Advertisement

NeuroMolecular Medicine

, Volume 16, Issue 4, pp 658–668 | Cite as

Diabetes Mellitus and Disturbances in Brain Connectivity: A Bidirectional Relationship?

  • Rodrigo B. Mansur
  • Danielle S. Cha
  • Hanna O. Woldeyohannes
  • Joanna K. Soczynska
  • Andre Zugman
  • Elisa Brietzke
  • Roger S. McIntyre
Original Paper

Abstract

Diabetes mellitus (DM) is associated with deficits across multiple cognitive domains. The observed impairments in cognitive function are hypothesized to be subserved by alterations in brain structure and function. Several lines of evidence indicate that alterations in glial integrity and function, as well as abnormal synchrony within brain circuits and associated networks, are observed in adults with DM. Microangiopathy and alterations in insulin homeostasis appear to be principal effector systems, although a unitary explanation subsuming the complex etiopathology of white matter in DM is unavailable. A contemporary model of disease pathophysiology for several mental disorders, including but not limited to mood disorders, posits abnormalities in the synchronization of cellular systems in circuits. The observation that similar abnormalities occur in diabetic populations provides the basis for hypothesizing the convergence of pathoetiological factors. Herein, we propose that abnormal structure, function and chemical composition as well as synchrony within and between circuits is an accompaniment of DM and is shared in common with several mental disorders.

Keywords

Diabetes mellitus Cognition Functional connectivity Mental disorder Pathophysiology 

Notes

Acknowledgments

R.B.M. is the guarantor of this work and, as such, takes responsibility for the integrity of the perspective provided. R.B.M., D.S.C., H.O.W., J.K.S., A.Z., E.B. and R.S.M. researched data, wrote sections and reviewed/edited the manuscript.

Conflict of interest

There are no potential conflicts of interests relevant to this article.

References

  1. Ali, S., Stone, M. A., Peters, J. L., Davies, M. J., & Khunti, K. (2006). The prevalence of co-morbid depression in adults with Type 2 diabetes: A systematic review and meta-analysis. Diabetic Medicine, 23(11), 1165–1173.PubMedGoogle Scholar
  2. Antenor-Dorsey, J. A., Meyer, E., Rutlin, J., et al. (2013). White matter microstructural integrity in youth with type 1 diabetes. Diabetes, 62(2), 581–589.PubMedCentralPubMedGoogle Scholar
  3. Artola, A., Kamal, A., Ramakers, G. M., Biessels, G. J., & Gispen, W. H. (2005). Diabetes mellitus concomitantly facilitates the induction of long-term depression and inhibits that of long-term potentiation in hippocampus. European Journal of Neuroscience, 22(1), 169–178.PubMedGoogle Scholar
  4. Asevedo, E., Cunha, G. R., Zugman, A., Mansur, R. B., & Brietzke, E. (2012). N-acetylcysteine as a potentially useful medication to prevent conversion to schizophrenia in at-risk individuals. Reviews in the Neurosciences, 23(4), 353–362.PubMedGoogle Scholar
  5. Assaf, Y., & Pasternak, O. (2008). Diffusion tensor imaging (DTI)-based white matter mapping in brain research: A review. Journal of Molecular Neuroscience, 34(1), 51–61.PubMedGoogle Scholar
  6. Atlantis, E. (2012). Excess burden of type 1 and type 2 diabetes due to psychopathology. Journal of Affective Disorders, 142(Suppl), S36–S41.PubMedGoogle Scholar
  7. Attwell, D., & Laughlin, S. B. (2001). An energy budget for signaling in the grey matter of the brain. Journal of Cerebral Blood Flow and Metabolism, 21(10), 1133–1145.PubMedGoogle Scholar
  8. Aye, T., Barnea-Goraly, N., Ambler, C., et al. (2012). White matter structural differences in young children with type 1 diabetes: A diffusion tensor imaging study. Diabetes Care, 35(11), 2167–2173.PubMedCentralPubMedGoogle Scholar
  9. Banks, W. A., Owen, J. B., & Erickson, M. A. (2012). Insulin in the brain: There and back again. Pharmacology & Therapeutics, 136(1), 82–93.Google Scholar
  10. Barnard, K. D., Skinner, T. C., & Peveler, R. (2006). The prevalence of co-morbid depression in adults with Type 1 diabetes: Systematic literature review. Diabetic Medicine, 23(4), 445–448.PubMedGoogle Scholar
  11. Berk, M., Kapczinski, F., Andreazza, A. C., et al. (2011). Pathways underlying neuroprogression in bipolar disorder: Focus on inflammation, oxidative stress and neurotrophic factors. Neuroscience and Biobehavioral Reviews, 35(3), 804–817.PubMedGoogle Scholar
  12. Berthoud, H. R. (2012). The neurobiology of food intake in an obesogenic environment. Proceedings of the Nutrition Society, 71(4), 478–487.PubMedCentralPubMedGoogle Scholar
  13. Bosco, D., Fava, A., Plastino, M., Montalcini, T., & Pujia, A. (2011). Possible implications of insulin resistance and glucose metabolism in Alzheimer’s disease pathogenesis. Journal of Cellular and Molecular Medicine, 15(9), 1807–1821.PubMedGoogle Scholar
  14. Bosy-Westphal, A., Kossel, E., Goele, K., et al. (2009). Contribution of individual organ mass loss to weight loss-associated decline in resting energy expenditure. American Journal of Clinical Nutrition, 90(4), 993–1001.PubMedGoogle Scholar
  15. Bourdel-Marchasson, I., Mouries, A., & Helmer, C. (2010). Hyperglycaemia, microangiopathy, diabetes and dementia risk. Diabetes and Metabolism Journal, 36(Suppl 3), S112–S118.Google Scholar
  16. Brands, A. M., Biessels, G. J., de Haan, E. H., Kappelle, L. J., & Kessels, R. P. (2005). The effects of type 1 diabetes on cognitive performance: A meta-analysis. Diabetes Care, 28(3), 726–735.PubMedGoogle Scholar
  17. Buckner, R. L., Sepulcre, J., Talukdar, T., et al. (2009). Cortical hubs revealed by intrinsic functional connectivity: Mapping, assessment of stability, and relation to Alzheimer’s disease. Journal of Neuroscience, 29(6), 1860–1873.PubMedCentralPubMedGoogle Scholar
  18. Bullmore, E., & Sporns, O. (2012). The economy of brain network organization. Nature Reviews Neuroscience, 13(5), 336–349.PubMedGoogle Scholar
  19. Chan, O., Lawson, M., Zhu, W., Beverly, J. L., & Sherwin, R. S. (2007). ATP-sensitive K(+) channels regulate the release of GABA in the ventromedial hypothalamus during hypoglycemia. Diabetes, 56(4), 1120–1126.PubMedGoogle Scholar
  20. Chen, H., Epstein, J., & Stern, E. (2010). Neural plasticity after acquired brain injury: Evidence from functional neuroimaging. PM&R, 2(12 Suppl 2), S306–S312.Google Scholar
  21. Chen, Z. J., He, Y., Rosa-Neto, P., Gong, G., & Evans, A. C. (2011). Age-related alterations in the modular organization of structural cortical network by using cortical thickness from MRI. Neuroimage, 56(1), 235–245.PubMedGoogle Scholar
  22. Cheng, G., Huang, C., Deng, H., & Wang, H. (2012). Diabetes as a risk factor for dementia and mild cognitive impairment: A meta-analysis of longitudinal studies. Internal Medicine Journal, 42(5), 484–491.PubMedGoogle Scholar
  23. Chklovskii, D. B. (2004). Exact solution for the optimal neuronal layout problem. Neural Computation, 16(10), 2067–2078.PubMedGoogle Scholar
  24. Clouse, R. E., Lustman, P. J., Freedland, K. E., Griffith, L. S., McGill, J. B., & Carney, R. M. (2003). Depression and coronary heart disease in women with diabetes. Psychosomatic Medicine, 65(3), 376–383.PubMedGoogle Scholar
  25. Cooray, G. K., Hyllienmark, L., & Brismar, T. (2011a). Decreased cortical connectivity and information flow in type 1 diabetes. Clinical Neurophysiology, 122(10), 1943–1950.PubMedGoogle Scholar
  26. Cooray, G., Nilsson, E., Wahlin, A., Laukka, E. J., Brismar, K., & Brismar, T. (2011b). Effects of intensified metabolic control on CNS function in type 2 diabetes. Psychoneuroendocrinology., 36(1), 77–86.PubMedGoogle Scholar
  27. Craft, S., Peskind, E., Schwartz, M. W., Schellenberg, G. D., Raskind, M., & Porte, D, Jr. (1998). Cerebrospinal fluid and plasma insulin levels in Alzheimer’s disease: Relationship to severity of dementia and apolipoprotein E genotype. Neurology, 50(1), 164–168.PubMedGoogle Scholar
  28. Daneman, D. (2006). Type 1 diabetes. Lancet, 367(9513), 847–858.PubMedGoogle Scholar
  29. de Groot, M., Anderson, R., Freedland, K. E., Clouse, R. E., & Lustman, P. J. (2001). Association of depression and diabetes complications: A meta-analysis. Psychosomatic Medicine, 63(4), 619–630.PubMedGoogle Scholar
  30. de Haan, W., Mott, K., van Straaten, E. C., Scheltens, P., & Stam, C. J. (2012). Activity dependent degeneration explains hub vulnerability in Alzheimer’s disease. PLoS Computational Biology, 8(8), e1002582.PubMedCentralPubMedGoogle Scholar
  31. de la Monte, S. M. (2012). Contributions of brain insulin resistance and deficiency in amyloid-related neurodegeneration in Alzheimer’s disease. Drugs, 72(1), 49–66.PubMedGoogle Scholar
  32. Edwards, J. D., Jacova, C., Sepehry, A. A., Pratt, B., & Benavente, O. R. (2013). A quantitative systematic review of domain-specific cognitive impairment in lacunar stroke. Neurology, 80(3), 315–322.PubMedCentralPubMedGoogle Scholar
  33. Fong, D. S., Aiello, L. P., Ferris, F. L, 3rd, & Klein, R. (2004). Diabetic retinopathy. Diabetes Care, 27(10), 2540–2553.PubMedGoogle Scholar
  34. Franc, D. T., Kodl, C. T., Mueller, B. A., Muetzel, R. L., Lim, K. O., & Seaquist, E. R. (2011). High connectivity between reduced cortical thickness and disrupted white matter tracts in long-standing type 1 diabetes. Diabetes, 60(1), 315–319.PubMedCentralPubMedGoogle Scholar
  35. Frier, B. M. (2011). Cognitive functioning in type 1 diabetes: the diabetes control and complications trial (DCCT) revisited. Diabetologia, 54(2), 233–236.PubMedGoogle Scholar
  36. Friston, K. J., Frith, C. D., Liddle, P. F., & Frackowiak, R. S. (1993). Functional connectivity: The principal-component analysis of large (PET) data sets. Journal of Cerebral Blood Flow and Metabolism, 13(1), 5–14.PubMedGoogle Scholar
  37. Fu, M., & Zuo, Y. (2011). Experience-dependent structural plasticity in the cortex. Trends in Neurosciences, 34(4), 177–187.PubMedCentralPubMedGoogle Scholar
  38. Gaudieri, P. A., Chen, R., Greer, T. F., & Holmes, C. S. (2008). Cognitive function in children with type 1 diabetes: A meta-analysis. Diabetes Care, 31(9), 1892–1897.PubMedCentralPubMedGoogle Scholar
  39. Gold, S. M., Dziobek, I., Sweat, V., et al. (2007). Hippocampal damage and memory impairments as possible early brain complications of type 2 diabetes. Diabetologia, 50(4), 711–719.PubMedGoogle Scholar
  40. Golden, S. H., Lazo, M., Carnethon, M., et al. (2008). Examining a bidirectional association between depressive symptoms and diabetes. JAMA, 299(23), 2751–2759.PubMedCentralPubMedGoogle Scholar
  41. Goldstein, B. I., Liu, S. M., Zivkovic, N., Schaffer, A., Chien, L. C., & Blanco, C. (2011). The burden of obesity among adults with bipolar disorder in the United States. Bipolar Disorders, 13(4), 387–395.PubMedCentralPubMedGoogle Scholar
  42. Greicius, M. D., Krasnow, B., Reiss, A. L., & Menon, V. (2003). Functional connectivity in the resting brain: A network analysis of the default mode hypothesis. Proceedings of the National Academy of Sciences of the United States of America, 100(1), 253–258.PubMedCentralPubMedGoogle Scholar
  43. Hamer, M., Batty, G. D., & Kivimaki, M. (2011). Haemoglobin A1c, fasting glucose and future risk of elevated depressive symptoms over 2 years of follow-up in the English Longitudinal Study of Ageing. Psychological Medicine, 41(9), 1889–1896.PubMedCentralPubMedGoogle Scholar
  44. Hitze, B., Hubold, C., van Dyken, R., et al. (2010). How the selfish brain organizes its supply and demand. Front Neuroenergetics, 2, 7.PubMedCentralPubMedGoogle Scholar
  45. Hsu, J. L., Chen, Y. L., Leu, J. G., et al. (2012). Microstructural white matter abnormalities in type 2 diabetes mellitus: a diffusion tensor imaging study. Neuroimage, 59(2), 1098–1105.PubMedGoogle Scholar
  46. Iwai, T., Suzuki, M., Kobayashi, K., Mori, K., Mogi, Y., & Oka, J. (2009). The influences of juvenile diabetes on memory and hippocampal plasticity in rats: Improving effects of glucagon-like peptide-1. Neuroscience Research, 64(1), 67–74.PubMedGoogle Scholar
  47. Kaidanovich-Beilin, O., Cha, D. S., & McIntyre, R S. (2012). Crosstalk between metabolic and neuropsychiatric disorders. F1000 Biol Rep. 4 14.Google Scholar
  48. Kalaria, R. N. (2009). Neurodegenerative disease: Diabetes, microvascular pathology and Alzheimer disease. Nature Reviews. Neurology, 5(6), 305–306.PubMedGoogle Scholar
  49. Karbowski, J. (2007). Global and regional brain metabolic scaling and its functional consequences. BMC Biology, 5, 18.PubMedCentralPubMedGoogle Scholar
  50. Karunakaran, U., & Park, K. G. (2013). A systematic review of oxidative stress and safety of antioxidants in diabetes: Focus on islets and their defense. Diabetes and Metabolism Journal, 37(2), 106–112.PubMedCentralPubMedGoogle Scholar
  51. Kodl, C. T., Franc, D. T., Rao, J. P., et al. (2008). Diffusion tensor imaging identifies deficits in white matter microstructure in subjects with type 1 diabetes that correlate with reduced neurocognitive function. Diabetes, 57(11), 3083–3089.PubMedCentralPubMedGoogle Scholar
  52. Kullmann, S., Heni, M., Veit, R., et al. (2012). The obese brain: Association of body mass index and insulin sensitivity with resting state network functional connectivity. Human Brain Mapping, 33(5), 1052–1061.PubMedGoogle Scholar
  53. Lasselin, J., Laye, S., Barreau, J. B., et al. (2012). Fatigue and cognitive symptoms in patients with diabetes: Relationship with disease phenotype and insulin treatment. Psychoneuroendocrinology, 37(9), 1468–1478.PubMedGoogle Scholar
  54. Li, Y., Liu, Y., Li, J., et al. (2009). Brain anatomical network and intelligence. PLoS Computational Biology, 5(5), e1000395.PubMedCentralPubMedGoogle Scholar
  55. Lo, C. Y., Wang, P. N., Chou, K. H., Wang, J., He, Y., & Lin, C. P. (2010). Diffusion tensor tractography reveals abnormal topological organization in structural cortical networks in Alzheimer’s disease. Journal of Neuroscience, 30(50), 16876–16885.PubMedGoogle Scholar
  56. Lustman, P. J., Anderson, R. J., Freedland, K. E., de Groot, M., Carney, R. M., & Clouse, R. E. (2000). Depression and poor glycemic control: A meta-analytic review of the literature. Diabetes Care, 23(7), 934–942.PubMedGoogle Scholar
  57. Madsen, P. L., Hasselbalch, S. G., Hagemann, L. P., et al. (1995). Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation: Evidence obtained with the Kety–Schmidt technique. Journal of Cerebral Blood Flow and Metabolism, 15(3), 485–491.PubMedGoogle Scholar
  58. Maina, G., Salvi, V., Vitalucci, A., D’Ambrosio, V., & Bogetto, F. (2008). Prevalence and correlates of overweight in drug-naive patients with bipolar disorder. Journal of Affective Disorders, 110(1–2), 149–155.PubMedGoogle Scholar
  59. Mansur, R. B., Cha, D. S., Asevedo, E., McIntyre, R. S., & Brietzke, E. (2013). Selfish brain and neuroprogression in bipolar disorder. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 43, 66–71.PubMedGoogle Scholar
  60. Maritim, A. C., Sanders, R. A., & Watkins, J. B, 3rd. (2003). Diabetes, oxidative stress, and antioxidants: A review. Journal of Biochemical and Molecular Toxicology, 17(1), 24–38.PubMedGoogle Scholar
  61. Matsuzaki, T., Sasaki, K., Tanizaki, Y., et al. (2010). Insulin resistance is associated with the pathology of Alzheimer disease: The Hisayama study. Neurology, 75(9), 764–770.PubMedGoogle Scholar
  62. McCrimmon, R. J., Ryan, C. M., & Frier, B. M. (2012). Diabetes and cognitive dysfunction. Lancet, 379(9833), 2291–2299.PubMedGoogle Scholar
  63. McIntyre, R. S., Soczynska, J. K., Konarski, J. Z., et al. (2007). Should depressive syndromes be reclassified as “metabolic syndrome type II”? Annals of Clinical Psychiatry, 19(4), 257–264.PubMedGoogle Scholar
  64. McIntyre, R. S., Vagic, D., Swartz, S. A., et al. (2008). Insulin, insulin-like growth factors and incretins: neural homeostatic regulators and treatment opportunities. CNS Drugs, 22(6), 443–453.PubMedGoogle Scholar
  65. McNay, E. C., & Recknagel, A. K. (2011). Brain insulin signaling: A key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes. Neurobiology of Learning and Memory, 96(3), 432–442.PubMedCentralPubMedGoogle Scholar
  66. Mielke, J. G., Taghibiglou, C., & Wang, Y. T. (2006). Endogenous insulin signaling protects cultured neurons from oxygen–glucose deprivation-induced cell death. Neuroscience, 143(1), 165–173.PubMedGoogle Scholar
  67. Moylan, S., Maes, M., Wray, N. R., & Berk, M. (2013). The neuroprogressive nature of major depressive disorder: Pathways to disease evolution and resistance, and therapeutic implications. Journal of Molecular Psychiatry, 18(5), 595–606.Google Scholar
  68. Mulder, A. H., Tack, C. J., Olthaar, A. J., Smits, P., Sweep, F. C., & Bosch, R. R. (2005). Adrenergic receptor stimulation attenuates insulin-stimulated glucose uptake in 3T3-L1 adipocytes by inhibiting GLUT4 translocation. American Journal of Physiology. Endocrinology and Metabolism, 289(4), E627–E633.PubMedGoogle Scholar
  69. Musen, G., Jacobson, A. M., Bolo, N. R., et al. (2012). Resting-state brain functional connectivity is altered in type 2 diabetes. Diabetes, 61(9), 2375–2379.PubMedCentralPubMedGoogle Scholar
  70. Naguib, J. M., Kulinskaya, E., Lomax, C. L., & Garralda, M. E. (2009). Neuro-cognitive performance in children with type 1 diabetes: A meta-analysis. Journal of Pediatric Psychology, 34(3), 271–282.PubMedGoogle Scholar
  71. Nelson, P. T., Smith, C. D., Abner, E. A., et al. (2009). Human cerebral neuropathology of Type 2 diabetes mellitus. Biochimica et Biophysica Acta, 1792(5), 454–469.PubMedCentralPubMedGoogle Scholar
  72. Niven, J. E., & Laughlin, S. B. (2008). Energy limitation as a selective pressure on the evolution of sensory systems. Journal of Experimental Biology, 211(Pt 11), 1792–1804.PubMedGoogle Scholar
  73. Northam, E. A., Anderson, P. J., Jacobs, R., Hughes, M., Warne, G. L., & Werther, G. A. (2001). Neuropsychological profiles of children with type 1 diabetes 6 years after disease onset. Diabetes Care, 24(9), 1541–1546.PubMedGoogle Scholar
  74. Ohmann, S., Popow, C., Rami, B., et al. (2010). Cognitive functions and glycemic control in children and adolescents with type 1 diabetes. Psychological Medicine, 40(1), 95–103.PubMedGoogle Scholar
  75. Olsson, G. M., Hulting, A. L., & Montgomery, S. M. (2008). Cognitive function in children and subsequent type 2 diabetes. Diabetes Care, 31(3), 514–516.PubMedGoogle Scholar
  76. Oltmanns, K. M., Melchert, U. H., Scholand-Engler, H. G., et al. (2008). Differential energetic response of brain vs. skeletal muscle upon glycemic variations in healthy humans. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 294(1), R12–R16.PubMedGoogle Scholar
  77. Osborn, D. P., Wright, C. A., Levy, G., King, M. B., Deo, R., & Nazareth, I. (2008). Relative risk of diabetes, dyslipidaemia, hypertension and the metabolic syndrome in people with severe mental illnesses: A systematic review and metaanalysis. BMC Psychiatry, 8, 84.PubMedCentralPubMedGoogle Scholar
  78. Patino-Fernandez, A. M., Delamater, A. M., Applegate, E. B., et al. (2010). Neurocognitive functioning in preschool-age children with type 1 diabetes mellitus. Pediatric Diabetes, 11(6), 424–430.PubMedCentralPubMedGoogle Scholar
  79. Peters, A., Schweiger, U., Pellerin, L., et al. (2004). The selfish brain: Competition for energy resources. Neuroscience and Biobehavioral Reviews, 28(2), 143–180.PubMedGoogle Scholar
  80. Pocai, A., Lam, T. K., Gutierrez-Juarez, R., et al. (2005). Hypothalamic K(ATP) channels control hepatic glucose production. Nature, 434(7036), 1026–1031.PubMedGoogle Scholar
  81. Reagan, L. P. (2012). Diabetes as a chronic metabolic stressor: Causes, consequences and clinical complications. Experimental Neurology, 233(1), 68–78.PubMedCentralPubMedGoogle Scholar
  82. Reijmer, Y. D., Brundel, M., de Bresser, J., Kappelle, L. J., Leemans, A., & Biessels, G. J. (2013a). Microstructural white matter abnormalities and cognitive functioning in type 2 diabetes: A diffusion tensor imaging study. Diabetes Care, 36(1), 137–144.PubMedCentralPubMedGoogle Scholar
  83. Reijmer, Y. D., Leemans, A., Brundel, M., Kappelle, L. J., & Biessels, G. J. (2013b). Disruption of the cerebral white matter network is related to slowing of information processing speed in patients with type 2 diabetes. Diabetes, 62(6), 2112–2115.Google Scholar
  84. Renn, B. N., Feliciano, L., & Segal, D. L. (2011). The bidirectional relationship of depression and diabetes: A systematic review. Clinical Psychology Review, 31(8), 1239–1246.PubMedGoogle Scholar
  85. Ringo, J. L. (1991). Neuronal interconnection as a function of brain size. Brain, Behavior and Evolution, 38(1), 1–6.PubMedGoogle Scholar
  86. Rodgers, E. E., & Theibert, A. B. (2002). Functions of PI 3-kinase in development of the nervous system. International Journal of Developmental Neuroscience, 20(3–5), 187–197.PubMedGoogle Scholar
  87. Ronnemaa, E., Zethelius, B., Sundelof, J., et al. (2008). Impaired insulin secretion increases the risk of Alzheimer disease. Neurology, 71(14), 1065–1071.PubMedGoogle Scholar
  88. Roriz-Filho, J. R., Sa-Roriz, T. M., Rosset, I., et al. (2009). (Pre)diabetes, brain aging, and cognition. Biochimica et Biophysica Acta, 1792(5), 432–443.Google Scholar
  89. Rotella, F., & Mannucci, E. (2013a). Depression as a risk factor for diabetes: A meta-analysis of longitudinal studies. Journal of Clinical Psychiatry, 74(1), 31–37.PubMedGoogle Scholar
  90. Rotella, F., & Mannucci, E. (2013b). Diabetes mellitus as a risk factor for depression. A meta-analysis of longitudinal studies. Diabetes Research and Clinical Practice, 99(2), 98–104.PubMedGoogle Scholar
  91. Ryan, M. C., Collins, P., & Thakore, J. H. (2003). Impaired fasting glucose tolerance in first-episode, drug-naive patients with schizophrenia. American Journal of Psychiatry, 160(2), 284–289.PubMedGoogle Scholar
  92. Ryan, J. P., Sheu, L. K., Critchley, H. D., & Gianaros, P. J. (2012). A neural circuitry linking insulin resistance to depressed mood. Psychosomatic Medicine, 74(5), 476–482.PubMedCentralPubMedGoogle Scholar
  93. Scheid, M. P., & Woodgett, J. R. (2003). Unravelling the activation mechanisms of protein kinase B/Akt. FEBS Letters, 546(1), 108–112.PubMedGoogle Scholar
  94. Schoonheim, M. M., Geurts, J. J., & Barkhof, F. (2010). The limits of functional reorganization in multiple sclerosis. Neurology, 74(16), 1246–1247.PubMedGoogle Scholar
  95. Seaquist, E. R., Damberg, G. S., Tkac, I., & Gruetter, R. (2001). The effect of insulin on in vivo cerebral glucose concentrations and rates of glucose transport/metabolism in humans. Diabetes, 50(10), 2203–2209.PubMedGoogle Scholar
  96. Shemesh, E., Rudich, A., Harman-Boehm, I., & Cukierman-Yaffe, T. (2012). Effect of intranasal insulin on cognitive function: A systematic review. Journal of Clinical Endocrinology and Metabolism, 97(2), 366–376.PubMedGoogle Scholar
  97. Skeberdis, V. A., Lan, J., Zheng, X., Zukin, R. S., & Bennett, M. V. (2001). Insulin promotes rapid delivery of N-methyl-D- aspartate receptors to the cell surface by exocytosis. Proceedings of the National Academy of Sciences of the United States of America, 98(6), 3561–3566.PubMedCentralPubMedGoogle Scholar
  98. Soczynska, J. K., Kennedy, S. H., Woldeyohannes, H. O., et al. (2011). Mood disorders and obesity: Understanding inflammation as a pathophysiological nexus. Neuromolecular Medicine, 13(2), 93–116.PubMedGoogle Scholar
  99. Steen, E., Terry, B. M., Rivera, E. J., et al. (2005). Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease: Is this type 3 diabetes? Journal of Alzheimer’s Disease, 7(1), 63–80.PubMedGoogle Scholar
  100. Strachan, M. W., Deary, I. J., Ewing, F. M., & Frier, B. M. (1997). Is type II diabetes associated with an increased risk of cognitive dysfunction? A critical review of published studies. Diabetes Care, 20(3), 438–445.PubMedGoogle Scholar
  101. Suzuki, K., Jayasena, C. N., & Bloom, S. R. (2012). Obesity and appetite control. Experimental Diabetes Research, 2012, 824305.PubMedCentralPubMedGoogle Scholar
  102. Taguchi, A. (2009). Vascular factors in diabetes and Alzheimer’s disease. Journal of Alzheimer’s Disease, 16(4), 859–864.PubMedGoogle Scholar
  103. Thakore, J. H., Mann, J. N., Vlahos, I., Martin, A., & Reznek, R. (2002). Increased visceral fat distribution in drug-naive and drug-free patients with schizophrenia. International Journal of Obesity and Related Metabolic Disorders, 26(1), 137–141.PubMedGoogle Scholar
  104. Tong, Q., Ye, C., McCrimmon, R. J., et al. (2007). Synaptic glutamate release by ventromedial hypothalamic neurons is part of the neurocircuitry that prevents hypoglycemia. Cell Metabolism, 5(5), 383–393.PubMedCentralPubMedGoogle Scholar
  105. Tran, B., Oliver, S., Rosa, J., & Galassetti, P. (2012). Aspects of inflammation and oxidative stress in pediatric obesity and type 1 diabetes: an overview of ten years of studies. Experimental Diabetes Research, 2012, 683680.PubMedCentralPubMedGoogle Scholar
  106. Trudeau, F., Gagnon, S., & Massicotte, G. (2004). Hippocampal synaptic plasticity and glutamate receptor regulation: Influences of diabetes mellitus. European Journal of Pharmacology, 490(1–3), 177–186.PubMedGoogle Scholar
  107. Unger, J. W., & Betz, M. (1998). Insulin receptors and signal transduction proteins in the hypothalamo-hypophyseal system: A review on morphological findings and functional implications. Histology and Histopathology, 13(4), 1215–1224.PubMedGoogle Scholar
  108. van den Heuvel, M. P., Stam, C. J., Kahn, R. S., & Hulshoff Pol, H. E. (2009). Efficiency of functional brain networks and intellectual performance. Journal of Neuroscience, 29(23), 7619–7624.PubMedGoogle Scholar
  109. van der Heide, L. P., Kamal, A., Artola, A., Gispen, W. H., & Ramakers, G. M. (2005). Insulin modulates hippocampal activity-dependent synaptic plasticity in a N-methyl-d-aspartate receptor and phosphatidyl-inositol-3-kinase-dependent manner. Journal of Neurochemistry, 94(4), 1158–1166.PubMedGoogle Scholar
  110. van Duinkerken, E., Klein, M., Schoonenboom, N. S., et al. (2009). Functional brain connectivity and neurocognitive functioning in patients with long-standing type 1 diabetes with and without microvascular complications: A magnetoencephalography study. Diabetes, 58(10), 2335–2343.PubMedCentralPubMedGoogle Scholar
  111. van Duinkerken, E., Schoonheim, M. M., Ijzerman, R. G., et al. (2012a). Diffusion tensor imaging in type 1 diabetes: decreased white matter integrity relates to cognitive functions. Diabetologia, 55(4), 1218–1220.PubMedCentralPubMedGoogle Scholar
  112. van Duinkerken, E., Schoonheim, M. M., Sanz-Arigita, E. J., et al. (2012b). Resting-state brain networks in type 1 diabetic patients with and without microangiopathy and their relation to cognitive functions and disease variables. Diabetes, 61(7), 1814–1821.PubMedCentralPubMedGoogle Scholar
  113. van Harten, B., de Leeuw, F. E., Weinstein, H. C., Scheltens, P., & Biessels, G. J. (2006). Brain imaging in patients with diabetes: A systematic review. Diabetes Care, 29(11), 2539–2548.PubMedGoogle Scholar
  114. Yao, Z., Zhang, Y., Lin, L., Zhou, Y., Xu, C., & Jiang, T. (2010). Abnormal cortical networks in mild cognitive impairment and Alzheimer’s disease. PLoS Computational Biology, 6(11), e1001006.PubMedCentralPubMedGoogle Scholar
  115. Yau, P. L., Javier, D., Tsui, W., et al. (2009). Emotional and neutral declarative memory impairments and associated white matter microstructural abnormalities in adults with type 2 diabetes. Psychiatry Research, 174(3), 223–230.PubMedCentralPubMedGoogle Scholar
  116. Yim, C. Y., Soczynska, J. K., Kennedy, S. H., Woldeyohannes, H. O., Brietzke, E., & McIntyre, R. S. (2012). The effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder. European Psychiatry, 27(3), 223–228.PubMedGoogle Scholar
  117. Zhang, K., & Sejnowski, T. J. (2000). A universal scaling law between gray matter and white matter of cerebral cortex. Proceedings of the National Academy of Sciences of the United States of America, 97(10), 5621–5626.PubMedCentralPubMedGoogle Scholar
  118. Zhong, Y., Miao, Y., Jia, W. P., Yan, H., Wang, B. Y., & Jin, J. (2012). Hyperinsulinemia, insulin resistance and cognitive decline in older cohort. Biomedical and Environmental Sciences, 25(1), 8–14.PubMedGoogle Scholar
  119. Zhou, H., Lu, W., Shi, Y., et al. (2010). Impairments in cognition and resting-state connectivity of the hippocampus in elderly subjects with type 2 diabetes. Neuroscience Letters, 473(1), 5–10.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Rodrigo B. Mansur
    • 1
    • 2
    • 3
  • Danielle S. Cha
    • 1
  • Hanna O. Woldeyohannes
    • 1
  • Joanna K. Soczynska
    • 1
  • Andre Zugman
    • 2
    • 3
  • Elisa Brietzke
    • 2
    • 3
  • Roger S. McIntyre
    • 1
  1. 1.Mood Disorders Psychopharmacology Unit (MDPU), University Health NetworkUniversity of TorontoTorontoCanada
  2. 2.Interdisciplinary Laboratory of Clinical Neuroscience (LINC), Department of PsychiatryFederal University of São PauloSão PauloBrazil
  3. 3.Program for Recognition and Intervention in Individuals in At-Risk Mental States (PRISMA), Department of PsychiatryFederal University of São PauloSão PauloBrazil

Personalised recommendations