Brain structural abnormalities as well as neurocognitive dysfunction, are found in schizophrenia and in bipolar disorder. Based on the fact that both brain structure and neurocognitive functioning are significantly heritable and affected in both schizophrenia and bipolar disorder, relationships between them are expected. However, previous studies report inconsistent findings. Also, schizophrenia and bipolar disorder are classified as separate disease entities, but demonstrate overlap with regard to symptomatology and genetic liability. Few studies have directly compared brain structure abnormalities or relationships between brain structure and neurocognitive functioning between the diseases and, it remains unclear if findings are similar or different between patients with schizophrenia or bipolar disorder. The aims of the thesis were 1) to characterize brain structure and the relationships with neurocognitive performance in schizophrenia and bipolar disorder and healthy control subjects and, 2) to investigate these characteristics for differences and similarities between the subject groups.
Two independent subject samples from two similar ongoing research projects at Karolinska Institutet in Sweden (HUBIN) and at the University of Oslo in Norway (TOP), were included. The participants were patients with schizophrenia or bipolar disorder, and healthy control subjects. All subjects were characterized using magnetic resonance imaging (MRI) of the brain and neuropsychological test methods. Brain cortical thickness and surface area measurements, as well as subcortical structure volumes were obtained using automated computer image analysis methods.
Schizophrenia and bipolar disorder type 1 patients demonstrated cortical thinning in overlapping prefrontal and temporo-parietal brain regions compared with healthy controls, and schizophrenia and bipolar disorder patients demonstrated similar findings of subcortical volume abnormalities, compared to healthy controls. The identified abnormalities were more pronounced among schizophrenia patients. Cortical thickness and surface area in predominantly frontal and temporal regions, but also occipital regions, and several of the subcortical structure volumes, were related to neurocognitive performance in both patients and healthy controls. Between-group comparisons showed that some structure/function relationships were specific to schizophrenia and/or bipolar disorder.
In conclusion, the results demonstrate numerous similar brain structure abnormalities in schizophrenia and bipolar disorder, consistent with a common underlying pathophysiology. Mostly similar brain structure/function relationships were found between patients and controls. Few relationships were found to be similar in schizophrenia and bipolar disorder, but different from healthy controls. Consequently, our findings do not indicate that the neurocognitive dysfunction found in both schizophrenia and bipolar disorder have common brain structural correlates. Some disease-specific relationships were found between brain structure and neurocognition, possibly reflecting disruptions in brain regions that contribute to specific cognitive functions and, could be of relevance to the pathophysiology in schizophrenia and bipolar disorder.
List of papers. Papers I and II are removed from the thesis due to copyright restrictions.
Paper I Hartberg, C.B., Lawyer, G., Nyman, H., Jonsson, E.G., Haukvik, U.K., Saetre, P., Bjerkan, P.S., Andreassen, O.A., Hall, H. and Agartz, I. Investigating relationships between cortical thickness and cognitive performance in patients with schizophrenia and healthy adults. Psychiatry Research. 2010, 182, 123-133. doi:10.1016/j.pscychresns.2010.01.001
Paper II Rimol, L.M., Hartberg, C.B., Nesvag, R., Fennema-Notestine, C., Hagler, D.J., Jr., Pung, C.J., Jennings, R.G., Haukvik, U.K., Lange, E., Nakstad, P.H., Melle, I., Andreassen, O.A., Dale, A.M. and Agartz, I. Cortical thickness and subcortical volumes in schizophrenia and bipolar disorder. Biological Psychiatry. 2010, 68, 41-50. doi:10.1016/j.biopsych.2010.03.036
Paper III Hartberg, C.B., Sundet, K, Rimol, L., Haukvik, U., Lange, E., Nesvåg, R., Dale, A.M., Melle, I., Andreassen, O.A, Agartz, I. Brain cortical thickness and surface area correlates of neurocognitive performance in patients with schizophrenia, bipolar disorder and healthy control subjects. Manuscript, a revised version is published in: Journal of the International Neuropsychological Society. 2011, 17, 1080-1083. Copyright 2011 INS. doi:10.1017/S1355617711001081
Paper IV Hartberg, C.B., Sundet, K, Rimol, L., Haukvik, U., Lange, E., Nesvåg, R., Melle, I., Andreassen, O.A, Agartz, I. Subcortical brain volumes relate to neurocognition in schizophrenia and bipolar disorder and healthy controls. NOTICE: this is the author’s version of a work that was accepted for publication in Progress in Neuro-Psychopharmacology and Biological Psychiatry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in: Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2011, 35, 1122-1130. doi:10.1016/j.pnpbp.2011.03.014