By E. Fuller Torrey, M.D.

It has been suspected for over a century that schizophrenia and manic-depressive disorder (bipolar disorder) are diseases 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 manic-depressive disorder are diseases of the brain, just as multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease are diseases of the brain. The brains of individuals with these diseases are measurably different from individuals who do not have these diseases, both structurally and functionally. A brief summary of some of the evidence that proves this point follows:

• Individuals with schizophrenia and manic-depressive disorder, including those who have never been treated, have enlarged ventricles in the brain, as demonstrated in over 100 studies to date.
  

Van Horn JD, McManus IC.  Ventricular enlargement in schizophrenia. A meta-analysis of studies of the ventricle: brain ratio (VBR). British Journal of Psychiatry 160:687–697, 1992.
Soares JC, Mann JJ.  The anatomy of mood disorders: review of structural neuroimaging studies. Biological Psychiatry 41:86–106, 1997.
Elkis H, Friedman L, Wise A, et al.  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 52:735–746, 1995.

• 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.
  

Lawrie SM, Abukmeil SS: Brain abnormality in schizophrenia: a systematic and quantitative review of volumetric magnetic resonance imaging studies. British Journal of Psychiatry 172:110–120, 1998.

• Individuals with manic-depressive disorder have an enlarged amygdala and increased numbers of white matter hyperintensities.
  

Strakowski SM, DelBello MP, Sax KW, et al.   Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Archives of General Psychiatry 56:254–260, 1999.
Dupont RM, Jernigan TL, Heindel W, et al.  Magnetic resonance imaging and mood disorders: localization of white matter and other subcortical abnormalities. Archives of General Psychiatry 52:747–755, 1995.
Videbech P. MRI findings in patients with affective disorder: a meta-analysis. Acta Psychiatrica Scandinavica 96:157–168, 1997.

• Individuals with schizophrenia and manic-depressive disorder, including those who have never been treated, have more neurological abnormalities, as shown in over 25 studies.
  

Schroder J, et al. Neurological soft signs in schizophrenia.  Schizophrenia Research 6:25–30, 1992.
Torrey EF, et al. Schizophrenia and Manic-Depressive Disorder.  New York: Basic Books, 1994, pp. 127 ff. and pp. 176–177.

• Individuals with schizophrenia and manic-depressive disorder, including those who have never been treated, have more neuropsychological abnormalities that impair their cognitive function, including such things as information processing and verbal memory.
  

Goldberg TE, Gold JM. Neurocognitive functioning in patients with schizophrenia: an overview. In: Psychopharmacology: The Fourth Generation of Progress, Bloom FE and Kupfer DJ (eds). New York: Raven Press, 1995, pp. 1245–1257.
Hoff AL, Shukla S, Aronson T, et al. Failure to differentiate bipolar disorder from schizophrenia on measures of neuropsychological function. Schizophrenia Research 3:253–260, 1990.
Morice R. Cognitive inflexibility and pre-frontal dysfunction in schizophrenia and mania. British Journal of Psychiatry 157:50–54, 1990.

• 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.