD, SCZ and controls, and 3) correlate lifetime psychopathology with structural abnormalities in PBD and SCZ. This 5-year program will involve training in specific neuroimaging methodologies and the neurobiology of bipolar disorder, as well as general research and ethics. Imaging methods used in this proposal will be Large-Deformation High-Dimensional Brain Mapping and Diffusion Tensor Imaging. Deanna Barch, Ph.D. (Dept. of Psychiatry, Washington University), John Csernansky, MD (Northwestern University), Joshua Shimony, MD, PhD and Abraham Snyder, PhD, MD (both at the Dept. of Radiology, Washington University) will co-mentor the principal investigator's scientific development. All co-mentors have substantial experience in various areas of neuroimaging and in the application of related research methods, as well as experience training postdoctoral fellows and NIH grant recipients. The proposal is also supported by a rich diversity of collaborators and consultants to provide education and guidance in various aspects of research. The principal investigator has completed residency training in Psychiatry and a Masters in Psychiatric Epidemiology (MPE) at Washington University School of Medicine in St. Louis.

Public Health Relevance

In clinical practice, treatments used in schizophrenia and bipolar disorder often overlap, and selected medications are not effective in all those affected by these disorders. Identification of specific structural brain abnormalities that cross traditional diagnostic boundaries, as is proposed, would allow for the development of more specific treatments for those affected, and identify those at risk. Specific biological abnormalities will also help validate psychiatric diagnoses and improve the classification of disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08MH085948-03
Application #
8196757
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Wynne, Debra K
Project Start
2009-12-01
Project End
2014-11-30
Budget Start
2011-12-01
Budget End
2012-11-30
Support Year
3
Fiscal Year
2012
Total Cost
$171,204
Indirect Cost
$12,682
Name
Washington University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Mamah, Daniel; Alpert, Kathryn I; Barch, Deanna M et al. (2016) Subcortical neuromorphometry in schizophrenia spectrum and bipolar disorders. Neuroimage Clin 11:276-86
Mamah, Daniel; Wen, Jie; Luo, Jie et al. (2015) Subcomponents of brain T2* relaxation in schizophrenia, bipolar disorder and siblings: A Gradient Echo Plural Contrast Imaging (GEPCI) study. Schizophr Res 169:36-45
Arnedo, Javier; Mamah, Daniel; Baranger, David A et al. (2015) Decomposition of brain diffusion imaging data uncovers latent schizophrenias with distinct patterns of white matter anisotropy. Neuroimage 120:43-54
Womer, Fay Y; Wang, Lei; Alpert, Kathryn I et al. (2014) Basal ganglia and thalamic morphology in schizophrenia and bipolar disorder. Psychiatry Res 223:75-83
Smith, Matthew J; Cobia, Derin J; Wang, Lei et al. (2014) Cannabis-related working memory deficits and associated subcortical morphological differences in healthy individuals and schizophrenia subjects. Schizophr Bull 40:287-99
Mamah, Daniel; Owoso, Akinkunle; Mbwayo, Anne W et al. (2013) Classes of psychotic experiences in Kenyan children and adolescents. Child Psychiatry Hum Dev 44:452-9
Mamah, Daniel; Barch, Deanna M; Repovš, Grega (2013) Resting state functional connectivity of five neural networks in bipolar disorder and schizophrenia. J Affect Disord 150:601-9
Mamah, Daniel; Harms, Michael P; Barch, Deanna et al. (2012) Hippocampal shape and volume changes with antipsychotics in early stage psychotic illness. Front Psychiatry 3:96
Mamah, Daniel; Mbwayo, Anne; Mutiso, Victoria et al. (2012) A survey of psychosis risk symptoms in Kenya. Compr Psychiatry 53:516-24
Smith, Matthew J; Wang, Lei; Cronenwett, Will et al. (2011) Thalamic morphology in schizophrenia and schizoaffective disorder. J Psychiatr Res 45:378-85

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