Schizophrenia and bipolar disorder are disorders of the brain

by Dr. E. Fuller Torrey

It has been suspected for over a century that schizophrenia and bipolar disorder (manic-depressive illness) are disorders of the brain. In 1837, Dr. W.A.F. Browne, the best-known English psychiatrist of his generation, wrote: “Insanity, then, is inordinate or irregular, or impaired action of the mind, of the instincts, sentiments, intellectual, or perceptive powers, depending upon and produced by an organic change in the brain.”

In that same year, Dr. Amariah Brigham, one of the founders of American psychiatry, also wrote that insanity “is now considered a physical disorder, a disease of the brain.”

It would be 150 years, however, before these statements could be proven. Since the early 1980s, with the availability of brain imaging techniques and other developments in neuroscience, the evidence has become overwhelming that schizophrenia and bipolar disorder are diseases of the brain, just like multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. The brains of individuals with these diseases are measurably different from individuals who do not have these diseases, both structurally and functionally.

  • Individuals with schizophrenia and bipolar disorder, including those who have never been treated, have enlarged ventricles in the brain, as demonstrated in over 100 studies to date. 1, 2, 3
  • Individuals with schizophrenia, including those who have never been treated, have a reduced volume of gray matter in the brain, especially in the temporal and frontal lobes. 4
  • Individuals with manic-depressive disorder have an enlarged amygdala and increased numbers of white matter hyperintensities. 5, 6, 7
  • Individuals with schizophrenia and bipolar disorder, including those who have never been treated, have more neurological abnormalities, as shown in more than 25 studies. 8, 9
  • Individuals with schizophrenia and manic-depressive disorder, including those who have never been treated, have more neuropsychological abnormalities that impair their cognitive functions, including information processing and verbal memory. 10, 11, 12
  • Individuals with schizophrenia, including those who have never been treated, show decreased function of the prefrontal area, an area of the brain that we use for planning and thinking about ourselves. 13, 14

Approximately 50 percent of individuals with schizophrenia and bipolar disorder, including those who have never been treated, have impaired awareness of their own illness. This is a clinical symptom called anosognosia that has been shown in at least 50 different studies. Such individuals do not realize that they are sick, and they will, therefore, usually not accept treatment voluntarily. Studies suggest that this impaired awareness is probably related to the decreased function of the prefrontal area. These individuals are thus similar to some patients who have had a stroke and, because of brain damage, are unaware of their disability and deny it. The lack of awareness of illness in individuals with schizophrenia and manic-depressive disorder is the most common reason that they do not take their medication. 15, 16, 17


1 Van Horn, J.D., and McManus, I.C. (1992). Ventricular enlargement in schizophrenia. A meta-analysis of studies of the ventricle:brain ratio (VBR). British Journal of Psychiatry, 160, 687–97.
2 Soares, J.C., and Mann, J.J. (1997). The anatomy of mood disorders: Review of structural neuroimaging studies. Biological Psychiatry, 41, 86–106.
3 Elkis, H., Friedman, L., Wise, A. et. al. (1995) Meta-analyses of studies of ventricular enlargement and cortical sulcal prominence in mood disorders. Comparisons with controls or patients with schizophrenia. Archives of General Psychiatry, 52, 735–46.
4 Lawrie, S.M, and Abukmeil, S.S. (1998) Brain abnormality in schizophrenia: A systematic and quantitative review of volumetric magnetic resonance imaging studies. British Journal of Psychiatry 172,110–20.
5 Strakowski, S.M., DelBello, M.P, Sax, K.W. et. al. (1999). Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Archives of General Psychiatry 56, 254–60.
6 Dupont, R.M., Jernigan, T.L., Heindel, W. et. al. (1995). Magnetic resonance imaging and mood disorders: Localization of white matter and other subcortical abnormalities. Archives of General Psychiatry, 52,747–55.
7 Videbech, P. (1997). MRI findings in patients with affective disorder: A meta-analysis. Acta Psychiatrica Scandinavica, 96, 157–68.
8 Schroder, J. et. al. (1992). Neurological soft signs in schizophrenia. Schizophrenia Research, 6, 25–30.
9 Torrey, E.F. et. al. (1994). Schizophrenia and manic-depressive disorder. New York: Basic Books: 127, 176-7 (1994).
10 Goldberg, T.E., and Gold, J.M. (1995) Neurocognitive functioning in patients with schizophrenia: an overview. In: Bloom, F.E. and Kupfer, D.J. (eds). Psychopharmacology: The fourth generation of progress. New York: Raven Press.

11 Hoff, A.L., Shukla, S., Aronson, T. et. al. (1990). Failure to differentiate bipolar disorder from schizophrenia on measures of neuropsychological function. Schizophrenia Research,3, 253–60.
12 Morice, R. (1990). Cognitive inflexibility and pre-frontal dysfunction in schizophrenia and mania. British Journal of Psychiatry, 157, 50–4.
13 Berman, K.F., and Weinberger, D.F. (1991). Functional localization in the brain in schizophrenia. In: Tasman, A. and Goldfinger, S. (eds.). Review of Psychiatry, vol. 10. Washington, D.C.: American Psychiatric Press, 24–59.
14 Andreasen, N.C., et. al. (1992). Hypofrontality in neuroleptic-naive patients and in patients with chronic schizophrenia. Archives of General Psychiatry, 49, 943–58.
15 Amador, X.F., and David, A.S. (1998). Insight and psychosis. New York: Oxford.
16 Ghaemi, S.N. (1997). Insight and psychiatric disorders: A review of the literature, with a focus on its clinical relevance for bipolar disorder. Psychiatric Annals, 27, 782–90.
17 Peralta, V., and Cuesta, M.J. (1998). Lack of insight in mood disorders. Journal of Affective Disorders, 49, 55–8.