Abstract
Several models have been proposed to account for observed overlaps in clinical features and genetic predisposition between schizophrenia and autism spectrum disorder. This study assessed similarities and differences in topological patterns and vectors of glucose metabolism in both disorders in reference to these models. Co-registered 18fluorodeoxyglucose PET and MRI scans were obtained in 41 schizophrenia, 25 ASD, and 55 healthy control subjects. AFNI was used to map cortical and subcortical regions of interest. Metabolic rates were compared between three diagnostic groups using univariate and multivariate repeated-measures ANOVA. Compared to controls, metabolic rates in schizophrenia subjects were decreased in the frontal lobe, anterior cingulate, superior temporal gyrus, amygdala and medial thalamic nuclei; rates were increased in the occipital cortex, hippocampus, basal ganglia and lateral thalamic nuclei. In ASD subjects metabolic rates were decreased in the parietal lobe, frontal premotor and eye-fields areas, and amygdala; rates were increased in the posterior cingulate, occipital cortex, hippocampus and basal ganglia. In relation to controls, subjects with ASD and schizophrenia showed opposite changes in metabolic rates in the primary motor and somatosensory cortex, anterior cingulate and hypothalamus; similar changes were found in prefrontal and occipital cortices, inferior parietal lobule, amygdala, hippocampus, and basal ganglia. Schizophrenia and ASD appear to be associated with a similar pattern of metabolic abnormalities in the social brain. Divergent maladaptive trade-offs, as postulated by the diametrical hypothesis of their evolutionary relationship, may involve a more circumscribed set of anterior cingulate, motor and somatosensory regions and the specific cognitive functions they subserve.
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Abu-Akel, A. M., Apperly, I. A., Wood, S. J., & Hansen, P. C. (2016). Autism and psychosis expressions diametrically modulate the right temporoparietal junction. Social Neuroscience, 3, 1–13.
Adolphs, R. (2009). The social brain: neural basis of social knowledge. Annual Review of Psychology, 60, 693–716.
Aoki, Y., Cortese, S., & Tansella, M. (2015). Neural bases of atypical emotional face processing in autism: a meta-analysis of fMRI studies. World Journal of Biological Psychiatry, 16(5), 291–300.
Apps, M. A., Rushworth, M. F., & Chang, S. W. (2016). The anterior cingulate gyrus and social cognition: tracking the motivation of others. Neuron, 90(4), 692–707.
Báez-Mendoza, R., & Schultz, W. (2013). The role of the striatum in social behavior. Frontiers of Neuroscience, 7, 233.
Baron-Cohen, S. (2009). Autism: the empathizing-systemizing (E-S) theory. Annals of New York Academy of Sciences, 1156, 68–80.
Baron-Cohen, S. (2010). Empathizing, systemizing, and the extreme male brain theory of autism. Progress in Brain Research, 185, 167–175.
Baron-Cohen, S., Knickmeyer, R. C., & Belmonte, M. K. (2005). Sex differences in the brain: implications for explaining autism. Science, 310, 819–823.
Bertone, A., Mottron, L., & Faubert, J. (2004). Autism and schizophrenia: similar perceptual consequence, different neurobiological etiology? Behavioral and Brain Sciences, 27(4), 592–593.
Bralet, M.-C., Buchsbaum, M. S., DeCastro, A., Hazlett, E. A., Haznedar, M. M., Shihabuddin, L., & Mitelman, S. A. (2016). FDG-PET scans in patients with Kraepelinian and non-Kraepelinian schizophrenia. European Archives of Psychiatry and Clinical Neurosciences, 266(6), 481–494.
Brosnan, M., Lewton, M., & Ashwin, C. (2016). Reasoning on the autism spectrum: a dual process theory account. Journal of Autism and Developmental Disorders, 46, 2115–2125.
Buchsbaum, M. S., & Hazlett, E. A. (1998). Positron emission tomography studies of abnormal glucose metabolism in schizophrenia. Schizophrenia Bulletin, 24(3), 343–364.
Ciaramidaro, A., Bölte, S., Schlitt, S., Hainz, D., Poustka, F., Weber, B., Bara, B. G., Freitag, C., & Walter, H. (2015). Schizophrenia and autism as contrasting minds: neural evidence for the hypo-hyper-intentionality hypothesis. Schizophrenia Bulletin, 41(1), 171–179.
Cox, R. W. (1996). AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages. Computers and Biomedical Research, 29(3), 162–173.
Crespi, B. J., & Badcock, C. (2008). Psychosis and autism as diametrical disorders of the social brain. Behavioral and Brain Sciences, 31(3), 241–161.
Crespi, B. J., & Go, M. C. (2015). Diametrical diseases reflect evolutionary-genetic tradeoffs: evidence from psychiatry, neurology, rheumatology, oncology and immunology. Evolution, Medicine and Public Health, 2015(1), 216–253.
Crespi, B., Stead, P., & Elliot, M. (2010). Comparative genomics of autism and schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 107(Suppl 1), 1736–1741.
Davey, C. G., Pujol, J., & Harrison, B. J. (2016). Mapping the self in the brain’s default mode network. NeuroImage, 132, 390–397.
Delis, D., Kramer, J., Kaplan, E., & Ober, B. (1987). The California verbal learning test. New York: Psychological Corporation.
Dichter, G. S. (2012). Functional magnetic resonance imaging of autism spectrum disorders. Dialogues in Clinical Neuroscience, 14(3), 319–351.
Elsabbagh, M., & Johnson, M. H. (2016). Autism and the social brain: the first-year puzzle. Biological Psychiatry, 80(2), 94–99.
Frith, C. D. (2007). The social brain? Philosophical Transactions of the Royal Society of London, Series B Biological Sciences, 362(1480), 671–678.
Glezerman, T.B. (2013). Autism and the brain: neurophenomenological interpretation. New York: Springer, pp. 194 and 228–231.
Harrison, B. J., Yücel, M., Pujol, J., & Pantelis, C. (2007). Task-induced deactivation of midline cortical regions in schizophrenia assessed with fMRI. Schizophrenia Research, 91(1–3), 82–86.
Hartwright, C. E., Apperly, I. A., & Hansen, P. C. (2014). Representation, control, or reasoning? Distinct functions for theory of mind within the medial prefrontal cortex. Journal of Cognitive Neuroscience, 26(4), 683–698.
Hazlett, E. A., Buchsbaum, M. S., Hsieh, P., Haznedar, M. M., Platholi, J., LiCalzi, E. M., Cartwright, C., & Hollander, E. (2004a). Regional glucose metabolism within cortical Brodmann areas in healthy individuals and autistic patients. Neuropsychobiology, 49(3), 115–125.
Hazlett, E. A., Buchsbaum, M. S., Kemether, E., Bloom, R., Platholi, J., Brickman, A. M., Shihabuddin, L., Tang, C., & Byne, W. (2004b). Abnormal glucose metabolism in the mediodorsal nucleus of the thalamus in schizophrenia. American Journal of Psychiatry, 161(2), 305–314.
Hazlett, E. A., Byne, W., Brickman, A. M., Mitsis, E. M., Newmark, R., Haznedar, M. M., Knatz, D. T., Chen, A. D., & Buchsbaum, M. S. (2010). Effects of sex and normal aging on regional brain activation during verbal memory performance. Neurobiology of Aging, 31(5), 826–838.
Haznedar, M. M., Buchsbaum, M. S., Hazlett, E. A., LiCalzi, E. M., Cartwright, C., & Hollander, E. (2006). Volumetric analysis and three-dimensional glucose metabolic mapping of the striatum and thalamus in patients with autism spectrum disorders. American Journal of Psychiatry, 163(7), 1252–1263.
Hommer, R. E., & Swedo, S. E. (2015). Schizophrenia and autism – related disorders. Schizophrenia Bulletin, 41(2), 313–314.
Horwitz, B., Rumsey, J. M., Grady, C. L., & Rapoport, S. I. (1988). The cerebral metabolic landscape in autism. Intercorrelations of regional glucose utilization. Archives of Neurology, 45(7), 749–755.
Katz, J., d’Albis, M.-A., Boisgontier, J., Poupon, C., Mangin, J.-F., Guevara, P., Duclap, D., Hamdani, N., Petit, J., Monnet, D., Le Corvoisier, P., Leboyer, M., Delorme, R., & Houenou, J. (2016). Similar white matter but opposite grey matter changes in schizophrenia and high-functioning autism. Acta Psychiatrica Scandinavica, 134(1), 31–39.
Keefe, R. S., Mohs, R. C., Losonszy, M. F., Davidson, M., Silverman, J. M., Kendler, K. S., Horvath, T. B., Nora, R., & Davis, K. L. (1987). Characteristics of very poor outcome schizophrenia. American Journal of Psychiatry, 144, 889–895.
Lee, S. H., Ripke, S., Neale, B. M., Faraone, S. V., et al. (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics, 45(9), 984–994.
Leech, R., & Sharp, D. J. (2014). The role of the posterior cingulate cortex in cognition and disease. Brain, 137(1), 12–32.
Lehrer, D. S., Christian, B. T., Mantil, J., Murray, A. C., Buchsbaum, B. R., Oakes, T. R., Byne, W., Kemether, E. M., & Buchsbaum, M. S. (2005). Thalamic and prefrontal FDG uptake in never medicated patients with schizophrenia. American Journal of Psychiatry, 162(5), 931–938.
Mitelman, S. A., Bralet, M.-C., Haznedar, M. M., Hollander, E., Shihabuddin, L., Hazlett, E. A., & Buchsbaum, M. S. (2016). Diametrical relationship between gray and white matter volumes in autism spectrum disorder and schizophrenia. Brain Imaging and Behavior. doi:10.1007/s11682-016-9648-9.
Mitelman, S. A., Byne, W., Kemether, E. M., Hazlett, E. A., & Buchsbaum, M. S. (2005). Metabolic disconnection between the mediodorsal nucleus of the thalamus and cortical Brodmann’s areas of the left hemisphere in schizophrenia. American Journal of Psychiatry, 162(9), 1733–1735.
Otti, A., Wohlschlaeger, A. M., & Noll-Hussong, M. (2015). Is the medial prefrontal cortex necessary for theory of mind? PloS One, 10(8), e0135912.
Pagani, M., Manouilenko, I., Stone-Elander, S., Odh, R., Salmaso, D., Hatherly, R., Brolin, F., Jacobsson, H., Larsson, S. A., & Bejerot, S. (2012). Brief report: alterations in cerebral blood flow as assessed by PET/CT in adults with autism spectrum disorder with normal IQ. Journal of Autism and Developmental Disorders, 42(2), 313–318.
Pfefferbaum, A., Chanraud, S., Pitel, A. L., Müller-Oehring, E., Shankaranarayanan, A., Alsop, D. C., Rohlfing, T., & Sullivan, E. V. (2011). Cerebral blood flow in posterior cortical nodes of the default mode network decreases with task engagement but remains higher in most brain regions. Cerebral Cortex, 21(1), 233–244.
Piggott, M. A., Marshall, E. F., Thomas, N., Lloyd, S., Court, J. A., Jaros, E., Costa, D., Perry, R. H., & Perry, E. K. (1999). Dopaminergic activities in the human striatum: rostrocaudal gradients of uptake sites and of D1 and D2 but not of D3 receptor binding or dopamine. Neuroscience, 90(2), 433–445.
Poeppl, T. B., Langguth, B., Rupprecht, R., Safron, A., Bzdok, D., Laird, A. R., & Eickhoff, S. B. (2016). The neural basis of sex differences in sexual behavior: a quantitative meta-analysis. Frontiers in Neuroendocrinology, 3022(16), 28–43.
Rapoport, J. L., Giedd, J. N., & Gogtay, N. (2012). Neurodevelopmental model of schizophrenia: update 2012. Molecular Psychiatry, 17(12), 1228–1238.
Schöll, M., Damián, A., & Engler, H. (2014). Fluorodeoxyglucose PET in neurology and psychiatry. PET Clinics, 9(4), 371–390.
Siegel Jr., B. V., Asarnow, R., Tanguay, P., Call, J. D., Abel, L., Ho, A., Lott, I., & Buchsbaum, M. S. (1992). Regional cerebral glucose metabolism and attention in adults with a history of childhood autism. Journal of Neuropsychiatry and Clinical Neurosciences, 4(4), 406–414.
Siegel Jr., B. V., Nuechterlein, K. F., Abel, L., Wu, J. C., & Buchsbaum, M. S. (1995). Glucose metabolic correlates of continuous performance test performance in adults with a history of infantile autism, schizophrenia, and controls. Schizophrenia Research, 17(1), 85–94.
Stevenson, J. L., & Gernsbacher, M. A. (2013). Abstract spatial reasoning as an autistic strength. PloS One, 8(3), e59329.
Stoléru, S., Fonteille, V., Cornélis, C., Joyal, C., & Moulier, V. (2012). Functional neuroimaging studies of sexual arousal and orgasm in healthy men and women: a review and meta-analysis. Neuroscience and Behavioral Reviews, 36, 1481–1509.
Tamminga, C. A., Stan, A. D., & Wagner, A. D. (2010). The hippocampal formation in schizophrenia. American Journal of Psychiatry, 167(10), 1178–1193.
van Overwalle, F. (2011). A dissociation between social mentalizing and general reasoning. NeuroImage, 54(2), 1589–1599.
Whitfield-Gabrieli, S., Thermenos, H. W., Milanovic, S., Tsuang, M. T., Faraone, S. V., McCarley, R. W., Shenton, M. E., Green, A. I., Nieto-Castanon, A., LaViolette, P., Wojcik, J., Gabrieli, J. D., & Seidman, L. J. (2009). Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 106(11), 4572.
Woods, R. P., Mazziotta, J. C., & Cherry, S. R. (1993). MRI-PET registration with automated algorithm. Journal of Computer Assisted Tomography, 17, 536–546.
Yahata, N., Morimoto, J., Hashimoto, R., Lisi, G., Shibata, K., Kawakubo, Y., Kuroda, M., Yamada, T., Megumi, F., Imamizu, H., Nañez Sr., J. E., Takahashi, H., Okamoto, Y., Kasai, K., Kato, N., Sasaki, Y., Wanatabe, T., & Kawato, M. (2016). A small number of abnormal brain connections predicts adult autism spectrum disorder. Nature Communications, 14(7), 11254.
Zürcher, N. R., Bhanot, A., McDougle, C. J., & Hooker, J. M. (2015). A systematic review of molecular imaging (PET and SPECT) in autism spectrum disorder: current state and future research opportunities. Neuroscience and Biobehavioral Reviews, 52, 56–73.
Grant support
This work was partly supported by NARSAD Young Investigator Award and NIMH MH 077146 grant to Serge A. Mitelman and by NIMH grants P50 MH 66392–01, MH 60023, and MH 56489 to Monte S. Buchsbaum.
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All procedures performed in this study were in accordance with the ethical standards of the Mount Sinai institutional research committee, as well as with the 1964 Helsinki declaration and its later amendments. The project was approved by the institutional review board of The Icahn School of Medicine at Mount Sinai.
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Serge A. Mitelman declares that he has no conflict of interest to report.
Marie-Cecile Bralet declares that she has no conflict of interest to report.
M. Mehmet Haznedar declares that he has no conflict of interest to report.
Eric Hollander has received consultation fees from Transceit, Neuropharm, and Nastech.
Lina Shihabuddin declares that she has no conflict of interest to report.
Erin A. Hazlett declares that she has no conflict of interest to report.
Monte S. Buchsbaum declares that he has no conflict of interest to report.
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Mitelman, S.A., Bralet, MC., Mehmet Haznedar, M. et al. Positron emission tomography assessment of cerebral glucose metabolic rates in autism spectrum disorder and schizophrenia. Brain Imaging and Behavior 12, 532–546 (2018). https://doi.org/10.1007/s11682-017-9721-z
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DOI: https://doi.org/10.1007/s11682-017-9721-z