Pathology Reveals Overlap Between Schizophrenia and Bipolar Disorder

Glenn T. Konopaske, MD McLean Hospital, Belmont, Massachusetts Department of Psychiatry, Harvard Medical School Boston, Interview with:
Glenn T. Konopaske, MD
McLean Hospital, Belmont, Massachusetts
Department of Psychiatry, Harvard Medical School
Boston, Massachusetts

Medical Research: What are the main findings of the study?

Dr. Konopaske: Using postmortem human brain tissue this study did reconstructions of basilar dendrites localized to pyramidal cells in the deep layer III of the dorsolateral prefrontal cortex. Tissue from individuals with schizophrenia, bipolar disorder or controls was examined. Dendritic spine density (number of spines per μm dendrite) was significantly reduced in bipolar disorder and also reduced in schizophrenia at a trend level. The number of dendritic spines per dendrite and dendrite length were significantly reduced in subjects with schizophrenia and bipolar disorder.

Medical Research: What was most surprising about the results?

Dr. Konopaske: Reduced dendritic spine density in the dorsolateral prefrontal cortex from subjects with schizophrenia has been previously reported by two groups. This is the first time it has been reported in bipolar disorder. What was quite surprising was that the dendritic spine loss appears to be of similar magnitude in both disorders.

Medical Research: What should clinicians and patients take away from your report?

Dr. Konopaske: Although schizophrenia and bipolar disorder can look very dissimilar clinically, this finding supports the idea that there is a fair amount of overlap between the two pathophysiologically. For over 100 years, psychiatry has followed the dichotomy set forth by Emil Kraepelin separating psychosis into dementia praecox (schizophrenia) and manic psychosis (bipolar disorder). We now recognize that numerous pathophysiological entities can lead to psychotic symptoms. Nevertheless, schizophrenia and bipolar disorder remain distinct entities in the DSM. A loss of dendritic spines in the DLPFC in both schizophrenia and bipolar disorder suggest that the two disorders share pathophysiological features and the two disorders might be much more closely related than previously appreciated.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Konopaske: Several avenues of research are suggested by this finding:

  1. How generalizable is dendritic spine loss in schizophrenia and bipolar disorder?
  2. What mechanisms might account for the observed spine losses? Are they similar in both disorders?
  3. Explore the feasibility of developing a radioligand to study dendritic spine changes in living patients.

Konopaske GT, Lange N, Coyle JT, Benes FM. Prefrontal Cortical Dendritic Spine Pathology in Schizophrenia and Bipolar Disorder. JAMA Psychiatry. Published online October 01, 2014. doi:10.1001/jamapsychiatry.2014.1582.